A Pilot Study of Exposure to Nicotine in Human Pregnancy and Maternal and Fetal Testosterone Levels at Birth

Nicotine exposure in pregnant rats and sheep has shown a more than 50% increase in female fetal testosterone (FFT) levels. Increased testosterone levels have also been linked to infertility, increased anogenital distance (AGD), and reduced second to fourth digit (2D:4D) finger length ratios (FLR). In humans, we hypothesized that maternal total testosterone (MTT) levels would increase in smoking mothers and would cause increased FFT levels, increased AGD, and decreased 2D:4D FLR. This prospective study separated women expecting a female fetus into nonsmoking and smoking cohorts. Maternal cotinine (MC) was tested at 3rd trimester and delivery to assess nicotine exposure. MTT levels were drawn at delivery, and FFT levels were collected from cord blood. The AGD and 2D:4D FLRs were measured at birth. Data were analyzed using parametric and nonparametric tests. The data of 36 smokers and 28 nonsmokers were analyzed. Smoking mothers had higher parity, drug abuse history and were more likely white race. No statistical differences were seen among the primary outcomes of MTT and FFT. MTT was higher among nonsmokers versus smokers (144 versus 107 ng/dL). No correlations were noted between MC levels at delivery, MTT, and FFT levels. No statistical differences were noted among secondary outcomes of AGD and FLR. Although animal studies showed increased FFT levels after nicotine exposure, this was not seen in our human study. Placental differences in animals and humans may be at work. Our pilot study reveals a need for research on the effects of smoking in pregnancy on fetal hormones.