Tanya K. Sorensen

Recreational Physical Activity During Pregnancy and Risk of Preeclampsia

Abstract— The potential benefits and risks of physical activity before and during pregnancy are not well studied. We studied the relation between recreational physical activity and the risk of preeclampsia in a case‐control study of 201 preeclamptic and 383 normotensive pregnant women. Participants provided information about the type, intensity, frequency, and duration of physical activity performed during the first 20 weeks of pregnancy and during the year before pregnancy. Women who engaged in any regular physical activity during early pregnancy, compared with inactive women, experienced a 35% reduced risk of preeclampsia (odds ratio, 0.65; 95% confidence interval [CI], 0.43 to 0.99). Compared with inactive women, those engaged in light or moderate activities (ie, activities with metabolic‐equivalent scores <6) experienced a 24% reduced risk of preeclampsia (95% CI, 0.48 to 1.20). The corresponding reduction for women participating in vigorous activities (metabolic equivalent scores >=6) was 54% (95% CI, 0.27 to 0.79). Brisk walking (average walking pace >=3 mi/h), when compared with no walking at all, was associated with a 30% to 33% reduction in preeclampsia risk. Stair climbing was inversely associated with the risk of preeclampsia (P for trend=0.039). Recreational physical activity performed during the year before pregnancy was associated with similar reductions in preeclampsia risk. These data suggest that regular physical activity, particularly when performed during the year before pregnancy and during early pregnancy, is associated with a reduced risk of preeclampsia.

Placental microRNA expression in pregnancies complicated by preeclampsia

OBJECTIVE The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments. STUDY DESIGN Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Student t test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs. RESULTS Eight miRNAs were differentially expressed (1 up-regulated and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31 cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and signaling. CONCLUSION Expression of miRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.

Correlates of recreational physical activity in early pregnancy

Objective: Despite the well-documented benefits of a physically active lifestyle, over 25% of American adults report that they never engage in regular recreational physical activity. Little is known about the determinants of physical activity among pregnant women. We investigated the predictors of physical activity in 386 normotensive pregnant women. Methods: Participants provided information about the type, frequency and duration of each physical activity performed during the first 20 weeks of pregnancy. We calculated odd ratios (OR) for active compared with inactive women using logistic regression models. Results: Approximately 61% of women reported participating in some regular physical activity during pregnancy. Walking, swimming, gardening and jogging were the most common activities. Physical activity as an adolescent (OR 4.0) and during the year before pregnancy (OR 48.9) were the strongest predictors of physical activity in pregnancy. Active women who continued to exercise during pregnancy decreased the average intensity of their exercise and the weekly duration of exercise compared with the year before pregnancy. Nulliparas were twice as likely to engage in physical activity as compared with multiparas. Education and income were positively related with physical activity. Non-White women were 40-60% less likely to engage in physical activity as compared with White women. Smokers were also less likely to engage in physical activity. High protein intake was positively associated with physical activity, while the opposite was true for high carbohydrate intake. Conclusions: The identification of determinants of physical activity in pregnancy has important implications for developing strategies aimed at promoting a physically active lifestyle among young women.

Elevated second-trimester human chorionic gonadotropin and subsequent pregnancy-induced hypertension

OBJECTIVE Pregnancy-induced hypertension is believed to be a disorder of the vascular endothelium, possibly focused in the placenta. Markers such as cellular fibronectin appear early in patients in whom pregnancy-induced hypertension develops. We hypothesized that patients with elevated second-trimester levels of human chorionic gonadotropin would have an increased risk for pregnancy-induced hypertension. STUDY DESIGN We conducted a cohort study, using a database of patients undergoing second-trimester serum screening for Down syndrome and who were delivered at our institution between January 1990 and August 1991. We included all 180 women with human chorionic gonadotropin levels > or = 2.0 multiples of the median. A sequential sample of 369 women with levels < 2.0 multiples of the median served as the referent group. Standard American College of Obstetricians and Gynecologists definitions of pregnancy-induced hypertension and proteinuria were used. RESULTS Patients with elevated human chorionic gonadotropin levels were at increased risk for pregnancy-induced hypertension (risk ratio 1.7, 95% confidence interval 1.2 to 2.4) and proteinuric pregnancy-induced hypertension (risk ratio 5.1, 95% confidence interval 1.6 to 16.2). Adjusting for potential confounding factors did not alter these associations. CONCLUSIONS Patients with elevated human chorionic gonadotropin appear to be at higher risk of pregnancy-induced hypertension and proteinuric pregnancy-induced hypertension. Second-trimester human chorionic gonadotropin levels should be further investigated as a potential marker for pregnancy-induced hypertension.

Elevated Second-Trimester Serum Homocyst(e)ine Levels and Subsequent Risk of Preeclampsia

Objective: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. Study Design: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3,042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. Results: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels ≥5.5 μmol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3.2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1.1–9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1–14.1; p = 0.003). Women with a higher prepregnancy body mass index (≥21.4 kg/m2, or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4–32.1; p = 0.016). Conclusion: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.

Maternal pre-pregnancy overweight status and obesity as risk factors for cesarean delivery

Objective. To determine the extent to which, if at all, maternal pre-pregnancy adiposity and other anthropometric factors are related to risk of cesarean delivery. Methods. This hospital-based prospective cohort study included 738 nulliparous women who initiated prenatal care prior to 16 weeks gestation. Participants provided information about their pre-pregnancy weight and height and other sociodemographic and reproductive covariates. Labor and delivery characteristics were obtained from maternal and infant medical records. Risk ratios (RR) and 95% CI were estimated by fitting generalized linear models. Results. The proportion of cesarean deliveries in this population was 26%. Women who were overweight (BMI 25.00–29.99 kg/m2) were twice as likely to deliver their infants by cesarean section as lean women (BMI < 20.00 kg/m2) (RR = 2.09; 95% CI 1.27–3.42). Obese women (BMI ⩾ 30.00 kg/m2) experienced a three-fold increase in risk of cesarean delivery when compared with this referent group (RR = 3.05; 95% CI 1.80–5.18). The joint association between maternal pre-pregnancy overweight status and short stature was additive. When compared with tall (height ⩾ 1.63 m), lean women, short ( < 1.63 m), overweight (BMI ⩾ 25.00 kg/m2) women were nearly three times as likely to have a cesarean delivery (RR = 2.79; 95% CI 1.72–4.52). Conclusion. Our findings suggest that nulliparous women who are overweight or obese prior to pregnancy, and particularly those who are also short, have an increased risk of delivering their infants by cesarean section.

Family History of Hypertension and Type 2 Diabetes in Relation to Preeclampsia Risk

Abstract—In a case-control study of 190 preeclamptic patients and 373 control subjects, we assessed maternal family history of chronic hypertension and type 2 diabetes in relation to preeclampsia risk. Participants provided information on first-degree family history of the 2 conditions and other covariates during postpartum interviews. Logistic regression was used to estimate odds ratios and 95% confidence intervals adjusted for confounding by age, race, and obesity. Compared with women with no parental history of hypertension, women with maternal only (odds ratio=1.9), paternal only (odds ratio=1.8), or both maternal and paternal history of hypertension (odds ratio=2.6) had a statistically significant increased risk of preeclampsia. The odds ratio for women with at least one hypertensive parent and a hypertensive sibling was 4.7 (95% confidence interval, 1.9 to 11.6). Both maternal only (odds ratio=2.1; 95% confidence interval, 0.9 to 4.6) and paternal only (odds ratio=1.9; 95% confidence interval, 1.0 to 3.2) history of diabetes was associated with an increased risk of preeclampsia. Women with a diabetic sibling had a 4.7-fold increased risk of preeclampsia (95% confidence interval, 1.1 to 19.8). For women with at least one hypertensive parent and at least one diabetic parent, relative to those with parents with neither diagnosis, the odds ratio for preeclampsia was 3.2 (95% confidence interval, 1.6 to 6.2). Our results are consistent with the thesis that family history of hypertension and diabetes reflects genetic and behavioral factors whereby women may be predisposed to an increased preeclampsia risk.

Preeclampsia risk in relation to maternal mood and anxiety disorders diagnosed before or during early pregnancy.

BACKGROUND Mood and anxiety disorders are common, debilitating psychiatric illnesses that disproportionally affect women of childbearing age. Relatively few studies have evaluated the extent to which, if at all, maternal mood and anxiety disorders are risk factors for preeclampsia, and results from available studies are inconsistent. We examined the risk of preeclampsia in relation to maternal medical history of mood and anxiety disorders. METHODS We used data from a cohort study of 2,601 pregnant women. Maternal pregestational and early pregnancy (before completion of 20 weeks gestation) psychiatric diagnoses were ascertained from medical records. Generalized linear regression procedures were used to derive relative risk (RR) estimates and 95% confidence intervals (CIs). RESULTS A positive history of maternal mood or anxiety disorder was associated with a 2.12-fold increased risk of preeclampsia after adjustment for age, race/ethnicity, and pre-pregnancy body mass index (95% CI 1.02-4.45). The risk of preeclampsia appeared to be more strongly related with maternal mood or anxiety disorders first diagnosed during the index pregnancy (adjusted RR = 3.64; 95% CI 1.13-11.68). The corresponding RR for maternal mood and anxiety disorders diagnosed before pregnancy was 1.73 (95% CI 0.71-4.20). CONCLUSIONS Maternal mood and anxiety disorders are associated with increased preeclampsia risk. These observations must be explored in larger pharmacoepidemiological studies that allow precise evaluations of independent and joint effects of maternal psychopathologies and the use of psychotropic medications on preeclampsia risk.

Influence of pre-eclampsia on fetal growth.

Objective: We examined the effect of pre-eclampsia on fetal growth in a cohort of pregnant women delivering singleton infants. Methods: Analyses were restricted to 155 women with pre-eclampsia and 5570 normotensive women. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. We estimated ORs for very low birth weight (VLBW; < 1500 g), low birth weight (LBW ; < 2500 g), and small for gestational age (SGA; weight ≤ 10th centile by each gestational age, race, sex and parity strata) in relation to maternal pre-eclampsia status. Results: After adjusting for maternal age, race, smoking, Medicaid status and gestational age, the OR for VLBW was 30.7 (95% CI 7.0-134.9). Pre-eclampsia was associated with a 3.8-fold increased risk of LBW (95% CI 1.9-7.5). Women with pre-eclampsia were 3.6 times more likely to deliver an SGA newborn as compared with normotensive women (95% CI 2.3-5.7). Advanced maternal age, African-American race, parity or smoking status did not modify the associations of pre-eclampsia with LBW and SGA. Conclusions: Our results are consistent with other reports that have documented a strong relationship between pre-eclampsia and restricted fetal growth. Further, our results expand the literature by documenting a particularly strong association between pre-eclampsia and VLBW. However, our findings regarding the relationship between pre-eclampsia and fetal growth may be confounded by unmeasured factors including maternal weight prior to pregnancy and pregnancy weight gain.

Vitamin C and the risk of preeclampsia-results from dietary questionnaire and plasma assay

Background. Oxidative stress plays an important role in the pathophysiology of preeclampsia. Methods. In a case-control study of 109 women with preeclampsia and 259 controls, maternal dietary and plasma vitamin C in relation to preeclampsia risk were assessed. Dietary intake during the periconceptional period and pregnancy was ascertained using a semiquantitative food frequency questionnaire. Logistic regression procedures were used to derive odds ratios (OR) and 95% confidence intervals (CI). Plasma ascorbic acid was determined using automated enzymatic procedures. Results. After adjusting for maternal age, parity, prepregnancy body mass index, and energy intake, women who consumed <85 mg of vitamin C daily (below the recommended dietary allowance), as compared with others, experienced a doubling in preeclampsia risk (OR = 2.1; 95% CI = 1.1–3.9). The OR for extreme quartiles of plasma ascorbic acid (<42.5 vs ≥ 63.3 &mgr;mol/liter) was 2.3 (95% CI = 1.1–4.6). Compared with women in the highest quartile, those with plasma ascorbic acid <34.6 &mgr;mol/liter (lowest decile) experienced a 3.8-fold increased risk of preeclampsia (95% CI = 1.7–8.8). Conclusions. Our results, if confirmed, would suggest that current public health efforts to increase intake of fruits and vegetables rich in vitamin C and other antioxidants may reduce the risk of preeclampsia.