The mechanisms by which folic acid may contribute to reductions in risk of several congenital anomalies are unknown. The data gap includes a lack of information on possible effect modification between maternal folic acid use and other maternal exposures. We hypothesized that effects of congenital anomalies associated with maternal fever, cigarette smoking or alcohol use would be modified by intake of vitamins.Methods.
We explored case-control data that showed risk reductions among infants and fetuses whose mothers consumed vitamins. Data were from California deliveries of infants and fetuses in the period 1987–1989. Maternal telephone interviews were completed for 207 (87%) conotruncal cases, 489 (85%) orofacial cleft cases, 265 (84%) neural tube defect cases, 165 (82%) limb anomaly cases, and 734 controls (nonmalformed infants).Results.
Considering women who reported vitamin use and no periconceptional fever as referents, for each anomaly group we observed elevated effects for the combinations of maternal vitamin use/fever, no use/no fever and no use/fever. Effects were most elevated for the combination of no vitamin use and fever. Adjusted for maternal body mass index, education and race/ethnicity, odds ratios were 2.4 (95% confidence inter-val = 1.0–5.9) for conotruncal defects, 2.9 (1.4–5.8) for cleft lip with or without cleft palate, 1.3 (0.4–3.9) for cleft palate, 3.1 (1.4–6.8) for neural tube defects, and 2.6 (1.0–6.4) for limb-deficiency defects. These interactions were further investigated relative to maternal use of fever-reducing medications. Effects tended to be highest among those women who did not use vitamins, had fevers, and did not use fever-reducing medications. Compared with women who used vitamins and did not smoke periconceptionally, anomaly risks tended to be highest among women who did not use vitamins and smoked. No specific pattern emerged involving alcohol intake.Conclusions.
These data further suggest that the underlying mechanisms of folic acid associated with congenital anomalies may be complex.