Maternal Smoking During Pregnancy and Female Fetal Testosterone Levels

NCT ID: NCT02610751

Last Updated: 2019-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-01-31

Study Completion Date

2019-08-26

Brief Summary

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* The investigators hope their study will answer the question of whether or not fetal testosterone levels are increased in female newborns exposed to nicotine as a result of maternal smoking during pregnancy. Secondarily they plan to also evaluate maternal cotinine and testosterone levels and newborn anogenital distance, second digit to fourth digit (2D:4D) finger length ratio, newborn length and birth weight.
* The investigators hope by performing this study, they will help to uncover the effect of tobacco exposure in utero on human female fetal testosterone levels, thus improving the counseling for tobacco use in pregnancy.

Detailed Description

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Epidemiological studies and laboratory research performed on animal models have revealed that the effects of maternal smoking during pregnancy go beyond the perinatal period due to the effect of nicotine on increasing fetal testosterone levels. This is of great concern as an increase fetal testosterone has been linked to impaired reproductive development and infertility in both male and female offspring, early onset of menarche in females, shorter body height, increased BMI, shortened anogenital distance and low second digit to fourth digit finger length ratio. Additionally elevated fetal testosterone levels have been associated with development of psychosocial disorders such as Autism, ADHD, antisocial behavior, conduct disorder, adult criminal behavior, and sensation seeking behavior.

Although there have been a few animal studies that have investigated the effects of maternal nicotine exposure on fetal testosterone levels with review of the epidemiologic literature on subsequent adverse implications, no known human studies have been performed to further investigate the relationship between maternal smoking during pregnancy and female fetal testosterone levels.

Conditions

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Smoking

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Smoking

No interventions were applied to this group. Measurements of female fetal testosterone, maternal cotinine and testosterone levels, newborn anogenital distance, second digit to fourth digit (2D:4D) finger length ratio, newborn length and birth weight are collected.

No interventions assigned to this group

Non-smoking

No interventions were applied to this group. Measurements of female fetal testosterone, maternal cotinine and testosterone levels, newborn anogenital distance, second digit to fourth digit (2D:4D) finger length ratio, newborn length and birth weight are collected.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Women, \>/= 18 years old
* Current singleton pregnancy
* Recruited prior to 3rd trimester lab visit
* Known female fetus confirmed by Ultrasound, typically performed 18 to 22 weeks, or later gestational age (GA)
* Self reported smoker (of at least ½ pack per day) or non-smoker documented in electronic chart.
* Eligibility will not be limited by desired mode of delivery

Exclusion Criteria

* Patients who successfully quit smoking at \<14 weeks gestation and who have not resumed smoking during the pregnancy will be excluded from the case/control arm of study.
* Patients considered light smokers, who self report smoking less than ½ pack per day.
* Patients with Polycystic Ovarian Syndrome
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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TriHealth Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dave Dhanraj, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

TriHealth Inc.

Locations

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Good Samaritan Hospital

Cincinnati, Ohio, United States

Site Status

Bethesda North Hospital

Cincinnati, Ohio, United States

Site Status

Countries

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United States

References

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Smith LM, Cloak CC, Poland RE, Torday J, Ross MG. Prenatal nicotine increases testosterone levels in the fetus and female offspring. Nicotine Tob Res. 2003 Jun;5(3):369-74. doi: 10.1080/146222031000094196.

Reference Type BACKGROUND
PMID: 12791533 (View on PubMed)

Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK53017/

Reference Type BACKGROUND
PMID: 21452462 (View on PubMed)

Duskova M, Hruskovicova H, Simunkova K, Starka L, Parizek A. The effects of smoking on steroid metabolism and fetal programming. J Steroid Biochem Mol Biol. 2014 Jan;139:138-43. doi: 10.1016/j.jsbmb.2013.05.003. Epub 2013 May 14.

Reference Type BACKGROUND
PMID: 23685014 (View on PubMed)

Cornelius MD, Day NL. Developmental consequences of prenatal tobacco exposure. Curr Opin Neurol. 2009 Apr;22(2):121-5. doi: 10.1097/WCO.0b013e328326f6dc.

Reference Type BACKGROUND
PMID: 19532034 (View on PubMed)

Cornelius MD, Leech SL, Goldschmidt L, Day NL. Is prenatal tobacco exposure a risk factor for early adolescent smoking? A follow-up study. Neurotoxicol Teratol. 2005 Jul-Aug;27(4):667-76. doi: 10.1016/j.ntt.2005.05.006.

Reference Type BACKGROUND
PMID: 16014324 (View on PubMed)

Day NL, Richardson GA, Goldschmidt L, Cornelius MD. Effects of prenatal tobacco exposure on preschoolers' behavior. J Dev Behav Pediatr. 2000 Jun;21(3):180-8.

Reference Type BACKGROUND
PMID: 10883878 (View on PubMed)

Ernst A, Kristensen SL, Toft G, Thulstrup AM, Hakonsen LB, Olsen SF, Ramlau-Hansen CH. Maternal smoking during pregnancy and reproductive health of daughters: a follow-up study spanning two decades. Hum Reprod. 2012 Dec;27(12):3593-600. doi: 10.1093/humrep/des337. Epub 2012 Oct 2.

Reference Type BACKGROUND
PMID: 23034153 (View on PubMed)

Barbieri RL, York CM, Cherry ML, Ryan KJ. The effects of nicotine, cotinine and anabasine on rat adrenal 11 beta-hydroxylase and 21-hydroxylase. J Steroid Biochem. 1987 Jul;28(1):25-8. doi: 10.1016/0022-4731(87)90119-1.

Reference Type BACKGROUND
PMID: 3497305 (View on PubMed)

Matta SG, Valentine JD, Sharp BM. Nicotinic activation of CRH neurons in extrahypothalamic regions of the rat brain. Endocrine. 1997 Oct;7(2):245-53. doi: 10.1007/BF02778147.

Reference Type BACKGROUND
PMID: 9549051 (View on PubMed)

Stroud LR, Papandonatos GD, Shenassa E, Rodriguez D, Niaura R, LeWinn KZ, Lipsitt LP, Buka SL. Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study. Biol Psychiatry. 2014 Jan 1;75(1):47-55. doi: 10.1016/j.biopsych.2013.07.024. Epub 2013 Sep 10.

Reference Type BACKGROUND
PMID: 24034414 (View on PubMed)

Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996;18(2):188-204. doi: 10.1093/oxfordjournals.epirev.a017925. No abstract available.

Reference Type BACKGROUND
PMID: 9021312 (View on PubMed)

Benowitz NL, Jacob P 3rd, Fong I, Gupta S. Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther. 1994 Jan;268(1):296-303.

Reference Type BACKGROUND
PMID: 8301571 (View on PubMed)

James WH. Potential explanation of the reported association between maternal smoking and autism. Environ Health Perspect. 2013 Feb;121(2):a42. doi: 10.1289/ehp.1206268. No abstract available.

Reference Type BACKGROUND
PMID: 23380543 (View on PubMed)

Fowler PA, Bhattacharya S, Flannigan S, Drake AJ, O'Shaughnessy PJ. Maternal cigarette smoking and effects on androgen action in male offspring: unexpected effects on second-trimester anogenital distance. J Clin Endocrinol Metab. 2011 Sep;96(9):E1502-6. doi: 10.1210/jc.2011-1100. Epub 2011 Jul 13.

Reference Type BACKGROUND
PMID: 21752894 (View on PubMed)

Thankamony A, Ong KK, Dunger DB, Acerini CL, Hughes IA. Anogenital distance from birth to 2 years: a population study. Environ Health Perspect. 2009 Nov;117(11):1786-90. doi: 10.1289/ehp.0900881. Epub 2009 Jul 13.

Reference Type BACKGROUND
PMID: 20049133 (View on PubMed)

Ravnborg TL, Jensen TK, Andersson AM, Toppari J, Skakkebaek NE, Jorgensen N. Prenatal and adult exposures to smoking are associated with adverse effects on reproductive hormones, semen quality, final height and body mass index. Hum Reprod. 2011 May;26(5):1000-11. doi: 10.1093/humrep/der011. Epub 2011 Feb 18.

Reference Type BACKGROUND
PMID: 21335416 (View on PubMed)

Rizwan S, Manning JT, Brabin BJ. Maternal smoking during pregnancy and possible effects of in utero testosterone: evidence from the 2D:4D finger length ratio. Early Hum Dev. 2007 Feb;83(2):87-90. doi: 10.1016/j.earlhumdev.2006.05.005. Epub 2006 Jun 30.

Reference Type BACKGROUND
PMID: 16814493 (View on PubMed)

James WH. An update on the hypothesis that one cause of autism is high intrauterine levels of testosterone of maternal origin. J Theor Biol. 2014 Aug 21;355:33-9. doi: 10.1016/j.jtbi.2014.03.036. Epub 2014 Apr 1.

Reference Type BACKGROUND
PMID: 24703983 (View on PubMed)

Kandel DB, Udry JR. Prenatal effects of maternal smoking on daughters' smoking: nicotine or testosterone exposure? Am J Public Health. 1999 Sep;89(9):1377-83. doi: 10.2105/ajph.89.9.1377.

Reference Type BACKGROUND
PMID: 10474556 (View on PubMed)

Cornelius MD, Leech SL, Goldschmidt L, Day NL. Prenatal tobacco exposure: is it a risk factor for early tobacco experimentation? Nicotine Tob Res. 2000 Feb;2(1):45-52. doi: 10.1080/14622200050011295.

Reference Type BACKGROUND
PMID: 11072440 (View on PubMed)

Gordon SS, Dhanraj DN, Ganga Devaiah C, Lambers DS. A Pilot Study of Exposure to Nicotine in Human Pregnancy and Maternal and Fetal Testosterone Levels at Birth. Reprod Sci. 2022 Nov;29(11):3254-3259. doi: 10.1007/s43032-022-00967-2. Epub 2022 Jun 6.

Reference Type DERIVED
PMID: 35668167 (View on PubMed)

Other Identifiers

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15-063

Identifier Type: -

Identifier Source: org_study_id

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