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

  • Reproductive Endocrinology: Original Article
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Abstract

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.

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Data Availability

Clinical trial ID: NCT02610751. Website: https://clinicaltrials.gov/ct2/show/NCT02610751.

Code Availability

Not applicable.

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Acknowledgements

We would like to acknowledge the following people who had an integral role in helping us execute our study goals: thank you to the Medical Education Research Fund (MERF), who provided funding for the study. Thank you to the TriHealth Hatton Research Institute staff who helped in the screening, recruiting, enrollment, and data collection for our study. We would like to recognize the work of Vickie Glover, Carolyn Lindeman RN, Pam Plummer RN, and Kathyrn Waligura BA, BS. Thank you for your hard work.

Funding

Financial support was provided by Good Samaritan Hospital Medical Education Research Fund, this financial sponsor had no role in the study or decision to submit the study for publication.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, TriHealth Hatton Research Institute, Cincinnati, OH, USA

    Sashana S. Gordon MD, MS, David N. Dhanraj MD, MBA, C. Ganga Devaiah MS & Donna S. Lambers MD

  2. Department of Obstetrics and Gynecology, Northside Hospital, GA, Lawrenceville, USA

    Sashana S. Gordon MD, MS

Authors
  1. Sashana S. Gordon MD, MS
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  2. David N. Dhanraj MD, MBA
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  3. C. Ganga Devaiah MS
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  4. Donna S. Lambers MD
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Ethics declarations

Ethics Approval

The TriHealth Institutional Review Board (IRB) and Perinatal Scientific Review Committee (PSRC) approval was obtained prior to the initiation of the study.

Consent to Participate

Patients who agreed to be in the study signed informed consent prior to enrollment in the study.

Consent for Publication

This manuscript is submitted solely to The Reproductive Sciences Journal. No substantial part of this paper has been published elsewhere, except for a scientific abstract #F-095 presented as a virtual poster presentation at the Society for Reproductive Investigation’s 67th Annual Scientific Meeting, March 13, 2020, Vancouver, Canada. This publication has been approved by all co-authors. A transfer of copyright to the Society for Reproductive Investigation will be signed upon acceptance of publication.

Conflict of Interest

The authors declare no competing interests.

Additional information

Prospective cohort study comparing the female fetal testosterone levels of newborns of women who actively smoke tobacco in pregnancy and those who do not, results have shown no correlation between maternal smoking in pregnancy and maternal total testosterone levels or female fetal testosterone levels.

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Gordon, S.S., Dhanraj, D.N., Ganga Devaiah, C. et al. A Pilot Study of Exposure to Nicotine in Human Pregnancy and Maternal and Fetal Testosterone Levels at Birth. Reprod. Sci. 29, 3254–3259 (2022). https://doi.org/10.1007/s43032-022-00967-2

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  • DOI: https://doi.org/10.1007/s43032-022-00967-2

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