Family History of Venous Thromboembolism and Identifying Factor V Leiden Carriers During Pregnancy

To estimate whether there is a correlation between family history of venous thromboembolism and factor V Leiden mutation carriage in gravid women without personal history of venous thromboembolism

Risk-adjusted models for adverse obstetric outcomes and variation in risk-adjusted outcomes across hospitals

Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes

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

Perioperative Antibiotic Prophylaxis for Nonlaboring Cesarean Delivery

OBJECTIVE: To estimate the efficacy of antibiotic prophylaxis at time of non-laboring cesarean delivery in reducing postpartum infection-related complications. METHODS: We performed a secondary analysis of an observational study of cesarean deliveries performed at 13 centers from 1999-2000. Patients were included if they had a cesarean delivery prior to labor, did not have an antepartum or intrapartum infection, and were not given antibiotics at delivery for reasons other than prophylaxis. The occurrence of postpartum endometritis, wound infection, and other less common infection-related complications was compared between those who did and did not receive antibiotic prophylaxis. Results were adjusted for smoking, payor status, gestational age and body mass index (BMI) at delivery, race, diabetes, antepartum infections, presence of anemia, operative time, type of cesarean delivery (primary or repeat), and center. RESULTS: Of the 9,432 women who met study criteria, the 6,006 (64%) who received antibiotic prophylaxis were younger, heavier at delivery, and were more likely to be African American, receive public insurance, and have diabetes. Patients who received antibiotic prophylaxis were less likely to develop postpartum endometritis [121 (2.0%) vs 88 (2.6%); adjusted odds ratio [OR] 0.40; 95% confidence interval [CI] 0.28-0.59] or wound infection [31 (0.52%) vs 33 (0.96%); adjusted OR 0.49; 95% CI 0.28-0.86]. CONCLUSION: Antibiotic prophylaxis at the time of non-laboring cesarean delivery significantly reduces the risks of postpartum endometritis and wound infection

Antiphospholipid antibodies and pregnancy outcomes in women heterozygous for Factor V Leiden

Antiphospholipid antibodies are associated with a spectrum of pregnancy complications, including preeclampsia and small for gestational age (SGA) fetuses. We sought to assess anticardiolipin and anti-β2-glycoprotein I (anti-β2-GPI) IgG and IgM antibody prevalence and the relationship of these antibodies to pregnancy complications in women with the Factor V Leiden (FVL) mutation. The study comprised a secondary analysis of a multicenter, prospective observational study of FVL prevalence among 5188 asymptomatic pregnant women. A subset of 362 women (117 FVL heterozygotes, 245 matched controls) had serum collected at the time of the original study and underwent serum analysis for anticardiolipin and anti-β2-GPI IgG and IgM as a part of this analysis. The primary outcome was preeclampsia and/or SGA (<10%). The overall prevalence of anticardiolipin and anti-β2-GPI IgG and IgM antibodies was low and did not vary with FVL status. Forty-seven women (13.0%) developed preeclampsia and/or SGA. There were no differences in primary outcome rates between women with and without aPL antibodies, regardless of FVL mutation status. Among FVL carriers, the presence of antiphospholipid antibodies does not appear to contribute to adverse pregnancy outcome

Length of latency with preterm premature rupture of membranes before 32 weeks\u27 gestation

OBJECTIVE: To describe latency for patients with preterm premature membrane rupture (PPROM) between 24 0/7 and 31 6/7 weeks’ gestation. STUDY DESIGN: Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than 6 contractions per hour at enrollment who were candidates for expectant management (n=1377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. RESULTS: At each week of gestation, median latency between 24-28 weeks was similar at approximately 9 days, but was significantly shorter with PPROM at 29, 30, and 31 weeks (p<0.001). In addition, the percentage of patients remaining undelivered at 7 days and 14 days was similar for PPROM between 24-28 weeks, but decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to exponential pattern. CONCLUSION: Median latency after PPROM is similar from 24-28 weeks’ gestation, but shortens with PPROM at and after 29 weeks

The impact of tobacco use on preterm premature rupture of the membranes

OBJECTIVE: To determine if tobacco use increases the incidence of preterm premature rupture of the membranes (pPROM) or alters perinatal outcomes after pPROM. STUDY DESIGN: This is a secondary analysis of the databases of three completed Eunice Kennedy Shriver National Institute of Child Health and Human Development–supported Maternal Fetal Medicine Units Network studies. Self-reported tobacco exposure data was obtained. Its relationship with the incidence of pPROM and associated neonatal outcome measures were assessed. RESULTS: There was no difference in the incidence of pPROM when comparing non-smokers to those using tobacco. Although a trend was seen between the incidence of pPROM and the amount smoked, this did not reach statistical significance. Among the patients with pPROM, the use of tobacco was not associated with an increase in perinatal morbidity. CONCLUSION: Our data do not support a significant relationship between tobacco use and pPROM

Advanced lipoprotein measures and recurrent preterm birth

Lipoproteins are associated with atherogenic and inflammatory processes, and these processes may be related to adverse pregnancy outcomes. We therefore examined whether variations in lipoprotein particle size and concentration are associated with preterm birth (PTB) < 35 weeks’ gestation

Effect of magnesium sulfate administration for neuroprotection on latency in women with preterm premature rupture of membranes

This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks' gestation. This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups. Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency