{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:49:16Z","timestamp":1782107356131,"version":"3.54.5"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Reprod. Health"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between parental age, age gap, and neonatal health outcomes, and to provide epidemiological evidence for preconception counseling and perinatal risk assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included mother\u2013infant pairs who delivered at the Women's Hospital, Zhejiang University School of Medicine between January 2016 and December 2022. A total of 15,762 pairs were analyzed, comprising 7,557 healthy controls and 8,205 cases. The primary exposure was parental age comparison. Multivariable logistic regression was used to examine the association between parental age comparison and neonatal diseases, with adjustment for maternal BMI, hypertension, diabetes, gestational week, smoking, alcohol use, and educational level. Parental ages were also entered as continuous variables, and interaction terms were tested. Restricted cubic splines were applied to assess nonlinear dose\u2013response relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the equal-age group, both the father-older group (OR\u2009=\u20091.561, 95% CI: 1.203\u20133.201) and the mother-older group (OR\u2009=\u20091.652, 95% CI: 1.323\u20132.343) had significantly increased odds of neonatal diseases. After further adjustment for individual parental ages, the father-older association became non-significant (OR\u2009=\u20091.121,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.420), while the mother-older association remained marginally significant (OR\u2009=\u20091.012,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.022). Both maternal age (OR\u2009=\u20091.080,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) and paternal age (OR\u2009=\u20091.051,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002) were independent risk factors. Significant interactions were observed between age gap and maternal age (OR\u2009=\u20091.098,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.011) and between maternal and paternal ages (OR\u2009=\u20091.098,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.032). Restricted cubic spline analysis showed that the risk of adverse neonatal outcomes accelerated after maternal age &amp;gt;30.1 years and paternal age &amp;gt;40.2 years (nonlinear\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.01 for both).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both maternal and paternal ages are independent risk factors with nonlinear dose-response relationships. The combined structure of parental ages should be considered in preconception counseling and perinatal risk assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frph.2026.1818157","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:38:20Z","timestamp":1782106700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Parental age and age gap in relation to neonatal health: a cohort study in eastern China"],"prefix":"10.3389","volume":"8","author":[{"given":"Xuezhi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and School of Bioengineering, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongran","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Maternal and Infant Health, Women's Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1055\/s-0034-1395272","article-title":"Global fertility and population trends.","volume":"33","author":"Bongaarts","year":"2015","journal-title":"Semin Reprod Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1176\/appi.ajp.201312101352","article-title":"\u201cSelfish spermatogonial selection\u201d: a novelmechanism for the associaton between advanced paternal age and neurodevelopmentadisorders","volume":"170","author":"Goriely","year":"2013","journal-title":"Am J Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1017\/S0033291713001426","article-title":"Advanced paternal age at birth: phenotypic and etiologic associations with eating pathology in offspring.","volume":"44","author":"Racine","year":"2014","journal-title":"Psychol Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.fertnstert.2010.08.029","article-title":"The effect of paternal age on assisted reproduction outcome.","volume":"95","author":"Dain","year":"2011","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.3109\/14767058.2015.1051955","article-title":"Gestational age-specific neonatal morbidity among pregnancies complicated by advanced maternal age: a population-based retrospective cohort study.","volume":"29","author":"Valent","year":"2016","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12958-015-0028-x","article-title":"Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring.","volume":"13","author":"Sharma","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/S2215-0366(20)30057-2","article-title":"Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis.","volume":"7","author":"Davies","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.fertnstert.2015.03.011","article-title":"Male biological clock: a critical analysis of advanced paternal age.","volume":"103","author":"Ramasamy","year":"2015","journal-title":"Fertil Steril"},{"key":"B9","doi-asserted-by":"publisher","first-page":"486","DOI":"10.3390\/genes14020486","article-title":"Impact of advanced paternal age on fertility and risks of genetic disorders in offspring.","volume":"14","author":"Kaltsas","year":"2023","journal-title":"Genes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1093\/humrep\/dead209","article-title":"Gravidity modifies the associations of age and spousal age difference with couple\u2019s fecundability: a large cohort study from China.","volume":"39","author":"Zhang","year":"2024","journal-title":"Hum Reprod"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1093\/humrep\/deaa129","article-title":"Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis.","volume":"35","author":"Chua","year":"2020","journal-title":"Hum Reprod"},{"key":"B12","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1093\/humrep\/dead236","article-title":"The association between parental age differences and perinatal outcomes.","volume":"39","author":"Yu","year":"2024","journal-title":"Hum Reprod"},{"key":"B13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.arr.2014.10.007","article-title":"Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis","volume":"19","author":"Johnson","year":"2015","journal-title":"Ageing Res Rev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.fertnstert.2003.04.002","article-title":"Effects of age on DNA double-strand breaks and apoptosis in human sperm","volume":"80","author":"Singh","year":"2003","journal-title":"Fertil Steril"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1093\/humrep\/dem403","article-title":"Paternal age and adverse birth outcomes: teenager or 40+, who is at risk?","volume":"23","author":"Chen","year":"2008","journal-title":"Hum Reprod"},{"key":"B16","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1136\/bmj.38555.462685.8F","article-title":"Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort","volume":"331","author":"Skjaerven","year":"2005","journal-title":"Br Med J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1038\/s43587-025-00927-w","article-title":"Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging.","volume":"5","author":"Dong","year":"2025","journal-title":"Nat Aging"},{"key":"B18","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41586-025-09448-3","article-title":"Sperm sequencing reveals extensive positive selection in the male germline.","volume":"647","author":"Neville","year":"2025","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41586-025-09579-7","article-title":"Hotspots of human mutation point to clonal expansions in spermatogonia.","volume":"647","author":"Seplyarskiy","year":"2025","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41559-022-01958-x","article-title":"Transcriptional and mutational signatures of the Drosophila ageing germline.","volume":"7","author":"Witt","year":"2023","journal-title":"Nat Ecol Evol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1093\/humrep\/deae198","article-title":"Livebirth rates are influenced by an interaction between male and female partners\u2019 age: analysis of 59 951 fresh IVF\/ICSI cycles with and without male infertility","volume":"39","author":"Datta","year":"2024","journal-title":"Hum Reprod"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1016\/j.scib.2025.05.043","article-title":"Preconception maternal and paternal one-carbon metabolism homeostasis and perinatal adverse outcomes: a prospective multiple events case-control study","volume":"70","author":"Yan","year":"2025","journal-title":"Sci Bull"}],"container-title":["Frontiers in Reproductive Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2026.1818157\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:38:21Z","timestamp":1782106701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2026.1818157\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":22,"alternative-id":["10.3389\/frph.2026.1818157"],"URL":"https:\/\/doi.org\/10.3389\/frph.2026.1818157","relation":{},"ISSN":["2673-3153"],"issn-type":[{"value":"2673-3153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"article-number":"1818157"}}