Obstetrical and neonatal outcomes of cardio-facio-cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation.

We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio-facio-cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records. We identified 43 individuals with pathogenic variants in BRAF (81%), MEK1 (14%), or MEK2 (5%) genes. The median age was 8.5 years. Hyperemesis gravidarum, gestational diabetes, gestational hypertension, and preeclampsia occurred in 5/43 (12%), 4/43 (9%), 3/43 (7%), and 3/43 (7%) of pregnancies, respectively. Second and third trimester ultrasound abnormalities included polyhydramnios, macrocephaly, macrosomia, and renal and cardiac abnormalities. Delivery occurred via spontaneous vaginal, operative vaginal, or cesarean delivery in 15/42 (36%), 7/42 (16%), and 20/42 (48%), respectively. Median gestational age at delivery was 37 weeks and median birth weight was 3501 grams. Germline pathogenic vaiants had mutiple congenital consequences including polyhydramnios, renal and cardiac abnormalities, macrosomia, and macrocephaly on second and third trimester ultrasound. Elevated rates of operative delivery and neonatal complications were also noted. Understanding and defining a prenatal phenotype may improve prenatal prognostic counseling and outcomes.

Length of rupture of membranes in the setting of premature rupture of membranes at term and infectious maternal morbidity.

OBJECTIVE: This study was undertaken to define the time thresholds of increased risk for infectious maternal morbidities with relationship to length of ruptured membranes at term. STUDY DESIGN: We designed a retrospective cohort study of all women with premature rupture of membranes beyond 37 weeks' gestation at a single institution. Dichotomized time thresholds of length of ruptured membranes before delivery were examined in 2-hour increments using bivariate and multivariable analyses to assess the rates of chorioamnionitis and endomyometritis. RESULTS: Among the 3841 women meeting inclusion criteria, increased rates of chorioamnionitis and endomyometritis were noted at time thresholds of 12 hours (adjusted odds ratio 2.3 [95% confidence interval, 1.2-4.4]) and 16 hours (adjusted odds ratio 2.5 [95% confidence interval, 1.1-5.6]), respectively. CONCLUSION: We found that when length of time of ruptured membranes before delivery is examined via dichotomized time thresholds, the risks of chorioamnionitis and endomyometritis are significantly increased at 12 hours and 16 hours, respectively. These time thresholds derived from dichotomized time analyses should be considered during risk-based counseling and labor management in the setting of term premature rupture of membranes.

Perinatal outcomes among different Asian-American subgroups.

OBJECTIVE: The objective of the study was to investigate the differences in perinatal outcomes between various Asian ethnic subgroups at a national level. STUDY DESIGN: This is a retrospective cohort study of all non-Hispanic Chinese, Japanese, Filipino, Asian Indian, Korean, Vietnamese, Samoan, Guamanian, and Hawaiian women whose deliveries were recorded by US birth certificates within the year 2003. Perinatal outcomes were compared between groups and potential confounders controlled for with multivariable logistic regression. RESULTS: We found significant differences (P < .001) in the incidence of all perinatal outcomes of interest among the different Asian subgroups. These differences persisted after adjusting for potential confounders. The incidence of diabetes in pregnancy varied from 2.9% (Korean) to 5.7% (Filipina). CONCLUSION: Our study demonstrates significant differences in preterm labor, primary cesarean delivery, pregnancy-associated hypertension, eclampsia, diabetes in pregnancy, low birthweight, macrosomia, and cephalopelvic disproportion among Asian subgroups at a national level, affirming the importance of examining these subgroups separately.

Velamentous cord insertion: is it associated with adverse perinatal outcomes?

INTRODUCTION: Velamentous cord insertion (VCI) can be identified on prenatal ultrasound with an incidence of around 1%. We set out to examine the association between VCI and perinatal outcomes. METHODS: This was a retrospective cohort study of 482,812 pregnancies using the California vital statistics birth cohort dataset linked with patient discharge dataset from 2006 during which 2327 (0.48%) were complicated by VCI. Outcomes examined included intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, manual removal of the placenta and cesarean delivery. Statistical analysis was performed using Chi squared tests and multivariable logistic regression analyses. RESULTS: Pregnancies with VCI, compared to those without, were associated with an increased risk of IUFD (2.6% versus 0.28%, p = 0.001), SGA (16.93% versus 10.17%, p = 0.001), preterm delivery <37 weeks (12.5% versus 9.10%, p = 0.001), manual removal of placenta (14.47% versus 0.76%, p = 0.01) and postpartum hemorrhage (6.66% versus 2.88%, p = 0.001). Adjusting for confounders, the adjusted odds of IUFD were more than nine times in pregnancies with VCI (aOR 9.56; 95% CI 6.76-13.5) than those without. DISCUSSION: VCI is associated with an increased risk of adverse perinatal outcomes such as IUFD, SGA, preterm delivery <37 weeks, need for manual removal of placenta and post-partum hemorrhage. Routine identification of the placental cord insertion site should be considered. Close surveillance of these pregnancies should be undertaken. Future research should focus on the optimal management including the gestational age for delivery of these pregnancies.

The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia.

OBJECTIVE: While antenatal corticosteroids reduce the risk of neonatal morbidity and mortality, perhaps the maternal hyperglycemia they produce has other neonatal effects. Thus, we sought to examine the association between antenatal betamethasone exposure and neonatal hypoglycemia and hyperbilirubinemia. METHODS: We designed a retrospective cohort study of all preterm deliveries from 32 to 37 weeks of gestation at a single university hospital from 1990 to 2007. Data were collected on antenatal betamethasone administration and the neonatal outcomes. Univariable, multivariable and stratified analyses were conducted. RESULTS: Of 6675 preterm deliveries, significantly higher rates of neonatal hypoglycemia (5.7% versus 4.2%, p<0.05) and hyperbilirubinemia (45.9% versus 24.1%, p<0.05) were observed in neonates exposed to antenatal betamethasone. Controlling for potential confounders including gestational age, these findings persisted with betamethasone-exposed neonates 1.6 times more likely to have hypoglycemia (aOR 1.60, 95% CI 1.24-2.07) and 3.2 times more likely to have hyperbilirubinemia (aOR 3.23, 95% CI 2.92-3.58). CONCLUSIONS: Antenatal betamethasone was associated with neonatal hypoglycemia and hyperbilirubinemia. Further work to determine whether this association is related to maternal hyperglycemia should be conducted, given this could be addressed with strict maternal glycemic control during betamethasone administration.

Characteristics of women who undergo second-trimester abortion in the setting of a fetal anomaly.

BACKGROUND: Most women diagnosed with a fetal anomaly terminate the pregnancy. Little is known about utilization of two procedures: dilation and evacuation (D&E) and induction termination. STUDY DESIGN: This retrospective cohort study included all women seen at the University of California, San Francisco (UCSF) Prenatal Diagnosis Center (PDC) who underwent a second-trimester abortion for an anomalous pregnancy from 2005 to 2008. We abstracted variables from the PDC database and medical charts to identify predictors associated with undergoing D&E. RESULTS: Three quarters of the 192 women underwent D&E (n=148). Higher maternal age, proximity to UCSF, earlier gestational age, singleton gestation and genetic anomaly were associated with undergoing D&E. In adjusted analysis, earlier gestational age and singleton gestation were associated with undergoing D&E. CONCLUSIONS: The D&E procedure was more commonly utilized for terminating an anomalous pregnancy at UCSF than medical induction. Further inquiry is needed to explore how provider counseling influences the choice of D&E vs. induction.

Maternal and neonatal outcomes of elective induction of labor.

BACKGROUND: Induction of labor is on the rise in the U.S., increasing from 9.5 percent in 1990 to 22.1 percent in 2004. Although, it is not entirely clear what proportion of these inductions are elective (i.e. without a medical indication), the overall rate of induction of labor is rising faster than the rate of pregnancy complications that would lead to a medically indicated induction. However, the maternal and neonatal effects of induction of labor are unclear. Many studies compare women with induction of labor to those in spontaneous labor. This is problematic, because at any point in the management of the woman with a term gestation, the clinician has the choice between induction of labor and expectant management, not spontaneous labor. Expectant management of the pregnancy involves nonintervention at any particular point in time and allowing the pregnancy to progress to a future gestational age. Thus, women undergoing expectant management may go into spontaneous labor or may require indicated induction of labor at a future gestational age. OBJECTIVES: The Stanford-UCSF Evidence-Based Practice Center examined the evidence regarding four Key Questions: What evidence describes the maternal risks of elective induction versus expectant management? What evidence describes the fetal/neonatal risks of elective induction versus expectant management? What is the evidence that certain physical conditions/patient characteristics are predictive of a successful induction of labor? How is a failed induction defined? METHODS: We performed a systematic review to answer the Key Questions. We searched MEDLINE(1966-2007) and bibliographies of prior systematic reviews and the included studies for English language studies of maternal and fetal outcomes after elective induction of labor. We evaluated the quality of included studies. When possible, we synthesized study data using random effects models. We also evaluated the potential clinical outcomes and cost-effectiveness of elective induction of labor versus expectant management of pregnancy labor at 41, 40, and 39 weeks' gestation using decision-analytic models. RESULTS: Our searches identified 3,722 potentially relevant articles, of which 76 articles met inclusion criteria. Nine RCTs compared expectant management with elective induction of labor. We found that overall, expectant management of pregnancy was associated with an approximately 22 percent higher odds of cesarean delivery than elective induction of labor (OR 1.22, 95 percent CI 1.07-1.39; absolute risk difference 1.9, 95 percent CI: 0.2-3.7 percent). The majority of these studies were in women at or beyond 41 weeks of gestation (OR 1.21, 95 percent CI 1.01-1.46). In studies of women at or beyond 41 weeks of gestation, the evidence was rated as moderate because of the size and number of studies and consistency of the findings. Among women less than 41 weeks of gestation, there were three trials which reported no difference in risk of cesarean delivery among women who were induced as compared to expectant management (OR 1.73; 95 percent CI: 0.67-4.5, P=0.26), but all of these trials were small, non-U.S., older, and of poor quality. When we stratified the analysis by country, we found that the odds of cesarean delivery were higher in women who were expectantly managed compared to elective induction of labor in studies conducted outside the U.S. (OR 1.22; 95 percent CI 1.05-1.40) but were not statistically different in studies conducted in the U.S. (OR 1.28; 95 percent CI 0.65-2.49). Women who were expectantly managed were also more likely to have meconium-stained amniotic fluid than those who were electively induced (OR 2.04; 95 percent CI: 1.34-3.09). Observational studies reported a consistently lower risk of cesarean delivery among women who underwent spontaneous labor (6 percent) compared with women who had an elective induction of labor (8 percent) with a statistically significant decrease when combined (OR 0.63; 95 percent CI: 0.49-0.79), but again utilized the wrong control group and did not appropriately adjust for gestational age. We found moderate to high quality evidence that increased parity, a more favorable cervical status as assessed by a higher Bishop score, and decreased gestational age were associated with successful labor induction (58 percent of the included studies defined success as achieving a vaginal delivery anytime after the onset of the induction of labor; in these instances, induction was considered a failure when it led to a cesarean delivery). In the decision analytic model, we utilized a baseline assumption of no difference in cesarean delivery between the two arms as there was no statistically significant difference in the U.S. studies or in women prior to 41 0/7 weeks of gestation. In each of the models, women who were electively induced had better overall outcomes among both mothers and neonates as estimated by total quality-adjusted life years (QALYs) as well as by reduction in specific perinatal outcomes such as shoulder dystocia, meconium aspiration syndrome, and preeclampsia. Additionally, induction of labor was cost-effective at $10,789 per QALY with elective induction of labor at 41 weeks of gestation, $9,932 per QALY at 40 weeks of gestation, and $20,222 per QALY at 39 weeks of gestation utilizing a cost-effectiveness threshold of $50,000 per QALY. At 41 weeks of gestation, these results were generally robust to variations in the assumed ranges in univariate and multi-way sensitivity analyses. However, the findings of cost-effectiveness at 40 and 39 weeks of gestation were not robust to the ranges of the assumptions. In addition, the strength of evidence for some model inputs was low, therefore our analyses are exploratory rather than definitive. CONCLUSIONS: Randomized controlled trials suggest that elective induction of labor at 41 weeks of gestation and beyond may be associated with a decrease in both the risk of cesarean delivery and of meconium-stained amniotic fluid. The evidence regarding elective induction of labor prior to 41 weeks of gestation is insufficient to draw any conclusion. There is a paucity of information from prospective RCTs examining other maternal or neonatal outcomes in the setting of elective induction of labor. Observational studies found higher rates of cesarean delivery with elective induction of labor, but compared women undergoing induction of labor to women in spontaneous labor and were subject to potential confounding bias, particularly from gestational age. Such studies do not inform the question of how elective induction of labor affects maternal or neonatal outcomes. Elective induction of labor at 41 weeks of gestation and potentially earlier also appears to be a cost-effective intervention, but because of the need for further data to populate these models our analyses are not definitive. Despite the evidence from the prospective, RCTs reported above, there are concerns about the translation of such findings into actual practice, thus, there is a great need for studying the translation of such research into settings where the majority of obstetric care is provided.

Meconium-stained amniotic fluid is associated with puerperal infections.

OBJECTIVE: The purpose of this study was to determine whether meconium-stained amniotic fluid is associated with puerperal infection and whether the quality of the meconium is further associated with this risk. STUDY DESIGN: We designed a retrospective cohort study of all deliveries beyond 37 weeks gestational age from 1992 to 2002 at a single community hospital. Data were collected on rates of chorioamnionitis, endomyometritis, quality of amniotic fluid, and length of labor and analyzed with bivariate and multivariate analyses. RESULTS: We found that, among the 43,200 women who were delivered at term, 18.9% of the women had meconium staining (8.8% thin, 5.5% moderate, 4.6% thick). Compared with deliveries with clear amniotic fluid, those with meconium-stained amniotic fluid had higher rates of chorioamnionitis (2.3% vs 4.1%, P<.001) and endomyometritis (1.0% vs 1.7%, P<.001). Further, the severity of meconium staining was associated with increased rates of infection. CONCLUSION: We found that the presence and severity of meconium-stained amniotic fluid is associated with puerperal infection even when being controlled for confounders.