Faculty Bibliography

OBJECTIVE:The purpose of this study was to evaluate whether the increased risk of placental abruption among women with chronic hypertension is modified by ischemic placental disease, specifically pregnancy-induced hypertension (PIH) and fetal growth restriction (FGR). STUDY DESIGN/METHODS:We used the US linked natality and fetal death data files (1995-2002) and restricted the analysis to women who had a singleton birth at > or = 22 weeks of gestation and to fetuses who weighed > or = 500 g (n = 30,189,949). Fetal growth was defined both on a continuum (<1, 1-2, 3-4, 5-9, 10-19, ..., > or = 90) and as birthweight of < 10th percentile for gestational age (FGR) or birthweight of > 90th percentile (large for gestational age [LGA]). All analyses were adjusted for potential confounding factors through multivariable logistic regression. RESULTS:Rates of abruption among women with and without chronic hypertension were 15.6 and 5.8 per 1000 pregnancies, respectively (relative risk [RR], 2.4; 95% CI, 2.3, 2.5). In comparison with normotensive women with appropriately grown babies (ie, 10th-90th percentile), the association between chronic hypertension and abruption was modified in the presence of FGR (RR, 3.8; 95% CI, 3.6, 4.1) and PIH (RR, 7.7; 95% CI, 6.6, 8.9). However, the highest risk was seen among women with chronic hypertension, PIH, and LGA (RR, 9.0; 95% CI, 7.2, 11.3). A dose-response relationship was observed between the risk of abruption and fetal growth (assessed on a continuum), with the risk being lowest among LGA babies. CONCLUSION/CONCLUSIONS:The association between chronic hypertension and abruption is strong; ischemic placental disease (PIH and FGR) modified this relationship. These findings suggest an etiologic relationship between abruption and chronic placental disease. Chronic hypertension, if associated with LGA, is not associated with abruption; however, chronic hypertension with superimposed PIH accompanied by LGA is associated with significantly increased risk.

Fetal growth restriction can result from a variety of intrinsic or extrinsic insults, resulting from maternal, fetal, and placental factors. Determining the underlying cause of poor fetal growth can be difficult but is essential for assessing potential risks for future pregnancies. Importantly, recurrence risks greatly depend on these underlying conditions. Understanding these risks can allow more appropriate patient counseling and may influence management strategies to optimize future pregnancies.

To examine disparities in risk factors for stillbirths and its occurrence in the antepartum versus intrapartum periods. A population-based, cross-sectional study using data on women that delivered singleton births between 20 and 43 weeks in Missouri (1989-1997) was conducted (n = 626,883). Hazard ratios and 95% confidence intervals were derived from regression models and population attributable fractions were estimated to examine the impact of risk factors on stillbirth. Among African Americans, risks of antepartum and intrapartum stillbirth were 5.6 and 1.1 per 1,000 singleton births, respectively; risks among whites were 3.4 and 0.5 per 1,000 births, respectively. Maternal age > or = 35 years, lack of prenatal care, prepregnancy body mass index (BMI) > or = 30 kg/m2, and prior preterm or small-for-gestational age birth were significantly associated with increased risk for antepartum stillbirth among whites, but not African Americans. BMI < or = 18.5 kg/m2 was associated with antepartum and intrapartum stillbirth among African Americans, but not whites. The presence of any congenital anomaly, abruption, and cord complications were associated with antepartum stillbirth in both races. Premature rupture of membranes was associated with intrapartum stillbirth among whites and African Americans, but intrapartum fever was associated with intrapartum stillbirth among African Americans. These risk factors were implicated in 54.9% and 19.7% of antepartum and intrapartum stillbirths, respectively, among African American women, and in a respective 46.6% and 11.9% among white women. Considerable heterogeneity in risk factors between antepartum and intrapartum stillbirths is evident. Knowledge on timing of stillbirth specific risk factors may help clinicians in decreasing antepartum and intrapartum stillbirth risks through monitoring and timely intervention.

OBJECTIVES/OBJECTIVE:Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A-->G; I22M) and BHMT (742G-->A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes. METHODS:Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)-an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases (n=196), and controls (n=191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms. RESULTS:Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association. CONCLUSIONS:In this population, there was an association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.

OBJECTIVES/OBJECTIVE:We examined age, period, and cohort (APC) effects on temporal trends in stillbirths among Black and White women in the United States. METHODS:We conducted a cohort study of Black and White women who delivered a singleton live-born or stillborn infant during 1981 through 2000. We analyzed stillbirth rates at 20 or more weeks of gestation within 7 age groups, 4 periods, and 10 "central" birth cohorts after adjusting for confounders. RESULTS:In both racial groups, women younger than 20 years or 35 years or older were at increased risk of stillbirth; risks decreased over successive periods in all age groups. Birth cohort had no impact on stillbirth trends among Blacks and only a small, nonsignificant effect among Whites. Analyses of various APC combinations showed that Blacks were at a 1.2- to 2.9-fold increased risk for stillbirth relative to Whites. Attributable fractions for stillbirth because of age, period, and cohort effects were 16.5%, 24.9%, and 0.1%, respectively, among Black women and 14.5%, 36.2%, and 2.1%, respectively, among White women. CONCLUSIONS:Strong effects of age and period were observed in stillbirth trends, but these factors do not explain the persistent stillbirth disparity between Black and White women.

OBJECTIVE:This study was undertaken to determine whether the expression of extracellular matrix components (ECM) is altered in the umbilical arteries from preterm fetal growth-restricted (FGR) pregnancies. STUDY DESIGN/METHODS:Preterm pregnancies with FGR were compared with appropriately grown preterm pregnancies. Umbilical artery messenger RNA (mRNA) levels for fibrillar collagens I and III, nonfibrillar collagen XIV, and decorin were determined by using relative reverse transcriptase polymerase chain reaction (RT-PCR). The mRNA expression was compared between cases and controls by using the Student t test. P < or = .05 was considered significant. RESULTS:Eight FGR cases and 5 control pregnancies were analyzed. Mean counts per minute (cpm) +/- SEM for collagen I and collagen III were increased in FGR pregnancies. There were no differences in mRNA expression of collagen XIV or decorin. CONCLUSION/CONCLUSIONS:Increased mRNA expression of collagen I and III, but not collagen XIV or decorin, is found in the umbilical arteries of preterm FGR pregnancies.

While examination of causes for trends in smoking have largely focused on how changes have occurred with maternal age and, less commonly, time period, little is known as to how age, period and birth cohort interact on trends in the prevalence of smoking during pregnancy. We performed a population-based, retrospective cohort study based on the vital statistics records comprised of White (n=24,499,629) and Black (n = 5,096,625) women delivering in the United States in 1990-99. Smoking prevalence rates were derived by seven 5-year maternal age groups (15-19 to 45-49 years), two time periods (1990-94 and 1995-99), and eight 5-year maternal birth cohorts (1945-49 to 1980-84) after adjusting for the confounding effects of gravidity, education, marital status, and lack of prenatal care through multivariable logistic regression models. The prevalence of smoking was 17.3% among Whites, and 13.5% among Blacks, with substantial variations by age, time period, and birth cohort. The rate declined with increasing age among Whites during the 1990-94 and 1995-99 periods. Among Blacks, the rates increased steeply with advancing age up to 25-29 years and began to decline thereafter. Smoking rates declined among both Whites and Blacks with increasing birth cohort within each age strata. These rates were highest among multigravid women (gravida > or = 2), and lowest among primigravid women. The rates among Whites declined with increasing maternal age for each gravida. Among Blacks, smoking rates for each gravida increased with advancing age up to 25-29 years, and plateaued among older women. Variation in smoking prevalence by age, time period, and birth cohort provides impetus for designing interventions to reduce smoking. Such studies should not only consider cross-sectional trends, but also the divergent patterns by age and cohort among women of different race/ethnic groups and gravidity.

OBJECTIVE:To determine whether differences in the clinical entities of HELLP syndrome and severe preeclampsia are associated with different placental lesions. STUDY DESIGN/METHODS:This was a case control study of singleton pregnancies with HELLP syndrome or severe preeclampsia. Archived pathology slides were retrieved and reviewed. Clinical and histopathological features were compared between the two groups. RESULTS:There were 31 women with HELLP syndrome and 56 with severe preeclampsia. HELLP syndrome was associated with epigastric pain and higher levels of LDH, bilirubin, liver enzymes and fibrin degradation products. Hemoglobin, hematocrit and platelet counts were lower. Abruption lesions of the placenta were less common with HELLP syndrome (Odds Ratio 0.1 95% Confidence Interval 0.01,0.8). None of the other 22 placental features examined were different between the two conditions. CONCLUSION/CONCLUSIONS:The significant overlap between HELLP syndrome and severe preeclampsia for both clinical and placental features suggests that the two conditions represent a spectrum of essentially the same pathophysiologic process.