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

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.

Ultrasound prediction of birthweight and growth restriction in fetal gastroschisis.

OBJECTIVE: Most ultrasound estimated fetal weight (EFW) formulas incorporate abdominal circumference, which may overstimate growth restriction in fetal gastroschisis. The aim of this study was to determine the optimal ultrasound formula for prediction of birthweight and fetal growth restriction (FGR) in gastroschisis. STUDY DESIGN: We conducted a retrospective cohort analysis of singleton fetuses with gastroschisis. Percentage of error between ultrasound EFW (performed within 2 weeks of delivery) and birthweight was calculated. Agreement between EFW by ultrasound formulas and birthweight was determined by Bland-Altman limits of agreement; concordance between ultrasound and birthweight diagnosis of FGR was evaluated with McNemar's test. RESULTS: Birthweight was best predicted by the formulas of Shepard et al and Siemer et al. Only these formulas demonstrated significant agreement with birthweight for prediction of FGR at the 5th and 10th percentiles. CONCLUSION: The formulas of Shepard et al and Siemer et al best estimate birthweight, and their use has the potential to reduce rates of overdiagnosis of FGR.

Perinatal outcomes in isolated single umbilical artery.

We sought to determine the rate of adverse perinatal outcomes in pregnancies diagnosed with an isolated single umbilical artery (SUA). We performed a retrospective review comparing 68 pregnancies with an isolated SUA to 68 pregnancies with a three-vessel cord (3VC). Pregnancies with structural or karyotypic anomalies were excluded. Gestational age at delivery, birth weight, SGA rate, ponderal index, and rates of admission to the neonatal intensive care unit were compared between groups. Student T test and chi-square analysis were performed. Neonates with isolated SUA had a significantly smaller birth weight than those with a 3VC (3279 +/- 404 g versus 3423 +/- 374 g, P = 0.0168). There was no significant difference in rates of SGA (17.6% versus 8.8%, P = 0.06). Ponderal index was significantly less in those with SUA compared with 3VC (24.2 +/- 1.1 g/cm(3) versus 26.1 +/- 1.3 g/cm(3), P = 0.001). SUA neonates had a significantly longer length of neonatal intensive care unit stay than 3VC neonates (1.25 +/- 2.2 days versus 0.48 +/- 1.25 days, P < 0.023). Fetuses with a prenatal diagnosis of isolated umbilical artery have a significantly lower ponderal index compared with fetuses with a 3VC. Pregnancies with isolated SUA should undergo serial assessments for fetal growth.

Intrauterine growth patterns in fetal gastroschisis.

The objective of this study was to evaluate patterns of intrauterine growth in fetal gastroschisis. This was a retrospective review of prenatally diagnosed cases of fetal gastroschisis delivered at the University of North Carolina Hospital from January 2000 to January 2007. Fetal growth (biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight) and amniotic fluid volume were evaluated by gestational age. Gastroschisis was diagnosed in 83 pregnancies; outcomes were available in 71 fetuses. The mean gestational age at diagnosis was 17 weeks and 1 day. The mean gestational age at delivery was 35 weeks and 4 days. Mean birth weight was 2306 g. As early as the second trimester, all morphometric measures demonstrated impaired in utero growth, with growth curves shifted to the right of the 50th percentile when compared with a standard population. Estimated fetal weight below the 10th percentile was suspected in 23% of pregnancies, and birth weight at less than the 10th percentile occurred in 47% of neonates. Amniotic fluid volumes remained stable throughout gestation. Fetuses with gastroschisis display impaired intrauterine growth, which is noted in the midsecond trimester of pregnancy and does not appear to progress throughout gestation.

Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension.

Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women.

The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P < 0.05) for zidovudine (GMR, 0.25) and lopinavir (GMR, 0.03); postpartum lopinavir GT penetration continued to be significantly lower (GMR, 0.27). Cord BP exposures were highest for lamivudine and tenofovir (> or = 100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were > or = 100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were < or = 6% that of BP. We conclude that GT, cord BP, and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.

The effect of 17-alpha hydroxyprogesterone caproate on the risk of gestational diabetes in singleton or twin pregnancies.

OBJECTIVE: To compare the rates of gestational diabetes among women who received serial doses of 17-alpha hydroxyprogesterone caproate vs placebo. STUDY DESIGN: Secondary analysis of 2 double-blind randomized placebo-controlled trials of 17-alpha hydroxyprogesterone caproate given to women at risk for preterm delivery. The incidence of gestational diabetes was compared between women who received 17-alpha hydroxyprogesterone caproate or placebo. RESULTS: We included 1094 women; 441 had singleton and 653 had twin gestations. Combining the 2 studies, 616 received 17-alpha hydroxyprogesterone caproate and 478 received placebo. Among singleton and twin pregnancies, rates of gestational diabetes were similar in women receiving 17-alpha hydroxyprogesterone caproate vs placebo (5.8% vs 4.7%; P = .64 and 7.4% vs 7.6%; P = .94, respectively). In the multivariable model, progesterone was not associated with gestational diabetes (adjusted odds ratio, 1.04; 95% confidence interval, 0.62-1.73). CONCLUSION: Weekly administration of 17-alpha hydroxyprogesterone caproate is not associated with higher rates of gestational diabetes in either singleton or twin pregnancies.

Maternal periodontal disease and soluble fms-like tyrosine kinase-1 expression.

BACKGROUND: This study was conducted to examine the relationship between maternal periodontal disease and plasma angiogenic factor expression of soluble fms-like tyrosine kinase (sFlt)-1. METHODS: This was a nested case-control study of 220 women, including 45 healthy women with evidence of active periodontal disease, 98 women without evidence of active periodontal disease, 13 women with fetal exposure to oral pathogens, and 64 women without fetal exposure to oral pathogens. Active periodontal disease was defined as the presence of moderate/severe periodontal disease and evidence of periodontal disease progression. Fetal exposure to oral pathogens was determined by fetal immunoglobulin M (IgM) umbilical cord seropositivity. Maternal plasma was collected at <26 weeks of gestation; umbilical cord blood was collected at delivery. sFlt-1 was measured with an immunoradiometric assay. Demographic and medical data were chart abstracted. Maternal variables and sFlt-1 concentrations were compared between cases and controls using the Student t and chi(2) tests and analysis of variance. RESULTS: The median sFlt-1 concentration at the time of enrollment for all women was 2,374 pg/ml (interquartile range [IQR]: 1,504 to 3,194 pg/ml). Women with evidence of fetal exposure to oral pathogens had significantly higher sFlt-1 concentrations compared to IgM-negative fetuses (3,383 pg/ml [IQR: 2,610 to 4,244 pg/ml] versus 2,123 pg/ml [IQR: 1,456 to 3,011 pg/ml]; P = 0.03). CONCLUSION: Fetal exposure to oral pathogens was associated with increased plasma concentrations of sFlt-1 early in pregnancy.

Periodontal disease early in pregnancy is associated with maternal systemic inflammation among African American women.

BACKGROUND: Maternal periodontal disease is a chronic oral infection with local and systemic inflammatory responses and may be associated with adverse pregnancy outcomes. This study determined whether maternal periodontal disease in early pregnancy is associated with elevated serum C-reactive protein (CRP) levels and whether maternal race influences the relationship between maternal periodontal disease and systemic inflammatory responses. METHODS: A secondary analysis of prospectively collected data from the Oral Conditions and Pregnancy study was conducted. Healthy women at <26 weeks of gestation underwent an oral health examination and had blood collected. Periodontal disease was categorized by clinical criteria, and maternal serum was analyzed for CRP levels using highly sensitive enzyme-linked immunosorbent assay kits. An elevated CRP level was defined as >75th percentile. Demographic and medical data were obtained from the women's charts. Chi-square and multivariable logistic regression models were used to determine maternal factors associated with an elevated CRP. An adjusted odds ratio (OR) for elevated CRP levels was calculated and stratified by race and periodontal disease category. RESULTS: The median (interquartile) CRP level was 4.8 (0.6 to 15.7) microg/ml, and an elevated CRP level (>75th percentile) was 15.7 microg/ml. African American race and moderate/severe periodontal disease were significantly associated with elevated CRP levels. When stratified by race, moderate/severe periodontal disease remained associated with an elevated CRP level among African American women (adjusted OR: 4.0; 95% confidence interval [CI]: 1.2 to 8.5) but not among white women (adjusted OR: 0.9; 95% CI: 0.2 to 3.6) after adjusting for age, smoking, parity, marital status, insurance status, and weight. CONCLUSION: Among African American women, moderate/severe periodontal disease is associated with elevated CRP levels early in pregnancy.

Periodontal disease and preterm birth.

Preterm birth (delivery at fewer than 37 weeks' gestation) is the most common cause of infant morbidity and mortality among nonanomalous infants in the United States. Increasing evidence has focused on associations between clinical infection, inflammation, and preterm birth. Maternal periodontal disease, which is associated with systemic inflammation, has been associated with preterm birth. Intervention trails for treatment of periodontal disease during pregnancy, however have not consistently shown a reduction in preterm birth rates. Despite the lack of reduction in preterm birth, oral health maintenance is an important part of preventive care and should be supported during pregnancy.

Periodontal disease, oxidative stress, and risk for preeclampsia.

BACKGROUND: Maternal periodontal infection is associated with an increased risk for preeclampsia. Periodontal infection is also associated with increased oxidative stress. Our objective was to determine the relationship among maternal periodontal disease, maternal oxidative stress, and the development of preeclampsia. METHODS: A secondary analysis of prospectively collected data from the Oral Conditions and Pregnancy Study was performed. A cohort of healthy women enrolled at <26 weeks of gestation underwent an oral examination, serum sampling, and delivery follow-up. A periodontal infection was categorized by clinical parameters as healthy or mild or moderate/severe periodontal infection. Preeclampsia was defined by the American Congress of Obstetricians and Gynecologists criteria as blood pressure >140/90 mmHg and >or=1+ proteinuria on a catheterized specimen. Maternal blood was assayed for 8-isoprostane concentrations using an enzyme-linked immunosorbent assay and stratified as elevated (>or=75th percentile) or not elevated (<75th percentile). Odds ratios (ORs) for preeclampsia were calculated and stratified by periodontal disease and the level of 8-isoprostane concentration. RESULTS: A total of 34 (4.3%) of 791 women developed preeclampsia. Women with an 8-isoprostane concentration >or=75th percentile at enrollment were more likely to develop preeclampsia compared to women with an 8-isoprostane concentration <75th percentile (38.2% versus 24.4%, respectively; P = 0.07; OR: 1.91; 95% confidence interval [CI]: 0.94 to 3.90). Among women with moderate/severe periodontal disease, an elevated 8-isoprostane concentration (>or=75th percentile) did not significantly increase the likelihood for preeclampsia (adjusted OR: 2.08; 95% CI: 0.65 to 6.60). CONCLUSIONS: Women with oxidative stress early in pregnancy, as measured by an 8-isoprostane concentration >or=75th percentile, were at an increased risk for developing preeclampsia. The presence of periodontal disease did not appear to modify this risk.

Family history of venous thromboembolism and identifying factor V Leiden carriers during pregnancy.

OBJECTIVE: To estimate whether there is a correlation between family history of venous thromboembolism and factor V Leiden mutation carriage in gravid women without a personal history of venous thromboembolism. METHODS: This is a secondary analysis of a prospective observational study of the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden mutation. Family history of venous thromboembolism in either first- or second-degree relatives was self-reported. Sensitivity, specificity, and positive and negative predictive values of family history to predict factor V Leiden mutation carrier status were calculated. RESULTS: Women without a personal venous thromboembolism history and with available DNA were included (n=5,168). One hundred forty women (2.7% [95% confidence interval (CI) 2.3-3.2%]) were factor V Leiden mutation-positive. Four hundred twelve women (8.0% [95% CI 7.3-8.7%]) reported a family history of venous thromboembolism. Women with a positive family history were twofold more likely to be factor V Leiden mutation carriers than those with a negative family history (23 of 412 [5.6%] compared with 117 of 4,756 [2.5%], P<.001). The sensitivity, specificity, and positive predictive value of a family history of a first- or second-degree relative for identifying factor V Leiden carriers were 16.4% (95% CI 10.7-23.6%), 92.3% (95% CI 91.5-93.0%), and 5.6% (95% CI 3.6-8.3%), respectively. CONCLUSION: Although a family history of venous thromboembolism is associated with factor V Leiden mutation in thrombosis-free gravid women, the sensitivity and positive predictive values are too low to recommend screening women for the factor V Leiden mutation based solely on a family history.