Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort.
BACKGROUND
Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.


METHODS
An ongoing population-based birth cohort study of Dominican Republic and African-American children in New York prospectively assessed the use of analgesics during pregnancy and current wheeze at age 5 years in 301 children. Genotyping was conducted for GST polymorphisms. Binomial regression was used to adjust for potential confounders including postnatal acetaminophen use.


RESULTS
34% of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive interaction p=0.009) and was observed only among children with the GSTP1 minor allele.


CONCLUSIONS
Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.
Perzanowski
Matthew S
MS
Columbia Center for Children's Environmental Health (CCCEH), New York, NY 10032, USA.
Miller
Rachel L
RL
Tang
Deliang
D
Ali
David
D
Garfinkel
Robin S
RS
Chew
Ginger L
GL
Goldstein
Inge F
IF
Perera
Frederica P
FP
Barr
R Graham
RG
D000082:Acetaminophen / Q000009:adverse effects*; D000485:Allergens / Q000276:immunology; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012135:Respiratory Sounds / Q000209:etiology; D012959:Socioeconomic Factors; D014504:Urban Health / Q000706:statistics & numerical data
D000485:Allergens; D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D007073:Immunoglobulin E; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi