Jurnal Naoly

Obstetrics and Gynecology International
Volume 2014 (2014), Article ID 192087, 8 pages

http://dx.doi.org/10.1155/2014/192087
Review Article
Postcoital Bleeding: A Review on Etiology, Diagnosis,

and Management
Christopher M. Tarney1 and Jasmine Han2
Department of Obstetrics and Gynecology, Womack Army Medical
Center, 2817 Reilly Road, Fort Bragg, NC 28307, USA
2
Division of Gynecology-Oncology, Department of Obstetrics and
Gynecology, Womack Army Medical Center, 2817 Reilly Road, Fort
Bragg, NC 28307, USA
1
Received 1 May 2014; Revised 29 May 2014; Accepted 5 June 2014;

Published 17 June 2014
Academic Editor: W. T. Creasman
Copyright 2014 Christopher M. Tarney and Jasmine Han. This is an
open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly
cited.
Abstract
Postcoital bleeding refers to spotting or bleeding that occurs after
intercourse and is not related to menstruation. The prevalence of
postcoital bleeding ranges from 0.7 to 9.0 percent of menstruating
women. There are multiple etiologies for this common complaint in
which most are benign such as cervicitis or cervical polyps. However,
the most serious cause of postcoital bleeding is cervical cancer. There
are currently no recommendations from governing bodies such as the
American College of Obstetricians and Gynecologists on evaluating and
treating women with postcoital bleeding. The purpose of this paper is
to discuss the common causes of postcoital bleeding, the etiologies of
postcoital bleeding, and the likelihood that malignancy is the
underlying cause. After an extensive literature review, we compiled a
paper illustrating the key concepts a practitioner should know when it
comes to postcoital bleeding. Finally, this review will conclude with
treatment options for women who are found to have an identifiable
source for their bleeding and a discussion on the natural history of

postcoital bleeding in women who are found to have no identifiable
etiology on evaluation.
1. Introduction
Vaginal bleeding not related to menstruation is a common
multifactorial gynecologic complaint seen by the primary care clinician
and is a source of distress both to provider and patient as this can be a
sign of underlying malignancy. Postcoital bleeding consists of spotting
or bleeding that is not related to menstruation and occurs during or
after sexual intercourse. The point prevalence ranges from 0.7 to 9.0%
with one report indicating that the annual cumulative incidence is 6%
among menstruating women [13]. For premenopausal women who are
naturally menstruating, spontaneous resolution has been documented
in 51% at two years with no further signs of recurrence [4]. About 30%
of patients with postcoital bleeding also experience abnormal uterine
bleeding and 15% have dyspareunia [5, 6].
Postcoital bleeding mainly comes from surface lesions of the genital
tract to include cervical polyps, cervicitis, ectropion, cervical intraepithelial lesion (CIN), or carcinoma [7]. The prevalence of cervical
cancer in women with postcoital bleeding is 3.0 to 5.5% and
prevalence of CIN is 6.8% to 17.8% [6, 813]. The large range in
prevalence is due to variations in study design, but more importantly
on study location. Studies performed in developed countries have a
lower prevalence of cervical cancer and CIN due to access to screening
programs [1013]. The American College of Obstetricians and
Gynecologists and the Society for Gynecologic Oncologists have no
recommendations on the evaluation of postcoital bleeding in
menstruating women. In the United Kingdom, there are also no
established guidelines to ensure consistent practice. The United
Kingdom Department of Health reported in The Guidelines for
Suspected Cancer that urgent referral (within 2 weeks) should be made
for women more than 35 years of age with postcoital bleeding for more
than 4 weeks due to elevated risk for underlying cervical cancer and
early referral (within 46 weeks) may be made in all other cases of
unexplained postcoital bleeding [14]. These recommendations are
refuted by Khattab et al. who report that there is no significant
difference in the prevalence of cervical cancer or CIN in women either
older or younger than 35 years [15].
The Royal Australian College of Obstetricians and Gynaecologists, The

Royal Australian College of General Practitioners, The Australian
Society for Colposcopy and Cervical Pathology, and the Commonwealth
Department of Human Services and Health report that colposcopy
should be the primary diagnostic procedure in evaluating women with
persistent postcoital bleeding and have a suspicious lesion on their
cervix or women with a friable cervix [7]. Nevertheless, these
governing bodies report that postcoital bleeding alone is not an
absolute indication for colposcopy [16].
The purpose of this paper is to discuss different etiologies of postcoital
bleeding, to examine the current literature regarding diagnostic
evaluation, and to review treatments of this concerning symptom
according to underlying etiology. Currently, there is no evidence from
randomized clinical trials or recommendations from the American
College of Obstetricians and Gynecologists or the Royal College of
Obstetricians and Gynaecologists on standard of care for evaluation of
postcoital bleeding [12].
2. Etiology
The differential diagnosis for women who present with postcoital
bleeding is broad. Most women with postcoital bleeding have benign
disease, which is reassuring given that the initial concern for both
patient and provider is the possibility of underlying malignancy. Table 1
outlines some of the most common causes for postcoital bleeding.
Table 1: Common causes of postcoital bleeding.

2.1. Cancer
The greatest fear for patients experiencing postcoital bleeding and
providers taking care of these patients is the concern for underlying
malignancy. Postcoital bleeding is the presenting complaint in 11% of
women with cervical cancer [13]. Cervical cancer is the second most
common cancer in women throughout the world. Annual global
estimates for the year 2000 were 233,400 deaths and 470,600 new
cases; in the United States in 2009, there were estimates that there
were 11,270 new cases of cervical cancers and 4,070 deaths [17, 18].
The mean age for cervical cancer is 51.4 years [17]. The most
important risk factor for this disease include women who have been
infected with a high risk strain of the human papilloma virus (HPV), the
virus believed to cause cervical cancer. Other risk factors include
immunosuppression and smoking. Table 2 illustrates the risk of cervical
cancer in women with postcoital bleeding based on age [19]. The
incidence of women with postcoital bleeding from cervical cancer has
significantly decreased over the past decades due to enhanced
screening for cervical cancer. Cervical cancer screening, via cervical
cytology either with or without testing for HPV, allows for the
identification of premalignant and malignant cervical disease, which is
important given that CIN is largely asymptomatic [9, 20]. The most
common histopathologic types of cervical cancer include squamous
cell carcinoma (69%) and adenocarcinoma (25%) [21]. Of the two
types, adenocarcinoma may be less likely to present with postcoital
bleeding as lesions may be higher in the cervical canal and protected
from the trauma of intercourse [1, 9]. Women presenting with
postcoital bleeding who are found to have cervical cancer often are
diagnosed with a higher stage of cancer than asymptomatic women
[11, 22].
Table 2: Risk of cervical cancer in women with postcoital bleeding.

Although cervical cancer may be the initial concern of patients
presenting with postcoital bleeding, vaginal cancer is another
gynecologic malignancy for which postcoital bleeding may be the
presenting symptom. Primary vaginal cancer is responsible for 3% of
malignant neoplasms of the female genital tract. There are
approximately 3000 cases diagnosed each year in the United States
and approximately 900 deaths [23]. Vaginal intraepithelial neoplasia
(VAIN), the precursor lesion to invasive vaginal carcinoma, is also rare
with an incidence of approximately 0.2-0.3 cases per 100,000 women
in the United States [24]. Most patients with VAIN or vaginal cancer are
asymptomatic, but many women report postcoital spotting and unusual
vaginal discharge [25]. Primary vaginal carcinoma can often be located
on the posterior aspect of the upper one-third of the vagina. This area
of the vagina has close proximity to the cervix in which it is believed
that one of the most important risk factors for development of VAIN is
from previous or concomitant cervical dysplasia [26, 27].
Cancer of the endometrium is the most common gynecologic cancer in

the United States. In 2008, there were 40,100 cases of cancer of the
endometrium and 7474 deaths attributed to this disease [28]. Vaginal
bleeding in postmenopausal women is primarily secondary to atrophic
changes, but this symptom can be the presenting complaint in 90% of
women with endometrial carcinoma [29].
Finally, there are primary malignancies that may manifest in the lower
genital tract and present with postcoital bleeding. Primary malignant
lymphoma of the female genital tract is rare [30]. Non-Hodgkins
lymphoma has been found to be present in the cervix, vagina, and
uterus. There are over one hundred reports of primary cervical nonHodgkins lymphoma of the cervix in which primary cervical lymphoma
accounts for less than 1% of extranodal lymphomas [31]. Nevertheless,
it is more common to have cervical involvement of lymphoma
secondary to widespread disease [32].
2.2. Cervicitis
Cervicitis refers to an inflammation of the cervical stroma which can be
either acute or chronic. Cervicitis typically presents with watery and
mucopurulent discharge; however, postcoital bleeding is also
associated with this condition. Acute cervicitis may be caused by
infection with C. trachomatis, N. gonorrhea, T. vaginalis, G. vaginalis,
and mycoplasma species [2]. Chronic cervicitis usually does not have
an infectious source. Cervical infection is important to diagnose and
treat early as this infection can ascend into the upper genital tract and
lead to significant complications to include pelvic inflammatory
disease, infertility, chronic pelvic pain, and increased risk for ectopic
pregnancy.
2.3. Endometritis
Endometritis is an inflammation of the endometrium which can be
either acute or chronic; differentiation is based on pathologic
evaluation. Acute endometritis has the presence of microabscesses
within the endometrial glands, whereas chronic endometritis has
multiple plasma cells within the endometrial stroma [33, 34]. Chronic
endometritis is often caused by infectious agents but can also be
caused from foreign bodies, polyps, or fibroids within the uterine
cavity; nevertheless, no identifiable source is found in one-third of
patients [35]. Most women with symptomatic chronic endometritis can
present with heavy menstrual bleeding or intermenstrual bleeding;
however, some women may initially complain of postcoital bleeding.
2.4. Cervical Polyps

Cervical polyps are not an infrequent incidental finding during
speculum exams and can be a source of postcoital bleeding secondary
to cervical trauma with intercourse. Both endocervical and cervical
polyps are the most common benign neoplastic growth that occurs on
the cervix with an incidence of 4% of gynecologic patients [36]. Polyps
typically occur in multiparous patients in their 40s to 50s. Most
patients with cervical polyps only have one, but it is not uncommon to
have more than one. On gross examination, they appear as smooth,
reddish purple lobular structures that are friable and bleed easily when
touched. Most polyps are only a few centimeters in size. Polyps may
arise from the endocervical portion of the cervix or appear on the
cervical portio. It is believed that these polyps originate from recurrent
inflammation of the cervix versus focal response to hormonal
stimulation.
2.5. Cervical Ectropion
Cervical ectropion refers to the eversion of the endocervix which
exposes the columnar epithelium to the vaginal milieu. It is important
to note that the presence of ectropion does not indicate a pathologic
condition. This area of the cervix may have a reddish appearance and
be covered with yellow discharge in which most women with
symptomatic cervical ectropion complain of vaginal discharge. This
condition is often seen during adolescence, women taking oral
contraceptive pills, and pregnancy due to the remodeling process of
the cervix. The exposure of the columnar epithelium of the endocervix
to the vagina then increases the risk of bleeding with intercourse due
to the friability of these cells [37].
2.6. Pelvic Organ Prolapse
Pelvic organ prolapse refers to the herniation of pelvic organs [cervix,
bladder, rectum, and uterus] to or beyond the vaginal walls. It is hard
to determine the exact prevalence of pelvic organ prolapse for multiple
reasons: most women only present when symptoms become severe,
providers are poor at screening women during routine visits, many
women are embarrassed to report these symptoms to providers, and
women with minor prolapse often do not report these symptoms to
their providers. Risk factors for pelvic organ prolapse include parity,
obesity, age, hysterectomy, race, constipation, and chronic cough.
There can be significant irritation and trauma to the vagina and cervix
when these organs prolapse through the introitus which can lead to
postcoital bleeding [38].
2.7. Vaginal/Vulvar Etiologies

Vaginal atrophy, also known as urogenital atrophy, atrophic vaginitis,
or vulvovaginal atrophy, results from a loss of estrogen which can lead
to vulvovaginal complaints such as postcoital bleeding. This condition
typically occurs in menopausal women but may also occur in women
who experience a decrease in estrogen. Other complaints include
vaginal dryness, vaginal burning, dyspareunia, decreased lubrication,
vaginal discharge, and pelvic pressure. Lastly, lichenoid lesions such as
lichen planus and lichen sclerosis may also lead to postcoital bleeding.
2.8. Benign Vascular Neoplasms
Vascular tumors of the female genital tract are rare [39]. These lesions
include
hemangiomas,
lymphangiomas,
angiomatosis,
and
arteriovenous malformation. Most tumors are found incidentally on
exam due to their asymptomatic nature. However, when symptomatic,
postcoital bleeding may be a symptom associated with these
conditions [40].
2.9. Sexual Abuse
Domestic and sexual abuse is a serious public health problem in the
United States by which 32 million Americans are affected [41].
Gynecologists should screen women for abuse at every single visit
regardless of complaints. For example, one study demonstrated that
5.6% of women were diagnosed with sexual abuse prior to instituting a
universal screening program, whereas, after implementation of
universal screening, 30% of the population was found to be affected by
abuse [42]. Depending on the extent of the abuse, victims may
experience significant genital trauma.
3. Diagnosis
At this time, there are no established guidelines from the American
College of Obstetricians and Gynecologists or the Royal College of
Obstetricians and Gynaecologists or evidence from randomized clinical
trials to base recommendations on diagnosis and treatment of
postcoital bleeding. The following discussion provides various
considerations to take into account when approaching a patient with

postcoital bleeding. Figure 1 presents a diagnostic algorithm for
women with postcoital bleeding.
Figure 1: Diagnostic approach to postcoital bleeding.

3.1. History
A thorough emphasis on patient history often leads to an accurate
diagnosis of postcoital bleeding. With all gynecologic patients, it is
important to obtain an accurate menstrual history. Factors which
should be elicited from the patient include the frequency of the
patients menstrual cycle, days of menstruation, presence of heavy
bleeding, presence of intermenstrual bleeding, and whether cycles are
regular or irregular. The duration of normal menstrual flow is 5 days
with cycles typically lasting between 2135 days [43]. Clinicians should
also evaluate if the patient is postmenopausal which is defined as 12
months of amenorrhea without any other physiologic or pathologic
cause. Moreover, history should focus on whether the patients
postcoital bleeding is truly bleeding that occurs as a direct result of
intercourse or if it is secondary to irregular menstrual bleeding. History
may also help to differentiate between whether bleeding is originating
from the uterus or cervix. Patients with abnormal uterine bleeding
often report heavy periods, intermenstrual bleeding not related to
intercourse, and irregular menstrual cycles.
There are multiple considerations to take into account for patients past
medical history. Screening should be performed as to whether the
patient has been diagnosed or has any symptoms concerning a
bleeding disorder. Regarding surgical history, determine whether there
have been surgeries on the genital tract with focus on timing and
indication for the surgery. A detailed sexual history should be obtained
with focus on number of partners, new partners, and history of any
sexually transmitted infections for either the patient or her partners. It
is imperative to also screen patients for domestic abuse and/or sexual
abuse as genital tract trauma can lead to postcoital bleeding. Patients
may not be willing to volunteer this information for either
embarrassment or fear of retaliation. Providers should attempt to
establish rapport with the patient and create an environment in which
patients may be willing to share this information. If the patients
partner is present, then strategies may be employed to have the
partner step outside the exam room during the time of pelvic exam, at
which point one may also evaluate the patient privately for concerns of
abuse. Finally, providers should ensure cervical cancer screening is upto-date.
There are also multiple factors to ask on review of symptoms that can
help establish a diagnosis. For example, one should inquire about pain
with focus on pain during menstruation (dysmenorrhea) or with
intercourse (dyspareunia). Regarding the latter, a detailed history
should be obtained as to when the dyspareunia occurs: at all times,
with deep penetration, or in certain positions. Patients should be asked
if there has been any change in discharge, specifically color,
consistency, frequency, and odor. Finally, patients should be screened
for symptoms concerning for pelvic organ prolapse such as a feeling of
heaviness in the vagina, sensation that things are dropping, need to
splint in order to have bowel movement or urination, and visualization
of organs prolapsing from the vagina.
3.2. Physical Examination
Every woman presenting with postcoital bleeding requires a thorough
examination of the genital tract. A bivalve speculum exam should be
performed to evaluate the vaginal rugae and cervix. Attention should
be focused to determine if there are any lacerations or trauma to the
vaginal walls. Upon examining the cervix, one should evaluate any
obvious gross lesions on the cervix or lesions protruding through the
cervical canal. Colposcopy may be considered if there are any
suspicious lesions on the cervix to further evaluate the lesion under
high power. In obtaining cultures or clearing mucus from the cervix,
one should also determine whether gentle palpation alone of the cervix
with a swab is able to recreate bleeding.
Considerations may then be made to break down the bivalve speculum
and perform an inspection of the vagina with one blade of the
speculum. This may allow for a better visualization of the vaginal rugae
as there is less risk of obstruction by the blades of the speculum. This
technique may be used to evaluate signs of pelvic organ prolapse. A
blade should be placed along the anterior vaginal wall, while having
the patient Valsalva, to evaluate prolapse of the posterior structures.
A bimanual exam is performed to evaluate the size and contour of the
uterus as well as the presence of any adnexal masses. During this
exam, one may delineate whether there is presence of cervical motion
tenderness which may help with diagnosing an underlying infection. If
the patient has complained of dyspareunia or pelvic pain, then it is also

important to delineate the location of the pain. Most women will not
find a bimanual exam comfortable, so it is important to specifically ask
what on exam reproduces the patients pain. Finally, if there is concern
for underlying malignancy, then one should also evaluate the inguinal
lymph nodes to determine if there is any lymphadenopathy. A
rectovaginal exam should be performed to determine if there are any
masses or nodularities located on the anterior surface of the rectum or
extension of disease into the parametrium.
3.3. Laboratory Tests
On speculum exam, there are multiple cultures that may be obtained
to further evaluate postcoital bleeding. Nucleic acid amplification
testing (NAAT) for N. gonorrhoeae, C. trachomatis, and T. vaginalis
should routinely be obtained in women presenting with postcoital
bleeding. Even though wet mount is the most cost-effective means of
diagnosing Trichomonas, the overall sensitivity is low and is dependent
on the inoculum size; thus, NAAT testing has become popular due to its
relatively high sensitivity and specificity. Women who are not recent on
cervical cancer screening may also undergo cervical cytology, with or
without testing for high risk HPV. Nevertheless, it is important to note
that the false negative rate for Pap smears in the presence of invasive
cancer is 50%; thus, gynecologists must be cognizant that a normal
smear does not rule out underlying malignancy in women presenting
with postcoital bleeding [44].
There are multiple variations based on expert opinion on which
patients with postcoital bleeding should be referred for colposcopy.
There is little debate that women with an abnormal pap smear or a
grossly visible lesion that is suspicious for an underlying malignancy
should be referred for colposcopy. Nevertheless, there is controversy
on whether colposcopy should be performed on women with no visible
lesions and negative cervical cancer screening results on recently
performed testing. One may argue that postcoital bleeding alone is not
an absolute indication for colposcopy [12]. Providers should discuss
with their patients that there are no guidelines or evidence to base
recommendations in these scenarios [19]. One retrospective study of
314 women with postcoital bleeding seen by a gynecologic service
found that 20% of women diagnosed with cervical cancer or vaginal
cancer on colposcopy had a normal speculum exam with negative
cytology prior to the procedure [11]. In short, there is limited evidence
to base recommendations on colposcopy for women with negative Pap
smears and no obvious lesion on exam. However, the Working Group of

the Royal Australian College of General Practice and of Obstetrics and
Gynecology [7] recommend that general practitioners refer women for
colposcopy if they have one of the following qualifications;
nevertheless, it is important to realize that these recommendations are
not evidence based [15]:(1)persistent postcoital bleeding,(2)postcoital
bleeding associated with a single smear suggestive of LGSIL or worse,
(3)postcoital bleeding associated with repeated smears with minor
atypia or wart virus changes.
Directed biopsy with colposcopy remains the standard for disease
detection [43]. Recent studies, however, have compared directed
biopsy to blind four-quadrant ectocervical biopsies or loop excision
procedure as diagnostic criteria [45, 46]. These studies found that the
presence of CIN 2 and higher was missed on directed biopsy but
detected on random four-quadrant biopsies in 18.631.6% of times [46,
47]. Another study, however, demonstrated that diagnosis of CIN 2 and
higher was found in 57.1% of women with colposcopy directed biopsy
versus 37.4% with random biopsy [48]. Based on these studies, the
American College of Obstetricians Gynecologists recommends that
biopsies should be performed on all visible lesions [49]. These
recommendations and studies pertain to patients with abnormal
cytology. It is hard to interpret these recommendations in women with
postcoital bleeding and no history of abnormal cytology.
There are multiple ways to evaluate the endocervical and endometrial
cavity for sources of postcoital bleeding. One option is to perform an
office endometrial biopsy which can evaluate for the presence of
endometrial hyperplasia, malignancy, and endometrial polyps. If the
patient is not amenable to this procedure or if further imaging is
indicated, then a saline infused sonohysterogram is another useful
diagnostic technique to evaluate the contours of the uterine cavity.
Finally, depending on the presence of other complaints, one may also
consider diagnostic hysteroscopy to evaluate the cervical canal and
uterine cavity; although this procedure should be reserved for patients
with complaints of abnormal uterine bleeding which may suggest an
endometrial source for the abnormal bleeding.
The clinical approach to postmenopausal women presenting with
postcoital bleeding warrants other considerations to exclude carcinoma
of the endometrium. The American College of Obstetricians and
Gynecologists reports that there are two acceptable methods for
evaluating
malignancy:
endometrial
biopsy
or
transvaginal
ultrasonography. An endometrial thickness of greater than 4mm in a

patient with postmenopausal bleeding requires further evaluation with
sonohysterography, office endometrial biopsy, or hysteroscopy.
Alternatively, providers may also decide to initiate the evaluation of
postmenopausal bleeding with performing an endometrial biopsy [50].
4. Management
The majority of women presenting to their primary care physician with
the complaints of postcoital bleeding will be found to have no obvious
underlying cause for their bleeding based on history, exam, or
laboratory investigation [11]. Nevertheless, the reassuring aspect is
that 60% of naturally menstruating women with postcoital bleeding will
have spontaneous resolution of symptoms within six months [4]. Half
of these women will maintain resolution for two years [4].
4.1. Infection
Any woman who is found to have evidence of genital tract infection
should be immediately treated to prevent long term repercussions.
Treatment options should be guided based on laboratory and
microscopy findings. With respect to a clinical diagnosis of pelvic
inflammatory disease, treatment should not be withheld if testing for
chlamydia and gonorrhea are negative as the three major criteria
needed for the diagnosis of pelvic inflammatory disease per the
Centers for Diseases Control and the World Health Organization include
cervical motion tenderness, bilateral adnexal tenderness, and
abdominal tenderness.
4.2. Cervical Ectropion
Cervical ectropion does not require treatment unless bleeding is
persistent and bothersome to the patient. Prior to proceeding with
treatment, one should ensure that they have ruled out underlying
malignancy as certain treatments for cervical ectropion may mask or
exacerbate malignant lesions. Cervical ablation with either cryotherapy
or electrocautery is effective in mitigating further postcoital bleeding.
However, there are significant side effects to include copious vaginal
discharge until healing is complete and cervical stenosis which can
affect subsequent pregnancies [51]. An alternative therapy may be to
use acidifying agents such as boric acid suppositories 600mg vaginally
at bedtime [52].
4.3. Polyps
Clinicians should consider removal of symptomatic polyps or when they
appear atypical with concerns for malignancy. A cervical polypectomy
can often be performed in the office without sedation. Removal is
performed by first placing a speculum into the vagina to visualize the
cervical polyp. A forcep may then be used to grasp the polyp at its
base and twist it off. If the base is visualized, then cauterization should
be performed to prevent further bleeding. All polyps that are removed
should be sent to pathology to be evaluated for malignancy [5254].
Furthermore, if there is concern for endometrial polyps, then the
patient should be referred to operative hysteroscopy with possible
dilation and curettage.
4.4. Cancer
Colposcopy with directed biopsies is indicated for patients with
abnormal cytology. If patients are found to have CIN on cervical biopsy,
then one may follow the guidelines established by the American
College of Obstetricians and Gynecologists or the American Society for
Colposcopy and Cervical Pathology to determine whether the patient
needs to be referred for an excisional procedure versus surveillance.
Patients who are found to have genital tract cancer such as vaginal or
cervical cancer should be referred to a gynecologic oncologist for
further evaluation and treatment.
4.5. Vaginal Atrophy
Postcoital bleeding associated with vaginal dryness may first be
treated with vaginal moisturizers and lubricants which can be used
prior to and during intercourse. Although these methods may assist
with ameliorating discomfort during intercourse, they do not have any
direct effect on improving atrophic changes. Women who continue to
experience postcoital bleeding despite lubricants may require vaginal
estrogen therapy. Estrogen therapy is one of the most effective
treatment options for vaginal atrophy as it thickens the vaginal
epithelium and decreases dryness. Low dose vaginal estrogen therapy
should be the first line treatment for postmenopausal women with only
vaginal complaints as it is more effective and also prevents possible
side effects of systemic treatment. Special considerations should be
made with use of estrogen therapy for women who have breast cancer
and/or cardiovascular disease.
5. Conclusion
Postcoital bleeding can be an annoying complaint for patients and a

worrisome symptom for providers due to the risk of underlying
malignancy. Despite being a common gynecologic problem, there is
large diversity among gynecologists on the management of postcoital
bleeding [55]. Unlike abnormal uterine bleeding or the management of
abnormal cytology, there are no recommendations from governing
bodies on the management of postcoital bleeding. Patients presenting
with postcoital bleeding require a full history and physical examination
to help in developing a differential diagnosis to guide evaluation and
treatment. Although most patients with postcoital bleeding do not have
underlying malignancy, providers must pay close attetion to ensure
that appropriate screening tests are up-to-date. Physicians should also
be aware that a large portion of women presenting with postcoital
bleeding will not have an obvious source for their bleeding; however,
as long as malignancy is ruled out, most of these womens symptoms
will naturally resolve in premenopausal women.
Disclaimer
The opinions or assertions contained herein are the private views of
the authors and are not to be construed as the official policy of the
Department of the Army, Department of Defense, or the U.S.
Government.
Conflict of Interests
The authors report no conflict of interests.
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http://dx.doi.org/10.1155/2014/502081
Editorial
Preeclampsia Prediction and Management

Irene Rebelo1,2 and Joo Bernardes3,4,5,6
Department of Biochemistry, Faculty of Pharmacy, University of Porto,
Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
2
Institute for Molecular and Cell Biology (IBMC), University of Porto,
4150-180 Porto, Portugal
3
Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
4
Center for Research in Health Technologies and Information Systems
(CINTESIS), Faculty of Medicine, University of Porto, 4200-450 Porto,
Portugal
5
Department of Obstetrics and Gynecology, Pedro Hispano Hospital,
4454-509 Matosinhos, Portugal
6
Department of Obstetrics and Gynecology, S. Joo Hospital, 4200-450
Porto, Portugal
1
Received 11 August 2014; Accepted 11 August 2014; Published 9

November 2014
Copyright 2014 Irene Rebelo and Joo Bernardes. This is an open
access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited.
International guidelines still simply define preeclampsia (PE) as an

acute pregnancy related hypertensive condition characterized by
hypertension and proteinuria that typically appears after the 20 weeks
of gestation and resumes after delivery [1]. With these relatively
simple guidelines centered on blood pressure and proteinuria
assessment, along with eclampsia prevention with magnesium
sulphate and fetal delivery in the most severe cases, the developed
countries have managed to control the high maternal and fetal
mortality rates related with PE that still affect the developing countries
without adequate basic clinical ante- and intrapartum facilities [1].
However, we know today that PE is a more complex condition that
develops during the first weeks of pregnancy and that may have
consequences in the future health of the mother and child.
PE remains a leading cause not only of maternal and fetal mortality in
the developing countries, but also of morbidity in the developed
countries accounting for a high number of maternal admissions to
intensive care units, fetal growth restriction, and premature iatrogenic
deliveries, without effective early prediction and/or prevention.
Moreover, with the increased life expectancy of the developed
countries it is also known today that women with history of PE and
their offspring present an increased risk of future hypertension and
cardiovascular diseases, among others [1].
In this special issue, several authors address the above-mentioned
issues, namely, on early PE prediction, management, and risk of future
cardiovascular diseases [2].
L. C. Poon and K. H. Nicolaides remind us that PE screening by a
combination of maternal risk factors, uterine artery Doppler, mean
arterial pressure, maternal serum pregnancy associated plasma
protein-A, and placental growth factor can identify about 95% of cases
of early onset PE for a false-positive rate of 10%. This excellent news
can be already put in practice using specially commercialized kits. It
opens new perspectives on early prediction and diagnosis, allowing
better application of preventive and curative measures, namely, using,
respectively, aspirin and timely antihypertensive treatment and/or
pregnancy termination [1]. This hope for better perspectives on early
prediction of PE has also been exposed by C. Teixeira et al., who
managed to show that even a common program for first trimester
screening of aneuploidies may already improve our current capabilities
based only on the relatively soft above-mentioned clinical assessment
of blood pressure and proteinuria [1], although in a much more modest
way than when using the model presented by L. C. Poon and K. H.
Nicolaides.
On the other hand, S. C. Kane et al. elaborate on contemporary
management principles pertaining to maternal and fetal neurological
sequelae of PE. As they outline, the neurological complications of
preeclampsia and eclampsia are major contributors of PE related

maternal and fetal morbidity and mortality that need to be seriously
taken into account and adequately addressed.
Finally, A. Matos et al. and P. V. Pinto et al. tackle the issue of PE and
the risk of future cardiovascular disease. A. Matos et al. concluded that
previously PE women, either subsequently hypertensive or
normotensive, present significant differences in myeloperoxidase,
nitrites, liver enzymes, and other cardiovascular risk biomarkers,
whose variation may be modulated by haptoglobin 1/2 functional
genetic polymorphism. They provide more evidence not only on the
association between PE and future cardiovascular diseases, but also on
the putative pathogenic paths underlying this situation. However, in
contrast with all these developments on the recognition and
understanding of the association between PE and the development of
future cardiovascular disease, P. V. Pinto et al. showed that the majority
of 141 cases of preeclampsia and chronic hypertension with
superimposed preeclampsia diagnosed at their institution between
January 2010 and December 2013, as well as general practitioners, did
not take into consideration a previous pregnancy affected by
preeclampsia as a risk factor for future cardiovascular disease, namely,
in the implementation of healthy behaviours and/or adequate medical
treatment. This shows that educational and prevention programs urge
in this area, in both patients and the general practitioners levels.
We hope this special issue provides not only new data for daily clinical
practice, but also inspiration to pursue the hard way of PE research, in
all its multiple and complex areas.
Irene Rebelo
Joo Bernardes
References
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Blackwell, and B. M. Sibai, A history of prior preeclampsia as a
risk factor for preterm birth, American Journal of Perinatology,
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http://dx.doi.org/10.1155/2015/342065
Research Article
Effect of Umbilical Cord Entanglement and Position on

Pregnancy Outcomes
Natsuko Kobayashi,1 Shigeru Aoki,1 Mari S. Oba,2 Tsuneo
Takahashi,1 and Fumiki Hirahara3
Perinatal Center for Maternity and Neonates, Yokohama City University
Medical Center, 4-57 Urafunecyou, Minami-ku, Yokohama, Kanagawa
232-0024, Japan
2
Department of Biostatistics and Epidemiology, Yokohama City
University Graduate School of Medicine and University Medical Center,
Yokohama, Japan
1
Department of Obstetrics and Gynecology, Yokohama City University

Hospital, Yokohama, Japan
3
Received 16 May 2015; Accepted 29 June 2015

Academic Editor: Everett Magann
Copyright 2015 Natsuko Kobayashi et al. This is an open access
article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Abstract
Introduction. To investigate the effect of complex umbilical cord
entanglement primarily around the trunk on pregnancy outcomes.
Methods. We studied 6307 pregnant women with singleton pregnancies
who underwent vaginal delivery of an infant at 37 weeks of gestation.
Cases were classified into no cord, nuchal cord, and body cord groups
and defined as cases without umbilical cord entanglement, one or
more loops of the umbilical cord around the neck only, and umbilical
cord around the trunk only, respectively. Pregnancy outcomes were
compared among these three groups. Results. The no cord, nuchal
cord, and body cord group included 4733, 1451, and 123 pregnancies,
respectively. Although delivery mode was not significantly different
among the three groups, 1-minute Apgar scores <7 and umbilical
artery (UA) pH <7.10 were significantly more common in the umbilical
cord entanglement groups than in the no cord group. In particular, the
frequency of 5-minute Apgar scores <7 was significantly higher (),
whereas that of UA pH <7.10 tended to be higher () in the body cord
group than in the nuchal cord group. Conclusion. Compared to nuchal
cord, umbilical cord entanglement around the trunk was associated
with a higher risk of low Apgar scores and low UA pH.
1. Introduction
Umbilical cord entanglement is the most common pathological
condition among umbilical cord abnormalities [1], with an incidence
ranging from 14.7% to 33.7% of all deliveries [13]. Umbilical cord
entanglement reportedly increases the risk of prolonged labor and
nonreassuring fetal status due to umbilical cord compression [1, 312],
while some reports indicate that the risk of cesarean section or forced
delivery is not increased [1, 5, 7, 1316]. Therefore, consensus has not
been reached. In addition, to the best of our knowledge, the majority of
reports regarding umbilical cord entanglement concern nuchal cord

entanglement, with no reported case concerning any other type of
umbilical cord entanglement. Therefore, this study aimed to
investigate the effect of complex umbilical cord entanglement
primarily around the trunk on pregnancy outcome.
2. Materials and Methods

Data were retrospectively analyzed using the medical records of 8636
women with singleton pregnancies who had undergone attempted
vaginal delivery at 37 gestational weeks between January 2004 and
December 2013 at Yokohama City University Medical Center. Women
with a serious complication, such as hypertension or diabetes, who
delivered a newborn with congenital anomalies or with fetal
malpresentation, were excluded. Consequently, 6307 of the 8636
women were included in this study. This study has been approved by
the ethics committee of the Yokohama City University Medical Center.
The presence or absence of umbilical cord entanglement was
determined at the level of the umbilicus during delivery. The no cord
group included cases without umbilical cord entanglement. The nuchal
cord group included cases with at least one loop of the umbilical cord
around the neck only. The body cord group included cases with the
umbilical cord wrapped around the trunk, excluding the neck. Cases
with umbilical cord entanglement around multiple parts, such as
entanglement around both the neck and trunk or around both the neck
and upper/lower limbs, were excluded. Pregnancy outcomes were
compared among the 3 groups: no cord, nuchal cord, and body cord
groups.
The following maternal characteristics were collected: maternal age at
delivery, parity, and gestational age at delivery. The main outcome
measures were delivery mode, birth weight, birth height, 1-minute
Apgar scores 7, 5-minute Apgar scores 7, umbilical artery (UA) pH 7.1,
and an excessively long umbilical cord. An excessively long umbilical
cord was defined as an umbilical cord measuring 70cm in length. Data
are expressed as mean standard deviation or frequency (percentage).
The IBM SPSS Statistics version 19 program was used for statistical
analyses. Categorical variables were compared using tests. Analysis of
variance and t-tests were used to compare continuous variables.
Statistical tests were considered significant at a value 0.05.
3. Results
The no cord group included 4733 pregnancies, the nuchal cord group
included 1451 pregnancies, and the body cord group included 123
pregnancies. Table 1 shows the maternal characteristics. No significant
difference was observed among the groups in maternal age at delivery,
parity, or gestational age.
Table 1: Maternal characteristics, compared between the 3 groups.
Table 2 shows the main outcome measures for pregnancy outcomes
among the 3 groups. No significant difference in delivery mode was
observed among the groups. Moreover, the groups with umbilical cord
entanglement, which were the nuchal cord and body cord groups, had
significantly longer umbilical cords, compared with the no cord group.
In particular, the nuchal cord group had the longest umbilical cord and
included significantly more cases of excessively long umbilical cord.
Significant differences in the frequencies of 1-minute and 5-minute
Apgar scores 7 and 7, respectively, and UA pH 7.1 were observed
between the 3 groups, with higher frequencies observed in the body
cord group than in the other 2 groups. Significant differences were
observed in neonatal birth weight between the no cord group and
umbilical cord entanglement groups (), and birth weight was lower in
the nuchal cord and body cord groups than in the no cord group. There
were no significant differences in neonatal birth height among the 3
groups.
Table 2: Comparison of pregnancy outcomes between the 3 groups.
4. Discussion
Although delivery mode was not significantly different among the 3
groups, the frequencies of 1-minute Apgar scores 7 and UA pH 7.10
were significantly higher in the groups with umbilical cord
entanglement than in the no cord group. In particular, the frequency of
5-minute Apgar scores 7 was significantly higher () and frequency of
UA pH 7.10 tended to be higher () in the body cord group than in the
nuchal cord group.
In this study, the presence or absence of umbilical cord entanglement
did not affect the delivery mode. This finding is similar to that of the
majority of previous studies, in which there were no differences in
cesarean section rates based on the presence or absence of umbilical
cord entanglement [1, 5, 6, 1316]. Meanwhile, Larson et al. [4]
reported that the instrumental delivery rate was higher in cases with
multiple umbilical cord entanglement, but cesarean section rates were
not significantly different. Moreover, Bernad et al. [7] reported that

umbilical cord entanglement might be a cause of intrauterine fetal
death even though there was no difference in forced delivery rates
based on cord entanglement. The authors recommended that rigorous
management with fetal heart rate monitoring should be conducted
during delivery when ultrasonography clearly reveals umbilical cord
entanglement and cesarean section should be considered when
nonreassuring fetal status is detected.
In the groups with umbilical cord entanglement, the frequencies of 1minute Apgar scores 7 and UA pH 7.10 were higher than in the no cord
group. Assimakopoulos et al. [6] reported that cases with umbilical
cord entanglement more frequently had low Apgar scores and low UA
pH as have many other studies for either low Apgar scores or low UA
pH [1, 4, 6, 8, 10, 12]. The results of the present study also support the
findings of these studies and confirm that the presence or absence of
umbilical cord entanglement affects neonatal conditions at delivery.
The frequency of 5-minute Apgar scores 7 was significantly higher in
the body cord group compared with the nuchal cord group in the
present study, and the frequency of UA pH 7.10 also tended to be
higher. To our knowledge, the majority of studies regarding umbilical
cord entanglement concern nuchal cord entanglement, and no
previous study has investigated umbilical cord entanglement around
the trunk. The lower Apgar scores and UA pH in the body cord group
than in the nuchal cord group might be explained by a greater
likelihood to suffer umbilical cord compression during uterine
contraction in fetuses with umbilical cord entanglement around the
trunk compared with nuchal cord entanglement, because a space
between the head and trunk is not present in the former but is in the
latter.
Neonatal birth weight was 34g and 45g lower in the nuchal cord and
body cord groups, respectively, than in the no cord group. In a study of
neonatal outcomes based on the presence or absence of umbilical cord
entanglement in 57853 deliveries, Ogueh et al. [5] reported that the
birth weight of fetuses with nuchal cord entanglement was 55g lower
than without nuchal cord entanglement. The authors suggested that
chronic intermittent cord compression with hypoxia might lead to fetal
growth restriction; alternatively, smaller fetuses have more space to
move around in the uterus and are consequently more likely to have
umbilical cord entanglement. Meanwhile, Sheiner et al. [1] reported in
a similar study which included 166318 deliveries that the birth weight
of fetuses with nuchal cord entanglement tended to be higher.

Although the results of the present study support those reported by
Ogueh et al. [5], further studies are needed to establish firm
conclusions regarding the relationship between umbilical cord
entanglement and fetal growth.
The present study has several limitations. First, it was conducted with a
small sample in a single institution. Second, the effects of nuchal cord
entanglement were not evaluated based on the number of loops.
Moreover, cases with multiple umbilical cord entanglements involving
multiple parts of the body, such as entanglement around both the neck
and upper/lower limbs, were excluded.
In conclusion, umbilical cord entanglement is associated with an
increased risk of low Apgar scores and low UA pH. The present study
suggests that fetuses with complex umbilical cord entanglement
primarily around the trunk, but not the neck, are strongly affected by
umbilical cord compression during delivery. However, delivery modes
were not affected by any type of umbilical cord entanglement, which
supports the findings of previous studies. Umbilical cord entanglement
is a common pathological condition encountered in daily clinical
practice. Although it might affect neonatal conditions during delivery,
vaginal delivery can be safely performed in many cases, and undue
concern should not be passed on to the mothers, even when
ultrasonography reveals the presence of umbilical cord entanglement
before delivery.
The authors declare that they have no conflict of interests to declare.
The authors confirm that the results of this paper have not been
distorted by research funding or conflict of interests.
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http://dx.doi.org/10.1155/2015/501829
Review Article
Maternal and Pediatric Health Outcomes in relation to

Gestational Vitamin D Sufficiency
Stephen J. Genuis
Faculty of Medicine, University of Calgary and University of Alberta,
2935-66 Street, Edmonton, AB, Canada T6K 4C1
Received 29 September 2015; Revised 27 October 2015; Accepted 19
November 2015
Academic Editor: W. T. Creasman
Copyright 2015 Stephen J. Genuis. This is an open access article
distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Abstract
Juxtaposed with monumental improvement in maternal-fetal outcomes
over the last century, there has been the recent emergence of rising
rates of gestational complications including preterm birth, operative
delivery, and gestational diabetes. At the same time, there has been a
burgeoning problem with widespread vitamin D deficiency among
populations of many developed nations. This paper provides a brief
review of potential health outcomes recently linked to gestational
vitamin D deficiency, including preterm birth, cesarean delivery, and
gestational diabetes. Although immediate costs for obstetric
complications related to gestational vitamin D insufficiency may be
modest, the short- and long-term costs for pediatric healthcare
resulting from such gestational complications may be enormous and
present an enduring burden on healthcare systems. With increasing
evidence pointing to fetal origins of some later life disease, securing
vitamin D sufficiency in pregnancy appears to be a simple, safe, and
cost-effective measure that can be incorporated into routine
preconception and prenatal care in the offices of primary care
clinicians. Education on gestational nutritional requirements should be

a fundamental part of medical education and residency training,
instruction that has been sorely lacking to date.
1. Introduction and Background

In the early and mid-1800s, the maternal mortality rate in some
European obstetrical clinics approached 1 in 5 women as a result of
puerperal fever [1]. With the epic discovery of the origins of this
childbed fever by Ignaz Philipp Semmelweis in the mid-19th century
and the eventual knowledge translation of his simple hand washing
technique into the clinical domain, rates of postpartum mortality
eventually decreased [1]. Over the subsequent century, there
continued to be monumental advances in many areas of Maternal-Fetal
Medicine. Along with a profound decline in maternal mortality from 7.2
deaths per 1000 births in the early 1900s to 0.08 by the end of 2000
[2, 3], there was a concomitant decline in infant mortality from 96 to
less than 7 deaths per 1000 live births [2, 3]. With ongoing research
and study over the last decades, remarkable advances have continued
to be made in the assessment and management of a variety of
gestational and perinatal challenges. Despite much success, however,
there are new and emerging concerns in the early 21st century within
the field of Maternal-Fetal Medicine.
Along with an astonishing rise in the rate of cesarean delivery with
attendant complications to the human microbiome [4, 5], we have
witnessed a concerning escalation in preterm birth [6], a complication
associated with higher rates of long-term physical and mental health
problems in the offspring [68]. The Institute of Medicine (IOM)
estimated the annual costs for the burden of morbidity, disability, and
mortality associated with preterm birth in the United States to be at
least $26.2 billion [9]. Furthermore, the costs associated with neonatal
intensive care, healthcare now required by an increasing percentage of
the newborn population [10], are staggering [11]. It is also evident that
maternal complications do not necessarily stop with giving birth. Rates
of serious obstetrical complications such as postpartum depression, for
example, extract enormous personal cost and remain a serious and
widespread problem [12].
In addition, there is increasing discussion in the literature about fetal
origins of pediatric and adult disease [13, 14], resulting from
potentially modifiable gestational determinants such as disordered
maternal nutrition [15] and toxic exposures [1618]. As this is a new
area of study, however, the extent of sequelae associated with

modifiable gestational determinants is yet unrecognized; it is thus not
possible to assign precise costs associated with long-term outcomes. It
is important, however, to explore and implement clinical approaches
during the preconception and gestational period which address
determinants of suboptimal outcomes in order to maximize the
enduring health of mothers and their offspring.
2. Modifiable Gestational Determinants and Illness

With recent attention to epigenetic research, it is becoming apparent
that virtually all disease, including affliction in the gestational period, is
the result of the interaction between our genes and the environment
[19]. In fact, rather than genetic predestination [20], recent evidence
confirms that modifiable environmental factors appear to be
responsible for 7090 percent of clinical illness [21]. Yet within the
environmental domain, there appear to be only two determinants
which make up the environment sphere. (i) Are we getting what we
need? (ii) Are we being exposed to things that are toxic? [19].
Accordingly, it appears that the bulk of human disease, including
problems in pregnancy, is related to deficiency and toxicity [19].
Evidence in the obstetric literature appears to support this contention
and provides opportunity to make advances with regard to maternal
and fetal well-being. In fact, medical intervention and maternal
education delivered prior to conception (preconception care) to secure
nutritional adequacy and preclude toxic exposures are being extolled
as the next frontier of maternal and child healthcare [31]. The March of
Dimes, a nonprofit organization dedicated to the health of mothers and
babies, suggests that the [physician] must take advantage of every
health encounter to provide preconception care and risk reduction
before and between conceptionsthe time when it really can make a
difference [32]. With the evident link between fetal determinants and
later onset disease, measures to secure an optimal gestational
environment can have a profound impact on maternal and pediatric
health with enormous personal, social, and financial savings.
There is considerable attention in the literature to the direct link
between assorted toxicants in pregnancy and adverse maternal and
fetal outcomes [16]. Most recently, FIGO (The International Federation
of Obstetrics and Gynecology) released a special communication
highlighting the urgent need to address the issue of widespread
toxicant exposure and bioaccumulation in reproductive aged women
[18]. In addition, it is becoming increasingly apparent that various

nutritional deficiencies are widespread and may have an enormous
impact on subsequent maternal and fetal health. Increasing evidence
appears to confirm that at no point throughout the life cycle is it more
important to secure adequate nutrient intake than in pregnancy [26].
This fact, for example, accounts for the emphasis on folate sufficiency
in early gestation [33] as well as the increased study into the outcomes
related to gestational deficiency of required omega-3 fatty acids [34]
and magnesium [35].
With the emerging evidence that vitamin D acts epigenetically in the
regulation of over 2700 different genes [36], there has been much
recent research exploring the widespread prevalence of vitamin D
deficiency through the continuum of life, including the gestational and
neonatal period. This paper is designed to review the literature findings
about the enduring impact of gestational vitamin D sufficiency on
maternal and pediatric health and well-being.
3. Methods
This brief review was prepared by assessing available medical and
scientific literature from Medline as well as by reviewing several books,
nutritional journals, conference proceedings, government publications,
and nutrition related periodicals. Terms searched included gestational
vitamin D, pregnancy and vitamin D, fetus and vitamin D, nutrition in
pregnancy, as well as pediatric health and vitamin D. Relevant
references found in these publications were also searched in order to
glean pertinent information. A primary observation, however, was that
limited scientific literature is available on the issue of gestational
vitamin D insufficiency as it relates to long-term health outcomes.
The format of a traditional integrated narrative review was chosen as
such reviews play a pivotal role in scientific research and professional
practice in medical issues spanning different medical disciplines, in this
case obstetrics, pediatrics, and general medicine. Furthermore, this
type of publication approach seemed apposite when endeavoring to
answer specific clinical questions in a field with limited primary study
[37]. Finally, it was deemed that a traditional integrated review paper
might be optimal when exploring a myriad range of health outcomes,
both short and long term.
4. Clinical Relevance of Vitamin D Sufficiency in Reproductive

Healthcare
The widespread clinical importance of determining the correlation

between vitamin D levels and reproductive outcomes is evident. The
medical literature has achieved general consensus that vitamin D
levels throughout much of the globe, as reflected by population
measurements of 25(OH)D3 levels, are generally inadequate [38].
About 2/3 of the population in northern climates are considered
deficient with average 25(OH)D3 levels in one study of 67nmol/L [39],
well below the 120150nmol/L level that has recently been associated
with preferred health [24] (Table 1). With such widespread deficiency, it
is vital to determine whether or not low gestational levels of vitamin D
are a significant determinant of reproductive and pediatric health
outcomes.
Table 1: Optimal adult levels of vitamin D (as reflected by 25(OH)D
levels) from different sources.
The need for clarity on this issue has also been recognized because of
disparity about recommended dosing among esteemed medical
groups. While the Institute of Medicine (IOM) agrees that 4,000IU of
vitamin daily is allowable and nontoxic, their actual recommended
daily intake has been limited to 600IU daily in general and 400IU/day
during gestation [40, 41]. These IOM recommendations for required
vitamin D intake have been put into serious question [42], however, as
a significant statistical error has been identified in the way their
recommendations were arrived at [43]. Accordingly, exploration of
consensus findings on the clinical benefits of vitamin D
supplementation is in order in all medical disciplines including
reproductive healthcare.
5. Limitations of Vitamin D Research as Related to Gestational

Outcomes
Although maternal-fetal outcomes in the presence of adequate
gestational vitamin D are generally favorable as reported in the
medical literature, some reports have been inconsistent and cast doubt
on the link between gestational vitamin D sufficiency and health.
Specifically, supplementation of vitamin D in pregnancy in some
studies appears to suggest marked benefit while research in other
publications does not appear to confer significant improvement in
maternal-fetal outcomes [44]. For example, a systematic review and
meta-analysis by Prez-Lpez et al. found that gestational vitamin D
supplementation was associated with increased birth weight and birth
length but, unlike some other research, was not associated with other
beneficial maternal and neonatal outcomes such as reductions in

preeclampsia, gestational diabetes, small for gestational age infants,
preterm birth, or rates of cesarean delivery [44]. The apparent
disparity between findings in various studies has caused some to
reflexively conclude that vitamin D status in pregnancy is irrelevant to
maternal-fetal outcomes.
Studies
on
reproductive
outcomes
related
to
vitamin
D
supplementation, however, are inherently plagued by a number of
common confounders which cloud the picture. It is important to realize
that vitamin D status is very different from whether or not someone is
consuming vitamin D supplementation. Many factors may affect the
resultant status of vitamin D in the body (as reflected by measurement
of 25(OH)D levels) after ingested supplementation. Dosing of
supplements, body weight, levels of various toxicants, and individual
metabolism can all be factors in consequent vitamin D indices after
supplementation. Many of the recent publications challenging the
efficacy of gestational vitamin D sufficiency have been meta-analyses
which attempt to synthesize diverse data from numerous observational
and supplementation studies which do not necessarily incorporate
individual differences in these central determinants.
Specific concerns about several vitamin D meta-analyses can account
for the varying outcomes reported from this type of research. (i) There
is wide heterogeneity of studied populations with variations in vitamin
D supplement dosing, geophysical location, social and dietary
conditions, and other factors in studied groups [45]. Supplementation
at varying doses (e.g., 400IU/day versus 4000IU/day), for example,
may achieve remarkably different levels of serum 25(OH)D and thus
different outcomes. (ii) Commencement of supplementation at differing
times during the gestation may miss critical periods when vitamin D
may play a pivotal role. (iii) Different types of vitamin D (vitamin D 2
versus vitamin D3) have different physiological impact. And (iv) various
methodological concerns are evident [46], such as the lack of
standardized assays.
In addition, it is well recognized in healthcare that regardless of how
compelling the evidence on a specific scientific or medical issue,
introduction of doubt can be a potent impediment to the
implementation of effective public health and clinical measures [47,
48]. Accordingly, a critical appraisal of such meta-analyses is in order
to achieve an accurate perspective on the efficacy of gestational
vitamin D supplementation.
6. Gestational Vitamin D Status and Obstetrical Outcomes

The list of adverse gestational outcomes in pregnancy associated with
vitamin D insufficiency continues to mount. Early in pregnancy, for
example, an increased risk of first trimester miscarriage has been
linked to inadequate maternal vitamin D levels [49]. Interestingly, one
study demonstrated that nearly half the women assessed with habitual
miscarriage were found to have 25(OH)D levels below 75nmol/L [50].
This research found that lower vitamin D levels were associated with
immune dysregulation in a number of ways, including differences in
indices involving natural killer cells, various cytokines, and certain
regulatory proteins, when compared to those with sufficient vitamin D
levels [50]. The authors of this study also noted that women with lower
vitamin D levels had higher degrees of various autoantibodies
including antiphospholipid antibody [50], a clinical state that has been
associated with fetal death, recurrent early miscarriage, preeclampsia,
and placental insufficiency [51].
A number of papers have confirmed an increased risk of developing
gestational diabetes in those with inadequate vitamin D levels [52, 53].
Vitamin D sufficiency in pregnancy appears to be related to improved
insulin levels, as well as better glucose regulation as reflected by
HbA1c levels [54]. As pregnancies complicated by gestational diabetes
present risks for assorted adverse sequelae, efforts to avoid
dysregulated sugar control in pregnancy are worthwhile. Obesity
presents a confounding influence in this discussion, however, as a
greater BMI is associated with lower vitamin D levels as well as greater
insulin resistance and risk for gestational diabetes. Numerous studies
have also correlated low levels of vitamin D with the development of
preeclampsia [52, 53, 55, 56], perhaps through immune mechanisms
involving antiphospholipid antibody [51], and/or inflammatory
mechanisms involving cytokines [56].
Of particular significance is the reality that preterm birth before 37
weeks of gestation remains the leading cause of neonatal morbidity
and mortality [57]. Escalating evidence in the literature confirms a
protective association between maternal vitamin D sufficiency and the
incidence of preterm birth [5860]. A recent study found that the rate
of occurrence of preterm birth appeared to be inversely parallel to the
maternal serum 25-hydroxyvitamin D levels [58]. The authors report
that the incidence of preterm birth at less than 37 weeks of gestation
was (i) 11.3%, (ii) 8.6%, and (iii) 7.3% among mothers with respective
serum 25-hydroxyvitamin D levels of (i) less than 50, (ii) between 50
and 74.9, and (iii) 75nmol/L or greater. Another study found that
infants born before 32 weeks of gestation were 2.4 times more likely to
have vitamin D levels below 50nmol/L when compared with those born
after 32 weeks of gestation [61].
Other gestational issues also appear to be
vitamin D levels. Vitamin D insufficiency, for
correlated with maternal periodontal disease
of small for gestational age infants [63, 64],
bacterial vaginosis [65].
influenced by maternal
example, has also been
[62], a higher likelihood
and an increased risk of
As well as individual studies, systematic reviews exploring association

between vitamin D sufficiency and health outcomes have also been
illuminating. A systematic review and meta-analysis of 24 studies
suggested that low maternal vitamin D levels in pregnancy may be
associated with an increased risk of small for gestational age infants,
as well as being linked to preeclampsia, gestational diabetes, and
preterm birth [66]. Another systematic review and meta-analysis
published in the British Medical Journal also linked vitamin D
insufficiency with an increased risk of gestational diabetes,
preeclampsia, and small for gestational age infants [65].
Vitamin D status also appears to influence modes of delivery. Vitamin D
deficiency has been linked to increased odds of primary cesarean
delivery [67] as well as a higher likelihood of emergency cesarean
section [68]. In one study, women with vitamin D levels below 37.5
nmol/L were almost four times as likely to require a primary cesarean
delivery as women with higher levels [67]. Through the evolving work
on the Human Microbiome Project, it has recently been found that the
infants journey through the birth canal is instrumental in shaping a
healthy microbiome, a feature which appears to be a determinant of
subsequent health and which may be compromised by cesarean
delivery [69]. Accordingly, efforts to diminish the high rates of
Cesarean delivery are warranted.
Gestational vitamin D status also appears to influence outcomes
beyond the pregnancy and delivery. A very challenging problem for
many new mothers is postpartum depression. There is escalating
evidence in general that low vitamin D levels are correlated with higher
risk for a variety of mental health problems including depressive illness
[70], as vitamin D is known to play an important role in activating
genes that release neurotransmitters such as dopamine and serotonin
[70, 71]. Intervention to normalize levels of vitamin D appears to be
successful in restoring mental health [72]. In particular, in relation to
maternal health, a recent study published in the British Journal of

Obstetrics and Gynecology reported that serum 25[OH]D levels in
women with no postpartum depression were significantly higher than
those in women suffering with postpartum depression [73].
7. Gestational Vitamin D Status and Later Life Outcomes

Although research into fetal origins of disease in later life remains in its
infancy, there is increasing suspicion that gestational nutritional
sufficiency may be a determinant of health in later life. For example,
preliminary evidence suggests that insufficient levels of prenatal
vitamin D may be a factor in the development of autism [74] and lower
respiratory infections [75]. A Spanish study to this end found that
mothers who had gestational vitamin D levels above 75nmol/L had
offspring with a one-third lower rate of acute respiratory tract
infections during the first year of life [76].
A recent body of work has begun to suggest that lower gestational
vitamin D levels may also be associated with higher rates of pediatric
atopic disease [77], food sensitivities [78], atopic dermatitis [79],
eczema [80], asthma [81], impaired lung function [82], allergic disease
[83], and other conditions frequently characterized by a hypersensitive
immune state. It appears that fetal vitamin D levels may play a
modulating role in immune functions involved in atopic disorders. As
hypersensitivity outcomes may also be seen in those children born to
mothers contaminated with assorted xenobiotics in pregnancy [8489],
however, it is not known whether the immune dysregulation and
hypersensitivity may be the consequence of a primary gestational
insufficiency of vitamin D, or whether various chemical toxicants might
play a role by impairing vitamin D uptake, renal synthesis, and
assimilation [25, 90] while at the same time inducing immune
compromise and hypersensitivity through other mechanisms [91].
Maternal vitamin D status during gestation also appears to have
influence on many other health indices in the future of the offspring.
For example, gestational vitamin D status directly correlates with
subsequent whole-body and lumbar spine bone mineral content in
progeny at 9 years of age [92]. Furthermore, an interesting cohort
study correlating maternal vitamin D deficiency at 18 weeks of
pregnancy and health outcomes of progeny found that gestational
vitamin D deficiency was associated with impaired lung development
in 6-year-old offspring, neurocognitive difficulties at age 10, increased
risk of eating disorders in adolescence, and lower peak bone mass at
20 years [93]. The authors state that vitamin D may have an

important, multifaceted role in the development of fetal lungs, brain,
and bone [93]. Finally, gestational vitamin D levels may impact adult
health as there is early evidence that vitamin D sufficiency in
pregnancy may have a protective role in the development of adult
onset multiple sclerosis [94].
8. Economic Burden of Gestational Vitamin D Deficiency

The economic impact of vitamin D deficiency as it relates to maternalfetal health is difficult to objectively quantify as insufficient evidence
has accumulated thus far on the totality of short- and long-term
sequelae of vitamin D insufficiency. Furthermore, current appraisals
tend to underestimate the extent of the required resource utilization
for specific conditions associated with vitamin D insufficiency. For
example, cost estimates for the immediate care involved with the
increase in cesarean delivery rates can be calculated, but these do not
at all take into account unexpected surgical complications [95] that
may arise in the future or the enormous potential cost impact from
enduring microbiome changes resulting from operative delivery [69,
96]. The reality is that adverse gestational complications do not end
with the pregnancy and can result in morbidity and resource utilization
extending throughout the life of the offspring.
This is also demonstrated by the challenge of preterm birth, as
premature birth results in significant morbidity, mortality, healthcare
utilization, and associated costs starting in infancy and extending for
years to come [97]. This can be quite a burden on national healthcare
systems. In Canada, for example, the estimated additional 10-year cost
to care for the children born prematurely each year is hundreds of
millions of dollars [98]. Furthermore, many health problems sustained
by children born prematurely continue far beyond their tenth birthday
with a consequent and sometimes ongoing economic burden placed on
health, education, and social service resources. With regard to
economic challenges associated with vitamin D insufficiency, suffice it
to say that there are considerable costs potentially associated with
gestational vitamin D insufficiency [99] as well as corresponding
benefits and cost savings resulting from inexpensive supplementation
with this essential nutrient [99].
9. Conclusion
There is escalating attention in the scientific literature to the

association between myriad nutrients and health outcomes [100, 101].
Training in clinical nutritional biochemistry, nonetheless, still remains
woefully inadequate or nonexistent in most medical education
programs [102, 103]. As a result, there are ongoing calls of late for
curriculum revision to incorporate practical training in clinical nutrition
[103, 104]. It is apparent that training is required to establish clinical
competency in (i) understanding of the role of various nutrients in
human health, (ii) how to assess nutritional biochemistry in patients,
and (iii) and how to intervene to secure nutrient sufficiency for
individuals and population groups
With the mounting evidence of several health sequelae associated with
gestational vitamin D deficiency, the value of preconception education
and care by health providers and public health bodies to secure
vitamin D sufficiency throughout gestation is evident. As pregnant
women [105], particularly those with dark skin [106], are at
considerable risk for experiencing vitamin D insufficiency [39], it is
important to have a high index of suspicion and to effectively preclude,
assess for, and manage vitamin D inadequacy, as would be done with
other biochemical irregularities.
Although (to the authors knowledge) there are no specific target levels
for 25(OH)D during the various stages of pregnancy that correlate with
optimal results in relation to maternal and pediatric health outcomes,
some authors have made recommendations for supplemental levels
that appear to be safe and effective. These recommendations range
from 600IU/day from the Institute of Medicine [41] to 2000IU/day from
the Canadian Pediatric Society [107], to 4000IU/daily from various
researchers who have concluded that the latter dose is both efficacious
and safe [2630]. One researcher has suggested that the dietary
requirement during pregnancy and lactation may actually be as high as
6000IU/day [108], but most researchers have concluded, with our
current knowledge, that a supplemental vitamin D intake of 4000
IU/day is optimal [30]. As discussed, individual vitamin D indices can
be influenced by various determinants despite specific levels of
supplementation; it is thus the authors recommendation that a
personalized medical approach be taken via individual screening for
25(OH)D as a routine part of preconception and prenatal care.
With evidence that a major proportion of the adult population [38],
particularly in northern climates [39], is potentially deficient in vitamin
D, it appears that, at minimum, one out of every few expectant
mothers will have inadequate levels of this essential nutrient. With the
recognition that vitamin D plays an essential role in myriad genes that
encode for health and well-being in the offspring, it behooves the
medical and public health community to endeavor to secure vitamin D
adequacy in the gestational period. The ongoing personal health
burden associated with gestational vitamin D insufficiency throughout
many parts of the world has the potential to be ameliorated
considerably by straightforward educational and healthcare measures
in the preconception and prenatal period to secure vitamin D
sufficiency throughout pregnancy. It is time for maternity health
providers to be apprised of the potential for improved and enduring
health and well-being associated with inexpensive measures to secure
vitamin D nutritional adequacy during gestation, the most vulnerable
time in the life cycle of the developing child.
There is no conflict of interests.
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Obstetrics and Gynecology International

Volume 2014 (2014), Article ID 192087, 8 pages

Postcoital Bleeding: A Review on Etiology, Diagnosis,

Received 1 May 2014; Revised 29 May 2014; Accepted 5 June 2014;

source for their bleeding and a discussion on the natural history of

The Royal Australian College of Obstetricians and Gynaecologists, The

Table 1: Common causes of postcoital bleeding.

Table 2: Risk of cervical cancer in women with postcoital bleeding.

Cancer of the endometrium is the most common gynecologic cancer in

2.4. Cervical Polyps

2.7. Vaginal/Vulvar Etiologies

considerations to take into account when approaching a patient with

Figure 1: Diagnostic approach to postcoital bleeding.

the patient has complained of dyspareunia or pelvic pain, then it is also

smears and no obvious lesion on exam. However, the Working Group of

ultrasonography. An endometrial thickness of greater than 4mm in a

Postcoital bleeding can be an annoying complaint for patients and a

3. M. Shapley, K. Jordan, and P. R. Croft, An epidemiological survey

3, pp. 205208, 1998. View at Publisher View at Google Scholar

reproductive-aged women, Obstetrics & Gynecology, vol. 120,

Obstetrics & Gynecology, vol. 114, part 1, no. 2, pp. 409411,

Obstetrics and Gynecology International

Preeclampsia Prediction and Management

Received 11 August 2014; Accepted 11 August 2014; Published 9

International guidelines still simply define preeclampsia (PE) as an

preeclampsia and eclampsia are major contributors of PE related

Nova Science Publishers, New York, NY, USA, 2014. View at

Obstetrics and Gynecology International

Effect of Umbilical Cord Entanglement and Position on

Department of Obstetrics and Gynecology, Yokohama City University

Received 16 May 2015; Accepted 29 June 2015

reports regarding umbilical cord entanglement concern nuchal cord

2. Materials and Methods

not significantly different. Moreover, Bernad et al. [7] reported that

of fetuses with nuchal cord entanglement tended to be higher.

know? Obstetrics and Gynecology, vol. 106, no. 1, pp. 2328,

Obstetrics and Gynecology International

Maternal and Pediatric Health Outcomes in relation to

clinicians. Education on gestational nutritional requirements should be

1. Introduction and Background

area of study, however, the extent of sequelae associated with

2. Modifiable Gestational Determinants and Illness

[18]. In addition, it is becoming increasingly apparent that various

4. Clinical Relevance of Vitamin D Sufficiency in Reproductive

The widespread clinical importance of determining the correlation

5. Limitations of Vitamin D Research as Related to Gestational

beneficial maternal and neonatal outcomes such as reductions in

6. Gestational Vitamin D Status and Obstetrical Outcomes

As well as individual studies, systematic reviews exploring association

maternal health, a recent study published in the British Journal of

7. Gestational Vitamin D Status and Later Life Outcomes

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