Karen Bruder

Super-obesity and risk for early and late pre-eclampsia

Please cite this paper as: Mbah A, Kornosky J, Kristensen S, August E, Alio A, Marty P, Belogolovkin V, Bruder K, Salihu H. Super‐obesity and risk for early and late pre‐eclampsia. BJOG 2010;117:997–1004.

Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004).

Objectives:The study was designed to assess the safety, adherence, acceptability, and effect on vaginal microflora of 3% SPL7013 Gel (VivaGel), a novel dendrimer topical microbicide that inhibits HIV, herpes simplex virus-2, and human papillomavirus in vitro and in animal models. Design:Phase 1, randomized, double-blind, placebo-controlled study on sexually active women. Methods:Sixty-one sexually active women aged 18–24 years were recruited from three sites in the United States. Participants were randomized 1: 1: 1 to receive VivaGel, VivaGel placebo, or a hydroxyethylcellulose (HEC) placebo twice daily for 14 consecutive days. Safety endpoints included genitourinary and/or other adverse events. Changes in vaginal flora were determined from Gram-stained vaginal smears and quantitative vaginal culture. Results:No serious adverse events or withdrawals due to adverse events were reported. Genitourinary symptoms were reported as follows: VivaGel (n = 17/22; 77.3%), VivaGel placebo (n = 14/21; 66.7%), and HEC (n = eight of 18; 44.4%; not significant, P = 0.1). The incidence of abnormal pelvic examination findings was similar across all gel arms of the study. Using pairwise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary adverse events compared with women in the HEC gel arm (0.297 versus 0.111 per 100 person-years, respectively; P = 0.003). Exposure to VivaGel and VivaGel placebo resulted in minor shifts in the vaginal microflora, but there was no overall impact on incidence of bacterial vaginosis as assessed by Nugent score. Conclusion:VivaGel was generally well tolerated and comparable with the VivaGel placebo, although there was a higher incidence of low-grade related genital adverse events compared to the HEC placebo gel.

Systematic review on sleep disorders and obstetric outcomes: scope of current knowledge.

OBJECTIVE To assess the current state of knowledge regarding sleep disorders and their relationship to obstetric outcomes. STUDY DESIGN A systematic literature review of the previous two decades (1991 to 2010) was conducted. The exposure was sleep disorders during pregnancy, and the outcomes of interest were feto-infant morbidity and maternal complications. RESULTS Sleep apnea, snoring, and sleep quantity/duration were identified as the most frequently examined sleep disorders among pregnant women. Although our review found that studies examining the impact of sleep disorders on feto-infant outcomes were lacking, previous research indicates that such disorders may enhance the risk of preterm birth. Additionally, the current body of evidence suggests that sleep disorders adversely impact maternal health, increasing the likelihood of preeclampsia, and gestational diabetes. CONCLUSION Existing research points to the potentially harmful effects of sleep disorders on obstetric outcomes. The limited research in this arena highlights the need for further studies regarding the nature and strength of this relationship. Given the multiple dimensions of sleep and pregnancy, multivariate research approaches that incorporate biological and psychosocial factors are warranted.

Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach

AIMS We used propensity scores matching techniques to assess the association between maternal cocaine abuse in pregnancy and the occurrence of placenta-associated syndromes (PAS). STUDY DESIGN Mothers who abused cocaine (n=5026) were matched to controls (n=5026) from a sample of 1,693,197, unexposed mothers in Florida from 1998 to 2007. Cocaine abuse was identified using the ICD-9 principal and secondary diagnosis codes (304.2 for cocaine dependence and 305.6 for cocaine abuse). The outcome of interest, PAS, was identified as any indication in diagnosis field of ICD-9-CM codes for: placental abruption (641.2), oligohydramnios (658.0), placental infarction (656.7, 656.8, 656.9), gestational hypertension (642.3, 642.9), preeclampsia (642.4, 642.5, and 642.7) or eclampsia (642.6). RESULTS Nearly 6% of mothers in the study sample experienced a condition associated with PAS prior to matching. Women who abused cocaine were 58% more likely to have PAS when compared to women who did not (OR=1.48, 95% confidence interval: 1.33, 1.66). Women who abused cocaine were at elevated odds for placental abruption, placenta infarction and preeclampsia with the most pronounced odds noted for placental abruption (OR=2.79, 95% confidence interval: 2.19, 3.55). CONCLUSIONS These findings indicate that cocaine abuse during pregnancy is associated with more placenta-related disorders than previously reported.

Success of programming fetal growth phenotypes among obese women.

OBJECTIVE: To estimate the distribution and success of programmed fetal growth phenotypes among obese women. METHODS: This was a retrospective cohort study using the Missouri maternally linked cohort files (years 1978–1997). Maternal body mass index was classified as Normal (18.5–24.9) (referent group), Obese (class 1, 30.0–34.9; class 2, 35.0–39.9; and extreme or class 3, 40 or more). Fetal growth phenotypes were defined as large for gestational age (LGA), appropriate for gestational age (AGA), and small for gestational age (SGA). We used adjusted odds ratio with correction for intracluster correlation to estimate the risk of neonatal mortality for each fetal growth phenotype. RESULTS: As compared with normal weight mothers, obese gravidas tended to program LGA infants at a higher and increasing rate with ascending obesity severity. The opposite effect was observed with respect to AGA and SGA programming patterns. Neonatal mortality among LGA infants was similar for obese (6.2 in 1,000) and normal (4.9 in 1,000) weight mothers (OR 1.05, 95% confidence interval [CI] 0.75–1.48) and regardless of obesity subtype. By contrast, SGA and AGA infants programmed by obese mothers experienced greater neonatal mortality as compared with those born to normal weight mothers (AGA OR 1.45, 95% CI 1.32–1.59; SGA OR 1.72, 95% CI 1.49–1.98). CONCLUSION: Compared with normal weight mothers, obese women are least successful at programming SGA, less successful at programming AGA, and equally as successful at programming LGA infants. LEVEL OF EVIDENCE: II

Exposure to environmental tobacco smoke and risk of antenatal depression: application of latent variable modeling

This study sought to determine the impact of passive smoking on the risk for depressive symptoms during pregnancy. In this prospective study, 236 pregnant women were recruited at less than 20 weeks of gestation from a university-affiliated obstetric clinic from November 2009 through July 2011. Tobacco use/exposure was measured using questionnaire and confirmed by salivary cotinine analysis. The Edinburgh Perinatal Depression Scale (EPDS) was employed to capture perinatal depressive symptomatology. Traditionally, a cutoff of 13 is utilized to indicate depressive symptoms in the perinatal population. However, this approach is vulnerable to measurement errors that are inherent in assessing depression using cutoff points. Therefore, in this analysis, we apply a flexible approach (latent variable modeling) that accounts for measurement errors thereby reducing bias in the estimates of association. Significant differences were observed in the mean EPDS scores across non-smokers (mean ± SD = 4.8 ± 4.8), passive smokers (5.3 ± 5.5) and active smokers (7.4 ± 6.1) [p value = 0.02]. For each itemized response of the EPDS, passive smokers demonstrated an increased risk for depressive symptoms with the greatest risk exhibited by items 8 and 9 of the questionnaire (feeling sad or miserable and feeling unhappy [and]crying, respectively). In addition, for each item of the EPDS, a dose–response pattern was revealed with non-smokers having the least risk of depressive symptoms during pregnancy and active smokers having the greatest risk. Women who are exposed to secondhand smoke are at elevated risk for depressive symptoms during pregnancy.

Recurrent versus isolated pre-eclampsia and risk of feto-infant morbidity outcomes: racial/ethnic disparity

OBJECTIVE We examined the association between recurrent versus isolated pre-eclampsia and feto-infant morbidity outcomes. STUDY DESIGN This is a population-based retrospective study on Florida hospital discharge data linked to the birth cohort files from 1998 through 2007. The study population comprised women with singleton first and second births who experienced pre-eclampsia in both pregnancies, and a comparison group consisting of women who were normotensive during their first pregnancy but developed pre-eclampsia in their second pregnancy. Feto-infant morbidities (low birth weight, very low birth weight, preterm, very preterm and small for gestational age) were the outcome of interest. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between recurrent pre-eclampsia and feto-infant morbidity outcomes were obtained from logistic regression models. RESULT Women who experienced recurrent pre-eclampsia were at elevated risk for low birth weight, very low birth weight, preterm and very preterm. The risk was most pronounced for preterm infants (OR=1.58 CL=1.42-1.76). Subgroup analysis demonstrated that infants born to black mothers with recurrent pre-eclampsia experienced the most elevated risk across all the racial/ethnic subgroups and this was most pronounced for very low birth weight and very preterm with a more than three-fold increase in risk (OR=3.77, 95% CI=2.77-5.13 and OR=3.66, 95% CI=2.66-5.03, respectively) as compared to the referent category (white mothers who were normotensive in first pregnancy but developed pre-eclampsia in their second pregnancy). CONCLUSION Pre-eclampsia is very severe when it recurs and black women are affected more than white or Hispanic women.

Pre-eclampsia in the first pregnancy and subsequent risk of stillbirth in black and white gravidas

OBJECTIVE To examine the association between prior pre-eclampsia and subsequent stillbirth in black women and white women. STUDY DESIGN This is a population-based retrospective study of Missouri maternally linked birth cohort files from 1989 to 2005. We analyzed singleton first and second births to mothers in the state of Missouri. The study population comprised women who experienced pre-eclampsia in their first pregnancy and a comparison group consisting of women who did not. The two groups were followed to their second pregnancy to document stillbirth occurrence. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prior pre-eclampsia and subsequent stillbirth were obtained from logistic regression models. RESULTS Women who experienced prior pre-eclampsia had a 43% increased risk of subsequent stillbirth [OR=1.43; 95% CI=1.08-1.89]. Whereas women with a history of late-onset pre-eclampsia had no elevated risk for subsequent stillbirth, those whose first pregnancy resulted in early-onset pre-eclampsia had a more than 4-fold increased risk of stillbirth in their second pregnancy [OR=4.07; 95% CI=2.32-7.14]. When sub-analysis was performed on the two main racial groups in the State, we found that elevated risk for subsequent stillbirth in a second pregnancy was observed among black women with prior early-onset pre-eclampsia (OR=8.21; 95% CI=4.03-16.70) but not in whites (OR=1.95; 95% CI=0.72-5.26). CONCLUSION Initiation of pregnancy with pre-eclampsia elevates the risk for subsequent stillbirth. The risk elevation is most pronounced in black women with early-onset pre-eclampsia in their first pregnancy. This information is valuable for inter-pregnancy counseling of affected women.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.