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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.
Folic acid supplementation for prevention of neural tube defects (February 2017)
Folic acid supplementation and food fortification have reduced the incidence of neural tube defects (NTDs). A 2017 systematic review by the US Preventive Services Task Force (USPSTF) noted that post-food fortification studies of folic acid supplementation have not demonstrated a protective association , suggesting that current levels of food fortification may be sufficient to prevent most folate-sensitive NTDs. However, the USPSTF also reaffirmed its 2009 recommendation that all women of reproductive age planning or capable of pregnancy take a supplement containing 0.4 to 0.8 mg of folic acid daily to reduce their risk of having a child with a NTD . Given the limitations of the post-food fortification studies, we agree with this recommendation. (See "Folic acid supplementation in pregnancy", section on 'Folic acid supplements' and "Folic acid supplementation in pregnancy", section on 'Food fortification'.)
United States guidelines for fish consumption during pregnancy and lactation (February 2017)
Fish may be contaminated by environmental pollutants, such as methylmercury, which can cause fetal neurologic problems. The US Food and Drug Administration and Environmental Protection Agency released updated recommendations about fish consumption for women who are pregnant or nursing, or who might become pregnant . Revisions include guidance on many more types of fish and recommendations for best choices versus good choices (table 1). (See "Nutrition in pregnancy", section on 'Fish consumption'.)
Delayed cord clamping (January 2017)
Delaying umbilical cord clamping for at least 30 to 60 seconds after birth in both term and preterm vigorous infants is the recommendation of an updated committee opinion by the American College of Obstetricians and Gynecologists (ACOG) . Previously, ACOG had recommended individualizing the timing of cord clamping in term infants. Although the optimal amount of time before cord clamping has not been studied extensively, we believe data support a minimum duration of delay of at least one minute in term births and 30 seconds in preterm births. (See "Management of normal labor and delivery", section on 'Cord clamping'.)
Risk of birth defects with Zika virus infection during pregnancy (January 2017)
The risk of birth defects resulting from in utero exposure to Zika virus was 6 and 42 percent in two recent reports [5,6]. The wide range likely reflects differences in study design, populations studied, maternal Zika case definition, and the range of clinical abnormalities included. The most common fetal/newborn findings in these reports were abnormal brain imaging, microcephaly, small size for gestational age, and abnormal neurologic examination. The greatest risk of serious sequelae in offspring appeared to be with first or second trimester infection, but serious sequelae also occurred with third trimester infection. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies' and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)
Trends in marijuana use during pregnancy (December 2016)
The impact of recent laws legalizing marijuana for medical and recreational use on use by pregnant women is unknown. In a survey of marijuana use among reproductive-aged women, use of marijuana in the past month by pregnant women increased 62 percent between 2002 and 2014 (from 2.4 to 3.9 percent) and was highest among women aged 18 to 25 years . As there are multiple concerns about the neurodevelopmental impact of marijuana on the developing fetus, abstinence during pregnancy is advised. (See "Overview of substance misuse in pregnant women", section on 'Marijuana'.)
FDA issues warning about anesthesia for pregnant patients and children under three years of age (December 2016)
The US Food and Drug Administration has warned about potential negative effects on the developing brain from administration of anesthetics and sedatives to pregnant women and children under age three, especially for repeated exposures or procedures lasting more than three hours . However, the degree of risk remains unclear. A single, brief exposure to anesthesia probably does not cause neurotoxicity in healthy young children. Further study is required to determine the effects of prolonged or repeated anesthetics, variability among anesthetic agents and combinations of drugs, and patient factors that may confer vulnerability to anesthetic neurotoxicity. At present, there is no compelling evidence that any specific anesthetic agent should be avoided during pregnancy or in young children, or that necessary surgery should be delayed because of concerns about neurotoxicity. (See "Management of the pregnant patient undergoing nonobstetric surgery", section on 'Fetal brain development'.)
Pattern of anomalies in congenital Zika syndrome (November 2016)
The clinical spectrum of congenital Zika syndrome (CZS) is evolving as more cases are described. A comprehensive review of the available published data identified five unique features of CZS that are rarely seen with other congenital infections: (1) severe microcephaly with partially collapsed skull, (2) thin cerebral cortices with subcortical calcifications, (3) macular scarring and focal pigmentary retinal mottling, (4) congenital contractures (arthrogryposis), and (5) marked early hypertonia . Recognition of this distinctive phenotype can help clinicians identify infants with CZS and ensure appropriate etiologic evaluation and comprehensive clinical investigation. (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)
Extended versus narrow spectrum antibiotic prophylaxis for cesarean delivery (November 2016)
Use of extended versus narrow spectrum antibiotic prophylaxis for cesarean delivery is controversial. In the largest randomized trial, which was limited to women in labor or with ruptured membranes for at least four hours, the combination of azithromycin and cefazolin resulted in a 50 percent reduction in postcesarean infection compared with cefazolin alone . This trial had a high proportion of obese patients and lacked comparative data on the efficacy of weight-based cefazolin dosing, which may have accounted, at least in part, for the findings. We continue to use single-dose narrow-spectrum antibiotic prophylaxis for all patients before cesarean delivery; however, others may reasonably choose to use an extended spectrum regimen in the high-risk patient population targeted by the trial. (See "Cesarean delivery: Preoperative issues".)
Closed-loop insulin pump in pregnant women with type 1 diabetes (October 2016)
A recent crossover trial in 16 pregnant women with type 1 diabetes compared use of a closed-loop insulin pump (automatic adjustment of basal insulin dose) with manual adjustment of the basal insulin . The closed loop pump improved glycemic control with no difference in hypoglycemia rate, but the incidence of large for gestational age infants remained high. This technology is not readily available and, in this small trial, provided no clear pregnancy benefit. (See "Pregestational diabetes mellitus: Glycemic control during pregnancy", section on 'Types of insulin pumps'.)
Duration of passive protection of the infant from maternal influenza vaccination (September 2016, Modified September 2016)
A randomized trial of trivalent inactivated influenza vaccination of pregnant women reported 86 percent efficacy against laboratory confirmed influenza among infants ≤8 weeks of age and 25 to 30 percent efficacy among infants 8 to 24 weeks of age, compared with placebo vaccination . These data suggest that the passive protection afforded by maternal influenza vaccination declines significantly before the infant is eligible for influenza vaccination at six months of age. (See "Influenza and pregnancy", section on 'Infant protection'.)
Safety of magnetic resonance imaging and gadolinium in pregnancy (September 2016)
Magnetic resonance imaging (MRI) may be used for diagnostic imaging in pregnancy when ultrasound examination is inadequate; however, fetal safety has not been conclusively established. Recently, the largest study of MRI in pregnancy (over 1700 exposed and 1.4 million unexposed births) reported that first-trimester MRI was not associated with significantly increased risks for stillbirth, neonatal death, congenital anomaly, neoplasm, or vision or hearing loss in children followed up to age four years, when adjustments were made for differences between exposure groups . The study also found that gadolinium exposure at any time during pregnancy was associated with an increased risk for stillbirth and neonatal death. Children exposed in utero were at increased risk for rheumatological, inflammatory, or infiltrative skin conditions, but not congenital anomalies or nephrogenic systemic fibrosis (NSF). This study is a major addition to the body of evidence supporting the safety of MRI in pregnancy when medically indicated. It also provides the first data supporting existing recommendations to avoid use of gadolinium-based contrast agents in pregnant women, when possible. (See "Diagnostic imaging procedures during pregnancy", section on 'Magnetic resonance imaging'.)
Oxytocin induction not associated with autism (August 2016)
A possible association between oxytocin induction of labor and development of autism in offspring has been widely publicized in the lay press, based on findings from a single epidemiological study. Recently, a nationwide epidemiologic study in Sweden found no association between labor induction and autism in offspring when adjustments were made for environmental and genetic factors shared by siblings . A strength of this study was that comparison of exposure-discordant births to the same woman allowed control for all unmeasured factors shared by siblings. We believe an association between oxytocin induction and autism is unlikely. (See "Induction of labor", section on 'Other'.)
Low-dose aspirin for preeclampsia prophylaxis (August 2016)
In July 2016, the American College of Obstetricians and Gynecologists (ACOG) endorsed the United States Preventive Services Task Force (USPSTF) recommendation for use of low-dose aspirin prophylaxis in women at high risk of developing preeclampsia, and identified these women based on the same criteria designated by the USPSTF . Prior to July 2016, ACOG defined high risk more narrowly: history of early-onset preeclampsia and preterm delivery <34 weeks of gestation or more than one prior pregnancy complicated by preeclampsia. The broader USPSTF criteria included multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, and some autoimmune diseases. We continue to suggest low-dose aspirin prophylaxis for women included under the broader criteria, as well as some women with multiple moderate risk factors for preeclampsia. (See "Preeclampsia: Prevention", section on 'Guidelines from selected organizations'.)
No role for routine serologic screening for genital herpes infection (December 2016)
Genital herpes, which can be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2), is one of the most common sexually transmitted infections, and sexual transmission can occur even in the absence of symptoms. Despite this, routine serologic screening for herpes simplex is not recommended in asymptomatic adolescents and adults due to significant limitations of available tests, as highlighted in a recent US Preventive Services Task Force statement . Limitations include the low specificity and high false positive rate of serologic tests for HSV-2 and the inability of serologic tests for HSV-1 to differentiate oral from genital infection. Furthermore, there are no specific treatment interventions for asymptomatic patients, so the anxiety and disruption of personal relationships associated with a positive test outweigh any potential benefits. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Screening'.)
Vaginal prasterone for dyspareunia in postmenopausal women (November 2016)
In November 2016, the US Food and Drug Administration approved the use of prasterone (also known as dehydroepiandrosterone [DHEA]) for treatment of dyspareunia in women with vulvovaginal atrophy (VVA) due to menopause . In an earlier randomized trial of women with VVA and moderate to severe dyspareunia, 12 weeks of daily intravaginal DHEA resulted in improved scores for pain during sexual activity and other key domains of female sexual function (desire, arousal, lubrication, orgasm, satisfaction) compared with placebo . However, patients may find daily dosing more cumbersome than twice-weekly dosing with vaginal estrogen preparations. (See "Treatment of genitourinary syndrome of menopause (vulvovaginal atrophy)", section on 'Dehydroepiandrosterone (prasterone)'.)
Combination antiretroviral treatment in pregnancy (November 2016)
Combination antiretroviral treatment (ART) has become the worldwide standard of care for HIV-infected pregnant women, both for their own health and for prevention of HIV transmission to their infants. In a large randomized trial of HIV-infected pregnant women in Africa and India, antepartum ART (with one of two different protease inhibitor-based regimens) resulted in lower transmission rates compared with zidovudine plus single-dose nevirapine (0.5 versus 1.8 percent) . Rates of preterm birth at <37 weeks were higher with the ART regimens than with zidovudine, but more significant prematurity (<34 weeks) and neonatal deaths were not increased. Clinicians should discuss with patients the potential risk for adverse pregnancy outcome with certain ART regimens. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Preterm birth'.)
Long-acting reversible contraception and teenage pregnancy rates (November 2016)
In a systematic review of nine studies including nearly 27,000 adolescent and young adult women (≤25 years), the 12-month continuation rate was nearly twice as high with the intrauterine device or contraceptive implant as with other contraceptive methods (approximately 85 percent versus 40 to 50 percent) . Increased contraceptive use, particularly increased use of these highly effective long-acting reversible contraceptive (LARC) methods, contributed to the historically low teenage pregnancy rate in 2015 . These observations support our recommendations to highlight LARC methods when discussing contraception with adolescents and young adults. (See "Pregnancy in adolescents", section on 'Epidemiology' and "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
Updated US guidelines on HIV infection and pregnancy (November 2016)
The Department of Health and Human Services in the United States recently published updated guidelines on the evaluation and management of HIV-infected pregnant women to reduce the risk of perinatal transmission . Preferred antiretroviral agents for initiation in pregnant women are now tenofovir-disoproxil-fumarate plus emtricitabine or lamivudine, abacavir-lamivudine, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, and raltegravir. Other agents are not recommended for routine initiation in pregnant women because of limited data during pregnancy, but women who become pregnant while taking other commonly used agents can continue their regimen if they have achieved viral suppression. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings", section on 'Antiretroviral selection and management'.)
Incidence of sexually transmitted infections in the United States (November 2016)
The total number of cases of chlamydia (over 1.5 million), gonorrhea (nearly 400,000), and syphilis (nearly 24,000) reported to the Centers for Disease Control and Prevention in the United States in 2015 was the highest ever recorded in a given year . Chlamydia and gonorrhea continued to occur most commonly among 15 to 24 year olds, and men who have sex with men accounted for the majority of gonorrhea and primary/secondary syphilis cases. These surveillance data highlight the importance of sexually transmitted infection prevention efforts, screening, and treatment among at-risk individuals. (See "Epidemiology of Chlamydia trachomatis infections", section on 'Incidence' and "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Incidence' and "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology' and "Screening for sexually transmitted infections".)
Postmenopausal estrogen and cognitive function (August 2016)
While limited observational and clinical trial data have suggested that early, but not late, postmenopausal exposure to estrogen provides protection against later cognitive impairment, a new randomized trial found no benefit of estrogen regardless of when it was started. In the Early versus Late Intervention Trial with Estradiol (ELITE), 643 postmenopausal women, stratified according to time since menopause (<6 years [early] versus >10 years [late]), received oral estradiol (with progesterone for women with a uterus) or placebo for a median of five years . When compared with placebo, estradiol, whether it was started early or late, had no effect on verbal memory, executive function, or global cognition. (See "Estrogen and cognitive function", section on 'Younger menopausal women'.)
Guidance on hysteroscopic sterilization from the US FDA (November 2016)
Hysteroscopic placement of micro-inserts into the fallopian tubes is a minimally invasive approach to female sterilization; however, long-term complications are a concern. In October 2016 the US Food and Drug Administration (FDA) issued final guidance related to this procedure, recommending a boxed warning regarding potential adverse effects and the potential need for surgical removal to manage these effects . The FDA also recommended a checklist highlighting key risk and benefit information to be reviewed and signed by the patient and physician and provided an example of a procedural consent form. (See "Hysteroscopic sterilization", section on 'Statements from regulatory organizations'.)
Outcomes of hysteroscopic versus laparoscopic sterilization (September 2016)
Female sterilization may be performed via laparoscopy or hysteroscopy, but few studies have compared the outcomes of these approaches. In a large retrospective study, hysteroscopic sterilization overall was associated with a higher pregnancy rate than laparoscopic sterilization (4.2 versus 3.7 percent at five years) . However, women who completed the full protocol of hysteroscopic sterilization followed within six months by a hysterosalpingogram to confirm tubal occlusion had pregnancy rates similar to those who underwent a laparoscopic procedure. This suggests that the efficacy of these two procedures is comparable with ideal use, but hysteroscopic sterilization may have a higher failure rate with typical use. (See "Overview of female sterilization", section on 'Laparoscopy versus hysteroscopy'.)
Hysterectomy-corrected cervical cancer mortality rates and racial variation (February 2017)
Cervical cancer incidence and mortality rates are known to vary across racial groups in the United States but can be underestimated if data are not adjusted for prior hysterectomy. In a population-based study that corrected for the prevalence of hysterectomy, cervical cancer mortality in black women was more than twice that of white women from 2000 to 2012 (10.1 versus 4.7 per 100,000) . These data add to the body of evidence showing a racial disparity in cervical cancer mortality and support the need for research to identify and overcome the factors that account for this disparity. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Incidence and mortality'.)
Risk of preterm delivery following loop electrosurgical excision procedure (LEEP) (November 2016)
Studies have consistently found an increased risk for preterm delivery in pregnancies conceived after cold knife conization, but data are mixed regarding the risk with laser conization and loop electrosurgical excision procedure (LEEP). In the largest study of pregnancy outcomes after treatment for cervical intraepithelial neoplasia (CIN), a Norwegian registry study of almost 10,000 births confirmed that prior treatment for CIN was associated with an increased risk of preterm birth compared with no prior treatment . The strongest associations were for cold knife and laser conization, but a small increase in risk was also observed for LEEP. Women with CIN 2,3 who plan future childbearing should be counseled about the risks and benefits of both treatment and observation. (See "Cervical intraepithelial neoplasia: Reproductive effects of treatment", section on 'Risks of individual treatment methods'.)
Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer (October 2016)
In a phase III trial, niraparib was compared with placebo in approximately 550 patients with platinum-sensitive, recurrent ovarian cancer, stratified by germline mutation status . Niraparib improved progression-free survival in all patient groups, although over a third experienced severe hematologic toxicity. In the absence of overall survival data, and given significant toxicity, the appropriate timeframe and strategy for further treatment (with niraparib as maintenance therapy, or with chemotherapy upon disease progression) is unclear. Niraparib remains investigational and should not be used outside of a clinical trial. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease", section on 'Niraparib'.)
Frozen versus fresh embryo transfer for women with polycystic ovary syndrome (August 2016)
Traditionally, fresh embryos are transferred at the initial in-vitro fertilization (IVF) cycle and excess embryos are frozen for future use. However, women with polycystic ovary syndrome (PCOS) may have improved outcomes with transfer of frozen embryos. In a recent trial of 1500 subfertile women with PCOS in China randomly assigned to fresh or frozen embryo transfer, frozen embryo transfer resulted in a higher frequency of live birth and lower frequencies of pregnancy loss and ovarian hyperstimulation syndrome (OHSS), but the frequency of preeclampsia was increased . Of note, the study protocol differed from standard IVF protocols in the United States (US) and the mean body mass index (BMI) of the subjects was much lower than the BMI of women with PCOS in the US. Given these concerns and the higher risk for preeclampsia, we do not recommend routine transfer of frozen rather than fresh embryos in women with PCOS undergoing IVF in the US. (See "In vitro fertilization", section on 'Women with polycystic ovary syndrome (PCOS)'.)
Cranberry products and urinary tract infection in women (October 2016)
Numerous clinical studies on the effects of cranberry products on recurrent urinary tract infection (UTI) in women have failed to clearly demonstrate a preventive benefit. In a year-long randomized trial among female nursing home residents, cranberry capsules similarly did not reduce adjusted rates of bacteriuria plus pyuria or symptomatic UTI compared with placebo . While we do not suggest cranberry products to reduce the risk of recurrent UTI, there is likely little harmful effect. (See "Recurrent urinary tract infection in women", section on 'Cranberry products'.)
Treatment for refractory urgency urinary incontinence in women (October 2016)
Whether onabotulinumtoxinA (BoNT-A) or sacral neuromodulation (SNM) is the better treatment for women with refractory urgency urinary incontinence (UUI) is unclear. In a randomized trial directly comparing the two approaches, the BoNT-A group had greater reductions in daily UUI episodes and bothersome symptoms . However, the small statistical differences may not be clinically significant, particularly since the risk of urinary tract infection increased. Thus, we believe that both treatments are reasonable treatment options for refractory UUI. (See "Use of botulinum toxin for treatment of non-neurogenic lower urinary tract conditions".)
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