Abstract
BackgroundHistorically, neural tube defects (NTDs) have predominated in female infants but the reasons remain unclear. In South America, the pre- folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67. During the post- FAF period, unpublished routine reports have indicated changes in the sex ratio for these defects while some descriptive reports are controversial. To date and to our knowledge, however, no studies specifically focusing on these changes to test this hypothesis directly have been undertaken. The aim of this study was to analyze changes in the sex ratio of infants with NTDs after FAF in South American countries.Materials and methodsWith a descriptive cross-sectional study design, 2,597 infants with isolated NTDs born between 1990 and 2013 in 3 countries participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network were included: (Chile N = 521 and Argentina N = 1,619 [with FAF policies]; Venezuela N = 457 [without FAF policies; used as control]; total births = 2,229,561). The differences-in-differences method and Poisson regressions were used to evaluate the sex ratio shift from female to male before vs. after FAF, and to assess whether these differences were related to the fortification.Results and conclusionsIn Chile and Argentina the prevalence of NTDs, particularly anencephaly and cervico-thoracic spina bifida, showed a greater reduction rate in females than in males after FAF, resulting in a change of the sex ratio of infants with NTDs. Some mechanisms possibly involved in this differential reduction are proposed which might be useful to identify the pathogenesis of NTDs as a whole and specifically of those susceptible to the protective effect of folic acid.
Highlights
Neural tube defects (NTDs), including spina bifida, anencephaly and cephalocele, are severe birth defects of the central nervous system that occur during embryonic development when the neural tube fails to close completely
In previous studies we have shown the impact of these policies: in change during the whole study period (Chile) and Argentina the observed neural tube defects (NTDs) prevalence declined to almost a half after folic acid fortification [1, 12], while in Brazil such a strong reduction could not be as clearly observed, showing more heterogeneous rates [1, 17]
The total number of births with specified sex was 2,229,561 (98.6%), and the population SR (M/F) of the 3 countries did not change during the whole study period (Chile: before folic acid fortification (FAF) = 1.051, after FAF = 1.055, p = 0.1758; Argentina: before FAF = 1.041, after FAF = 1.049, p = 0.192; and Venezuela = 1.061) (Fig 1)
Summary
Neural tube defects (NTDs), including spina bifida, anencephaly and cephalocele, are severe birth defects of the central nervous system that occur during embryonic development when the neural tube fails to close completely. In South America before folic acid fortification, as well as in other countries without fortification policies, the overall prevalence of NTDs varied between 10 and 20 per 10,000 births [1], and showed a historical female sex predisposition for the three malformations. Based on the evident reduction of NTDs after periconceptional folic acid fortification (FAF) [9,10,11,12], three countries in South America have implemented national fortification policies: Chile in January 2000 [13], Argentina in December 2003 [14], and Brazil in July 2004 [15]. In South America, the pre- folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67. The aim of this study was to analyze changes in the sex ratio of infants with NTDs after FAF in South American countries
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