TABLE 10-2Selected Epidemiologic Studies—Neural-Tube Defects in Offspring of Subjectsa

Study PopulationExposed CasesbExposure of Interest/Estimated Relative Risk (95% CI)bReference
US Vietnam Veterans
US Air Force Health Study—Ranch Hand veterans vs SEA veterans (unless otherwise noted) All COIs 
Air Force Operation Ranch Hand personnel—neural-tube defects4cnrWolfe et al., 1995
CDC Birth Defects Study—Hospital records reviewed for offspring of 7,924 Vietnam veterans and 7,364 non–Vietnam veterans All COIs 
Vietnam veterans identified through CDC Metropolitan Atlanta Congenital Defects Program  Erickson et al., 1984a,b
Service in Vietnam
Spina bifida191.1 (0.6–1.7) 
Anencephaly120.9 (0.5–1.7) 
Military records indicate opportunity for exposure
Spina bifida202.7 (1.2–6.2) 
Anencephaly70.7 (0.2–2.8) 
US CDC Vietnam Experience Study—Cross-sectional study, with medical examinations, of Army veterans: 9,324 deployed vs 8,989 nondeployed All COIs 
VES cohort—reproductive outcomes  CDC, 1989b
Spina bifida
Vietnam veterans' children91.7 (0.6–5.0) 
Non–Vietnam veterans' children51.0 
Vietnam veterans' children3nr 
Non–Vietnam veterans' children01.0 
International Vietnam-Veteran Studies
Australian Vietnam Veterans—58,077 men and 153 women who served on land or in Vietnamese waters during 5/23/1962–7/1/1973 vs Australian population All COIs 
Validation Study Expected number of exposed casesAIHW, 1999
Spina bifida—maximums5033 expected (22–44) 
Anencephaly1316 expected (8–24) 
Australian Vietnam veterans—neural-tube defects All COIsADVA, 1983
160.9 (nr)
Norwegian farmers—spina bifida (maternal, paternal exposures) HerbicidesKristensen et al., 1997
Tractor spraying equipment281.6 (0.9–2.7) 
Tractor spraying equipment, orchards, greenhousesd52.8 (1.1–7.1) 
United States—birth defects in children born to licensed pesticide appliers in Minnesota linked to state birth registries Herbicides, pesticidesGarry et al., 1996
Central-nervous-system defects61.1 (0.5–2.4) 
Times Beach/Quail Run Cohorts Dioxin 
Persons in Missouri with documented TCDD soil contamination near residence (maternal, paternal, in utero exposure) TCDDStockbauer et al., 1988
Central-nervous-system defects33.0 (0.3–35.9) 
Other International Environmental Studies
France—Population-based birth defects registry in Rhône-Alpes region (1988–1997): maternal residence in municipality with solid-waste incinerator vs not DioxinCordier et al., 2004
490.9 (0.6–1.2)
Canada—British Columbian sawmill workers with exposure in upper 3 quartiles for any job held up to 3 months before conception HerbicidesDimich-Ward et al., 1996
Spina bifida, anencephaly222.4 (1.1–5.3) 
Spina bifida only181.8 (0.8–4.1) 
New Zealand—Residents of areas subject to aerial 2,4,5-T spraying 2,4,5-T 90% CIHanify et al., 1981
Anencephaly101.4 (0.7–2.9) 
Spina bifida131.1 (0.6–2.1) 
The Netherlands—Children of Dutch farmers who were born with spina bifida (1980–1992), 470 cases vs 456 healthy controls Herbicides, pesticidesBlatter et al., 1997
Spina bifida—moderate, heavy exposure
Pesticide use81.7 (0.7–4.0) 
Herbicide use71.6 (0.6–4.0)e 

NOTE: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; CDC, Centers for Disease Control and Prevention; CI, confidence interval; COI, chemical of interest; nr, not reported; SEA, Southeast Asia; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; VES, Vietnam Experience Study.


Unless otherwise indicated, studies show paternal exposure.


Given when available; results other than estimated risk explained individually.


Of four neural-tube defects reported in Operation Ranch Hand offspring, two were spina bifida (high dioxin exposure), one spina bifida (low dioxin), one anencephaly (low dioxin); no neural-tube defects reported in comparison cohort; 454 postservice births studied in Ranch Hand veterans; 570 in comparison cohort.


Greenhouse workers would not have been exposed to chemicals of interest.


Calculated from data presented in the paper.

From: 10, Effects on Future Generations

Cover of Veterans and Agent Orange
Veterans and Agent Orange: Update 2012.
Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Ninth Biennial Update); Board on the Health of Select Populations; Institute of Medicine.
Washington (DC): National Academies Press (US); 2014 Mar 6.
Copyright 2014 by the National Academy of Sciences. All rights reserved.

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