Maternal Pharmaceutical Intake, Tobacco Smoking, and Environmental Pesticide Exposures: High-Resolution Serum Pesticide Screening, Longitudinal Fetal Ultrasound Biometry, and Postnatal Anogenital Distance in a Brazilian Cohort

Maternal lifestyle exposures and pharmaceutical consumption during gestation represent key modulators of intrauterine growth and reproductive tract programming. This prospective cohort study evaluated the associations of maternal clinical history, medication use, and tobacco smoking with serial fetal ultrasound biometry, AGD, and postnatal infant anthropometry. A cohort of 51 pregnant women was prospectively enrolled during the first trimester (≤14 weeks) in Guarapuava, PR, Brazil, of whom 42 completed standardized longitudinal assessments across early gestation (11–14 weeks), mid-gestation (20–26 weeks), and late gestation (32–36 weeks), followed by pediatric evaluation at 8–10 months of life (n = 17). Clinical, sociodemographic, and pharmacological profiles were acquired through interviewer-administered structured questionnaires. Serial obstetric sonography was used to quantify the crown–rump length (CRL), estimated fetal weight (EFW), amniotic fluid index (AFI), and fetal AGD using electronic calipers. Postnatal infant AGD (anus to scrotum [AGD-AS] and anus to penis [AGD-AP] in males; anus to fourchette [AGD-AF] and anus to clitoral hood [AGD-AC] in females) was measured using digital calipers. Concurrently, high-resolution suspect pesticide screening (RP-UPLC-QTOF-MS) was performed on maternal serum collected early (≤14 weeks) and at mid-gestation (16–26 weeks) to identify circulating pesticide residues. Paracetamol was the most frequently reported drug (85.71%), followed by antibiotics (21.43%) and dipyrone (16.67%). Tobacco smoking during pregnancy was reported by 23.81% of mothers (mean: 10.10 ± 7.18 cigarettes/day). Fetal AGD expanded significantly from mid- to late gestation in both male fetuses (from 15.92 ± 3.50 mm to 31.22 ± 4.08 mm, p < 0.001) and female fetuses (from 12.11 ± 1.79 mm to 22.37 ± 4.46 mm, p < 0.001). In male infants aged 8–10 months, active maternal smoking during pregnancy was significantly associated with a marked reduction in AGD-AS (23.71 ± 3.67 mm vs. 32.89 ± 3.96 mm, p = 0.011) and an attenuation in AGD-AP (56.80 ± 0.99 mm vs. 71.31 ± 9.29 mm, p = 0.057). Exploratory analyses of therapeutic exposure to paracetamol, dipyrone, or antibiotics revealed no nominal differences in fetal biometric parameters or birth weight, although analyses were underpowered to rule out subtle effects. In female infants, birth weight correlated positively with AGD-AC (r = 0.956, p = 0.0435). Notably, pesticide residues were detected in 100% of the evaluated pregnant women (n = 42), revealing 55 distinct active xenobiotic ingredients across insecticides, herbicides, fungicides, and acaricides. The most prevalent compounds in early and mid-gestation included tebutam, pirimiphos-methyl, fenazaquin, butocarboxim, pendimethalin, silthiofam, and esprocarb. In conclusion, maternal tobacco smoking was associated with shorter male postnatal AGD in a very small subgroup (n = 2 exposed vs. n = 11 unexposed), which warrants cautious interpretation and validation in larger cohorts. High-resolution metabolomic screening provided qualitative evidence of multiclass pesticide residues in maternal circulation. Overall, this multimodal protocol illustrates a feasible surveillance framework, but the findings remain hypothesis-generating and require independent quantitative validation.