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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.
Coffee consumption and health (December 2017)
For most nonpregnant adults, moderate coffee consumption appears to be safe. In a review of meta-analyses of largely observational studies of multiple health outcomes, coffee consumption was more often associated with benefit than with harm . Drinking three to four cups of coffee per day was associated with the greatest benefit. Harmful associations were largely absent after adjustment for smoking except in pregnancy, where high consumption was associated with an increase in risk of low birth weight, preterm delivery, and pregnancy loss. Given the limitations of observational studies, UpToDate neither promotes nor discourages coffee consumption in nonpregnant adults but discourages more than 200 to 300 mg of caffeine intake per day in women who are pregnant or attempting to conceive. (See "Benefits and risks of caffeine and caffeinated beverages" and "The effects of caffeine on reproductive outcomes in women".)
Acetaminophen use in pregnancy and risk of attention-deficit/hyperactivity disorder (November 2017)
Epidemiologic studies have reported an association between in utero acetaminophen exposure and subsequent development of attention-deficit/hyperactivity disorder (ADHD)-like behaviors, but data are inconclusive. Now, a study from Norway that adjusted for maternal use of acetaminophen before pregnancy, familial risk of ADHD, and indications for using acetaminophen reported no association between ADHD and use <8 days, but an increased risk with use >29 days . Moreover, paternal and maternal use of acetaminophen were similarly associated with ADHD risk. The authors hypothesized that paternal acetaminophen use before pregnancy may have male germ-line epigenetic effects. These data may reassure pregnant women with fever or pain who are considering short-term use of acetaminophen. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Acetaminophen'.)
Elvitegravir-cobicistat use during pregnancy (November 2017)
Preferred antiretroviral regimens for pregnant women differ somewhat from those for the general HIV-infected adult population, in part because of altered pharmacokinetics during pregnancy. Recently updated Department of Health and Human Services perinatal guidelines now state that elvitegravir-cobicistat should not be selected as part of an initial antiretroviral regimen for treatment-naïve pregnant women because of emerging data suggesting decreased drug levels during pregnancy and an associated risk of loss of virologic suppression [3,4]. Furthermore, if an HIV-infected woman is already receiving a suppressive elvitegravir-cobicistat-containing regimen when she becomes pregnant, we suggest switching to a different regimen; if elvitegravir-cobicistat is continued, the potential risks and need for close viral monitoring should be discussed. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings", section on 'On ART with viral suppression'.)
Updated guidance for fetal ultrasound surveillance for congenital Zika virus syndrome (November 2017)
Prenatal ultrasound is used to screen for congenital Zika virus infection, although the sensitivity, specificity, and positive and negative predictive values are not well established, and optimal timing between exposure and initial and follow-up sonographic screening are unknown. A common protocol is to perform an initial ultrasound examination four weeks from the suspected exposure, followed by serial ultrasound examinations every four weeks, ensuring that at least one ultrasound is performed between 28 and 33 weeks of gestation. The Centers for Disease Control and Prevention has updated its guidance for women with laboratory evidence of infection and now states that clinicians may consider extending the time interval between follow-up ultrasound examinations in accordance with patient preferences and clinical judgment . In women with possible exposure during pregnancy but no laboratory evidence of infection, ultrasound screening beyond that obtained for routine prenatal care is no longer recommended. We agree with these recommendations. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Candidates'.)
Continuous glucose monitoring in pregnant women with type 1 diabetes (October 2017)
Good glycemic control before and during pregnancy in women with type 1 diabetes is a key factor impacting pregnancy outcome, but whether frequent daily capillary glucose monitoring or continuous glucose monitoring (CGM) results in better glycemic control and pregnancy outcome has not been established. In two parallel open-label trials, 325 women (215 pregnant, 110 planning pregnancy) with type 1 diabetes receiving intensive insulin therapy were randomly assigned to either CGM plus capillary glucose monitoring or capillary glucose monitoring alone . In women planning pregnancy, glycemic control at the end of the trial was similar in both groups. In pregnant women, glycemic control and some newborn outcomes (eg, frequency of hypoglycemia, large for gestational age) were better in the CGM group. Although the improvement in neonatal hypoglycemia with CGM appears promising, the lack of blinding may have biased decisions regarding neonatal management. Also, it is unclear whether the high level of maternal compliance with CGM in this trial could be achieved in other populations. (See "Pregestational diabetes mellitus: Glycemic control during pregnancy", section on 'Self-monitoring of blood glucose'.)
Poor prognosis of early fetal growth restriction (October 2017)
Few large studies of early fetal growth restriction (FGR) provide complete outcome data. In a prospective population-based study, when FGR was diagnosed at 21 to 25 weeks, only 34 to 51 percent of offspring were live born and survived to discharge, and only 27 to 43 percent were live born and survived to discharge without severe morbidity . Over 20 percent of the deaths were related to pregnancy termination and 77 percent of the cohort had birth weight <3rd percentile. These data illustrate the poor prognosis for early severe FGR and are useful for prenatal counseling. (See "Fetal growth restriction: Evaluation and management", section on 'Perinatal'.)
Syphilis incidence in the United States (October 2017)
Syphilis causes a wide range of clinical syndromes and is associated with HIV transmission. The United States Centers for Disease Control and Prevention reported an approximately 18 percent increase in the rate of primary and secondary syphilis (the most infectious stages of the disease) in 2016, with 8.7 cases per 100,000 population, the highest rate since 1993 . More than 600 cases of congenital syphilis were also reported. Although syphilis rates increased among men and women, the rise was primarily attributable to men who have sex with men (MSM). These findings stress the importance of screening and treatment for sexually transmitted infection, especially in MSM and pregnant women. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology'.)
pH1N1-containing influenza vaccine and miscarriage (October 2017)
Multiple studies have reported that administration of inactivated influenza vaccines to pregnant women is not associated with an increased risk of maternal, fetal, or neonatal complications. One exception is a case-control study of a possible increase in spontaneous abortion among the subgroup of women vaccinated with two consecutive pH1N1-containing vaccines during the 2010-2011 and 2011-2012 seasons . This study had several limitations that might have influenced the findings, and further confirmation is needed. We continue to strongly recommend routine influenza vaccination with trivalent or quadrivalent inactivated influenza vaccine, as the benefits outweigh any risks. (See "Influenza and pregnancy", section on 'Safety'.)
Safety of tenofovir disoproxil fumarate during pregnancy (September 2017)
For HIV-infected pregnant women, tenofovir disoproxil fumarate (TDF) is a preferred agent to use as part of combination antiretroviral therapy (ART) in both resource-rich and limited settings. A recent meta-analysis reported that TDF increased neonatal mortality, and an accompanying British Medical Journal clinical practice guideline thus suggested zidovudine rather than TDF for HIV-infected pregnant women [10,11]. This conclusion was based on a single trial from Africa in which TDF-based ART resulted in higher rates of very preterm birth (<34 weeks) and neonatal mortality compared with zidovudine-based ART (each given with lopinavir-ritonavir), but not compared with zidovudine alone . Given uncertainties regarding the trial results, potential interactions between TDF and lopinavir-ritonavir, and observational data suggesting safety of other TDF-containing regimens in pregnancy, we do not believe the evidence is clear enough to stop using TDF as a preferred agent (although we do not initiate TDF and lopinavir-ritonavir containing regimens during pregnancy). The British HIV Association also released a statement consistent with our position . (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Very preterm birth/neonatal mortality'.)
2017-2018 influenza immunization recommendations for the United States (September 2017)
The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [14,15]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 1) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)
Severity of maternal Zika virus infection and birth outcome (September 2017)
Maternal-to-fetal transmission of Zika virus can occur with either symptomatic or asymptomatic maternal infection; the risk factors for transmission are unknown. In a prospective study from Rio de Janeiro of women with confirmed Zika virus infection during pregnancy, no association was observed between maternal disease severity (signs, symptoms, virus load) or prior dengue virus infection and adverse birth outcome defined as fetal loss or birth of a live infant with grossly abnormal clinical or brain imaging findings . This finding supports the Centers for Disease Control and Prevention (CDC) recommendation for serial fetal ultrasound examinations in pregnant women with laboratory evidence of Zika virus infection, regardless of maternal disease severity. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)
Revised ACOG diagnostic criteria for gestational diabetes mellitus (August 2017)
The American College of Obstetricians and Gynecologists updated practice bulletin on gestational diabetes mellitus (GDM) now states that some clinicians may choose to make this diagnosis in patients with one elevated glucose value on a glucose tolerance test (GTT), although the diagnosis generally requires that two or more glucose thresholds must be met or exceeded . This change was based on a 2016 systematic review that concluded that women with one abnormal value on the three-hour, 100-gram GTT were at increased risk for the same poor outcomes as women with two abnormal values . (See "Diabetes mellitus in pregnancy: Screening and diagnosis", section on '100-gram three-hour oral glucose tolerance test'.)
Increased nuchal translucency and Noonan syndrome (August 2017)
Increased nuchal translucency on first trimester ultrasound screening has been associated with over 100 developmental and genetic syndromes. In a retrospective study in which a Noonan syndrome gene sequencing panel was obtained in 39 euploid fetuses with nuchal translucency ≥3.0 mm (median thickness 4.0 mm), 10 percent had variants consistent with Noonan syndrome . It may be reasonable to offer screening for genetic mutations associated with Noonan syndrome in euploid fetuses with nuchal translucency ≥3.0 mm, but prospective studies are still needed to validate this result. (See "Cystic hygroma and increased nuchal translucency", section on 'Targeted genetic studies'.)
Genomic sequencing to identify inherited pathogenic genes in families of individuals with multiple congenital malformations (August 2017)
Next-generation sequencing, such as whole exome or whole genome sequencing, is used to aid in diagnosis of complex diseases such as severe intellectual disability or developmental delay. A study that used these techniques to evaluate patients with multiple congenital malformations and their family members identified four families with loss-of-function variants in two genes leading to nicotinamide adenine dinucleotide (NAD) deficiency (HAAO, encoding 3-hydroxyanthranilic acid 3,4-dioxygenase, and KYNU, encoding kynureninase) . In a mouse model of these defects, niacin supplementation during gestation corrected the NAD deficiency and prevented abnormal embryogenesis and fetal death. (See "Birth defects: Causes", section on 'Disorders due to single gene defects' and "Principles and clinical applications of next-generation DNA sequencing", section on 'Diagnosis of complex diseases'.)
Sugar-sweetened beverage consumption in pregnancy (August 2017)
A growing body of data suggests that prenatal exposures influence susceptibility to obesity. In a prospective cohort study, higher maternal consumption of sugar-sweetened beverages during pregnancy was associated with increasing adiposity among in utero-exposed school-aged offspring . The association persisted after adjustment for multiple confounding variables and was independent of the offspring's beverage intake. We advise pregnant women to avoid or limit intake of sugar-sweetened beverages because they tend to be high in calories, low in nutritive value, and may impact offspring adiposity. (See "Nutrition in pregnancy", section on 'Sugar-sweetened beverages'.)
Updated guidance on diagnosis of Zika virus infection in pregnancy (July 2017)
The Centers for Disease Control and Prevention have updated their guidance for diagnosis of Zika virus infection in asymptomatic pregnant women (algorithm 1) . Two major changes are: (1) for asymptomatic women with possible Zika virus exposure but no ongoing exposure, nucleic acid testing (NAT) is no longer recommended; and (2) for asymptomatic women with ongoing Zika virus exposure, first and second trimester IgM antibody testing is no longer recommended, but NAT should be performed three times during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Asymptomatic women with limited or ongoing risk of Zika virus exposure'.)
Dose of aspirin for prevention of preeclampsia (July 2017)
In women at high risk for developing preeclampsia, increasing evidence suggests that low-dose aspirin prophylaxis should be started early in gestation and at a dose higher than 81 mg/day. In a multicenter trial in nearly 1800 women at high risk for preterm preeclampsia, use of aspirin 150 mg from the end of the first trimester (12 to 13 weeks) until 36 weeks of gestation reduced the frequency of preterm preeclampsia by over 60 percent compared with placebo . Based on these and other data, we now suggest a dose of 100 to 150 mg of aspirin rather than a lower dose. In the US, this can be achieved by taking one and one-half 81 mg tablets; however, taking one 81 mg tablet is also reasonable since this is the commercially available dose and has proven efficacy. (See "Preeclampsia: Prevention".)
In utero exposure to beta-blockers and congenital heart disease (June 2017)
Although several previous studies have suggested an association between in utero exposure to beta-blockers and congenital heart disease, the most recent study found no association after adjusting for maternal age, maternal body mass index, and maternal comorbidities . Further research is required given the limitations of available studies, including inability to analyze data by type of beta-blocker, variability in timing of exposure within the first trimester, differences in indications for beta-blocker therapy, and recall, recording, publication, and survivor biases. When first trimester antihypertensive therapy is indicated, we suggest using either methyldopa or labetalol. (See "Management of hypertension in pregnant and postpartum women", section on 'Beta-blockers'.)
Risk of congenital Zika virus syndrome (June 2017)
The magnitude of risk of birth defects resulting from in utero exposure to Zika virus is uncertain. The Centers for Disease Control and Prevention identified over 2500 pregnant women in US territories with Zika virus infection in early 2017 . Maternal Zika virus infection in the first trimester was associated with an 8 percent incidence of offspring with birth defects, but fell to 4 to 5 percent with infection in the second and third trimesters. Because of study limitations, these figures likely understate the true risk of any congenital adverse outcome. Importantly, structural birth defects were seen with similar frequency in infants born to women with and without clinical signs and symptoms of Zika virus infection during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)
IVF-conceived pregnancy and Down syndrome screening (June 2017)
In vitro fertilization (IVF) (with or without intracytoplasmic sperm injection) can affect maternal serum marker levels to mimic the pattern associated with Down syndrome. In a meta-analysis of studies that compared free β-human chorionic gonadotropin (hCG) levels, pregnancy-associated plasma protein A (PAPP-A) levels, and nuchal translucency measurements in IVF pregnancies with those in spontaneously-conceived pregnancies, PAPP-A was reduced by 15 percent, free beta-hCG was slightly increased, and nuchal translucency was unaffected by IVF . Based on these and other data, we recommend that clinicians inform the laboratory when specimens are taken from patients with IVF-conceived pregnancies, so that the laboratory can make appropriate adjustments in reported multiples of median (MoM), to reduce the need for follow-up invasive testing or secondary cell-free-DNA screening. (See "Laboratory issues related to maternal serum screening for Down syndrome", section on 'Assisted reproduction techniques'.)
Antenatal exposure to lithium and congenital cardiac defects (June 2017)
Fetal lithium exposure may increase the risk of cardiac malformations, although the data are conflicting. In a retrospective study examining cardiac defects in infants exposed to lithium or lamotrigine during the first trimester, cardiac malformations occurred more frequently in infants exposed to lithium (2.4 versus 1.4 percent) . There was a dose-response relationship between the lithium dose and the risk of cardiac malformations. These results support using lamotrigine for euthymic patients with bipolar disorder who are pregnant or planning a pregnancy and are receiving maintenance pharmacotherapy. (See "Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy", section on 'Cardiac'.)
INTRAPARTUM AND POSTPARTUM OBSTETRICS
Severe maternal morbidity in overweight and obese women (December 2017)
In a population-based study including over 740,000 pregnant women, women who were overweight or obese were at increased risk of severe maternal morbidity and mortality compared with women with a normal body mass index (BMI), and the risk increased with increasing BMI . Morbidity included hemorrhage requiring transfusion; serious cardiac, respiratory, cerebrovascular, or hematologic complications; venous thrombosis/embolism; sepsis; shock; hepatic or renal failure; anesthesia-related complications; and uterine rupture. These findings underscore the importance of counseling overweight and obese women about their increased risk for serious complications during pregnancy, as well as for adverse birth outcomes, and encouraging prepregnancy weight loss. (See "Obesity in pregnancy: Complications and maternal management", section on 'Overall risk of severe morbidity or mortality'.)
Delayed respiratory depression after neuraxial morphine at cesarean delivery (November 2017)
The incidence of delayed respiratory depression after neuraxial morphine at cesarean delivery is unknown. In a prospective observational study of patients who received intrathecal morphine 150 mcg at cesarean delivery, a mild oxygen desaturation event (median peripheral arterial oxygen saturation [SpO2] <90 percent in a 30-second monitoring window) was detected in 23 percent, and a severe desaturation event (median SpO2 <85 percent) in 4 percent of patients . Desaturations most frequently occurred four to eight hours after administration of intrathecal morphine. Patients with risk factors for respiratory depression may require pulse oximetry monitoring for 24 hours after neuraxial morphine. (See "Anesthesia for cesarean delivery", section on 'Choice of spinal medication'.)
Management of oxytocin in the active phase (November 2017)
In a meta-analysis of randomized trials comparing discontinuation versus continuation of oxytocin in the active phase of induced labor, discontinuation resulted in lower rates of cesarean delivery (approximately 9 versus 15 percent) and tachysystole (approximately 6 versus 13 percent) . Although discontinuation increased the duration of the active phase, the duration of the second stage was similar in both groups. Given the limitations in the meta-analysis (including heterogeneity of regimens and criteria for active phase), we believe the optimum approach has not been established, and it is reasonable for clinicians to either continue or discontinue oxytocin during the active phase. (See "Induction of labor with oxytocin", section on 'Dose titration and maintenance'.)
Protective effect of breastfeeding against SIDS (November 2017)
Breastfeeding appears to have an independent protective effect against sudden infant death syndrome (SIDS). In a new meta-analysis of individual-level data from case-control studies, any breastfeeding for at least two months nearly halved the risk for SIDS, after controlling for potential confounders . Protection against SIDS increased with longer duration of breastfeeding, but not with exclusive breastfeeding compared with partial breastfeeding. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Protective factors'.)
Delayed cord clamping in preterm infants (November 2017)
Delayed cord clamping has been recommended for vigorous preterm infants to decrease infant morbidity and increase iron stores, based on meta-analyses of a few small randomized trials. Now, the largest randomized trial of delayed versus immediate cord clamping in over 1500 infants <30 weeks of gestation found no reduction in death or major morbidity from the intervention . There was no clear reason for the discordancy from previous trials. We delay cord clamping for at least 30 seconds in vigorous preterm infants but believe clinicians should use their judgment about whether and how long to delay cord clamping in individual preterm infants until definitive data are available. (See "Management of normal labor and delivery", section on 'Cord clamping'.)
Postpartum antibiotic prophylaxis for cesarean delivery in obese women (October 2017)
Traditionally, antibiotic prophylaxis has not been continued postpartum because trials in general surgical populations showed no benefit. Now, a randomized trial of oral cephalexin plus metronidazole for 48 hours following cesarean delivery found a 60 percent reduction in surgical site infections compared with placebo . All of the participants were obese and received preoperative prophylaxis. This trial should prompt further study to confirm or refute these findings, determine whether specific populations are more likely to experience clinically meaningful benefits, and evaluate both short- and long-term risks of extending the period of prophylaxis. (See "Cesarean delivery of the obese woman", section on 'Antibiotic prophylaxis'.)
Vaginal cleansing before cesarean delivery (August 2017)
Whether vaginal cleansing before cesarean delivery further reduces infection-related morbidity in patients already receiving parenteral antibiotic prophylaxis has been unclear. In a 2017 meta-analysis of randomized trials of this issue, vaginal cleansing reduced the incidence of endometritis whether or not preoperative antibiotics were administered, but the reduction appeared to be limited to women in labor or with ruptured membranes . Based on these data, we perform a povidone-iodine vaginal scrub with a sponge stick for 30 seconds before cesarean delivery in women in labor or with ruptured membranes. (See "Cesarean delivery: Preoperative planning and patient preparation", section on 'Vaginal preparation'.)
Long-term risk of hypertension in women with pregnancy-associated hypertension (August 2017)
For women with a history of gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome, at least annual lifelong measurement of blood pressure is important due to their increased risk for chronic hypertension. In a long-term population-based study, the rate of hypertension in the first decade postpartum for primiparous women in their 20s with pregnancy-associated hypertension was 14 percent, compared with 4 percent for those without pregnancy-associated hypertension . For primiparous women in their 40s, the rates were 32 and 11 percent, respectively. The risk of chronic hypertension in this population may be reduced by adherence to a beneficial lifestyle (eg, achieving/maintaining a healthy weight, salt restriction, exercise, limited alcohol intake) . (See "Management of hypertension in pregnant and postpartum women", section on 'Long-term prognosis of women with hypertension during pregnancy'.)
Intrapartum fluid administration (August 2017)
We provide maintenance intravenous fluids with glucose when intrapartum oral intake is restricted or otherwise inadequate to avoid volume depletion and ketosis. Some studies have suggested that a rapid intravenous fluid infusion rate or glucose supplementation are also associated with a shorter length of labor in such women. However, in one of the only trials to evaluate both interventions together, the length of labor was similar for women randomly assigned to 250 mL/hour of normal saline, 125 mL/hour of normal saline with dextrose, or 250 mL/hour of normal saline with dextrose . We do not adjust intravenous fluid administration to try to reduce labor duration. (See "Management of normal labor and delivery", section on 'Fluids and oral intake'.)
Left uterine displacement for cesarean delivery (July 2017)
Left uterine displacement is routinely used to avoid aortocaval compression during cesarean delivery, but the supporting evidence for this practice is not robust. In a trial that randomly assigned 100 healthy parturients having elective cesarean delivery to supine positioning or 15 degree lateral tilt, there was no difference in fetal acid base status . Blood pressure was maintained at baseline with intravenous fluid co-loading and phenylephrine in both groups. While these results raise a question of the need for left uterine displacement in healthy parturients, they may not apply to patients with uteroplacental insufficiency or to emergency procedures, and we continue to advise left uterine displacement for most women. (See "Anesthesia for cesarean delivery", section on 'Intraoperative positioning'.)
Cesarean delivery and future preterm birth (July 2017)
A retrospective cohort study observed that a second stage cesarean delivery more than doubled the odds of spontaneous preterm birth at the next birth compared with a prior spontaneous vaginal birth . The risk did not appear to be related to a prolonged second stage. Future studies should further evaluate this possible association and possible causative factors (eg, incision placement, method of delivering fetus from a low station, previous attempt at operative vaginal delivery). (See "Cesarean delivery: Postoperative issues", section on 'Preterm birth'.)
Neuraxial anesthesia in parturients with thrombocytopenia (June 2017)
The risk of spinal epidural hematoma (SEH) associated with neuraxial anesthesia (NA) techniques in patients with thrombocytopenia is poorly defined because SEH is rare. In a systematic review of over 1500 NA procedures in parturients with platelet counts less than 100,000 /microL, no cases of epidural hematoma requiring decompressive laminectomy were identified . A statistical analysis based on data from this cohort suggests that the incidence of epidural hematoma may range from 0.2 percent (for platelet counts 70 to 100,000/microL) to 11 percent (for platelet counts <49,000/microL). These estimates may inform clinical decision-making regarding performance of NA in parturients with thrombocytopenia. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics".)
IUD use associated with lower cervical cancer incidence (November 2017)
Prior studies have suggested that intrauterine devices (IUDs), one of the most reliable forms of long-acting reversible contraception, are associated with a reduction in cervical cancer. Now, a meta-analysis including 16 studies reported that the incidence of cervical cancer was reduced by about one-third in IUD users compared with nonusers . This protective effect is particularly important for women at higher risk of cervical cancer, such as those who have not received the human papillomavirus vaccine or who do not have access to cervical cancer screening. It is not known if the type of device influences the reduction in cervical cancer risk. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'Benefits'.)
Contraception counseling and bariatric surgery (November 2017)
Women who undergo bariatric surgery are advised to use contraception during the first 12 to 18 postoperative months to avoid pregnancy during the rapid weight-loss phase. However, a prospective study of over 700 women who underwent bariatric surgery reported that 4 percent actively tried to conceive, and 41 percent had unprotected intercourse during the first postsurgical year . Risk factors for not using contraception included advancing age, being married or cohabitating, and preoperatively rating future pregnancy as important. This study highlights the need for preoperative and postoperative contraceptive counseling, particularly for women with risk factors for unprotected sexual activity. (See "Fertility and pregnancy after bariatric surgery", section on 'Contraception'.)
Vaginal dehydroepiandrosterone for genitourinary symptoms in postmenopausal cancer survivors (October 2017)
Treatment of genitourinary syndrome of menopause (GSM) in survivors of estrogen-sensitive malignancies is challenging because vaginal estrogen may be contraindicated. In a randomized trial comparing two doses of vaginal dehydroepiandrosterone (DHEA) with a nonhormonal vaginal moisturizer in postmenopausal cancer survivors (primarily breast cancer), all three groups reported similar improvement in dyspareunia and vaginal dryness symptoms at 12 weeks, but only the higher dose DHEA group reported significant improvement in sexual function over baseline on a validated sexual health measure . Vaginal DHEA holds promise as a GSM treatment for breast cancer survivors, but safety concerns remain because it increases serum estrogen levels. (See "Treatment of genitourinary syndrome of menopause (vulvovaginal atrophy)", section on 'Women with breast cancer'.)
Single-dose secnidazole for bacterial vaginosis (September 2017)
Metronidazole is a preferred treatment for bacterial vaginosis (BV) and is given topically or orally as a multi-day course. In September 2017, the US Food and Drug Administration approved secnidazole, a related oral antibiotic with a longer half-life, for the treatment of BV . In an earlier study, a single dose of secnidazole was as effective as, but not superior to, metronidazole for seven days. Secnidazole is an option for BV when a single dose is desired (eg, to enhance adherence), but it is more expensive than other regimens. (See "Bacterial vaginosis: Treatment", section on 'Secnidazole'.)
Electroacupuncture for stress urinary incontinence in women (August 2017)
Treatment options for stress urinary incontinence (SUI) in women include lifestyle modifications, bladder training, medications, devices, and surgery. The use of electroacupuncture for SUI has been reported in a multicenter randomized trial in China . Compared with sham treatments, electroacupuncture reduced the volume of urine leaked and number of leakage episodes. Availability of this therapy may limit this option. Additionally, confirmation of these results in other trial settings is needed before its general use can be widely recommended. (See "Treatment of urinary incontinence in women", section on 'Other specialty treatments'.)
Overweight and risk of pelvic organ prolapse (June 2017)
Studies assessing the impact of body weight on risk of pelvic organ prolapse (POP) have reported conflicting results. A meta-analysis of 22 studies now reports that the risk of POP is increased by at least 36 percent in overweight and obese women compared with normal-weight peers . This finding is noteworthy because body weight is one of the few modifiable risk factors for POP. (See "Pelvic organ prolapse in women: Epidemiology, risk factors, clinical manifestations, and management", section on 'Obesity'.)
Hysteroscopic sterilization device no longer available except in United States (October 2017)
The risk of complications associated with hysteroscopic sterilization with the Essure micro-insert is controversial. In 2016, the US Food and Drug Administration issued a boxed warning regarding these risks. Concerns about complications have resulted in the removal of the device from many markets worldwide. In September 2017, the manufacturer withdrew the Essure device from all markets, except the United States . Before inserting the device, clinicians should counsel patients regarding the risk of complications, particularly women at higher risk (ie, preexisting pelvic pain), and about other contraceptive options. Asymptomatic women with the device in place do not need to have it removed. (See "Hysteroscopic sterilization", section on 'Availability'.)
Risk of endometrial cancer after endometrial ablation (September 2017)
Endometrial ablation is a common treatment for heavy menstrual bleeding but introduces obstacles to the detection and diagnosis of endometrial neoplasia. Whether this delays diagnosis of endometrial cancer is unclear. In a retrospective cohort study from Finland of over 5400 women who underwent endometrial ablation and were followed for a mean of seven years, only three women developed endometrial cancer after ablation (ratio of observed to expected cases: 0.56 [95% CI 0.12-1.64]); two cancers were at an early stage and one at an unknown stage . Endometrial hyperplasia, a precursor to cancer, was found in 1.8 percent of the subset of women who underwent post-ablation hysterectomy. This study found no evidence of a delay in diagnosis of endometrial cancer after ablation, but with so few events, further study is needed. (See "An overview of endometrial ablation", section on 'Risk factors for endometrial cancer'.)
Post-conization HPV testing for predicting recurrence risk (December 2017)
In women with high-grade cervical intraepithelial neoplasia (CIN 2,3), positive margins on the cone biopsy specimen are predictive of recurrent high-grade or invasive disease (CIN 2+). However, a recent meta-analysis found that a positive test for high-risk human papillomaviruses (HPV) after excision was a more accurate indicator of treatment failure (sensitivity 91 percent for HPV versus 56 percent with positive margins) . HPV and margin status had similar specificity. These findings can help in counseling women treated for high-grade CIN about their recurrence risk. (See "Cervical intraepithelial neoplasia: Treatment and follow-up", section on 'Positive margins'.)
Pembrolizumab as a second-line option in metastatic or recurrent cervical cancer (November 2017)
Metastatic or recurrent squamous cell cervical cancer has a poor prognosis. First-line treatment includes chemotherapy with bevacizumab, an antiangiogenic agent. There are few data to guide second-line therapy. Pembrolizumab, a programmed cell death 1 (PD-1) immune checkpoint inhibitor, was evaluated in a prospective phase Ib study in women with PD-L1-positive tumor cells and disease progression after first-line therapy for metastatic or recurrent cervical cancer. The overall response rate was 17 percent (4 of 24 patients) and median duration of response was 5.4 months . While potentially promising, we await data from further studies before using pembrolizumab for this indication. Pembrolizumab has been approved for use in a variety of other advanced solid tumors (including endometrial, gastrointestinal, breast, prostate, bladder, and thyroid) that show deficiency in DNA mismatch repair, have progressed following prior treatment, and for which alternative treatment options are not available. (See "Management of recurrent or metastatic cervical cancer", section on 'Second-line therapy'.)
Bevacizumab and chemotherapy benefit confirmed in metastatic cervical cancer (October 2017)
Metastatic, persistent, or recurrent squamous cell cervical carcinoma has a poor prognosis, but survival has shown stepwise improvement with treatment with chemotherapy and, most recently, the angiogenesis inhibitor bevacizumab. The final results of the GOG 240 trial confirmed the 2012 interim results . The combination of bevacizumab and chemotherapy resulted in longer overall survival (16.8 versus 13.3 months) and progression-free survival (8.2 versus 6.0 months) than chemotherapy alone. Severe hypertension was more frequent in the bevacizumab group. The final results of this study further support our recommendation to treat women with recurrent or metastatic cervical cancer (who are not surgical candidates) with bevacizumab combined with chemotherapy. (See "Management of recurrent or metastatic cervical cancer", section on 'Chemotherapy plus bevacizumab as first-line treatment'.)
PARP inhibitor maintenance therapy in platinum-sensitive, recurrent ovarian cancer (March 2017, Modified September 2017)
Inhibitors of poly-ADP ribose polymerase (PARP) are being actively evaluated as maintenance therapy in platinum-sensitive relapsed ovarian cancer. In phase III trials of women with recurrent ovarian cancer who achieved a response to their most recent platinum-based treatment, the PARP inhibitors niraparib, olaparib, and rucaparib have each demonstrated progression-free survival benefits as maintenance therapy compared with placebo [52-55]. These data have led to approvals by the US Food and Drug Administration of both niraparib and olaparib in this setting [56,57]. However, overall survival data for PARP inhibitors as maintenance therapy are immature, and these agents have not been compared with bevacizumab, which is better established in the maintenance setting. Pending further data, we reserve use of PARP inhibition as maintenance therapy for patients with relapsed ovarian cancer who are not candidates for bevacizumab and who are in a complete or partial response to platinum-based chemotherapy. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease".)
Oral contraceptives and ovarian cancer risk (June 2017)
Use of oral estrogen-progestin contraceptives is associated with a reduction in risk of ovarian cancer. In the largest and longest duration study of oral contraceptive use, the Royal College of General Practitioners’ Oral Contraception Study followed over 46,000 women for up to 44 years and found that ever-use of oral contraceptives was associated with a 33 percent reduction in ovarian cancer risk . This finding supports previous data and our recommendation for use of oral contraceptives in women who desire ovarian cancer risk reduction who have not undergone risk reduction surgery and who are not trying to conceive. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal cancer" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Oral contraceptives'.)
Breastfeeding and risk of endometrial cancer (June 2017)
Breastfeeding has many maternal and infant benefits. In a meta-analysis of epidemiologic studies of women with endometrial cancer, ever-breastfeeding was associated with an 11 percent reduction in risk compared with never breastfeeding, and the greatest reduction was among those who breastfed for at least three months per child . A decreased risk of endometrial cancer appears to be an additional maternal benefit of breastfeeding. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Breastfeeding'.)
Sentinel lymph node biopsy in endometrial cancer (May 2017)
Sentinel lymph node biopsy for staging endometrial carcinoma is increasingly performed instead of selective or extended nodal dissection. In the largest multicenter prospective study of the procedure in over 300 women with clinical stage I endometrial carcinoma, successful mapping of at least one sentinel lymph node was achieved in 86 percent and the sensitivity of the sentinel lymph node was 97 percent . Nevertheless, we believe further study is needed before sentinel lymph node biopsy is established as a reasonable alternative to full pelvic lymphadenectomy in endometrial carcinoma. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment".)
Ovarian biomarkers for predicting ability to conceive (October 2017)
Serum anti-Müllerian hormone (AMH) and follicle stimulation hormone (FSH) levels are commonly measured to assess ovarian reserve in women wishing to conceive. However, a large prospective cohort study of women age 30 to 44 years, without a history of infertility, reported similar conception rates for women with normal and abnormal AMH and FSH levels . This study adds to the body of evidence suggesting that AMH and FSH levels do not predict the probability of pregnancy in women without a diagnosis of infertility, even among women of older age. The study did not address conception rates for women with a known diagnosis of infertility. For women in this age group with known infertility who are considering in vitro fertilization, these tests do have some prognostic value. (See "Evaluation and management of infertility in women of advancing age", section on 'Diminished ovarian reserve'.)
Polycystic ovary syndrome: No role for metformin in ovulation induction (September 2017)
Metformin was widely used in the past for women with polycystic ovary syndrome (PCOS) for ovulation induction and prevention of miscarriage, multiple gestations, and pregnancy complications. However, the American Society for Reproductive Medicine now suggests that there is insufficient evidence to recommend metformin for any of these indications . Unlike the first-line ovulation induction agents letrozole and clomiphene, which improve live birth rates, metformin increases ovulatory rates and pregnancy rates, but not live birth rates. (See "Metformin for treatment of the polycystic ovary syndrome", section on 'Anovulatory infertility'.)
Investigational gene editing in human embryos to prevent disease (August 2017)
In vitro fertilization with preimplantation genetic diagnosis (IVF/PGD) is an established strategy for selecting embryos for implantation that lack specific pathogenic gene mutations. In a landmark study of the use of gene editing to correct a pathogenic gene mutation in human embryos, a mutant paternal allele was repaired using the homologous wild-type maternal gene . The embryos were not transferred or allowed to mature beyond the blastocyst stage. This technology is experimental; the efficacy, safety, and clinical utility of gene editing remain unknown. (See "In vitro fertilization", section on 'Other uses'.)
Fertility preservation with cryopreserved ovarian tissue transplantation (July 2017)
For women at risk of ovarian failure due to planned gonadotoxic therapy and who desire fertility preservation, increasing evidence supports use of ovarian tissue cryopreservation followed by autotransplantation (OTT) after completion of therapy. In a 2017 meta-analysis, endocrine function was restored for at least four months after OTT in over 60 percent of women . OTT was associated with similar live birth rates as conventional frozen embryo transfer, and over 60 percent of women who conceived after an orthotopic transplant conceived naturally. (See "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection", section on 'Outcomes'.)
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