Journal of exposure science & environmental epidemiology · 2026
Maternal agrochemical exposure during pregnancy and risk of orofacial clefts: a case-control study in eight low- and middle-income countries.
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McCulloch Sofia, Boivie Patrik, Feigelson Devin, Auslander Allyn, Magee William, Operation Smile International Family Study Group
Аннотация
BACKGROUND: Orofacial clefts impose a substantial burden on low- and middle-income countries (LMICs), yet evidence on preventable environmental determinants, including agrochemicals, remains sparse.
OBJECTIVE: To quantify the association between maternal agrochemical exposure during pregnancy and nonsyndromic orofacial clefts (NSOFCs) across eight LMICs.
METHODS: This population-sampled, unmatched case-control study included questionnaires administered to mothers of children with NSOFCs (cases) and mothers of unaffected children (controls) in the Democratic Republic of Congo (DRC), Guatemala, Honduras, Madagascar, Morocco, Nicaragua, the Philippines, and Vietnam. Binary logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported agrochemical exposure. Sub-analyses examined cleft subtypes and country-specific effects.
RESULTS: 3791 cases and 3190 controls recruited from 2012 to 2020 were included for the descriptive statistics. Agrochemical exposure was uncommon (5.4% of cases; 1.3% of controls), and DRC, Guatemala, Morocco, and Nicaragua were excluded from the binary logistic regression due to insufficient exposure reports. After adjustment, any pregnancy exposure was associated with an increased odds of NSOFC (OR 2.34, 95% CI 1.47-3.71); a comparable estimate was observed for first-trimester exposure (OR 2.63, 95% CI 1.37-5.04). The odds ratio was elevated for cleft lip ± cleft palate (OR 2.35, 1.45-3.81), with an elevated but non-significant point estimate for isolated cleft palate (OR 1.52; 95% CI: 0.73-3.15). Country-stratified models identified significantly elevated associations in Vietnam (OR 3.91, 1.35-11.30) and Honduras (OR 4.65, 1.81-11.91).
SIGNIFICANCE: Maternal agrochemical exposure during pregnancy was linked to NSOFC in the largest multicountry study in LMICs to date examining this exposure. Identifying environmental risk factors specific to agricultural communities in LMICs is crucial for informing effective public health interventions, ultimately reducing the burden of orofacial clefts among underserved populations.
IMPACT: This study of nearly 7000 participants across eight low- and middle-income countries found that maternal agrochemical exposure during pregnancy was associated with increased odds of nonsyndromic orofacial clefts in children. Elevated estimates observed in Vietnam and Honduras highlight the importance of understanding environmental determinants of cleft risk in specific agricultural contexts and informing targeted prevention strategies in agricultural communities.
OBJECTIVE: To quantify the association between maternal agrochemical exposure during pregnancy and nonsyndromic orofacial clefts (NSOFCs) across eight LMICs.
METHODS: This population-sampled, unmatched case-control study included questionnaires administered to mothers of children with NSOFCs (cases) and mothers of unaffected children (controls) in the Democratic Republic of Congo (DRC), Guatemala, Honduras, Madagascar, Morocco, Nicaragua, the Philippines, and Vietnam. Binary logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported agrochemical exposure. Sub-analyses examined cleft subtypes and country-specific effects.
RESULTS: 3791 cases and 3190 controls recruited from 2012 to 2020 were included for the descriptive statistics. Agrochemical exposure was uncommon (5.4% of cases; 1.3% of controls), and DRC, Guatemala, Morocco, and Nicaragua were excluded from the binary logistic regression due to insufficient exposure reports. After adjustment, any pregnancy exposure was associated with an increased odds of NSOFC (OR 2.34, 95% CI 1.47-3.71); a comparable estimate was observed for first-trimester exposure (OR 2.63, 95% CI 1.37-5.04). The odds ratio was elevated for cleft lip ± cleft palate (OR 2.35, 1.45-3.81), with an elevated but non-significant point estimate for isolated cleft palate (OR 1.52; 95% CI: 0.73-3.15). Country-stratified models identified significantly elevated associations in Vietnam (OR 3.91, 1.35-11.30) and Honduras (OR 4.65, 1.81-11.91).
SIGNIFICANCE: Maternal agrochemical exposure during pregnancy was linked to NSOFC in the largest multicountry study in LMICs to date examining this exposure. Identifying environmental risk factors specific to agricultural communities in LMICs is crucial for informing effective public health interventions, ultimately reducing the burden of orofacial clefts among underserved populations.
IMPACT: This study of nearly 7000 participants across eight low- and middle-income countries found that maternal agrochemical exposure during pregnancy was associated with increased odds of nonsyndromic orofacial clefts in children. Elevated estimates observed in Vietnam and Honduras highlight the importance of understanding environmental determinants of cleft risk in specific agricultural contexts and informing targeted prevention strategies in agricultural communities.