General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial.

BACKGROUND: In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. METHODS: A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. RESULTS: Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). CONCLUSIONS: General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis.

BACKGROUND: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective. OBJECTIVE: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc). SEARCH STRATEGY: We searched literature databases, trial registries and references in published articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies. DATA COLLECTION AND ANALYSIS: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation. MAIN RESULTS: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes. CONCLUSION: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration. TWEETABLE ABSTRACT: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Pregnancy and active Huntington disease: a rare combination.

We describe the complicated course of a rare pregnant woman with symptomatic Huntington disease (HD) and discuss multidisciplinary care issues that may be encountered. A 31-year-old gravida 2, para 1 with advanced HD was admitted at 30 weeks gestation for preterm labor. Her course was complicated by progressive cognitive and physical impairment, dysphagia, malnutrition, diabetes insipidus, aspiration pneumonia, chorioamnionitis, preterm delivery and pyelonephritis. Pregnant women with symptomatic HD may present multiple challenges requiring extensive multidisciplinary input.

Factors associated with the awareness and practice of evidence-based obstetric care in an African setting.

OBJECTIVE: To identify the factors associated with important (> or =50%) variation in awareness and practice of evidence-based obstetric interventions in an African setting where we have previously reported poor awareness and use of evidence-based reproductive interventions. DESIGN: Cross-sectional analysis of data from our Reproductive Health Interventions Study. SETTING: North-west province, Cameroon, Africa. POPULATION: Health workers including obstetricians, other physicians, midwives, nurses and other staff providing reproductive care. MAIN OUTCOME MEASURES: Prevalence ratios (PR) of uniform awareness and practice of four key evidence-based obstetric interventions from the World Health Organization Reproductive Health Library (WHO RHL): antiretrovirals to prevent mother-to-child transmission of HIV/AIDS, antenatal corticosteroids for prematurity, uterotonics to prevent postpartum haemorrhage and magnesium sulphate for seizure prophylaxis. METHODS: Comparisons of descriptive covariates, applying logistic regression to estimate independent relationships with awareness and use of evidence-based interventions. RESULTS: A total of 15.5% (50/322) of health workers were aware of all the four interventions while only 3.8% (12/312) reported optimal practice. Evidence-based awareness was strongly associated with practice (PR = 15.4; 96% CI: 4.3-55.0). Factors significantly associated with awareness were: attending continuing education, access to the WHO RHL, employment as an obstetrician/gynaecologist and working in autonomous military or National Insurance Fund facilities. Controlling for potential confounding, working as an obstetrician was associated with increased awareness (adjusted prevalence odds ratio [aPOR] = 8.3; 95% CI: 1.3-53.8) as was median work experience of 5-15 years (aPOR = 2.0; 95% CI: 1.0-3.8). Internet access was associated with increased practice (aPOR = 3.4; 95% CI: 1.0-11.8). Other potentially important variations were observed, although they did not attain statistical significance. CONCLUSIONS: Several factors including obstetric training and continuous education positively influence evidence-based awareness and practice of key obstetric interventions. Confirmation and application of this information may enhance the effectiveness of programmes to improve maternal and perinatal outcomes.

Rates of twinning before and after fortification of foods in the US with folic acid, Texas, 1996 to 1998.

Several investigators have reported a 40% increase in the prevalence of twinning among women who have taken folic acid or multivitamins containing folic acid at the time of conception. Given that infant morbidity and mortality are greatly increased among twins, such a large increase in twinning could have serious implications. We undertook this study to determine if US fortification of enriched cereal-grain products with folic acid was associated with an unexpected increase in the prevalence of twinning in the state of Texas. We examined 1 003 207 deliveries conceived in Texas, between 1 January 1996 and 31 December 1998. We compared the prevalence of twin deliveries conceived before, during and after fortification with folic acid, mandated to begin on 1 January 1998. Comparing pregnancies conceived in 1997 with those conceived in 1996, we observed a 2.4% yearly increase in twinning, 1.024 [0.98, 1.07]. Comparing pregnancies conceived in 1998 with those conceived in 1997, we observed a 4.6% yearly increase in twinning, 1.046 [1.00, 1.09]. These increases were adjusted for maternal age, race, education, parity and season of conception. The size and pattern of these increases are consistent with the ongoing increase in twinning of 1-4% per year which began in the US prior to fortification.

Seasonality in conception of births and influence on late initiation of prenatal care.

OBJECTIVE: To determine whether there is a summer peak in conception of births to adolescents (up to 17 years) compared with older teenagers (18-19 years) and adults (20-29 years), and to assess the influence of season of conception on late initiation of prenatal care. METHODS: We analyzed 1,178,607 singleton births to women aged 29 years and younger in Texas between 1994 and 1998. Dates of conception were estimated using last menstrual period and clinical estimates of gestation. Proportions of births conceived per month were assessed for seasonal patterns. Proportions of births with late initiation of prenatal care were also compared by month of conception. The outcomes were further stratified by sociodemographic variables. RESULTS: There was a consistent summer trough (7.5% in August) and year-end peak (9.1% in December) in conception of births to adolescents (P <.001), a pattern similar to that of older teenagers and adults. Among the adolescents, students and non-Hispanic women giving birth presented a secondary early summer peak (8.8% each in May and June) in their conceptions. There was a modest bimodal effect of season of conception on initiation of prenatal care in all age groups. Adolescent conceptions in April-May and September-October were 14-18% and 6% significantly more likely to have late prenatal care compared with other months, respectively. CONCLUSION: Adolescents giving birth in Texas were not more likely to conceive in the summer. They did present seasonal patterns of conception and late initiation of prenatal care similar to older women.