Rebecca G Clifton

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

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Publications (14)47.68 Total impact

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    ABSTRACT: We asked, is uric acid as effective as proteinuria at identifying perinatal risk in high-risk women with gestational hypertension? Uric acid was measured in samples obtained ≈4.6 weeks predelivery in 259 women with prior preeclampsia from the National Institute of Child Health and Human Development network study of low-dose aspirin to prevent preeclampsia. Participants were grouped according to the presence/absence of gestational hypertension (H), proteinuria (P), and hyperuricemia (U). Adverse perinatal outcomes were not different between H or U and women with normal values (normal blood pressure, urinary protein, and uric acid [NNN]). Preterm birth was greater in hypertension and proteinuria (HP) and hypertension and hyperuricemia (HU) compared to NNN (relative risk [RR] = 2.4, P = .03 and 3.8, P < .01), respectively. In addition, in HU women, delivery was earlier (36.6 ± 3.4 vs 38.4 ± 2.3 weeks, P < .001) and small for gestational age infants <fifth centile more frequent (RR = 8.2, P = .01) compared to NNN women. This study sought to determine if uric acid is as effective as proteinuria at identifying perinatal risk in high-risk women with gestational hypertension. Our results suggest that hyperuricemia is at least as accurate as proteinuria at identifying perinatal risk in high-risk women with gestational hypertension. © The Author(s) 2015.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2015; DOI:10.1177/1933719115572477 · 2.18 Impact Factor
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    ABSTRACT: Objective Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking.Design/Setting/PopulationA secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9–16 weeks in low-risk nulliparous women with singleton gestations.Methods We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow–Day test for interaction.Main outcome measuresThe trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption.ResultsThere were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00–0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52–1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58–0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90–1.17) (P = 0.046).Conclusion In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.
    BJOG An International Journal of Obstetrics & Gynaecology 12/2014; DOI:10.1111/1471-0528.13201 · 3.86 Impact Factor
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    ABSTRACT: To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1.2 mg/dL or greater, or evidence of hemolysis on peripheral smear. Mild pregnancy-associated hypertension was defined as blood pressure 140-159/90-109 mm Hg. Severe pregnancy-associated hypertension was defined as persistent blood pressure 160/110 mm Hg or greater, acute antihypertensive treatment, or any blood pressure elevation associated with clinical signs of end-organ dysfunction (one or more of headache, epigastric pain, blurred vision, pulmonary edema, eclampsia, or oliguria). Pregnancy outcomes were compared across four groups: I, mild hypertension alone; II, mild hypertension+abnormal laboratory values; III, severe pregnancy-associated hypertension alone; and IV, severe pregnancy-associated hypertension+abnormal laboratory values. Of 9,969 women, 2,752 (27.9%) developed pregnancy-associated hypertension and of these, laboratory abnormalities occurred in 7.3%. Laboratory abnormalities increased with severity of hypertension: mild hypertension alone (4.9%), severe hypertension alone (8.9%), and mild or severe hypertension with clinical signs of end-organ dysfunction (12.2%) (P for trend<.001). Compared with women with mild hypertension alone, the adjusted odds for the perinatal composite (2-fold to 4.8-fold in Category III-IV), preterm birth (2.1-fold to 7.8-fold in Category II-IV), and other adverse perinatal outcomes increase with disease severity, particularly with laboratory abnormalities and severe clinical signs. The frequency of abnormal laboratory values in women with pregnancy-associated hypertension increases with disease severity. Adverse perinatal outcomes increase in the presence of abnormal laboratory values, particularly in those with clinical signs, likely atttributable in part to the decision to deliver early. : II.
    Obstetrics and Gynecology 11/2014; 124(5):933-40. DOI:10.1097/AOG.0000000000000509 · 4.37 Impact Factor
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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; 31(9). DOI:10.1055/s-0033-1358771 · 1.60 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. DOI:10.1097/AOG.0b013e31828aea03 · 4.37 Impact Factor
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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.
    Obstetrics and Gynecology 10/2012; 120(4):815-822. DOI:10.1097/AOG.0b013e31826af7fb · 4.37 Impact Factor
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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.
    Obstetrics and Gynecology 06/2012; 119(6):1227-33. DOI:10.1097/AOG.0b013e318256cf1a · 4.37 Impact Factor
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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.
    Obstetrics and Gynecology 06/2012; 119(6):1234-42. DOI:10.1097/AOG.0b013e3182571669 · 4.37 Impact Factor
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    ABSTRACT: The purpose of this study was to determine whether mid-trimester insulin resistance is associated with subsequent preeclampsia. This was a secondary analysis of 10,154 nulliparous women who received vitamin C and E or placebo daily from 9-16 weeks gestation until delivery. Of these, 1187 women had fasting plasma glucose and insulin tested between 22 and 26 weeks gestation. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index. Obese women were twice as likely to have a HOMA-IR result of ≥75th percentile. Hispanic and African American women had a higher percentage at ≥75th percentile for HOMA-IR than white women (42.2%, 27.2%, and 16.9%, respectively; P < .001). A HOMA-IR result of ≥75th percentile was higher among the 85 nulliparous women who subsequently had preeclampsia, compared with women who remained normotensive (40.5% vs 24.8%; adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Quantitative insulin sensitivity check index results were similar to the HOMA-IR results. Midtrimester maternal insulin resistance is associated with subsequent preeclampsia.
    American journal of obstetrics and gynecology 04/2011; 204(4):327.e1-6. DOI:10.1016/j.ajog.2011.02.024 · 3.97 Impact Factor
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    ABSTRACT: Evaluate association of the inflammatory marker C-reactive protein with recurrent preeclampsia. Serum samples collected longitudinally in women with previous preeclampsia from the Maternal-Fetal Medicine Units Network trial of aspirin to prevent preeclampsia were assayed for CRP. Of 255 women studied, 50 developed recurrence. Baseline C-reactive protein concentration was similar between women who did and did not recur. After adjusting for confounders, neither elevated baseline C-reactive protein nor its change over gestation was associated with recurrence. In this group of women with previous preeclampsia, neither baseline C-reactive protein concentration nor change in concentration over gestation was associated with recurrent preeclampsia.
    Hypertension in Pregnancy 11/2010; 29(4):399-409. DOI:10.3109/10641950903214633 · 1.19 Impact Factor
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    ABSTRACT: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.
    PLoS ONE 10/2010; 5(10):e13270. DOI:10.1371/journal.pone.0013270 · 3.53 Impact Factor
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    ABSTRACT: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.
    PLoS ONE 10/2010; 5(10):e13263. DOI:10.1371/journal.pone.0013263 · 3.53 Impact Factor
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    ABSTRACT: To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth. This is a secondary analysis of a randomized, double-masked, placebo-controlled trial in nulliparous women at low-risk administered 1,000 mg vitamin C and 400 international units vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery. Outcomes include preterm birth attributable to premature rupture of membranes (PROM) and total spontaneous preterm births (spontaneous preterm birth attributable to PROM or spontaneous labor). Of the 10,154 women randomized, outcome data were available for 9,968 (4,992 vitamin group and 4,976 placebo group). A total of 1,038 women (10.4%) delivered preterm, of whom 698 (7.0%) had spontaneous preterm birth. A spontaneous preterm birth occurred in 356 women (7.1%) assigned to daily vitamin C and E supplementation and in 342 (6.9%) assigned to placebo. There were 253 women (2.5%) who delivered after preterm PROM and 445 (4.5%) after a spontaneous preterm labor. In women supplemented with vitamins C and E, births attributed to preterm PROM were similar at less than 37 and 35 weeks of gestation, but births were less frequent before 32 weeks of gestation (0.3% compared with 0.6%, adjusted odds ratio 0.3-0.9). However, total spontaneous preterm births across gestation in women supplemented with vitamins C and E or a placebo were similar. Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135707. I.
    Obstetrics and Gynecology 09/2010; 116(3):653-8. DOI:10.1097/AOG.0b013e3181ed721d · 4.37 Impact Factor
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    ABSTRACT: We compared outcomes for neonates with forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. This is a secondary analysis of a randomized trial in laboring, low-risk, nulliparous women at >or=36 weeks' gestation. Neonatal outcomes after use of forceps, vacuum, and cesarean were compared among women in the second stage of labor at station +1 or below (thirds scale) for failure of descent or nonreassuring fetal status. Nine hundred ninety women were included in this analysis: 549 (55%) with an indication for delivery of failure of descent and 441 (45%) for a nonreassuring fetal status. Umbilical cord gases were available for 87% of neonates. We found no differences in the base excess (P = 0.35 and 0.78 for failure of descent and nonreassuring fetal status) or frequencies of pH below 7.0 (P = 0.73 and 0.34 for failure of descent and nonreassuring fetal status) among the three delivery methods. Birth outcomes and umbilical cord blood gas values were similar for those neonates with a forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. The occurrence of significant fetal acidemia was not different among the three delivery methods regardless of the indication.
    American Journal of Perinatology 06/2010; 27(6):493-9. DOI:10.1055/s-0030-1247605 · 1.60 Impact Factor

Publication Stats

185 Citations
47.68 Total Impact Points

Institutions

  • 2010–2015
    • George Washington University
      • Biostatistics Center
      Washington, Washington, D.C., United States
  • 2012–2014
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York, New York, United States
    • Drexel University
      Filadelfia, Pennsylvania, United States