Smoking during pregnancy may damage daughters’ future fertility

Sept 2019

Baby girls, born to mothers who smoked during pregnancy, exhibit signs of increased testosterone exposure, which may affect their hormone and reproductive function, according to research presented today at the 58th Annual European Society for Paediatric Endocrinology Meeting. The findings of this study suggest that cigarette is an endocrine disruptor that can masculinise girls in the womb and that daughters of women that smoked during pregnancy may suffer from hormonal and reproductive health problems in the long-term.

Smoking during pregnancy is widely known to be bad for the health of both mother and baby, yet some women persist and many are exposed to second-hand smoke. In addition to the many toxins present in cigarette smoke, it is also suspected of having endocrine-disrupting properties that may increase testosterone levels. Baby girls exposed to higher levels of male hormone, testosterone, in the womb are at greater risk of abnormal development and long-term negative effects on their fertility and metabolism. Anogenital distance (AGD), the distance from the midpoint of the anus to the genitalia, is regulated by testosterone levels during foetal development, so is a sensitive marker of testosterone exposure and life-long reproductive health.

In this study, Dr Deniz Özalp Kızılay and colleagues at Cigli State Training Hospital in Turkey, measured the AGD in 56 newborn girls and 64 newborn boys, from mothers who smoked during pregnancy. AGD was significantly longer in the baby girls and correlated with the amount the mothers smoked. No effect was found on the AGD in the boys.

Dr Kızılay states, “This significant increase in AGD in girls exposed to maternal smoking may be an indicator of excessive testosterone exposure that poses a risk for short and long-term health problems, including metabolism and fertility. Further investigation is needed to explain the relationship between maternal smoking, increased AGD and future health issues in girls.”

Although Dr Kızılay, cautions, “The mechanisms behind the potential reproductive problems caused by exposure to cigarette smoke in the womb are not fully understood. Our results do suggest that girls have higher testosterone exposure but not how this relates to reproductive function. More extensive and carefully-designed studies are required to explain this relationship.”

The team now plan to monitor the long-term effects of exposure to higher testosterone levels caused by smoke exposure in the same group of baby girls, to assess how this may affect their future health and fertility.

Dr Kızılay comments, “To our knowledge this is the first time that the unfavourable effects of prenatal smoke exposure on AGD, as a marker of testosterone exposure, has been demonstrated in female newborns. These findings are a valuable contribution to our better understanding of the intergenerational effects of maternal smoking."

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Abstract

Prenatal smoke-exposure is associated with increased anogenital distance in female infants

Deniz Özalp Kızılay1, Cansever Aydın2, Ayşe Aygün2, Hale Ünver Tuhan1, Özgür Olukman3

1Çiğli State Training Hospital, Department of Pediatrics, Division of Pediatric Endocrinology, Izmir, Turkey. 2Çiğli State Training Hospital, Department of Pediatrics, Izmir, Turkey. 3Çiğli State Training Hospital, Department of Pediatrics, Division of Neonatology, Izmir, Turkey

Background: Cigarette contains more than 4,000 toxins and is suspected of having endocrine-disrupting properties. Anogenital distance (AGD) is an important biomarker of fetal androgen exposure and intrauterine masculinization. There are limited number of studies examining whether AGD is affected by prenatal smoke-exposure. The aim of this study is to investigate the effects of maternal smoking during pregnancy on newborn infants' AGD.

Method: Fifty-six female and sixty-four male newborn infants from mothers who smoked during pregnancy were included in this study. The 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 hours after birth. In boys, AGD has been measured from anus to posterior insertion of the penis (AGDapp), scrotum (AGDas), and cephalad insertion of the penis (AGDap).  In girls, AGD has been measured from anus to posterior insertion of the clitoris (AGDapc), base of the posterior fourchette (AGDaf), and the top of the clitoris (AGDac). AGD(app/apc) were also normalized according to birthweight (AGD/weight in grams), length (AGD/CRL in millimeters), and ponderal index [AGD/(weight in grams/CRL in cubic centimeters)]. Anogenital index (AGI) was calculated by dividing the AGDapp/apc by cube root of birthweight.

Results: Prenatal smoke exposure was associated with significantly increased weight-adjusted AGD in female infants at birth (p = 0.03). There was also a significant correlation between mothers' daily smoking rates and weight-adjusted AGD (r = 0.27 / p = 0.03). Fetal smoke-exposure was not associated with any AGD measurements, SPL and penil width in boys.

Discussion: 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 and metabolic problems. In this context, more extensive studies are needed to explain the relationship between maternal smoking and AGD change.

Keywords: Anogenital distance, Fetal smoke-exposure, Androgenic effect, Endocrine disruptors

Notes for editors:

1. The study “Prenatal smoke-exposure is associated with increased anogenital distance in female infants” was presented by Dr Deniz Özalp Kızılay on Friday 20 September (abstract LB-14), at the 58th Annual European Society for Paediatric Endocrinology Meeting in Vienna, Austria.

2. The 58th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2019 Meeting) is held 19-21 September 2019 in Vienna, Austria. The ESPE annual meeting is recognised worldwide as being of high scientific and educational quality.

3. The European Society for Paediatric Endocrinology (ESPE) is a truly international organisation aiming to improve the clinical care of children and adolescents with endocrine conditions, including diabetes, through research and education. www.eurospe.org