Hyagriv N Simhan

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (203)932.74 Total impact

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    ABSTRACT: To test the feasibility of conducting a pragmatic randomized controlled trial (RCT) comparing the International Association of Diabetes in Pregnancy Study Groups (IADPSG) versus Carpenter-Coustan diagnostic criteria for gestational diabetes (GDM), and to examine patient and provider views on GDM screening. A single-blinded pragmatic pilot RCT. Participants with a singleton pregnancy between 24 and 28 weeks gestation received a 50 g oral glucose challenge test and if the value was <200 mg/dL were randomized to either the 2 h 75 g OGTT using the IADPSG criteria or the 3 h 100 g OGTT using the Carpenter-Coustan criteria. Primary outcome was the feasibility of randomization and screening. Secondary outcomes included patient and provider views (or preferences) on GDM testing. Sixty-eight women were recruited, 48 (71 %) enrolled and 47 (69 %) were randomized. Participants in both study arms identified the main challenges to GDM testing to be: drinking the glucola, fasting prior to testing, waiting to have blood drawn, and multiple venipuntures. Women in both study arms would prefer the 2 h 75 g OGTT or whichever test is recommended by their doctor in a future pregnancy. Physicians and nurse midwives endorsed screening and were comfortable with being blinded to the GDM testing strategy and results values. Both pregnant women and providers value GDM screening, and pregnant women can be recruited to a blinded, randomized GDM screening trial with minimal attrition and missing data.
    Maternal and Child Health Journal 11/2014; 19(7). DOI:10.1007/s10995-014-1651-4 · 2.24 Impact Factor
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    ABSTRACT: Placenta accreta spectrum is one of the most morbid conditions obstetricians will encounter. The incidence has dramatically increased in the last twenty years. The major contributing factor to this is believed to be the increase in the rate of cesarean delivery. Despite the increased incidence of placenta accreta, most obstetricians have personally managed only a small number of women with placenta accreta. The condition poses dramatic risk for massive hemorrhage and associated complication such as consumption coagulopathy, multisystem organ failure and death. In addition, there is an increased risk for surgical complications such as injury to bladder, ureters and bowel and the need for re-operation. Most women require blood transfusion, often in large quantities, and many require admission to an intensive care unit. As a result of indicated, often emergent preterm delivery, many babies require admission to a neonatal care intensive care unit. Outcomes are improved when delivery is accomplished in centers with multi-disciplinary expertise and experience in the care of placenta accreta. Such expertise may include maternal-fetal medicine, gynecologic surgery, gynecologic oncology, vascular, trauma and urologic surgery, transfusion medicine, intensivists, neonatalogists, interventional radiologists, anesthesiologists, specialized nursing staff, and ancillary personnel. This article highlights the desired features for a center of excellence in placenta accreta, and which patients should be referred for evaluation and / or delivery in such centers.
    American Journal of Obstetrics and Gynecology 11/2014; 212(5). DOI:10.1016/j.ajog.2014.11.018 · 4.70 Impact Factor
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    ABSTRACT: Context: Telomere biology plays a fundamental role in genomic integrity, cellular regeneration, physiology, aging, disease risk and mortality. The initial setting of telomere length (TL) in early life has important implications for telomere maintenance and related disorders throughout the lifespan. However, little is known about the predictors of this initial setting. Objective: Given the established role of estrogen on adult TL and the role of estriol (E3) in the context of fetal development, the goal of this study was to test the hypothesis that higher maternal E3 concentration during early pregnancy is associated with longer infant telomere length. Design, Participants and Setting: Study participants comprised a cohort of N=100 infants followed prospectively from intrauterine life and birth through early childhood from a population-based, representative sample of pregnant mothers recruited in early pregnancy at university-based obstetric clinics in Southern California. Maternal unconjugated plasma (E3) concentrations were assessed in plasma in early gestation (around week 15). Infant TL was assessed in buccal cells at approximately 15 months age. Results: After accounting for the effects of potential confounding maternal and infant variables, there was a significant, independent effect of maternal E3 concentration on infant TL (unstandardized β = 0.297, p=0.001; 95% Cl: 0.121 - 0.473). Specifically, a 1 multiple-of-the-median (MoM) increase in maternal E3 concentration during early pregnancy was associated with a 14.42% increase in infant TL. Conclusions: This study supports the concept of developmental plasticity of the telomere biology system and highlights specifically the role of a potentially modifiable intrauterine factor for further mechanistic and clinical investigation.
    Journal of Clinical Endocrinology &amp Metabolism 10/2014; 100(1):jc20142744. DOI:10.1210/jc.2014-2744 · 6.21 Impact Factor
  • Alison D. Gernand · Hyagriv N. Simhan · Katharyn Baca · Steve Caritis · Lisa M. Bodnar ·

    Journal of Women's Health 10/2014; 23(10):858-859. · 2.05 Impact Factor
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    Alison D. Gernand · Mark A. Klebanoff · Hyagriv N. Simhan · Lisa M. Bodnar ·
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    ABSTRACT: Objective To examine the association between maternal 25-hydroxyvitamin D (25(OH)D) and adverse labor and delivery outcomes. Study design We measured serum 25(OH)D at ≤26 weeks gestation in a random subsample of vertex, singleton pregnancies in women who labored (n=2798) from the 12 site Collaborative Perinatal Project (1959–66). We used labor and delivery data to classify cases of adverse outcomes. Results Twenty-four percent of women were vitamin D deficient (25(OH)D <30 nmol/L) and 4.5%, 3.3%, 1.9%, and 7.5% of women had prolonged stage 1 labor, prolonged stage 2 labor, primary cesarean delivery, or indicated instrumental delivery, respectively. After adjustment for prepregnancy BMI, race, and study site, 25(OH)D concentrations were not associated with risk of prolonged stage 1 or 2, cesarean delivery, or instrumental delivery. Conclusion Maternal vitamin D status at ≤26 weeks was not associated with risk of prolonged labor or operative delivery in an era with a low cesarean rate.
    Journal of perinatology: official journal of the California Perinatal Association 08/2014; 35(1). DOI:10.1038/jp.2014.139 · 2.07 Impact Factor
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    Erick Forno · Omar M Young · Rajesh Kumar · Hyagriv Simhan · Juan C Celedón ·
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    ABSTRACT: Background and objective: Environmental or lifestyle exposures in utero may influence the development of childhood asthma. In this meta-analysis, we aimed to assess whether maternal obesity in pregnancy (MOP) or increased maternal gestational weight gain (GWG) increased the risk of asthma in offspring. Methods: We included all observational studies published until October 2013 in PubMed, Embase, CINAHL, Scopus, The Cochrane Database, and Ovid. Random effects models with inverse variance weights were used to calculate pooled risk estimates. Results: Fourteen studies were included (N = 108 321 mother-child pairs). Twelve studies reported maternal obesity, and 5 reported GWG. Age of children was 14 months to 16 years. MOP was associated with higher odds of asthma or wheeze ever (OR = 1.31; 95% confidence interval [CI], 1.16-1.49) or current (OR = 1.21; 95% CI, 1.07-1.37); each 1-kg/m(2) increase in maternal BMI was associated with a 2% to 3% increase in the odds of childhood asthma. High GWG was associated with higher odds of asthma or wheeze ever (OR = 1.16; 95% CI, 1.001-1.34). Maternal underweight and low GWG were not associated with childhood asthma or wheeze. Meta-regression showed a negative association of borderline significance for maternal asthma history (P = .07). The significant heterogeneity among existing studies indicates a need for standardized approaches to future studies on the topic. Conclusions: MOP and high GWG are associated with an elevated risk of childhood asthma; this finding may be particularly significant for mothers without asthma history. Prospective randomized trials of maternal weight management are needed.
    Pediatrics 07/2014; 134(2). DOI:10.1542/peds.2014-0439 · 5.47 Impact Factor
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    H. N. Simhan ·

    BJOG An International Journal of Obstetrics & Gynaecology 07/2014; 122(3). DOI:10.1111/1471-0528.12970 · 3.45 Impact Factor
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    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 · 3.73 Impact Factor
  • Christina Scifres · Katie Malczewski · Janet Catov · Hyagriv Simhan ·

    American Journal of Obstetrics and Gynecology 01/2014; 210(1):S138. DOI:10.1016/j.ajog.2013.10.290 · 4.70 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 · 4.70 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 · 4.70 Impact Factor

  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S49. DOI:10.1016/j.ajog.2013.10.106 · 4.70 Impact Factor
  • Alison D Gernand · Hyagriv N Simhan · Steve Caritis · Lisa M Bodnar ·
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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 · 5.18 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 · 6.20 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 · 4.70 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 · 5.23 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 · 5.18 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 · 6.77 Impact Factor
  • Paul D Speer · Timothy Canavan · Hyagriv N Simhan · Lyndon M Hill ·
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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 · 1.91 Impact Factor

Publication Stats

3k Citations
932.74 Total Impact Points


  • 2015
    • University of Pennsylvania
      Filadelfia, Pennsylvania, United States
    • McGill University
      Montréal, Quebec, Canada
  • 2003-2015
    • Magee-Womens Hospital
      • • Department of Obstetrics
      • • Magee-Womens Research Institute
      Pittsburgh, Pennsylvania, United States
    • 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
  • 2012
    • University of California, Irvine
      Irvine, California, United States
  • 2010
    • University of Texas Health Science Center at Houston
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      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
  • 2005
    • Duke University Medical Center
      Durham, North Carolina, United States