The Effects of Prenatal Cigarette Smoke Exposure on Developmental Milestones

In Kentucky, a reported 12.7% of mothers smoke cigarettes during pregnancy. Nicotine readily crosses the placental and blood-brain barriers, with fetal blood concentrations reaching 15% higher than maternal levels. By stimulating and desensitizing nicotinic acetylcholine receptors in the autonomic nervous system, nicotine disrupts uteroplacental blood flow, potentially altering fetal growth and development. To investigate the effects of prenatal cigarette smoke exposure (CSE) on developmental milestones, C57Bl6 mice were exposed to either cigarette smoke (CSE, n = 30) or filtered room air (Sham, n = 20) for 3 hours daily from two days before mating until the day before birth. Offspring were monitored from birth to weaning, with measurements including body weight, crown-to-rump length, anogenital distance, and developmental milestones such as surface righting reflex from postnatal day (PD) 3 to PD 8, eye opening, ear detachment, and pubertal timing (vaginal opening and preputial separation). We hypothesized that even a moderate daily exposure duration would negatively impact early growth and development, leading to reduced birth size, delayed motor and sensory milestones, and altered pubertal timing. CSE pups had decreased crown-to-rump length and delayed eye opening at the individual level but not by litter average. CSE females had delayed motor development at PD 5 but caught up by PD 6. Additionally, vaginal opening occurred earlier in CSE females. These findings suggest that prenatal CSE disproportionately affects female offspring, particularly in motor development and pubertal timing.