Johnston ZC, et al. - During this study, experts gauged the adrenal steroid levels and steroidogenic enzyme expression in normal second-trimester human fetuses, with regard to the effects of maternal smoking. Throughout the second trimester, it was noted that human fetal adrenal gland produced cortisol but very low levels of Δ⁴ androgens, with no detectable aldosterone. Cortisol presence in fetal adrenals depicted that adrenal regulation of circulating fetal adrenocorticotropic hormone (ACTH) served as a factor in the development of congenital adrenal hyperplasia during the second trimester. Moreover, salt-wasting disorders frequently seen in extreme pre-term neonates were elucidated via a relative lack of aldosterone. Researchers deduced that maternal smoking could alter fetal adrenal sensitivity to ACTH, which possibly imparted knock-on effects on the post-natal health.