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Birth defects, smoking and host susceptibility

Institution: March of Dimes Birth Defects Foundation
Investigator(s): Suzan Carmichael, Ph.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12RT-0098 Award: $466,200
Subject Area: Epidemiology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
This research will improve our understanding of the contribution of maternal smoking to the risk of birth defects; taking into account the potential modifying effects of other exposures and genetic factors, by achieving the following specific aims: 1) To examine whether women who smoke around the time of conception are at increased risk of delivering infants with craniosynostosis (i.e., premature fusion of bones in the skull, which leads to skull and craniofacial deformities), and whether factors such as intake of multivitamin/mineral supplements modify this association; 2) To determine whether women who smoke around the time of conception are at increased risk of delivering infants with hypospadias (i.e., the urethral opening occurs on the underside side of the penis), and whether factors such as intake of multivitamin/mineral supplements modify this association; and 3) To examine whether the association between maternal smoking around the time of conception and risk of limb defects is modified by variation in infant genes important to the breakdown of toxins in cigarette smoke.

Aims 1 and 2 use newly collected maternal interview data from the National Birth Defects Prevention Study, an on-going case-control study being conducted in California and seven other states, with support from the Centers for Disease Control and Prevention (CDC). In year 1, we have cleaned the data and completed an analysis of the association between hypospadias and smoking, which did not provide evidence for an increased risk of hypospadias among women who smoke. In year 2 we will further analyze these data to determine whether there is an association among any subsets of women, e.g., women who did versus did not take vitamin supplements during early pregnancy. When adequate sample size has been reached for craniosynostosis cases, we will perform similar analyses for that outcome.

Aim 3 combines maternal interview data from a completed case-control study that was conducted in California only with newly generated genetic data derived from archived DNA specimens. In year l, we have completed genotyping for all study subjects for the glutathione S-transferase genes GSTM1 and GSTT1 and the N-acetyltransferase gene NAT1. We have recently developed a new method of mass spectrometry analysis for genotyping NAT2, which uses considerably less DNA than previous methods. During year 2, we will conduct the NAT2 genotyping on our study subjects and begin data analysis.

This research will result in a better understanding of the contribution of smoking to birth defects risks and of the mechanisms that cause birth defects, and therefore enable the development of more effective messages for smoking prevention and cessation.
Publications

Hypospadias and maternal exposures to cigarette smoke.
Periodical: American Public Health Association Index Medicus:
Authors: Carmichael SL, Shaw GM, Laurent C, Lammer E, Olney R ABS
Yr: 2003 Vol: Nbr: Abs: Pg: