Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use.
BACKGROUND
Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N-acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring.


METHODS
In this case-control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites.


RESULTS
Slow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4-2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3-1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk.


CONCLUSIONS
Maternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use.
van Rooij
Iris A L M
IA
Department of Epidemiology and Biostatistics, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Groenen
Pascal M W
PM
van Drongelen
Merel
M
Te Morsche
René H M
RH
Peters
Wilbert H M
WH
Steegers-Theunissen
Régine P M
RP
D000700:Analgesics / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000927:Anticonvulsants / Q000009:adverse effects; D000928:Antidepressive Agents / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000032:analysis / Q000235:genetics*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000209:etiology*; D002972:Cleft Palate / Q000209:etiology*; D064420:Drug-Related Side Effects and Adverse Reactions; D004639:Emetics / Q000009:adverse effects; D005260:Female; D006801:Humans; D008019:Life Style; D008423:Maternal Age; D008431:Maternal-Fetal Exchange; D010298:Parity; D010641:Phenotype; D011247:Pregnancy; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016135:Spinal Dysraphism / Q000209:etiology*
D000700:Analgesics; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D004639:Emetics; D001191:Arylamine N-Acetyltransferase