{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:57:46Z","timestamp":1779310666694,"version":"3.51.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011967","name":"Columbia Population Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011967","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Prenatal exposure to testosterone is implicated in the etiology of autism spectrum disorder (ASD). Hypertensive disorders of pregnancy and polycystic ovary syndrome are associated with both hyperandrogenism and increased risk for ASD. We examined whether increased maternal testosterone mediates the relationship between these hyperandrogenic disorders (HDs) during pregnancy and child communication and social skills. Maternal plasma was collected during the second trimester and parent-report measures of child communication and social skills were obtained at 4.5-6.5 years of age from 270 participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). Our retrospective frequency-matched cohort study design identified 58 mothers with one or both of the HDs and 58 matched controls. Women diagnosed with an HD who carried a female had higher testosterone levels compared to those carrying a male (<jats:italic>t<\/jats:italic>(56) = -2.70, <jats:italic>p<\/jats:italic> = 0.01). Compared to females controls, females born to women with an HD had significantly higher scores on the Social Communication Questionnaire (<jats:italic>t<\/jats:italic>(114) = -2.82, <jats:italic>p<\/jats:italic> =0.01). Maternal testosterone partially mediated the relationship between a diagnosis of an HD and SCQ scores among females. These findings point to sex-specific associations of two HDs \u2013 hypertensive disorders of pregnancy and polycystic ovary syndrome \u2013 on child communication and social skills and a mediating effect of maternal testosterone during pregnancy. Further research is needed to understand placental-mediated effects of maternal testosterone on child brain development and neurodevelopmental outcomes.<\/jats:p>","DOI":"10.3389\/fendo.2022.1000732","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T15:40:30Z","timestamp":1664466030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Hypertensive disorders during pregnancy and polycystic ovary syndrome are associated with child communication and social skills in a sex-specific and androgen-dependent manner"],"prefix":"10.3389","volume":"13","author":[{"given":"Morgan R.","family":"Firestein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell D.","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailey","family":"Winstead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle A.","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Grobman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Parry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma M.","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Silver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald J.","family":"Wapner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances A.","family":"Champagne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.48","article-title":"Elevated fetal steroidogenic activity in autism","volume":"20","author":"Baron-Cohen","year":"2015","journal-title":"Mol Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1268-2","article-title":"Prenatal and postnatal hormone effects on the human brain and cognition","volume":"465","author":"Auyeung","year":"2013","journal-title":"Pflugers Arch"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210101601","article-title":"Fetal testosterone and sex differences in typical social development and in autism","volume":"21","author":"Knickmeyer","year":"2006","journal-title":"J Child Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/17470910600992239","article-title":"Fetal testosterone and empathy: Evidence from the empathy quotient (EQ) and the \u201cReading the mind in the eyes\u201d test","volume":"1","author":"Chapman","year":"2006","journal-title":"Soc Neurosci"},{"key":"B5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s10508-007-9291-z","article-title":"Prenatal sex hormones (Maternal and amniotic fluid) and gender-related play behavior in 13-month-old infants","volume":"38","author":"van de Beek","year":"2007","journal-title":"Arch Sex Behav"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2003.12.002","article-title":"2nd to 4th digit ratios, fetal testosterone and estradiol","volume":"77","author":"Lutchmaya","year":"2004","journal-title":"Early Hum Dev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.07.030184.002213","article-title":"Gonadal steroid induction of structural sex differences in the central nervous system","volume":"7","author":"Arnold","year":"1984","journal-title":"Annu Rev Neurosci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13293-015-0022-1","article-title":"Early androgen exposure and human gender development","volume":"6","author":"Hines","year":"2015","journal-title":"Biol Sex Differences"},{"key":"B9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1146\/annurev.ps.45.020194.002133","article-title":"Sexual differentiation of the human nervous system","volume":"45","author":"Breedlove","year":"1994","journal-title":"Annu Rev Psychol"},{"key":"B10","article-title":"Amniotic fluid testosterone levels in midpregnancy","volume":"48","author":"Judd","year":"1976","journal-title":"Obstet. Gynecol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(79)90649-5","article-title":"Maternal and amniotic fluid steroids throughout human pregnancy","volume":"134","author":"Nagamani","year":"1979","journal-title":"Am J Obstetrics Gynecol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-45-4-755","article-title":"Amniotic fluid androgens and estrogens in midgestation","volume":"45","author":"Robinson","year":"1977","journal-title":"J Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1970050303","article-title":"Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid","volume":"5","author":"Rodeck","year":"1985","journal-title":"Prenat Diagn"},{"key":"B14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0002-9378(77)90815-8","article-title":"Testosterone and dihydrotestosterone in maternal and cord blood and in amniotic fluid","volume":"129","author":"Dawood","year":"1977","journal-title":"Am J Obstet. Gynecol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/00221325.1989.9914580","article-title":"A window for the study of prenatal sex hormone influences on postnatal development","volume":"150","author":"Finegan","year":"1989","journal-title":"J Genet Psychol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2004.06.010","article-title":"Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: What is the best source of information to investigate the effects of fetal hormonal exposure","volume":"46","author":"van de Beek","year":"2004","journal-title":"Hormones Behav"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023934518975","article-title":"Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United states)","volume":"14","author":"Troisi","year":"2003","journal-title":"Cancer Causes Control"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0560621","article-title":"Foetal plasma testosterone levels at mid-pregnancy and at term: Relationship to foetal sex","volume":"56","author":"Abramovich","year":"1973","journal-title":"J Endocrinol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1122","article-title":"Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism","volume":"35","author":"Gore","year":"2014","journal-title":"Endocr Rev"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(16)32694-1","article-title":"Placental clearance rate of maternal plasma androstenedione through placental estradiol formation: An indirect method of assessing uteroplacental blood flow","volume":"141","author":"Edman","year":"1981","journal-title":"Am J Obstetrics Gynecol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1992.tb13712.x","article-title":"Luteoma of pregnancy: masculinisation of a female fetus prevented by placental aromatisation [Internet]","volume":"99","author":"Illingworth","year":"1992","journal-title":"BJOG: Int J Obstetrics Gynaecol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-120015041","article-title":"Aromatase in primate pregnancy: A review","volume":"28","author":"Kragie","year":"2002","journal-title":"Endocr Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70150-X","article-title":"Androgens in preeclampsia","volume":"180","author":"Acromite","year":"1999","journal-title":"Am J Obstetrics Gynecol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0139682","DOI":"10.1371\/journal.pone.0139682","article-title":"Placental aromatase is deficient in placental ischemia and preeclampsia","volume":"10","author":"Perez-Sepulveda","year":"2015","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2018.0854","article-title":"Association of hypertensive disorders of pregnancy with risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis","volume":"75","author":"Maher","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.07.061","article-title":"Hypertensive diseases of pregnancy and the development of behavioral problems in childhood and adolescence: The Western Australian pregnancy cohort study","volume":"154","author":"Robinson","year":"2009","journal-title":"J Pediatr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.2645","article-title":"Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay","volume":"169","author":"Walker","year":"2015","journal-title":"JAMA Pediatr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-009-0903-4","article-title":"Pre-eclampsia, birth weight, and autism spectrum disorders","volume":"40","author":"Mann","year":"2010","journal-title":"J Autism Dev Disord"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/aur.2105","article-title":"Maternal diabetes and hypertensive disorders in association with autism spectrum disorder","volume":"12","author":"Cordero","year":"2019","journal-title":"Autism Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1530\/REP-18-0278","article-title":"Androgens in maternal vascular and placental function: Implications for preeclampsia pathogenesis","volume":"156","author":"Kumar","year":"2018","journal-title":"Reproduction"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2005.07.007","article-title":"Androgen levels in the third trimester of pregnancy in patients with preeclampsia","volume":"126","author":"Salamalekis","year":"2006","journal-title":"Eur J Obstetrics Gynecol. Reprod Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg094","article-title":"Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies","volume":"32","author":"Troisi","year":"2003","journal-title":"Int J Epidemiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2018.07.004","article-title":"Abnormal steroidogenesis and aromatase activity in preeclampsia","author":"Berkane","year":"2018","journal-title":"Placenta"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2011.101","article-title":"Fetal sex-related dysregulation in testosterone production and their receptor expression in the human placenta with preeclampsia","volume":"32","author":"Sathishkumar","year":"2012","journal-title":"J Perinatol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.183","article-title":"Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden","author":"Kosidou","year":"2015","journal-title":"Mol Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32832afd4d","article-title":"Androgens and polycystic ovary syndrome","volume":"16","author":"Nisenblat","year":"2009","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B37","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1111\/j.1365-2265.2012.04443.x","article-title":"Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: A longitudinal case\u2013control study","volume":"77","author":"Palomba","year":"2012","journal-title":"Clin Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4103\/2230-8210.107830","article-title":"Pregnancy in polycystic ovary syndrome","volume":"17","author":"Kamalanathan","year":"2013","journal-title":"Indian J Endocrinol Metab"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/17.10.2573","article-title":"Maternal serum androgens in pregnant women with polycystic ovarian syndrome: Possible implications in prenatal androgenization","volume":"17","author":"Sir-Petermann","year":"2002","journal-title":"Hum Reprod"},{"key":"B40","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41398-018-0186-7","article-title":"Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory","volume":"8","author":"Cherskov","year":"2018","journal-title":"Trans Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa192","article-title":"Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: A Finnish population-based cohort study","volume":"35","author":"Chen","year":"2020","journal-title":"Hum Reprod"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291719000424","article-title":"Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: Prenatal androgen exposure or genetic confounding","volume":"50","author":"Cesta","year":"2020","journal-title":"Psychol Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0398-0","article-title":"Maternal polycystic ovarian syndrome in autism spectrum disorder: A systematic review and meta-analysis","volume":"24","author":"Katsigianni","year":"2019","journal-title":"Mol Psychiatry"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwaa219","article-title":"Associations of maternal androgen-related conditions with risk of autism spectrum disorder in progeny and mediation by cardiovascular, metabolic, and fertility factors","volume":"190","author":"Rotem","year":"2021","journal-title":"Am J Epidemiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"539.e1","DOI":"10.1016\/j.ajog.2015.01.019","article-title":"A description of the methods of the nulliparous pregnancy outcomes study: monitoring mothers-to-be (nuMoM2b)","volume":"212","author":"Haas","year":"2015","journal-title":"Am J Obstetrics Gynecol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-006-0279-7","article-title":"Validity of the social communication questionnaire in assessing risk of autism in preschool children with developmental problems","volume":"37","author":"Allen","year":"2007","journal-title":"J Autism Dev Disord"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1584","article-title":"The sensitivity and specificity of the social communication questionnaire for autism spectrum with respect to age","volume":"9","author":"Barnard-Brak","year":"2016","journal-title":"Autism Res"},{"key":"B48","article-title":"Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex","volume":"100","author":"Steier","year":"2002","journal-title":"Obstetrics Gynecol."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2008.07.010","article-title":"Prenatal exposure to sex steroid hormones and behavioral\/cognitive outcomes","volume":"57","author":"Manson","year":"2008","journal-title":"Metabolism"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2004.11.004","article-title":"Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings","volume":"29","author":"Cohen-Bendahan","year":"2005","journal-title":"Neurosci Biobehav Rev"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s40489-020-00197-9","article-title":"The female autism phenotype and camouflaging: a narrative review","volume":"7","author":"Hull","year":"2020","journal-title":"Rev J Autism Dev Disord"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb02478.x","article-title":"Longitudinal study of maternal plasma bioavailable testosterone and androstanediol glucuronide levels during pregnancy","volume":"40","author":"Kerlan","year":"1994","journal-title":"Clin Endocrinol."}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1000732\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T15:40:33Z","timestamp":1664466033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1000732\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":52,"alternative-id":["10.3389\/fendo.2022.1000732"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1000732","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]},"article-number":"1000732"}}