Lisa Mele

George Washington University, Washington, Washington, D.C., United States

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Publications (24)134.55 Total impact

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    ABSTRACT: Objective To evaluate inadequate gestational weight gain and fetal growth among overweight and obese women (O/O). Study Design Analysis of prospective singleton term pregnancies in which 1053 O/O gained greater (14.4± 6.2 kg) or 188 who either lost or gained <5 kg (1.1± 4.4 kg). Birth weight, fat(FM) and lean mass (LM) were assessed using anthropometry. Small for gestational age (SGA) was defined as < 10thpercentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry. Results There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤ 5 kg was associated with SGA, 18/188 (9.6%) vs. 51/1053 (4.9%); (adjusted OR 2.6, 95% CI 1.4, 4.7; p=0.003). Neonates of women who lost or gained ≤ 5 kg had lower birth weight (3258 ± 443 g vs. 3467 ± 492g, p<0.0001), FM (403±175 vs. 471 ± 193g, p<0.0001), LM (2855±321 vs. 2995 ± 347g, p<0.0001) and smaller length, %FM and head circumference (HC). Adjusting for diabetic status, pre-pregnancy BMI, smoking, parity, study site, gestational age and gender; neonates of women who gained ≤ 5 kg had significantly lower birth weight, LBM, FM, %FM, HC and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained < 5 kg. Conclusion In O/O weight loss or gain < 5 kg is associated with increased risk of SGA and decreased neonatal FM, LM and HC.
    American journal of obstetrics and gynecology 01/2014; · 3.28 Impact Factor
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    ABSTRACT: Objective To evaluate the relationship between gestational age (GA) and induction of labor (IOL) and the rate of cesarean delivery (CD) in women with mild gestational diabetes (GDM). Study Design Secondary analysis of data from a multi-center RCT of mild GDM treatment. CD rate of women delivering at term (> 37 weeks) was evaluated using two complementary approaches: 1) IOL vs. spontaneous labor: women induced at each GA compared with those who spontaneously labored at the same GA, and 2) IOL vs. expectant management: women delivered after IOL at each GA compared with those delivering after spontaneous labor at the same GA or subsequently after spontaneous or induced labor (outcome at each week compared with expectant management at that week). Logistic regression adjusted for potential confounders. Results The overall CD rate was 13%. When compared to 39 weeks (either IOL or spontaneous labor) as the referent, there was no significant difference in the CD rate in women delivered at 37, 38, or 40 weeks. However, IOL was associated with a 3-fold increase in CD rate at 41 weeks and beyond as compared with IOL at 39 weeks. Similarly, there was a 3-fold increase in CD rate in women who were induced when compared to those managed expectantly at 40 completed weeks. Conclusions Induction of labor in women with mild gestational diabetes mellitus (GDM) does not increase the rate of cesarean delivery prior to 40 weeks gestation.
    American journal of obstetrics and gynecology 01/2014; · 3.28 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: 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 assess the relationship between a low 50-g 1-hour glucose loading test (GLT) and maternal and neonatal outcomes in women without diabetes.Study Design This was a secondary analysis of a multicenter observational cohort from a randomized trial of treatment for mild gestational diabetes. Maternal and neonatal outcomes were compared between women with GLT values < 90 mg/dL and those with results 90 to 119 mg/dL.Results Of 436 enrolled women, 297 (68.1%) had a GLT result of 90 to 119 mg/dL and 139 (31.9%) had a result of < 90 mg/dL. There was a lower incidence of neonatal hypoglycemia in those with a GLT < 90 mg/dL (5.7% versus 16.5%, p = 0.006). Other outcomes were not associated with test results.Conclusion A GLT result < 90 mg/dL compared with 90 to 119 mg/dL is associated with a lower risk of neonatal hypoglycemia, but no other significant findings.
    American Journal of Perinatology 12/2012; · 1.57 Impact Factor
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    ABSTRACT: Objective To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM).Study Design Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birth weight percentiles were calculated using ethnicity- and gender-specific population and customized norms (Gardosi).Results Two hundred three (9.8%) and 288 (13.8%) neonates were large for gestational age by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, but neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birth weight percentiles for predicting APOs were poor (area under the receiver operating characteristic curve < 0.6 for six of eight APOs).Conclusion Neither customized nor normalized population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM.
    American Journal of Perinatology 11/2012; · 1.57 Impact Factor
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    ABSTRACT: Abstract Objective: Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods: Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat vs single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR, or infection. Results: Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31=84%) was similar to cases with IUGR or preeclampsia (16/18=89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33=30%) (P<0.001). Conclusions: Placental villous hypermaturation, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB.
    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 11/2012; · 1.36 Impact Factor
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    ABSTRACT: OBJECTIVE:: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance. METHODS:: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use. RESULTS:: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10-2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04-3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18-3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92-2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33-6.60). CONCLUSION:: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. LEVEL OF EVIDENCE:: II.
    Obstetrics and Gynecology 11/2012; 120(5):1099-1104. · 4.80 Impact Factor
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    ABSTRACT: We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender. This is a secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes. Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass (P = .04) and birthweight percentile (P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes. The magnitude of the reduction of a newborn's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates.
    American journal of obstetrics and gynecology 05/2012; 206(5):422.e1-5. · 3.28 Impact Factor
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    ABSTRACT: To compare endothelial nitric oxide synthase expression and capillary density (CDS) in placentas exposed to single or multiple courses of betamethasone. Placental specimens exposed to single vs repeat courses of betamethasone were analyzed through immunohistochemistry and digital image quantification for endothelial nitric oxide synthase and CD34. Quantified endothelial nitric oxide synthase staining, calculated capillary density, ratio of endothelial nitric oxide synthase to capillary density, and clinical characteristics were compared. Linear regression was performed with these as dependent variables. Mean and maximum capillary density were increased (P = .013 and .005) and the ratio of endothelial nitric oxide synthase to capillary density decreased (P = .016) in specimens exposed to 4 courses of betamethasone compared with 1 to 3 courses. Exposure to 4 courses of betamethasone was associated with increased capillary density, but not with endothelial nitric oxide synthase expression. Exposure to 4 courses of betamethasone is associated with increased placental capillary density. The placental effects of multiple courses of betamethasone are unrelated to endothelial nitric oxide synthase expression.
    American journal of obstetrics and gynecology 04/2011; 204(6):545.e11-6. · 3.28 Impact Factor
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    ABSTRACT: To estimate the association between fasting and 2-hour postprandial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes. In this secondary analysis of a multicenter randomized treatment trial of mild gestational diabetes, the median fasting and 2-hour postprandial glucose levels were analyzed in 2-week intervals and change over time (slope) was calculated for women with gestational diabetes (abnormal oral glucose tolerance test) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed. Regression analyses were performed to estimate the relationship between median fasting and postprandial glucose and neonatal fat mass, cord blood C-peptide, birth weight, large-for-gestational-age neonates, macrosomia (greater than 4,000 g), and neonatal hypoglycemia. Among 460 women with gestational diabetes, median fasting (P<.001), postprandial breakfast (P<.001), and postprandial lunch (P<.001) glucose values declined over the treatment period, whereas postprandial dinner values remained stable (P=.83). Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass (1.35; 95% CI 1.09-1.66; P=.006) and elevated C-peptide (1.29; CI 1.09-1.52; P=.003). Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates (1.27; CI 1.05-1.53; P=.01), macrosomia (1.32; CI 1.04-1.65; P = .02), and elevated C-peptide (1.19; CI 1.03-1.38; P=.02). In women treated for mild gestational diabetes, higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia, large-for-gestational age, and elevated C-peptide. II.
    Obstetrics and Gynecology 04/2011; 117(4):819-27. · 4.80 Impact Factor
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    ABSTRACT: We sought to evaluate the interaction between repeated-course antenatal corticosteroids and inflammation gene polymorphisms with neurodevelopmental outcomes at age 2 years. We conducted nested case-control analysis of a randomized controlled trial of single- vs repeated-course antenatal corticosteroids. Cases had mental and/or psychomotor delay at age 2 years. Controls had normal neurodevelopment. Previous analyses of 125 cases and 147 controls identified 4 inflammation gene polymorphisms associated with neurodevelopmental delay at age 2 years. The interaction between repeated-course corticosteroids and the interleukin (IL)-6 -174 genotype with neurodevelopmental delay was significant (P = .046). The IL-6 -174 GG genotype was associated with neurodevelopmental delay at age 2 years in the single-course corticosteroid group (odds ratio, 6.47; 95% confidence interval, 1.86-22.50). Exposure to repeated-course antenatal corticosteroids abrogated this genotype effect (odds ratio, 1.30; 95% confidence interval, 0.48-3.54). Results were unchanged after controlling for potential confounders. Repeated-course antenatal steroids may reduce the increased risk of neurodevelopmental delay at age 2 years associated with IL-6 -174 GG genotype.
    American journal of obstetrics and gynecology 02/2011; 205(1):79.e1-5. · 3.28 Impact Factor
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    ABSTRACT: To examine the relationship between varying degrees of maternal hyperglycemia and pregnancy outcomes. This was a secondary analysis of a treatment trial for mild gestational diabetes including four cohorts: 1) 473 women with untreated mild gestational diabetes; 2) 256 women with a positive 50-g screen and one abnormal oral glucose tolerance test (OGTT) value; 3) 675 women with a positive screen and no abnormal OGTT values; and 4) 437 women with a normal 50-g screen. Groups were compared by test of trend for a composite perinatal outcome (neonatal hypoglycemia, hyperbilirubinemia, elevated cord C-peptide level, and perinatal trauma or death), frequency of large for gestational age neonates, shoulder dystocia, and pregnancy-related hypertension. Three-hour OGTT levels (fasting, 1-, 2-, and 3-hour) levels were divided into categories and analyzed for their relationship to perinatal and maternal outcomes. There were significant trends by glycemic status among the four cohorts for the composite and all other outcomes (P<.001). Analysis for trend according to OGTT categories showed an increasing relationship between fasting and all postload levels and the various outcomes (P<.05). Fasting glucose 90 mg/dL or greater and 1 hour 165 mg/dL or greater were associated with an increased risk for the composite outcome (odds ratios and 95% confidence intervals of 2.0 [1.03–4.15] and 1.46 [1.02–2.11] to 1.52 [1.08–2.15] for the fasting and 1 hour, respectively). A 1 hour glucose 150 mg/dL or greater was associated with an increased risk for large for gestational age (odds ratios, 1.8 [1.02–3.18] to 2.35 [1.35–4.14]); however, 2- and 3-hour glucose levels did not increase the risk for the composite or large for gestational age until well beyond current gestational diabetes diagnostic thresholds. A monotonic relationship exists between increasing maternal glycemia and perinatal morbidity. Current OGTT criteria require reevaluation in determining thresholds for the diagnosis and treatment of gestational diabetes. II
    Obstetrics and Gynecology 02/2011; 117(2 Pt 1):218-24. · 4.80 Impact Factor
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    ABSTRACT: OBJECTIVE: To examine the relationship between varying degrees of maternal hyperglycemia and pregnancy outcomes. METHODS: This was a secondary analysis of a treatment trial for mild gestational diabetes including four cohorts: 1) 473 women with untreated mild gestational diabetes; 2) 256 women with a positive 50-g screen and one abnormal oral glucose tolerance test (OGTT) value; 3) 675 women with a positive screen and no abnormal OGTT values; and 4) 437 women with a normal 50-g screen. Groups were compared by test of trend for a composite perinatal outcome (neonatal hypoglycemia, hyperbilirubinemia, elevated cord C-peptide level, and perinatal trauma or death), frequency of large for gestational age neonates, shoulder dystocia, and pregnancy-related hypertension. Three-hour OGTT levels (fasting, 1-, 2-, and 3-hour) levels were divided into categories and analyzed for their relationship to perinatal and maternal outcomes. RESULTS: There were significant trends by glycemic status among the four cohorts for the composite and all other outcomes (P<.001). Analysis for trend according to OGTT categories showed an increasing relationship between fasting and all postload levels and the various outcomes (P<.05). Fasting glucose 90 mg/dL or greater and 1 hour 165 mg/dL or greater were associated with an increased risk for the composite outcome (odds ratios and 95% confidence intervals of 2.0 [1.03–4.15] and 1.46 [1.02–2.11] to 1.52 [1.08–2.15] for the fasting and 1 hour, respectively). A 1 hour glucose 150 mg/dL or greater was associated with an increased risk for large for gestational age (odds ratios, 1.8 [1.02–3.18] to 2.35 [1.35–4.14]); however, 2- and 3-hour glucose levels did not increase the risk for the composite or large for gestational age until well beyond current gestational diabetes diagnostic thresholds. CONCLUSION: A monotonic relationship exists between increasing maternal glycemia and perinatal morbidity. Current OGTT criteria require reevaluation in determining thresholds for the diagnosis and treatment of gestational diabetes. LEVEL OF EVIDENCE: II
    Obstetrics and Gynecology 01/2011; 117(2, Part 1):218-224. · 4.80 Impact Factor
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    ABSTRACT: Administration of antenatal corticosteroids to women who are at risk for preterm delivery and carry singletons decreases the incidence of respiratory distress syndrome in their prematurely born infants. However, it is unclear whether antenatal corticosteroids decrease the incidence of respiratory distress syndrome in women with multiple gestations. The effect of maternal obesity on the volume of distribution of betamethasone has not been evaluated, and some investigators are concerned that the concentration of drug available to the fetus may be different in an obese mother as compared with a nonobese mother. This study was designed to determine whether the concentration of betamethasone in maternal serum or fetal cord blood differed between singleton and twin pregnancies and between obese and nonobese women. Data were obtained from analysis of biological fluids collected within a randomized, double-blinded, placebo-controlled clinical trial. All participants receiving weekly doses of betamethasone were identified. Univariate analysis was used to compare betamethasone concentrations in singleton versus twin gestations and in obese (body mass index, <30 kg/m2) versus normal weight (body mass index, <30 kg/m2) women. A total of 100 samples were analyzed (45 cord blood and 55 maternal blood). In univariate analysis, there was a significant increase in median cord blood betamethasone concentrations among twin gestations (4.4 ng/mL, interquartile range [IQR], 2.5–8.2, vs. singletons, 1.4 ng/mL; IQR, 1.0–3.0 [P = 0.002]) and a nonsignificant increase in median maternal serum betamethasone concentrations among obese (5.0 ng/mL; IQR, 2.7–7.6) versus nonobese (4.3 ng/mL; IQR, 3.0–6.1) women (P = 0.74). However, after adjustment for possible confounders, no differences were noted in concentrations of betamethasone in maternal serum and cord blood between singletons and twins or between nonobese and obese women. These findings fail to support that there is a significant association between serum betamethasone concentrations and either plurality or obesity.
    Obstetrical and Gynecological Survey 12/2010; 66(1):1-2. · 2.51 Impact Factor
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    ABSTRACT: Our objective was to assess the effects of repeated antenatal corticosteroid treatments on the neonatal auditory brainstem response (ABR), a sensitive measure of neonatal brain maturity and auditory function. To achieve this, we performed and blindly evaluated neonatal ABRs on a subset of infants delivering within a multicenter randomized placebo-controlled clinical trial comparing single versus repeated courses of antenatal corticosteroid treatments for women at 23-31 weeks gestation who remained at increased risk for preterm birth. The women were randomly assigned to either the single or the repeated antenatal corticosteroid treatment group. Women in the repeated antenatal corticosteroid group received weekly antenatal corticosteroid treatments until 34 weeks gestation or until they reached a study-determined limited number of courses, whereas women in the single antenatal corticosteroid group received an initial course of corticosteroid followed by weekly placebo injections. We performed ABR testing on their infants prior to discharge. The latencies of waves I, III and V and the peak-to-trough amplitudes of waves I and V were compared between those in the single (n=27) and repeated antenatal corticosteroid treatment (n=24) groups. The majority of repeated antenatal corticosteroid infants (20 of 24) were exposed to ≥ 4 antenatal corticosteroid treatments. Even though gestational age was similar between our subset of single and repeated antenatal corticosteroid treatment groups, infant birth weight and length and head circumference were significantly smaller in the repeated antenatal corticosteroid group (p <0.05). Despite these differences in birth sizes, there were no significant group differences in the ABR wave latencies or amplitudes. We concluded that our repeated antenatal corticosteroid treatments, in comparison to a single treatment, did not significantly benefit or harm the neonatal ABR despite significant effects on birth size.
    Neurotoxicology and Teratology 11/2010; 32(6):605-10. · 3.18 Impact Factor
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    ABSTRACT: Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect medication distribution volume. We evaluated whether maternal or neonatal cord betamethasone concentrations differed in twin gestations or obese patients. Participants receiving betamethasone in a randomized controlled trial of weekly ACS were identified. We analyzed maternal delivery and cord serum betamethasone concentrations comparing singletons with twins and obese (BMI > or =30 kg/m(2)) with nonobese women. Fifty-five maternal and 45 cord blood samples were available. Unadjusted median maternal serum concentrations appeared paradoxically higher in both twin gestations and the obese. However, after controlling for confounders, there were no differences in betamethasone concentrations in maternal serum or cord blood between singletons and twins (P = .61 vs P = .14) or nonobese and obese women (P = .67 vs .12). Maternal and umbilical cord blood serum betamethasone concentrations are not different in twin gestations or obese women.
    American journal of obstetrics and gynecology 09/2010; 203(3):219.e1-5. · 3.28 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the association between fetal inflammation and coagulation gene single-nucleotide polymorphisms (SNPs) and neurodevelopmental delay at age 2 years. We conducted a case-controlled secondary analysis of a randomized trial of single- vs multiple-course corticosteroids. Multiplex assay assessed 46 SNPs. Cases had mental developmental and/or psychomotor delay at age 2 years. Control subjects had normal neurodevelopment. One hundred twenty-five cases and 147 control subjects were analyzed. Allele frequencies were different between cases and control subjects for interleukin (IL)1beta-511 (P = .009), IL4R-148 (P = .03), IL6-174 (P = .02), and IL6-176 (P = .007). Genotype frequencies were different for IL1beta-511 (P = .03) and IL6-174 (P = .04). Results for IL1beta-511, IL4R-148, and IL6-176 remained significant after logistic regression analysis. IL1beta-511 and IL6-176 minor alleles were associated with increased risk of neurodevelopmental delay (odds ratio, 3.1; 95% confidence interval [CI], 1.2-8.2 and 2.2; 95% CI, 1.2-3.9, respectively). IL4R-148 minor allele was protective (odds ratio, 0.6; 95% CI, 0.4-0.9). Fetal SNPs in IL1beta, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years.
    American journal of obstetrics and gynecology 07/2010; 203(1):83.e1-83.e10. · 3.28 Impact Factor
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    ABSTRACT: Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.
    American Journal of Perinatology 03/2010; 27(8):631-40. · 1.57 Impact Factor
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    ABSTRACT: To estimate the effect of single and recurrent doses of antenatal corticosteroids on fetal bone metabolism. This was a secondary analysis of a cohort of pregnant women from a previously reported randomized, placebo-controlled, multicenter trial of women at risk for preterm delivery who received weekly courses of betamethasone (active) or placebo after an initial course of corticosteroids. Umbilical cord serum levels of carboxy-terminal carboxy-terminal propeptide of type I procollagen and cross-linked carboxy-terminal telopeptide of type I procollagen were measured to assess the rate of fetal bone formation and resorption, respectively. Analysis was stratified according to number of repeat antenatal study courses of betamethasone or placebo (one to three compared with at least four courses, not including the initial course). Of the 251 umbilical cord serum samples, the median serum carboxy-terminal telopeptide of type I procollagen levels, but not carboxy-terminal propeptide of type I procollagen levels, was significantly lower with repeat betamethasone exposure (55.0 compared with 57.9 micrograms/L, P=.01). In the fetuses exposed to at least four repeat study courses, there was a significant decrease in median carboxy-terminal telopeptide of type-I procollagen levels between repeat betamethasone exposure and placebo (53.4 compared with 58.6 micrograms/L, respectively, P=.04), but there was no difference between groups in the fetuses exposed to 1-3 repeat study courses (57.4 compared with 56.7 micrograms/L, respectively, P=.29). Levels of umbilical cord serum markers of bone resorption but not formation are reduced in fetuses exposed to repeat courses of antenatal betamethasone. Up to four courses of antenatal betamethasone do not seem to affect fetal bone metabolism. II.
    Obstetrics and Gynecology 08/2009; 114(1):38-44. · 4.80 Impact Factor

Publication Stats

234 Citations
134.55 Total Impact Points

Institutions

  • 2010–2014
    • George Washington University
      • Biostatistics Center
      Washington, Washington, D.C., United States
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York City, NY, United States
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, MI, United States
  • 2012
    • Society for Maternal-Fetal Medicine
      Detroit, Michigan, United States
    • University of Texas Medical Branch at Galveston
      • Department of Obstetrics and Gynecology
      Galveston, TX, United States
  • 2011
    • The Ohio State University
      • Department of Obstetrics and Gynecology
      Columbus, OH, United States
  • 2009
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
  • 2008
    • University of Houston
      Houston, Texas, United States