John M Thorp

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (312)1502.67 Total impact

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    ABSTRACT: Objective This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks' gestation. Study Design This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death. Results A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups. Conclusion Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.
    American Journal of Perinatology 09/2014; · 1.57 Impact Factor
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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.
    American Journal of Perinatology 06/2014; · 1.57 Impact Factor
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    ABSTRACT: Objective The objective of the article is to describe latency for patients with preterm premature membrane rupture (PPROM) between 240/7 and 316/7 weeks' gestation. Study Design Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than six contractions per hour at enrollment who were candidates for expectant management (n = 1,377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. Results At each week of gestation, median latency between 24 and 28 weeks was similar at approximately 9 days, but it was significantly shorter with PPROM at 29, 30, and 31 weeks (p < 0.001). In addition, the percentage of patients remaining undelivered at 7 days and 14 days was similar for PPROM between 24 and 28 weeks, but it decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to an exponential pattern. Conclusion Median latency after PPROM is similar from 24 to 28 weeks' gestation, but it shortens with PPROM at and after 29 weeks.
    American Journal of Perinatology 05/2014; · 1.57 Impact Factor
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    ABSTRACT: To estimate the frequency of severe maternal morbidity, assess its underlying etiologies, and develop a scoring system to predict its occurrence.Supplemental Digital Content is Available in the Text. This was a secondary analysis of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network cohort of 115,502 women and their neonates born in 25 hospitals across the United States over a 3-year period. Women were classified as having severe maternal morbidity according to a scoring system that takes into account the occurrence of red blood cell transfusion (more than three units), intubation, unanticipated surgical intervention, organ failure, and intensive care unit admission. The frequency of severe maternal morbidity was calculated and the underlying etiologies determined. Multivariable analysis identified patient factors present on admission that were independently associated with severe maternal morbidity; these were used to develop a prediction model for severe maternal morbidity. Among 115,502 women who delivered during the study period, 332 (2.9/1,000 births, 95% confidence interval 2.6-3.2) experienced severe maternal morbidity. Postpartum hemorrhage was responsible for approximately half of severe maternal morbidity. Multiple patient factors were found to be independently associated with severe maternal morbidity and were used to develop a predictive model with an area under the receiver operating characteristic curve of 0.80. Severe maternal morbidity occurs in approximately 2.9 per 1,000 births, is most commonly the result of postpartum hemorrhage, and occurs more commonly in association with several identifiable patient characteristics. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 04/2014; 123(4):804-810. · 4.80 Impact Factor
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    ABSTRACT: Abstract Objective: The anti-oxidant and proangiogenic protein haptoglobin (Hp) is believed to be important for implantation and pregnancy, although its specific role is not known. The three phenotypes (1-1, 2-1 and 2-2) differ in structure and function. Hp 2-2 is associated with increased vascular stiffness in other populations. We examined whether Hp phenotype is associated with abnormal uterine artery Doppler (UAD) in pregnancy. Methods: We conducted a secondary analysis of a preeclampsia prediction cohort nested within a larger placebo-controlled randomized clinical trial of antioxidants for prevention of preeclampsia. We determined Hp phenotype in 2184 women who completed UAD assessments at 17 weeks gestation. Women with notching were re-evaluated for persistent notching at 24 weeks' gestation. Logistic regression was used to assess differences in UAD indices between phenotype groups. Results: Hp phenotype did not significantly influence the odds of having any notch (p = 0.32), bilateral notches (p = 0.72), or a resistance index (p = 0.28) or pulsatility index (p = 0.67) above the 90th percentile at 17 weeks' gestation. Hp phenotype also did not influence the odds of persistent notching at 24 weeks (p = 0.25). Conclusions: Hp phenotype is not associated with abnormal UAD at 17 weeks' gestation or with persistent notching at 24 weeks.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2014; · 1.36 Impact Factor
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    ABSTRACT: Many behaviors and substances have been purported to induce labor. Using data from the Third Pregnancy, Infection, and Nutrition cohort, we focus on 663 women who experienced spontaneous labor. Of the women who reported a specific labor trigger, 32% reported physical activity (usually walking), 24% a clinician-mediated trigger, 19% a natural phenomenon, 14% some other physical trigger (including sexual activity), 12% reported ingesting something, 12% an emotional trigger, and 7% maternal illness. With the exceptions of walking and sexual intercourse, few women reported any one specific trigger, although various foods/substances were listed in the “ingesting something” category. Discussion of potential risks associated with “old wives’ tale” ways to induce labor may be warranted as women approach term.
    Journal of Perinatal Education 01/2014; 23(3).
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    ABSTRACT: Objective The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. Methods We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Results Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Conclusion Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.
    American Journal of Perinatology 12/2013; · 1.57 Impact Factor
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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.
    American Journal of Perinatology 12/2013; · 1.57 Impact Factor
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    ABSTRACT: Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001). (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.
    Drug and alcohol dependence 11/2013; · 3.60 Impact Factor
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    ABSTRACT: We review clinical care issues related to illicit and therapeutic opioid use among pregnant and postpartum women, and outline the major responsibilities of obstetric providers who care for these patients during the antepartum, intrapartum, and postpartum periods.Selected patient management issues are highlighted, and case examples are provided. Securing a strong rapport and trust with these patients is crucial for success in delivering high quality obstetric care and in coordinating services with other specialists as needed. Obstetric providers have an ethical obligation to screen, assess, and provide brief interventions and referral to specialized treatment to patients with drug use disorders. Opioid-dependent pregnant women can often be effectively treated with methadone or buprenorphine. These medications are classified as pregnancy Category C medications by the Food and Drug Administration, and their use in the treatment of opioid-dependent pregnant patients should not be considered "off-label". Except in rare special circumstances, medication-assisted withdrawal during pregnancy should be discouraged due to a high relapse rate. Acute pain management in this population deserves special consideration because opioid-using patients can be hypersensitive to pain and use of mixed opioid-agonist/antagonists can precipitate opioid withdrawal. In the absence of other indications, opioid-using pregnant women do not require more intense medical care than other pregnant patients in order to ensure adequate management and best possible outcomes. Together with specialists in pain and addiction medicine, obstetricians can coordinate comprehensive care for opioid-using pregnant and postpartum women.
    American journal of obstetrics and gynecology 10/2013; · 3.28 Impact Factor
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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.
    American journal of obstetrics and gynecology 10/2013; · 3.28 Impact Factor
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    ABSTRACT: Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes. A cohort of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. Venous thromboembolism occurred too infrequently (0.03%, 95% CI 0.02% - 0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage 2.29% (95% CI 2.20-2.38), peripartum infection 5.06% (95% CI 4.93-5.19), severe perineal laceration at spontaneous vaginal delivery 2.16% (95% CI 2.06-2.27), neonatal composite 2.73% (95% CI 2.63-2.84)). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance.
    American journal of obstetrics and gynecology 07/2013; · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: Lipoproteins are associated with atherogenic and inflammatory processes, and these processes may be related to adverse pregnancy outcomes. We therefore examined whether variations in lipoprotein particle size and concentration are associated with preterm birth (PTB) < 35 weeks' gestation. METHODS: This is a case-control ancillary study to a randomized trial of omega-3 fatty acid supplementation to prevent recurrent PTB. We measured standard lipids and used nuclear magnetic resonance (NMR) spectroscopy to characterize 17 lipoprotein particles from plasma collected at the baseline randomization visit (16-21 weeks gestation) in 128 cases (PTB < 35 weeks' gestation) and 132 term controls. Logistic regression models controlled for study center, race/ethnicity, number of prior PTB, smoking and treatment group, as well as total LDL, HDL and triglyceride concentrations when examining LDLNMR lipoproteins, HDLNMR lipoproteins and VLDLNMR lipoproteins, respectively. RESULTS: Only one of the 17 NMR lipoproteins was associated with recurrent PTB. We observed an increased odds of recurrent PTB of 1.04 (95% CI= 1.01-1.08; p=0.02) per nanometer increase in VLDLNMR particle size and an odds ratio of 3.00 (CI= 1.40-6.43; p=0.005) for the 3(rd) tertile of VLDLNMR particle size compared with the 1(st) tertile. CONCLUSION: In women with prior PTB, variations in mid-pregnancy lipoproteins were not associated with recurrent PTB overall, however the trend observed with VLDLNMR particle size is suggestive that PTB may be amenable to lifestyle, nutritional or pharmacologic interventions.
    American journal of obstetrics and gynecology 06/2013; · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: To estimate a gestational age threshold at which the benefits of treatment with weekly courses of antenatal corticosteroids (ACS) during preterm labor outweigh the risks. STUDY DESIGN: Risk-benefit ratios by gestational age are determined using a Markov microsimulation decision-analysis model with a 1-week cycle length. Single course and multiple (weekly to max of 4) courses of ACS by gestational age of entry (23 to 31 6/7 weeks) are compared. Benefits are composite events (respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia or stillbirth) averted. Risks are small head circumference and small for gestational age. RESULTS: More composite events are averted (benefits) than risks acquired (6:1) when multiple courses of ACS are initiated at 26 weeks' gestation. When multiple courses of ACS are initiated at 29 weeks' gestation, the risk-benefit ratio is 1. Beyond 29 weeks, there is a suggestion of more risk than benefit. CONCLUSION: The model suggests that multiple courses of ACS initiated at less than 29 'weeks' gestation may have increased benefit compared to risks. Further analyses are needed to determine the long term clinical significance of these findings.
    American journal of obstetrics and gynecology 06/2013; · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine whether an individualized growth standard (IS) improves identification of preterm small-for-gestational-age (SGA) neonates at risk of developing moderate/severe cerebral palsy (CP) or death. STUDY DESIGN: Secondary analysis of data from a randomized trial of MgSO4 for prevention of CP or death among anticipated preterm births. Singleton non-anomalous liveborns delivered before 34 weeks' were classified as SGA (< 10th % for their GA) by a population standard (PS) or an IS (incorporating maternal age, height, weight, parity, race/ethnicity, and neonatal gender). The primary outcome was prediction of moderate or severe CP or death by age 2. RESULTS: Of 1588 eligible newborns, 143 (9.4%) experienced CP (N=33) or death (N=110). Forty-four (2.8%) were SGA by the PS and 364 (22.9%) by the IS. All PS-SGA newborns also were identified as IS-SGA. SGA newborns by either standard had a similarly increased risk of CP or death (PS: RR 2.4, 95% CI 1.3-4.3 vs. IS: RR 1.8, 95% CI 1.3-2.5, respectively). The similarity of RRs remained after stratification by MgSO4 treatment group. The IS was more sensitive (36% vs. 6%, p <.001), but less specific (78% vs. 98%, p <.001) for CP or death. ROC curve analysis revealed a statistically lower AUC for the PS, although the ability of either method to predict which neonates would subsequently develop CP or death was poor (PS: 0.55, 95% CI 0.49-0.60 vs. IS: 0.59, 95% CI 0.54-0.64, p<.001). CONCLUSION: An individualized SGA growth standard does not improve the association with, or prediction of, CP or death by age 2.
    American journal of obstetrics and gynecology 06/2013; · 3.28 Impact Factor
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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.
    Obstetrics and Gynecology 06/2013; · 4.80 Impact Factor
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    ABSTRACT: To estimate the relationship between 1-hour 50 g glucose challenge test values and perinatal outcomes. This was a secondary analysis of data from a multicenter treatment trial of mild gestational diabetes mellitus. Women with glucose challenge test values of 135-199 mg/dL completed a 3-hour oral glucose tolerance test. Mild gestational diabetes mellitus was defined as fasting glucose less than 95 mg/dL and two or more abnormal oral glucose tolerance test values: 1-hour 180 mg/dL or more; 2-hour 155 mg/dL or more; and 3-hour 140 mg/dL or more. Our study included untreated women with glucose challenge test values of 135-139 mg/dL and 140-199 mg/dL and a comparison group with values less than 120 mg/dL. Primary outcomes included a perinatal composite (stillbirth, neonatal death, hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, and birth trauma), large for gestational age (LGA, birth weight above the 90 percentile based on sex-specific and race-specific norms), and macrosomia (greater than 4,000 g). There were 436 women with glucose challenge test values less than 120 mg/dL and 1,403 with values of 135 mg/dL or more (135-139, n=135; 140-199, n=1,268). The composite perinatal outcome occurred in 25.6% of those with glucose challenge test values less than 120 mg/dL compared with 21.1% for values of 135-139 mg/dL and 35.3% for values of 140-199 mg/dL. Rates of LGA by group were 6.6%, 6.8%, and 12.4%, respectively. Rates of macrosomia by group were 7.8%, 6.1%, and 12.1%, respectively. Compared with glucose challenge test values less than 120 mg/dL, the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for values of 140-199 mg/dL were 1.48 (1.14-1.93) for the composite outcome, 1.97 (1.29-3.11) for LGA, and 1.61 (1.07-2.49) for macrosomia. For glucose challenge test values of 135-139 mg/dL, adjusted ORs and 95% CIs were 0.75 (0.45-1.21), 1.04 (0.44-2.24), and 0.75 (0.30-1.66), respectively. The subcategories with glucose challenge test values of 140-144 mg/dL and 145-149 mg/dL also were associated with an increase in selected outcomes when compared with those with values less than 120 mg/dL. Glucose challenge test values of 135-139 mg/dL were not associated with adverse outcomes compared with values less than 120 mg/dL; however, glucose challenge test values of 140 mg/dL or more were associated with an increase in odds of the composite perinatal outcome, LGA, and macrosomia. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 06/2013; 121(6):1241-1247. · 4.80 Impact Factor
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    ABSTRACT: OBJECTIVE:: To evaluate pregnancy outcomes according to 2009 Institute of Medicine (IOM) gestational weight gain guidelines. METHODS:: This study is a secondary analysis of a preeclampsia prevention trial among nulliparas carrying singletons. Odds ratios and 95% confidence intervals (adjusted for maternal age, race, smoking, and treatment group) were calculated based on total weight gain below or above the IOM guidelines stratified by prepregnancy body mass index (BMI). The referent group was weight gain within the guidelines. RESULTS:: Of 8,293 pregnancies, 9.5% had weight gain below, 17.5% within, and 73% above IOM guidelines. With excess weight gain, all BMI categories had an increased risk of hypertensive disorders; normal weight and overweight women also had increased risk of cesarean delivery and neonatal birth weight at or above the 90 centile but a decreased risk of weight below the 10 centile. There were no consistent associations with insufficient weight gain and adverse outcomes. CONCLUSION:: Excess weight gain was prevalent and associated with an increased risk of hypertensive disorders, cesarean delivery, and large-for-gestational-age neonates.
    Obstetrics and Gynecology 05/2013; 121(5):969-975. · 4.80 Impact Factor
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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.
    PLoS ONE 04/2013; 8(4):60479-. · 3.53 Impact Factor
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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.
    Obstetrics and Gynecology 04/2013; 121(4):805-811. · 4.80 Impact Factor

Publication Stats

6k Citations
1,502.67 Total Impact Points

Institutions

  • 1989–2014
    • University of North Carolina at Chapel Hill
      • • Department of Obstetrics and Gynecology
      • • Department of Medicine
      • • Department of Health Policy & Management
      • • Department of Anesthesiology
      • • Department of Nutrition
      • • Department of Epidemiology
      North Carolina, United States
  • 2013
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
  • 2012–2013
    • George Washington University
      • Biostatistics Center
      Washington, Washington, D.C., United States
    • University of Texas Medical Branch at Galveston
      • Department of Obstetrics and Gynecology
      Galveston, TX, United States
  • 2006–2013
    • Northwestern University
      • • Division of General Obstetrics and Gynecology
      • • Department of Obstetrics and Gynecology
      Evanston, IL, United States
    • University of Texas Southwestern Medical Center
      • Department of Obstetrics and Gynecology
      Dallas, TX, United States
    • University of North Carolina at Pembroke
      North Carolina, United States
    • University of California, Los Angeles
      • Department of Obstetrics and Gynecology
      Los Angeles, CA, United States
    • University of Chicago
      • Department of Obstetrics & Gynecology
      Chicago, IL, United States
    • Drexel University College of Medicine
      • Department of Obstetrics and Gynecology
      Philadelphia, PA, United States
  • 2009–2012
    • University of Pittsburgh
      • • Department of Obstetrics, Gynecology and Reproductive Sciences
      • • School of Medicine
      • • Division of General Obstetrics and Gynecology
      Pittsburgh, PA, United States
    • Oregon Health and Science University
      • Department of Obstetrics & Gynecology
      Portland, OR, United States
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
    • Centers for Disease Control and Prevention
      • National Center for Chronic Disease Prevention and Health Promotion
      Druid Hills, GA, United States
    • Vanderbilt University
      • Department of Biostatistics
      Nashville, MI, United States
  • 2007–2012
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York City, NY, United States
    • Case Western Reserve University
      • Department of Pathology (University Hospitals Case Medical Center)
      Cleveland, OH, United States
  • 2006–2012
    • University of Alabama at Birmingham
      • Department of Obstetrics and Gynecology
      Birmingham, AL, United States
  • 2005–2012
    • University of Cincinnati
      • Department of Obstetrics and Gynecology
      Cincinnati, OH, United States
    • University of Virginia
      • Department of Obstetrics and Gynecology
      Charlottesville, VA, United States
  • 2011
    • Brown University
      • Department of Obstetrics and Gynecology
      Providence, RI, United States
    • University of Tennessee
      • Department of Obstetrics and Gynecology
      Knoxville, Tennessee, United States
  • 2010–2011
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maryland, United States
  • 2005–2011
    • University of Utah
      • Department of Obstetrics and Gynecology
      Salt Lake City, UT, United States
  • 2004–2011
    • The Ohio State University
      • Department of Obstetrics and Gynecology
      Columbus, OH, United States
    • National Institutes of Health
      • Division of Epidemiology, Statistics and Prevention Research (DESPR)
      Bethesda, MD, United States
    • University of Iowa
      • College of Public Health
      Iowa City, IA, United States
  • 2007–2010
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, MI, United States
  • 2003–2010
    • Wake Forest University
      Winston-Salem, North Carolina, United States
  • 2008–2009
    • University of Toronto
      • Department of Mathematics
      Toronto, Ontario, Canada
    • RTI International
      Durham, North Carolina, United States
    • University of Houston
      Houston, Texas, United States
    • Christiana Care Health System
      Wilmington, Delaware, United States
  • 2005–2008
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 1996–1997
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • Obstetrics and Gynecology
      Hershey, Pennsylvania, United States
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 1994
    • Mission Hospital
      Asheville, North Carolina, United States