Hyagriv N Simhan

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (190)755.89 Total impact

  • Christina M Scifres, Janet M Catov, Hyagriv N Simhan
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    ABSTRACT: Objective We evaluated the impact of maternal overweight/obesity and excessive weight gain on maternal serum lipids in the first and second trimester of pregnancy. Design and Methods Prospective data were collected for 225 women. Maternal serum lipids and fatty acids were measured at <13 weeks and between 24–28 weeks. Analyses were stratified by normal weight versus overweight/obese status and excessive vs. non-excessive weight gain. Results Overweight/obese women had higher baseline cholesterol (161.3±29.6 vs 149.4±26.8 mg/dL, p<0.01), LDL (80.0±19.9 vs 72.9 ±18.8 mg/dL, p<0.01) and triglycerides ( 81.7±47.2 vs 69.7±40.3 mg/dL, p=0.05) when compared to normal weight women, while HDL (43.6 ±10.4 47.6±11.5 mg/dL, p<0.01) was lower. However, cholesterol and LDL increased at a higher weekly rate in normal weight women, resulting in higher total cholesterol in normal weight women (184.1±28.1 vs. 176.0 ±32.1 mg/dL, p=0.05) at 24–28 weeks. Excessive weight gain did not affect the rate of change in lipid profiles in either group. Overweight/obese women had higher levels of arachidonic acid at both time points. Conclusions Overweight/obese women have significantly more atherogenic lipid profiles than normal weight women during the period of early pregnancy, delineating one physiologic pathway that could explain differences in pregnancy outcomes between normal weight and overweight/obese women.
    Obesity 03/2014; 22(3). DOI:10.1002/oby.20576 · 4.39 Impact Factor
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    ABSTRACT: We sought to determine the association between maternal vitamin D status at ≤26 weeks' gestation and the risk of preeclampsia by clinical subtype. We conducted a case-cohort study among women enrolled at 12 US sites from 1959 to 1966 in the Collaborative Perinatal Project. In serum collected at ≤26 weeks' gestation (median 20.9 weeks) from 717 women who later developed preeclampsia (560 mild and 157 severe cases) and from 2986 mothers without preeclampsia, we measured serum 25-hydroxyvitamin D, over 40 years later, using liquid chromatography-tandem mass spectrometry. Half of women in the subcohort had 25-hydroxyvitamin D (25(OH)D) >50 nmol/L. Maternal 25(OH)D 50 to 74.9 nmol/L was associated with a reduction in the absolute and relative risk of preeclampsia and mild preeclampsia compared with 25(OH)D <30 nmol/L in the crude analysis but not after adjustment for confounders, including race, prepregnancy body mass index, and parity. For severe preeclampsia, 25(OH)D ≥50 nmol/L was associated with a reduction in three cases per 1000 pregnancies (adjusted risk difference = -0.003 [95% confidence interval = -0.005 to 0.0002]) and a 40% reduction in risk (0.65 [0.43 to 0.98]) compared with 25(OH)D <50 nmol/L. Conclusions were unchanged (1) after restricting to women with 25(OH)D measured before 22 weeks' gestation or (2) with formal sensitivity analyses for unmeasured confounding. Maternal vitamin D deficiency may be a risk factor for severe preeclampsia but not for its mild subtypes. Contemporary cohorts with large numbers of severe preeclampsia cases would be needed to confirm or refute these findings.
    Epidemiology (Cambridge, Mass.) 01/2014; 25(2). DOI:10.1097/EDE.0000000000000039 · 6.18 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S49. DOI:10.1016/j.ajog.2013.10.106 · 3.97 Impact Factor
  • Jennifer Hutcheon, Lisa Bodnar, Hyagriv Simhan
    American Journal of Obstetrics and Gynecology 01/2014; 210(1):S259-S260. DOI:10.1016/j.ajog.2013.10.560 · 3.97 Impact Factor
  • Rosemary Froehlich, Hyagriv Simhan, Jacob Larkin
    American Journal of Obstetrics and Gynecology 01/2014; 210(1):S77. DOI:10.1016/j.ajog.2013.10.160 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S138. DOI:10.1016/j.ajog.2013.10.290 · 3.97 Impact Factor
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    ABSTRACT: To examine the association between second-trimester maternal serum 25-hydroxyvitamin D concentrations and risk of small for gestational age (SGA) in singleton live births. We assayed serum samples at 12-26 weeks of gestation for 25-hydroxyvitamin D in a sample of participants in a multicenter clinical trial of low-dose aspirin for the prevention of preeclampsia in high-risk women (n=792). Multivariable log-binomial regression models were used to assess the association between 25-hydroxyvitamin D and risk of SGA (birth weight less than the 10 percentile for gestational age) after adjustment for confounders including maternal prepregnancy obesity, race, treatment allocation, and risk group. Thirteen percent of neonates were SGA at birth. Mean (standard deviation) 25-hydroxyvitamin D concentrations were lower in women who delivered SGA (57.9 [29.9] nmol/L) compared with non-SGA neonates (64.8 [29.3] nmol/L, P=.028). In adjusted models, 25-hydroxyvitamin D concentrations of 50-74 nmol/L and 75 nmol/L or greater compared with less than 30 nmol/L were associated with 43% (95% confidence interval [CI] 0.33-0.99) and 54% (95% CI 0.24-0.87) reductions in risk of SGA, respectively. Race and maternal obesity each modified this association. White women with 25-hydroxyvitamin D 50 nmol/L or greater compared with less than 50 nmol/L had a 68% reduction in SGA risk (adjusted risk ratio 0.32, 95% CI 0.17-0.63) and nonobese women with 25-hydroxyvitamin D 50 nmol/L or greater compared with less than 50 nmol/L had a 50% reduction in SGA risk (adjusted risk ratio 0.50, 95% CI 0.31-0.82). There was no association between 25-hydroxyvitamin D and risk of SGA in black or obese mothers. Maternal vitamin D status in the second trimester is associated with risk of SGA among all women and in the subgroups of white and nonobese women. : II.
    Obstetrics and Gynecology 01/2014; 123(1):40-8. DOI:10.1097/AOG.0000000000000049 · 4.37 Impact Factor
  • Leslie A Moroz, Hyagriv N Simhan
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    ABSTRACT: To estimate the relation between midtrimester cervical length (CL) and maternal serum markers of systemic inflammation, activation of the maternal-fetal hypothalamic-pituitary axis, and alterations in thrombosis-hemostasis STUDY DESIGN: This is a secondary analysis of a prospective cohort study designed to predict preterm birth in the general obstetric population. Women had serial CL ultrasounds and assessment of maternal serum corticotrophin releasing hormone (CRH), C-reactive protein (CRP), and Thrombin-Antithrombin III (TAT) complexes between 20-33wks gestation and were followed until delivery. Results: Shortening of CL was associated with rate of rise in CRH (r2=0.34, p=0.014) and CRP (r2=0.44, p=0.001) for women with CL<25mm, but not for the cohort overall. There was no association of change in CL with change in TAT concentration. Among women with a midtrimester sonographically short cervix, changes in serum markers suggest that shortening CL may be associated with systemic inflammation and activation of the maternal-fetal hypothalamic-pituitary axis, but not systemic thrombosis-hemostasis.
    American journal of obstetrics and gynecology 12/2013; 210(6). DOI:10.1016/j.ajog.2013.12.037 · 3.97 Impact Factor
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    ABSTRACT: The objective of this study was to determine the association between maternal 25-hydroxyvitamin D (25(OH)D) and the risk of spontaneous preterm birth (sPTB) before 35 weeks' gestation. A random subcohort from the US Collaborative Perinatal Project (1959-1965) was sampled (n = 2,629) and augmented with all remaining cases of sPTB before 35 weeks' gestation for a total of 767 cases. Banked serum samples collected at 26 weeks' gestation or earlier were assayed for 25(OH)D. Constructs for vascular histology and inflammatory histology were developed from placental pathology examinations. There was no relationship between 25(OH)D and sPTB among white women. Among nonwhite mothers, serum 25(OH)D levels of 30-<50, 50-<75, and ≥75 nmol/L were associated with reductions of 1.0-1.6 cases of sPTB per 100 live births and 20%-30% reductions in risk of sPTB compared with 25(OH)D levels less than 30 nmol/L after adjustment for prepregnancy body mass index (weight (kg)/height (m)(2)), season, and other confounders. This association was driven by inflammation-mediated cases of sPTB and sPTB cases without placental lesions. A sensitivity analysis for unmeasured confounding by exercise, fish intake, and skin color suggested some bias away from the null in the conventional results, but conclusions were generally supported. The vitamin D-sPTB relationship should be examined in modern cohorts with detailed data on skin pigmentation and other covariates.
    American journal of epidemiology 10/2013; 179(2). DOI:10.1093/aje/kwt237 · 4.98 Impact Factor
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    ABSTRACT: To estimate the effects of gestational weight gain (GWG), central adiposity and subcutaneous fat on maternal post-load glucose concentration, pregnant women [n = 413, 62 % black, 57 % with pregravid body mass index (BMI) ≥25] enrolled in a cohort study at ≤13 weeks gestation. GWG was abstracted from medical records. In a sub-sample of women (n = 214), waist circumference (WC), and biceps and triceps skinfold thicknesses were measured at enrollment. At 24-28 weeks gestation, post-load glucose concentration was measured using a 50-g 1-h oral glucose tolerance test. After adjustment for pre-pregnancy BMI, age, parity, race/ethnicity, smoking, marital status, annual family income, education, family history of diabetes, and gestational age of GDM screening, each 0.3-kg/week increase in weight in the first trimester was associated with a 2.2 (95 % CI 0.1, 4.3)-mg/dl increase in glucose concentration. Each 8.6-mm increase in biceps skinfold thickness and each 11.7-mm increase in triceps skinfold thickness was associated with 4.3 (95 % CI 0.2, 8.5)-mg/dl increase in maternal glucose, independent of BMI and other confounders. Neither GWG in the second trimester nor WC at ≤13 weeks was significantly associated with glucose concentration after confounder adjustment. Independent of pre-pregnancy BMI, high early pregnancy GWG and maternal subcutaneous body fat may be positively associated with maternal glucose concentrations at 24-28 weeks.
    Maternal and Child Health Journal 10/2013; 18(5). DOI:10.1007/s10995-013-1361-3 · 2.24 Impact Factor
  • Francesca L Facco, Hyagriv N Simhan
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    ABSTRACT: To understand the relationship between cervical length and the risk of prematurity in parous women without a history of preterm delivery. Data from 2,998 singleton pregnancies enrolled in a multicenter, observational cohort study were analyzed. We subgrouped the population into the following categories: those with history of at least one spontaneous preterm birth (n=467); nulliparous (n=1,237); and parous with a history of at least one term birth and no previous preterm birth (low-risk history group, n=1,284). The relationship between cervical length (measured between 22 and 22 6/7 weeks of gestation) and preterm birth was examined using logistic regression. Assuming a 40% risk reduction with the use of vaginal progesterone, we calculated the number needed to screen to prevent one preterm birth. An inverse relationship between cervical length and risk of preterm birth was demonstrated for each subgroup. A short cervix (15 mm or less) was identified in only 0.93% of the low-risk group participants compared with 3.4% of the previous preterm birth group participants and 2.1% of nulliparous women. The overall rate of preterm birth was lowest (10.5%) in the low-risk history group; however, the rate of preterm birth for these women with a short cervix was 25%. For a cervical length cutoff of 15 mm or less, preventing one spontaneous delivery before 34 weeks of gestation would require screening 167 (95% confidence interval [CI] 112-317) women with a previous preterm birth, 344 (95% CI 249-555) nulliparous women, and 1,075 (95% CI 667-2,500) women at low risk. Although ultrasonographic short cervix is a risk factor for preterm birth among parous women with exclusively term births, the incidence of a short cervix is very low. The number needed to screen to prevent one preterm birth is considerably greater for women who have a low-risk obstetric history. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 10/2013; 122(4):858-862. DOI:10.1097/AOG.0b013e3182a2dccd · 4.37 Impact Factor
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    ABSTRACT: Maternal vitamin D deficiency has been linked to fetal growth restriction, but the underlying mechanisms are unclear. We tested the hypothesis that poor maternal 25-hydroxyvitamin D [25(OH)D] was associated with increased risk of placental vascular pathology. Maternal serum 25(OH)D was measured at ≤26 wk of gestation in a random subcohort of term, singleton infants in the Collaborative Perinatal Project (1959-1966; n = 2048). A dichotomous vascular construct was created from the presence of any of 12 pathologies identified on placental examinations, including evidence of placental abruption, infarction, hypoxia, decidual vasculopathy, or thrombosis of fetal vessels (n = 240 cases). The relation between 25(OH)D and vascular pathology was modified by infant sex (P = 0.003). A maternal 25(OH)D concentration ≥80 compared with <50 nmol/L was associated with 49% lower risk of pathology in boys [adjusted OR (95% CI): 0.27, 0.95] after conditioning on study site. No associations were observed between maternal 25(OH)D and pathology in mothers with female offspring. Subsequent analyses showed that, in pregnancies with a female fetus, vascular pathology was associated with a reduced birth-weight z score when the mother's 25(OH)D concentration was <30 nmol/L (β: -0.73; 95% CI: -1.17, -0.30). No association was observed between pathology and birth weight in mothers of female offspring with 25(OH)D concentrations ≥30 nmol/L or in boys, regardless of maternal 25(OH)D status. Our findings suggest complex relations between vitamin D, placental vascular pathology, and birth weight that differ by infant sex. Maternal vitamin D status may be beneficial for male and female offspring through different mechanisms.
    American Journal of Clinical Nutrition 06/2013; 98(2). DOI:10.3945/ajcn.112.055426 · 6.92 Impact Factor
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    ABSTRACT: Objective To determine if the length of fetal long bones (LB) at mid-trimester ultrasound is predictive of small-for-gestational-age (SGA) newborns at term delivery.Methods Retrospective evaluation of 6,781 women between 18 and 24 weeks' gestation at Magee-Womens Hospital (MWH). Gestational age (GA) was confirmed by first- or second-trimester ultrasound and patient's last menstrual period. Data were accrued from the institutional database at MWH. LB measurements were normalized to GA at the time of the ultrasound. The ratio was correlated with the probability of delivering an SGA newborn at term.Results In all, 583 women were identified with an SGA newborn (8.6%). LB-to-GA ratios were associated with the probability of delivering an SGA newborn at term (p < 0.001). There was no single LB that proved to be superior in predicting an SGA newborn.Conclusion There is a significant association between LB-to-GA ratio at midtrimester and the probability of SGA at term.
    American Journal of Perinatology 05/2013; 31(3). DOI:10.1055/s-0033-1345260 · 1.60 Impact Factor
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    L E Tomedi, H N Simhan, L M Bodnar
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    ABSTRACT: AIMS: To estimate the association between serum 25-hydroxyvitamin D concentrations and maternal hyperglycaemia (post-load glucose concentration ≥ 7.5 mmol/l). METHODS: Pregnant women (n = 429; 61% black, 36% obese, 45% smokers) enrolled in a cohort study at <16 weeks gestation. Non-fasting blood samples were assayed for serum 25-hydroxyvitamin D at enrolment. At 24-28 weeks gestation, maternal hyperglycaemia was determined using a 50-g 1-h oral glucose challenge test. RESULTS: A total of 67% of women had 25-hydroxyvitamin D concentrations < 50 nmol/l and 11% had maternal hyperglycaemia. Among smokers, each 23-nmol/l increase in serum 25-hydroxyvitamin D was associated with a reduction in the odds of maternal hyperglycaemia [odds ratio: 0.30 (95% CI: 0.13, 0.68)] after adjustment for parity, race/ethnicity, age, pre-pregnancy BMI, marital status, income, family history of diabetes, and gestational age of gestational diabetes mellitus screening. Among non-smokers, we found no association between early pregnancy vitamin D status and maternal hyperglycaemia. CONCLUSIONS: Smoking status may modify the relationship between poor maternal vitamin D status and maternal hyperglycaemia. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 05/2013; DOI:10.1111/dme.12229 · 3.06 Impact Factor
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    ABSTRACT: BACKGROUND: To establish the unbiased relation between maternal weight gain in pregnancy and perinatal health, a classification for maternal weight gain is needed that is uncorrelated with gestational age. OBJECTIVE: The goal of this study was to create a weight-gain-for-gestational-age percentile and z score chart to describe the mean, SD, and selected percentiles of maternal weight gain throughout pregnancy in a contemporary cohort of US women. DESIGN: The study population was drawn from normal-weight women with uncomplicated, singleton pregnancies who delivered at the Magee-Womens Hospital in Pittsburgh, PA, 1998-2008. Analyses were based on a randomly selected subset of 648 women for whom serial prenatal weight measurements were available through medical chart record abstraction (6727 weight measurements). RESULTS: The pattern of maternal weight gain throughout gestation was estimated by using a random-effects regression model. The estimates were used to create a chart with the smoothed means, percentiles, and SDs of gestational weight gain for each week of pregnancy. CONCLUSION: This chart allows researchers to express total weight gain as an age-standardized z score, which can be used in epidemiologic analyses to study the association between pregnancy weight gain and adverse or physiologic pregnancy outcomes independent of gestational age.
    American Journal of Clinical Nutrition 03/2013; 97(5). DOI:10.3945/ajcn.112.051706 · 6.92 Impact Factor
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    ABSTRACT: Background Although the etiology of preeclampsia is not well understood, it has been suggested that excessive systemic inflammation may lead to oxidative stress, promoting the endothelial dysfunction characteristic of preeclampsia. Few prospective studies have examined the role of infection, an immune system stimulator, as a risk factor for preeclampsia.Methods We conducted a longitudinal study of the relationships between Chlamydia trachomatis (CT), Chlamydophila pneumoniae (CP), cytomegalovirus (CMV), herpes simplex virus (HSV) and preeclampsia among 509 preeclamptic cases and 336 normotensive controls nested within the Danish National Birth Cohort study. Antibodies were analyzed at a first prenatal visit (mean 17.0 weeks) and at a late second/third trimester study visit. Prenatal infections were identified as IgG/IgM seroconversion or a fourfold rise in IgG antibody titers. Multiple regression models were adjusted for maternal age, BMI, smoking status, and time between blood draws.ResultsCT infection was associated with preeclampsia (ORadj 1.6, 95% CI 0.7, 3.6), severe preeclampsia (ORadj 1.8, 95% CI 0.6, 5.3), and preeclampsia resulting in preterm birth (ORadj 1.7, 95% CI 0.6–4.9) or birth of a small for gestational age infant (ORadj 2.1, 95% CI 0.6, 7.5), although CT infection was uncommon (n = 33, 4.0%) and associations were not statistically significant. CP, CMV, and HSV infection were not associated with preeclampsia.Conclusions Women with serological evidence of prenatal CT infection were more likely to develop preeclampsia, although infection was infrequent and confidence intervals were wide. Studies in populations at higher risk for STIs are needed to corroborate this association.
    01/2013; 3(1):28–33. DOI:10.1016/j.preghy.2012.09.002
  • American Journal of Obstetrics and Gynecology 01/2013; 208(1):S44. DOI:10.1016/j.ajog.2012.10.238 · 3.97 Impact Factor
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    ABSTRACT: Objective To compare intra-amniotic inflammation versus microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. Study Design Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S rDNA. Cases were categorized into 5 groups: Infection (MIAC, IL-6>11.3 ng/mL); Severe Inflammation (no MIAC, IL-6>11.3 ng/mL); Mild Inflammation (no MIAC, IL-6 2.6-11.2 ng/mL); Colonization (MIAC, IL-6<2.6 ng/mL); Negative (no MIAC, IL-6<2.6 ng/mL). Results Infection (N=27) and Severe Inflammation (N=36) had similar latency (median <1 day, 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81%, 72%). Colonization (N=4) and Negative (N=195) had similar outcomes (median latency 23.5, 25 days, composite morbidity and mortality 21%, 25%, respectively). Mild Inflammation (N=47) had outcomes intermediate to Severe Inflammation and Negative (median latency 7 days, composite morbidity and mortality 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 >11.3 and 2.6-11.2 ng/mL, but not MIAC, were significantly associated with composite morbidity and mortality (odds ratio [95% confidence interval] 4.9 [0.6-5.5], 3.1 [1.5-6.4], 1.8 [0.6-5.5], respectively). Conclusions We confirm prior reports that intra-amniotic inflammation is associated with adverse perinatal outcomes whether or not intra-amniotic microbes are detected. Colonization without inflammation appears relatively benign. Intra-amniotic inflammation is not simply present or absent, but has degrees of severity that correlate with adverse outcomes. We propose the designation Amniotic Inflammatory Response Syndrome (AIRS) to denote the adverse outcomes associated with intra-amniotic inflammation.
    American journal of obstetrics and gynecology 01/2013; 210(2). DOI:10.1016/j.ajog.2013.11.032 · 3.97 Impact Factor
  • Jacob Larkin, Hyagriv Simhan
    American Journal of Obstetrics and Gynecology 01/2013; 208(1):S16. DOI:10.1016/j.ajog.2012.10.198 · 3.97 Impact Factor
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    ABSTRACT: OBJECTIVE: In adults one of the major determinants of leukocyte telomere length (LTL), a predictor of age-related diseases and mortality, is cumulative psychosocial stress exposure. More recently we reported that exposure to maternal psychosocial stress during intrauterine life is associated with LTL in young adulthood. The objective of the present study was to determine how early in life this effect of stress on LTL is apparent by quantifying the association of maternal psychosocial stress during pregnancy with newborn TL. STUDY DESIGN: In a prospective study of N=27 mother-newborn dyads maternal pregnancy-specific stress was assessed in early gestation and cord blood PBMCs were subsequently collected and analyzed for LTL measurement. RESULTS: After accounting for the effects of potential determinants of newborn LTL (gestational age at birth, weight, sex and exposure to antepartum obstetric complications), there was a significant, independent, linear effect of pregnancy-specific stress on newborn LTL that accounted for 25% of the variance in adjusted LTL (β=-0.099; p=0.04). CONCLUSIONS: Our finding provides the first preliminary evidence in humans that maternal psychological stress during pregnancy may exert a "programming" effect on the developing telomere biology system that is already apparent at birth, as reflected by the setting of newborn leukocyte telomere length.
    American journal of obstetrics and gynecology 11/2012; 208(2). DOI:10.1016/j.ajog.2012.11.033 · 3.97 Impact Factor

Publication Stats

3k Citations
755.89 Total Impact Points

Institutions

  • 2015
    • University of Pennsylvania
      Filadelfia, Pennsylvania, United States
  • 2003–2015
    • University of Pittsburgh
      • • Division of General Obstetrics and Gynecology
      • • Department of Obstetrics, Gynecology and Reproductive Sciences
      • • Department of Epidemiology
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
    • Magee-Womens Hospital
      • • Department of Obstetrics
      • • Magee-Womens Research Institute
      Pittsburgh, Pennsylvania, United States
  • 2012
    • University of California, Irvine
      Irvine, California, United States
  • 2011
    • University of Rochester
      • Department of Obstetrics and Gynecology
      Rochester, NY, United States
  • 2010
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maryland, United States
  • 2008
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2007–2008
    • Columbia University
      New York, New York, United States
    • University of Washington Seattle
      • Department of Obstetrics and Gynecology
      Seattle, Washington, United States