Disclosures: Kristen Eckler, MD, FACOG Nothing to disclose. Sandy J Falk, MD, FACOG Nothing to disclose. Vanessa A Barss, MD, FACOG Nothing to disclose.
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.
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.
Prescription medications during pregnancy (August 2015)
Concerns have been raised regarding the frequency with which medication is prescribed during pregnancy, especially for those drugs that may have adverse outcomes for the mother or her fetus. In a study of over one million pregnant women in the United States Medicaid program, nearly 40 percent were prescribed a potentially harmful medication (category D, most commonly codeine and hydrocodone) and 5 percent were prescribed a medication contraindicated during pregnancy (category X, most commonly hormonal contraceptives that were prescribed prior to the diagnosis of pregnancy) . Overall, 83 percent were dispensed at least one medication of any kind (most commonly antibiotic or antifungal agents). While medication can be safely used in pregnancy, the lowest risk option is to avoid drug exposure if possible. When medication is to be taken, the risks and benefits must be discussed, particularly for medications with harmful potential, such as addiction. (See "Initial prenatal assessment and first trimester prenatal care", section on 'Medications commonly used in pregnancy'.)
Noninvasive prenatal screening and occult malignancy detection (August 2015)
The occurrence of more than one aneuploidy on noninvasive prenatal cell free DNA screening is rare and may suggest occult maternal malignancy. In a series including over 125,000 pregnant women who underwent noninvasive prenatal screening for aneuploidy of chromosomes 21, 18, 13, and, in some patients, X or Y, more than one aneuploidy was detected in 0.03 percent of tests . Various types of cancer were subsequently diagnosed during or after pregnancy in 7 of 16 women with multiple aneuploidies that were unrelated to the fetus or placenta. We do not consider noninvasive prenatal fetal aneuploidy testing a screening test for maternal malignancy, given the paucity of data on this association, the potential for false-positive results, and the emotional and medical impact of such results on the patient’s well-being. The appropriate clinical evaluation of such patients is unclear at this time. (See "Noninvasive prenatal testing using cell-free nucleic acids in maternal blood", section on 'Trisomy 21, 18, 13'.)
Limited value of fetal ST-segment analysis (August 2015)
The STAN S31 fetal heart monitor is a relatively new device used to monitor the fetal electrocardiogram during labor. Fetal ST-segment changes have been associated with hypoxemia and acidosis necessitating prompt delivery. The largest randomized trial of this approach to intrapartum fetal assessment assigned over 11,000 women to "open" or "masked" fetal ST-segment analysis and reported no significant between-group differences in the rate of cesarean delivery, any operative delivery, or the primary composite outcome (stillbirth, neonatal death, five-minute Apgar score ≤3, cord artery pH ≤7.05 and base deficit in extracellular fluid ≥12, intubation in the delivery room, seizures, neonatal encephalopathy) . The results of this large, well-designed trial are important because previous small trials had suggested ST-segment analysis reduced the frequency of fetal scalp sampling, operative vaginal delivery, and neonatal metabolic acidosis. We do not perform fetal ST-segment analysis as there is no convincing evidence that it improves maternal or neonatal outcome. (See "Intrapartum fetal heart rate assessment", section on 'ST analysis'.)
Pregnancy and surgical outcomes (July 2015)
There has been increasing evidence that pregnancy does not appear to increase the risk of poor surgical outcomes. In a retrospective cohort study of over 2500 pregnant women undergoing non-elective general surgery procedures, 30-day morbidity and mortality rates were comparable to those among procedure-matched non-pregnant controls . Non-elective surgical intervention should not be delayed because of pregnancy. (See "Management of the pregnant patient undergoing nonobstetric surgery", section on 'Outcome of surgery'.)
Use of venlafaxine during early pregnancy and risk of birth defects (June 2015)
Venlafaxine is often used as an alternative to selective serotonin reuptake inhibitors for treating antenatal depression, but the risk of birth defects with venlafaxine is not clear due to inconsistent findings across small observational studies. A study of national registries from multiple countries identified infants who were exposed to venlafaxine during the first trimester (n>2700) and infants who were not exposed (n>2,100,000); the analyses controlled for several potential confounding factors, such as maternal age, smoking, diabetes, and use of other medications (eg, antiepileptics) . The risk of major birth defects was comparable for the two groups, as was the specific risk for cardiac defects. However, this study did not address other perinatal risks, such as preterm birth or hypertension, which have been associated with venlafaxine in other studies. (See "Risks of antidepressants during pregnancy: Drugs other than selective serotonin reuptake inhibitors", section on 'Teratogenicity'.)
Expectant management of mild preeclampsia near term (June 2015)
The optimum time for delivery of women with preeclampsia without features of severe disease and stable maternal and fetal conditions at 34 to 36 weeks of gestation is uncertain. The recent randomized HYPITAT-II trial confirmed findings from observational studies showing that most patients with late-onset mild preeclampsia managed expectantly will reach term without progressing to severe disease or developing an adverse outcome . Newborns benefited from the extra time in utero: the rate of respiratory distress syndrome was 70 percent less with expectant management compared with immediate delivery. Mild preeclampsia with onset at 34 to 36 weeks can be managed expectantly to enable further fetal growth and maturation. Delivery is indicated at 37 weeks. (See "Preeclampsia: Management and prognosis", section on 'Preeclampsia without features of severe disease'.)
Gestational age apps (June 2015)
Electronic techniques, such as apps available for download to smart phones, are generally more accurate for determining gestational age than mechanical wheels. However, a high proportion of gestational age apps are also inaccurate . Clinicians and patients should be aware of this possibility when using a gestational age app, and clinicians should test the accuracy of the app they use. UpToDate provides calculators that determine the estimated date of delivery and current gestational age. (See "Prenatal assessment of gestational age and estimated date of delivery", section on 'Calculator'.)
Skin closure at cesarean delivery (June 2015)
The best method for skin closure at cesarean delivery is controversial. In a recent meta-analysis of staples versus subcuticular sutures for skin closure, stapled closure increased the rate of wound complications (infection and/or separation), while shortening operating time by only a few minutes . Cosmetic appearance, pain perception at discharge, and patient satisfaction were similar for both approaches. Although stapled closure took seven minutes less than sutured closure, the time involved to remove staples also needs to be considered. We suggest reapproximation of the skin with subcuticular sutures rather than staples. (See "Cesarean delivery: Technique", section on 'Skin'.)
Vitamin D supplementation during pregnancy (May 2015)
Several observational studies suggest an association between poor maternal vitamin D status and adverse pregnancy outcomes. A meta-analysis of 13 trials showed that, compared with a control group, vitamin D administration (in varied dosing, types, and schedules) resulted in higher serum 25(OH)D levels at delivery but no difference in the incidence rates of preeclampsia or gestational diabetes . There was also no difference in the incidence rates of small for gestational age, low birth weight, and preterm birth in the neonates. Although routine prenatal vitamin D supplementation does not appear to prevent low birthweight, preterm birth, or preeclampsia, the earliest interventions in the published trials were made in the late first trimester. Initiation of therapy with vitamin D prior to conception has not been evaluated. (See "Vitamin D and extraskeletal health", section on 'Pregnancy outcomes'.)
Endotracheal suctioning may not benefit nonvigorous neonates with meconium-stained amniotic fluid (May 2015)
Current guidelines recommend intubation and tracheal suctioning (endotracheal suctioning) of residual meconium for nonvigorous (depressed) infants (ie, absent or depressed respirations, decreased muscle tone, or heart rate less than 100 beats/minute) with meconium-stained amniotic fluid (MSAF), although supportive data are limited. In a recent randomized clinical trial of 122 nonvigorous term infants with MSAF in India, there was no additional benefit to endotracheal suctioning compared with no intubation and suctioning . Specifically, there were no differences between the two groups in the incidence of meconium aspiration syndrome (33 versus 31 percent), need for mechanical ventilation (23 versus 25 percent), survival at nine months of age (70 versus 72 percent), and mental and motor developmental status at nine months of age. Although these results suggest that endotracheal suctioning may not be needed in all infants with MSAF regardless of the level of activity, additional confirmatory evidence with larger clinical trials is needed before we recommend a change in practice for nonvigorous infants with MSAF. (See "Prevention and management of meconium aspiration syndrome", section on 'Neonatal care'.)
Effectiveness of pertussis vaccine in infants (May 2015)
Infants younger than 12 months have the highest incidence of pertussis and pertussis-related complications, including death. In a large case control study, having received ≥1 dose of pertussis vaccine was associated with a 72 percent reduction in the risk of death and a 31 percent reduction in the risk of hospitalization in infants ≥6 weeks of age (the minimum age for the first dose of pertussis vaccine) . However, 64 percent of the deaths occurred in infants younger than six weeks. These findings highlight the importance of timely pertussis immunization for infants, as well as maternal immunization during pregnancy and immunization of the infant's close contacts, as recommended by the Global Pertussis Initiative . (See "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age", section on 'Efficacy and effectiveness' and "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Bordetella pertussis infection in adolescents and adults: Treatment and prevention", section on 'Tdap booster'.)
Nicotine replacement therapy during pregnancy (May 2015)
Cigarette smoking during pregnancy is associated with adverse pregnancy outcomes. Nicotine replacement therapy has had limited use in pregnant women because of concerns regarding potential adverse fetal effects and limited evidence supporting efficacy. In a retrospective study of nearly 200,000 children born in the United Kingdom, the rates of major congenital anomalies were not statistically different among infants of women using nicotine replacement therapy, women who smoked, and women who did not use either . System-specific analysis reported an increased risk of respiratory anomalies in the nicotine replacement-exposed children, but the absolute risk was 3 per 1000 births, and based on 10 exposed cases out of 157 children with respiratory anomalies. Given the known benefits of smoking cessation during pregnancy, nicotine replacement therapy appears to be a reasonable treatment option for pregnant women who wish to stop smoking. (See "Cigarette smoking and pregnancy", section on 'Nicotine replacement'.)
Induction for imminent macrosomia (April 2015)
Previous studies have reported that induction of labor in pregnancies with suspected macrosomia (estimated fetal weight >4000 grams) has no advantages compared with expectant management. However, induction at a lower weight threshold may be advantageous. In a multicenter randomized trial that evaluated the consequences of induction of pregnancies with imminent macrosomia at 37 to 38 weeks and within three days of randomization, induction reduced the risk of the composite outcome of significant shoulder dystocia and associated morbidity compared with expectant management (2 versus 6 percent) . Imminent macrosomia was defined as estimated fetal weight >3700 grams at 37 weeks or greater than 3900 grams at 38 weeks. We believe these findings are insufficient to recommend induction of labor for imminent macrosomia at 37 and 38 weeks of gestation. For such a strategy to be acceptable, additional large trials would need to confirm a reduction in neonatal morbidity from shoulder dystocia and no increase in neonatal morbidity from iatrogenic prematurity. (See "Shoulder dystocia: Risk factors and planning delivery of at risk pregnancies", section on 'Pregnancies where high birth weight is suspected'.)
Iron supplementation in pregnancy (April 2015)
The total maternal iron requirement associated with pregnancy is about 1000 mg. For this reason, many clinicians prescribe a prenatal vitamin with iron for pregnant women. In a 2015 systematic review for the US Preventive Services Task Force, routine iron supplementation in pregnancy resulted in a 50 to 80 percent reduction in the frequency of iron deficiency anemia at term, but effects on other pregnancy outcomes were inconsistent . We suggest prenatal vitamins with iron for pregnant women for prevention of maternal iron deficiency anemia. (See "Nutrition in pregnancy", section on 'Iron'.)
False positive Down syndrome screening tests (April 2015)
Noninvasive prenatal Down syndrome screening using cell free DNA results in lower false positive and false negative rates than conventional aneuploidy screening tests. In a recent study of Down syndrome screening in an unselected population including almost 16,000 women, the false positive rates of cell free DNA and conventional screening were 0.1 and 5 percent, respectively, and false negative rates were 0 and 21 percent, respectively . False positive results can be due to factors such as maternal mosaicism, maternal tumors, maternal copy number variants, vanishing twins, confined placental mosaicism, or a failure of the complex bioinformatics necessary to generate a result [17-24]. Despite the low false positive rate with cell free DNA screening, confirmatory diagnostic testing (genetic amniocentesis or chorionic villus sampling) is mandatory after a screen positive result. (See "Noninvasive prenatal testing using cell-free nucleic acids in maternal blood", section on 'Trisomy 21, 18, 13'.)
Statins and pregnancy (April 2015)
The safety of statins in pregnancy is uncertain, but animal studies have raised concerns about fetal harm; human data are mixed. A cohort study of women enrolled in the US Medicaid program found that an association between statins and malformations was no longer present after a propensity analysis that controlled for potential confounders; pre-existing diabetes appeared to be the most important confounder . However, the wide confidence intervals in this study do not exclude a potential increase (or decrease) in risk with statin therapy. We continue to recommend that statins be discontinued prior to conception if possible. (See "Statins: Actions, side effects, and administration", section on 'Risks in pregnancy and breastfeeding'.)
Medication approved for low sexual desire in women (August 2015)
Flibanserin is the first and currently only drug approved by the US Food and Drug Administration (FDA) for female sexual dysfunction . Daily use results in modest increases in the frequency of sexually satisfying events and sexual desire. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and by safety concerns or lack of safety data regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, CYP3A4 inhibitors, antidepressants). (See "Sexual dysfunction in women: Management", section on 'Flibanserin'.)
Improving uptake of long-acting reversible contraceptives (July 2015)
Long-acting reversible contraceptives (LARC), which include implants and intrauterine devices, are the most effective reversible methods to prevent pregnancy. Interventions that increase LARC use lower the rate of unintended pregnancy. In a trial of 1500 women who were randomly assigned to receive either standardized counseling for LARC or routine contraceptive counseling, standardized counseling resulted in increased LARC use and a reduction in unintended pregnancies (8 versus 15 percent) . Introduction of affordable LARC methods in the state of Colorado from 2009 to 2013 was associated with an approximately 40 percent reduction in teen birth and abortion rates compared with previous years . These data add further support to our suggestion to use LARC for women who desire reversible contraception. (See "Overview of contraception", section on 'Effectiveness'.)
Repeat testing for women treated for trichomoniasis (July 2015)
The risk of repeat infection following treatment for a sexually transmitted infection (STI) is high. In the United States, reinfection with Trichomonas vaginalis has been reported to occur in up to 17 percent of women following treatment for an initial infection. The 2015 Centers for Disease Control and Prevention (CDC) guidelines on the management of STIs recommend that women treated for confirmed T. vaginalis infection undergo repeat testing within three months of treatment, regardless of partner treatment status . Prior guidelines had only listed retesting as a consideration. The preferred diagnostic test for repeat testing is a nucleic acid amplification test (NAAT) on a vaginal swab, which can be performed as soon as two weeks after treatment. Data are insufficient to support retesting men. (See "Trichomoniasis", section on 'Follow-up'.)
Bethesda 2014 guidelines published for cervical cytology specimens (July 2015)
The Bethesda 2014 guidelines (table 1) for the reporting of cervical cytology specimens include two changes from Bethesda 2001 [30-32]. Low-grade squamous intraepithelial lesion specimens that contain a few cells that are suspicious for but not diagnostic of high-grade squamous intraepithelial lesion are reported as ASC-H; previously there was no guidance on how to classify these specimens. Benign-appearing endometrial cells (BEC) are reported only in women ≥45 years. At the previous age threshold of ≥40 years, a finding of BEC was not found to be effective for predicting endometrial hyperplasia or carcinoma. (See "Cervical and vaginal cytology: Interpretation of results", section on 'Changes in the Bethesda 2014 guidelines'.)
Updated CDC guidelines on the management of sexually transmitted infections (June 2015)
The US Centers for Disease Control and Prevention (CDC) updated its guidelines on the management of sexually transmitted infections in June 2015 . Major revisions include a lower threshold for the diagnosis of urethritis based on microscopy of a urethral specimen, a new emphasis on the role of Mycoplasma genitalium in persistent urethritis and cervicitis, preference for nucleic acid amplification-based testing for the diagnosis of Trichomonas vaginalis, and a recommendation to retest women after treatment for T. vaginalis to evaluate for reinfection. New screening recommendations include annual hepatitis C virus (HCV) testing for HIV-infected men who have sex with men and T. vaginalis testing for HIV-infected women annually and when pregnant. (See "Urethritis in adult men", section on 'Diagnostic criteria' and "Mycoplasma genitalium infection in men and women", section on 'Nongonococcal urethritis' and "Trichomoniasis", section on 'Follow-up' and "Primary care of the HIV-infected adult", section on 'Sexually transmitted infections'.)
Menopausal hormone therapy and cardiovascular risk: Timing of exposure (June 2015)
Current evidence suggests that the use of menopausal hormone therapy (MHT) in the early menopausal years (<10 years from menopause) may not be associated with excess cardiovascular risk when compared with use in the later menopausal years. This has been referred to as the "timing hypothesis." Additional support for this hypothesis comes from a 2015 meta-analysis of 19 trials of oral (including the Womens Health Initiative), but not transdermal, MHT in over 40,000 postmenopausal women . A subgroup analysis in women who started MHT less than 10 years after menopause showed a lower risk of coronary heart disease (CHD) compared with placebo (RR 0.52; 8 fewer cases of heart disease per 1000 women treated/year) and a lower mortality rate (RR 0.70; 6 fewer deaths per 1000 women treated/year). However, there were important limitations in this analysis; when one methodologically flawed trial was removed, the beneficial effects on CHD and mortality were no longer significant (but no adverse effects were seen). These data provide additional evidence that oral MHT use in younger postmenopausal women is not associated with excess CHD risk. (See "Menopausal hormone therapy: Benefits and risks", section on 'Younger postmenopausal women'.)
Benefit of long-term management on risk for vulvar carcinoma in women with vulvar lichen sclerosus (June 2015)
Vulvar lichen sclerosus is a chronic disease associated with an increased risk for vulvar carcinoma. The findings of a prospective cohort study of 507 women with vulvar lichen sclerosus suggest that topical corticosteroid therapy, used both to achieve disease control and for long-term maintenance treatment, may reduce cancer risk . Women who reported consistent adherence to treatment instructions had a lower incidence of vulvar carcinoma or vulvar intraepithelial neoplasia than women who reported less consistent adherence (0 versus 4.7 percent). In addition, patients who adhered to treatment had better symptom control and reduced risk for vulvar scarring. These findings suggest that consistent treatment rather than an "as needed" approach to the long-term management of vulvar lichen sclerosus may improve patient outcomes. (See "Vulvar lichen sclerosus", section on 'Topical corticosteroids'.)
Reduced HPV vaccination rate among women who have sex with women (May 2015)
Prior research has suggested that women who have sex with women (WSW) may be less likely to initiate human papillomavirus (HPV) vaccination than their age-matched heterosexual peers. One possible reason for this discrepancy is that both WSW and their healthcare providers may erroneously believe that WSW are not at risk for HPV infection or cervical cancer. In one study of over 12,000 United States women from 2006 to 2010, of women who were aware of the HPV vaccine, only 8 percent of lesbian women had initiated vaccination compared with 28 percent of heterosexual women and 32 percent of bisexual women . This study highlights the need for healthcare providers to discuss HPV vaccination with all patients. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend vaccination for females and males ages 11 or 12 years of age, up to age 26. (See "Medical care of women who have sex with women", section on 'Prevention of sexually transmitted diseases'.)
Safety concerns regarding hysteroscopic sterilization (July 2015)
Safety concerns have been raised about female sterilization via hysteroscopic placement of micro-inserts into the fallopian tubes. A prospective study of this procedure reported that, at five years, up to 38 percent of women reported recurrent menstrual irregularities and up to 5 percent reported recurrent pelvic pain . Between 2002 and 2015, the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database received 5093 adverse effects reports related to this device, including over 4700 related to menstrual abnormalities or pelvic pain . In September 2015, the FDA will convene a meeting of the Obstetrics and Gynecology Devices Panel to review the safety and effectiveness of hysteroscopic sterilization. (See "Hysteroscopic sterilization", section on 'FDA panel'.)
Pretreatment with misoprostol in women undergoing hysteroscopy (June 2015)
Adequate cervical dilation is an important step in hysteroscopy, as nearly 50 percent of hysteroscopic complications are associated with difficult passage of the hysteroscope through the cervical canal. Preoperative dilation with cervical ripening agents is generally preferred to mechanical dilation at the time of the procedure, which is associated with pain, uterine perforation, and false track creation. In a 2015 systematic review and meta-analysis of 19 trials, pre- and postmenopausal women treated with preoperative misoprostol were much less likely to require additional mechanical dilation and had fewer complications than women treated with placebo or no intervention prior to hysteroscopy . These data support our suggestion to use preoperative misoprostol in women undergoing hysteroscopy. (See "Overview of hysteroscopy", section on 'Cervical preparation and dilation'.)
Hormonal risk factors for endometrial cancer in women with Lynch syndrome (July 2015)
For women with Lynch syndrome, hormonal risk factors for the development of endometrial cancer appear to be the same as those in the general population. A multicenter international retrospective cohort study of a registry of 1128 women with a mismatch repair gene mutation included 133 women who developed endometrial cancer . Later age at menarche (≥13 years), higher parity (≥1 live birth), and longer use of hormonal contraceptives (≥1 year) were associated with a decrease in the risk of endometrial cancer. The biologic behavior of endometrial cancer in Lynch syndrome in terms of hormonal risk factors appears similar to sporadic cases. (See "Endometrial and ovarian cancer screening and prevention in women with Lynch syndrome (hereditary nonpolyposis colorectal cancer)", section on 'Endometrial cancer'.)
Frozen donor oocyte use impacts live birth rate (August 2015)
Use of donor oocytes (eggs) in assisted reproductive technology has allowed women unable to conceive with their own eggs the opportunity to achieve pregnancy. The use of frozen oocytes is more convenient and less costly compared with fresh oocytes because the donor and recipient don't have to be hormonally synchronized and frozen eggs can be shipped anywhere. Although initial studies reported equivalent pregnancy and live birth rates for donor egg transfers, a study of over 11,000 oocyte donation cycles, including 20 percent using frozen eggs, reported the live birth rate per transfer for frozen donor oocytes was lower than the live birth rate for fresh donor oocytes (47 versus 56 percent) . Despite the possible discrepancy in live birth rate, the improved efficiency and lower cost of cryopreserved donor oocytes makes their use a reasonable and attractive option. (See "Management of infertility and pregnancy in women of advanced age", section on 'Oocyte or embryo donation'.)
Empiric progesterone supplementation of no benefit in recurrent pregnancy loss (April 2015)
Recurrent pregnancy loss is an extremely stressful experience for families and clinicians. One proposed mechanism of recurrent pregnancy loss is luteal phase deficiency, or inadequate progesterone production by the corpus luteum. A 2015 Committee Opinion by the American Society of Reproductive Medicine concluded that there is no evidence that empiric treatment of luteal phase deficiency with progesterone supplementation is beneficial to women with recurrent pregnancy loss in natural, unstimulated cycles (ie, no use of fertility therapy) . When abnormal luteal function is the result of an identified medical condition, such as elevated prolactin, the underlying medical problem should be addressed. (See "Management of couples with recurrent pregnancy loss", section on 'Progesterone'.)
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