Serious maternal complications after early preterm delivery (24-33 weeks’ gestation)

To describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route and type of cesarean incision

Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals

We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection

The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth

Background Infants born <37 weeks’ gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. Objective We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. Study Design In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesterone receptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. Results The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P =.68,.44,.08, and.44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P =.29,.10,.76,.09, and.43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61–0.99; P =.04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P =.13,.08,.10,.08, and.13, respectively). Conclusion The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients

Bladder Function After Fetal Surgery for Myelomeningocele

BACKGROUND: A substudy of the Management of Myelomeningocele Study evaluating urological outcomes was conducted. METHODS: Pregnant women diagnosed with fetal myelomeningocele were randomly assigned to either prenatal or standard postnatal surgical repair. The substudy included patients randomly assigned after April 18, 2005. The primary outcome was defined in their children as death or the need for clean intermittent catheterization (CIC) by 30 months of age characterized by prespecified criteria. Secondary outcomes included bladder and kidney abnormalities observed by urodynamics and renal/bladder ultrasound at 12 and 30 months, which were analyzed as repeated measures. RESULTS: Of the 115 women enrolled in the substudy, the primary outcome occurred in 52% of children in the prenatal surgery group and 66% in the postnatal surgery group (relative risk [RR]: 0.78; 95% confidence interval [CI]: 0.57–1.07). Actual rates of CIC use were 38% and 51% in the prenatal and postnatal surgery groups, respectively (RR: 0.74; 95% CI: 0.48–1.12). Prenatal surgery resulted in less trabeculation (RR: 0.39; 95% CI: 0.19–0.79) and fewer cases of open bladder neck on urodynamics (RR: 0.61; 95% CI: 0.40–0.92) after adjustment by child’s gender and lesion level. The difference in trabeculation was confirmed by ultrasound. CONCLUSIONS: Prenatal surgery did not significantly reduce the need for CIC by 30 months of age but was associated with less bladder trabeculation and open bladder neck. The implications of these findings are unclear now, but support the need for long-term urologic follow-up of patients with myelomeningocele regardless of type of surgical repair

What we have learned about best practices for recruitment and retention in multicenter pregnancy studies.

For thirty years, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network has had significant impact on clinical practice in obstetrics. The MFMU Network has conducted 50 randomized clinical trials and observational studies designed to improve pregnancy outcomes for mothers and children. Each center has a designated clinical research nurse coordinator who coordinates the day-to-day operations of each trial and leads a research team that is responsible for recruitment, and retention, of participants. Some of the lessons learned by the nurse coordinators over the past 30 years are described with examples from recent studies. Best practices that we have amassed from our experience are also described

Bladder Function After Fetal Surgery for Myelomeningocele

BackgroundA substudy of the Management of Myelomeningocele Study evaluating urological outcomes was conducted.MethodsPregnant women diagnosed with fetal myelomeningocele were randomly assigned to either prenatal or standard postnatal surgical repair. The substudy included patients randomly assigned after April 18, 2005. The primary outcome was defined in their children as death or the need for clean intermittent catheterization (CIC) by 30 months of age characterized by prespecified criteria. Secondary outcomes included bladder and kidney abnormalities observed by urodynamics and renal/bladder ultrasound at 12 and 30 months, which were analyzed as repeated measures.ResultsOf the 115 women enrolled in the substudy, the primary outcome occurred in 52% of children in the prenatal surgery group and 66% in the postnatal surgery group (relative risk [RR]: 0.78; 95% confidence interval [CI]: 0.57-1.07). Actual rates of CIC use were 38% and 51% in the prenatal and postnatal surgery groups, respectively (RR: 0.74; 95% CI: 0.48-1.12). Prenatal surgery resulted in less trabeculation (RR: 0.39; 95% CI: 0.19-0.79) and fewer cases of open bladder neck on urodynamics (RR: 0.61; 95% CI: 0.40-0.92) after adjustment by child's gender and lesion level. The difference in trabeculation was confirmed by ultrasound.ConclusionsPrenatal surgery did not significantly reduce the need for CIC by 30 months of age but was associated with less bladder trabeculation and open bladder neck. The implications of these findings are unclear now, but support the need for long-term urologic follow-up of patients with myelomeningocele regardless of type of surgical repair

Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU Network hospitals

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