  Evidence from animal models and epidemiological studies has linked prenatal
alcohol exposure (PAE) to a broad range of long-term cognitive and behavioral
deficits. However, there is virtually no information in the scientific
literature regarding the levels of PAE associated with an increased risk of
clinically significant adverse effects. During the period from 1975-1993,
several prospective longitudinal cohort studies were conducted in the U.S., in
which maternal reports regarding alcohol use were obtained during pregnancy and
the cognitive development of the offspring was assessed from early childhood
through early adulthood. The sample sizes in these cohorts did not provide
sufficient power to examine effects associated with different levels and
patterns of PAE. To address this critical public health issue, we have
developed a hierarchical meta-analysis to synthesize information regarding the
effects of PAE on cognition, integrating data on multiple endpoints from six
U.S. longitudinal cohort studies. Our approach involves estimating the
dose-response coefficients for each endpoint and then pooling these correlated
dose-response coefficients to obtain an estimated `global' effect of exposure
on cognition. In the first stage, we use individual participant data to derive
estimates of the effects of PAE by fitting regression models that adjust for
potential confounding variables using propensity scores. The correlation matrix
characterizing the dependence between the endpoint-specific dose-response
coefficients estimated within each cohort is then run, while accommodating
incomplete information on some endpoints. We also compare and discuss
inferences based on the proposed approach to inferences based on a full
multivariate analysis
