Jennifer K. Straughen

Maternal Serum Leptin During Pregnancy and Infant Birth Weight: the Influence of Maternal Overweight and Obesity

Few studies have examined whether the distinct metabolic patterns found in obese and nonobese pregnant women have different effects on the growing fetus. Our objective was to estimate the influence of longitudinal variation in maternal serum leptin levels on variation in infant birth weight in overweight/obese versus normal‐weight women.

Racism in the form of micro aggressions and the risk of preterm birth among black women

PURPOSE This study sought to examine whether perceived interpersonal racism in the form of racial micro aggressions was associated with preterm birth (PTB) and whether the presence of depressive symptoms and perceived stress modified the association. METHODS Data stem from a cohort of 1410 black women residing in Metropolitan Detroit, Michigan, enrolled into the Life-course Influences on Fetal Environments (LIFE) study. The Daily Life Experiences of Racism and Bother (DLE-B) scale measured the frequency and perceived stressfulness of racial micro aggressions experienced during the past year. Severe past-week depressive symptomatology was measured by the Centers for Epidemiologic Studies-Depression scale (CES-D) dichotomized at ≥ 23. Restricted cubic splines were used to model nonlinearity between perceived racism and PTB. We used the Perceived Stress Scale to assess general stress perceptions. RESULTS Stratified spline regression analysis demonstrated that among those with severe depressive symptoms, perceived racism was not associated with PTB. However, perceived racism was significantly associated with PTB among women with mild to moderate (CES-D score ≤ 22) depressive symptoms. Perceived racism was not associated with PTB among women with or without high amounts of perceived stress. CONCLUSIONS Our findings suggest that racism, at least in the form of racial micro aggressions, may not further impact a group already at high risk for PTB (those with severe depressive symptoms), but may increase the risk of PTB for women at lower baseline risk.

The Influence of Overweight and Obesity on Maternal Soluble fms-Like Tyrosine Kinase 1 and Its Relationship With Leptin During Pregnancy

We studied obesity-related differences in the relation of maternal levels of leptin to levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein that influences placentation and risk of adverse pregnancy outcomes. In a prospective cohort of 286 gravidas, we measured maternal serum levels of sFlt1 and leptin at 5 time points across pregnancy. Analyses stratified on prepregnancy body mass index (<25 vs ≥25) were done using mixed linear models. The mean leptin concentrations were significantly higher in overweight/obese compared to normal-weight women, while mean sFlt1 levels in second and third trimester were significantly higher in normal weight compared to overweight/obese women. The relationship between sFlt1 and leptin differed between the 2 strata. After controlling for maternal weight, a 1 ng/mL increase in leptin was associated with an 19.4 pg/mL increase in sFlt1 (P = .01) in normal-weight women, while leptin was not associated with sFlt1 (β = 1.1, P = .75) in overweight/obese women. Such differences suggest that metabolic differences in overweight/obese women compared to their normal weight peers may differentially impact the physiologic changes during pregnancy.

Direct and proxy recall of childhood socio-economic position and health.

BACKGROUND The utility of proxy reporting within the life course framework has not been adequately assessed; therefore we sought to assess the magnitude and type of agreement that exists between index and proxy reports for bodyweight, health, and socio-economic position (SEP) in childhood. METHODS Participants were enrolled as part of an ongoing study of preterm birth in African American women in Metro Detroit. Post-partum women and their mothers (n = 333 pairs) provided retrospective reports about the womans childhood bodyweight, health, and SEP. Agreement was assessed using kappa, weighted kappa (κ), and intraclass correlation coefficients (ICC). Log-linear models were used to describe the pattern of agreement for ordinal data. RESULTS Birthweight and weight at age 18 was reported with a high level of agreement (ICC = 0.86 and 0.71, respectively). Kappa indicated moderate agreement for early and late childhood/adolescent weight. Log-linear models suggested that there was diagonal agreement plus linear by linear association for early childhood weight and linear by linear association in late childhood/adolescence. Reports of childhood medical problems and hospitalisations had only moderate agreement. Agreement for SEP in both early (κ = 0.14) and late childhood/adolescence (κ = 0.20) was poor. Log-linear models suggest a linear by linear association, indicating a positive association between the responses. CONCLUSIONS Results suggest that proxy reports may be utilised in conjunction with an index report to provide an estimate of the accuracy of report or to more fully capture experiences over the life course. This may be particularly useful when multiple developmental periods are examined.

Racial differences in IGF1 methylation and birth weight.

BackgroundThe birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. Data was collected on a cohort of 87 live born infants. IGF1 methylation was measured in DNA isolated from the mononuclear fraction of umbilical cord blood collected after delivery. Quantitative, loci-specific methylation was assessed using the Infinium HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific methylation of the IGF1 CpG site was validated on a subset of the original sample (N = 61) using pyrosequencing. Multiple linear regression was used to examine relationships between IGF1 methylation, race, and birth weight. A formal mediation analysis was then used to estimate the relationship of IGF1 methylation to race and birth weight.ResultsBlack race was associated with a 7.45% decrease in gestational age-adjusted birth weight (aBW) (P = 0.04) and Black infants had significantly higher IGF1 methylation than non-Black infants (P < 0.05). A one standard deviation increase in IGF1 methylation was associated with a 3.32% decrease in aBW (P = 0.02). Including IGF1 methylation as a covariate, the effect of Black race on aBW was attenuated. A formal mediation analysis showed that the controlled direct effect of Black race on aBW was −6.26% (95% CI = −14.15, 1.06); the total effect of Black race on IGF1 methylation was −8.12% (95% CI = −16.08, −0.55); and the natural indirect effect of Black race on aBW through IGF1 methylation was −1.86% (95% CI = −5.22, 0.18)ConclusionThe results of the mediation analysis along with the multivariable regression analyses suggest that IGF1 methylation may partially mediate the relationship between Black race and aBW. Such epigenetic differences may be involved in racial disparities observed in perinatal outcomes.

Partner support in a cohort of African American families and its influence on pregnancy outcomes and prenatal health behaviors

BackgroundWe examined how two indicators of partner involvement, relationship type and paternal support, influenced the risk of pregnancy outcomes (preterm birth, low birth weight) and health behaviors (prenatal care, drug use, and smoking) among African American women.MethodsInterview and medical record data were obtained from a study of 713 adult African American women delivering singletons between March 2001 and July 2004. Women were enrolled prenatally if they received care at one of three Johns Hopkins Medical Institution (JHMI) prenatal clinics or post-partum if they delivered at JHMI with late, no or intermittent prenatal care. Relationship type was classified as married, unmarried/cohabitating, or unmarried/non-cohabitating. Partner support was assessed using an 8-item scale and was dichotomized at the median. Differences in partner support by pregnancy outcome and health behaviors were assessed using linear regression. To assess measures of partner support as predictors of adverse pregnancy outcomes and health behaviors, Poisson regression was used to generate crude and adjusted prevalence ratios (PR) and 95% confidence intervals (CI).ResultsThere were no statistically significant differences in pregnancy outcomes or health behaviors by relationship type or when partner support was examined as a continuous or categorical variable. Modeled as a dichotomous variable, partner support was not associated with the risk of preterm birth (PR = 0.81, 95% CI = 0.56, 1.56), low birth weight (PR = 0.77, 96% CI = 0.48, 1.26), or health behaviors.ConclusionsPaternal involvement was not associated with pregnancy outcomes or maternal health behaviors. Attention to measurement issues and other factors relevant for African American women are discussed.

Allostatic load and health: Can perinatal epidemiology lead the way forward?

In this issue of the Journal, Wallace and colleagues add to the small but growing literature endeavouring to understand both how allostatic load can be defined in pregnancy and how it may play a role in the aetiology of adverse birth outcomes. As articulated by Sterling and Eyer, ‘. . . allostasis defines health as a state of responsiveness and optimal predictive fluctuation to adapt to the demands of the environment’. Allostasis implies a dynamic system in which multiple factors are interconnected, and there is a balancing act as the system responds to change. Extending from this is the concept of allostatic load, described by McEwen and Stellar as representing ‘the “wear and tear” the body experiences when repeated allostatic responses are activated during stressful situations’. Wallace and colleagues capitalised on preconceptional allostatic load indicators available from the Bogalusa Heart Study matched to birth certificates. No associations were found between allostatic load and preterm or small for gestational age births, with no apparent effect modification by race or education. The concept of allostatic load aligns with the thinking of many perinatal researchers, particularly the evolution of research on psychosocial stressors. Early work on stress and preterm delivery focused on acute stressors, measured, for example, as counts of life events occurring during pregnancy. The inadequacy of this approach was soon realised, and investigators began to develop and implement measures of chronic stressors. Subsequently, chronic stressors were recognised as particularly salient for poor and minority women who suffered the highest rates of adverse birth outcomes. The field continued to advance and began incorporating a more explicit consideration of the response to stressors as distinct from exposure to stressors. Later work by both Lu and Misra incorporated psychosocial as well as other types of stressors within life course frameworks that explicitly separate stressors/exposures from responses to the stressors/exposures. These models also identified the need to consider mediation pathways. The life course frameworks also identified acute and chronic stressors related to racism. As others in the field have embraced these frameworks, the challenge of how to measure life course stressors and their impacts (e.g. stress and allostatic load) has become integral in efforts to advance this field forward. In our own work, we have begun to measure socio-economic environment and body weight across the life course in an effort to characterise levels and trajectories of these ‘stressors’ and relate them to birth outcomes. Psychologists have utilised this concept of allostatic load to try to understand how stressors, particularly chronic stressors, impact health (see http://www .macses.ucsf.edu/research/allostatic/allostatic.php). Most work has focused on health in later adulthood, particularly cardiovascular and metabolic disease and aging. Allostatic load has been represented as an unweighted composite index of identified biomarkers in which a point is contributed if the individual is above a certain threshold (e.g. above the 75th percentile). There are a number of problems with this approach generally as well as with respect to perinatal research. First, not all studies use the same biomarkers, and the issue of repeated measures and longitudinal patterns are not sufficiently addressed. Such issues are very relevant in perinatal research. Wallace et al. astutely focus on preconceptional biomarkers as variation outside of non-pregnant norms in the pregnancy levels is well established in even healthy pregnancies. However, there is no clear justification as to when factors should be measured: a single time point 3 months prior to conception? Year before conception? Beginning in childhood every five years? If longitudinal data are available, is the pattern important or the level? Second, while much has been written about the way in which multiple mediators of adaptation are interconnected in a non-linear network with non-linear effects on organ systems, little has Correspondence: Dawn P. Misra, Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, 3939 Woodward Avenue, Detroit, MI 48170, USA. E-mail: dmisra@med.wayne.edu bs_bs_banner

The effect of maternal soluble FMS-like tyrosine kinase 1 during pregnancy on risk of preterm delivery

Objective: Soluble fms-like tyrosine kinase 1 (sFlt1) is an antiangiogenic protein that is associated with a number of disorders of placental angiogenesis. It has been hypothesized that disruption of placental angiogenesis may contribute to the pathophysiology of preterm delivery (PTD). However, the relationship of PTD risk to variation in sFlt1 levels is not well known. We investigate the relationship between longitudinal variation in maternal serum concentrations of sFlt1 and risk of PTD. Methods: Data were collected in a longitudinal cohort study involving 278 pregnant women. Maternal serum sFlt1 concentrations were measured at 6–10, 10–14, 16–20, 22–26, and 32–36 weeks gestation. Data analyses used longitudinal regression models using repeated measures that allow robust inferences from our modest sample size. The outcome was birth prior to 37 weeks gestation. Results: sFlt1 concentrations were higher in first trimester for preterm compared to term deliveries. This relationship reversed in second trimester because sFlt1 concentrations increased more rapidly across gestation for term deliveries. In Cox proportional hazards analyses, a 2 ng higher sFlt1 concentration across gestation was associated with a hazard ratio of 1.3 (95% CI: 1.1, 1.5) for PTD suggesting the importance of levels in early pregnancy. Conclusion: Elevated maternal serum sFlt1 concentration during pregnancy is associated with increased risk of PTD.

Preterm Delivery as a Unique Pathophysiologic State Characterized by Maternal Soluble FMS-Like Tyrosine Kinase 1 and Uterine Artery Resistance During Pregnancy: A Longitudinal Cohort Study

Background: Preterm delivery (PTD) may be characterized by altered interrelationships among angiogenic factors and measures of placental function. We analyzed the longitudinal relationship between maternal serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt1), an important antiangiogenic factor, and uterine artery resistance in pregnancies resulting in preterm and term deliveries. Methods: Data were collected in a longitudinal cohort study involving 278 women monitored at 6 to 10, 10 to 14, 16 to 20, 22 to 26, and 32 to 36 weeks of gestation. Concentrations of maternal serum sFlt1 were determined using solid-phase enzyme-linked immunosorbent assay, and uterine artery resistance indices (RI) were measured by Doppler velocimetry at each interval. Preterm delivery was defined as birth before 37-weeks completed gestation. Data analyses used multivariable repeated measures regression models. Results: Uterine artery RI decreased across gestation. As pregnancy progressed, RI trajectories diverged for term and preterm deliveries; the mean RI was significantly higher in third trimester for pregnancies resulting in PTD (P = .08). sFlt1 was stable through 21 3/7 weeks of gestation and then increased rapidly; women who delivered preterm had significantly higher sFlt1 levels in the third trimester (P = .04). The relationship between uterine artery RI and sFlt1 from the prior visit was significantly different between the groups (P < .0001). For term deliveries, higher sFlt1 concentrations were associated with a smaller RI at the subsequent visit (β = −.08, 95% confidence interval [CI]: −0.14 to −0.02). For PTD, higher sFlt1 concentrations were associated with a larger uterine artery RI (β = .14, 95% CI: 0.06 to 0.22). Conclusion: PTD is characterized by altered relationships between angiogenic factors and placental vascular blood flow starting in early pregnancy.

Maternal body weight trajectories across the life course and risk of preterm delivery

We examined the association between life course body weight percentile trajectories and risk for preterm delivery (PTD). Data about womens weight at birth, age 18, and before pregnancy were obtained by retrospective self-report in a cohort of 1410 black women in metropolitan Detroit. Growth mixture models were used to categorize women with similar weight percentile trajectories across these time points. Log-Poisson models were used to examine the association between the trajectory groups and PTD. Four trajectory groups with different beginning and endpoints of their weight percentiles (high-high, high-low, low-high and low-low) best fit the data. The groups with the highest prevalence of PTD were those that started low (low-high, 21%; low-low, 18%). The low-high group had a higher prevalence of PTD than the high-high trajectory group in unadjusted models (prevalence ratio=1.49 [95% confidence interval (CI) 1.11, 2.00]). The association became not significant after adjusting for maternal age at delivery, income, diabetes and hypertension. When compared with the high-high trajectory group, the low-low trajectory seemed to also have a higher prevalence of PTD after adjusting for maternal age at delivery, income, diabetes and hypertension (prevalence ratio=1.35 [95% CI 1.00, 1.83]). Results suggest that a womans risk for PTD is influenced by her body weight trajectory across the life course.