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What's new in obstetrics and gynecology
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What's new in obstetrics and gynecology

Disclosures: Kristen Eckler, MD, FACOG Employee of UpToDate, Inc. Sandy J Falk, MD, FACOG Employee of UpToDate, Inc. Vanessa A Barss, MD, FACOG Employee of UpToDate, Inc.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2015. | This topic last updated: Feb 25, 2015.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

OBSTETRICS

Safety of inhaled long-acting beta agonist/glucocorticoid for asthma during pregnancy (February 2015)

An important clinical question for pregnant women with asthma is whether using a combination long-acting beta-agonist (LABA) plus inhaled glucocorticoid confers an increased risk for adverse fetal outcomes, compared with monotherapy using a higher dose of the inhaled glucocorticoid. In a study of 1302 pregnant women with asthma, the risk for a major congenital malformation was not increased when a LABA plus low dose inhaled glucocorticoid was compared with a medium dose inhaled glucocorticoid, or when a LABA plus medium-dose inhaled glucocorticoid was compared with a high-dose inhaled glucocorticoid [1]. (See "Management of asthma during pregnancy", section on 'Long-acting beta-adrenergic agents'.)

Target diastolic blood pressure in pregnancy (February 2015)

In pregnant women with chronic (preexistent) or gestational hypertension, the effect of less-tight versus tight control of hypertension on pregnancy complications is unclear. A randomized trial that assigned pregnant women with gestational or chronic hypertension to diastolic blood pressure treatment targets of 85 or 100 mmHg reported similar maternal, fetal, and neonatal outcomes in both groups [2]. More women in the 100 mmHg target group developed severe hypertension, although this was not associated with an increase in transient ischemic attack or stroke. The trial was not powered to exclude a clinically important increase in fetal growth restriction in the 85 mmHg target group. For these reasons, we continue to suggest a diastolic pressure target of 90 to 100 mmHg for pregnant women with hypertension without end-organ damage. (See "Management of hypertension in pregnant and postpartum women", section on 'Blood pressure goal'.)

Risk of depression among pregnant women with epilepsy (February 2015)

Individuals with epilepsy have an increased prevalence of depression compared with individuals without epilepsy, and this appears to be true during pregnancy and the postpartum period as well. In a population-based study that included 706 pregnancies in women with epilepsy and over 100,000 pregnancies in those without epilepsy, peripartum depression affected 27 percent of women with epilepsy compared with 23 percent of women with other chronic diseases and 19 percent of the entire non-epilepsy population [3]. Risk factors for depression included high seizure frequency, antiepileptic drug use, and prepregnancy depression or anxiety. Detection of depression during pregnancy is important because both pharmacologic and nonpharmacologic treatments are available, and untreated illness may have consequences for both mother and child. (See "Risks associated with epilepsy and pregnancy", section on 'Other risks'.)

Mortality decreasing for extremely preterm infants (January 2015)

Although infants born extremely premature have the highest mortality rate, mortality has decreased with advances in prenatal and neonatal care. This was illustrated in a large prospective study of 22,248 extremely premature infants (defined as gestational age between 22 and 28 6/7 weeks) conducted by the National Institute of Child Health and Human Development Neonatal Research Network that compared mortality across three time periods (2000 to 2003, 2004 to 2007, and 2008 to 2011) [4]. In this analysis, mortality was lowest in the third time period (2008 to 2011) due to decreased rates of deaths related to pulmonary causes (neonatal respiratory distress syndrome and bronchopulmonary dysplasia), immaturity, infection, and central nervous system injury. The study also documented improved prenatal care among mothers of these preterm infants, as the percentage of women who received prenatal care increased throughout the three study periods including higher rates of prenatal glucocorticoid administration. (See "Incidence and mortality of the premature infant", section on 'Extremely preterm infants'.)

Timing of antiretroviral initiation during pregnancy (January 2015)

The risk of HIV transmission from an infected mother to her infant is proportional to the level of maternal viremia at delivery. Among women not already taking an antiretroviral regimen, viral suppression at delivery is more likely when a regimen is initiated earlier during gestation. In a large US cohort of antiretroviral-naïve HIV-infected women who initiated a combination antiretroviral regimen during pregnancy, a detectable viral load at delivery was documented in 13 percent overall, but in 24 percent of those who initiated the regimen during the third trimester [5]. See "Use of antiretroviral medications in pregnant HIV-infected patients and their infants in resource-rich settings", section on 'When to initiate antiretroviral medications during pregnancy'.)

Risk of congenital anomalies in offspring of consanguineous couples (January 2015)

There is increasing evidence that the prevalence of congenital and genetic disorders among offspring of consanguineous couples is about double that compared to non-consanguineous couples. In a retrospective study of a multiethnic population referred to a specialist center in Berlin, Germany, the prevalence of major anomalies among fetuses with consanguineous and non-consanguineous parents was 6.1 and 2.8 percent, respectively [6]. This information is useful for managing pregnancy in a consanguineous couple or counseling consanguineous couples who are contemplating pregnancy. (See "Genetic and environmental causes of birth defects", section on 'Consanguinity'.)

No change to recommendations for pain medicine use in pregnancy (January 2015)

Studies of pain medicine use by pregnant women have suggested associations between prescription nonsteroidal antiinflammatory drugs (NSAIDs) and the risk of miscarriage, the use of acetaminophen and subsequent childhood attention deficit hyperactivity disorder (ADHD), and the use of opioids and the development of fetal neural tube defects. A 2015 US Food and Drug Administration (FDA) Drug Safety Communication has found methodologic limitations to these studies and inconclusive results regarding NSAIDs and acetaminophen use [7]. Further investigation is needed regarding maternal opioid use and the risk of fetal neural tube defects. It is always advisable for pregnant women to avoid medications that are not clearly needed. However, specific recommendations regarding analgesic use need not change based on this current analysis. (See "Initial prenatal assessment and first trimester prenatal care", section on 'Treatment of pain and fever'.)

Success of preterm labor induction (January 2015)

Induction of labor is less likely to be successful in very preterm pregnancies, but reliable estimates of success rates have not been published. In a study of data from the National Institute of Child Health and Human Development Consortium on Safe Labor, 57 percent of pregnancies induced at 24 to 28 weeks, and 54 percent of those at 28 to 31 weeks had a successful vaginal delivery [8]. Success rates were highest in multiparous women and pregnancies ≥34 weeks. (See "Induction of labor", section on 'Predicting a successful induction'.)

Congenital anomalies associated with increased nuchal translucency on prenatal ultrasonography (December 2014)

Measurement of fetal nuchal translucency on prenatal ultrasonography is a first trimester screening test for Down syndrome. Increased nuchal translucency is associated with Down syndrome, but also with an increased risk of congenital cardiac and noncardiac anomalies. In a large population-based study of euploid liveborn infants without critical congenital heart defects, the risk of hydrocephalus, osteodystrophy, and anomalies of the lung, diaphragm, and small intestine was increased approximately threefold in infants with first trimester nuchal translucency measurement ≥95th percentile compared with those <95th percentile [9]. These findings highlight the importance of a thorough fetal anatomic survey when increased fetal nuchal translucency is identified. (See "First trimester cystic hygroma and increased nuchal translucency", section on 'Noncardiac'.)

Blunt versus sharp uterine incision expansion (December 2014)

The uterine incision at cesarean delivery can be expanded using a blunt or sharp technique. In a 2014 meta-analysis of randomized trials of blunt versus sharp incision expansion, blunt expansion resulted in a 50 percent reduction in the rate of unintended extensions and a lower drop in postpartum hemoglobin and hematocrit, and reduced operative time by two minutes [10]. These data support our recommendation for blunt incision expansion. (See "Cesarean delivery: Technique", section on 'Procedure'.)

Low Apgar scores: Predictors of neonatal and infant deaths (November 2014)

Although not used to guide resuscitation, Apgar scores, first introduced in 1953, have been used as a measure of the newborn's overall clinical status and response to resuscitation during the first minutes after delivery. The accurate predictability of low Apgar scores for mortality was confirmed by a study that reviewed discharge and mortality data for all births in Scotland between 1992 and 2010 [11]. Linear regression analysis showed Apgar scores ≤3 at five minutes, compared with normal scores (between 7 and 10), were associated with 300-fold increased risk of early neonatal death (birth to seven days of life), 30-fold increased risk of late neonatal death (7 to 28 days of life), and 50-fold increased infant death (up to one year of age). (See "Neonatal resuscitation in the delivery room", section on 'Apgar scores'.)

Risk of gestational hypertension or preeclampsia in kidney donors (November 2014)

The assessment of risk conferred by living kidney donation is critically important in determining the suitability of individual donor candidates. A retrospective cohort study demonstrated an increased risk of gestational hypertension or preeclampsia compared with well-matched nondonors [12]. Women of childbearing age who wish to donate a kidney should be advised of this increased risk. (See "Evaluation of the living kidney donor and risk of donor nephrectomy", section on 'Maternal and fetal outcomes'.)

Anticoagulation and placenta-mediated complications (October 2014)

Placenta-mediated pregnancy complications include pregnancy loss, severe/early-onset preeclampsia, and birth of small for gestational age infant. Anticoagulation has been recommended to prevent placenta-mediated pregnancy complications in women with thrombophilia, but the effectiveness of this approach is controversial. In a multinational randomized trial (TIPPS), prophylactic use of dalteparin in women with thrombophilia and a history of previous placenta-mediated pregnancy complications did not reduce the occurrence of the composite outcome (pregnancy loss, severe/early-onset preeclampsia, birth of small for gestational age infant, major venous thromboembolism) compared with women who did not receive dalteparin [13]. We believe the available evidence supports not prescribing anticoagulants to prevent adverse obstetrical outcomes in pregnant women with thrombophilia. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of pregnancy complications'.)

Aspirin for preventing preeclampsia (September 2014)

For women at high risk of developing preeclampsia, the US Preventive Services Task Force (USPSTF) now recommends use of low dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia, preterm birth, and fetal growth restriction [14]. Low dose aspirin prophylaxis results in potentially substantial benefit and no more than minimally harmful effects. This recommendation is consistent with recommendations of other professional organizations. The USPSTF also offered a pragmatic approach for selecting a high risk population, while acknowledging that there are no validated methods for identifying these women. (See "Preeclampsia: Prevention", section on 'Approach to therapy'.)

Maternal mortality among women with epilepsy (August 2014)

Individuals with chronic epilepsy are at increased risk for sudden death, and a new study suggests that this risk may contribute to increased maternal mortality among women with epilepsy. A study that examined all epilepsy-related deaths in a United Kingdom population-based registry of over two million pregnancies found 14 deaths in women with epilepsy over a two-year period; 80 percent of these were attributed to sudden unexpected death in epilepsy (SUDEP) [15]. The estimated maternal death rate, 1 in 1000 among women with epilepsy, was 10-fold higher than the rate in the general population of pregnant women but similar to estimates of SUDEP risk in the chronic epilepsy population. Additional studies are needed to confirm this finding and to determine whether there are modifiable risk factors for SUDEP during pregnancy. (See "Risks associated with epilepsy and pregnancy", section on 'Maternal mortality'.)

OFFICE GYNECOLOGY

Interim guidelines for cervical cancer screening with primary HPV testing (February 2015)

Interim guidelines from the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology are the first US guidelines to suggest primary human papillomavirus (HPV) testing as an option for cervical cancer screening in women starting at age 25 years (table 1) [16]. This option is provided based on a randomized trial comparing primary HPV testing with cytology (Pap test) or co-testing (Pap test and HPV testing) [17]. Among women ≥25 years, primary HPV testing was more sensitive for the detection of cervical intraepithelial neoplasia (CIN) 3 or greater. However, the study is limited by having only three years of follow-up, use of a surrogate outcome (CIN3 rather than cancer), and highly structured follow up protocols that may not be feasible in practice. Given these limitations, we continue to suggest that women age <30 years not be screened for cervical cancer with primary HPV testing. (See "Screening for cervical cancer", section on 'Primary HPV testing'.)

Urine testing for human papillomavirus (November 2014)

Urine tests for human papillomavirus (HPV) DNA have been developed for detecting cervical HPV infection in women, although this testing is not clinically available. The efficacy of urine testing for different genotypes of HPV was evaluated in a meta-analysis of 14 studies including 1443 women [18,19]. For detection of high-risk HPV, the sensitivity was 77 percent and specificity was 88 percent. For detection of HPV 16 and 18 specifically, sensitivity was 73 percent and specificity was 98 percent. This method of testing may have potential in large research studies or as an alternative test where routine cervico-vaginal exams are not economically feasible or less likely to be performed due to cultural barriers. (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing", section on 'Other methods'.)

Long-acting reversible contraception for adolescents (October 2014)

The intrauterine device and etonogestrel implant are two types of long-acting reversible contraception (LARC). Although LARC is more effective than other methods, few adolescents choose LARC. Lack of access to services, lack of information, and increased cost may be barriers to LARC for adolescents. Removal of these barriers appears to be associated with increased use of LARC and decreased rates of pregnancy. In a prospective study, 1404 urban adolescents 15 to 19 years of age were educated about reversible contraception (emphasizing the benefits of LARC), provided with their choice of reversible contraception at no cost, and followed for two to three years [20]. Nearly three-quarters of participants chose LARC. The pregnancy rate among participants was nearly five times less than that in a contemporaneous cohort of sexually active teenagers in the United States (34.0 versus 158.5 per 1000). The American Academy of Pediatrics now recommends the etonogestrel implant and intrauterine device as first-line contraceptive options for adolescents [21]. (See "Contraception: Overview of issues specific to adolescents", section on 'Overcoming barriers'.)

Levonorgestrel IUD in endometrial carcinoma prevention (September 2014)

The levonorgestrel-releasing intrauterine device (LNg-IUD) is a popular option for both contraception and treatment of abnormal uterine bleeding (AUB). It also appears to have a preventive effect on endometrial carcinoma, at least in women with AUB. One of the largest studies of this issue was a national registry study from Finland that reported that women using the LNg-IUD for treatment of menorrhagia had one-half the expected incidence of endometrial carcinoma [22]. The results of this study support a potential preventive, as well as therapeutic, role of the LNg-IUD in women with AUB. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Hormonal contraceptives'.)

KEEPS hormone therapy trial in newly menopausal women (September 2014)

The Women's Health Initiative (WHI), a set of menopausal hormone therapy (MHT) trials in older postmenopausal women (average age 63 years) reported an excess risk of coronary heart disease (CHD) with MHT. Emerging data, including secondary analyses from the WHI, now suggest that use of MHT in the early menopausal years is not associated with excess CHD risk. The Kronos Early Estrogen Prevention Study (KEEPS) is the first randomized trial of MHT in younger menopausal women (727 women ages 45 to 54 years) [23]. When combined with cyclical monthly oral progesterone, low dose oral conjugated estrogen (0.45 mg daily) or transdermal estradiol (50 mcg daily) for four years relieved menopausal symptoms. While several markers of cardiovascular risk improved in the MHT group, there was no significant effect on surrogate markers of atherosclerosis progression (coronary artery calcium and carotid intima-medial thickness) when compared to placebo. This trial provides additional reassurance that early use of MHT is safe for the treatment of menopausal symptoms, though it does not support a role for MHT in prevention. (See "Menopausal hormone therapy and cardiovascular risk", section on 'Timing of exposure'.)

Injectable progestins and risk of venous thrombosis (September 2014)

In contrast to other progestin-only contraceptives, depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of venous thrombosis and embolism (VTE). In a case-control study, women with a first episode of VTE were twice as likely to be DMPA users than were controls in the general population [24]. In this study, VTE was not associated with use of progestin-only pills, the levonorgestrel-releasing intrauterine device, or the progestin-only contraceptive implant. However, in the absence of data about absolute risk of VTE in DMPA users, we continue to think that the advantages of using DMPA generally outweigh the risks for women with a history of VTE. (See "Depot medroxyprogesterone acetate for contraception", section on 'Cardiovascular risk'.)

GYNECOLOGIC SURGERY

Efficacy of surgical treatment for ovarian remnant syndrome (February 2015)

Ovarian remnant syndrome is the presence of residual ovarian tissue after oophorectomy, which may cause pelvic pain. Most studies have reported high success rates with surgical treatment. In a retrospective series of women with ovarian remnant syndrome or the related disorder ovarian retention syndrome (when the ovaries are purposefully left intact), rates of success with surgical treatment were lower than described in previous studies [25]. Only 10 of 20 women with ovarian remnant syndrome experienced improvements in pain scores. Endometriosis was a significant risk factor for lack of treatment success. (See "Ovarian remnant syndrome", section on 'Choice of treatment method'.)

GYNECOLOGIC ONCOLOGY

FDA approval for bevacizumab for cervical cancer (August 2014)

For women with advanced, recurrent, or metastatic cervical cancer, a Gynecologic Oncology Group randomized trial (GOG 240) showed that chemotherapy plus bevacizumab significantly improved outcomes, including a prolongation of overall survival, compared with the administration of chemotherapy alone. Based on these results, the US Food and Drug Administration approved the use of bevacizumab in combination with chemotherapy for these patients in August 2104 [26]. Despite these developments, issues related to costs of therapy may need to be considered, especially in underdeveloped areas. (See "Management of recurrent or metastatic cervical cancer", section on 'Chemotherapy plus bevacizumab as first-line treatment'.)

REPRODUCTIVE ENDOCRINOLOGY

First live birth after uterine transplantation (October 2014)

Uterine transplantation is an investigational procedure performed in a few centers worldwide. The first live birth after uterine transplantation was recently reported  [27]. The donor was a 61-year-old unrelated family friend. The recipient was a 35-year-old woman with congenital Müllerian agenesis who delivered a healthy, appropriately grown infant via cesarean section at 32 weeks because of preeclampsia. The mother and baby were doing well two weeks postdelivery. This report supports the feasibility of uterine transplantation as a potential treatment for uterus-associated infertility. (See "Surgical management of congenital uterine anomalies", section on 'Uterine transplantation'.)

Letrozole versus clomiphene citrate for ovulation induction in PCOS (October 2014)

Clomiphene citrate (CC) has been the first line ovulation induction drug for women with polycystic ovary syndrome (PCOS) for many years. However, a multicenter trial in 750 women with PCOS suggests that letrozole results in higher cumulative birth rates (over five cycles) when compared to CC (27.5 percent and 19.1 percent, respectively) [28]. Body mass index (BMI) had a significant impact on live birth rates. For women with a BMI ≤30.3, the cumulative live birth rate (approximately 30 percent) was similar in the CC and letrozole groups. For women with a BMI ≥30.3, the cumulative live birth rates were significantly higher with letrozole when compared to CC (20 versus 10 percent). The possible advantage of letrozole was supported by a meta-analysis of six trials, including this multicenter trial, comparing letrozole and CC, which found higher birth rates with letrozole although BMI data were not provided [29].

Safety data suggest that letrozole is not associated with an increased risk of congenital malformations, but the evidence is based upon a relatively small number of pregnancies. Unlike CC, letrozole is not approved in any country for ovulation induction. However, based upon available data, for women with PCOS pursuing ovulation induction, we now suggest letrozole for those with a BMI >30 kg/m2, while we still suggest CC for those with a BMI ≤30 kg/m2.

(See "Ovulation induction with letrozole", section on 'Ovulation induction in PCOS'.)

UROGYNECOLOGY

Transobturator versus retropubic slings for stress urinary incontinence in women (December 2014)

Five-year follow-up data from the Trial of Midurethral Slings (TOMUS), which randomized women to either a retropubic sling or a transobturator sling, demonstrated decreasing continence rates for women in both treatment groups [30]. The continence rate was higher in retropubic sling patients as compared with transobturator sling patients, but not statistically different (51.3 percent versus 43.4 percent). A greater proportion of women who underwent a transobturator sling procedure reported a "much better or very much better" urinary status. The overall mesh erosion rate was low, but new mesh exposures developed remote from surgery. Both retropubic slings and transobturator slings are reasonable choices for the surgical management of stress urinary incontinence in women, but the continence rates of both procedures decrease with time. (See "Surgical management of stress urinary incontinence in women: Choosing a type of midurethral sling", section on 'Transobturator versus retropubic midurethral slings'.)

OTHER GYNECOLOGY

New human papillomavirus (HPV) vaccine targets nine HPV types (February 2015)

Infection with human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58 is implicated in approximately 90 percent of invasive cervical cancers. The US Food and Drug Administration has approved Gardasil 9, a 9-valent HPV vaccine that targets those seven HPV types in addition to the two types associated with genital warts (6 and 11), for the prevention of HPV-related disease [31]. In a trial that included approximately 14,000 females randomly assigned to receive the 9-valent or quadrivalent HPV vaccine, immune responses with the two vaccines were comparable for the HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent HPV vaccine was 97 percent effective for preventing precancerous and cancerous lesions of the cervix, vagina, and vulva associated with the other targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall similar. We favor the 9-valent HPV vaccine for its broader HPV type coverage.

Routine immunization should be offered to boys and girls aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 and females between 13 to 26 years who have not been previously vaccinated. Repeat vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.

(See "Recommendations for the use of human papillomavirus vaccines", section on 'Available vaccines'.)

Circulating influenza A H3N2 viruses and influenza vaccine effectiveness in the United States (December 2014, MODIFIED January 2015)

In December 2014, the United States Centers for Disease Control and Prevention (CDC) released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines [32]. Most isolated influenza viruses to date have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. In seasons where predominant circulating influenza viruses have antigenically drifted, decreased vaccine effectiveness has been observed. Nevertheless, vaccination typically provides some cross-protection against drifted viruses and should still reduce hospitalization and death. As of early January 2015, overall vaccine effectiveness against laboratory-confirmed influenza associated with medically attended acute respiratory illness was only 23 percent [33]. Influenza vaccination is still highly recommended [32]. The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season' and "Seasonal influenza in children: Prevention with vaccines", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)

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REFERENCES

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