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An Analysis of Specific Categories of Birth Defects and Developmental Disabilities for Children of Participants of the air force health study

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Open Journal of Epidemiology 2024年第2期14卷 312-330页

作者： George J. Knafl School of Nursing University of North Carolina at Chapel Hill Chapel Hill NC USA

Background: The air force health study collected reproductive outcomes for live-born children of male air force veterans of the Vietnam War. Methods: Dioxin values for participants were obtained from blood samples. Analyses were conducted of occurrence of 16 specific categories of birth defects and developmental disabilities. Children were categorized as conceived before and after the start of participants’ Vietnam War service. Children conceived before the start of Vietnam War service were treated as being conceived when their fathers had unquantifiable dioxin values. Children conceived after the start of Vietnam War service for participants with missing dioxin values were excluded from primary analyses, but were used to assess the impact of their exclusion on conclusions. Correlation between values for specific categories for multiple children fathered by the same participant was accounted for. The dose-response relationship was treated as a step function increasing for dioxin values larger than adaptively identified individual thresholds changing with the specific category. Results: For 15 of 16 specific categories, the probability of occurrence increased substantially for a sufficiently high dioxin level above identified thresholds. Exclusion of children due to missing dioxin likely did not affect these results. Conclusions: Results supported the conclusion of substantial adverse effects on a wide variety of specific categories of birth defects and developmental disabilities due to sufficiently high exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Results may hold more generally, but might also have been affected by a variety of limitations.

关键词： Agent Orange air force health study Birth Defects Developmental Disabilities Dioxin Dose-Response Relationship Vietnam War

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Adaptive Regression for Nonlinear Interrupted Time Series Analyses with Application to Birth Defects in Children of Vietnam War Veterans

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Open Journal of Statistics 2022年第6期12卷 789-809页

作者： George J. Knafl School of Nursing University of North Carolina at Chapel Hill Chapel Hill NC USA

The purpose of this article is to provide an overview of adaptive regression modeling and demonstrate its use in conducting nonlinear analyses of interrupted time series (ITS) data. Adaptive regression modeling is based on heuristic search over alternative models for data controlled by likelihood-cross validation (LCV) scores with larger scores indicating better models. Extended linear mixed models are used for correlated data like ITS data. Power transforms of predictor variables are used to account for nonlinearity. The use of adaptive regression modeling for assessing ITS effects is demonstrated using data on annual proportions of major birth defects in children fathered by male air force veterans of the Vietnam War over a 59-year period. The interruption for this ITS is conception after versus before the start of a participant’s first tour in the Vietnam War. Whether the ITS effect is related to dioxin exposure is also addressed. Dioxin is a highly toxic contaminant of the herbicide Agent Orange used in the Vietnam War. The core findings of the reported analyses are that a substantial adverse ITS interruption effect is identified and that this adverse effect can reasonably be attributed to participants having a high dioxin exposure level. Moreover, these results indicate that adaptive regression modeling can identify nonlinear ITS effects in general situations that can lead to consequential insights into nonlinear relationships over time, possibly varying with other available predictors.

关键词： Adaptive Regression air force health study Birth Defects Dioxin Inter-rupted Time Series

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