The asssociation between maternal psychological variables, particularly maternal antenatal anxiety, has been linked with clinical [1,2] and biochemical [3] outcomes in the offspring of their pregnancies. These observations support possibility of prenatal programming mediated through the developing hypothalamo-pituitary-adrernal (HPA) axis of the fetus. There have been two reports of an association between maternal stress in early childhood and the development of wheeze [4] and asthma [5] in children. We have also reported in ALSPAC an association between prenatal maternal anxiety and asthma in the offspring at age seven years [6]. Although it has been speculated that this association may also be mediated through the HPA axis and thus affect the developing immune system, we found no strong evidence to support a stronger effect in atopic compared with non-atopic asthmatic children.

We have developed a collaboration with a group in Western Canada that has published on maternal stress and asthma [5] and has recently identified evidence of an interaction between chronic maternal stress and a functional polymorphism of the MTHFR gene in association with childhood asthma. We found no association of maternal or child genotype for the C677T polymorphism of MTHFR and asthma [7], in contrast to a study of Danish adults [8] but we have not invesitgated the possibility of an interaction between this genotype and maternal psychological variables. Therefore, we wish to test the hypothesis that maternal stress (anxiety and depression) in the prenatal and postnatal periods (particularly chronic stress) interacts with the C677T allele of MTHFR in association with asthma at age 7 years in the ALSPAC cohort.

1. O'Connor TG, Heron J, Golding J, Glover V. Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. J Child Psychol Psychiatry. 2003 Oct;44(7):1025-36.

2. Glover V, O'Connor TG, Heron J, Golding J. Antenatal maternal anxiety is linked with atypical handedness in the child. Early Hum Dev. 2004 Sep;79(2):107-18.

3. O'Connor TG, Ben-Shlomo Y, Heron J, Golding J, Adams D, Glover V. Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. Biol Psychiatry. 2005 Aug 1;58(3):211-7.

4. Wright RJ, Cohen S, Carey V, Weiss ST, Gold DR. Parental stress as a predictor of wheezing in infancy: a prospective birth-cohort study. Am J Respir Crit Care Med. 2002 Feb 1;165(3):358-65.

5. Kozyrskyj AL, Mai XM, McGrath P, Hayglass KT, Becker AB, Macneil B. Continued exposure to maternal distress in early life is associated with an increased risk of childhood asthma. Am J Respir Crit Care Med. 2008 Jan 15;177(2):142-7.

6. Cookson H, Granell R, Joinson C, Ben-Shlomo Y, Henderson J. Mothers' anxiety during pregnancy is associated with asthma in their children. J Allergy Clin Imunol (submitted)

7. Granell R, Heron J, Lewis S, Davey Smith G, Sterne JAC, Henderson J. The association between mother and child MTHFR C677T polymorphisms, dietary folate intake and childhood atopy in a population-based, longitudinal birth cohort. Clin Exp Allergy. 2008 Feb;38(2):320-8.

8. Husemoen LL, Toft U, Fenger M, Jorgensen T, Johansen N, Linneberg A. The association between atopy and factors influencing folate metabolism: is low folate status causally related to the development of atopy? Int J Epidemiol. 2006 Aug;35(4):954-61.