A repeated measures approach for simultaneous modeling of multiple neurobehavioral outcomes in newborns exposed to cocaine in utero.

Multiple binary outcomes are encountered frequently in epidemiologic research. This work was motivated by the Maternal Lifestyle Study, 1993-1995, where newborns exposed prenatally to cocaine and a comparison cohort were examined for the presence of central and autonomic nervous system (CNS/ANS) signs. Thus, each infant contributed to multiple, possibly interrelated, binary outcomes that may collectively constitute one syndrome (even though specific outcomes that are affected by cocaine are of scientific interest). Because it is neither scientifically appropriate nor statistically efficient to fit separate models for each outcome, here we adopt a multivariate repeated measures approach to simultaneously model all the CNS/ANS outcomes as a function of cocaine exposure and other covariates. This formulation has a number of advantages. First, it implicitly recognizes that all the CNS/ANS outcomes may together constitute one syndrome. Second, simultaneous modeling boosts statistical efficiency by allowing for correlations among the outcomes, and it avoids multiple comparisons. Third, it allows for outcome-specific exposure effects, so that the specific signs that are affected by cocaine exposure can be identified.

[1]  Edward C. Chao,et al.  Generalized Estimating Equations , 2003, Technometrics.

[2]  Janet S. Dodd,et al.  References , 2003, Dividing Paradise.

[3]  Eric R. Ziegel,et al.  Generalized Linear Models , 2002, Technometrics.

[4]  L. Wright,et al.  The Maternal Lifestyle Study: drug exposure during pregnancy and short-term maternal outcomes. , 2002, American journal of obstetrics and gynecology.

[5]  Helen Brown,et al.  Applied Mixed Models in Medicine , 2000, Technometrics.

[6]  Xiao-Hua Zhou,et al.  Statistical Computing Software Reviews Comparisons of Software Packages for Generalized Linear Multilevel Models , 1999 .

[7]  Stuart R. Lipsitz,et al.  Review of Software to Fit Generalized Estimating Equation Regression Models , 1999 .

[8]  B. Everitt,et al.  Analysis of longitudinal data , 1998, British Journal of Psychiatry.

[9]  Scott L. Zeger,et al.  Latent Variable Regression for Multiple Discrete Outcomes , 1997 .

[10]  B. Lester,et al.  Effects of in utero substance exposure on infant neurobehavior. , 1996, Pediatrics.

[11]  N M Laird,et al.  Bivariate logistic regression analysis of childhood psychopathology ratings using multiple informants. , 1995, American journal of epidemiology.

[12]  P. Diggle,et al.  Modelling multivariate binary data with alternating logistic regressions , 1993 .

[13]  N. Breslow,et al.  Approximate inference in generalized linear mixed models , 1993 .

[14]  J M Neuhaus,et al.  Statistical methods for longitudinal and clustered designs with binary responses , 1992, Statistical methods in medical research.

[15]  J. Kalbfleisch,et al.  A Comparison of Cluster-Specific and Population-Averaged Approaches for Analyzing Correlated Binary Data , 1991 .

[16]  S. Lipsitz,et al.  Generalized estimating equations for correlated binary data: Using the odds ratio as a measure of association , 1991 .

[17]  S. Dixon,et al.  Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. , 1988, The Journal of pediatrics.

[18]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[19]  J. Ware,et al.  Random-effects models for serial observations with binary response. , 1984, Biometrics.

[20]  C. Pippenger,et al.  Pharmacologic observations on the neonatal withdrawal syndrome. , 1976, The Journal of pediatrics.

[21]  E. Wasserman,et al.  Neonatal narcotic addiction: 10 year observation. , 1971, Pediatrics.

[22]  Louise Ryan,et al.  Efficiency and power of tests for multiple binary outcomes , 1995 .

[23]  S L Zeger,et al.  Regression analysis for correlated data. , 1993, Annual review of public health.

[24]  A. Stewart,et al.  Measuring Functioning and Well-Being: The Medical Outcomes Study Approach , 1992 .

[25]  R. Roberts.  Drug therapy in infants : pharmacologic principles and clinical experience , 1984 .