INDONESIA • 2018

ISSN 2411-0183
VOL. 44 NO. 3

JOURNAL OF PAEDIATRICS,
OBSTETRICS & GYNAECOLOGY

YOUR PARTNER IN PAEDIATRIC, OBSTETRIC & GYNAECOLOGY PRACTICE

PAEDIATRICS
How can Your
Microbiologist Help
you Manage
Paediatric Infection?

GYNAECOLOGY
Management of
Urinary Incontinence
in Frail Elderly Women

CME ARTICLE
Human Papillomavirus
and Cervical Cancer
EMPOWERING
HEALTHCARE
COMMUNITIES
 MIMS JPOG 2018 VOL. 44 NO. 3 i

2018 VOL. 44 NO. 3

Editorial Board
Board Director, Paediatrics
Professor Pik-To Cheung
Associate Professor, Department of Paediatrics and Adolescent Medicine
The University of Hong Kong, Hong Kong
Board Director, Obstetrics and Gynaecology
Professor Pak-Chung Ho
Director, Centre of Reproductive Medicine
The University of Hong Kong - Shenzhen Hospital, China
Professor Biran Affandi
University of Indonesia, Indonesia
Professor Hextan
Yuen-Sheung Ngan
The University of Hong Kong, Hong Kong
Professor Kenneth Kwek
KK Women’s and Children’s Hospital,
Singapore
Professor Kok Hian Tan
KK Women’s and Children’s Hospital,
Singapore
Professor Dato’
Dr. Ravindran Jegasothy
Dean Faculty of Medicine,
MAHSA University, Malaysia
Associate Professor Daisy Chan
Singapore General Hospital, Singapore
Associate Professor Raymond
Hang Wun Li
The University of Hong Kong, Hong Kong
CONFERENCE COVERAGE
34th Annual Meeting of the European Society of
Human Reproduction and Embryology (ESHRE),
July 1-4, Barcelona, Spain
89
• Slow-release insemination ups pregnancy rate for
young infertile women
Professor Seng-Hock Quak
• GnRH agonist + hCG improves oocyte retrieval in IVF
National University of Singapore, patients
Singapore
Adjunct Associate Professor
Tan Ah Moy
KK Women’s and Children’s Hospital,
Singapore
Dr. Catherine Lynn Silao
JOURNAL WATCH
University of the Philippines Manila,
Philippines
Dwiana Ocviyanti, MD, PhD
University of Indonesia, Indonesia
90
Dr. Karen Kar-Loen Chan • Kids eat more veggies when
The University of Hong Kong,
Hong Kong plates have those images
Dr. Kwok-Yin Leung • Alcohol intake during
The University of Hong Kong,
Hong Kong breastfeeding affects cognition
Dr. Mary Anne Chiong in babies
University of the Philippines Manila,
Philippines

Adjunct Associate Professor Dr. Wing-Cheong Leung

Ng Kee Chong
Kwong Wah Hospital, Hong Kong, 91
Hong Kong
Division of Medicine & Academic Clinical
Program (Paediatrics), c/o KK Women’s and • HPV testing could detect cervical precancers earlier
Children’s Hospital, Singapore than cytology

92
• Prenatal depression increases
over time
 MIMS JPOG 2018 VOL. 44 NO. 3 iii

2018 VOL. 44 NO. 3

REVIEW ARTICLE
OBSTETRICS
CEO Yasunobu Sakai
Managing Editor Elvira Manzano
Medical Editor Elaine Soliven
Designer Sam Shum
93
Production Tetsuya Hamaki, Agnes Chieng, Raymond Choo
Circulation Christine Chok Hypertension in Pregnancy
Accounting Manager Minty Kwan
Advertising Coordinator Pannica Goh
Hypertensive disorders of pregnancy
remain a common complication of
Published by: pregnancy and a major cause of
MIMS (Hong Kong) Limited
27th Floor, OTB Building, 160 Gloucester Road, Wan Chai, Hong Kong maternal and perinatal morbidity and
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mortality worldwide. Hypertensive
disorders range from mild gestational
hypertension to early onset pre-
eclampsia which remains a leading cause of maternal death
Enquiries and Correspondence worldwide. Due to their unpredictable nature and potential poor
China Philippines
outcomes, patients with hypertensive disorders of pregnancy
Yang Xuan Rowena Belgica warrant cautious care including consultant obstetric, neonatal,
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iv MIMS JPOG 2018 VOL. 44 NO. 3

2018 VOL. 44 NO. 3

REVIEW ARTICLE MIMS JPOG welcomes papers in the

following categories:
GYNAECOLOGY
Review Articles
Comprehensive reviews providing the latest clinical information
115 on all aspects of the management of medical conditions affecting
children and women.
Management of Urinary Incontinence in
Frail Elderly Women Case Studies
Urinary incontinence (UI) is defined by Interesting cases seen in general practice and their management.
the International Continence Society
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CONTINUING
MEDICAL EDUCATION
125
Human Papillomavirus and Cervical
Cancer 2 SKP

Cervical cancer is the fourth most common cancer in women in

the world, and there were about 528,000 new patients and 266,000
deaths in 2012. This article aims to review the causal relationship
between human papillomavirus (HPV) and cervical cancer and
discuss existing methods that prevent HPV from leading to cervical
cancer.
Ka Yu Tse, Philip Pun Ching Ip, Karen Kar Loen Chan

The Cover:
Hypertension in Pregnancy
©2018 MIMS Pte Ltd

Peggy Tio, Designer

CONFERENCE COVERAGE
34th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE),
July 1-4, Barcelona, Spain – Elaine Soliven reports
Slow-release insemination
ups pregnancy rate for
young infertile women
Young infertile women who undergo in-
trauterine slow-release insemination (SRI)
may achieve a higher rate of pregnancy,
according to a study presented at ESHRE
2018.
“SRI [theorized] that if persistent
low concentration of sperm might pro-
long the period of potential fertilization,
thereby it mimics the physiological
sperm transportation into the fallopian
tubes because it is a slow release of
sperm,” said study lead author Dr Julian
Marschalek from the Division of Gynae-
cological Endocrinology and Reproduc-
tive Medicine at the Medical University of
Vienna, Austria.
This randomized crossover study in-
volved 182 women with infertility (median
age 33 years) who were randomized to re-
ceive either standard intrauterine insemi-
nation (IUI, n=96) or SRI (n=86) as their
first cycle of treatment, of whom 7 and 11
became pregnant, respectively. The 102
women who did not achieve pregnancy
were crossed over to the other method as
their second cycle of treatment (IUI, n=44
and SRI, n=58). [ESHRE, abstract O-118]
There were no significant differences
with regard to cause of infertility, male pa-
rameters, or reproductive medications, in-
cluding clomiphene, gonadotrophin, and
progesterone, between groups.
While the rate of pregnancy did
not statistically differ between women
who received SRI and IUI (13.2 percent
vs 10.0 percent, relative risk [RR], 1.31;
p=0.202), a subgroup analysis of wom-
en aged <35 years showed a significant-
ly higher overall pregnancy rate among
women who underwent SRI compared
with IUI (16.9 percent vs 7.2 percent, RR,
2.33; p=0.032).
“We are aware that the crossover de-
sign might be seen as a limitation of this
study. Some authors reject the utilization
of this study design in infertility trials. How-
ever, others claim this [as] an efficient and
pragmatic design, particularly as only one
cycle of each treatment is given to each
woman,” Marschalek said.
“[Nevertheless,] we think that this
is an interesting finding; the extent to
which advanced male or female age
influences pregnancy rates after SRI
needs to be addressed, and we want
to perform further studies on that,” said
Marschalek.
Dr Julian Marschalek, et al, European Society of Human Re-
production and Embryology (ESHRE) 2018, July 1-4, Barce-
lona, Spain [abstract O-118].
GnRH agonist + hCG improves
oocyte retrieval in IVF patients
Dual triggering with a gonadotropin-re-
leasing hormone (GnRH) agonist and hu-
man chorionic gonadotropin (hCG) may
increase the number of oocytes among
women undergoing in vitro fertilization
(IVF), according to a study presented at
ESHRE 2018.
This single-centre, prospective dou-
ble-blind trial consisted of 160 women
(mean age 36 years, mean BMI 24 kg/
m2) on their first to third IVF cycle at-
tempts. Participants were given hCG
alone (10,000 IU and placebo, n=80) or
hCG plus a GnRH agonist (dual trigger
group; 10,000 IU and 0.5 mg, n=80) 36
hours prior to oocyte retrieval. The base-
line and stimulation cycle characteris-
tics were similar between the treatment
groups. [ESHRE 2018, abstract O-208]
MIMS JPOG 2018 VOL. 44 NO. 3 89
Compared with women given hCG
only, those in the dual trigger group had
significantly more oocytes retrieved (12.9
vs 10.6; p=0.02).
Women treated with dual trigger vs
hCG also had a significantly higher rate
of oocyte recovery (number of oocytes
in each follicle, 96.1 percent vs 76.6 per-
cent; p=0.001 [above 10 mm] and 145.1
percent vs 121.8 percent; p=0.03 [above
15 mm]).
A majority, but not all of the oocytes
were mature, said study lead author
Dr Jigal Haas from the IVF unit at TRIO
Fertility Clinic in Toronto, Ontario,
Canada.
Compared with those in the hCG
only group, women in the dual trigger
group had significantly more metaphase
II oocytes (10.1 vs 8.6; p=0.04), zygotes
(7.9 vs 6.3; p=0.04), embryos (6.6 vs
5.7; p=0.03), and blastocysts (3.7 vs 3.1;
p=0.02), as well as top-quality blasto-
cysts (2.5 vs 1.8; p=0.02).
A higher rate of cumulative pregnan-
cy was observed in women who had dual
trigger vs hCG treatment (64 percent vs
57 percent), though the difference was
not statistically significant due to small
sample size.
“We think that the increase in the
number of mature oocytes may poten-
tially improve the outcome of the IVF
cycle,” said Haas, recommending a
larger study assessing pregnancy out-
comes in women given the dual trigger
combination.
“We believe that by hCG, we get
great results, but by the dual trigger, we
can get better results,” Haas noted.
Dr Jigal Haas, et al, European Society of Human Reproduc-
tion and Embryology (ESHRE) 2018, July 1-4, Barcelona,
Spain [abstract O-208].
90 MIMS JPOG 2018 VOL. 44 NO. 3
P more (4.04 grams) vs baseline, but
Paediatrics
Kids eat more veggies when
plates have those images
Preschool children consumed more veg-
etables when their plates had images of
fruits and vegetables, according to a lon-
gitudinal study. However, this effect was
not observed for fruit consumption, offer-
ing important insights for those manag-
ing paediatric nutrition.
Children who used plates with
images took 13.82 grams more veg-
etables daily compared to when they
used plain white plates (p<0.001),
said Drs Emily Melnick and Meng Li,
both from the Department of Health
and Behavioural Sciences at the Uni-
versity of Colorado Denver in Denver,
Colorado, US. This led them to con-
sume 7.54 grams more vegetables
(p=0.001). These children also took
more fruit (3.66 grams) and consumed
neither of those increases were statis-
tically significant.
“This approach of using nudge
methods to change what people eat is re-
ally important and there has been a lot of
research on it in the general population,
but there is little on how that affects kids,”
Li said. “I think the exposure kids have
to food is really impactful in their adult
behaviour in the long term.”
The study included 235 children
from Colorado evenly split between
boys and girls. All used white plates at
baseline and were shifted to segment-
ed plates with images 4 weeks later.
The researchers gave introduction
about the pictures of fruits and vegeta-
bles on their plates. In both instances,
the menus were the same each day.
The strongest effect was seen in the
intervention group on the second day
when fruit was omitted from the menu
and included cucumbers and carrots
instead.
The authors admitted that the sam-
ple size being small was one of the study
JOURNAL WATCH PEER REVIEWED
caveats and a study of a much larger
scale is warranted in the future.
Melnick EM, Li M. Association of plate design with consump-
tion of fruits and vegetables among preschool children. JAMA
Pediatr 2018;doi:10.1001/jamapediatrics.2018.1915.
Alcohol intake during
breastfeeding affects
cognition in babies
Children whose mums consumed alco-
hol when breastfeeding them were more
likely to experience dose-dependent
reductions in abstract reasoning at age
6–7 years, a study has shown. The effect
waned by age 8–11 years.
Researchers said alcohol passes
quickly through the breast milk and re-
duces milk production. The practice of
pumping and dumping breast milk after
alcohol consumption does not decrease
ethanol concentration in breast milk be-
cause for as long as alcohol is present
in the maternal blood, ethanol in breast
milk will remain high.
Researchers from the Macquarie
University in Sydney, Australia analysed
data from the Growing Up in Australia:
The Longitudinal Study of Australian
Children, which included 5,107 babies
who were assessed every 2 years. Multi-
variable linear regression analyses were
used to determine the link between al-
cohol use and smoking by breastfeed-
ing mothers and babies’ scores on three
measures (Matrix Reasoning, Peabody
Picture Vocabulary Test–Third Edition,
and Who Am I?) over time.
Breastfed infants whose mothers con-
sumed alcohol were more likely to have
reduced Matrix Reasoning scores at age
6–7 years (B coefficient [B], -0.11, 95 per-
cent confidence interval [CI], -0.18 to -0.04;
p=0.01). This association was not found in
women who had never breastfed (p=0.87).
JOURNAL WATCH PEER REVIEWED
“Alcohol exposure through breast
milk was responsible for the findings.
What is more difficult to ascertain and
quantify, however, are the potential ef-
fects of other environmental and genetic
risks that can lead to these results,” said
Dr Lauren Jansson from the Johns Hop-
kins University in Baltimore, Maryland,
US, in a commentary. “The finding is not
surprising when we consider the poten-
tial pharmacokinetic basis for it and the
known harmful effects of alcohol on the
developing brain.”
She added that alcohol concentra-
tions in breast milk resemble those in
maternal blood within 30–60 minutes of
ingestion — about <5–6 percent of the
weight-adjusted maternal dose — and
newborns metabolize alcohol at approxi-
mately half the rate of adults. No link was
found for smoking during breastfeeding.
The researchers admitted that they
didn’t record the quantity of alcohol con-
sumed by the mothers nor the timing
of alcohol intake, which make for study
limitations.
Gibson L and Porter M. Drinking or Smoking While
Breastfeeding and Later Cognition in Children. Pediatrics
2018;142(2):e20174266; Jansson LM. Maternal Alcohol Use
During Lactation and Child Development. Pediatrics 2018;
142:e20181377.
G 25–65 years who were randomized
Gynaecology
HPV testing could detect
cervical precancers earlier
than cytology
Women who received primary human
papillomavirus (HPV) test alone were
less likely to develop grade 3 or worse
cervical intraepithelial neoplasia (CIN3+)
at 48 months vs those who had Pap cy-
tology screen, a study has shown.
The 2-year risk of CIN2+ neo-
plasia was also reduced with the HPV
test compared with Pap smear alone.
“These suggest that primary HPV test-
ing detects cervical neoplasia earlier
and more accurately than cytology,”
said Dr Ogilvie from the Universi-
ty of British Columbia in Vancouver,
Canada.
The Human Papilloma Virus for
Cervical Cancers Screening study in-
MIMS JPOG 2018 VOL. 44 NO. 3 91
cluded 19,009 Canadian women aged
to Pap liquid-based cytology (control
group, n=9,457) or primary HPV test-
ing (intervention group, n=9,552).
The primary outcome was the rate
of CIN3+ at 48 months. Secondary
endpoints included the 48-month rate
of CIN2+, the threshold for colposcopy
referral, and the effect of primary HPV
testing on colposcopy.
At 48 months, the rate of CIN3+
was significantly lower in the interven-
tion group than in the control group (2.3
vs. 5.5 per 1,000; risk ratio [RR], 0.42),
with an absolute difference of 3.2 fewer
cases per 1,000. Overall, both methods
detected about the same number of
cases by 48 months.
The greatest benefit was in HPV
negative women at baseline; HPV in-
cidence rate was 1.4 per 1,000 by 48
months vs 5.4 per 1,000 in the control
group. This translates to an RR of 0.25
or an absolute reduction of 4 cases per
1,000 women.
92 MIMS JPOG 2018 VOL. 44 NO. 3 JOURNAL WATCH PEER REVIEWED

The intervention group was 61 per-

cent more likely to have a CIN2+ result
by 12 months (RR, 1.61), but 53 percent
less likely to have it at 48 months (RR,
0.47).
“By 48 months, significantly fewer
CIN2+ cases were detected overall and
across all age groups in the intervention
group compared with the control group,”
the researchers said. At 48 months, the
CIN2+ rate was 5 per 1,000 vs 10.6 per
1,000 – a 53 percent reduced risk (RR,
0.47) and an absolute reduction of 5.6
cases per 1,000.
Again, the benefit accrued early
and mostly in women who were neg-
ative by HPV or cytology at baseline.
Among these, the CIN2+ risk for the
intervention, compared with the con-
trol group, was 64 percent lower (RR,
0.36), and the absolute difference in
incidence was 6.38 per 1,000. At the
end of the study, cumulative colposco- Researchers sought to compare women than in their mothers’ generation
py referral rates were similar between the prevalence of depression during (relative risk [RR], 1.51). Results didn’t
groups. pregnancy in young mothers today change when the analyses were restrict-
“The similarity in colposcopy rates and their mothers’ generation. Partic- ed to the 66 mother-child pairs. Mater-
shows that fears about overdiagnosis with ipants included the original mothers, nal prenatal depression was associated
HPV testing are unfounded,” said Ogilvie. who were recruited when they were with daughters’ prenatal depression
pregnant, and their female children, or (RR, 3.33).
Ogilvie GS et al. Effect of Screening With Primary Cervical
HPV Testing vs Cytology Testing on High-grade Cervical In- female partners of male children, who The finding persists even after ad-
traepithelial Neoplasia at 48 Months: The HPV FOCAL Rand-
became pregnant. Both groups were justing for factors that differ across gen-
omized Clinical Trial. JAMA 2018;320:43-52.
of the same age range (19–24 years). erations and in analyses restricted to
The first generation of pregnancies mother-child pairs.
occurred in 1990–1992 (n=2,390), As prenatal depression has major

O the second in 2012–2016 (n=1,80).

Both groups completed the Edin-
burgh Postnatal Depression Scale
Obstetrics (EPDS) – a 10-item self-report meas-
ure of depression – at 18 weeks of
Prenatal depression pregnancy.
increases over time Of pregnant women in the first
generation, 17 percent had high EPDS
The prevalence of prenatal depression is scores (≥13) compared with 25 percent
higher today than in the 90s, according in the second generation. Having high
to the Avon Longitudinal Study of Par- EPDS scores was more common in the
ents and Children study. second generation of young pregnant
implications for service providers and
public health efforts, more research to
identify potential causes are needed,
said the study authors. The findings also
highlight the need for increased support
to young pregnant women to minimize
the far-reaching effects of depression.
Pearson RM, et al. Prevalence of Prenatal Depression Symp-
toms Among 2 Generations of Pregnant Mothers – The Avon
Longitudinal Study of Parents and Children. JAMA Network
Open 2018;doi:10.1001/jamanetworkopen.2018.0725.
OBSTETRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 3 93

Hypertension in Pregnancy
Roisin Ryan MB BCh BAO; Fergus McCarthy PhD MSc Dip MRCOG MRCPI

Hypertensive disorders of pregnancy remain a common complication of pregnancy

and a major cause of maternal and perinatal morbidity and mortality worldwide.
Hypertensive disorders range from mild gestational hypertension to early onset
pre-eclampsia which remains a leading cause of maternal death worldwide.
Although there have been major advances in understanding the pathophysiology
of the disease in recent years, interventions to screen for and prevent hypertensive
disorders of pregnancy have had disappointing results. Due to their unpredictable
nature and potential poor outcomes, patients with hypertensive disorders of
pregnancy warrant cautious care including consultant obstetric, neonatal, and
anaesthetic involvement to optimise both maternal and foetal outcomes.

INTRODUCTION classifies hypertension in pregnancy as

Hypertensive disorders of pregnancy are
frequently encountered complications of
pregnancy and have a number of possible
aetiologies. The International Society for
the Study of Hypertension in Pregnancy
follows: chronic hypertension, gestational
hypertension, pre-eclampsia de novo, or
superimposed on chronic hypertension;
or white coat hypertension. In the United
Kingdom, the number of maternal deaths
94 MIMS JPOG 2018 VOL. 44 NO. 3
Table 1. Risk Factors for Pre-eclampsia
Risk factor Unadjusted relative risk
(95% confidence interval)
Age ≥40 years, primiparous 1.68 (1.23–2.29)
Age ≥40 years, multiparous 1.96 (1.34–2.87)
Family history 2.90 (1.70–4.93)
Nulliparity 2.91 (1.28–6.61)
Multiple pregnancy 2.93 (2.04–4.21)
Pre-existing diabetes 3.56 (2.54–4.99)
Pre-pregnancy body mass index ≥35 4.29 (3.52–5.49)
Previous pre-eclampsia 7.19 (5.85–8.83)
Antiphospholipid syndrome 9.72 (4.34–21.75)
from hypertension in pregnancy has fallen steadily
over the past few decades, as well as the asso-
ciated complication rates. However, hypertensive
disorders remain a major cause of maternal and
perinatal morbidity and mortality and are respon-
sible for 14% of total maternal deaths worldwide.
Interventions to prevent hypertensive disor-
ders in pregnancy, including pre-eclampsia, in the
general antenatal population have been disap-
pointing, and the mainstay of treatment involves
close antenatal supervision of mother and foetus
and timely delivery to prevent deterioration of the
condition and subsequent morbidity and mortality.
CASE 1: RISK AND RECURRENCE OF
PRE-ECLAMPSIA
A patient is referred to you for pre-pregnancy coun-
selling. She is 40 years old, smokes 20 cigarettes
a day, and has been taking treatment (enalapril
20 mg once daily) for hypertension for the past
2 years. This woman had one previous pregnan-
cy 6 years ago which was complicated by severe
pre-eclampsia and HELLP (haemolysis, elevated
liver enzymes, and low platelets) syndrome result-
ing in delivery by emergency caesarean section at
27 weeks’ gestation. Her mother and two sisters all
had pregnancies complicated by pre-eclampsia.
On examination, her BMI is 38 and her blood pres-
OBSTETRICS PEER REVIEWED
sure (BP) is 160/96 mm Hg. The woman informs
you that she wishes to have another child as she
is now in a new relationship. She also tells you that
she has heard about a test that she can take which
will tell you if she will get pre-eclampsia in this
pregnancy again and would like more information.
Risk factors and recurrence
This patient has multiple risk factors for recur-
rence of pre-eclampsia. These include increased
maternal age, poorly controlled chronic hyper-
tension, previous early onset pre-eclampsia (<34
weeks’ gestation), raised BMI, family history of
pre-eclampsia, and new partner. Women with
severe pre-eclampsia, have an increased risk of
recurrence in their next pregnancy (about 1 in 6
[16%] pregnancies), but the disorder is generally
less severe and manifests 2–3 weeks later than in
the first pregnancy. This risk increases to about 1
in 4 (25%) pregnancies if the pre-eclampsia was
complicated by severe pre-eclampsia, HELLP
syndrome, or eclampsia and led to birth before 34
weeks’ gestation. The risk of recurrence is about 1
in 2 (55%) pregnancies if the pre-eclampsia led to
birth before 28 weeks’ gestation. Considering her
increased age and poorly controlled BP, this risk
may be higher. Her risk of HELLP syndrome recur-
ring is approximately 3–4%. Other risk factors for
pre-eclampsia are presented in Table 1.
Management
The patient should be counselled to avoid
pregnancy until her BP is optimally controlled.
Given her age, this should be done in a time-
ly, efficient, and safe manner. A careful histo-
ry should be taken, and contact made with her
general practitioner to ensure all causes of sec-
ondary hypertension have been excluded and
the patient has been appropriately investigated
(Table 2). Once a diagnosis of essential hyperten-
sion is made, BP should be optimally managed.
As the women wishes to conceive, you may con-
sider switching her to an alternative agent (see
later section on management of hypertension)
as enalapril, an angiotensin converting enzyme
OBSTETRICS PEER REVIEWED
Table 2. Causes of Secondary Chronic Hypertension and Key Diagnostic Tests
Idiopathic Essential hypertension
Vascular disorders Renovascular hypertension
Aortic coarctation
Endocrine disorders Diabetes mellitus
Hyperthyroidism
Hypothyroidism
Phaeochromocytoma
Acromegaly
Cushing’s syndrome
Primary hyperaldosteronism
Renal disorders Renal failure resulting from:
Diabetic nephropathy
Reflux nephropathy
Chronic glomerulonephritis
Nephritic and nephrotic
syndrome
Polycystic kidney
Connective tissue Systemic lupus erythematosus
disorders
Systemic sclerosis
Polyarteritis nodosa
Rheumatoid disease
(ACE) inhibitor is contraindicated in pregnancy
due to teratogenesis (increased risk of cardio-
vascular and neurological malformations if used
in the first trimester). As the patient is high risk
for recurrence of pre-eclampsia, low-dose aspirin
should be commenced once conception occurs.
General obstetric advice such as weight loss,
MIMS JPOG 2018 VOL. 44 NO. 3 95
Key diagnostic test/clinical clues
Renal ultrasound
Hypertension in upper limbs/diminished or delayed femoral pulses;
Echocardiography
Adrenergic symptoms (tremor, pallor, tachycardia, palpitations) and symptoms
of hypoglycaemia (fatigue, lethargy, headaches, drowsiness, coma); Glucose
tolerance test
Anxiety, weakness, tremor, palpitations, heat intolerance, increased perspiration;
Thyroid function tests
Weight gain, lethargy; Thyroid function tests
Headache, palpitations, sweating: Measurement of 24-hour urine fractionated
catecholamines and metanephrines
Macrognathia, enlargement of hands and feet; Measurement of serum insulin-
like growth factor-1
Cushingoid facies, central obesity, proximal muscle weakness, and ecchymoses;
Initially measurement of ACTH
Hypokalaemia, metabolic alkalosis; measurement of plasma renin and
aldosterone concentrations
History of urinary tract infections
Nephrotic syndrome: heavy proteinuria (>3.5 g/day). Nephritic syndrome:
variable degrees of proteinuria with the presence of red cells and/or white
blood cells
Family history
Malar rash, photosensitivity, discoid rash, oral ulcers, arthritis; raised protein
creatinine ratio, presence of Anti-dsDNA, Anti-Sm, and/or ANA
Skin thickening; anti-topoisomerase I (anti-Scl-70), anti-centromere, and anti-
RNA polymerase III antibodies
General symptoms such as fatigue, weight loss, weakness, fever, arthralgia,
or skin lesions. Systemic signs such as hypertension, renal insufficiency, or
neurologic dysfunction
Inflamed painful joints; rheumatoid factor
smoking cessation, and pre-conceptual folic acid
should also be given.
Prediction of pre-eclampsia
In terms of prediction, women can be catego-
rised as high risk (as this woman is) and low
risk. She should be reassured that she will be
96 MIMS JPOG 2018 VOL. 44 NO. 3
followed closely during pregnancy to monitor
for signs of pre-eclampsia, but that there is
no test which reliably predicts pre-eclampsia.
A combination of maternal risk factors, Pla-
cental Growth Factor, and uterine artery Dop-
pler may identify women who would benefit
from treatment with aspirin to prevent pre-
term pre-eclampsia as shown recently in the
ASPRE study, but this screening approach
has not yet been universally accepted or
implemented.
CASE 2: CHRONIC HYPERTENSION/
PREGNANCY-INDUCED HYPERTENSION
A 35-year-old woman attends your antenatal clin-
ic at 12 weeks’ gestation in her first pregnancy.
She has a BMI of 22 and is a non-smoker. Her
BP is 150/95 mmHg. She is non-proteinuric and
asymptomatic.
Diagnosis of hypertension
in pregnancy
Pre-eclampsia is associated with significant ma-
ternal and perinatal morbidity and mortality. As
such, it is imperative that every effort is made
to accurately classify women with hypertension
in pregnancy as having chronic hypertension,
non-proteinuric PIH, or pre-eclampsia as the ae-
tiology and management of the three conditions
is very different.
Measurement of blood pressure
BP should be measured with the woman rested
and seated at a 45-degree angle with the arm at
the level of the heart. It is imperative that an ap-
propriately sized cuff is used. To avoid incorrect
measurement of BP, if the mid-arm circumfer-
ence is greater than 33 cm, a large cuff should
be used. Korotkoff phase 1 is used to measure
systolic BP and Korotkoff 5 is appropriate for
measurement of diastolic BP, as it is most con-
sistent in pregnancy. The method used to re-
cord BP should be consistent and documented,
and a machine validated for use in pregnancy
such as Microlife® should be used.
OBSTETRICS PEER REVIEWED
Chronic hypertension
Chronic hypertension is defined as hypertension
preceding pregnancy. BP falls in the first and
second trimesters. Therefore, women, such as
in this case, with high BP before the 20th week
of pregnancy, are assumed to have pre-existing
or essential hypertension. As many women of
reproductive age present for BP measurement
for the first time when pregnant, chronic hyper-
tension is often revealed in the first half of preg-
nancy. Approximately 90–95% of cases of chron-
ic hypertension are considered to be essential.
Secondary causes which account for approx-
imately 5–10% are listed in Table 2. In women
presenting with hypertension in the first half of
pregnancy, it is important to look for an under-
lying cause. These investigations should at least
include:
• 
Urine analysis and protein creatinine ratio
(looking for blood, protein, or glucose and
quantification of the degree of proteinuria)
• Urea and electrolytes
• Renal tract ultrasound
Women with underlying renal disease, par-
ticularly with raised pre-pregnancy creatinine,
are at significantly increased risk of poor preg-
nancy outcome and require multidisciplinary
care.
Gestational hypertension
Gestational hypertension is a rise in the BP
in the absence of proteinuria after 20 weeks’
gestation. True non-proteinuric pregnancy in-
duced hypertension does not appear to be
associated with an increase in maternal or foe-
tal morbidity. However, the risk of progression
from gestational hypertension to pre-eclamp-
sia is approximately 20–30%, and therefore
vigilance is required. This rate increases to
approximately 50% when gestational hyper-
tension develops before 32 weeks’ gestation.
As a result of this risk of progression to pre-ec-
lampsia, weekly urinalysis and BP checks are
generally recommended in women with gesta-
tional hypertension.
OBSTETRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 3 97

Box 1. Management of Hypertension in Pregnancy

• Screening
š Women should be screened for signs of hypertension using BP checks and urinalysis monthly until 30 weeks’ gestation, fortnightly from
30 weeks’ gestation and weekly from 36 weeks’ gestation.
š If elevated BP ± proteinuria, refer for admission or monitoring in antenatal day unit.
• Maternal assessment
š Repeat (at least 4 hourly) BP measurement.
š Quantitative measurement of protein in urine. (Pre-eclampsia = >0.3 g protein 24-hour urine collection).
š Platelet count, serum uric acid concentration, and tests of liver function (alanine and aspartate aminotransferase levels). Coagulation
screen if altered liver function.
• Antihypertensive therapy
š Consider admission, monitor closely, and treat if blood pressure is persistently above 160/100 mm Hg. Aim for target diastolic BP 85
mm Hg.
• Anticonvulsant therapy
š If convulsions occur, use magnesium sulphate, intravenously or intramuscularly.
š In cases of severe pre-eclampsia, consider prophylactic magnesium sulphate.
• Foetal management
š Give prophylactic steroids if the duration of gestation is less than 34 weeks’ gestation.
š Perform an ultrasound assessment of foetal weight on initial presentation and repeat fortnightly.
š Doppler ultrasonographic assessment of umbilical blood-flow velocity if evidence of growth restriction.
š Regular cardiotocography (CTG/non-stress tests).
š Ultrasonography at least twice a week for liquor volume.
š Multidisciplinary approach regarding timing and mode of delivery.
• Post-partum care
š Continued close monitoring of the mother by experienced carers.
š If on magnesium therapy, continue for at least 24-hour post-partum until stable.
š Careful fluid balance (total 80 mls/hour intake) and early use of diuretics if pulmonary oedema secondary to fluid overload is
suspected.
š Decrease dose of antihypertensive agents as indicated. Avoid sudden cessation immediately post-partum as rebound hypertension
likely.
• Follow-up
š Long-term follow-up to make sure that the BP falls (within 6 weeks post-partum), and suitable referral if it does not.
š Discussion about the illness and the significance for the future.
š Recommend pre-conceptual counselling for future pregnancies.

Treatment of hypertension to either “less tight” control (aiming for diastolic

in pregnancy (Box 1)
The use of antihypertensive drugs in hyperten-
sive women without renal impairment is con-
sidered by some to be beneficial in preventing
sudden increases in BP, cerebral haemorrhage,
or hypertensive encephalopathy. The Control of
Hypertension in Pregnancy Study (CHIPS) was
a randomised controlled trial in which women
with hypertension in pregnancy were randomised
BP of 100 mm Hg) or “tight” control (aiming for
diastolic BP of 85 mm Hg) of their hypertension.
The trial demonstrated that women in “less tight”
compared with “tight” control groups had similar
rates of adverse perinatal (31.4% vs 30.7%) and
maternal outcomes (3.7% vs 2.0%), despite high-
er mean diastolic BP by 4.6 mm Hg. However, se-
vere hypertension (≥160/110 mm Hg) developed
more frequently in “less tight” vs “tight” control
98 MIMS JPOG 2018 VOL. 44 NO. 3
A systolic BP greater than 160 mm Hg should be considered a medical emergency
and quick effective treatment is advocated to prevent haemorrhagic stroke.
(40.6% vs. 27.5%). As a result, tight control of BP
is advocated to prevent potential adverse mater-
nal outcomes.
Both CMACE and NICE Clinical Guidelines
on Hypertension in Pregnancy recommend that all
pregnant women with a systolic BP of 150 mm Hg
or more require antihypertensive treatment. Consid-
eration should also be given to initialising treatment
at lower pressures if the overall clinical picture sug-
gests rapid deterioration and/or where the develop-
ment of severe hypertension can be anticipated.
A systolic BP greater than 160 mm Hg should
be considered a medical emergency and quick ef-
fective treatment is advocated to prevent haemor-
rhagic stroke.
Antihypertensive agents which may be used
in pregnancy include:
• Labetalol; a combined ß-adrenoceptor block-
er that also blocks α-adrenoceptors. Ordinary
ß-adrenoceptor blockers are unsuitable for pro-
ducing a quick antihypertensive effect because
a quick fall in BP triggers a compensatory sym-
OBSTETRICS PEER REVIEWED
pathetic discharge that increases the periph-
eral vascular resistance via α-adrenoceptors.
Blocking the ß-adrenoceptors alone cannot
prevent this compensatory response, but the
addition of an α-adrenoceptor blocker can. It
is this action that renders labetalol suitable for
gaining quick control of the BP. Labetalol, like
all ß-adrenoceptors, is contraindicated in wom-
en with a history of asthma.
• Nifedipine is a calcium channel blocker used
in the treatment of chronic hypertension in
pregnancy. Data suggest that it is safe, but cu-
mulative evidence is not as extensive as with
older drugs such as labetalol and methyldo-
pa. The principal side effect is headache,
which can be severe, may last for several days
after commencing treatment and may return
after increasing the dose. Use of the long-act-
ing once-daily preparation improves compli-
ance. Nifedipine is a potent antihypertensive
agent but should not be given sublingually as
it may cause a precipitate fall in BP, which can
lead to foetal distress. The concomitant use of
nifedipine and magnesium sulphate must be
with caution due to potential risk of serious ad-
verse maternal effects such as hypotension.
α-Methyldopa (a centrally acting α-adrenergic
• 
agonist that inhibits vasoconstricting impulses
from the medulla oblongata) has traditionally
been the most commonly used agent for the
control of BP during pregnancy, particularly in
those with chronic hypertension. Its safety has
been well established both in pregnancy and
in the long-term follow-up of the infants. One
of the most frequent side effects is sedation,
which can be profound. This is often poorly tol-
erated and leads to unpredictable compliance.
However, α-methyldopa remains the preferred
agent of the National High Blood Pressure Ed-
ucation Programme.
ACE inhibitors and angiotensin receptor
blockers (ARBs) and diuretics should be avoided
in pregnancy. Diuretics may reduce uteroplacental
perfusion. Second- and third-trimester exposure to
ACE inhibitors appears to be fetotoxic, producing
OBSTETRICS PEER REVIEWED
foetal hypocalvaria, and renal defects. The cause
of these defects seems to be related to foetal hy-
potension and reduced renal blood flow. Anuria as-
sociated with oligohydramnios can produce foetal
limb contractures, craniofacial deformations, and
pulmonary hypoplasia. Intrauterine growth restric-
tion, prematurity, persistence of a patent ductus
arteriosus, severe neonatal hypotension, neonatal
anuria, and neonatal or foetal death have all been
observed with use of these drugs, and they should
therefore be discontinued pre-conceptually or as
early in the first trimester as possible.
Angiotensin receptor blockers are newer
agents that have not been formally studied in
pregnancy, they are probably best avoided given
their common pathway with ACE inhibitors.
CASE 3: MANAGEMENT OF
PRE-ECLAMPSIA
A woman attends the emergency room complain-
ing of headaches and epigastric pain. She is at 34
weeks’ gestation in her first pregnancy. Her blood
pressure was mildly elevated (140/90 mm Hg) at her
28- and 31-week antenatal visits during this preg-
nancy, but she was asymptomatic, did not have
proteinuria, her liver function tests were normal, and
her BP settled on repeated measurements. On ex-
amination she has 3+ protein on urine dipstick and
her BP on four occasions over a 2-hour period rang-
es from 160–172/90–102 mm Hg. She complains of
reduced foetal movements and reports some
unprovoked bleeding from her vagina.
Pre-eclampsia
Pre-eclampsia is defined by the International So-
ciety for the Study of Hypertension in Pregnancy
as gestational hypertension of at least 140/90 mm
Hg on two separate occasions measured at least
4 hours apart accompanied by one or more of the
following:
• Significant proteinuria of at least 300 mg in a
24-hour collection of urine or protein creati-
nine ratio of ≥30 mg/mmoL on a spot urine or
at least 1 g/L (2+ on urine dipstick).
• 
Other maternal organ dysfunction including
MIMS JPOG 2018 VOL. 44 NO. 3 99
renal insufficiency (creatinine <90 μmol/L),
liver involvement (elevated liver transaminas-
es of at least twice upper value of normal),
neurological complications, and haematologi-
cal complications (eg, thrombocytopenia with
platelet count below 150 x 109/L).
• Uteroplacental dysfunction; foetal growth re-
striction.
Pre-eclampsia is a potentially life-threatening
hypertensive disorder of pregnancy characterized
by vascular dysfunction and systemic inflamma-
tion involving the brain, liver, and kidneys of the
mother. In developed countries, the incidence of
pre-eclampsia has risen in the United States of
America, but maternal mortality from pre-eclamp-
sia has decreased significantly in the UK in recent
decades at a rate of 0.13 per 100,000 maternities
in the 2017 MBRACCE report.
It usually occurs during the second half of
pregnancy and complicates approximately 5% of
first time pregnancies and 2–3% of pregnancies
overall.
Pathophysiology of pre-eclampsia
Pre-eclampsia results from impaired trophoblast
differentiation and invasion in early pregnancy re-
sulting in the failure of trophoblast cells to destroy
the muscularis layer of the spiral arterioles result-
ing in the development of a poorly perfused pla-
centa and stimulation of a systemic inflammatory
response. However, this reduced placental perfu-
sion alone is not sufficient to cause the maternal
syndrome of pre-eclampsia, and it is thought that
this process requires the influence of additional
maternal factors including genetic make-up and
environmental factors (such as obesity and diet),
which together results in widespread endothelial
dysfunction and hypertension.
Management of pre-eclampsia
Ideally women at high risk of pre-eclampsia
should be reviewed pre-conceptually and advised
to take 75 mg of aspirin daily from 12 weeks’ ges-
tation until delivery. Table 1 highlights risk factors
for the development of pre-eclampsia.
100 MIMS JPOG 2018 VOL. 44 NO. 3 OBSTETRICS PEER REVIEWED

Table 3. Investigations and Monitoring of Pre-eclampsia

Laboratory tests Full blood count Elevated haematocrit, thrombocytopenia

Uric acid
Urea and electrolytes
Liver function tests
Coagulation screen
Urinalysis
24-hour urine collection
Protein creatinine ratio
Ultrasound Foetal weight
Serial growth scans
Amniotic fluid index
Umbilical artery
Doppler velocimetry
Sensitive, but only of clinical importance if levels are extremely high or increasing
Alanine transaminase (ALT), aspartate transaminase (AST) will be elevated in
HELLP
Prothrombin time (PT), activated partial thromboplastin time (APTT), prolonged in
HELLP. Only required if platelet count is abnormal
1+ = 0.3 g/L, 2+ = 1 g/L, and 3+ = 3 g/L
>0.3 g protein excretion
30 mg/mmoL correlates with 0.3 g in the 24-hour collection
Perform at time of diagnosis and 4 weekly thereafter, subject to clinical
condition

Investigations and monitoring of the suspect- come including progression to pre-eclampsia.

ed pre-eclamptic patient are listed in Table 3. The
pre-eclampsia integrated estimate of risk (PIERS)
multivariable risk model uses gestational age,
chest pain or dyspnoea, oxygen saturation, plate-
let level, creatinine, and aspartate transaminase. It
aims to predict the risk of adverse maternal out-
comes in the first 48 hours of hospital admissions.
The pharmacological treatment of pre-ec-
lampsia focuses on controlling maternal hyper-
tension. No drugs in current clinical use benefi-
cially affect the human placenta. As a result,
management involves treatment of maternal
hypertension and close antenatal supervision
of the mother and foetus with timely delivery to
prevent deterioration of the mother and foetus.
Pre-eclampsia can occasionally be managed
conservatively. Maternal and foetal monitoring
should continue until foetal maturity has been
achieved, at which stage the cervix is assessed
with Bishops scoring and, if favourable, induc-
tion of labour is carried out. As a result of the
HYPITAT trial, delivery is generally advocated
by 37 weeks’ gestation. This is associated with
a significant reduction in adverse maternal out-
Furthermore, no differences were observed
in neonatal outcomes or caesarean section
rates.
Patients with pregnancy induced hyperten-
sion may be monitored through a combination of
general practitioners and hospital day care units.
Severe pre-eclampsia necessitates inpatient care
with a close monitoring of the symptoms, signs,
and biochemical parameters. “Severe” pre-ec-
lampsia is difficult to define, however, the follow-
ing features generally indicate the development of
severe pre-eclampsia.
• Eclampsia
• Severe hypertension eg, a systolic BP over
160 mm Hg with at least 2+ proteinuria
• 
Moderate hypertension associated with any
of severe headache with visual disturbance,
epigastric pain, signs of clonus, liver tender-
ness, platelet count falling to below 100 x
109/L, creatinine >100 mmol/L, and alanine
aminotransferase rising to above 50 IU/L
In extreme prematurity, transfer to hospi-
tal with adequate neonatal facilities (with steroid
administration to enhance lung maturity) is indi-
OBSTETRICS PEER REVIEWED
cated. Severe pre-eclampsia presenting prior to
foetal viability is an indication for termination of
pregnancy due to the risk of maternal death.
The optimum time of delivery is of crucial
importance and remains a balance between
the risks of major complications to the mother
and intrauterine growth restriction in the foetus
against the risks of delivery and prematurity to
the foetus. The mode of delivery is a balance
between caesarean section and vaginal delivery.
Caesarean section is a better option for rapid
deteriorating maternal and foetal condition, or
alternatively for those remote from term with an
unfavourable cervix. Epidural analgesia may be
beneficial by preventing the increase of catecho-
lamine release, in order to prevent further eleva-
tions of BP during uterine contractions. It may
also allow a more controlled second stage.
Oral antihypertensive are discussed above.
In severe pre-eclampsia, there are two antihyper-
tensive regimens to choose from:
• Labetalol (200 mg) can be given orally prior
to or in the absence of intravenous access,
and if there is no response within 30 minutes,
a second oral dose can be given. If there is
no initial response to oral therapy or if it is
not tolerated, a bolus of 50 mg given intra-
venously over at least 5 minutes can be ad-
ministrated, repeated to a maximum of 200
mg, at 10 minutes intervals. Following this,
or as treatment for moderate hypertension, a
labetalol infusion can be commenced (5 mg/
mL at 4 mL/hour via a syringe pump, the infu-
sion rate being doubled every 30 minutes to a
maximum of 32 mL [160 mg]/hour until the BP
has dropped and stabilised at an acceptable
level). Labetalol is contraindicated in women
with asthma and should be used with caution
in cardiac disease.
• Hydralazine is given by bolus infusion (10–20
mg over 10–20 minutes measuring the BP
every 5 minutes). This may be followed by an
infusion (40 mg hydralazine in 40 mL normal
saline, which should run at 1–5 mL/hour [1–5
mg/hour]).
MIMS JPOG 2018 VOL. 44 NO. 3 101
Box 2. Key Points in the Management of the Severe Pre-eclamptic Patient
• Insert an indwelling catheter and measure hourly urine output until stable.
• Record blood pressure and pulse every 15 minutes until stable and then half
hourly.
• Oxygen saturation should be measured continuously and charted with the
BP. If saturation falls below 95% then medical review is essential to rule out
pulmonary oedema and other complications.
• Strict fluid balance should be recorded with detailed input and output
measurements.
• Respiratory rate should be measured hourly. A reducing respiratory rate may
indicate magnesium toxicity.
• Temperature should be measured four hourly.
• 
When present, central venous pressure and arterial lines should be
measured continuously and charted with the BP.
• Neurological assessment should be performed hourly using either the Alert,
Voice, Pain, Unresponsive system, or Glasgow Coma Scale.
• Foetal wellbeing should be monitored using a cardiotocography.
• 
Blood tests should be repeated at least every 12 hours whilst on the
magnesium sulphate protocol. In the event of complications, such as
haemorrhage or abnormal or deteriorating haematological, and/or biochemical
parameters, more frequent blood tests should be taken eg, every 4–8 hours.
In pre-eclampsia, magnesium sulphate is in-
dicated as the first-line anticonvulsant. Formal clin-
ical review should occur every 4 hours, observing
for side effects (motor paralysis, absent reflexes,
respiratory depression, and cardiac arrhythmia).
The antidote is 10 mL of 10% calcium gluconate
given slowly intravenously. About 97% of the mag-
nesium sulphate is excreted in the urine. Oligu-
ria (<80 mL/24 hours) can thus lead to toxicity.
Therefore, in the presence of oliguria, magne-
sium sulphate should be reduced or withheld. If
magnesium is not excreted, levels should not fall.
Box 2 highlights key management steps in the
treatment of patients with severe pre-eclampsia.
CASE 4: MANAGEMENT OF
ECLAMPSIA
You receive an urgent call to attend the emergen-
cy room. A patient has just arrived unbooked.
Her husband tells you she is roughly 7 months
102 MIMS JPOG 2018 VOL. 44 NO. 3
Box 3. Diagnostic Criteria Used for Eclampsia
• Any woman with convulsion(s) during pregnancy or in the first 10 days of
post-partum, together with at least two of the following features within 24
hours of the convulsion(s).
• Hypertension (a booking diastolic pressure of <90 mm Hg, a maximum
diastolic of ≥90 mm Hg, and a diastolic increment of ≥25 mm Hg).
• Proteinuria (at least + protein in a random urine sample or ≥0.3 g in a 24-hour
collection).
• Thrombocytopenia (platelet count of less than 100 x 109/L).
• Raised plasma alanine aminotransferase concentration (≥42 IU/L) or an
increased plasma aspartate aminotransferase concentration (≥42 IU/L).
Practice Points
• Automated BP devices may underestimate the BP in pregnancy and
therefore caution should be exercised in their use. If used, machines
validated for use in pregnancy should be utilised.
• 
An appropriately sized BP cuff should be used. If the mid-arm
circumference is >33 cm, a large cuff should be used.
• 
Labetalol remains the antihypertensive of choice. Methyldopa and
nifedipine may be used as second- or third-line agents.
• Systolic BPs over 150 mm Hg should be treated.
• Anaesthetists should anticipate an additional rise in BP at intubation
in women with severe pre-eclampsia who are undergoing caesarean
section under general anaesthesia and take measures to avoid a speed
that compromises maternal wellbeing, even when there are concerns
about foetal wellbeing.
• If the platelet count is <20 x 109/L, a platelet transfusion is recommended
prior to caesarean section or vaginal delivery.
• A patient with pre-eclampsia should be fluid restricted to ≤80 mls total
fluid/hour until a natural diuresis occurs following delivery.
• Syntometrine should not be given for the active management of the third
stage if the mother is hypertensive, or her blood pressure has not been
checked.
• Postpartum, women should be counselled appropriately regarding their
risk of recurrence of pre-eclampsia, as well as their increased risk of
developing cardiovascular and renal disease.
pregnant in her first pregnancy. She has just ar-
rived in the United Kingdom and is seeking asy-
lum from Congo. Her husband tells you she has
been unwell over the past 3 days and has com-
plained of epigastric pain and blurred vision for
OBSTETRICS PEER REVIEWED
the past day. He reports that she started shaking
1 hour ago and became unresponsive. On ex-
amination, BP is 200/140 mm Hg and the patient
is rigid, with a Glasgow Coma Scale score of 5.
Eclampsia
Eclampsia refers to the occurrence of one or
more generalized convulsions and/or coma
in the setting of pre-eclampsia and in the ab-
sence of other neurological conditions. The UK
Obstetric Surveillance System (UKOSS) report
gives an estimated incidence of 27.5 cases per
100,000 maternities with a case fatality rate es-
timated to be 3.1%. This was almost a halving
of the incidence of eclampsia since 1992. Ec-
lampsia is associated with significant maternal
morbidity, in particular cerebrovascular events
(2.3%) which are now the major cause of death
(previously this was pulmonary oedema). The
benefit of magnesium sulphate in the prevention
of eclampsia has been well demonstrated and
magnesium sulphate has been shown to halve
the risk of eclampsia among women with pre-ec-
lampsia. Box 3 indicates the diagnostic criteria
for eclampsia. Cerebral haemorrhage has been
reported to be the most common cause of death
in patients with eclampsia and stroke is known
to be the most common cause of death (45%) in
women with HELLP syndrome.
The management of this woman will focus
initially on resuscitation, and assessment of foetal
viability. A multidisciplinary team will be required,
with anaesthetic, perinatal, haematological, and
consultant obstetric input. An ABC approach
should be followed in this case, followed by load-
ing with magnesium sulphate, a magnesium sul-
phate infusion, stabilisation, and delivery.
CASE 5: POST-NATAL CARE
A patient presents for post-natal follow-up. She
tells you that she was delivered at 34 weeks’ ges-
tation, 8 weeks ago for severe pre-eclampsia. She
required magnesium sulphate for 24 hours follow-
ing delivery but did not have a seizure. She was
discharged on 200 mg labetalol twice daily.
OBSTETRICS PEER REVIEWED
Post-partum management of
hypertension in pregnancy
BP rises progressively over the first five post-na-
tal days, peaking on days three to six after deliv-
ery. Research has focused on the antenatal com-
plications, for both mother and baby, and the
risks and benefits of administering antihyperten-
sive therapy prior to delivery. There is very little
information on how best to manage post-partum
hypertension, regardless of type or severity, to
optimize maternal safety and minimize hospital
stay. Women with post-partum hypertension may
also experience longer hospital stays and pos-
sibly, heightened anxiety about their recovery.
NICE recommendations for post-natal care of
women with hypertension in pregnancy include
stopping methyldopa within 2 days of birth and
asking the woman about severe headache and
epigastric pain every time BP is measured. In
cases of mild or moderate pre-eclampsia plate-
let count, transaminases and serum creatinine
should be measured 48–72 hours after birth or
step-down. These do not need to be repeated if
results are normal. In most cases of gestational
hypertension and pre-eclampsia, there is a rapid
and complete resolution within 6 weeks of de-
livery of the foetus. Patients requiring antihyper-
tensive agents should be weaned off slowly and
medications should not be stopped suddenly as
there may often be a rebound hypertension.
Long-term risks
Pre-eclampsia also carries implications in adult
life, with offspring of affected pre-eclamptic preg-
nancies demonstrating poor growth in childhood,
and an increased risk of hypertension, heart dis-
ease, and diabetes. Women with pre-eclampsia
have a 3.7 times higher risk of later hypertension,
a 2.2 times increased risk of coronary heart dis-
ease, and a 1.8 times higher risk of stroke.
All women who have had pre-eclamp-
sia should be offered a medical review at the
postnatal review (6–8 weeks) after the birth.
Women who have had pre-eclampsia should
be educated regarding their increased risk of
MIMS JPOG 2018 VOL. 44 NO. 3 103
development of cardiovascular disease, renal
disease, and cardiovascular risk factors for sev-
eral years following pregnancy and regular BP
checks with their general practitioner should be
recommended.
CONCLUSION
Hypertensive disorders are one of the common-
est complications of pregnancy and may be
associated with significant maternal and foetal
morbidity and mortality. Although the aetiology
of these disorders is becoming increasingly bet-
ter understood, interventions to prevent hyper-
tensive disorders of pregnancy have had poor
results. The mainstay of treatment remains the
use of antihypertensive medications, the use of
magnesium sulphate in the prevention of ec-
lampsia, and multidisciplinary input to ensure a
timely delivery.
FURTHER READING
1. Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild
to moderate hypertension during pregnancy. Cochrane Database Syst
Rev, 2007; CD002252.
2. Hypertension in pregnancy. The management of hypertensive disor-
ders during pregnancy. August 2010. National Institute for Health and
Clinical Excellence, www.nice.org.uk/guidance/CG107.
3. Knight M. Eclampsia in the United Kingdom 2005. BJOG 2007;
114:1072–8.
4. Koopmans CM, Bijlenga D, Groen H, et al. Hypitat study group. Induc-
tion of labour versus expectant monitoring for gestational hypertension
or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicen-
tre, open-label randomised controlled trial. Lancet 2009 Sep 19; 374:
979–88.
5. Magee LA, vonDadelszen P, Rey E, et al. Less-tight versus tight control
of hypertension in pregnancy. N Engl J Med 2015 Jan 29; 372: 407–17.
6. Milne F, Redman C, Walker J, et al. The pre-eclampsia community
guideline (PRECOG): how to screen for and detect onset of pre-ec-
lampsia in the community. BMJ 2005 Mar 12; 330: 576–80.
7. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnan-
cies at high risk for preterm preeclampsia. N Engl J Med 2017 Aug 17;
377: 613–22. https://doi.org/10.1056/NEJMoa1704559. Epub 2017 Jun
28. PMID: 28657417.
8. The classification, diagnosis and management of the hypertensive dis-
orders of pregnancy: a revised statement from the ISSHP Pregnancy
Hypertension. Int J Women’s Cardiovasc Health 2014; 4: 97–104. avail-
able at: http://isshp.org/wp-content/uploads/2011/ 08/Revised-state-
ment-ISSHP-2014.pdf.
9. von Dadelszen P, Payne B, Li J, et al. PIERS Study Group. Prediction of
adverse maternal outcomes in pre-eclampsia: development and valida-
tion of the fullPIERS model. Lancet 2011 Jan 15; 377: 219–27.
© 2018 Elsevier Ltd. All rights reserved. Initially published in Obstetrics,
Gynaecology and Reproductive Medicine 2018;28(5):141–147.
About the authors
Roisin Ryan is a master’s student at the London School of Hygiene and
Tropical Medicine and a trainee in Obstetrics and Gynaecology, Ireland.
Conflict of interest: none declared.
Fergus McCarthy is a Senior Lecturer at The Irish Centre for Fetal and Ne-
onatal Translational Research, University College Cork, Consultant in Ob-
stetrics and Gynaecology, Maternal Fetal Medicine Subspecialist at Cork
University Maternity Hospital, Cork, Ireland, and Honorary Clinical Lectur-
er, Department of Women and Children’s Health, School of Life Course
Sciences, King’s College London, UK. Conflict of interest: none declared.
104 MIMS JPOG 2018 VOL. 44 NO. 3 PAEDIATRICS PEER REVIEWED

How can Your Microbiologist

Help you Manage Paediatric
Infection?
Ciara O’Connor B. Ed MB MRCPI MRCPUK MD FRCPath; Richard J Drew MB FRCPI FRCPath DipHIC MD PGDip PID (Oxon)

The presentation of a child to hospital with an acute illness is distressing for the child
and his/her parents or carers. The clinical aim of the admitting paediatric team is to
identify the cause of the illness, to treat it effectively, and to discharge the child home
quickly and safely. Multidisciplinary care between the paediatric and the clinical mi-
crobiology team, who oversee and support the laboratory work of skilled scientists,
is essential to manage paediatric infection. In this review, we will focus on current
diagnostic methods for common paediatric microbiology consultations, with a focus
on newer molecular technology to reduce laboratory turnaround time and discuss
the emergence of multidrug resistant organisms that are impacting on antimicrobial
prescribing practices. We will also highlight useful infection prevention and control
advice that will be beneficial to the on-call paediatrician.

INTRODUCTION that either colonise that site or can read-

In approaching any child with a potential- ily gain access to the site to cause infec-
ly infectious illness, it is worth considering tion, and what are the optimal specimens
the following: (1) what is the likely source to send and can molecular technology
of infection, what are the usual organisms such polymerase chain reaction (PCR)
PAEDIATRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 3 105

Table 1. Classification of Common Organisms Causing Paediatric Diseases

Organisms detected via Gram stain

Typical shape of the organism when Gram stained and viewed under the microscope
Coccus Bacillus Coccobacillus Vibrio
(sphere shaped) (rod shaped) (variable (curved rod/
appearance) comma-shaped)
Gram-positive Staphylococcus spp. Nocardia spp.
Streptococcus spp.a Bacillus spp.
Enterococcus spp. Clostridium spp.
Micrococcus spp. Listeria spp.
Corynebacteria spp.
Gram-negative Kingella spp. Pseudomonas spp. Haemophilus influenzae Vibrio spp.
Neisseria spp. Bordatella spp.
Moraxella spp. Legionella spp.
Stenotrophomonas spp.
Pasteurella spp.
Capnocytophagus spp.
Bacteroides spp.
Fusobacterium spp.
Acinetobacter spp.
Shigella spp.
Campylobacter spp.
Helicobacter pylori
Salmonella spp.
Citrobacter spp.
Enterobacter spp.
Klebsiella spp.
Escherichia coli
Organisms not detected using Gram stain method. If suspect infection due to microorganisms listed below, contact the clinical microbiology
team to discuss local methods of diagnostic testing performed. Samples may be referred to a reference laboratory.
Spirochaetes Treponema spp.
Leptospira spp.
Borrelia spp.
Non-culturable as no cell wall Mycoplasma spp.
Obligate intracellular pathogens Rickettsia spp.
Chlamydia spp.
Coxiella spp.
Special staining process Mycobacteria spp.
performed to detect presence of
acid fast bacilli (AFB)
a
Streptococcus spp. can be classified by their appearance on blood agar after overnight incubation. A greenish appearance on the blood agar plate signifies the presence of
α-haemolytic Streptococcus spp., usually S. pneumoniae or a member of the viridans group, which encapsulates a broad range of Streptococci including S. oralis, S. sanguis,
S. mutans, and S. mitis, which are commensals of the oral cavity and upper respiratory tract. A clear zone of complete haemolysis on the blood agar plate around visible
colonies after an overnight incubation demonstrates the presence of ß-haemolytic Streptococcus spp., which includes Groups A, B, C, G Streptococci.
106 MIMS JPOG 2018 VOL. 44 NO. 3 PAEDIATRICS PEER REVIEWED

Table 2. Topical Antimicrobials carers. Occasionally, conjunctivitis may occur in

Antimicrobial name Organisms covered (in the absence of resistance
mechanisms)
Topical antiviral
Aciclovir Herpes simplex virus
Varicella zoster virus
Topical antibacterials
Chloramphenicol a
Most Gram-positive organisms
Most Gram-negative organisms but no cover for
Pseudomonas spp.
Fusidic acid Staphylococcus aureus
Also has streptococcal activity
a
Most frequently prescribed topical antimicrobial for superficial eye infections as the majority
are caused by Staphylococcus aureus.
be utilised; (2) does the child have any past micro-
biology results and/or is the child colonised with
a multidrug resistant organism (MDRO) that may
limit prescribing practices; (3) is the child poten-
tially harbouring a transmissible organism and if so
what infection prevention and control precautions
do I need to implement pending confirmation; (4)
is prophylaxis needed for parents/carers or staff
who have come into contact with this child; and (5)
is a vaccination or vaccination booster required.
INTERPRETING PRELIMINARY
MICROBIOLOGY RESULTS
Paediatric trainees are often phoned with prelim-
inary results from the microbiology laboratory
describing a Gram stain result. Table 1 is a refer-
ence guide for the common organisms that cause
paediatric infections, divided into Gram-positive
and Gram-negative organisms and those that are
identified by alternative methods.
COMMON PAEDIATRIC
MICROBIOLOGY CONSULTATIONS
The eye
Conjunctivitis is an inflammation of the conjunc-
tiva of either one or both eyes and is frequently
described as “red or sticky eyes” by parents or
association with infection of the cornea (keratocon-
junctivitis) or eyelid (blepharoconjunctivitis). The
most common causes of bacterial conjunctivitis are
Staphylococcus aureus, Streptococcus pneumo-
niae, and Haemophilus influenzae, while the most
common causes of viral conjunctivitis are adenovi-
ruses, herpes simplex virus (HSV)-1/-2, and varicel-
la zoster virus (VZV). Neisseria gonorrhoea, Haemo-
philus parainfluenzae, and Group B Streptococcus
(GBS) can cause infection in the neonatal period.
When conjunctivitis is suspected, eye swabs should
be sent for culture and/or viral PCR analysis. Orbital
cellulitis is an infection of the orbital tissue that can
occur secondary to trauma, surgery, or following
the spread of infection from the paranasal sinuses.
The most common causes of orbital cellulitis are S.
aureus, anaerobes, and various streptococci. Eye
swabs are of limited value in the investigation of or-
bital cellulitis. Intra-operative aspirates from infect-
ed tissues should be sent to the laboratory. Table
2 shows the spectrum of cover of commonly pre-
scribed topical ophthalmic antimicrobials.
The brain and spine
Encephalitis is an inflammatory process in the
brain accompanied by cerebral dysfunction man-
ifesting as an altered level of consciousness. Sei-
zures are common. Encephalitis is predominantly
caused by viruses including VZV, Ebstein Barr virus
(EBV), cytomegalovirus (CMV), HSV-1/-2, and en-
teroviruses. Meningitis is defined as inflammation
of the meninges. From neonates to babies up to
2 months of age, GBS, Escherichia coli, Listeria
monocytogenes, and N. meningitidis are com-
monly isolated. In older children, viral meningitis
is more common than bacterial meningitis. Other
bacterial causes of meningitis include S. pneumo-
niae, N. meningitidis, and H. influenzae type b (Hib),
in unvaccinated children. In taking the child’s his-
tory, it is essential to discuss potential risk factors
for meningitis including the previous diagnosis of
a cerebral tumour, the presence of cerebrospinal
fluid (CSF) shunts or cochlear implants, whether
the child has a meningomyelocele or other spinal
PAEDIATRICS PEER REVIEWED
congenital malformations, and preceding infec-
tions of contiguous sites such as the orbit, para-
nasal sinuses, middle ear cavity, or recent trauma
such as a basilar skull fracture. Chronic meningitis
is defined by the continued signs and symptoms of
meningitis for greater than 4 weeks with abnormal
CSF findings, most commonly caused by Myco-
bacterium tuberculosis. Rare non-infectious caus-
es of meningitis include sarcoid meningitis, post
intravenous immunoglobulin (IVIG) administration,
or treatment with co-trimoxazole or non-steroidal
anti-inflammatories (NSAIDs).
The diagnosis of meningitis is established by
the examination of CSF. It is essential to write on
the request form if a CSF shunt (ventriculo-atrial or
ventriculo-peritoneal) and/or extra ventricular drain
(EVD) are in situ. CSF should be collected into
three or more containers numbered consecutive-
ly. No more than 2 hours should elapse between
CSF collection and laboratory microscopy and cul-
ture as cells can disintegrate rapidly. Never place
a CSF sample in any hospital refrigerator until mi-
croscopy and culture have been performed. Lab-
oratory examination of CSF includes a complete
cell count, differential leucocyte count, and exam-
ination of a Gram stained smear and culture. Nor-
mal CSF values are detailed in Table 3. In-house
testing of CSF using multiplex PCR panels, with
the capability to identify bacteria, viruses and fungi
simultaneously, such as the FilmArray® Meningitis/
Encephalitis (Biomérieux, France), are increasing-
ly utilised. Blood cultures, pharyngeal swabs and
stool specimens should also be sent when menin-
gitis and/or encephalitis are suspected.
The ear
Otitis externa is defined as infection of the exter-
nal auditory canal. Acute localised otitis externa
is usually caused by S. aureus. Acute diffuse otitis
externa, also known as “swimmer’s ear”, is associ-
ated with anaerobes, S. aureus, and Pseudomonas
aeruginosa. Chronic otitis externa can cause by fun-
gi such Candida or Aspergillus species. Malignant
otitis externa is an invasive form of necrotising oti-
tis externa almost always caused by P. aeruginosa.
MIMS JPOG 2018 VOL. 44 NO. 3 107
Otitis media is defined by the coexistence of fluid in
the middle ear and signs and symptoms of acute
illness. It occurs when oropharyngeal flora ascends
the eustachian tube. Typical causative organisms
include S. pneumoniae, H. influenzae, and Morax-
ella catarrhalis. Superficial external ear swabs are
not helpful in the investigation of otitis media unless
there is perforation of the ear drum as ordinary res-
ident or commensal flora will be cultured. Deeper
swabs of pus or exudate from the affected ear are
the most useful laboratory specimens. If a fungal
infection is suspected, scrapings of material from
the ear canal are needed for laboratory culture.
The throat
Pharyngitis or inflammation of the pharynx is usu-
ally caused by viral pathogens. Typical bacterial
pathogens include Group A streptococci (GAS),
also known as S. pyogenes, various Corynebac-
terium spp., and occasionally Fusobacterium nec-
rophorum. Epiglottitis is an inflammation of the
epiglottis characteristically associated with stridor.
Throat swabs should never be taken if there is any
concern for epiglottitis as doing so may precipitate
an acute airway obstruction. Blood cultures should
be sent. Where there is strong suspicion for GAS
infection, an antistreptolysin O titre (ASOT) should
be checked by drawing a blood sample. Tonsillitis
is frequently viral in aetiology. Peritonsillar abscess
or quinsy is a rare bacterial complication of tonsil-
litis where a unilateral collection of pus develops
between the capsule of the palatine tonsil and the
superior constrictor muscle. It is usually associat-
ed with infection by S. anginosus group, GAS, and
F. necrophorum and F. nucleatum. Intra-operative
pus should be sent for culture in the laboratory.
Laryngitis or inflammation of the larynx (voice box)
typically presents with hoarseness and is general-
ly viral in aetiology. When taking throat swabs, al-
ways avoid the tongue and uvula and aim to swab
the tonsillar area and/or posterior pharynx.
The lower respiratory tract
The term lower respiratory tract infection (LRTI)
encompasses a wide spectrum of clinical pres-
108 MIMS JPOG 2018 VOL. 44 NO. 3 PAEDIATRICS PEER REVIEWED

Table 3. Normal CSF Values

Opening pressure Normal opening pressure is 10–20 mm Hg. When measuring opening pressure, the child must be laid on his/her
side and should not be placed sitting upright.
Bacterial meningitis Elevated
Viral meningitis Usually normal
Fungal meningitis Variable
Tuberculous meningitis Variable
Erythrocytes No red blood cells should be present in normal CSFa
Leucocytesb,c Neonates Infants Children
(less 28 days of life) (1 to 12 months old) (older than 1 year)
0–30 cells x 106/L 0–15 cells x 106/L 0–5 cells x 106/L
Protein Neonates Infants Children
(less 28 days of life) (29-56 days of life) (2 months to 18 years old)
0.65–1.5 g/L 0.5–0.9 g/L 0.05–0.35 g/L
Glucose d
Neonates Infants Infants Children
(less 28 days of life) (29-58 days of life) (2-12 months old) (older than 1 year)
1.94–5.55 mmol/L 1.55–5.55 mmol/L 1.94–5.0 g/L 2.22–4.44 g/L

a
The presence of red blood cells (RBCs) in the CSF can result from an intracerebral or subarachnoid haemorrhage (SAH) or from a “traumatic” lumbar puncture (LP), in which
peripheral blood contaminates the CSF. A traumatic tap occurs in approximately 20% of LPs performed. Peripheral blood in the CSF after a “traumatic tap” will result in an
artificial increase in white blood cells (WBCs) by one WBC for every 500–1,000 RBCs in the CSF. This correction factor is accurate as long as the peripheral WBC count is not
extremely high or low. Examine the RBC count from sequential LP samples labelled 1, 2, and 3. Uniform bloodstaining of all samples suggests previous haemorrhage into the
subarachnoid space. Reducing red blood cell counts in sequential CSF samples, with the lowest count in sample 3, suggests bleeding induced by the LP procedure; a “trau-
matic tap”. Remember normal CSF is crystal clear. Xanthochromia is a more reliable predictor of haemorrhage and is present in greater than 90% of patients within 12 hours of
SAH onset. It is a yellow, orange, or pink discoloration of the CSF, caused by the lysis of RBCs resulting in haemoglobin breakdown to oxyhaemoglobin, methaemoglobin, and
bilirubin. Discoloration begins after RBCs have been in spinal fluid for about 2 hours and remains for 2–4 weeks.
b
A leucocyte or WBC: RBC ratio of 1.500–1:1000 is not indicative of infection. CSF obtained more than 12 hours after a CT or MRI brain confirmed intracranial haemorrhage may
show raised WCC counts of up to 500 x 106/L as a consequence of the normal physiological inflammatory response.
c
The CSF polymorph: Lymphocyte ratio is an unreliable with regard to whether meningitis is bacterial, viral, or mycobacterial in origin. This is particularly important in inter-
preting neonatal CSF results or when total leucocyte counts are less than 1000 x 106/L. In viral meningitis, there is a typically a lymphocytic predominance in the CSF, but in the
early course of the disease both neutrophils and lymphocytes can be found. Tuberculous meningitis can be associated with a neutrophil rather than a lymphocytic infiltrate
early in infection. It is important to remember that neutropenic patients may not produce any polymorph or neutrophil response in the CSF and lumbar puncture results should
be correlated with the clinical situation.
d
CSF glucose is normally two thirds of the serum glucose, measured during the preceding 2–4 hours before an LP is performed; can be higher in neonates. This ratio decreases
with increasing serum glucose levels. Bacterial meningitis can cause lowered CSF glucose levels. Glucose levels are usually normal in viral infections. Normal glucose levels
however do not rule out infection, because up to 50% of patients who have bacterial meningitis will have normal CSF glucose levels. A range of non-infectious inflammatory
conditions, SAH, and hypoglycaemia also cause hypoglycorrhachia (low glucose level in CSF).

Adapted from Public Health England, UK Standards for Microbiological Investigations: Investigation of Cerebrospinal Fluid (issue date 31.05.2017). Always check with local
laboratory with regard to cut-off values for CSF analysis. Always rule out any contraindications to performing an acute lumbar puncture before proceeding and if in doubt,
seek senior advice.

entations including pneumonia (inflammation ent greater than 48-hour post-hospitalisation).

of the lung parenchyma), bronchiolitis (infection
of the small airways), lung abscess (where lung
parenchyma is replaced by pus-filled cavities),
and empyema (where pus occupies the pleural
space). When documenting in the child’s medical
notes, the term ‘LRTI’ should be avoided and the
anatomical site of the suspected infection clear-
ly specified. The aetiology of pneumonia and its
management varies as to whether it had been
acquired in the community or nosocomial (pres-
S. pneumoniae accounts for 60% of all cases of
community acquired pneumonia (CAP). In-house
multiplex PCR assays, such as the FilmArray®
Respiratory Panel (Bio-mérieux, France), for the
detection of a wide range of bacteria and virus-
es using nasopharyngeal aspirates or swabs are
now widely used. The sensitivity of expectorated
sputum culture is poor for many pathogens due
to contamination with commensal oropharyngeal
flora and saliva. Early-morning sputum samples
PAEDIATRICS PEER REVIEWED
are preferred as they contain pooled overnight se-
cretions. Bronchoalveolar lavage (BAL) samples
have greater sensitivity and specificity compared
to expectorated sputum. Pertussis, also referred
to as “whooping cough” is a high infectious res-
piratory disease caused by the Gram-negative
organism Bordatella pertussis. Laboratory confir-
mation of clinically suspected pertussis is made
via culture or more commonly DNA detection on
molecular assays using nasopharyngeal aspi-
rates or nasopharyngeal swabs/pernasal swabs.
PCR is increasingly utilised for the diagnosis of
pertussis as it has better sensitivity compared with
culture-based methods. As with all PCR methods,
culture is still necessary in order to perform sus-
ceptibility testing, so it is beneficial to send sam-
ples for culture and PCR testing simultaneously.
The gastrointestinal tract
Peritonitis is inflammation of the peritoneum,
which is the serous membrane lining the abdom-
inal cavity and the abdominal viscera. Primary
bacterial peritonitis, without evidence of intra-ab-
dominal organ perforation, is rare accounting for
less than 1% if all cases of bacterial peritonitis.
It can be seen occasionally in children with ne-
phrotic syndrome. Secondary bacterial peritonitis
arises following gastrointestinal leakage within
the peritoneal cavity following perforation of vis-
cera or abdominal trauma. In paediatrics, second-
ary bacterial peritonitis commonly complicates
the perforation of an acute gangrenous appendix.
Samples of pus collected into sterile containers
are preferred to swab of pus.
The urinary tract
There is a wide spectrum of urinary tract infections
(UTIs) but the two most common presentations
in paediatrics are cystitis (bladder infection) and
acute or chronic pyelonephritis (infection of the
kidney and renal pelvis). Confirmation of a UTI in
a child is dependent on the quality of the speci-
men. Mid-stream urine (MSU) samples and clean-
catch urine specimens are preferred. Bag and pad
urine sampling is discouraged as these are easi-
MIMS JPOG 2018 VOL. 44 NO. 3 109
ly contaminated with the child’s own faecal flora.
The probability of a UTI is increased by the isola-
tion of the same organism from two specimens.
Generally, a pure growth of between 107–108 cfu/L
(104–105 cfu/mL) is indicative of a UTI. E. coli is the
most common organism associated with UTI ac-
counting for nearly 70% of all isolates cultured. It
is worth remembering that the National Institute for
Health and Care Excellence (NICE) guidelines on
the management of UTIs in infants, children, and
young people (under 16 years), published in 2013
and updated 2017, classifies all non-E. coli UTIs as
“atypical infections” and additional investigations
are warranted. Microscopy for the presence of red
cells, white cells, casts, cellular components, and
bacteria is performed in the laboratory. Chromog-
enic agar plates, which allow the rapid identifica-
tion of bacteria present after overnight incubation,
based on a defined colour scheme of colonial
growth, are increasing in popularity and help to
guide empiric treatment pending final culture
results.
The skin and soft tissues
The key to a rapid diagnosis of skin and soft tis-
sue infection is a thorough history. When the skin
is broken and infection ensues, it is important to
know if there is a history of underlying skin disorder
such as psoriasis, eczema, or recurrent furuncles/
carbuncles, whether there was preceding trauma
(indoor or outdoor), burn, bite (human, animal, in-
sect), recent swimming pool/freshwater/saltwater
exposure, recent foreign travel, recent surgical pro-
cedure/wounds, and parental/carer occupation as
healthcare worker exposure can increase the risk
of colonisation with methicillin-resistant S. aureus
(MRSA). The majority of skin/soft tissue infections
are due to S. aureus and the beta-haemolytic strep-
tococci groups A, C, G, and B.
The bones and joints
Osteomyelitis is infection resulting in inflammation
of bone. Common causative organisms include S.
aureus, coagulase negative staphylococci (CoNS)
and Enterococcus species. Osteomyelitis asso-
110 MIMS JPOG 2018 VOL. 44 NO. 3 PAEDIATRICS PEER REVIEWED

Table 4. Commonly Prescribed Beta-Lactam Antimicrobials and Their Potential Spectrum of Cover – Not all Susceptible
Organisms are Listed

Always discuss with your local laboratory regarding resistance patterns, review past microbiology results if available and follow
empiric antimicrobial guidelines in your hospital. Susceptibility of an organism to an antimicrobial does not infer that it is the best
treatment option; always consider the anatomical site of infection.

Antimicrobial(s) Route Clinical use Commonly reported

side effectsc
Gram-positive cover Gram-negative cover

Penicillin-based Benzylpenicillin lVa Streptococcus pneumoniae Neisseria meningitidis Allergic reactions in <10%
antimicrobialse (penicillin G), Beta-haemolytic streptococci (not covered by penicillin V) exposed eg, urticaria,
(A, B, C, G) maculopapular rash
(especially with glandular
Phenoxymethyl- POb fever). Angioedema and
penicillin anaphylaxis rare (0.004
(penicillin V) –0.4%)
GI – diarrhoea, nausea,
Amoxicillin, lV, PO vomiting (2–5%)
Streptococcus pneumoniae
Escherichia coli Renal – interstitial
Ampicillin Beta-haemolytic streptococci
(only 30–60% cover) nephritis, haemorrhagic
(A, B, C, G)
Helicobacter pylori cystitis
Clostridium perfringens
(never as monotherapy Liver – elevated
Enterococcus faecalis
– usually triple therapy) transaminases. Highest
Listeria monocytogenes
risks with co-amoxiclav
(always IV treatment)
and flucloxacillin
CNS – encephalopathy or
Flucloxacillin lV, PO MSSA No cover for Gram-negatives
seizures can rarely occur
Beta-haemolytic streptococci
in renal failure or if very
(A, B, C, G)
high doses of penicillin
is used
Co-amoxiclav lV, PO Streptococcus pneumoniae Escherichia coli
Beta-haemolytic streptococci Klebsiella spp.
(A, B, C, G) Proteus spp.
Clostridium perfringens Anaerobes
MSSA

Piperacillin lV Streptococcus pneumoniae Escherichia coli

-tazobactam Beta-haemolytic Klebsiella spp.
streptococci (A, B, C, G) Proteus spp.
MSSA Anaerobes
Clostridium perfringens Pseudomonas spp.d
Enterococcus faecalis

Aztreonam Aztreonam lV No cover for Gram-positives Escherichia coli

Klebsiella spp.
Proteus spp.
Pseudomonas spp.
(not all are sensitive)

ciated with water exposure increases the risk of upper respiratory tract infection (URTI). Radio-
infection with P. aeruginosa, sickle cell disease is logically obtained percutaneous bone biopsies
associated with Salmonella species and Kingella or intra-operative bone biopsies are the preferred
kingae can cause bone and joint infections after specimens for culture or molecular analysis. Septic
PAEDIATRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 3 111

Table 4. Commonly Prescribed Beta-Lactam Antimicrobials and Their Potential Spectrum of Cover – Not all Susceptible
Organisms are Listed (continued )

Always discuss with your local laboratory regarding resistance patterns, review past microbiology results if available and follow
empiric antimicrobial guidelines in your hospital. Susceptibility of an organism to an antimicrobial does not infer that it is the best
treatment option; always consider the anatomical site of infection.

Antimicrobial(s) Clinical use Commonly reported side

Route effectsc
Gram-positive cover Gram-negative cover

Carbapenems Meropenem lV MSSA Moraxella catarrhalis GI – nausea, vomiting,

Streptococcus Neisseria meningitidis diarrhoea
pneumoniae Enterobacteriaceae Liver – elevated
Beta-haemolytic Acinetobacter spp. transaminases
streptococci (A, B, C, G) Pseudomonas Blood dyscrasias –
Viridans streptococci aeruginosa thrombocytopenia,
Listeria monocytogenes Anaerobes leucopenia
Haemophilus spp. CNS – increased risk of
seizure activity if
Ertapenem lV MSSA Haemophilus spp. concurrent
Streptococcus Anaerobes renal impairment.
pneumoniae Enterobacteriaceae Meropenem
also interacts with
Viridans streptococci (but not
sodium valproate
Beta-haemolytic Pseudomonas
Skin – rarely Stevens-
streptococci (A, B, C, G) aeruginosa Johnson syndrome
or Acinteobacter spp.) (SJS), toxic
epidermal necrolysis (TEN)

Cephalosporins

1st Generation 2nd Generation 3rd Generation 3rd Generation

eg, Cefalexin (PO only) eg, Cefuroxime eg, Ceftazidime eg, Ceftriaxone,
Enterococci (IV, available PO but poor (IV) cefotaxime (IV)
are inherently bioavailability in liquid format)
resistant to
cephalosporins Gram-positive Gram-negative Gram-positive Gram-negative Gram-negative Gram-positive Gram-negative
cover cover cover cover cover cover cover
Streptococcus Klebsiella spp. Streptococcus Proteus spp. Proteus spp. Streptococcus Escherichia
pneumoniae Escherichia pneumoniae Klebsiella spp. Klebsiella spp. pneumoniae coli
Group A, B coli Group A, B Escherichia coli Escherichia Group A, B Haemophilus
streptococci streptococci Haemophilus coli streptococci spp.
MSSA Viridans spp. Pseudomonas MSSA Neisseria
streptococci Moraxella spp. Spirochaetes meningitidis
MSSA catarrhalis Borrelia Neisseria
burgdorferi gonorrhoea
(Ceftriaxone
only)
Proteus spp.
Klebsiella spp.

Abbrevition: MSSA = methicillin-sensitive Staphylococcus aureus

a
IV = intravenous route of administration.
b
PO = oral route of administration.
c
Side effect profile similar for penicillins and cephalosporins.
d
Meropenem, piperacillin-tazobactam. Pseudomonas species are usually susceptible to meropenem and piperacillin-tazobactam.
e
5% of patients with an allergy to penicillin-based antimicrobials will also be allergic to cephalosporins. Up to 10% of patients with an allergy to penicillin-based
antimicrobials will also be allergic to carbapenems.
112 MIMS JPOG 2018 VOL. 44 NO. 3
Table 5. Managing Infectious Pathogens
Syndrome
Central nervous system
Respiratory
Gastroenteritis
Systemic viral illness
Group A Streptococcus
Resistant organisms
a
Human Herpesvirus Type 6.
Adapted from Siegel JD, Rhinehart E, Jackson M, Chiarello L, and the Healthcare Infection Control Practices Advisory Committee, 2007 Guideline for Isolation Precautions:
Preventing Transmission of Infectious Agents in Healthcare Settings. Updated February 2017. Available at: https://www.cdc.gov/infectioncontrol/guidelines/isolation/.
Always refer to local guidelines and contact the infection prevention and control team if any queries.
PAEDIATRICS PEER REVIEWED
Diagnosis Does the child need to be isolated, and if so, for how
long should the child be isolated for?
Meningococcus Remove from isolation once the patient has had 24 hours
Pneumococcus of IV antibiotics
Haemophilus influenzae
Unidentified bacterial meningitis
Group B Streptococcus The child does not need to be isolated
Escherichia coli
Enterovirus For the duration of the admission, the child should
Parechovirus be isolated
VZV Isolate until all the lesions have been crusted over and
the patient is afebrile
HSV The child does not need to be isolated
a
HHV-6 Isolate until the patient is at least 48 hours afebrile
Bronchiolitis Isolate until the patient is 48 hours asymptomatic
Bacterial pneumonia Remove from isolation once has had 24 hours of IV
antimicrobials
Pertussis Isolate until 24 hours after the 5th (final) dose of
azithromycin
Viral pneumonia Isolate until the patient is 48 hours afebrile
TB Discuss with infectious diseases team and/or infection
control
Bacterial (Salmonella spp., Shigella spp., Discuss with infection control or microbiology
Campylobacter spp., Escherichia coli O157)
Viral (Rotavirus, Adenovirus) Isolate until the patient is 48 hours asymptomatic
Clostridium difficile
Infective gastroenteritis (? cause)
Parvovirus Maintain precautions for duration of hospitalisation
when chronic disease occurs in an immunocompromised
patient. For patients with transient aplastic crisis or
red-cell crisis, maintain precautions for 7 days
Measles Isolate until 4 days after onset of rash
Mumps Isolate until 9 days after onset of swelling
Enterovirus Discuss with infection control or microbiology
Varicella Isolate until all the lesions have crusted over
Tonsillitis, pneumonia, or post-varicella infection Remove from isolation once the patient has had
24 hours of IV antibiotics
MRSA Discuss with infection control
VRE/ESBL/CPE
PAEDIATRICS PEER REVIEWED
arthritis is a pyogenic infection of a joint. Infection
occurs via a haematogenous spread or directly
from contiguous lesions. Any organism can be iso-
late from aspirated joint fluid, but S. aureus is the
commonest. Skin wounds are the most likely por-
tals of entry of infection and again S. aureus is the
most common isolate. All types of sterile fluid can
be cultured. Broad range 16S (bacterial PCR) and
18S PCR (fungal PCR) can be utilised in certain
circumstances in the diagnosis of culture-negative
bone and joint samples. To increase the diagnostic
yield from culture, it is recommended to perform a
joint aspirate off antimicrobials if possible, particu-
larly when chronic osteomyelitis is suspected.
Possible mycobacterial infections
Tuberculosis or (TB) is caused by members of the
M. tuberculosis complex (MTBC), most common-
ly M. tuberculosis, and M. bovis. Consideration
should always be given to TB in any child with
exposure to a TB endemic area, family members
with confirmed TB, and any child living in socio-
economic circumstances associated with over-
crowding, homelessness, and poverty. Nontuber-
culous mycobacteria (NTM) are also increasingly
encountered as a cause of disease. One of the
most common NTM species is M. marinum as-
sociated with a localized skin lesion, commonly
referred to as a “fish tank” or “swimming pool”
granuloma, following contamination of an open
wound or an abrasion with water from fish tanks,
swimming pools, and natural areas of fresh or salt
water. Another NTM, M. abscessus, is now regard-
ed as an infection to be considered in all patients
with cystic fibrosis, in the context of declining lung
function and poor response to standard therapies.
Where there is clinical suspicion for mycobacterial
infection, many specimens are suitable for testing
including fluid from sterile body sites (CSF, pleu-
ral fluid, ascites, joint fluid), skin or tissue biopsies,
bone marrow, BAL washings, blood, sputum, and
gastric washings. The most important tool in the
diagnosis of tuberculosis is direct microscopic
examination of appropriately stained specimens
for acid-fast bacilli (AFB) using an auramine stain.
MIMS JPOG 2018 VOL. 44 NO. 3 113
Following auramine staining, and regardless of
whether AFB are detected or not, all specimens
are referred to the laboratory for mycobacterial cul-
ture for up to 8 weeks. Molecular techniques using
real-time PCR have substantially changed the field
of tuberculosis diagnosis and have been proven to
yield rapid results while being highly sensitive. The
GeneXpert® (Cepheid, USA) test is now one of the
most widely used PCR assays worldwide, which
can both diagnose TB and also test for resistance
to the drug rifampicin, which forms part of the first-
line drug treatment for TB.
ANTIMICROBIAL RESISTANCE,
MULTIDRUG RESISTANT ORGANISMS,
AND STEWARDSHIP
Multidrug resistant Gram-negative bacteria
(MDRGNB) are defined as having three or more
antimicrobial resistance mechanisms affecting
different classes of antimicrobials. Opportunistic
Gram-negative bacteria that present increasing re-
sistance issues include E. coli, Klebsiella spp., En-
terobacter spp., Serratia spp., Citrobacter spp., P.
aeruginosa, and A. baumannii. MDRGNBs colonise
the human gut asymptomatically, creating a reser-
voir for transfer to other body sites and to other
patients. Much concern has been raised over the
past decade regarding carbapenemase-produc-
ing Enterobacteriaceae (CPE), also known as car-
bapenemase-resistant Enterobacteriaceae (CRE),
which confer resistance to carbapenem antimicro-
bials, for example meropenem or ertapenem. The
acquisition of extended-spectrum beta-lactamase
(ESBL)-producing enzymes in Gram-negative or-
ganisms confers the ability to hydrolyse penicillins,
cephalosporins, and aztrenoam. Genes for ES-
BLs are also frequently encoded on transferable
plasmids, that encode resistance genes for other
classes of antimicrobials, such as beta-lactams,
fluoroquinolones, aminoglycosides, and sulpho-
namides, and as a consequence, ESBL-produc-
ing organisms are frequently resistant to multiple
classes of antimicrobials. With regard to Gram-pos-
itive MDROs, the incidence of vancomycin-resist-
ance Enterococci (VRE) and community-acquired
114 MIMS JPOG 2018 VOL. 44 NO. 3
Practice Points
• In the management of paediatric infection, the guidance of a clinical
microbiologist can be helpful in identifying laboratory diagnostic methods
to expedite a child’s diagnosis and subsequently advising regarding
switching from empiric to directed antimicrobial therapy if indicated.
• A thorough history is essential to the aid the diagnosis of infection.
• Preventing the onward transmission of infectious diseases is paramount
to protecting the safety of all hospital staff.
• Always prescribe the most narrow-spectrum antimicrobial(s) possible to
reduce the risk of adverse events and the potential for the development of
antimicrobial resistance.
• The need for prophylaxis and vaccination is easily forgotten but is crucial
to the safe management of some infectious presentations.
strains of methicillin-resistant S. aureus (CA-MRSA)
are increasing. MRSA is the only MDRO for which
a decolonisation regimen is available, affording the
potential to clear colonisation. VRE, CPE/CRE, and
ESBLs are all associated with gut carriage, which
may or may not spontaneously clear with the pas-
sage of time, but in practice, children with repeated
antimicrobial and hospital exposure are unlikely to
lose carriage of these MDROs. Table 4 demon-
strates the common organisms covered by each
type of beta-lactam antimicrobial.
INFECTION PREVENTION AND
CONTROL ESSENTIALS FOR THE
PAEDIATRICIAN ON-CALL
All paediatric staff have a vital part to play in the
prevention of onward transmission of infection,
particularly outside of routine hours, when on-call,
staffing numbers are often low, and availability of
beds can become an issue. The isolation times of
common infectious paediatric pathogens are listed
in Table 5. This should be seen as only a guideline
and every child should be judged on a case-by-
case basis.
IS ANTIBIOTIC PROPHYLAXIS
NEEDED?
When the diagnosis of either meningococcal
meningitis or pertussis is made always remember
PAEDIATRICS PEER REVIEWED
to consider the need for prophylaxis for parents/
carers of the child. In the UK, local occupational
health teams will usually support paediatricians
and where necessary arrange prophylaxis for staff.
Neonatologists must be particularly aware of the
risk of GAS when invasive disease occurs in either
mothers or their babies within 30 days of delivery.
These cases should be discussed on a case-by-
case basis with a consultant staff.
IS A “NON-ROUTINE” VACCINATION
NEEDED?
Vaccination or booster vaccination for protection
against rabies (bat exposure, dog or cat bites)
and tetanus (environmental wound contamina-
tion) may occasionally be required. It is advisable
to check local policies and to administer as soon
as possible.
FURTHER READING
1. Public Health England, UK standards for microbiological investiga-
tions. Available at: https://www.gov.uk/government/collections/stand-
ards-for-microbiology-investigations-smi.
- Investigation of Specimens for Screening for MRSA. Issue date 03.04.2014
- Investigation of Cerebrospinal Fluid. Issue date 31.05.2017
- Investigation of specimens for Mycobacterium species. Issue date
10.01.2017
- Investigation of Ear Infections and Associated Specimens. Issue date
04.06.2014
- Investigation of Bacterial Eye Infections. Issue date 04.05.2017
- Culture of specimens for Bordatella pertussis and Bordatella paraper-
tussis. Issue date 10.11.2014
- Investigation of Throat Related Specimens. Issue date 15.04.2015
- Investigation of Fluids from Normally Sterile Sites. Issue date
08.03.2017
- Investigation of Viral Encephalitis. Issue date 16.04.2014
- Investigation of bronchoalveolar lavage, sputum and associated spec-
imens. Issue date 24.08.2017
- Investigation of bone and soft tissue associated with osteomyelitis.
Issue date 14.12.2015
- Investigation of urine. Issue date 16.08.2017
2. Report of the Cystic Fibrosis Trust of the Mycobacterium abscessus
Infection Control Working Group. Cystic Fibrosis Trust. Mycobacterium
abscessus-Suggestions for infection prevention and control. (Interim
guidance – October 2013). Available at: https://www. cysticfibrosis.org.
uk/the-work-we-do/clinical-care/consensus-documents.
3. Sandford guide to antimicrobial therapy. 44th Edn. Virginia, USA: Antimi-
crobial Therapy Inc., 2014.
4. U.S Department of Health and Human Services. Centers for Disease Con-
trol and Prevention (CDC). Antibiotic resistance threats in the US 2013.
Available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/
ar-threats-2013-508.pdf.
5. Wilson AP, Livermore DM, Otter JA, et al. Prevention and control of mul-
tidrug-resistant gram-negative bacteria: recommendations from a joint
working party. J Hosp Infect 2016; 92(suppl 1): S1–44.
© 2018 Elsevier Ltd. All rights reserved. Initially published in Paediatrics and
Child Health 2018;28(6):254–262.
About the authors
Ciara O’Connor is a Clinical Microbiology Specialist Registrar in the Depart-
ment of Clinical Microbiology, Temple Street Children’s University Hospital,
Dublin 1, Ireland.
Richard J Drew is a Consultant Microbiologist in the Department of Clinical
Microbiology, Temple Street Children's University Hospital, Dublin 1 and in
the Department of Microbiology, Royal College of Surgeons in Ireland.
GYNAECOLOGY PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 3 115

Management of Urinary
Incontinence in Frail
Elderly Women
Gabrielle Prud’homme BMBS; Leanne Alexander MBChB (Hons) BA (Hons) MRCP DGM; Susan Orme BMBS (Hons) BMedSci FRCP

Urinary incontinence (UI) is defined by the International Continence Society as

any involuntary leakage of urine. It is a common clinical problem, and its incidence
increases with age. It is a particular problem in the frail elderly, who can sometimes pose
a diagnostic and therapeutic challenge by virtue of their complexity. UI is a major cause
of disability and dependency, and adversely affects the psychological and physical
health of the older person. However, treatment can lead to significant improvements.

INTRODUCTION
Estimations of UI prevalence vary according to the definitions used but is thought to
be around 15–30% in the ambulant community dwelling elderly, rising between 50 and
80% among those in long-term care.
Normal ageing is not a cause of urinary incontinence, although age-related chang-
es in lower urinary tract function can predispose older people to UI which is then exac-
erbated by comorbidities. UI is a major cause of disability and dependency, significantly
increasing the risk of care home placement and adversely affecting the psychological,
physical, and social wellbeing of older people. It also predisposes to carer negativity
and stress, which itself is a major factor in placement for institutional care.
116 MIMS JPOG 2018 VOL. 44 NO. 3 GYNAECOLOGY PEER REVIEWED

Table 1. Conditions Contributing to Urinary Incontinence

Condition Type of incontinence Notes

Dementia Urge incontinence Causes UI by variety of mechanisms:
Functional incontinence a) Decreased motivation and initiative to go to the toilet
b) Social disinhibition
c) Decreased executive function
d) Immobility or gait disturbance
e) Severe autonomic failure (Lewy Body Dementia)
Stroke Urge incontinence Varying effects on bladder and bowel function, mobility and functional
Functional incontinence ability to toilet
Occasionally urinary retention UI post stroke often improves over time
Poor prognostic indicator for those in whom it persists
Parkinson’s Functional incontinence Also, autonomic failure in “Parkinson’s Plus” syndromes
disease Urge incontinence
Delirium Delirium can be associated with detrusor underactivity or bladder outflow
obstruction causing urinary retention (“cystocerebral syndrome”) as well
as infection causing UI.
Normal pressure Incontinence, gait, and cognitive deficits
hydrocephalus Potentially reversible with VP shunt
Anxiety and Can result from incontinence
depression Less motivation to stay continent
Can also cause mildly impaired cognition
Arthritis Functional incontinence
Urge incontinence
Diabetes Functional incontinence Polyuria in poorly controlled DM
Peripheral neuropathy
Autonomic neuropathy
Increased susceptibility to UTI
Peripheral oedema Nocturia Reabsorption of peripheral oedema causing increased circulating
(Heart failure, venous Nocturnal polyuria volume and increased nocturnal urine production.
insufficiency, Nocturnal enuresis Increased ANP levels secondary to myocardial stretch from increased
circulating volume may also contribute to increased nocturnal urine
medications)
production.
Constipation and Combined faecal and urinary incontinence Outflow tract obstruction causing urge incontinence from detrusor
faecal impaction Urge incontinence overactivity. Straining can result in weakened pelvic floor muscles.
Urinary retention
COPD Stress incontinence Cough can exacerbate stress incontinence

The frail elderly has traditionally been under
treated due to fears over the side effects of the med-
ications, under reporting of symptoms, and low ex-
pectations of treatment outcomes by both patients
and doctors. However, significant improvements
can be achieved with correct assessment and treat-
ment. The following forms a framework to aid the
management of this challenging group of patients.
PREVALENCE
A 1993 MORI poll in the UK showed a lifetime prev-
alence of UI at all ages of 6.6% in men, and 14%
in women with approximately 3.9 million sufferers
in the UK alone. Prevalence continues to increase
as a consequence of an ageing population with re-
source implications for the NHS and social care.
The true prevalence of UI is difficult to accurately
estimate as many sufferers never seek treatment
due to embarrassment, lack of awareness of treat-
ment options, and the myth that UI is a normal con-
sequence of ageing.
Estimations also vary widely according to
the definition used, but a review of the literature
suggests a prevalence of 15–30% for community
dwelling older people. All studies report a higher
incidence of UI among care home residents in the
GYNAECOLOGY PEER REVIEWED
range of 50–80% because UI are associated with
older age, frailty, cognitive impairment, and limited
mobility leading to a greater level of dependency.
All of these factors are more prevalent amongst
those in long-term care.
The severity of UI has been defined in various
ways, but mostly according to the frequency of
urine loss. The general prevalence of severe urinary
incontinence (weekly or more) in all age groups is
thought to be between 3 and 7%. The Newcastle
85+ cohort study in 2009 reported an overall inci-
dence of severe UI in 21%, commoner in women.
ASSOCIATED FACTORS
UI is associated with other comorbidities and can
contribute significantly towards declining functional
status and poor quality of life. It is also associated
with substantially increased risk of admission to 24-
hour care. Incontinence in this context may be func-
tional and treatment should be modified according-
ly. A list of some of the major conditions contributing
to UI can be found in Table 1. Appropriate treatment
of the conditions listed is a necessary part of conti-
nence management in this patient group.
The more common medications associated
with exacerbations of UI are listed in Box 1. In particu-
lar, diuretics increase the volume of urine produced.
Changing to a loop diuretic with a longer half-life
such as torasemide can make some improvement
in incontinence associated with diuretic timing.
Medication review is therefore essential with
particular reference to drugs that contribute towards
incomplete bladder emptying or cause constipation.
CONDITIONS CAUSED BY URINARY
INCONTINENCE
UI is generally thought to be a predictor of adverse
outcomes in older people. Those with UI have a
greater mortality, but generally also have more
significant comorbidities, which may partly explain
this association. There is no universally agreed
definition of frailty, but it is thought of as a multisys-
tem syndrome of impaired mobility, fatigue, mus-
cle strength, and balance. Common conditions
caused by UI are listed in Table 2.
MIMS JPOG 2018 VOL. 44 NO. 3 117
Box 1. Drugs that Cause or Exacerbate Urinary Incontinence
• Alcohol
• Alpha adrenergic agonists (eg, midodrine, pseudoephedrine)
• Alpha blockers (eg, doxazosin, tamsulosin)
• ACE inhibitors (eg, ramipril, lisinopril)
• Caffeine
• Cholinesterase inhibitors (eg, donepezil, rivastigmine)
• Diuretics (eg, bendrofluazide, furosemide, bumetanide)
• Anticholinergic drugs
• Oral oestrogen therapies (eg, HRT)
• Opioids (eg, codeine, morphine, tramadol)
• Sedatives and hypnotics (eg, benzodiazepines, zopiclone)
HOW IS CONTINENCE MAINTAINED?
Maintaining continence is a complex process, and
depends on:
1. An intact bladder, sphincter, and pelvic floor
function with normal innervation.
2. An ability to communicate the need to go to the
toilet if immobile.
3. Adequate cognition to know how to find the toi-
let and to keep continence until on the toilet.
4. 
Sufficient mobility and manual dexterity to
remove clothing.
5. 
Ability to voluntarily initiate micturition at the
appropriate time.
The frontal cortex is responsible for voluntary
control of micturition with the sensation of a full
bladder as well as external sphincter contraction
and relaxation. The motor cortex controls bladder
motor function, as well as the ability to mobilize to
the toilet, bypassing any environmental hazards
en route. All of these processes can be affected by
intercurrent illness.
AGE-RELATED CHANGES AFFECTING
THE URINARY TRACT
Multiple age-related changes occur in the lower uri-
nary tract as well as age-associated comorbidities
that are linked with UI.
Bladder changes
Collagen deposition within the bladder wall results
in a reduction in functional bladder capacity and
118 MIMS JPOG 2018 VOL. 44 NO. 3
Table 2. Conditions Caused by Urinary Incontinence
Condition Notes
Depression Also reduced quality of life and social isolation.
and anxiety
Falls and Falls and fractures can result from UI, especially
fractures UUI and OAB.
Nocturia Nocturia can result in daytime sleepiness, and
have an adverse effect on cognition. It is associated
with an increased falls risk between 10% and 21%
with two or more voids per night, as well as an
increased fracture risk and nocturnal enuresis.
Pressure areas UI is an important feature in the development of
pressure areas, and slows their healing. Can also
cause skin rashes and dermatitis.
Urinary tract UTI is associated with chronic urinary retention, as
infection well as indwelling catheters and condom drainage
systems.
lower urinary flow rates through a reduction in blad-
der elasticity. Decreased innervation results in less
cholinergic transmission and a reduced sensation
of bladder filling so that the first sensation of need-
ing to void is closer to the functional bladder ca-
pacity, giving less time to get to the toilet, and void
appropriately.
Residual volume
A residual volume of more than 100 mL is indic-
ative of incomplete bladder emptying in younger
person but in the elderly up to 200 mL can be con-
sidered normal. Very large residual volumes (>300
mL) are associated with increased risk of upper
urinary tract dilation and renal impairment.
Urethral changes
Ageing results in increased collagen deposition
in the urethra and loss of circular smooth muscle
in the urethral sphincter. This results in decreased
urethral closing pressure.
Vaginal changes
Post-menopausal atrophy can cause loss of lactoba-
cilli leading to colonization with pathogens such as
E. coli, enterococci, etc, as well as atrophic vaginitis.
GYNAECOLOGY PEER REVIEWED
Other changes
Ageing causes reduced pituitary production of an-
tidiuretic hormone (ADH) reducing urine-concen-
trating ability. Nocturia is also more common due to
reversed diurnal urine production through increased
production of atrial natriuretic peptide (ANP). This
acts on the kidney to produce greater volumes of
more dilute urine at night. Nocturnal urine production
can also be increased by peripheral oedema re-en-
tering the circulation at night whilst lying in bed.
Changes in the immune system related to age
can lead to an increased likelihood of UTI. Practical
problems with maintaining anal and vulval hygiene
may also contribute.
WHAT ARE THE SYMPTOMS AND
SUBTYPES OF UI?
Overactive bladder
Overactive bladder (OAB) is defined as urgen-
cy that occurs with or without urge UI, usually with
frequency and nocturia and in the absence of other
pathology. OAB that occurs with urge UI is known as
“OAB wet”. OAB that occurs without urge UI is known
as “OAB dry”. OAB is the most common cause of UI
in the elderly. In the elderly, these are most common-
ly cerebrovascular or neurodegenerative in origin.
Several studies have reported a link between larger
numbers of white matter lesions and worsening ur-
gency urinary incontinence (UUI) symptoms.
Stress incontinence
Stress urinary incontinence (SUI) is the com-
plaint of involuntary leakage of small amounts of
urine on effort or exertion, sneezing, or coughing.
It is more common after the menopause.
Incontinence due to incomplete bladder
emptying
Is usually secondary to an underactive bladder, or
a bladder outflow obstruction, and tends to cause
a continuous loss of small amounts of urine. Caus-
es include spinal cord lesions (MS, cord compres-
sion), peripheral nerve lesions (eg, diabetic neu-
ropathies), and constipation. Constipation is the
GYNAECOLOGY PEER REVIEWED
most prevalent cause of this in hospital inpatients
and long-term care settings.
Mixed incontinence
This is a combination of OAB and SUI symptoms.
Treatment initially should be aimed at the predom-
inant symptom.
Functional incontinence
Functional incontinence is a general term to de-
scribe the factors outside the lower urinary tract that
contribute to UI, including mobility, environmen-
tal factors, medications, and other comorbidities.
There are a variety of ways to manage mobility and
continence that are discussed later in this article.
Nocturia
The International Continence Society defines noc-
turia as having to wake one or more times to void
urine at night. Nocturnal polyuria is defined as pro-
ducing more than 35% of total daily urine output
at night. Incidence increases with age and usually
50% men and women over the age of 60 will have
nocturia. By the age of 80, the majority of women
will have symptoms.
ASSESSMENT OF FRAIL OLDER
PATIENTS WITH URINARY
INCONTINENCE
History
A comprehensive history is the most important
part of any assessment of a frail older patient and
should include a thorough assessment of function-
al ability and social circumstances in order to en-
able comprehensive holistic management (Box 2).
In patients with cognitive impairment, some history
should be elicited from the carer if possible.
Examination
See Box 3.
Investigation
Investigations should include baseline blood
tests as well as a bladder diary. NICE guidelines
MIMS JPOG 2018 VOL. 44 NO. 3 119
Box 2. History Taking
Urinary symptoms
• Storage – any urgency, frequency, or nocturia symptoms
• What is the flow of urine like?
• Any urinary leakage, amount lost, and its precipitants
• Distress caused and current coping strategies
• Haematuria/UTI symptoms?
Bowels
• Constipation symptoms? Is the patient taking any treatment for this?
• Straining (can weaken pelvic floor muscles)
• Presence and frequency of any faecal incontinence
Fluid intake
• Caffeine intake
• Alcohol intake
• Volume and timing of drinks in comparison to symptoms
PMHx
• Previous urological/renal problems, haematuria, or recurrent UTI
• Previous pelvic surgery
• Details of pregnancies, mode of delivery, and birth weight of children
• Other comorbidities contributing to UI
• Any cognitive impairment?
DHx
• Sedatives and hypnotics
• Antimuscarinics
• Diuretics and timing of diuretics
• Constipating medications (opiates, calcium channel blockers)
SHx
• General functional status and ability to perform activities of daily living
• Mobility
• Access to toilets/continence aids
• Impact on quality of life – incontinence questionnaire (ICIQ)
• Availability of carers around timing of symptoms
recommend the use of bladder diaries over a
minimum of 3 days in order to initially assess
anyone with UI. Fluid intake, voiding times and
quantities, and episodes of urinary incontinence
are recorded. This can be done either by the pa-
tient or a carer and is a useful tool in identifying
the cause of the UI but it is not always possible to
achieve in the frail. In the setting of severe cog-
nitive or functional impairment, a modified diary
where the number of voids, episodes of UI and
number of drinks consumed gives some useful
information.
120 MIMS JPOG 2018 VOL. 44 NO. 3
Box 3. Examination
• Record BMI
• Assess general mobility
• Test for cognitive impairment with AMT. If score <8/10, consider MMSE
(score <27 is abnormal)
• Abdominal examination and PR
• External genitalia
• PV examination if indicated
•  eurological exam – especially legs and for signs of unrecognized
N wipes paying attention to adequate drying. Advise
Parkinsonism
Box 4. Reversible Causes of Urinary Incontinence
• Constipation
• Metabolic disturbance (eg, hypercalcaemia, and hyperglycaemia)
• Urinary tract infection
• Delirium and acute confusional states
• Atrophic vaginitis
• Medications (see Box 1)
• Restricted mobility
Urinalysis and a post-void bladder scan are
also indicated.
Specialist investigation
Urodynamics: Frail older women may be considered
more suitable for conservative management and so
urodynamics may be unnecessary. A functional as-
sessment of walking and undressing will usually be
of more diagnostic value in this patient group.
Management
General measures and lifestyle modifications:
The management of UI requires a multidisciplinary
approach. This is of particular importance in the frail.
National guidelines such as the NICE guidelines for
the management of UI tend to focus on younger
fitter patients, although recommendations are now
included for frailer adults. NICE clinical guidelines
on UI in neurological disease focus on incontinence
in patients with multiple sclerosis, Parkinson’s dis-
ease, dementia, and stroke which may be applica-
ble to some of the frail elderly patients.
GYNAECOLOGY PEER REVIEWED
Factors such as the aetiology of incontinence,
mobility, comorbidities, anaesthetic risk, potential side
effects, and patient choice all need to be considered.
Conservative measures: Certain conservative
measures apply to all aetiologies of UI and it is im-
portant to give simple advice first.
Hygiene – Advise washing daily and after
every accident using unscented soap or baby
loose fitting clothes to reduce the risk of skin dam-
age from soiling.
Fluid, caffeine, and alcohol intake – Advise
drinking 2–3 pints of fluid a day. Less than this
can exacerbate irritable bladders and more will
increase the volume or urine production. Advise
avoiding caffeine (switch to decaffeinated tea and
coffee if possible) and excess alcohol as both have
a diuretic effect and can exacerbate incontinence.
Weight loss – Obesity carries an increased risk
of SI and UUI, and in these cases weight reduction
and education programmes can help especially in
those with a body mass index greater than 30 kg/m2.
Smoking – Whilst stopping smoking has no
direct effect on urinary incontinence, persistent
cough contributes to stress incontinence and stop-
ping smoking may reduce this.
Reversible causes – See Box 4.
Medication review – Medication review is
essential (Box 5).
Environmental interventions – Difficulty in
accessing toilet facilities is potentially a major factor
in incontinence in the frail. This is known as func-
tional incontinence and usually coexists with other
forms of incontinence. In many, poor mobility may
be a contributing factor but environment also plays
a part. Occupational therapists assess functional
difficulties and problems with home environment.
They may be able to provide downstairs commodes
and adjust lighting and flooring. Clothing that is
elasticated or with Velcro fastening can be used to
aid rapid removal. It is important to consider such
GYNAECOLOGY PEER REVIEWED
factors in hospitals and care homes in addition to
patients’ own residences because a change in a frail
person’s environment can exacerbate any UI.
Containment devices – Many frail elderlies
will require the use of devices to contain urine to
preserve dignity when incontinent. A wide range
of absorbent pads is available. Pads can be worn
next to the skin or as absorbent sheets for beds.
Body worn pads are superior to sheets as they are
less likely to wrinkle and cause pressure damage
and less likely to affect pressure relieving mattress-
es. Such devices are not treatments in themselves
but are used in addition to other therapies or as a
long-term management strategy in those with re-
fractory symptoms despite treatment. The patient
and carer preferences should be considered when
choosing containment products.
Catheters – The indications for catheteriza-
tion include chronic urinary retention where medi-
cal management has failed, and surgery is thought
to be inappropriate, pressure sores, or wounds
prone to urinary contamination.
The different methods of catheterization include
intermittent catheterization (either by patient or car-
er), long-term urethral catheterization, or suprapubic
catheter. Intermittent catheterization and suprapubic
catheterization have lower risks of urinary tract infec-
tion and also have less impact on sexual function.
It is important that in any patient requiring catheter-
ization that patients and carers are counselled re-
garding the indications, complications, and care.
Specific measures
Stress incontinence (SI)
Conservative
Pelvic floor exercises and vaginal cones –
Both of these techniques though demonstrated to
be highly efficacious in younger women, but are
likely to be less effective in certain groups of frail
elderly as patients must have adequate higher
mental functions and sufficient motivation.
Bladder training and habit retraining –
Bladder training aims to gradually increase the
MIMS JPOG 2018 VOL. 44 NO. 3 121
Box 5. Side Effects of Anticholinergic Medication
CNS
• Sedation
• Cognitive impairment
• Delirium
Gastrointestinal
• Dry mouth
• Constipation
Ophthalmic
• Mydriasis (Glaucoma)
• Impaired accommodation (blurred vision)
CVS
• Arrhythmia
• Tachycardia
• Orthostatic intolerance
Urinary
• Retention
intervals between each void. It utilises scheduled
voiding when awake, and relaxation techniques
to suppress the sensation of urgency in the time
between voids. It can be very effective in those
with normal cognitive function.
Prompted voiding and scheduled toileting
– In those with cognitive impairment who do not
have the cognitive capacity to comply with behav-
ioural interventions, timed and prompted voiding
can reduce the risk of UI. Prompted voiding in-
volves asking patients at regular intervals whether
they would like to go to the toilet. It is carer and
patient dependent and requires a moderate de-
gree of remaining cognition.
Timed toileting is carer dependent and may
be more appropriate in those with severe cognitive
impairment. Both techniques aim to reduce incon-
tinent episodes but do not affect bladder function
and they may increase the workload for carers.
They are only effective for daytime incontinence.
Pharmacological therapy
Serotonin and noradrenaline reuptake inhibi-
tors (Duloxetine) – SNRIs have been shown in a
recent Cochrane review to improve quality of life
in patients with UI, although it has little impact on
the numbers cured. The inhibition of serotonin and
122 MIMS JPOG 2018 VOL. 44 NO. 3
Table 3. Drugs with Anticholinergic Side Effects
Anti-emetics Hyoscine, cyclizine, prochlorperazine
Antiparkinsonian Procyclidine, trihexyphenidyl
medication
Antispasmodic Oxybutynin, trospium, tolterodine, solifenacin
Anti-arrhythmic Disopyramide, procainamide, quinidine
Antihistamine Chlorpheniramine
Antidepressants Amitriptyline, imipramine, doxepin, nortriptyline
Antipsychotics Chlorpromazine, dozapine, fluphenazine, thioridazine
noradrenaline reuptake specifically in the sacral
spinal cord increases the tone of the sphincter
through parasympathetic inhibition and improves
urethral closure. Side effects are significant. At
present, duloxetine is recommended should pel-
vic floor therapy be unsuccessful and the patient
prefer to avoid surgery. Whilst this is a common sit-
uation in the frail elderly, side effects of duloxetine
may limit its use in this group. NICE suggest it may
be considered as a second-line treatment for those
unsuitable for surgery.
Oestrogen therapy – Around the meno-
pause withdrawal of oestrogen may result in a
reduction of periurethral pressure. Theoretically
replacing this oestrogen locally will reduce SI.
There is some evidence that topical oestrogens
may improve incontinence for the duration of
treatment, but the effect is modest and only small
proportions of women benefit. NICE recommend
its use in OAB patients who are post-menopau-
sal with vaginal atrophy. It also has a role in the
prevention of recurrent urinary tract infection and
local symptoms in women with atrophic vaginitis.
Urge incontinence/overactive bladder
Conservative measures: As above.
Pharmacological treatment
Anticholinergic therapy – Anticholinergic
drugs used in UUI act on smooth muscle recep-
tors of which there are five types: M1–M5. Type
M2 causes bladder relaxation during filling and M3
mediates bladder contraction, therefore the inter-
GYNAECOLOGY PEER REVIEWED
action between these receptors contribute to the
symptoms of OAB.
Type M1 is found the in hippocampus and
forebrain and plays an important role in memory
and cognition.
It is the presence of muscarinic receptors in
other organs that causes the extensive side effects
found with anticholinergic agents (Table 3). Use of
other drugs with anticholinergic properties (eg, tri-
cyclic antidepressants, antipsychotics, ranitidine,
ACE inhibitors, and bronchodilators) is common
in the elderly and concomitant use increases the
risk of anticholinergic side effects. The side effect
profiles of available drugs govern choice of agent
in the frail. It is recommended that use of such
drugs be reviewed early and frequently. NICE
state that oxybutynin, an antimuscarinic, is con-
traindicated in the frail elderly. It is associated
with acute confusion in this patient group. Fes-
oterodine has a good evidence base for use in
the elderly as does solifenacin. They are generally
well tolerated. Artificial saliva and osmotic laxative
can be prescribed at the outset of treatment to
counteract common side effects of dry mouth and
constipation, therefore improving treatment com-
pliance and success.
B3-adrenoceptor agonist – Mirabegron is a
novel drug in treatment of OAB. Beta-3 agonists
are a class of non-antimuscarinic medications
which use the sympathetic nerve pathway to
stimulate beta-3 receptors in the bladder, caus-
ing smooth muscle relaxation. Use of drugs in
this class offer targeted treatment for OAB as 97%
of the beta-adrenergic receptor subtypes within
the bladder are of beta-3. Beta-3 agonists do not
cause antagonism of M3 receptors and as such
has a reduced risk of urinary retention and oth-
er anticholinergic side effects, making it a viable
treatment option for patients who cannot tolerate
these side effects or in whom the anticholinergics
are contraindicated or where there is concern
over overall anticholinergic load. Anticholiner-
gic medications should be used with caution in
the elderly due to evidence suggesting that high
cumulative doses of these medications can be
GYNAECOLOGY PEER REVIEWED
associated with increased risks of dementia and
Alzheimer’s disease, making beta-3 agonists an
effective treatment choice in this patient group.
The main contraindication is uncontrolled hyper-
tension. Care should be taken if the patient is on
digoxin.
Desmopressin – Desmopressin is an ana-
logue of vasopressin that reduces water excretion
from the kidneys. Taken at night, it may reduce
symptoms in those with troublesome nocturia.
However, due to increasing evidence of hypon-
atraemic electrolyte disturbance and interaction
with other medications, this should not be used
in the frail elderly unless all alternatives have been
considered and treatment is supervised by dai-
ly U&E measurement in the first week. This is an
off-licence treatment and requires informed con-
sent from the patient.
Anticholinergics and cognitive impairment
There has been concern that interaction of an-
ticholinergic drugs with M1 receptors in the brain
can cause problems with attention, concentration,
memory, and visuospatial awareness. The most re-
cent NICE guidelines have stated that oxybutynin
is contraindicated in the frail elderly because of this
effect, this has long been known to clinicians.
The concern that all antimuscarinics have
this effect has been addressed in the literature
on OAB. Recently, the SOFIA trial studied the effi-
cacy, tolerability, and safety of fesoterodine, an
anticholinergic, in 794 individuals over the age of
65, providing robust data in the elderly age group.
It was a prospective, randomized, double-blind,
placebo-controlled multicentre trial that inves-
tigated the effect of fesoterodine on the symp-
toms of OAB and specifically examined cognitive
function. The trial established that fesoterodine
reduced OAB symptoms and that there was no
significant reduction in cognitive function demon-
strated by monitoring of the MMSE.
There was a meta-analysis of the effects of
antimuscarinics on health-related quality of life,
which includes cognition, in OAB treatment by
Khuller, et al, 2006, which showed that treatment
MIMS JPOG 2018 VOL. 44 NO. 3 123
Practice Points
• Urinary incontinence is not a normal feature of ageing.
• A full history and examination including functional and cognitive status should
be performed as part of the assessment.
• The impact of medication on continence should always be considered.
• 
Physiologically young elderly patients should be considered for surgical
intervention if conservative management fails.
• Timed toileting can be of use in managing UI even in the frail cognitively
impaired elderly.
• It is important to exclude and to treat constipation in the frail.
• When considering treatment with an antimuscarinic total anticholinergic drug
load should be considered.
• Refer to NICE clinical guideline 171 Urinary Incontinence in Women and NICE
clinical guideline 148 Urinary Incontinence in neurological disease for best
practice.
of OAB with anticholinergics compared with pla-
cebo had statistically significant differences in
favour of antimuscarinic therapy. It provided evi-
dence that antimuscarinics provide health-related
quality of life benefits to patients with OAB.
Surgical therapies: Details about specific surgical
intervention are beyond the scope of this article,
however it is important to consider the appropri-
ateness of surgery in the elderly. Experienced sur-
geons and anaesthetists should make any deci-
sions regarding surgery.
Frailty has been shown to independently pre-
dict postoperative complications, length of stay,
and discharge to care homes. However, it is im-
portant not to discount such management purely
on the basis of age, and “physiological age” is an
increasingly common concept in modern surgery
within the ageing population.
In patients with prolapse, pessaries or surgery
can be considered. Prolapse does not tend to cause
stress incontinence. However, anterior repair with
urethral buttressing whilst no longer a recommend-
ed treatment for SUI in the younger population,
may be of value in the frail elderly with concomitant
SUI and anterior vaginal wall prolapse.
The use of pessaries in the frail elderly is often
well tolerated and if effective may avoid the need for
surgery.
124 MIMS JPOG 2018 VOL. 44 NO. 3
Incontinence associated with
incomplete bladder emptying
Medication review is essential as anticholinergic
medications can increase incomplete bladder
emptying and should be avoided. Constipation
should be avoided. Specific treatment depends
on the cause.
URINARY INCONTINENCE AND
COGNITIVE IMPAIRMENT
The incidence of dementia rises substantially after
the age of 75, and UI in the cognitively impaired
can range from 11% in an outpatient setting to 90%
in care homes. Dementia can cause UI by a variety
of mechanisms ranging from decreased motiva-
tion and initiative to go to the toilet, social disinhi-
bition, decreased executive function, immobility or
gait disturbance, or even severe autonomic failure.
In Alzheimer’s disease UI presents an average
of 6.5 years after dementia onset. However, in Lewy
Body Dementia UI presents sooner after dementia
onset (3.2 years) and in vascular dementia UI can
precede dementia onset by 5 years or more.
Managing UI in the patient with cognitive im-
pairment presents a challenge. Patients are often
difficult to assess as they may not be able to give
an accurate history and may not comply with ex-
amination or investigations. Patients with demen-
tia tend to have other major comorbidities and
may be on medications that cause UI. They are
more likely to be susceptible to the side effects
of drugs, particularly anticholinergics and may be
on other drugs that interact with medications for
UI. Patients may be difficult to nurse, may pull out
catheters, and pads putting significant strain on
carers. However, the benefits of any improvement
in continence in this patient group cannot be un-
derestimated.
Methods such as prompted and timed toilet-
ing are effective and avoiding constipation is im-
portant. A medication review is vital in these pa-
tients. Anticholinergic drugs can be considered but
use with care (see Box 5 and Table 3). NICE clinical
guideline on Urinary incontinence in neurological
disease provides advise for patients with dementia.
GYNAECOLOGY PEER REVIEWED
CONCLUSION
Chronological age is no indicator of frailty. Treat-
ment options in the biologically young cognitively
intact female should not differ from those of the
chronologically young.
The frail older woman is disproportionate-
ly more disadvantaged by UI. It can affect both
social and domiciliary functioning and negatively
impact on their relationship with their carers. The
supposition that the frail female will inevitably be
incontinent and that nothing can be done to alle-
viate her symptoms is a myth.
The importance of comprehensive medi-
cal and multidisciplinary assessment cannot be
overemphasized. Goal setting that is realistic and
perhaps based on improvement rather than abso-
lute cure can be more appropriate in this group.
Assessment of functional status, carer availability,
and cognition allows these goals to be tailored to
the needs of the individual. Avoidance of consti-
pation, appropriate medication review, promotion
of hygiene, and availability of appropriate aids
and containment products can help frail older
women maintain social activity and to remain in
their preferred environment.
FURTHER READING
1. Abrams P, Cardozo L, Fall M. The standardisation of terminology of lower
urinary tract function: report from the Standardisation Sub-committee
of the International Continence Society. Neurourol Urodyn 2002; 21:
167–78.
2. Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarin-
ic treatments in overactive bladder: a systematic review and meta-anal-
ysis. Eur Urol 2005; 48: 5–26.
3. DuBeau C, Kuchel G, Johnson T, Palmer M, Wagg A. Incontinence in
the frail elderly: report from the 4th International Consultation on Inconti-
nence. Neurourol Urodyn 2010; 29: 165–78.
4. Khullar V, Chappel C, Gabriel Z, Dooley JA. The effects of antimuscarin-
ics on health-related quality of life in overactive bladder: a systematic
review and meta-analysis. Urology (Impact Factor 2.42) 09/2006; 68(2
Suppl):38–48.
5. Staskin DR, Peters KM, MacDairmid S, Shore N, de Groat WC. Percu-
taneous tibial nerve stimulation: a clinically and cost-effective addition
to the overactive bladder algorithm of care. Curr Urol Rep 2012 Oct; 13:
327–34.
6. Wagg A, Verdejo C, Molander U. Review of cognitive impairment with
antimuscarinic agents in elderly patients with overactive bladder. Int J
Clin Pract Aug 2010; 64: 1279–86.
© 2017 Elsevier Ltd. All rights reserved. Initially published in Obstetrics, Gy-
naecology and Reproductive Medicine 2017;28(2):39–45.
About the authors
Gabrielle Prud’homme is a GP Registrar at Barnsley Hospital NHS Founda-
tion Trust, UK. Conflict of interest: none declared.
Leanne Alexander is a Speciality Doctor in Geriatric Medicine at Barnsley
Hospital NHS Foundation Trust, UK. Conflicts of interest: none declared.
Susan Orme is a Consultant in Geriatric Medicine at Barnsley Hospital NHS
Foundation Trust Hospital, Barnsley, UK. Conflicts of interest: none declared.
CONTINUING MEDICAL EDUCATION MIMS JPOG 2018 VOL. 44 NO. 3 125

Human Papillomavirus 2 SKP

and Cervical Cancer

Ka Yu Tse, MRCOG, Cert RCOG (Gyn Onc); Philip Pun Ching, Ip FRCPath, FHKCPath; Karen Kar Loen Chan, FRCOG, Cert RCOG (Gyn Onc)

INTRODUCTION
Cervical cancer is the fourth most com-
mon cancer in women in the world, and
there were about 528,000 new patients
and 266,000 deaths in 2012. In Hong
Kong, its crude incidence rate dropped
from about 14 per 100,000 women
in late 1990s to around 10.5 in early
2010s, and is currently the 9th com-
monest female cancer. (Table 1a and
1b)1 This phenomenon may be attrib-
uted to the implementation of cervical
smear screening programme. Never-
theless, it remains as the 8–9th lead-
ing cause of female cancer death over
the last decade and the crude mortal-
ity rate rose from its trough at 3.0 per
100,000 women in 2003 to 4.0 in 2011.
From these results, it is obvious that
cervical cancer still poses a threat to
women’s health. This article aims to Cervical cancer is the fourth most common cancer in the world — with about 528,000
review the causal relationship between patients diagnosed in 2012.
human papillomavirus (HPV) and cervi-
cal cancer and discuss existing meth- it HPV type 16, which 61.1 percent of in the anogenital tract diseases.5 HPV
ods that prevent HPV from leading to the cervical cancer samples from their is present in about 90% of high-grade
cervical cancer. German cohort revealed this DNA. 3
cervical intraepithelial neoplasia (CIN)
One year later they found another and cervical cancer 6
(Figure 1) and
BIOLOGY OF HUMAN virus in their cervical cancer cell lines 70–80% are related to HPV-16 and 18.
PAPILLOMAVIRUS and biopsy samples and designated Other high-risk subtypes of HPV in-
Herpes simplex virus was once con- it as HPV 18.4 They also hypothesized clude 31, 33, 35, 39, 45, 51, 52, 56, 58,
sidered the culprit for cervical cancer. that the viral DNA might be integrated and 59 as classified by the International
Professor Zur Hausen first proposed into the host cell genome. After this Agency for Research on Cancer.7 They
the possible association of HPV with initial work, extensive research was are acquired sexually. Other routes of
genital cancer in 1970s.2 In 1983, his performed on this virus. More than 100 transmission, like vertical transmission
team identified new HPV DNA from HPV subtypes have now been identi- from mothers to infants, have also been
one cervical cancer biopsy and named fied and more than 40 are implicated described.
126 MIMS JPOG 2018 VOL. 44 NO. 3 CONTINUING MEDICAL EDUCATION

Table 1a. Incidence of Cervical Cancer in 1995–2011 in Hong Kong 1

Incidence
Years New cases Rank in new female Crude incidence Age standardised Median age at
registered cancer rate* rate* diagnosis
1995 498 NA 16.2 14.8 NA
1996 445 NA 13.8 12.5 NA
1997 474 NA 14.6 12.4 NA
1998 491 4 14.9 11.6 53
1999 436 4 13 9.8 54
2000 444 5 13.1 10.7 53
2002 442 5 12.7 9.9 52.5
2003 408 5 11.6 8.9 50
2004 439 5 12.3 9.4 54
2006 459 5 12.8 9.4 54
2007 399 7 11 7.7 52
2010 400 10 10.7 7.3 NA
2011 391 9 10.4 7.2 53
NA – not applicable
*All rates are expressed as per 100,000 women.

HPV is a non-enveloped virus
containing double-stranded circular
DNA. The DNA sequence consists of
early and late open reading frames,
encoding proteins E1–8 and L1–2, re-
spectively. HPV usually targets at the
proliferating basal cells of the squa-
mous epithelium. Once inside the cell,
the viral genome replicates migrating
away from the basal layer to the upper
epithelium. The episomal HPV DNA is
also integrated into the host genome
and the viral genome usually opens in
the E1–2 region. E2 is a repressor of
the E6–7 promoter, disruption of which
will result in unregulated expression of
E6 and E7. 8 E6 protein of those high-
risk HPV acts by binding to and thus
inactivating TP53 tumour suppressor
gene product which plays an impor-
tant role in apoptosis and cell growth
arrest. On the other hand, E7 protein
binds to and inactivates retinoblasto-
ma (Rb) protein which regulates cell
cycle by controlling the transition at
G1/S phase. E4 protein may further
disrupt the cytoplasma cytokeratin
matrix mediating the release of HPV
particles.
A meta-analysis comprising of
194 studies and more than one million
women with normal cervical cytology
showed that the global prevalence of
HPV infection was 11.7% (confidence
interval [CI], 11.6–11.7) and was up
to 24.0% in Sub-Saharan Africa.9 The
prevalence was highest in women
younger than 25 years, with a second
peak at ≥45 years in the Americas and
Africa. In Hong Kong, the HPV preva-
lence was estimated to be 6.7% with
a peak at 26–30 years followed by an-
other smaller peak at 46–55 years. 10
Young age, having ≥4 sexual partners
and smoking were independent risk
factors for HPV infection on multivar-
iate analyses. About half of the HPV
infection persists for 6–12 months,
and high-risk HPV persists longer than
low-risk HPV (9.3 vs 8.4 months). 11 Up
to 70–100% of the HPV infection can
be cleared in 2–5 years especially in
young women. 12 About 1.6% of high-
grade CIN would progress to cancer
in 10 years if left untreated and the
median time is 23.5 years (95% CI,
20.8–26.6 years). 13
CONTINUING MEDICAL EDUCATION MIMS JPOG 2018 VOL. 44 NO. 3 127

Table 1b. Mortality of Cervical Cancer in 1995–2011 in Hong Kong 1

Mortality
Years Deaths Rank in female Crude mortality Age standardised Median age at
registered cancer deaths rate* rate* death
1995 159 NA 5.2 4.6 NA
1996 134 NA 4.2 3.5 NA
1997 144 NA 4.4 3.8 NA
1998 145 7 4.4 3.2 68
1999 159 7 4.8 3.5 64
2000 128 8 3.8 3 68
2002 121 9 3.5 2.6 68
2003 106 >10 3 2.1 69
2004 128 8 3.6 2.6 66
2006 133 9 3.7 2.4 66
2007 129 8 3.5 2.3 70
2010 146 9 3.9 2.4 NA
2011 151 8 4 2.5 63
NA – not applicable
*All rates are expressed as per 100,000 women.

HUMAN PAPILLOMAVIRUS
TESTING
It has been shown that conventional
cytology only has 76% sensitivity of de-
tecting CIN 2 or worse (CIN 2+).
the other hand, some centres found that
liquid-based cytology is not more sensi-
tive or specific than conventional cytolo-
gy, though it can reduce the rate of un-
satisfactory smears as by conventional
cytology and allow HPV testing in the
same specimen. 15-16
In order to optimize
the performance of cervical screening
in detecting high-grade CIN and cancer,
the role of HPV testing has been evalu-
ated in different settings such as prima-
ry screening either as a stand-alone test
or co-test, triage for low-grade lesions,
and follow-up after treatment of CIN.
The HPV testing was first ap-
proved by the US Food and Drug Ad-
ministration (FDA) in 1988 but was only
used for follow-up of ASCUS (atypical
14
On squamous cells of undetermined sig-
nificance) in 1999. The ASCUS/LSIL
(low-grade squamous intraepithelial
lesion) Triage Study (ALTS) was one of
the earliest studies demonstrating an
improved sensitivity of detection of CIN
3 by triaging patients to colposcopy
based on testing high-risk HPV DNA by
Hybrid Capture 2 (HC2) and thin-layer
cytology results. 17
Subsequently, var-
ious studies showed that HPV-based
screening strategies had approximate-
ly 95% sensitivity in detecting CIN 2+,
when compared with cytology tests
where the sensitivity was between 55–
75%.18-20 In a recent meta-analysis, the
pooled sensitivity of HC2 in detecting
CIN 2+ was higher than that of repeat-
ing cytology, with relative sensitivity of
1.27 (95% CI, 1.16–1.39; p<0.0001)
and 1.23 (95% CI, 1.06–1.4; p=0.007)
for patients with ASCUS and LSIL, re-
spectively.21 However, while the spe-
cificities between the two methods in
triaging patients with ASCUS were sim-
ilar, specificity of HC2 was significantly
worse than that of repeating cytology
in case of LSIL (relative specificity 0.66,
95% CI, 0.58–0.75; p<0.0001). Using
cancer as the study endpoint, Ronco,
et al, had pooled the results of four
European randomized trials including
the Swedescreen, POBASCAM, AR-
TISTIC, and NTCC, and found that the
128 MIMS JPOG 2018 VOL. 44 NO. 3
Figure 1 (A): High-grade squamous intraepithelial lesion (CIN II) involving cervix; and (B):
Cell cycle marker p16 immunostain shows diffuse block staining, serves as a surrogate
marker for high-risk HPV infection.
study-adjusted rate ratio for invasive
cervical carcinoma after a median fol-
low-up of 6.5 years was 0.60 (95% CI,
0.40–0.89) for HPV-based screening
compared with cytology-based screen-
ing.22 Although there was no difference
in the detection rate of cancer between
the two methods during the first 2.5
years, it became significantly lower in
the HPV-based screening arm thereaf-
ter (0.45, 95% CI, 0.25–0.81).
Because of the better sensitivity
and negative predictive value of HPV
testing than cervical cytology, it is rec-
ommended by the American Cancer
Society (ACS), the American Society
for Colposcopy and Cervical Pathology
(ASCCP), and the American Society of
Clinical Pathology (ASCP) that women
be screened every 3 years with cytolo-
gy alone or at 5-year interval using cy-
tology and high-risk HPV co-testing.
For patients with ASCUS, those posi-
tive for high-risk HPV will be referred for
colposcopy, while those negative are
advised to have co-testing in 3 years.
HPV testing is not recommended for
women below the age of 30 because
of the high prevalence and clearance
rate of HPV infection in young patients
which may otherwise lead to over-diag-
nosis and hence unnecessary colpos-
CONTINUING MEDICAL EDUCATION
copy and treatment. Primary screening
by HPV testing alone is also not rec-
ommended because of concerns about
the possible increase in colposcopy
referrals.
Currently there are five HPV tests
approved by the US FDA to detect
the presence of high-risk HPV. Some
have found that it is more sensitive
than cytology alone in detecting CIN
3+ (92.0% vs 53.5%; p<0.0001), and
the sensitivity was further increased
to 96.7% when combining the two
methods compared with HPV testing
alone. 24 In a recent review, using the
New Mexico HPV Pap Registry, 35.7%
of CIN 2+ and 30.9% of CIN 3+ were
diagnosed following normal cytology,
among which 62.3% and 78.2%, re-
spectively, were positive for high-risk
HPV.25 The ACS/ASCCP/ASCP advo-
23
cates testing the HPV 16 and 18 gen-
otypes specifically in order to triage
women over 30 years who have nor-
mal cytology but positive pooled high-
risk HPV tests.23 These women can ei-
ther be followed up in 12 months with
repeat cytology and HPV test, or be
genotyped for HPV 16 and 18. For the
latter, if either HPV 16 or 18 is positive,
women would then be referred for col-
poscopy, whereas those who are neg-
ative for both can be co-tested again
in 12 months.
A survey conducted in April 2012
by the Department of Health in Hong
Kong found that, only 69.2% of women
had ever had a cervical smear and near-
ly 44% did not have a cervical smear in
the last 3 years.26 With HPV co-testing or
triage with HPV testing can potentially
reduce the number of repeating cytolo-
gy and may alleviate the problem of de-
faulting. HPV testing using self-collect-
ed samples may be an another option to
improve screening coverage, although
this is slightly less sensitive and spe-
cific compared with samples taken by
clinicians.27
HUMAN PAPILLOMAVIRUS
VACCINES
There are two HPV vaccines available
in the world. The bivalent vaccine cov-
ers HPV 16 and 18, and is approved
to prevent cervical cancer and its pre-
cursors in females 9 years and above.
The quadrivalent vaccine prevents HPV
6-, 11-, 16-, and 18-related diseases,
including cervical, vulval, and vaginal
cancers and their precursors, as well
as genital warts in females and males
9 years and above. It is noteworthy that
direct comparison between the two
vaccines is not possible without proper
trials due to different vaccine prepara-
tions, study design and cohorts.
Efficacy
Multiple phase III trials have confirmed
the efficacy of the two vaccines. For biva-
lent vaccine, the PApilloma TRIal against
Cancer In young Adults (PATRICIA)
study showed an efficacy up to 90.4%
(97.9% CI, 53.4–99.3; p<0.0001) against
CIN 2 or 3, adenocarcinoma (AIS), and
invasive carcinoma associated with HPV
CONTINUING MEDICAL EDUCATION MIMS JPOG 2018 VOL. 44 NO. 3 129

16 and 18 in the total vaccinated cohort

(TVC)–naïve group (ie, those who were
DNA and serum negative at entry) after a
mean follow-up of 14.8 months.28 Using
CIN 3 and AIS or worse as endpoints, the
4-year end-of-study of the PATRICIA trial
showed that the efficacy against those
HPV 16/18-related lesions was 100%
(95% CI, 85.5–100) in the TVC-naïve
group and 45.7% (95% CI, 22.9–62.2) in
the TVC group (ie, those who received at
least one vaccine dose including those
who were sexually active irrespective of
baseline HPV status).29 The HPV vaccine
also reduced the number of colposcopy
referrals by 29.0% (95% CI, 21.6–35.8)
and 14.8% (95% CI, 8.9–20.3), and cer-
vical excisional procwedures by 70.2%
(95% CI, 57.8–79.3) and 33.2% (95% CI,
20.8–43.7) in the TVC-naive and TVC, re-
spectively.
Combining the data of four similar
studies including the Females United
to Unilaterally Reduce Endo/Ectocervi- There are two HPV vaccines available in the world. The bivalent covering HPV 16 and 18
cal Disease (FUTURE) I and II studies, is approved for females 9 years and above.
a recent review evaluated the efficacy
of quadrivalent vaccine in prevent- vaccines based on the combined re- Cross-protection
ing HPV 16/18-related CIN 2–3, AIS in sults of the FUTURE I and II trials, with As HPV 16 and 18 constitutes only about
those aged 16–26 years after a 3-year an efficacy of 96% for CIN I (95% CI, 70–80% of cervical cancer, cross-protec-
follow-up.30 In the per-protocol suscep- 91-98) in the per protocol susceptible tion against other non-vaccine oncogen-
tible group (ie, those who were naïve group. 31
The results were similar to ic HPV types can potentially further pre-
to HPV 16/18 as shown on DNA or the PATRICIA trial, which also showed vent cervical cancer. The end-of-study
serologic tests at enrolment, received modest efficacy against HPV 16/18-as- analysis of the PATRICIA study after 4
all vaccine doses within 1 year with- sociated CIN 1+ (89.2%, 97.9% CI, years of follow-up evaluated the efficacy
out protocol violations, and remained 59.4–98.5; p<0.0001). 28
of bivalent vaccine in its cross-protection
DNA-negative for the specific HPV A recent randomized controlled trial in- against HPV 31, 33, 35, 39, 45, 51, 52, 56,
types through 1 month after the admin- volving 1,781 sexually naïve boys and girls 58, 59, 66, and 68. The efficacy against
istration of the last vaccine or placebo). aged 9–15 years showed that anti-HPV re- 6-month persistent infection with HPV 31
The overall efficacy against these le- sponse induced by quadrivalent HPV vac- was 76.8%, 77.1%, and 46.3% in accord-
sions was 99% (95% CI, 93–100), while cine persisted over 96 months. Besides,
32
ing-to-protocol cohort for efficacy (ATP-E,
it was 44% (95% CI, 31–55) in the inten- none of the 429 adolescents who received ie, those who were HPV DNA negative at
tion-to-treat group (ITT) (ie, including the vaccine at mean age of 12 developed enrolment and at 6 months for the spe-
those with previous infection). HPV 6/11/16/18-releated diseases or cific HPV type being analysed, adhered
On the other hand, low-grade le- persistent infection of ≥12 months’ to the protocol and had a normal or low-
sions could also be prevented by HPV duration. grade baseline cytology), TVC-naïve (ie,
130 MIMS JPOG 2018 VOL. 44 NO. 3
those who received at least one vaccine
dose and HPV DNA for all 14 HPV types
and seronegative for HPV 16 and 18 and
had a negative baseline cytology) and
TVC, and that with HPV 33 was 44.8%,
43.1%, and 26.3%, respectively. 33
CIN 2+ lesions not related to HPV 16/18,
consistent protective effect was ob-
served in HPV 31 in all cohorts and was
up to 84.3% (95% CI, 59.5–95.2) in the
ATP-E and 83.4% (95% CI, 43.4–96.9) in
the TVC-naïve. Efficacy against HPV 33
was also noted in the ATP-E (59.4%, 95%
CI, 20.5–80.4) and TVC-naïve (76.3%,
95% CI, 35.5–93.0). On the other hand,
quadrivalent HPV vaccine could reduce
HPV 31/45 infection by 40.3% (95% CI,
13.9–59.0) and CIN 1–3 or AIS by 43.6%
(95% CI, 12.9–64.1) in patients negative
for 14 non-vaccine HPV types. 34
Similar
to bivalent vaccine, the most remarkable
protective effect was observed in HPV
31. Nevertheless, it appears that these
cross-protective effects fade with time
and further study and vaccine modifica-
tion are definitely needed.
Safety
Although early post-licensure reviews
reported that the incidence of venous
thromboembolism appeared higher
than expected, this phenomenon could
not be confirmed by other series.
fact, HPV vaccines are relatively well tol-
erated. Those receiving vaccines tend
to have more fatigue, headache, and
myalgia within 7 days of vaccination
compared with the control group.
rious complications related to the vac-
cine was rare and occurred in <0.1% of
the vaccination population.28-29 Adverse
pregnancy outcomes such as sponta-
neous miscarriage and abnormal in-
fants occurred in 7–10% and 1–2.5%,
respectively, in the vaccination group,
CONTINUING MEDICAL EDUCATION
which were comparable to those with-
out vaccination. 28-29,36
The Global Advi-
sory Committee on Vaccine Safety of
the World Health Organization (WHO)
advised that the vaccine is safe though
For continuous surveillance is necessary. 37
Cost-effectiveness
Despite the heterogeneity among differ-
ent studies, most concluded that HPV
vaccination is cost-effective especially
in young girls before sexual debut, and
in middle-low and low-income countries
where there is a high burden of cervi-
cal cancer, and the screening system is
not well established. 38-39
A WHO-funded
study estimated that vaccination of 58
million 12-year-old girls before sexual
debut across 179 countries could pre-
vent 690,000 cases of cervical cancer
and 420,000 deaths during their lifetime
at a net cost of US$ 4 billion. By com-
40
paring the cost per disability-adjusted
life-years (DALYs) averted with the gross
domestic product (GDP) per capita,
HPV vaccination was considered to be
very effective in 156 (87%) countries.
Medical expenses may further be
reduced by herd protection from male
vaccination, protection against non-cer-
vical diseases, reduction of abnormal
cervical smear results and hence col-
35
In poscopic examinations and excision-
al procedures, and the introduction of
nonavalent HPV vaccine. In addition,
the Strategic Advisory Group of Experts
on Immunization (SAGE) has just an-
28
Se- nounced that the two-dose schedule
given within a minimum of 6-month in-
terval is not inferior to the convention-
al 3-dose schedule (at 0, 1–2, and 6
months) especially in girls younger than
15 years. This, in turn, may reduce the
number of visits and hence the cost of
vaccination.41
Acceptability
Any programme will become futile with-
out public awareness and acceptability.
A questionnaire study involving more
than 1,000 mothers in 2008 and 2012
showed that 68.5% (95% CI, 65.5–71.3)
mothers in 2012 had heard of HPV, in
comparison of 40.5% (95% CI, 37.5–
43.6) in 2008.42 Vaccine cost, low family
income, low maternal education level,
uncertainty about the effect duration,
low perceived risk of HPV infection, an-
ticipated family or peer disapproval, fear
of pain, and lack of support from the
care providers and the government, can
all hinder the vaccine uptake.43-44 Inten-
tion of the adolescents to receive HPV
vaccination and the acceptability of the
mothers could be improved by enhanc-
ing their knowledge using information
pamphlets and education programs.43-45
CONCLUSION
The introduction of cervical cytology
screening and HPV vaccine has not
been translated into a decrease in cervi-
cal cancer mortality in Hong Kong. One
of the possible reasons is the relatively
low screening and vaccination cover-
age. There has been robust evidence
that HPV co-testing can improve the
effectiveness of cervical cancer screen-
ing, where colposcopy referral can be-
come more efficient and the screening
interval may also be lengthened. Nev-
ertheless, a stringent tracking system
on women’s adherence is mandatory.
The impact of other novel tests such
as testing for mRNA of high-risk HPV
and immunostaining of p16INK4a and
Ki-67 remains to be further elucidated.
On the other hand, until now HPV vac-
cination is still not incorporated into the
government-funded routine vaccination
programme, and many women are not
CONTINUING MEDICAL EDUCATION
aware or have misconceptions about
HPV infection. Improving public knowl-
edge can enhance the acceptability and
uptake of cervical cancer screening and
HPV vaccination. More research on the
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Dr Ka Yu Tse and Dr Karen Kar Loen Chan are specialists at
the Department of Obstetrics and Gynaecology, Queen Mary
Hospital, the University of Hong Kong, Hong Kong.
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132 MIMS JPOG 2018 VOL. 44 NO. 3 CME QUESTIONS

Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh

MIMS, bekerjasama dengan Ikatan Dokter Indonesia.
Setelah membaca artikel ‘Human Papillomavirus and Cervical Cancer’,
jawab pertanyaan berikut kemudian kirimkan dengan menggunakan
formulir jawaban yang sudah disediakan ke CME MIMS Journal of
Paediatrics, Obstetrics & Gynaecology, untuk mendapatkan 2 SKP.

ARTIKEL CME

Human Papillomavirus and Cervical

Cancer 2 SKP

Jawab pertanyaan di bawah ini dengan Benar atau Salah.

1. E6 protein of high-risk HPV inactivates retinoblastoma TP53 while E7 protein inactivates TP53.
2. HPV testing can improve the sensitivity and specificity in detecting high-grade cervical intraepithelial
neoplasia.
3. Women who are found to have ASCUS but are negative for high-risk HPV can be followed up with
cytology and HPV-testing again in 12 months.
4. According to the ACS/ASCCP/ASCP guidelines, women who have negative cytology but positive pooled
high-risk HPV test still require a colposcopy referral.
5. HPV testing is not recommended for women below the age of 30 due to the high prevalence and
clearance rate of HPV infection in young patients.
6. The most remarkable cross-protection effect of the bivalent and the quadrivalent vaccines is against HPV-
33 with an efficacy of up to 90 percent.
7. There have been reports that the incidence of venous thromboembolism was higher than expected for
those receiving HPV vaccination.
8. HPV vaccination is still more cost-effective in young girls before sexual debut than those who are sexually
active.
9. Until now there is still no evidence for reducing the vaccination schedule from three-doses to two-doses.
10. Vaccine cost and fear of disapproval by family and friends can negatively affect the acceptability of HPV
vaccines.