Marshall Carpenter

Brown University, Providence, Rhode Island, United States

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Publications (108)962.12 Total impact

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    ABSTRACT: Objective The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. Study Design This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. Results CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. Conclusion Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.
    No preview · Article · Oct 2015 · American Journal of Perinatology
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    ABSTRACT: To evaluate the relationship of maternal antenatal magnesium sulfate (MgSO4) with neonatal cranial ultrasound abnormalities and cerebral palsy (CP). In a randomized trial of MgSO4 or placebo in women at high risk of preterm delivery, up to 3 cranial ultrasounds were obtained in the neonatal period. Images were reviewed by at least 2 pediatric radiologists masked to treatment and other clinical conditions. Diagnoses were predefined for intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly. CP was diagnosed at 2 years of age by standardized neurologic examination. Intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly were all strongly associated with an increased risk of CP. MgSO4 administration did not affect the risk of cranial ultrasound abnormality observed at 35 weeks postmenstrual age or later. However, for the 82% of infants born at <32 weeks gestation, MgSO4 was associated with a reduction in risk of echolucency or echodensity. The reduction in risk for echolucency explained 21% of the effect of MgSO4 on CP (P = .04), and for echodensity explained 20% of the effect (P = .02). MgSO4 given prior to preterm delivery was associated with decreased risk of developing echodensities and echolucencies at <32 weeks gestation. However, this effect can only partially explain the effect of MgSO4 on CP at 2 years of age. ClinicalTrials.gov: NCT00014989. Published by Elsevier Inc.
    Full-text · Article · Aug 2015 · The Journal of pediatrics
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    ABSTRACT: To examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes (GDM) and maternal and perinatal outcomes. A secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were randomized to treatment versus usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal mortality. Other outcomes examined included the frequency of large for gestational age (LGA), birth weight, neonatal intensive care unit admission (NICU), gestational hypertension / preeclampsia and cesarean delivery. The interaction between GA at treatment initiation (stratified as 24-26 weeks, 27 weeks, 28 weeks, 29 weeks, ≥30 weeks) and treatment group (treated vs. routine care), with the outcomes of interest, was used to determine whether GA at treatment initiation was associated with outcome differences. Of 958 women analyzed, those who initiated treatment at an earlier GA did not gain an additional treatment benefit compared to those who initiated treatment at a later GA (p-value for interaction with the primary outcome is 0.44). Similarly, there was no evidence that other outcomes were significantly improved by earlier initiation of GDM treatment (LGA p=0.76; NICU admission p=0.8; cesarean delivery p=0.82). The only outcome that had a significant interaction between GA and treatment was gestational hypertension/preeclampsia (p=0.04), although there was not a clear cut GA trend where this outcome improved with treatment. Earlier initiation of treatment of mild GDM was not associated with stronger effect of treatment on perinatal outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · American journal of obstetrics and gynecology
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    ABSTRACT: Objective The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. Study Design This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight <10th versus ≥10th percentile. Results Weight z-score at 2 years was significantly lower in the <10th than in the ≥10th percentile group (median [interquartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p < 0.001), and remained after adjusting for maternal education (p < 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p < 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p < 0.001 for both), but were not strong (R (2) = 0.04 and 0.02, respectively). Conclusion Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    No preview · Article · Mar 2015 · American Journal of Perinatology
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    ABSTRACT: To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy. We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy. A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) and 17 of 90 monochorionic twins (19.0%). The sensitivity and specificity of sonographic diagnosis of monochorionicity were 81.1% and 96.0%, respectively. In a multivariable analysis, pregnancies with initial sonographic examinations before 14 weeks' gestation were less likely to have misclassified chorionicity than those with sonographic examinations at 15 to 20 weeks (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.23-0.96). For each week increase in gestational age, the odds of misclassification rose by 10% (OR, 1.10; 95% CI, 1.01-1.2). In the multivariable analysis, maternal age, body mass index, parity, and prior cesarean delivery were not associated with sonographic accuracy. Sonography before 20 weeks incorrectly classified chorionicity in 6.4% of twin gestations. Those with first sonographic examinations performed at earlier gestational ages had improved chorionicity diagnosis. © 2013 by the American Institute of Ultrasound in Medicine.
    No preview · Article · Dec 2014 · Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine
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    ABSTRACT: Objective: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). Study design: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. Results: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI. Conclusion: Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.
    No preview · Article · Jun 2014 · American Journal of Perinatology
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    ABSTRACT: CONCLUSIONS: Placental lesions were highly associated with stillbirth compared with live births. All lesions associated with stillbirth were found in live births but often with variations by gestational age at delivery. Knowledge of lesion prevalence within gestational age groups in both stillbirths and live birth controls contributes to an understanding of the association between placental abnormality and stillbirth. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.
    Full-text · Article · Jan 2014 · Obstetrics and Gynecology
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    ABSTRACT: Objective: The aim of the study is to determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children. Study design: Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP, and MPO levels, adverse newborn outcomes, and PTB < 32 weeks of gestational age (GA). Results: Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for GA at delivery and treatment group. No significant associations between CRP or MPO and RDS, CLD, NEC, sepsis, or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (odds ratio, 0.10; 95% confidence interval, 0.02-0.41). No associations between umbilical cord IL-6, CRP, or MPO and MDI < 70 or PDI < 70 were evident. Umbilical cord serum concentrations of IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks of GA. Conclusion: Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for GA at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum was associated with PTB < 32 weeks of GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes.
    No preview · Article · Dec 2013 · American Journal of Perinatology
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    ABSTRACT: 17-alpha hydroxyprogesterone caproate (17-OHPC) 250 mg weekly reduces recurrent spontaneous preterm birth (SPTB) in women with a prior SPTB by 33%. The dose is not based on pharmacological considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-OHPC plasma concentrations and the rate of SPTB in women with singleton gestation. A single blood sample was obtained between 25 and 28 weeks gestation from 315 women with a SPTB who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-OHPC and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-OHPC concentration. There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-OHPC concentration. Plasma concentrations of 17-OHPC ranged from 3.7- 56 ng/ml. Women with plasma concentrations of 17-OHPC in the lowest quartile had a significantly higher risk of spontaneous preterm birth (p= 0.03) and delivered at significantly earlier gestational ages (p = 0.002) than did women in the 2(nd) to 4(th) quartiles. The lowest preterm birth rates were seen when median 17-OHPC concentrations exceeded 6.4 ng/ml. Low plasma 17-OHPC concentration is associated with an increased risk of SPTB. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.
    No preview · Article · Oct 2013 · American journal of obstetrics and gynecology
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    ABSTRACT: OBJECTIVE:: To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24-28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies. METHODS:: Serum samples from women who participated in a clinical trial of 17 α-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestations (2004-2006) were assayed for 25-hydroxyvitamin D concentrations using liquid chromatography tandem mass spectrometry (n=211). Gestational age was determined early in pregnancy using a rigorous algorithm. Preterm birth was defined as delivery of the first twin or death of either twin at less than 35 weeks of gestation. RESULTS:: The mean serum 25-hydroxyvitamin D concentration was 82.7 nmol/L (standard deviation 31.5); 40.3% of women had concentrations less than 75 nmol/L. Preterm birth at less than 35 weeks of gestation occurred in 49.4% of women with 25-hydroxyvitamin D concentrations less than 75 nmol/L compared with 26.2% among those with concentrations of 75 nmol/L or more (P<.001). After adjustment for maternal race and ethnicity, study site, parity, prepregnancy body mass index, season, marital status, education, gestational age at blood sampling, smoking status, and 17 α-hydroxyprogesterone caproate treatment, maternal 25-hydroxyvitamin D concentration of 75 nmol/L or more was associated with a 60% reduction in the odds of preterm birth compared with concentrations less than 75 nmol/L (adjusted odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.8). A similar protective association was observed when studying preterm birth at less than 32 weeks of gestation (OR 0.2, 95% CI 0.1-0.6) and after confounder adjustment. CONCLUSIONS:: Late second-trimester maternal 25-hydroxyvitamin D concentrations less than 75 nmol/L are associated with an increase in the risk of preterm birth in this cohort of twin pregnancies. LEVEL OF EVIDENCE:: II.
    No preview · Article · Jun 2013 · Obstetrics and Gynecology
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    ABSTRACT: Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.
    Full-text · Article · Apr 2013 · PLoS ONE
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    ABSTRACT: OBJECTIVE:: To estimate the associations of change in immune response with preterm delivery, omega-3 supplementation, and fish diet. METHODS:: This was an ancillary study to a randomized trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. In vitro maternal peripheral blood mononuclear leukocyte production of the anti-inflammatory cytokine, interleukin-10, and the proinflammatory cytokine, tumor necrosis factor-α, in response to stimulation with lipopolysaccharide, was measured at 16-22 weeks of gestation (baseline) and again at 25-28 weeks of gestation (follow-up) among women with prior spontaneous preterm birth. Changes in concentrations from baseline to follow-up ([INCREMENT]) were compared separately among groups defined by gestational age category at delivery, fish diet history, and omega-3 compared with placebo treatment assignment with Kruskal-Wallis tests. RESULTS:: Interleukin-10 [INCREMENT] differed by gestational age category among 292 women with paired assays. Concentrations increased less in women delivering between 35 and 36 6/7 weeks of gestation (48.9 pg/mL) compared with women delivering at term (159.3 pg/mL) and decreased by 65.2 pg/mL in women delivering before 35 weeks of gestation (P=.01). Tumor necrosis factor-α Δ also differed by gestational age category among 319 women, but the pattern was inconsistent. Those delivering between 35 and 36 6/7 weeks of gestation exhibited decreased concentrations of tumor necrosis factor-α at follow-up compared with baseline (-356.0 pg/mL); concentrations increased among women delivering before 35 weeks of gestation and those delivering at term, 132.1 and 86.9 pg/mL (P=.03). Interleukin-10 Δ and tumor necrosis factor-α Δ were unaffected by either omega-3 supplementation or fish diet. CONCLUSION:: Recurrent preterm birth was associated with decreased peripheral blood mononuclear leukocyte production of interleukin-10 in response to a stimulus during the second trimester. CLINICAL TRIAL REGISTRATION:: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902. LEVEL OF EVIDENCE:: II.
    No preview · Article · Apr 2013 · Obstetrics and Gynecology
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    ABSTRACT: OBJECTIVE: To estimate the associations of change in immune response with preterm delivery, omega-3 supplementation, and fish diet. METHODS: This was an ancillary study to a randomized trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. In vitro maternal peripheral blood mononuclear leukocyte production of the anti-inflammatory cytokine, interleukin-10, and the proinflammatory cytokine, tumor necrosis factor-α, in response to stimulation with lipopolysaccharide, was measured at 16-22 weeks of gestation (baseline) and again at 25-28 weeks of gestation (follow-up) among women with prior spontaneous preterm birth. Changes in concentrations from baseline to follow-up ([INCREMENT]) were compared separately among groups defined by gestational age category at delivery, fish diet history, and omega-3 compared with placebo treatment assignment with Kruskal-Wallis tests. RESULTS: Interleukin-10 [INCREMENT] differed by gestational age category among 292 women with paired assays. Concentrations increased less in women delivering between 35 and 36 6/7 weeks of gestation (48.9 pg/mL) compared with women delivering at term (159.3 pg/mL) and decreased by 65.2 pg/mL in women delivering before 35 weeks of gestation (P=.01). Tumor necrosis factor-α Δ also differed by gestational age category among 319 women, but the pattern was inconsistent. Those delivering between 35 and 36 6/7 weeks of gestation exhibited decreased concentrations of tumor necrosis factor-α at follow-up compared with baseline (-356.0 pg/mL); concentrations increased among women delivering before 35 weeks of gestation and those delivering at term, 132.1 and 86.9 pg/mL (P=.03). Interleukin-10 Δ and tumor necrosis factor-α Δ were unaffected by either omega-3 supplementation or fish diet. CONCLUSION: Recurrent preterm birth was associated with decreased peripheral blood mononuclear leukocyte production of interleukin-10 in response to a stimulus during the second trimester.
    No preview · Article · Apr 2013 · Obstetrics and Gynecology
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    ABSTRACT: Objective: Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. Methods: Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta. Results: One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P<.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P>.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P>.99). Conclusion: A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low.
    No preview · Article · Dec 2012 · Obstetrics and Gynecology
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    ABSTRACT: OBJECTIVE:: The underlying pathophysiology of preeclampsia is thought to be abnormal trophoblast invasion of the spiral arteries leading to maldevelopment of uteroplacental perfusion. We estimated whether uterine artery Doppler measurements made in the early second trimester would predict the subsequent development of preeclampsia. METHODS:: Uterine artery Doppler measurements before 21 weeks of gestation (median 16.6 weeks) were correlated with subsequent development of preeclampsia in a cohort of 2,188 low-risk nulliparous women in a randomized control trial of antioxidant supplementation for prevention of preeclampsia. Preeclampsia developed in 165 (7.5%) women. RESULTS:: Development of preeclampsia overall was associated with increased resistance index, pulsatility index, a pulsatility index or resistance index multiple of the median at or above the 75th percentile but not the presence of a notch or a bilateral notch before 21 weeks of gestation. The sensitivity was 43% (95% confidence interval [CI] 35-51) and specificity 67% (95% CI 65-69) for prediction of preeclampsia overall. The presence of a notch or bilateral notch, resistance index, and pulsatility index multiple of the median was significantly associated with early onset (before 34 weeks of gestation) compared with late onset or no preeclampsia (odds ratio [OR] 6.9, 95% CI 2.3-20.9; sensitivity 78%, 95% CI 52-94; specificity 66%, 95% CI 64-68). The presence of a notch or resistance index multiple of the median at or above the 75th percentile increased the odds of developing severe compared with mild or no preeclampsia (OR 2.2, 95% CI 1.4-3.7; sensitivity 53%, 95% CI 40-65; specificity 66%, 95% CI 64-68). CONCLUSION:: Our data show poor sensitivity of second-trimester Doppler ultrasound measurements for prediction of preeclampsia overall in a well-characterized, low-risk, nulliparous population. The technique has utility in identifying poor trophoblast invasion of spiral arteries of a magnitude that severely compromises uteroplacental blood flow and gives early-onset disease. LEVEL OF EVIDENCE:: II.
    No preview · Article · Oct 2012 · Obstetrics and Gynecology
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    ABSTRACT: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability. This was a nested case-control analysis of a randomized trial of magnesium sulfate administered to women at imminent risk for early (before 32 weeks) preterm birth for the prevention of death or cerebral palsy in their offspring. We evaluated 21 single-nucleotide polymorphisms (SNPs) in 17 genes associated with neuronal homeostasis, neuroprotection, or oxidative stress in umbilical cord blood. Cases included infant deaths (n=43) and children with cerebral palsy (n=24), mental delay (Bayley Mental Developmental Index less than 70; n=109), or psychomotor delay (Bayley Psychomotor Developmental Index less than 70; n=91) diagnosed. Controls were race-matched and sex-matched children with normal neurodevelopment. Associations between each SNP and each outcome were assessed in logistic regression models assuming an additive genetic pattern, conditional on maternal race and infant sex, and adjusting for study drug assignment, gestational age at birth, and maternal education. The odds of cerebral palsy were increased more than 2.5 times for each copy of the minor allele of vasoactive intestinal polypeptipe (VIP, rs17083008) (adjusted odds ratio 2.67, 95% confidence interval 1.09-6.55, P=.03) and 4.5 times for each copy of the minor allele of N-methyl-D-aspartate receptor subunit 3A (GRIN3A, rs3739722) (adjusted odds ratio 4.67, 95% CI 1.36-16.01, P=.01). The association between the advanced glycosylation end product-specific receptor (AGER, rs3134945) SNP and mental delay was modulated by study drug allocation (P=.02). Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm.
    No preview · Article · Sep 2012 · Obstetrics and Gynecology
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    ABSTRACT: Objective: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action. Study design: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed. Results: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group. Conclusion: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation.
    No preview · Article · Aug 2012 · American journal of obstetrics and gynecology
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    ABSTRACT: To estimate whether there is an association between excessive early gestational weight gain and the development of gestational diabetes mellitus (GDM) and excessive fetal growth. This is a secondary analysis of a randomized controlled trial of vitamins C and E in nulliparous low-risk women. Maternal weight gain from prepregnancy (self-reported) to 15-18 weeks of gestation was measured, and expected gestational weight gain was determined using the Institute of Medicine 2009 guidelines for each prepregnancy body mass index category. Excessive early gestational weight gain was defined as gestational weight gain greater than the upper range of the Institute of Medicine guidelines. Rates of GDM, birth weight greater than 4,000 g, and large for gestational age (LGA, birth weight 90 percentile or higher) were calculated and compared between women with excessive early gestational weight gain and early nonexcessive gestational weight gain (within or below Institute of Medicine guidelines). A total of 7,985 women were studied. Excessive early gestational weight gain occurred in 47.5% of women. Ninety-three percent of women with excessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines. In contrast, only 55% of women with nonexcessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines (P<.001). Rates of GDM, LGA, and birth weight greater than 4,000 g were higher in women with excessive early gestational weight gain. In our population, excessive early gestational weight gain occurred in 93% of women who had total gestational weight gain greater than the Institute of Medicine guidelines. In low-risk nulliparous women, excessive early gestational weight gain is associated with the development of GDM and excessive fetal growth. II.
    Full-text · Article · Jun 2012 · Obstetrics and Gynecology
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    ABSTRACT: To identify clinical characteristics and biochemical markers in first-trimester samples that would possibly predict the subsequent development of preeclampsia. We conducted a multicenter observational study in 2,434 nulliparous women at low risk to identify biomarkers that possibly predict preeclampsia. Clinical history, complete blood count, and biochemical markers were assessed in the first trimester. The trophoblast and angiogenesis markers ADAM-12, pregnancy-associated plasma protein-A, placental protein 13, placental growth factor, soluble fms-like tyrosine kinase-1, and endoglin were measured in a case-control subset of 174 women with preeclampsia and 509 women in the control group. Univariable analysis revealed maternal age, race, marital status, years of education, source of medical payment, prenatal caregiver, body mass index (BMI, calculated as weight (kg)/[height (m)]), and systolic blood pressure at enrollment were significantly associated with preeclampsia. Mean platelet volume was greater at enrollment in women who later had development of preeclampsia (median 9.4 compared with 9.0 femtoliter (fl); P=.02). First-trimester concentrations (multiples of the median) of ADAM-12 (1.14 compared with 1.04; P=.003), pregnancy-associated plasma protein-A (0.94 compared with 0.98; P=.04), and placental growth factor (0.83 compared with 1.04; P<.001) were significantly different in women who had development of preeclampsia compared with women in the control group. The optimal multivariable model included African American race, systolic blood pressure, BMI, education level, ADAM-12, pregnancy-associated plasma protein-A, and placental growth factor, and yielded an area under the curve of 0.73 (95% confidence interval 0.69-0.77) and a sensitivity of 46.1% (95% confidence interval 38.3-54.0) for 80% specificity. A multivariable analysis of clinical data and biochemical markers in the first trimester did not identify a model that had clinical utility for predicting preeclampsia in a nulliparous population at low risk. II.
    Full-text · Article · Jun 2012 · Obstetrics and Gynecology
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    ABSTRACT: The purpose of this study was to estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome. In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, which was defined as a 50-g glucose loading test between 135 and 199 mg/dL and fasting glucose level of <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity. Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI also was associated positively with large-for-gestational-age infants; both maternal BMI and fasting glucose were associated with birthweight z-score and neonatal fat mass. Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birthweight, and neonatal fat mass, independent of OGTT values.
    Full-text · Article · May 2012 · American journal of obstetrics and gynecology

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6k Citations
962.12 Total Impact Points

Institutions

  • 2004-2015
    • Brown University
      • • Department of Obstetrics and Gynecology
      • • Alpert Medical School
      Providence, Rhode Island, United States
  • 2007-2013
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York, New York, United States
  • 2012
    • Drexel University
      Filadelfia, Pennsylvania, United States
  • 2011
    • Tufts University
      Бостон, Georgia, United States
  • 2002-2011
    • The Ohio State University
      • Department of Obstetrics and Gynecology
      Columbus, OH, United States
  • 2010
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maryland, United States
    • University of Utah
      Salt Lake City, Utah, United States
    • Wake Forest University
      Winston-Salem, North Carolina, United States
    • Tufts Medical Center
      Boston, Massachusetts, United States
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
    • George Washington University
      Washington, Washington, D.C., United States
  • 2009
    • University of Tennessee
      • Department of Obstetrics and Gynecology
      Knoxville, Tennessee, United States
  • 2006
    • Geisel School of Medicine at Dartmouth
      Hanover, New Hampshire, United States
    • University of Miami
      • Department of Obstetrics and Gynecology
      كورال غيبلز، فلوريدا, Florida, United States
  • 2005
    • Alpert Medical School - Brown University
      • Department of Obstetrics and Gynecology
      Providence, Rhode Island, United States