Eur J Clin Microbiol Infect Dis (2015) 34:223230
DOI 10.1007/s10096-014-2224-6
ARTICLE
Risk of intrauterine growth restriction among HIV-infected
pregnant women: a cohort study
M. Lpez & M. Palacio & A. Gonc & S. Hernndez &
F. J. Barranco & L. Garca & M. Lonc & J. O. Coll &
E. Gratacs & F. Figueras
Received: 5 June 2014 / Accepted: 29 July 2014 / Published online: 9 August 2014
# Springer-Verlag Berlin Heidelberg 2014
Abstract The purpose of this investigation was to study the
risk of intrauterine growth restriction in human immunodefi-
ciency virus (HIV)-infected women and to describe the asso-
ciated risk factors. A cohort study was performed among HIV-
infected women who delivered in a single tertiary centre in
Barcelona, Spain, from January 2006 to December 2011.
Consecutive singleton pregnancies delivered beyond 22 weeks
of pregnancy were included. Intrauterine growth restriction
(IUGR) was defined as a birth weight below the 10th
customised centile for gestational age and IUGR babies were
compared to non-IUGR newborns. Intrauterine Doppler find-
ings were described among IUGR foetuses. Baseline charac-
teristics, HIV infection data and perinatal outcome were com-
pared between groups. The results were adjusted for potential
confounders. A total of 156 singleton pregnancies were in-
cluded. IUGR occurred in 23.4 % of cases (38/156). In two-
thirds of the cases detected before birth, Doppler abnormali-
ties compatible with placental insufficiency were observed.
IUGR pregnancies presented a worse perinatal outcome,
mainly due to a higher risk of iatrogenic preterm delivery
[adjusted odds ratio 6.9, 95 % confidence interval (CI) 1.4
33.5]. IUGR foetuses also had a higher risk of emergent
Caesarean section and neonatal intensive care unit admission.
No cases of intrauterine foetal death occurred. A high rate of
IUGR was observed among HIV pregnancies, and it was
M. Lpez (*) : M. Palacio : A. Gonc : S. Hernndez :
F. J. Barranco : L. Garca : J. O. Coll : E. Gratacs : F. Figueras
BCNatal - Barcelona Center of Maternal-Fetal and Neonatal
Medicine (Hospital Clnic and Hospital Sant Joan de Du),
IDIBAPS, University of Barcelona, and Centre for Biomedical
Research on Rare Diseases (CIBER-ER), C/Sabino de Arana, 1,
08028 Barcelona, Spain
e-mail: lopezro@clinic.ub.es
M. Lonc
Infectious Diseases Department, Hospital Clinic, University of
Barcelona, C/Villarroel, 170, 08036 Barcelona, Spain
associated with adverse perinatal outcomes, mainly iatrogenic
preterm and very preterm birth due to placental insufficiency.
Our results support that ultrasound detection and follow-up of
IUGR foetuses should be part of routine antenatal care in this
high-risk population to improve antenatal management.
Introduction
Mother-to-child transmission of human immunodeficiency
virus (HIV) is almost negligible if the current preventive
strategies are applied. Nevertheless, a higher incidence of
severe adverse perinatal outcomes among HIV-infected preg-
nant women is still of concern. Preterm birth and low birth
weight have largely been described as major contributors to
significant neonatal morbidity and mortality in this population
[16].
Low birth weight generally refers to newborns below
2,500 g, without considering gestational age at birth. There-
fore, as an individual outcome, it cannot discriminate preterm
births from real small-for-gestational-age babies and may lead
to significant misinterpretations when assessing perinatal out-
comes and their associated factors [79]. The term small for
gestational age (SGA) is more appropriate, as the definition
includes not only the weight but also gestational age. New-
borns below the 10th centile are usually considered SGA, thus
affecting 10 % of the population [10]. However, this term still
represents a heterogeneous population that includes constitu-
tionally small babies along with true forms of intrauterine
growth restriction (IUGR) due to placental insufficiency
[11]. While the former are simply the end of the spectrum of
normal babies, the latter is a major contributor to perinatal
morbidity and mortality [1216]. The standard method for
differentiating the two conditions is by using customised
growth standards, whereby the foetal and the birth weights
are adjusted by gestational age, maternal characteristics and
224
foetal gender [17]. Doppler evaluation of maternal uterine
arteries and foetal vessel can help to discriminate severely
restricted foetuses who are at risk of foetal hypoxia, foetal
demise or adverse neonatal outcome. Overall, SGA rates
among HIV-infected women range from 4 to 23 % in the
literature [4, 6, 18, 19], and, to our knowledge, no previous
studies have described perinatal outcomes among IUGR
babies. Several factors have been associated with SGA in
HIV-infected women, including immunological status [20],
toxic use [20, 21], Hispanic origin [22] or perinatally acquired
HIV [19]. In addition, the reported association of SGA with
antiretroviral treatment is controversial. Lower neonatal
weights have been described in at-term highly active antire-
troviral therapy (HAART)-exposed uninfected infants in Bo-
tswana when compared to Zidovudine-exposed infants [23]
and also in the National Study of HIV in Pregnancy and
Childhood (NSHPC) from the UK and Ireland between
1990 and 2005 [24]. On the other hand, no increased risk
was observed in a French HIV cohort treated with a lopinavir/
ritonavir-containing regimen [25] and neither was an associa-
tion found with antiretroviral treatment among 600 newborns
from HIV-infected mothers in Italy [21]. However, none of
these series have attempted to stratify the results according to
the presence of IUGR. When including all SGA, the findings
may be biased by the inclusion of an unknown proportion of
constitutionally healthy babies. Moreover, among IUGR
babies, those with Doppler abnormalities suggesting placental
insufficiency are the subgroup with the highest risk of adverse
perinatal outcome [12, 14]. To our knowledge, scarce infor-
mation exists about Doppler findings in pregnancies of HIV-
infected women.
The aims of our study were, therefore, to assess IUGR in
HIV-infected women and to describe Doppler findings and the
associated risk factors. For that purpose, the maternal and
perinatal characteristics between IUGR and non-IUGR babies
of this cohort were compared.
Materials and methods
Study design and population
A cohort study was performed in HIV-infected women
who delivered in the Hospital Clnic, a university referral
hospital in Barcelona, Spain, from January 2006 to De-
cember 2011. Consecutive singleton pregnancies delivered
beyond 22 weeks of pregnancy were included. Estimation
of foetal weight was performed in all patients at 28 weeks
and between 32 and 34 weeks of pregnancy according to
our standard protocol. All participants gave written in-
formed consent for ultrasound foetal assessment according
to the local Ethics Committee.
Eur J Clin Microbiol Infect Dis (2015) 34:223230
Ultrasound and Doppler evaluation
In all cases, foetal biometry and prenatal Doppler ultrasound
examinations were performed by experienced operators using
either a Siemens Sonoline Antares (Siemens Medical Sys-
tems, Malvern, PA, USA) or a General Electric Voluson E8
(GE Medical Systems, Zipf, Austria) ultrasound machine
equipped with a 62 MHz linear curved-array transducer.
The estimated foetal growth was calculated with Hadlock
et al.s formula [26], which includes the biparietal diameter,
head circumference, abdominal circumference and femur
length. In the IUGR-suspected foetuses, Doppler evaluation
was performed by calculating the pulsatility index in the
umbilical artery (UA PI), middle cerebral artery (MCA PI)
and the mean pulsatility index of the uterine arteries (mUtA
PI), according to the methodology described elsewhere [27].
The maternal compartment of the placenta was evaluated by
using mUtA PI [28], while the foetal compartment was
assessed by UA PI, MCA PI and the cerebroplacental ratio
(MCA PI/UA PI) [29].
Definitions
Gestational age was corrected by first trimester ultrasound (or
by the earliest available ultrasound in late gestational con-
trols). IUGR was defined as a birth weight below the 10th
customised centile for gestational age according to local val-
idated and published standards [30].
Preterm delivery (PTD) and very preterm birth were de-
fined as occurring before 37.0 and 34.0 gestational weeks,
respectively. Spontaneous PTD included spontaneous labour
and preterm premature rupture of membranes (PPROM). Iat-
rogenic PTD was considered if medically indicated for pre-
eclampsia (blood pressure of at least 140/90 mmHg on two
occasions at least 4 h apart with >0.3 g of urine protein per
24 h), other maternal medical conditions, IUGR, foetal dis-
tress (category III foetal heart rate tracings [31]) or intrauterine
foetal death. One pregnancy could have more than one indi-
cation for delivery. Placental histopathologic findings were
classified according to the system adopted by the International
Federation of Placenta Associations (IFPA) [32]. Maternal
underperfusion criteria mainly included villous infarct, de-
creased placental weight, increased intervillous fibrin, distal
villous hypoplasia and vascular lesions of basal plate arteries
or decidual arterioles.
Statistical analysis
For the analysis, IUGR babies were compared to non-IUGR
newborns. Baseline characteristics, HIV infection data and
perinatal outcome were compared between groups. The Stu-
dents t-test was used for continuous variables and the Chi-
square test for proportions. The MannWhitney test was used
Eur J Clin Microbiol Infect Dis (2015) 34:223230
for non-parametric variables. Simple comparisons used a two-
sided level of 0.05. Odds ratios (ORs) were adjusted for
maternal age, smoking during pregnancy, past or present drug
use, low educational level and maternal body mass index
(BMI), being all potential confounders between HIV infection
and foetal growth restriction. The SPSS 17.0 software (Statis-
tical Package for the Social Sciences 17.0 statistical software;
International Business Machines Corporation, USA) was used
for the statistical analysis.
Results
A total of 156 singleton pregnancies were included. The
median gestational age at the first visit to our perinatal infec-
tions unit was 10 weeks of pregnancy. IUGR occurred in 38
(23.4 %) cases, of whom 21 (55.3 %) were detected before
birth. In two-thirds of the cases detected, Doppler abnormal-
ities compatible with placental insufficiency were observed
(14/21; 66.6 %). The Doppler abnormalities are described in
Table 1. The median gestational age at diagnosis of cases
detected before birth was 34 weeks of pregnancy (range 24
40 weeks).
Table 2 shows the baseline characteristics of the cohort. It
was of note that past intravenous drug use (IDU) was more
frequent among the IUGR group, but toxic use during preg-
nancy, including cigarette smoking, cannabis, cocaine, am-
phetamine or IDU, was similar among groups. No other
differences were observed apart from lower maternal BMI
among the IUGR group. Doppler abnormalities in the uterine
arteries were not present in the first trimester of pregnancy in
the IUGR group.
Regarding HIV infection parameters (Table 3), women in
the IUGR group were more likely to have been infected by the
parenteral and vertical routes, although the most frequent
mode of transmission in both groups was heterosexual
Table 1 Doppler assessment among IUGR foetuses
Doppler assessment IUGR detected during
pregnancy (n=21)
No. % cant (adjusted OR 6.9, 95 % CI 1.433.5 and adjusted OR
Normal 7 33.3
Abnormal 14 66.7
- Maternal placental insufficiency* 5 35.7
- Foetal placental insufficiency** 7 50
- Maternal and foetal placental insufficiency 2 14.3
IUGR: intrauterine growth restriction
*mUtA PI>95th centile
**UA PI>95th centile, MCA PI<5th centile or UA PI/MCA PI<5th
centile
225
transmission. HIV infection was detected during pregnancy
in 17.3 % of women (27/156). No differences were observed
in the HIV infection evolution with a similar length of infec-
tion, level of immunosuppression and viral load being ob-
served among groups. Overall, 95.5 % of patients were on
combined antiretroviral treatment. Three pregnant women
received Zidovudine monotherapy and, in four cases, no
antiretroviral treatment was used during pregnancy due to
the late diagnosis of HIV infection or late-presenting women
for care. No significant differences were found in the types of
treatment or in the time of initiation before or during pregnan-
cy between groups. Protease inhibitors were used during
pregnancy in 67.9 % of women (106/156).
Perinatal outcome is described in Table 4. Overall, the rate of
PTD among all HIV-infected women was 20.5 % (32/156).
Gestational age at birth was lower in the IUGR group, with a
higher risk of PTD below 34 weeks of pregnancy (OR 4.2, 95 %
CI 1.214.8). Regarding the type of prematurity, globally, 68.7 %
of cases were spontaneous preterm births, while the remaining
31.3 % were iatrogenic or medically indicated. On the contrary,
among the IUGR group, iatrogenic preterm birth was significant-
ly more frequent than in the normal weight group (OR 8.7, 95 %
CI 2.135.4) (Fig. 1), even when regarding very preterm births of
less than 34 weeks (OR 13.8, 95 % CI 1.5127.3). The main
indications for delivery were severe preeclampsia (n=4), gravidic
cholestasis (n=1), severe maternal respiratory infection (n=1) or
foetal distress/suspected foetal compromise in an IUGR foetus
(n=4). Preeclampsia was more frequent in the IUGR group,
albeit not reaching statistical significance.
Histological criteria for maternal underperfusion in the
placenta were observed in more than half of IUGR foetuses,
being significantly less frequent in the non-IUGR group.
IUGR babies had a significantly higher risk of emergent
Caesarean section and neonatal intensive care unit (NICU)
admission, with a tendency towards a higher frequency of an
abnormal 5-minute Apgar score. No cases of intrauterine
foetal death occurred.
Multivariate analysis was performed with adjustment for
potential confounders (maternal age, smoking during preg-
nancy, past or present drug use, low educational level and
maternal BMI). The association between IUGR and iatrogenic
preterm and very preterm birth remained statistically signifi-
13.0, 95 % CI 1.2145.2, respectively), with a higher inci-
dence of maternal underperfusion in the histological analysis
of the placenta in the IUGR group and a significantly in-
creased risk of NICU admission among IUGR newborns.
Discussion
A high risk of IUGR was observed among HIV-infected
women (38/156 below the 10th centile). Diagnosis was made
226 Eur J Clin Microbiol Infect Dis (2015) 34:223230

Table 2 Baseline characteristics

of the study groups IUGR (n=38) Non-IUGR (n=118) p-Value

Age; mean (SD) 33.1 (6.2) 33.2 (5.8) 0.904

Black ethnicity; n (%) 4 (10.5) 23 (19.5) 0.204
Low educational level; n (%) 10 (27.0) 37 (31.4) 0.617
Maternal BMI; mean (SD) 21.8 (3.9) 23.5 (4.0) 0.021
Smoking during pregnancy; n (%) 15 (39.5) 34 (28.8) 0.218
Previous intravenous drug use; n (%) 10 (26.3) 14 (11.9) 0.032
Other drug use during pregnancy (cocaine, cannabis, 3 (7.9) 7 (5.9) 0.668
amphetamine, active IDU); n (%)
Nulliparity; n (%) 17 (44.7) 41 (34.7) 0.268
IUGR: intrauterine growth re-
striction; SD: standard deviation; Chronic hypertension; n (%) 3 (7.9) 4 (3.4) 0.243
BMI: body mass index; mUtA PI: Assisted reproduction technique; n (%) 2 (5.3) 12 (10.2) 0.357
mean pulsatility index of the 1st trimester mUtA PI>95th; n (%) (n=98) 0 (0) 7 (9.3) 0.123
uterine arteries

prenatally by ultrasound examination in about half of
the cases, which is concordant with the standard detec-
tion rate of 3rd trimester ultrasound for the detection of
IUGR [33, 34]. Interestingly, Doppler findings compat-
ible with placental insufficiency were found in two-
thirds of the cases, which is higher than that reported
in the general population [35]. This high proportion of
placental insufficiency may explain the high rate of
adverse perinatal outcome in the HIV population.
In previous studies in which the outcome was low birth
weight [79] or SGA [4, 19, 21, 23, 24, 36, 37], a reliable
estimate of the incidence of IUGR cannot be achieved. Briand
et al. described an overall SGA rate of 4 % among the ANRS
French Perinatal Cohort [18]. This low rate of SGA may be

Table 3 HIV infection data of the

study groups IUGR (n=38) Non-IUGR p-Value
(n=118)

HIV diagnosis in pregnancy; n (%) 7 (18.4) 20 (16.9) 0.835

HIV transmission
- Heterosexual; n (%) 26 (68.4) 105 (89.0) 0.003
- Injection drug use; n (%) 9 (23.7) 12 (10.2) 0.034
- Blood transfusion; n (%) 0 1 (0.8) 0.569
- Vertical transmission; n (%) 2 (5.3) 0 0.012
- Unknown; n (%) 1 (2.6) 0 0.077
Months of HIV infection; median (range) 84 (0284) 68.5 (0312) 0.801
Previous opportunistic infection; n (%) 10 (27.0) 17 (14.5) 0.081
CD4 cell count<200 cells/l at 1st trimester; 2 (7.1) 7 (7.5) 0.946
n (%) (n=121)
CD4 cell count at 1st trimester (cells/l); median 445.5 (25799) 448 (1311,462) 0.663
(range) (n=121)
CD4 cell count at delivery (cells/l); median 458 (1581,273) 484.5 (432,213) 0.836
(range) (n=150)
Viral load <50 copies/ml at 1st trimester; n (%) (n=123) 17 (54.8) 61 (66.3) 0.252
Viral load<50 copies/ml at delivery; n (%) (n=150) 32 (84.2) 95 (84.8) 0.928
HAART before pregnancy; n (%) 22 (57.9) 75 (63.6) 0.531
Weeks of HAART before pregnancy; median (range) 128 (0640) 146.5 (0709) 0.667
HAART during pregnancy; n (%) 38 (100) 111 (94.1) 0.124
Weeks of HAART during pregnancy; median (range) 27.50 (241) 35 (042) 0.280
Initiation of HAART above the 2nd trimester; n (%) 18 (47.4) 42 (35.6) 0.194
IUGR: intrauterine growth re- PI during pregnancy; n (%) 28 (73.7) 78 (66.1) 0.384
striction; HAART: highly active
antiretroviral treatment; PI: prote- PI in the 1st trimester; n (%) 12 (31.6) 40 (33.9) 0.792
ase inhibitors; NNRTI: non-nu- Initiation PI above the 2nd trimester; n (%) 16 (42.1) 38 (32.2) 0.264
cleoside reverse transcriptase NNRTI during pregnancy; n (%) 11 (28.9) 39 (33.1) 0.637
inhibitors
Eur J Clin Microbiol Infect Dis (2015) 34:223230 227

Table 4 Perinatal outcome

Global IUGR (n=38) Non-IUGR p-Value Adjusted p-valuea

(n=156) (n=118)

Gestational age at birth; mean (SD) 38.1 (2.7) 37.1 (3.6) 38.4 (2.2) 0.009 0.044
Preterm delivery; n (%)
- <37 weeks 32 (20.5) 10 (26.3) 22 (18.6) 0.308 0.836
- <34 weeks 11 (7.1) 6 (15.8) 5 (4.2) 0.016 0.126
Spontaneous preterm delivery; n (%) 22 (14.1) 3 (7.9) 19 (16.1) 0.206 0.052
Iatrogenic preterm delivery; n (%)
- <37 weeks 10 (6.4) 7 (18.4) 3 (2.6) 0.001 0.017
- <34 weeks 5 (3.2) 4 (10.5) 1 (0.8) 0.003 0.037
Preeclampsia 8 (5.1) 4 (10.5) 4 (3.4) 0.083 0.052
Intrauterine foetal death; n (%) 0 0 0 NA NA
Placental histological criteria for maternal underperfusion; n (%) 24/56 (42.9) 13/21 (61.9) 11/35 (31.4) 0.026 0.014
Mode of delivery
Elective CS; n (%) 66 (42.3) 16 (42.1) 50 (42.4) 0.977 0.655
Emergent CS; n (%)b 9 (10) 5 (22.7) 4 (5.9) 0.022 0.236
Neonatal outcomes
Birth weight (g); mean (SD) 2,928.1 (692.8) 2,273.7 (643.4) 3,138.8 (566.7) <0.001 <0.001
5-minute Apgar score <7; n (%) 3 (1.9) 2 (5.3) 1 (0.8) 0.085 0.090
UA pH<7.20; n (%) 25 (16.2) 4 (10.8) 21 (17.9) 0.305 0.300
NICU admission; n (%) 27 (17.3) 13 (34.2) 14 (11.9) 0.002 0.039
HIV mother-to-child transmission; n (%) (n=152; 3 lost, 1 dead) 1 (0.7) 0 1 (0.9) 0.569 0.996

IUGR: intrauterine growth restriction; UA pH: umbilical artery pH; CS: Caesarean section; NICU: neonatal intensive care unit
a
Adjusted for maternal age, smoking during pregnancy, past or present drug use, low educational level and maternal body mass index
b
Elective CS excluded from denominator (n=90)

explained by the fact that they considered SGA a birth weight and in most other publications, according to the recommen-
Z-score under 2SD, which roughly corresponds to the 3rd dations of most guidelines [10, 38, 39]. Moreover, stillbirths
centile rather than the 10th centile used in the present study were excluded from that study, despite growth restriction

Fig. 1 Type of prematurity among preterm deliveries. Iatrogenic preterm birth was significantly more frequent among the IUGR group than in the
normal weight group. IUGR: intrauterine growth restriction; PTD: preterm delivery. *Adjusted for potential confounders
228
being one of the main causes of intrauterine foetal death.
Maternal BMI and previous IDU were the only epidemiolog-
ical variables that differed between pregnancies with and
without IUGR. Regarding BMI, as customised standards of
expected foetal weight are already adjusted by maternal height
and weight, the higher frequency of IUGR in the present study
is unbiased to this potential confounder. On the other hand,
although more women in the IUGR group had been intrave-
nous drug users in the past or had acquired HIV by the
parenteral route, active toxic use during the current pregnancy
did not differ from that of the non-IUGR group. Regarding
mothers infected by the vertical transmission route, although a
statistically significant association with IUGR was observed,
the small number of such cases in this study does not allow
any conclusions to be drawn. Nevertheless, similar data have
recently been published showing a higher risk of SGA among
14 women with perinatally acquired HIV [19]. Further studies
are thus needed in order to confirm this association and
investigate the possible mechanisms.
In the present study, we were not able to identify any
association between IUGR and antiretroviral treatment. How-
ever, as this was a recent HIV cohort in a developed country
with free access to antiretrovirals, more than 95 % of pregnant
women were on treatment, making it difficult to find any
association or causal effect. No significant differences were
observed with the length of treatment during pregnancy, types
of treatment or time of initiation before or during pregnancy.
In a previous study including a large number of pregnant
women without HAART, we found an association between
iatrogenic PTD and the use of HAART during the second
half of pregnancy [40]. Although IUGR was not evaluated
in that study, it is one of the main causes of iatrogenic
PTD. Similar results were observed by a French cohort
[41], which reported a significant association of induced
PTD with the initiation of ritonavir-boosted protease in-
hibitors therapy during pregnancy. The association of an-
tiretroviral treatment with IUGR requires further evalua-
tion. Possible pathogenic pathways may involve placental
vascular damage related to protease inhibitors or mito-
chondrial toxicity mechanisms, which have already been
described in cord blood and placentas of antiretroviral-
exposed pregnancies [4, 42].
A worse perinatal outcome was observed among IUGR
newborns. The median gestational age at birth was lower,
and, most importantly, this group had a higher risk of iatro-
genic preterm (below 37 weeks) and very preterm delivery
(below 34 weeks) (6- and 13-fold increased likelihood of
iatrogenic prematurity, respectively), even after adjusting for
potential confounders. Iatrogenic PTD was responsible for
70 % of preterm births among the IUGR group, but only
14 % among the non-IUGR group (Fig. 1). Preeclampsia
and foetal compromise were the main causes for the medical
indication of PTD. The observation of different types of
Eur J Clin Microbiol Infect Dis (2015) 34:223230
prematurity among groups may mean that different pathogen-
ic mechanisms are involved in each entity, as has been sug-
gested in previous publications [40]. IUGR may be related to a
direct foetal or placental toxic effect in the late 2nd or 3rd
trimesters, rather than to an earlier process in pregnancy
affecting placentation. The fact that maternal uterine artery
Doppler abnormalities were not observed in the 1st trimester
evaluation and that most cases (34/38; 89.5 %) delivered
beyond 34 weeks may support this hypothesis of late emerg-
ing placental disease [43]. Similarly, Savvidou et al. reported
normal placental perfusion in the 1st trimester among 76 HIV-
infected women, with no differences in the uterine arteries
pulsatility index when compared to HIV-negative controls,
despite a lower birth weight percentile. This superimposed
placental disease is consistent with the finding of placental
histological criteria for maternal underperfusion in most
IUGR cases. An increased risk of placental insufficiency in
the histologic analysis has previously been described among
HIV-infected women receiving HAART who delivered still-
births in Botswana [44]. Interestingly, stillbirths had a signif-
icantly lower median weight when compared to those from
untreated HIV-infected or HIV-uninfected women.
This study shows that the selection of women for closer
follow-up cannot be reliably based upon any combination of
risk factors, whether epidemiological or related to the HIV
infection. Therefore, serial ultrasound scanning during the 3rd
trimester seems to be a reasonable approach in the antenatal
surveillance for all HIV-infected pregnant women. Although
we cannot establish a causal relationship, the absence of cases
of stillbirths or neonatal death in our population indirectly
supports this strategy. In fact, prior to the policy of serial
ultrasound, we had previously reported a high rate of still-
births among HIV-infected women [45]. It has been demon-
strated that Doppler assessment in high-risk pregnancies
(mainly IUGR and pregnancy-related hypertensive disorders)
decreases the number of adverse outcomes and reduces peri-
natal mortality by 30 % [46, 47]. Therefore, the optimisation
of prenatal care as a high-risk pregnancy with specific moni-
toring for pregnancy complications may help to detect IUGR
foetuses prenatally and decide the best time for delivery,
before severe foetal compromise or foetal death occur. None-
theless, at present, the routine detection of IUGR foetuses is
not included in most current guidelines due to the lack of
supporting evidence [4850]. Our results provide the first
evidence on this issue. We have already included serial ultra-
sound in order to detect IUGR in a recent updating of Spanish
guidelines for HIV-infected pregnant women [51].
We acknowledge that our study has some limitations. First-
ly, the small sample size did not allow the pathogenic mech-
anisms related to IUGR among the HIV population to be
clarified. Almost all the women studied were receiving com-
bined antiretroviral therapy, making it difficult to find any
association between IUGR and antitretroviral treatment.
Eur J Clin Microbiol Infect Dis (2015) 34:223230
Moreover, long-term specific paediatric follow-up was lack-
ing among the cohort. Therefore, further studies are required
in order to assess the reported association between IUGR
foetuses and the risk of neurodevelopmental impairment or
long-term adverse effects.
In conclusion, a high rate of IUGR was observed among
HIV pregnancies, and it was associated with adverse perinatal
outcomes, mainly iatrogenic preterm and very preterm birth,
due to placental insufficiency. Our results support that ultra-
sound detection and follow-up with Doppler assessment of
IUGR foetuses should be part of routine antenatal care in this
high-risk population so as to improve antenatal management
and consider the optimal time for delivery.
Acknowledgements M.L., F.F., M.P. and J.O.C. contributed to the
conception and design of the study. They also performed the analysis,
statistics and interpretation of the results. M.L., A.G., S.H., M.Lonca and
J.O.C. performed the patient follow-up and collected the clinical infor-
mation of the study participants. M.L., S.H., L.G. and F.J.B. worked on
database updating. All authors underwent a critical revision of the man-
uscript and gave their final approval of the version to be published.
Ethical standards All participants gave written informed consent for
ultrasound foetal assessment according to the local Ethics Committee and
in accordance with the ethical standards laid down in the 1964 Declara-
tion of Helsinki and its later amendments. The analysis of data was
performed anonymously from medical records collected for clinical man-
agement, with omission of details that might disclose the identity of the
subjects under study.
Conflict of interest The authors declare that they have no conflict of
interest.
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