Targeted Analysis of Placental Steroid Hormones in Relation to Maternal Tobacco Smoke Exposure: Early Markers Relevant to DOHaD (Developmental Origins of Health and Disease)

TL;DR

This study finds that maternal smoking disrupts placental steroid hormones, which could affect fetal development and long-term health.

Contribution

The study identifies specific placental steroid hormone changes linked to maternal tobacco exposure, independent of birth weight.

Findings

All six measured placental steroids differed significantly between smoking and non-smoking groups.

Active smoking reduced estrogens and progestins while increasing testosterone, even after adjusting for birth weight.

A steroid panel accurately classified smoking exposure status with high cross-validated accuracy.

Abstract

Maternal tobacco smoke exposure is associated with impaired fetal growth and long-term disease risk (DOHaD, Developmental Origins of Health and Disease). Whether placental steroid hormones are independently altered remains a matter of debate. We quantified six placental steroids (estradiol, estriol, estrone, progesterone, testosterone, and pregnanediol) using HPLC–Corona CAD in 70 deliveries (C = 30; PS = 20; AS = 20). Distributional differences were assessed with Kruskal–Wallis and pairwise Mann–Whitney tests with Benjamini–Hochberg (BH) control. Adjusted associations used log-linear OLS with HC3 robust SE: Model A (gestational age, maternal BMI, newborn sex) and Model B (Model A + birth weight), reported as percent change vs. controls, computed as (exp(β) − 1) × 100 with 95% CI. Secondary analyses tested (i) multiclass logistic classification of C/PS/AS from the steroid panel (5-fold stratified CV) and (ii) prediction of birth weight (OLS and 2-component PLS). All six steroids differed by group (BH-adjusted p ranging from 9.18 × 10−12 to 6.66 × 10−8). In Model A, AS vs. C showed lower estrogens/progestins (estradiol, −46.2%; estriol, −24.7%; estrone, −25.9%; progesterone, −28.2%; pregnanediol, −31.4%) and higher testosterone (+40.8%); these effects persisted in Model B after adjusting for birth weight. The panel classified C/PS/AS with 0.900 cross-validated accuracy (weighted OvR AUC 0.994). Hormones poorly predicted birth weight (PLS CV R2 = −0.777). Maternal active and passive smoking is associated with a coherent and independent disruption of placental steroidogenesis. A targeted placental steroid panel offers biologically meaningful early markers relevant to DOHaD.

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