Faculty Bibliography

OBJECTIVE:To determine if the histology of placental abruption differs by maternal thrombophilia status. STUDY DESIGN/METHODS:This was a multicentre, case-control study of women with abruption and delivering at >or=20 weeks' gestation, collected as part of the ongoing New Jersey-placental abruption study. Women were identified by clinical criteria of abruption. Maternal blood was collected postpartum and tested for anticardiolipin antibodies, and mutations in the Factor V Leiden and prothrombin genes. Cases were comprised of women with an abruption and a positive thrombophilia screen. Controls were comprised of women with an abruption and a negative thrombophilia screen. All placental histology was systematically reviewed by two perinatal pathologists, blinded to the abruption status. RESULTS:A total of 135 women with placental abruption were identified, of which 63.0% (n = 85) had at least one diagnosed maternal thrombophilia. There were increases in the rates of meconium-stained membranes (7.9%vs. 2.1%, p = 0.015) and decidual necrosis (4.5%vs. 2.1%, p = 0.023) when a maternal thrombophilia was diagnosed. Although there was no difference in the overall presence of infarcts between the two groups (27.0%vs. 38.3%, p = 0.064), the presence of an old infarct was more common among women with a positive thrombophilia screen (83.3%vs. 44.4%, p = 0.003). CONCLUSION/CONCLUSIONS:Placental abruption with a positive maternal thrombophilia screen is associated with higher rates of old placental infarcts and decidual necrosis compared with abruption when thrombophilia is not diagnosed. These lesions suggest a chronic etiology of placental abruption in the presence of a maternal thrombophilia.

Folate deficiency and maternal smoking are strong risk factors for placental abruption. We assessed whether the reduced folate carrier [NM_194255.1: c.80A-->G (i.e., p.His27Arg)] (RFC-1) polymorphism was associated with placental abruption, and evaluated if maternal smoking modified the association between plasma folate and abruption. Data were derived from the New Jersey-Placental Abruption Study--a multicenter, case-control study of placental abruption (2002-2007). Maternal DNA was assayed for the RFC-1 c.80A-->G polymorphism using a PCR-dependent diagnostic test. Maternal folate (nmol/l) was assessed from maternal plasma, collected immediately following delivery. Due to assay limitations, folate levels at > or =60 nmol/l were truncated at 60 nmol/l. Therefore, case-control differences in folate were assessed from censored log-normal regression models following adjustment for potential confounders. Distribution of the mutant allele (G) of the RFC-1 c.80A-->G polymorphism was similar between cases (52.3%; n = 196) and controls (50.5%; n = 191), as was the homozygous mutant (G/G) genotype (OR 1.1, 95% CI 0.6-2.2). In a sub-sample of 136 cases and 140 controls, maternal plasma folate levels (mean +/- standard error) corrected for assay detection limits were similar between placental abruption cases (63.6 +/- 5.1 nmol/l) and controls (58.3 +/- 4.7 nmol/l; P = 0.270), and maternal smoking did not modify this relationship (interaction P = 0.169). We did not detect any association between the RFC-1 c.80A-->G polymorphism and placental abruption, nor was an association between plasma folate and abruption risk evident. These findings may be the consequence of high prevalence of prenatal multivitamin and folate supplementation in this population (over 80%). It is therefore not surprising that folate deficiency may be rare and that the RFC-1 c.80A-->G polymorphism is less biologically significant for placental abruption.

PURPOSE OF REVIEW/OBJECTIVE:Fetal growth restriction is a complicated perinatal condition, with multiple causes. It shares common pathophysiologies with other important disorders, such as preeclampsia and abruption. As a group, these conditions associated with ischemic placental disease are responsible for a large percentage of indicated preterm births. The ability to accurately predict, diagnose and manage these pregnancies has significant and far-reaching implications, including potential effects on long-term adult health. RECENT FINDINGS/RESULTS:Placental ischemia is the most common cause of fetal growth restriction. Alterations in placental development are being linked to various angiogenic mediators, which may be of future use in early risk-determination. Until then, the use of ultrasound to accurately diagnose fetal growth restriction and time delivery is the mainstay of management. Research in this area has revealed some commonalities in the deterioration of the growth restricted fetus, but has also indicated that not every affected fetus will follow the same progression in Doppler and other wellbeing parameters. Most importantly, gestational age at delivery is consistently being documented as a critical factor in perinatal morbidity and mortality. SUMMARY/CONCLUSIONS:Fetal growth restriction is a late manifestation of early abnormal placental development. Once abnormal Doppler velocimetry is present, surveillance and timing of delivery should be based on the antepartum test results and on the gestational age.

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.

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.

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.

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.