Gwendolyn S. Norman

The preterm prediction study: Maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation ☆ ☆☆ ★

OBJECTIVE Our purpose was to determine whether various measures of poor psychosocial status in pregnancy are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight. STUDY DESIGN Anxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593 gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression analyses provided the odds ratios and 95% confidence intervals. RESULTS Analyses revealed that stress was significantly associated with spontaneous preterm birth and with low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for psychosocial status, substance use, and demographic traits, black race was the only variable significantly associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low education were associated with spontaneous preterm birth and low birth weight. CONCLUSION Stress was associated with spontaneous preterm birth and low birth weight even after adjustment for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress, substance use, and other demographic factors.

Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women.

BACKGROUND Although preeclampsia is an important and relatively common medical problem, its pathophysiology remains unresolved and the search for a biochemical marker that precedes the hemodynamic abnormalities of preeclampsia continues. We designed a study to investigate the hemodynamic changes that characterize preeclampsia and to evaluate the metabolism of platelet intracellular calcium as a possible predictor of the development of preeclampsia. METHODS Hemodynamic measurements and spectrofluorometric determinations of the levels of intracellular calcium in platelets in the basal state and after stimulation with an agonist were performed in 48 nulliparous black women during each trimester of pregnancy. The data on the 14 women (29 percent) in whom preeclampsia developed were then compared with the data on the other 34, who served as normotensive controls. RESULTS There was no significant difference between the two groups in the basal levels of intracellular calcium at any time. In contrast, the levels measured after arginine vasopressin was administered during the first trimester indicated an exaggerated response in the group with preeclampsia as compared with the control group (1494 +/- 388 [+/- SEM] percent vs. 545 +/- 55 percent of base line; P less than 0.0002), which was sustained through the second and third trimesters. All but three of the women with preeclampsia had responses higher than the highest response among the controls. Platelet intracellular calcium responses to arginine vasopressin during the first trimester were a sensitive predictor of the subsequent development of preeclampsia (P less than 0.00009). Although vascular resistance was similar in the two groups during the first trimester, it subsequently decreased in the control group (P less than 0.02) but not in the group with preeclampsia. CONCLUSIONS Our findings indicate that preeclampsia is characterized by the absence of the normal pregnancy-related decrease in vascular resistance, which is preceded in most instances by an exaggerated response of platelet intracellular calcium to arginine vasopressin early in pregnancy. We therefore propose that an increase in the sensitivity of platelet calcium to arginine vasopressin can be used as an early predictor of subsequent preeclampsia.

Follow-up of Children Exposed In Utero to 17 α-Hydroxyprogesterone Caproate Compared With Placebo

OBJECTIVE: To assess whether there are evident adverse effects of 17 &agr;-hydroxyprogesterone caproate after in utero exposure. METHODS: This study evaluated surviving children of mothers who participated in a multicenter placebo-controlled trial of weekly intramuscular 17 &agr;-hydroxyprogesterone caproate, with a 2:1 allocation to 17 &agr;-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child’s general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory. RESULTS: Of 348 eligible surviving children, 278 (80%) were available for evaluation (194 in the 17 &agr;-hydroxyprogesterone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 &agr;-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 &agr;-hydroxyprogesterone caproate and placebo groups. CONCLUSION: 17 &agr;-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters. LEVEL OF EVIDENCE: II

Markers for endothelial injury, clotting and platelet activation in preeclampsia

SummaryThe etiology of disseminated intravascular coagulation (DIC) in preeclampsia is not well understood. We measured plasma levels of fibronectin (FN), which may reflect endothelial cell injury, fibrinopeptide A (FPA), a specific marker of clotting, platelet counts (PLC) and mean platelet volumes (MPV), as well as β-thromboglobulin (βTG) and platelet factor 4 (Pf4), products of irreversible platelet activation in 24 preeclamptic patients and 24 controls matched for age, gestational age, labor status, and parity. In preeclampsia, FN and FPA were significantly elevated while PLC were significantly decreased (P<0.0001, <0.05 and <0.01, respectively). βTG, Pf4, and MPV values did not show significant differences. These findings support the hypothesis that endothelial injury, clotting activation and platelet consumption are increased in preeclampsia. However, the much closer association of preeclampsia with FN levels as compared to FPA, βTG, Pf4, suggests that endothelial injury is a more basic mechanism of preeclampsia than clotting or platelet activation.

Mechanisms for reduced colloid osmotic pressure in preeclampsia

The determinants of plasma colloid osmotic pressure were studied in 32 patients with preeclampsia and their matched control subjects. Although plasma colloid osmotic pressure was significantly related to preeclampsia, its severity, and proteinuria, it was most highly correlated with an elevated fibronectin level, suggesting that endothelial injury, rather than proteinuria, is the major mechanism of reduced colloid osmotic pressure in preeclampsia.

Pregnancy recruitment for population research: the National Children's Study vanguard experience in Wayne County, Michigan.

BACKGROUND To obtain a probability sample of pregnancies, the National Childrens Study conducted door-to-door recruitment in randomly selected neighbourhoods in randomly selected counties in 2009-10. In 2011, an experiment was conducted in 10 US counties, in which the two-stage geographic sample was maintained, but participants were recruited in prenatal care provider offices. We describe our experience recruiting pregnant women this way in Wayne County, Michigan, a county where geographically eligible women attended 147 prenatal care settings, and comprised just 2% of total county pregnancies. METHODS After screening for address eligibility in prenatal care offices, we used a three-part recruitment process: (1) providers obtained permission for us to contact eligible patients, (2) clinical research staff described the study to women in clinical settings, and (3) survey research staff visited the home to consent and interview eligible women. RESULTS We screened 34,065 addresses in 67 provider settings to find 215 eligible women. Providers obtained permission for research contact from 81.4% of eligible women, of whom 92.5% agreed to a home visit. All home-visited women consented, giving a net enrolment of 75%. From birth certificates, we estimate that 30% of eligible county pregnancies were enrolled, reaching 40-50% in the final recruitment months. CONCLUSIONS We recruited a high fraction of pregnancies identified in a broad cross-section of provider offices. Nonetheless, because of time and resource constraints, we could enrol only a fraction of geographically eligible pregnancies. Our experience suggests that the probability sampling of pregnancies for research could be more efficiently achieved through sampling of providers rather than households.

The National Children's Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach.

OBJECTIVE: In 2009, the National Children’s Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment. METHODS: The NCS aimed to recruit 18- to 49-year-old women who were pregnant or at risk for becoming pregnant who lived in designated geographic segments within primary sampling units, generally counties. Using provider-based recruitment, 10 study centers engaged providers to enroll eligible participants at their practice. Recruitment models used different levels of provider engagement (full, intermediate, information-only). RESULTS: The percentage of eligible women per county ranged from 1.5% to 57.3%. Across the centers, 3371 potential participants were approached for screening, 3459 (92%) were screened and 1479 were eligible (43%). Of those 1181 (80.0%) gave consent and 1008 (94%) were retained until delivery. Recruited participants were generally representative of the county population. CONCLUSIONS: Provider-based recruitment was successful in recruiting NCS participants. Challenges included time-intensity of engaging the clinical practices, differential willingness of providers to participate, and necessary reliance on providers for participant identification. The vast majority of practices cooperated to some degree. Recruitment from obstetric practices is an effective means of obtaining a representative sample.