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Licensed Unlicensed Requires Authentication Published by De Gruyter October 9, 2020

Prenatal smoke exposure is associated with increased anogenital distance in female infants: a prospective case–control study

Deniz Özalp Kızılay, Cansever Aydın, Ayşe Pakel Aygün, Hale Ünver Tuhan and Özgür Olukman



To investigate the effects of maternal smoking during pregnancy on newborn infants’ anogenital distance (AGD).


Fifty-six female and sixty-four male newborn infants from mothers who smoked during pregnancy were included in this study. A control group for each sex was selected from infants whose mothers had no active or passive (in either the household or the workplace) smoke exposure before or during pregnancy. Questionnaire data on maternal demographic characteristics and information about cigarette use were collected. We assessed genital anthropometry which included AGD for both male and female neonates, and stretched penile length (SPL), penile girth for males within the first 48 h after birth. AGD measurements were also normalized according to birth weight (AGD/weight in grams), length (AGD/height in millimeters), and ponderal index [AGD/(weight in grams/height in cubic centimeters)]. Anogenital index (AGI) was calculated by dividing the AGD by cube root of birth weight.


In female infants, prenatal smoke exposure was associated with significantly increased weight-adjusted AGD (p=0.03). There was also a significant correlation between mothers’ daily smoking rates and weight-adjusted AGD (r=0.27/p=0.03). In male infants, fetal smoke exposure was not associated with any AGD measurements, SPL and penile girth.


A significant increase in weight-adjusted AGD in female infants exposed to maternal smoking may be an indicator of antenatal androgen exposure and may pose a risk for short and long-term endocrine, metabolic and behavioral problems.

Corresponding author: Deniz Özalp Kızılay, Bakırçay University Çiğli Training and Research Hospital, Department of Pediatrics, Division of Pediatric Endocrinology, 35620, Izmir, Turkey, Phone: +90 5334489244, Fax: +90 232 3983719, E-mail:


The authors would like to thank Prof. Dr. Tülay Güran (Department of Pediatric Endocrinology and Diabetes, Marmara University, School of Medicine, Istanbul, Turkey) for a great deal of support and her valuable guidance. We would like to thank Prof. Dr. Beyhan Cengiz (Department of Public Health, Faculty of Medicine, Celal Bayar University, Manisa, Turkey) and Dr. Cigdem Selli (MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh) for helping statistical analysis of the study. We thank Dr. Louise Bath (Consultant of Pediatric Endocrinology and Diabetes in Royal Hospital for Sick Children, Edinburgh, Scotland) for English language editing of this manuscript.

  1. Research funding: We have no direct or indirect commercial financial incentive associated with publishing the article. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

  2. Authors’ contribution: D.Ö.K. contributed in study design, conducting training sessions, analyzing and interpreting the data, and taking the lead in writing and revision of the manuscript. C.A. performed the measurements, contributed in collecting and inputting the data. A.P.A informed the participants about the study, obtained consent and organized the questionnaires. H.Ü.T participated in study design and critical reading. Ö.O participated in conducting training sessions, collecting and interpreting the data, supervised the manuscript and provided critical feedback.

  3. Conflict of interest: The authors declare there was no any conflict of interest. All authors declare no competing interests.

  4. Ethical approval: The study was approved by the Behçet Uz Children's Hospital Ethics committee and adhered to the Declaration of Helsinki for Medical Research involving Human Subjects.


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Received: 2020-04-04
Accepted: 2020-08-06
Published Online: 2020-10-09
Published in Print: 2021-01-27

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