Flavia P Kapos1,2, Lauren A White1,3, Kelsey A Schmidt4,5, Stephen E Hawes1, Jacqueline R Starr6,7. 1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA. 2. Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, USA. 3. School of Social Work, University of Michigan, Ann Arbor, MI, USA. 4. Nutritional Sciences Program, School of Public Health, University of Washington, Seattle, WA, USA. 5. Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. The Forsyth Institute, Cambridge, MA, USA. 7. Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, USA.
Abstract
BACKGROUND: Orofacial clefts (OFC) have multifactorial aetiology. Established risk factors explain a small proportion of cases. OBJECTIVES: To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification. METHODS: This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers. RESULTS: The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n = 2136 cases). Among controls (n = 25 826), 76% of mothers were urban residents and 72% were of White race/ethnicity. OFC risk was slightly higher for infants born to rural than to urban mothers, adjusting for race/ethnicity (OR 1.12, 95% CI 1.01, 1.25). The association was similar before and after US-mandated folic acid fortification. Compared with infants born to White mothers, OFC risk was higher for American Indian mothers (OR 1.73, 95% CI 1.35, 2.23) and lower for Black (OR 0.62, 95% CI 0.48, 0.81), Hispanic (OR 0.75, 95% CI 0.64, 0.87), and Asian/Pacific Islander (API) mothers (OR 0.87, 95% CI 0.74, 1.02). Bias analysis suggests the observed difference for Black mothers may be explained by selection bias. Post-fortification, the association of OFC with maternal API race/ethnicity decreased and with maternal Black race/ethnicity increased relative to maternal White race/ethnicity. CONCLUSIONS: Infants born to rural mothers and to American Indian mothers in Washington State during 1989-2014 were at higher OFC risk before and after US-mandated folic acid fortification.
BACKGROUND: Orofacial clefts (OFC) have multifactorial aetiology. Established risk factors explain a small proportion of cases. OBJECTIVES: To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification. METHODS: This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers. RESULTS: The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n = 2136 cases). Among controls (n = 25 826), 76% of mothers were urban residents and 72% were of White race/ethnicity. OFC risk was slightly higher for infants born to rural than to urban mothers, adjusting for race/ethnicity (OR 1.12, 95% CI 1.01, 1.25). The association was similar before and after US-mandated folic acid fortification. Compared with infants born to White mothers, OFC risk was higher for American Indian mothers (OR 1.73, 95% CI 1.35, 2.23) and lower for Black (OR 0.62, 95% CI 0.48, 0.81), Hispanic (OR 0.75, 95% CI 0.64, 0.87), and Asian/Pacific Islander (API) mothers (OR 0.87, 95% CI 0.74, 1.02). Bias analysis suggests the observed difference for Black mothers may be explained by selection bias. Post-fortification, the association of OFC with maternal API race/ethnicity decreased and with maternal Black race/ethnicity increased relative to maternal White race/ethnicity. CONCLUSIONS: Infants born to rural mothers and to American Indian mothers in Washington State during 1989-2014 were at higher OFC risk before and after US-mandated folic acid fortification.
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