Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor a (FRa), as well as possible effects of parental demographics or prenatal exposures.
We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FRa was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors.
There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FRa (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FRa.
Inhibition of folic acid binding to FRa in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.
Cites: MMWR Morb Mortal Wkly Rep. 2004 May 7;53(17):362-515129193
Cites: N Engl J Med. 2004 Jan 8;350(2):134-4214711912
Cites: Lancet. 1991 Jul 20;338(8760):131-71677062
Cites: N Engl J Med. 1992 Dec 24;327(26):1832-51307234
Cites: Q J Med. 1993 Nov;86(11):703-88265769
Cites: Am J Clin Nutr. 1994 Oct;60(4):559-668092091
Cites: Int J Gynaecol Obstet. 2006 May;93(2):142-316546188
Cites: Am J Epidemiol. 2005 Sep 1;162(5):448-5316076837
Cites: Hum Reprod. 1998 May;13(5):1312-69647565
Cites: Eur J Epidemiol. 2006;21(8):619-2517031521
Cites: Int J Epidemiol. 2006 Oct;35(5):1146-5016926217
Cites: Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):693-70517029289
Cites: BMJ. 2007 Mar 3;334(7591):46417259187
Cites: Dev Med Child Neurol. 2008 May;50(5):346-5218355335