Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development - the LIFE Study: The LIFE Study

Buck Louis GM, Schisterman EF, Sweeney AM, Wilcosky TC, Gore-Langton RE, Lynch CD, Boyd Barr D, Schrader SM, Kim S, Chen Z, Sundaram R, on behalf of the LIFE Study. Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development – the LIFE Study. Paediatric and Perinatal Epidemiology 2011; 25: 413–424

Rationale, design, and method of the Diabetes & Women’s Health study – a study of long-term health implications of glucose intolerance in pregnancy and their determinants

Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women’s Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses’ Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population

Dichorionic twin trajectories: the NICHD Fetal Growth Studies

BACKGROUND: Systematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation, performed in controlled clinical settings. Currently there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated using the same benchmarks as singleton growth. OBJECTIVES: Our objective was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal two-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard developed by our group for singletons. STUDY DESIGN: A prospective cohort of 171 women with twin gestations was recruited from eight U.S. sites from 2012 to 2013. After an initial sonogram at 11w0d–13w6d where dichorionicity was confirmed, women were randomized to one of two serial ultrasonology schedules. Growth curves and percentiles were estimated using linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1,731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories using likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements where there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, defined as below the 10(th) percentile that would be introduced if fetal growth estimation for twins was based upon an unweighted singleton standard. RESULTS: Women underwent a median of 5 ultrasounds. The 50(th) percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks, while biparietal diameter in twins was smaller from 34 through 36 weeks. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks, indicating a comparatively asymmetric growth pattern. At 35 weeks, the average gestational age at delivery for twins, the estimated fetal weights for the 10(th), 50(th) and 90(th) percentiles were 1960, 2376, and 2879 g for dichorionic twins and 2180, 2567, and 3022 g for the singletons. At 32 weeks, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age using a singleton, non-Hispanic white standard. By 35 weeks, 38% of twins would be classified as small for gestational age. CONCLUSIONS: The comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard

An emerging income differential for adolescent emotional problems

Background: While there is considerable evidence of income gradients in child and adolescent behaviour problems, evidence relating to children and young people’s emotional difficulties is more mixed. Older studies reported no income differentials, while recent reports suggest that adolescents from lowincome families are more likely to experience emotional difficulties than their more affluent peers. Methods: We compared the association between low- versus medium-/high-family income and parent-reported emotional difficulties in 15- and 16-year-olds in three large nationally representative cohorts studied in 1974, 1986 and 1999/2004. We then examined whether increases in the income differential could be accounted for by changes in the association of a range of sociodemographic factors (family type or size, maternal education or housing tenure) with either family income or emotional difficulties. Finally, in the most recent cohorts, we considered whether the effects of these sociodemographic variables were mediated by more proximal family factors (maternal distress, stressful life events or family dysfunction). Results: An increasing income differential in adolescent emotional problems emerged over the period, with standardized coefficients for associations with low income increasing from .07 in 1974 and 1986 to .30 in 1999/2004. This was due partially (-10%) to sociodemographic risk factors for emotional difficulties becoming more strongly associated with low-income families over time, and partially (-40%) to the increasing impact of these risk factors. In the most recent cohorts, about 40% of the effects of sociodemographic risks appear to have been mediated by more proximal family factors. Conclusions: These findings have implications for our understanding of the health burden of emotional problems, recognition of the health burden associated with inequality and public concern about the consequences of social change

Dichorionic twin trajectories: the NICHD Fetal Growth Studies.

BackgroundSystematic evaluation and estimation of growth trajectories in twins require ultrasound measurements across gestation that are performed in controlled clinical settings. Currently, there are few such data for contemporary populations. There is also controversy about whether twin fetal growth should be evaluated with the use of the same benchmarks as singleton growth.ObjectivesOur objective was to define the trajectory of fetal growth in dichorionic twins empirically using longitudinal 2-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard that was developed by our group for singletons.Study designA prospective cohort of 171 women with twin gestations was recruited from 8 US sites from 2012-2013. After an initial sonogram at 11 weeks 0 days-13 weeks 6 days of gestation during which dichorionicity was confirmed, women were assigned randomly to 1 of 2 serial ultrasonography schedules. Growth curves and percentiles were estimated with the use of linear mixed models with cubic splines. Percentiles were compared statistically at each gestational week between the twins and 1731 singletons, after adjustment for maternal age, race/ethnicity, height, weight, parity, employment, marital status, insurance, income, education, and infant sex. Linear mixed models were used to test for overall differences between the twin and singleton trajectories with the use of likelihood ratio tests of interaction terms between spline mean structure terms and twin-singleton indicator variables. Singleton standards were weighted to correspond to the distribution of maternal race in twins. For those ultrasound measurements in which there were significant global tests for differences between twins and singletons, we tested for week-specific differences using Wald tests that were computed at each gestational age. In a separate analysis, we evaluated the degree of reclassification in small for gestational age, which was defined as <10th percentile that would be introduced if fetal growth estimation for twins was based on an unweighted singleton standard.ResultsWomen underwent a median of 5 ultrasound scans. The 50th percentile abdominal circumference and estimated fetal weight trajectories of twin fetuses diverged significantly beginning at 32 weeks of gestation; biparietal diameter in twins was smaller from 34-36 weeks of gestation. There were no differences in head circumference or femur length. The mean head circumference/abdominal circumference ratio was progressively larger for twins compared with singletons beginning at 33 weeks of gestation, which indicated a comparatively asymmetric growth pattern. At 35 weeks of gestation, the average gestational age at delivery for twins, the estimated fetal weights for the 10th, 50th, and 90th percentiles were 1960, 2376, and 2879 g for dichorionic twins, respectively, and 2180, 2567, and 3022 g for the singletons, respectively. At 32 weeks of gestation, the initial week when the mean estimated fetal weight for twins was smaller than that of singletons, 34% of twins would be classified as small for gestational age with the use of a singleton, non-Hispanic white standard. By 35 weeks of gestation, 38% of twins would be classified as small for gestational age.ConclusionThe comparatively asymmetric growth pattern in twin gestations, initially evident at 32 weeks of gestation, is consistent with the concept that the intrauterine environment becomes constrained in its ability to sustain growth in twin fetuses. Near term, nearly 40% of twins would be classified as small for gestational age based on a singleton growth standard