Académique Documents
Professionnel Documents
Culture Documents
Review Article
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
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].
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.
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].
when these organs prolapse through the introitus which can lead to
postcoital bleeding [38].
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
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
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
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.
References
1. M. Viikki, E. Pukkala, and M. Hakama, Bleeding symptoms and
subsequent risk of gynecological and other cancers, Acta
Obstetricia et Gynecologica Scandinavica, vol. 77, no. 5, pp. 564
569, 1998. View at Google Scholar View at Scopus
2. L. E. Lindner, S. Geerling, J. A. Nettum, S. L. Miller, and K. H.
Altman, Clinical characteristics of women with chlamydial
cervicitis, Journal of Reproductive Medicine for the Obstetrician
and Gynecologist, vol. 33, no. 8, pp. 684690, 1988. View at
Google Scholar View at Scopus
18.
A. Jemal, R. Siegel, E. Ward et al., Cancer statistics, 2009,
CA: A Cancer Journal for Clinicians, vol. 59, no. 4, article 225,
2009. View at Publisher View at Google Scholar
19.
M. Shapley, J. Jordan, and P. R. Croft, A systematic review of
postcoital bleeding and risk of cervical cancer, British Journal of
General Practice, vol. 56, no. 527, pp. 453460, 2006. View at
Google Scholar View at Scopus
20.
Z. Khan, F. Appleton, and J. Turner, Is cervical intraepithelial neoplasia symptomatic? Journal of Obstetrics and
Gynaecology, vol. 28, no. 3, pp. 336337, 2008. View at Publisher
View at Google Scholar View at Scopus
21.
R. J. Kurman, H. J. Norris, and E. J. Wilkinson, Atlas of Tumor
Pathology: Tumors of the Cervix, Vagina, and Vulva, Armed Forces
Institute of Pathology, Washington, DC, USA, 3rd edition, 1992.
22.
N. M. de Souza, W. P. Soutter, G. A. McIndoe, D. J. Gilderdale,
and T. Krausz, Stage I cervical cancer: tumor volume by
magnetic resonance imaging of screen-detected versus
symptomatic lesions, Journal of the National Cancer Institute,
vol. 89, no. 17, pp. 13141315, 1997. View at Google Scholar
View at Scopus
23.
R. Siegel, J. Ma, Z. Zou, and A. Jemal, Cancer statistics,
2014, CA: A Cancer Journal for Clinicians, vol. 64, no. 9, 2014.
View at Google Scholar
24.
D. Henson and R. Tarone, An epidemiologic study of cancer
of the cervix, vagina, and vulva based on the Third National
Cancer Survey in the United States, The American Journal of
Obstetrics and Gynecology, vol. 129, no. 5, pp. 525532, 1977.
View at Google Scholar View at Scopus
25.
K. P. Zelings, K. Byrd, C. M. Tarney et al., A clinicopathologic
study of vaginal intraepithelial neoplasia, Obstetrics &
Gynecology, vol. 122, no. 6, pp. 12231230, 2013. View at
Publisher View at Google Scholar
26.
Y. C. Choo and D. G. Anderson, Neoplasms of the vagina
following cervical carcinoma, Gynecologic Oncology, vol. 14, no.
1, pp. 125132, 1982. View at Google Scholar View at Scopus
27.
G. W. Geelhoed, D. E. Henson, P. T. Taylor, and A. S.
Ketcham, Carcinoma in situ of the vagina following treatment for
carcinoma of the cervix: a distinctive clinical entity, The
American Journal of Obstetrics and Gynecology, vol. 124, no. 5,
pp. 510516, 1976. View at Google Scholar View at Scopus
28.
American Cancer Society, Cancer facts and figures 2008,
Atlanta,
Ga,
USA,
ACS,
2008,
http://www.cander.org/downloads/STT/2008CAFFfinalsecured.pdf.
29.
R. B. Goldstein, R. L. Bree, C. B. Benson et al., Evaluation of
the woman with postmenopausal bleeding: society of radiologists
in ultrasound-sponsored consensus conference statement,
Journal of Ultrasound in Medicine, vol. 20, no. 10, pp. 10251036,
2001. View at Google Scholar View at Scopus
30.
F. Abu Amna, R. Howell, and S. Raj, Lymphoma of the cervix
uteri, BMJ Case Reports, 2009. View at Publisher View at Google
Scholar
31.
K. Z. Hanley, T. S. Tadros, A. J. Briones, G. G. Birdsong, and
M. B. Mosunjac, Hematologic malignancies of the female genital
tract diagnosed on liquid-based pap test: cytomorphologic
features and review of differential diagnoses, Diagnostic
Cytopathology, vol. 37, no. 1, pp. 6167, 2009. View at Publisher
View at Google Scholar View at Scopus
32.
A. Grace, N. O'Connell, P. Byrne, et al., Malignant
lymphoma of the cervix: an unusual presentation and a rare
disease, European Journal of Gynaecological Oncology, vol. 20,
no. 1, pp. 2628, 1999. View at Google Scholar
33.
R. Kurman and M. Mazur, Benign disease of the
endometrium, in Pathology of the Female Genital Tract, A.
Blaustein, Ed., p. 279, Springer, New York, NY, USA, 2nd edition,
1982. View at Google Scholar
34.
S. M. Greenwood and J. J. Moran, Chronic endometritis:
morphologic and clinical observations,
Obstetrics and
Gynecology, vol. 58, no. 2, pp. 176184, 1981. View at Google
Scholar View at Scopus
35.
K. Vasudeva, T. V. Thrasher, and R. M. Richart, Chronic
endometritis: a clinical and electron microscopic study, The
American Journal of Obstetrics and Gynecology, vol. 112, no. 6,
pp. 749758, 1972. View at Google Scholar View at Scopus
36.
H. K. Farrar Jr. and B. R. Nedoss, Benign tumors of the
uterine cervix, The American Journal of Obstetrics and
Gynecology, vol. 81, pp. 124137, 1961. View at Google Scholar
View at Scopus
37.
M. J. Goldacre, N. Loudon, B. Watt et al., Epidemiology and
clinical significance of cervical erosion in women attending a
family planning clinic, British Medical Journal, vol. 1, no. 6115,
pp. 748750, 1978. View at Google Scholar View at Scopus
38.
S. M. Mawajdeh, R. J. Al-Qutob, and A. M. Farag, Prevalence
and risk factors of genital prolapse: a multicenter study, Saudi
Medical Journal, vol. 24, no. 2, pp. 161165, 2003. View at Google
Scholar View at Scopus
39.
V. V. Pethe, S. V. Chitale, R. N. Godbole, and S. V. Bidaye,
Hemangioma of the ovarya case report and review of
literature, Indian Journal of Pathology and Microbiology, vol. 34,
no. 4, pp. 290292, 1991. View at Google Scholar View at
Scopus
40.
A. B. Gerbie, M. R. Hirsch, and R. R. Green, Vascular
tumours of female genital tract, Obstetrics & Gynecology, vol. 4,
article 499, 1955. View at Google Scholar
41.
P. Tjaden and N. Thoennes, Extent, Nature, and
Consequences of Intimate Partner Violence: Findings from the
National Violence against Women Survey, US Department of
Justice, Washington, DC, USA, 2000.
42.
S. V. McLeer and R. Anwar, A study of battered women
presenting in an emergency department, The American Journal
of Public Health, vol. 79, no. 1, pp. 6566, 1989. View at Google
Scholar View at Scopus
43.
Committee on Practice Bulletins-Gynecology, Practice
bulletin no. 128: diagnosis of abnormal uterine bleeding in
Editorial
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
References
1. B. D. Connealy, C. A. Carreno, B. A. Kase, L. A. Hart, S. C.
Blackwell, and B. M. Sibai, A history of prior preeclampsia as a
risk factor for preterm birth, American Journal of Perinatology,
vol. 31, no. 6, pp. 483488, 2014. View at Publisher View at
Google Scholar View at Scopus
2. I. Rebelo, J. Bernardes, E. Tejera, and B. Patrcio, Can we predict
preeclampsia? in Controversies in Preeclampsia, E. Sheiner and
Y. Yogev, Eds., Obstetrics and Gynecology Advances, pp. 187210,
Research Article
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
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
Conflict of Interests
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.
References
1. E. Sheiner, J. S. Abramowicz, A. Levy, T. Silberstein, M. Mazor, and
R. Hershkovitz, Nuchal cord is not associated with adverse
perinatal outcome, Archives of Gynecology and Obstetrics, vol.
274, no. 2, pp. 8183, 2006. View at Publisher View at Google
Scholar View at Scopus
2. L. Schffer, T. Burkhardt, R. Zimmermann, and J. Kurmanavicius,
Nuchal cords in term and postterm deliveriesdo we need to
10.
E. Jauniaux, B. Ramsay, C. Peellaerts,
Perinatal features of pregnancies complicated
American Journal of Perinatology, vol. 12, no.
1995. View at Publisher View at Google Scholar
and Y. Scholler,
by nuchal cord,
4, pp. 255258,
View at Scopus
11.
G. D. V. Hankins, R. R. Snyder, J. C. Hauth, L. C. Gilstrap III,
and T. Hammond, Nuchal cords and neonatal outcome,
Obstetrics and Gynecology, vol. 70, no. 5, pp. 687691, 1987.
View at Google Scholar View at Scopus
12.
D. A. Rhoades, U. Latza, and B. A. Mueller, Risk factors and
outcomes associated with nuchal cord: a population-based
study, Journal of Reproductive Medicine for the Obstetrician and
Gynecologist, vol. 44, no. 1, pp. 3945, 1999. View at Google
Scholar View at Scopus
13.
J. M. Mastrobattista, L. M. Hollier, E. R. Yeomans et al.,
Effects of nuchal cord on birthweight and immediate neonatal
outcomes, The American Journal of Perinatology, vol. 22, no. 2,
pp. 8385, 2005. View at Publisher View at Google Scholar
View at Scopus
14.
G. S. Ghosh and S. Gudmundsson, Nuchal cord in post-term
pregnancyrelationship to suspected intrapartum fetal distress
indicating operative intervention, Journal of Perinatal Medicine,
vol. 36, no. 2, pp. 142144, 2008. View at Publisher View at
Google Scholar View at Scopus
15.
V. H. Gonzlez-Quintero, L. Tolaymat, A. C. Muller, L.
Izquierdo, M. J. O'Sullivan, and D. Martin, Outcomes of
pregnancies with sonographically detected nuchal cords remote
from delivery, Journal of Ultrasound in Medicine, vol. 23, no. 1,
pp. 4347, 2004. View at Google Scholar View at Scopus
16.
W. F. Miser, Outcome of infants born with nuchal cords,
Journal of Family Practice, vol. 34, no. 4, pp. 441445, 1992. View
at Google Scholar View at Scopus
Review Article
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
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.
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
9. Conclusion
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.
Conflict of Interests
There is no conflict of interests.
References
1. H. F. Spirer and L. Spirer, Death and numbers: Semmelweis the
statistician, Physicians for Social Responsibility Quarterly, vol. 1,
pp. 4352, 1991. View at Google Scholar
2. United States Department of Health Education and Welfare,
Infant, Fetal, and Maternal Mortality: United States1963, United
States Department of Health, Washington, DC, USA, 1966,
http://www.cdc.gov/nchs/data/series/sr_20/sr20_003acc.pdf.
3. United States Department of Health and Human Services, Health
United
States
2004,
Hyattsville,
Md,
USA,
http://www.cdc.gov/nchs/data/hus/hus04.pdf.
4. G. Biasucci, M. Rubini, S. Riboni, L. Morelli, E. Bessi, and C.
Retetangos, Mode of delivery affects the bacterial community in
the newborn gut, Early Human Development, vol. 86,
supplement 1, pp. S13S15, 2010. View at Publisher View at
Google Scholar View at Scopus
5. S. Dogra, O. Sakwinska, S. Soh et al., Dynamics of infant gut
microbiota are influenced by delivery mode and gestational
22.
M. F. Holick, Vitamin D and health: evaluation, biologic
functions, and recommended dietary intake for vitamin D, in
Vitamin D: Physiology, Molecular Biology, and Clinical
Applications, pp. 335, Springer, New York, NY, USA, 2010. View
at Google Scholar
23.
M. F. Holick, N. C. Binkley, H. A. Bischoff-Ferrari, et al.,
Evaluation, treatment, and prevention of vitamin D deficiency:
an Endocrine Society clinical practice guideline, The Journal of
Clinical Endocrinology & Metabolism, vol. 96, no. 7, pp. 1911
1930, 1911. View at Publisher View at Google Scholar
24.
K. Amrein, S. A. Quraishi, A. A. Litonjua et al., Evidence for
a U-shaped relationship between prehospital vitamin D status and
mortality: a cohort study, The Journal of Clinical Endocrinology &
Metabolism, vol. 99, no. 4, pp. 14611469, 2014. View at
Publisher View at Google Scholar
25.
G. K. Schwalfenberg and S. J. Genuis, Vitamin D, essential
minerals, and toxic elements: exploring interactions between
nutrients and toxicants in clinical medicine, The Scientific World
Journal, vol. 2015, Article ID 318595, 8 pages, 2015. View at
Publisher View at Google Scholar
26.
B. W. Hollis, D. Johnson, T. C. Hulsey, M. Ebeling, and C. L.
Wagner, Vitamin D supplementation during pregnancy: doubleblind, randomized clinical trial of safety and effectiveness,
Journal of Bone and Mineral Research, vol. 26, no. 10, pp. 2341
2357, 2011. View at Publisher View at Google Scholar
27.
A. Dawodu, H. F. Saadi, G. Bekdache, Y. Javed, M. Altaye, and
B. W. Hollis, Randomized controlled trial (RCT) of vitamin D
supplementation in pregnancy in a population with endemic
vitamin D deficiency, Journal of Clinical Endocrinology and
Metabolism, vol. 98, no. 6, pp. 23372346, 2013. View at
Publisher View at Google Scholar View at Scopus
28.
C. L. Wagner, R. B. McNeil, D. D. Johnson et al., Health
characteristics and outcomes of two randomized vitamin D
supplementation trials during pregnancy: a combined analysis,
The Journal of Steroid Biochemistry and Molecular Biology, vol.
136, pp. 313320, 2013. View at Publisher View at Google
Scholar
29.
C. L. Wagner, R. McNeil, S. A. Hamilton et al., A randomized
trial of vitamin D supplementation in 2 community health center
networks in South Carolina, American Journal of Obstetrics and
Gynecology, vol. 208, no. 2, pp. 137.e1137.e13, 2013. View at
Publisher View at Google Scholar
30.
A. Mithal and S. Kalra, Vitamin D supplementation in
pregnancy, Indian Journal of Endocrinology and Metabolism, vol.
18, no. 5, pp. 593596, 2014. View at Publisher View at Google
Scholar
31.
H. K. Atrash, K. Johnson, M. Adams, J. F. Cordero, and J.
Howse, Preconception care for improving perinatal outcomes:
the time to act, Maternal and Child Health Journal, vol. 10,
supplement 1, pp. S3S11, 2006. View at Publisher View at
Google Scholar
32.
March of Dimes Birth Defects Foundation, March of dimes
updates: is early prenatal care too late? Contemporary OB/GYN,
vol. 12, pp. 5472, 2002. View at Google Scholar
33.
G. Barkai, S. Arbuzova, M. Berkenstadt, S. Heifetz, and H.
Cuckle, Frequency of Down's syndrome and neural-tube defects
in the same family, The Lancet, vol. 361, no. 9366, pp. 1331
1335, 2003. View at Publisher View at Google Scholar View at
Scopus
34.
K. A. Mulder, D. J. King, S. M. Innis, and H. R. Baradaran,
Omega-3 fatty acid deficiency in infants before birth identified
using a randomized trial of maternal DHA supplementation in
pregnancy, PLoS ONE, vol. 9, no. 1, Article ID e83764, 2014.
View at Publisher View at Google Scholar
35.
J. Takaya and K. Kaneko, Small for gestational age and
magnesium in cord blood platelets: intrauterine magnesium
deficiency may induce metabolic syndrome in later life, Journal
of Pregnancy, vol. 2011, Article ID 270474, 5 pages, 2011. View
at Publisher View at Google Scholar View at Scopus
36.
S. V. Ramagopalan, A. Heger, A. J. Berlanga et al., A ChIPseq defined genome-wide map of vitamin D receptor binding:
associations with disease and evolution, Genome Research, vol.
52.
D. K. Dror, Vitamin D status during pregnancy: maternal,
fetal, and postnatal outcomes, Current Opinion in Obstetrics &
Gynecology, vol. 23, no. 6, pp. 422426, 2011. View at Publisher
View at Google Scholar
53.
P. M. Brannon, Vitamin D and adverse pregnancy
outcomes: beyond bone health and growth, Proceedings of the
Nutrition Society, vol. 71, no. 2, pp. 205212, 2012. View at
Publisher View at Google Scholar
54.
A. El Lithy, R. M. Abdella, Y. M. El-Faissal, A. M. Sayed, and R.
M. Samie, The relationship between low maternal serum vitamin
D levels and glycemic control in gestational diabetes assessed by
HbA1c levels: an observational cross-sectional study, BMC
Pregnancy and Childbirth, vol. 14, article 362, 2014. View at
Publisher View at Google Scholar
55.
L. M. Bodnar, J. M. Catov, H. N. Simhan, M. F. Holick, R. W.
Powers, and J. M. Roberts, Maternal vitamin D deficiency
increases the risk of preeclampsia, Journal of Clinical
Endocrinology and Metabolism, vol. 92, no. 9, pp. 35173522,
2007. View at Publisher View at Google Scholar View at Scopus
56.
D. Barrera, L. Daz, N. Noyola-Martnez, and A. Halhali,
Vitamin D and inflammatory cytokines in healthy and
preeclamptic pregnancies, Nutrients, vol. 7, no. 8, pp. 6465
6490, 2015. View at Publisher View at Google Scholar
57.
Y. J. Heng, S. Liong, M. Permezel, G. E. Rice, M. K. Di Quinzio,
and H. M. Georgiou, Human cervicovaginal fluid biomarkers to
predict term and preterm labor, Frontiers in Physiology, vol. 6,
article 151, 2015. View at Publisher View at Google Scholar
58.
L. M. Bodnar, R. W. Platt, and H. N. Simhan, Earlypregnancy vitamin D deficiency and risk of preterm birth
subtypes, Obstetrics & Gynecology, vol. 125, no. 2, pp. 439447,
2015. View at Publisher View at Google Scholar
59.
T. Zhu, T. J. Liu, X. Ge, J. Kong, L. J. Zhang, and Q. Zhao,
High prevalence of maternal vitamin D deficiency in preterm
births in northeast China, Shenyang, International Journal of
Clinical and Experimental Pathology, vol. 8, no. 2, Article ID
25973031, pp. 14591465, 2015. View at Google Scholar
60.
C. L. Wagner, C. Baggerly, S. McDonnell et al., Post-hoc
analysis of vitamin D status and reduced risk of preterm birth in
two vitamin D pregnancy cohorts compared with South Carolina
March of Dimes 20092011 rates, The Journal of Steroid
Biochemistry and Molecular Biology, 2015. View at Publisher
View at Google Scholar
61.
H. H. Burris, L. J. Van Marter, T. F. McElrath et al., Vitamin D
status among preterm and full-term infants at birth, Pediatric
Research, vol. 75, no. 1, pp. 7580, 2014. View at Publisher View
at Google Scholar View at Scopus
62.
K. A. Boggess, J. A. Espinola, K. Moss, J. Beck, S.
Offenbacher, and C. A. Camargo Jr., Vitamin D status and
periodontal disease among pregnant women, Journal of
Periodontology, vol. 82, no. 2, pp. 195200, 2011. View at
Publisher View at Google Scholar View at Scopus
63.
Y. H. Chen, L. Fu, J. H. Hao et al., Maternal vitamin D
deficiency during pregnancy elevates the risks of small for
gestational age and low birth weight infants in Chinese
population, The Journal of Clinical Endocrinology & Metabolism,
vol. 100, no. 5, pp. 19121919, 2015. View at Publisher View at
Google Scholar
64.
P. Zhu, S.-L. Tong, W.-B. Hu et al., Cord blood 25hydroxyvitamin D and fetal growth in the China-Anhui birth cohort
study, Scientific Reports, vol. 5, Article ID 14930, 2015. View at
Publisher View at Google Scholar
65.
F. Aghajafari, T. Nagulesapillai, P. E. Ronksley, S. C. Tough, M.
O'Beirne, and D. M. Rabi, Association between maternal serum
25-hydroxyvitamin D level and pregnancy and neonatal
outcomes: systematic review and meta-analysis of observational
studies, The BMJ, vol. 346, article f1169, 2013. View at Publisher
View at Google Scholar View at Scopus
66.
S. Q. Wei, H. P. Qi, Z. C. Luo, and W. D. Fraser, Maternal
vitamin D status and adverse pregnancy outcomes: a systematic
review and meta-analysis, The Journal of Maternal-Fetal &
Neonatal Medicine, vol. 26, no. 9, pp. 889899, 2013. View at
Publisher View at Google Scholar
67.
A. Merewood, S. D. Mehta, T. C. Chen, H. Bauchner, and M. F.
Holick, Association between vitamin D deficiency and primary
cesarean section, The Journal of Clinical Endocrinology &
Metabolism, vol. 94, no. 3, pp. 940945, 2009. View at Publisher
View at Google Scholar
68.
S. L. Loy, N. Lek, F. Yap et al., Association of maternal
vitamin D status with glucose tolerance and caesarean section in
a multi-ethnic Asian cohort: the growing up in Singapore towards
healthy outcomes study, PLoS ONE, vol. 10, no. 11, Article ID
e0142239, 2015. View at Publisher View at Google Scholar
69.
I. Solt, The human microbiome and the great obstetrical
syndromes: a new frontier in maternal-fetal medicine, Best
Practice & Research Clinical Obstetrics & Gynaecology, vol. 29,
no. 2, pp. 165175, 2015. View at Publisher View at Google
Scholar
70.
W. J. G. Hoogendijk, P. Lips, M. G. Dik, D. J. H. Deeg, A. T. F.
Beekman, and B. W. J. H. Penninx, Depression is associated with
decreased 25-hydroxyvitamin D and increased parathyroid
hormone levels in older adults, Archives of General Psychiatry,
vol. 65, no. 5, pp. 508512, 2008. View at Publisher View at
Google Scholar View at Scopus
71.
D. Eyles, J. Brown, A. Mackay-Sim, J. McGrath, and F. Feron,
Vitamin D3 and brain development, Neuroscience, vol. 118, no.
3, pp. 641653, 2003. View at Publisher View at Google Scholar
View at Scopus
72.
R. Vieth, S. Kimball, A. Hu, and P. G. Walfish, Randomized
comparison of the effects of the vitamin D3 adequate intake
versus 100mcg (4000IU) per day on biochemical responses and
the wellbeing of patients, Nutrition Journal, vol. 3, article 8,
2004. View at Publisher View at Google Scholar
73.
C. W. Fu, J. T. Liu, W. J. Tu, J. Q. Yang, and Y. Cao, Association
between serum 25-hydroxyvitamin D levels measured 24 hours
after delivery and postpartum depression, BJOG, vol. 122, no.
12, pp. 16881694, 2015. View at Publisher View at Google
Scholar
74.
E. Fernell, S. Bejerot, J. Westerlund et al., Autism spectrum
disorder and low vitamin D at birth: a sibling control study,
Molecular Autism, vol. 6, article 3, 2015. View at Publisher View
at Google Scholar
75.
M. C. Magnus, L. C. Stene, S. E. Haberg et al., Prospective
study of maternal mid-pregnancy 25-hydroxyvitamin D level and
early childhood respiratory disorders, Paediatric and Perinatal
Epidemiology, vol. 27, no. 6, pp. 532541, 2013. View at Publisher
View at Google Scholar
76.
E. Morales, I. Romieu, S. Guerra et al., Maternal vitamin D
status in pregnancy and risk of lower respiratory tract infections,
wheezing, and asthma in offspring, Epidemiology, vol. 23, no. 1,
pp. 6471, 2012. View at Publisher View at Google Scholar
View at Scopus
77.
C.-Y. Chiu, S.-Y. Huang, Y.-C. Peng et al., Maternal vitamin D
levels are inversely related to allergic sensitization and atopic
diseases in early childhood, Pediatric Allergy and Immunology,
vol. 26, no. 4, pp. 337343, 2015. View at Publisher View at
Google Scholar
78.
C.-Y. Chiu, T.-S. Yao, S.-H. Chen et al., Low cord blood
vitamin D levels are associated with increased milk sensitization
in early childhood, Pediatric Allergy and Immunology, vol. 25, no.
8, pp. 767772, 2014. View at Publisher View at Google Scholar
79.
N. Baz, P. Dargent-Molina, J. D. Wark, J.-C. Souberbielle, and
I. Annesi-Maesano, Cord serum 25-hydroxyvitamin D and risk of
early childhood transient wheezing and atopic dermatitis, Journal
of Allergy and Clinical Immunology, vol. 133, no. 1, pp. 147153,
2014. View at Publisher View at Google Scholar View at Scopus
80.
D. J. Palmer, T. R. Sullivan, C. M. Skeaff, L. G. Smithers, and
M. Makrides, Higher cord blood 25-hydroxyvitamin D
concentrations reduce the risk of early childhood eczema: in
children with a family history of allergic disease, World Allergy
Organization Journal, vol. 8, no. 1, article 28, 2015. View at
Publisher View at Google Scholar
81.
T. Gazibara, H. T. den Dekker, J. C. de Jongste et al.,
Associations of maternal and fetal 25-hydroxyvitamin D levels
89.
S. B. Stolevik, U. C. Nygaard, E. Namork et al., Prenatal
exposure to polychlorinated biphenyls and dioxins is associated
with increased risk of wheeze and infections in infants, Food and
Chemical Toxicology, vol. 49, no. 8, pp. 18431848, 2011. View at
Publisher View at Google Scholar
90.
J. Moon, The role of vitamin D in toxic metal absorption: a
review, Journal of the American College of Nutrition, vol. 13, no.
6, pp. 559564, 1994. View at Publisher View at Google Scholar
View at Scopus
91.
S. J. Genuis, Sensitivity-related illness: the escalating
pandemic of allergy, food intolerance and chemical sensitivity,
The Science of the Total Environment, vol. 408, no. 24, pp. 6047
6061, 2010. View at Publisher View at Google Scholar View at
Scopus
92.
M. K. Javaid, S. R. Crozier, N. C. Harvey et al., Maternal
vitamin D status during pregnancy and childhood bone mass at
age 9 years: a longitudinal study, The Lancet, vol. 367, no. 9504,
pp. 3643, 2006. View at Publisher View at Google Scholar
View at Scopus
93.
P. H. Hart, R. M. Lucas, J. P. Walsh, et al., Vitamin D in fetal
development: findings from a birth cohort study, Pediatrics, vol.
135, no. 1, pp. e167e173, 2015. View at Publisher View at
Google Scholar
94.
F. Mirzaei, K. B. Michels, K. Munger et al., Gestational
vitamin D and the risk of multiple sclerosis in offspring, Annals of
Neurology, vol. 70, no. 1, pp. 3040, 2011. View at Publisher
View at Google Scholar
95.
N. Al-Asmari and T. Tulandi, The relevance of post-cesarean
adhesions, Surgical Technology International, vol. 22, pp. 177
181, 2012. View at Google Scholar
96.
J. Sonnenburg and E. Sonnenburg, The Good Gut: Taking
Control of Your Weight, Your Mood, and Your Long-Term Health,
Bantam Press, London, UK, 2015.
97.
S. Beck, D. Wojdyla, L. Say et al., The worldwide incidence
of preterm birth: a systematic review of maternal mortality and
Clinical Biochemistry, vol. 46, no. 15, pp. 14891492, 2013. View
at Publisher View at Google Scholar View at Scopus
106.
M. Aucoin, R. Weaver, R. Thomas, and L. Jones, Vitamin D
status of refugees arriving in Canada: findings from the calgary
refugee health program, Canadian Family Physician, vol. 59, no.
4, pp. e188e194, 2013. View at Google Scholar View at Scopus
107.
Canadian Pediatric Society, Vitamin D supplementation:
recommendations for Canadian mothers and infants, Paediatrics
& Child Health, vol. 12, no. 7, pp. 583598, 2007. View at Google
Scholar
108.
B. W. Hollis, Vitamin D requirement during pregnancy and
lactation, Journal of Bone and Mineral Research, vol. 22,
supplement 2, pp. V39V44, 2007. View at Publisher View at
Google Scholar