The effect of tobacco exposure on the fetal hypothalamic–pituitary–adrenal axis


Dr SD McDonald, McMaster University, Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, 1200 Main St West, HSC 3N52B, Hamilton, Canada ON L8N 3Z5. Email


Objective  Our objective was to determine if maternal smoking is associated with programming of the fetal hypothalamic–pituitary-adrenal (HPA) axis. Cigarette smoking, which induces a state of hypoxia in the fetus, may promote in utero‘programming’ of the HPA axis. In utero, adaptations to the HPA axis, which become maladaptive later in life, have been hypothesised to contribute to the development of adult cardiovascular disease and metabolic disorders.

Design  This was a prospective cohort study of term infants.

Population and setting  The study involved 104 infants born by elective caesarean section, 21 of whom were exposed to in utero tobacco and 83 were nonexposed.

Methods  Healthy women with healthy pregnancies were recruited if they were undergoing elective caesarean section. Maternal blood was drawn for cortisol and cotinine in the morning, and the umbilical blood was drawn immediately after delivery of the baby.

Main outcome measures  Umbilical arterial cortisol and adrenocorticotropin hormone (ACTH) levels.

Results  ACTH levels were significantly elevated in smoke-exposed infants [17 (4–22) pmol/l versus 4 (2–11) pmol/l, respectively, P= 0.005], while cortisol levels were similar [182 (130–240) nmol/l versus 192 (127–265) nmol/l, respectively, P= 0.541].

Conclusions  For the first time, it was shown that infants exposed to in utero tobacco smoke have significantly elevated ACTH levels compared with nonexposed infants. The results of this study warrant further exploration of the effect of smoking on the neonatal HPA axis as a potential set up for ‘programming’.