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Associations of parental ages at childbirth with healthy aging among women

  • Aladdin H. Shadyab
    Correspondence
    Corresponding author at: Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine, 9500 Gilman Drive #0725, La Jolla, CA, 92093, USA.
    Affiliations
    Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego School of Medicine, 9500 Gilman Drive #0725, La Jolla, CA 92093, USA
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  • JoAnn E. Manson
    Affiliations
    Department of Epidemiology, Harvard T.H. Chan School of Public Health and Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA
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  • Wenjun Li
    Affiliations
    Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, 55 N Lake Ave, Worcester, MA 01655, USA
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  • Margery Gass
    Affiliations
    North American Menopause Society Emeritus, 30100 Chagrin Blvd, Pepper Pike, OH 44124, USA
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  • Robert L. Brunner
    Affiliations
    Department of Family and Community Medicine, University of Nevada School of Medicine, 1664 North Virginia Street, Reno, NV 89557, USA
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  • Michelle J. Naughton
    Affiliations
    Division of Population Sciences, Department of Internal Medicine, The Ohio State University, 1590 N High St, Columbus, OH 43201, USA
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  • Brad Cannell
    Affiliations
    Department of Biostatistics and Epidemiology, School of Public Health, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
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  • Barbara V. Howard
    Affiliations
    MedStar Health Research Institute and Georgetown-Howard Universities Center for Clinical and Translational Science, 6525 Belcrest Road, Hyattsville, MD 20782, USA
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  • Andrea Z. LaCroix
    Affiliations
    Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego School of Medicine, 9500 Gilman Drive #0725, La Jolla, CA 92093, USA
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      Highlights

      • Associations of parental ages at childbirth with aging outcomes among offspring are unknown.
      • Women with fathers aged 35 years and older at their births had higher odds of healthy aging.
      • A woman’s mother’s age at her birth was not associated with healthy aging.
      • Older paternal age at childbirth may predict healthy aging among women.

      Abstract

      Objective

      To examine associations of parental ages at childbirth with healthy survival to age 90 years among older women.

      Study Design

      This study included a racially and ethnically diverse sub-cohort of 8,983 postmenopausal women from the larger Women’s Health Initiative population, recruited during 1993–1998 and followed for up to 25 years through 2018.

      Main Outcome Measures

      The outcome was categorized as: 1) healthy survival, defined as survival to age 90 without major morbidities (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or mobility disability; 2) usual survival, defined as survival to age 90 without healthy aging (reference category); or 3) death before age 90. Women reported their own and their parents’ birth years, and parental ages at childbirth were calculated and categorized as <25, 25–29, 30–34, or ≥35 years.

      Results

      Women were aged on average 71.3 (standard deviation 2.7; range 65–79) years at baseline. There was no significant association of maternal age at childbirth with healthy survival to age 90 or death before age 90. Women born to fathers aged ≥35 compared with 30–34 years at their births were more likely to achieve healthy than usual survival (OR, 1.15; 95% CI, 1.00–1.32). There was no association of paternal age at childbirth with death before age 90.

      Conclusions

      Findings suggest that being born to older fathers was associated with healthy survival to age 90 among women who had survived to ages 65–79 years at study baseline. There was no association of maternal age at childbirth with healthy survival to age 90 among these older women.

      Keywords

      1. Introduction

      Maternal and paternal ages at childbirth have been rising during the past four decades in the United States [
      • Mathews T.J.
      • Hamilton B.E.
      Mean Age of Mothers Is on the Rise: United States.
      ,
      • Mathews T.J.
      • Hamilton B.E.
      ,
      • Khandwala Y.S.
      • Zhang C.A.
      • Lu Y.
      • Eisenberg M.L.
      The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015.
      ]. Average maternal age at first childbirth rose from 21.4 years in 1970 to 26.3 years in 2014 [
      • Mathews T.J.
      • Hamilton B.E.
      Mean Age of Mothers Is on the Rise: United States.
      ,
      • Mathews T.J.
      • Hamilton B.E.
      ]. Average paternal age at childbirth increased from 27.4 years to 30.9 years during this time [
      • Khandwala Y.S.
      • Zhang C.A.
      • Lu Y.
      • Eisenberg M.L.
      The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015.
      ]. The proportion of births to parents older than 35 years is also increasing [
      • Mathews T.J.
      • Hamilton B.E.
      Mean Age of Mothers Is on the Rise: United States.
      ,
      • Mathews T.J.
      • Hamilton B.E.
      ,
      • Khandwala Y.S.
      • Zhang C.A.
      • Lu Y.
      • Eisenberg M.L.
      The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015.
      ]. The desire to further one’s education and start a family after establishing one’s professional career may influence the decision to have a child at an older age [
      • Mathews T.J.
      • Hamilton B.E.
      ].
      Studies examining associations of parental ages at childbirth with offspring health outcomes have yielded inconsistent findings, and few studies have examined aging outcomes [
      • D’Onofrio B.M.
      • Rickert M.E.
      • Frans E.
      • Kuja-Halkola R.
      • Almqvist C.
      • Sjolander A.
      • Larsson H.
      • Lichtenstein P.
      Paternal age at childbearing and offspring psychiatric and academic morbidity.
      ,
      • Carslake D.
      • Tynelius P.
      • van den Berg G.
      • Davey Smith G.
      • Rasmussen F.
      Associations of parental age with health and social factors in adult offspring methodological pitfalls and possibilities.
      ,
      • Gavrilov L.A.
      • Gavrilova N.S.
      Biodemography of exceptional longevity: early-life and mid-life predictors of human longevity.
      ,
      • Hubbard R.E.
      • Andrew M.K.
      • Rockwood K.
      Effect of parental age at birth on the accumulation of deficits, frailty and survival in older adults.
      ,
      • Savage T.
      • Derraik J.
      • Miles H.
      • Mouat F.
      • Hofman P.L.
      • Cutfield W.S.
      Increasing maternal age is associated with taller stature and reduced abdominal fat in their children.
      ,
      • Myrskyla M.
      • Fenelon A.
      Maternal age and offspring adult health: evidence from the Health and Retirement Study.
      ,
      • Myrskyla M.
      • Elo I.T.
      • Kohler I.V.
      • Martikainen P.
      The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.
      ,
      • Hviid M.M.
      • Skovlund C.V.
      • Morch L.S.
      • Lidegaard O.
      Maternal age and child morbidity: a Danish national cohort study.
      ,
      • Lu Y.
      • Ma H.
      • Sullivan-Halley J.
      • Henderson K.D.
      • Chang E.T.
      • Clarke C.A.
      • Neuhausen S.L.
      • West D.W.
      • Bernstein L.
      • Wang S.S.
      Parents’ age at birth and risk of adult-onset hematologic malignancies among female teachers in California.
      ,
      • Robine J.M.
      • Cournil A.
      • Henon N.
      • Allard M.
      Have centenarians had younger parents than others?.
      ,
      • Eriksen W.
      • Sundet J.M.
      • Tambs K.
      Paternal age at birth and the risk of obesity in young adulthood: a register-based birth cohort study of Norwegian males.
      ,
      • Khandwala Y.
      • Baker V.L.
      • Shaw G.M.
      • Stevenson D.K.
      • Lu Y.
      • Eisenberg M.L.
      Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population-based cohort study.
      ,
      • Hurley E.G.
      • DeFranco E.A.
      Influence of paternal age on perinatal outcomes.
      ]. Some studies have linked older parental age at childbirth to outcomes including neurodevelopmental disorders, obesity, mortality, and morbidities including cancer among offspring in childhood and adulthood [
      • D’Onofrio B.M.
      • Rickert M.E.
      • Frans E.
      • Kuja-Halkola R.
      • Almqvist C.
      • Sjolander A.
      • Larsson H.
      • Lichtenstein P.
      Paternal age at childbearing and offspring psychiatric and academic morbidity.
      ,
      • Myrskyla M.
      • Fenelon A.
      Maternal age and offspring adult health: evidence from the Health and Retirement Study.
      ,
      • Myrskyla M.
      • Elo I.T.
      • Kohler I.V.
      • Martikainen P.
      The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.
      ,
      • Hviid M.M.
      • Skovlund C.V.
      • Morch L.S.
      • Lidegaard O.
      Maternal age and child morbidity: a Danish national cohort study.
      ,
      • Lu Y.
      • Ma H.
      • Sullivan-Halley J.
      • Henderson K.D.
      • Chang E.T.
      • Clarke C.A.
      • Neuhausen S.L.
      • West D.W.
      • Bernstein L.
      • Wang S.S.
      Parents’ age at birth and risk of adult-onset hematologic malignancies among female teachers in California.
      ,
      • Eriksen W.
      • Sundet J.M.
      • Tambs K.
      Paternal age at birth and the risk of obesity in young adulthood: a register-based birth cohort study of Norwegian males.
      ].
      There is some evidence that older paternal age at childbirth may confer health benefits among offspring. For example, older paternal age at childbirth has been associated with longer telomere length among adult offspring [
      • Prescott J.
      • Du M.
      • Wong J.Y.
      • Han J.
      • De Vivo I.
      Paternal age at birth is associated with offspring leukocyte telomere length in the Nurses’ Health Study.
      ,
      • De Meyer T.
      • Rietzschel E.R.
      • Buyzere M.L.
      • De Bacquer D.
      • Van Criekinge W.
      • De Becker G.G.
      • Gillebert T.C.
      • Van Oostveldt P.
      • Bekaert S.
      Asklepios Investigators Paternal age at birth is an important determinant of offspring telomere length.
      ]. Shortened telomere length is associated with decreased lifespan and increased risks of cancer, cardiovascular diseases, and type 2 diabetes among adults [
      • Wentzensen I.M.
      • Mirabello L.
      • Pfeiffer R.M.
      • Savage S.A.
      The association of telomere length and cancer: a meta-analysis.
      ,
      • Haycock P.C.
      • Heydon E.E.
      • Kaptoge S.
      • Butterworth A.S.
      • Thompson A.
      • Willeit P.
      Leukocyte telomere length and risk of cardiovascular disease: a systematic review and meta-analysis.
      ,
      • Zhao J.
      • Miao K.
      • Wang H.
      • Ding H.
      • Wang D.W.
      Association between telomere length and type 2 diabetes mellitus: a meta-analysis.
      ,
      • Cawthon R.M.
      • Smith K.R.
      • O’Brien E.
      • Sivatchenko A.
      • Kerber R.A.
      Association between telomere length in blood and mortality in people aged 60 years or older.
      ]. However, the hypothesis that older paternal age at childbirth is associated with healthy survival to an advanced age among offspring has not, to our knowledge, been yet examined in a large, epidemiologic study with follow-up into late ages.
      We examined associations of parental ages at childbirth with healthy aging, defined as survival to age 90 without major morbidities or mobility disability, among participants in the Women’s Health Initiative (WHI), a large, national, prospective study of postmenopausal women in the United States.

      2. Methods

      2.1 Study population and design

      Details of the WHI study design and population are described elsewhere [
      • The Women’s Health Initiative Study Group
      Design of the women’s health initiative clinical trial and observational study.
      ]. Briefly, 161,808 postmenopausal women aged 50–79 years were recruited from 40 United States clinical centers from 1993 to 1998 to participate in one or more of three clinical trials or an observational study. In 2005, 77% of eligible women agreed to be followed through 2010 in the first WHI Extension Study. In 2010, 87% of eligible women enrolled for an additional five years of follow-up in the second Extension Study. Follow-up is now continuing at least through 2020. All participants provided written informed consent, and institutional review board approval was received by all participating institutions.
      This study was restricted to participants born on or before March 31, 1928 who had potential, because of their birth years, to survive to age 90 during the follow-up period ending March 31, 2018. During the second Extension Study, women were asked to report the year in which their mothers and fathers were born. Women who had complete information on parental ages at childbirth, survival status, and mobility status if survived to age 90 were included in the present study. A sub-cohort of 8983 women with up to 25 years of follow-up met the inclusion criteria (Supplementary Figure 1).

      2.2 Parental ages at childbirth

      Parental ages at childbirth were determined by subtracting the self-reported parental birth years from the participant birth year and categorized as follows: <25, 25–29, 30–34, and ≥35 years. Teen births were not examined as a separate category due to low numbers of parental ages at childbirth ≤19 years. Older parental age at childbirth was considered ≥35 years, because sociodemographic trends indicate that the number of first births in this age group is increasing among men and women [
      • Mathews T.J.
      • Hamilton B.E.
      Mean Age of Mothers Is on the Rise: United States.
      ,
      • Mathews T.J.
      • Hamilton B.E.
      ,
      • Khandwala Y.S.
      • Zhang C.A.
      • Lu Y.
      • Eisenberg M.L.
      The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015.
      ]. Further, there were fewer women whose mothers or fathers were aged ≥40 compared with <40 years at their births. Henceforth, maternal and paternal ages refer to a woman’s mother’s and father’s ages at her own birth, respectively.

      2.3 Covariates

      Covariates collected at baseline included age, race/ethnicity, education, income, marital status, smoking, alcohol consumption, diet quality, body mass index (BMI), total leisure-time physical activity, depressive symptoms, and self-rated health. Additional information on these variables is provided in the Supplementary Methods.

      2.4 Outcome

      Participants were classified as having survived to age 90 or died before this age. Deaths were verified by physician adjudication using hospital records, autopsy or coroner’s reports, or death certificates. Periodic linkage to the National Death Index was performed for all participants, including those lost to follow-up, for verification if medical records or death certificates were not available.
      In prior studies, definitions of healthy aging were based on Rowe and Kahn’s model, which is characterized by avoidance of major diseases and disabilities [
      • Rillamas-Sun E.
      • LaCroix A.Z.
      • Waring M.E.
      • Kroenke C.H.
      • LaMonte M.J.
      • Vitolins M.Z.
      • Seguin R.
      • Bell C.L.
      • Gass M.
      • Manini T.M.
      • Masaki K.H.
      • Wallace R.B.
      Obesity and late-age survival without major disease or disability in older women.
      ,
      • Willcox B.J.
      • He Q.
      • Chen R.
      • Yano K.
      • Masaki K.H.
      • Grove J.S.
      • Donlon T.A.
      • Willcox D.C.
      • Curb J.D.
      Midlife risk factors and healthy survival in men.
      ]. In the present study, healthy aging was defined as survival to ≥90 years without a history of major morbidities (coronary heart disease, stroke, cancer, diabetes, or hip fracture) or mobility disability, which was determined using the physical function subscale of the RAND 36-item health survey [
      • Hays R.D.
      • Sherbourne C.D.
      • Mazel R.M.
      The RAND 36-item health survey, 1.0.
      ]. Women who reported needing crutches, a walker, or a wheelchair to walk on a level surface or who self-reported on the physical function subscale that their health greatly limited their ability to walk one block or climb one flight of stairs were characterized as having mobility disability [
      • Rillamas-Sun E.
      • LaCroix A.Z.
      • Waring M.E.
      • Kroenke C.H.
      • LaMonte M.J.
      • Vitolins M.Z.
      • Seguin R.
      • Bell C.L.
      • Gass M.
      • Manini T.M.
      • Masaki K.H.
      • Wallace R.B.
      Obesity and late-age survival without major disease or disability in older women.
      ]. The questionnaire that was collected within 2 years of the 90th birth year and with the least missing data for physical function was used. Information on collection of physician-adjudicated morbidities is provided in the Supplementary Methods.
      The aging outcome variable had three categories, similar to previous studies: healthy survival (survived to age 90 and met the definition of healthy aging); usual survival (survived to age 90 but did not meet the definition of healthy aging); and died before age 90 [
      • Rillamas-Sun E.
      • LaCroix A.Z.
      • Waring M.E.
      • Kroenke C.H.
      • LaMonte M.J.
      • Vitolins M.Z.
      • Seguin R.
      • Bell C.L.
      • Gass M.
      • Manini T.M.
      • Masaki K.H.
      • Wallace R.B.
      Obesity and late-age survival without major disease or disability in older women.
      ,
      • Willcox B.J.
      • He Q.
      • Chen R.
      • Yano K.
      • Masaki K.H.
      • Grove J.S.
      • Donlon T.A.
      • Willcox D.C.
      • Curb J.D.
      Midlife risk factors and healthy survival in men.
      ].

      2.5 Statistical analysis

      Baseline characteristics were compared by parental ages using chi-square tests for categorical variables, and analysis of variance and Kruskal-Wallis tests for normally-distributed and non-normally distributed continuous variables, respectively.
      The analytic approach for this study was similar to that from previous studies examining factors associated with aging outcomes [
      • Rillamas-Sun E.
      • LaCroix A.Z.
      • Waring M.E.
      • Kroenke C.H.
      • LaMonte M.J.
      • Vitolins M.Z.
      • Seguin R.
      • Bell C.L.
      • Gass M.
      • Manini T.M.
      • Masaki K.H.
      • Wallace R.B.
      Obesity and late-age survival without major disease or disability in older women.
      ,
      • Willcox B.J.
      • He Q.
      • Chen R.
      • Yano K.
      • Masaki K.H.
      • Grove J.S.
      • Donlon T.A.
      • Willcox D.C.
      • Curb J.D.
      Midlife risk factors and healthy survival in men.
      ]. Multinomial logistic regression models examined associations of maternal and paternal ages with the aging outcome. The reference category for maternal age at childbirth was 25–29 years and that for paternal age at childbirth was 30–34 years, which include the current average maternal (26.3 years) and paternal (30.9 years) ages at childbirth in the United States, respectively [
      • Mathews T.J.
      • Hamilton B.E.
      Mean Age of Mothers Is on the Rise: United States.
      ,
      • Khandwala Y.S.
      • Zhang C.A.
      • Lu Y.
      • Eisenberg M.L.
      The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015.
      ]. Usual survival was the reference category for the aging outcome. Multivariable models were adjusted for potential confounders including age at baseline, study assignment (Clinical Trial or Observational Study), race/ethnicity, education, income, marital status, smoking, alcohol consumption, BMI, physical activity, diet quality, depressive symptoms, and self-rated health. Linear trend associations were evaluated by examining parental ages as continuous predictors in the models. Results are reported as odds ratios (OR) and 95% confidence intervals (CI).
      In sensitivity analyses, multivariable models for maternal age adjusted for paternal age and vice versa; an interaction between parental ages was also evaluated. Because there is no universal definition of healthy aging, examination of an alternative definition for mobility disability evaluated the robustness of our findings. Women who reported that their health greatly limited their ability to walk one block or climb one flight of stairs were classified as having mobility disability; otherwise, they had intact mobility. Finally, models were adjusted for number of brothers and sisters to determine whether family size confounded any associations between parental ages and the aging outcome.
      P-values were two-tailed and considered significant at P <  0.05. Analyses were performed using SAS Version 9.4 (SAS Institute, Cary, NC).

      3. Results

      Women’s average age at baseline was 71.3 (standard deviation 2.7; range, 65–79) years. Among the overall cohort, 33.4% had healthy survival to age 90, 58.9% had usual (i.e., not healthy) survival to age 90, and 7.7% died before age 90. Overall, 32.1%, 31.8%, 20.3%, and 15.8% were born to mothers aged <25, 25–29, 30–34, and ≥35 years at their births, respectively. Further, 14.2%, 29.9%, 25.3%, and 30.6% were born to fathers aged <25, 25–29, 30–34, and ≥35 years at their births, respectively.
      Women born to younger mothers were less likely to be white, college graduates, never married, or normal weight, or have high income or excellent self-rated health (Table 1). Similar relationships were observed for baseline characteristics according to paternal age (Table 2).
      Table 1Baseline characteristics by maternal age at childbirth, Women’s Health Initiative (N = 8833).
      Maternal age at childbirth, years
      Characteristic<25 (n = 2833)25-29 (n = 2809)30-34 (n = 1795)≥35 (n = 1396)P-value
      Age, mean (SD), years71.3 (2.7)71.2 (2.6)71.2 (2.6)71.3 (2.7)0.20
      Race/ethnicity
      White2602 (92.0)2667 (95.0)1710 (95.4)1333 (95.6)
      Black106 (3.8)55 (2.0)35 (2.0)23 (1.7)<0.001
      Hispanic35 (1.2)25 (0.9)7 (0.4)12 (0.9)
      Other85 (3.0)60 (2.1)40 (2.2)27 (1.9)
      Educational level
      Less than high school113 (4.0)62 (2.2)37 (2.1)44 (3.2)
      High school515 (18.3)405 (14.5)251 (14.1)245 (17.6)<0.001
      Some college1207 (42.8)967 (34.6)640 (35.8)485 (34.9)
      College graduate985 (34.9)1361 (48.7)859 (48.1)617 (44.4)
      Income
      <$20,000484 (18.2)350 (13.3)230 (13.6)200 (15.2)
      $20,000-<$50,0001410 (53.0)1405 (53.4)885 (52.2)695 (52.9)<0.001
      ≥$50,000766 (28.8)875 (33.3)580 (34.2)418 (31.8)
      Marital status
      Married/living as married1670 (59.2)1700 (60.7)1066 (59.6)841 (60.4)
      Widowed799 (28.3)729 (26.0)463 (25.9)393 (28.2)<0.001
      Divorced/separated275 (9.7)287 (10.3)163 (9.1)95 (6.8)
      Never married78 (2.8)85 (3.0)98 (5.5)63 (4.5)
      Smoking behavior
      Never smoked1714 (61.3)1579 (56.8)1041 (58.6)809 (58.6)
      Past smoker1024 (36.6)1145 (41.2)705 (39.7)534 (38.7)0.01
      Current smoker60 (2.1)56 (2.0)31 (1.7)38 (2.8)
      Alcohol intake
      Nondrinker290 (10.3)231 (8.3)177 (9.9)161 (11.6)
      Past drinker472 (16.8)425 (15.2)257 (14.4)183 (13.2)<0.001
      Current drinker2051 (72.9)2141 (76.6)1351 (75.7)1048 (75.3)
      Recreational physical activity, mean (SD), MET-hours/week12.9 (12.7)14.1 (13.4)14.4 (13.9)14.8 (14.1)<0.001
      Healthy eating index score, mean (SD)69.5 (10.0)70.3 (9.9)70.3 (9.9)69.8 (9.9)0.007
      Body mass index, kg/m2
      Normal weight1038 (37.2)1118 (40.3)809 (45.9)537 (39.1)
      Overweight1110 (39.7)1070 (38.6)615 (34.9)548 (39.9)<0.001
      Obese646 (23.1)584 (21.1)338 (19.2)289 (21.0)
      Burnham depression scale score ≥0.06159 (5.7)133 (4.8)95 (5.4)69 (5.1)0.50
      History of major morbidities
      Coronary heart disease240 (8.5)239 (8.5)150 (8.4)120 (8.6)1.00
      Stroke208 (7.3)203 (7.2)124 (6.9)92 (6.6)0.81
      Cancer723 (25.5)733 (26.1)461 (25.7)368 (26.4)0.93
      Diabetes459 (16.2)442 (15.7)246 (13.7)207 (14.8)0.11
      Hip fracture226 (8.0)224 (8.0)143 (8.0)118 (8.5)0.95
      ≥1 disease1403 (49.5)1431 (50.9)892 (49.7)694 (49.7)0.71
      Self-rated health
      Excellent489 (17.4)581 (20.9)401 (22.4)282 (20.4)
      Very good1382 (49.2)1334 (47.9)879 (49.2)692 (50.0)<0.001
      Good834 (29.7)768 (27.6)460 (25.7)370 (26.8)
      Fair/poor107 (3.8)101 (3.6)47 (2.6)39 (2.8)
      Data are presented as no. (%), unless otherwise indicated.
      Table 2Baseline characteristics by paternal age at childbirth, Women’s Health Initiative (N = 8553).
      Paternal age at childbirth, years
      Characteristic<25 (n = 1218)25-29 (n = 2558)30-34 (n = 2163)≥35 (n = 2614)P-value
      Age, mean (SD), years71.4 (2.7)71.2 (2.6)71.2 (2.7)71.3 (2.6)0.16
      Race/ethnicity
      White1128 (92.7)2438 (95.4)2060 (95.4)2451 (93.9)
      Black50 (4.1)52 (2.0)38 (1.8)48 (1.8)<0.001
      Hispanic10 (0.8)24 (0.9)18 (0.8)24 (0.9)
      Other29 (2.4)42 (1.6)43 (2.0)88 (3.4)
      Educational level
      Less than high school55 (4.5)62 (2.4)47 (2.2)68 (2.6)
      High school236 (19.4)406 (15.9)300 (14.0)426 (16.4)<0.001
      Some college520 (42.8)970 (38.0)782 (36.4)923 (35.5)
      College graduate403 (33.2)1113 (43.6)1021 (47.5)1187 (45.6)
      Income
      <$20,000212 (18.7)362 (15.0)272 (13.4)355 (14.5)
      $20,000-<$50,000596 (52.4)1294 (53.5)1064 (52.3)1313 (53.8)0.001
      ≥$50,000329 (28.9)762 (31.5)700 (34.4)775 (31.7)
      Marital status
      Married/living as married764 (62.9)1518 (59.6)1313 (60.8)1538 (59.1)
      Widowed319 (26.3)695 (27.3)581 (26.9)700 (26.9)<0.001
      Divorced/separated107 (8.8)258 (10.1)178 (8.2)237 (9.1)
      Never married24 (2.0)77 (3.0)88 (4.1)128 (4.9)
      Smoking behavior
      Never smoked746 (62.0)1485 (58.9)1261 (58.8)1509 (58.3)
      Past smoker434 (36.1)976 (38.7)852 (39.7)1021 (39.5)0.11
      Current smoker24 (2.0)61 (2.4)32 (1.5)58 (2.2)
      Alcohol intake
      Nondrinker123 (10.2)244 (9.6)204 (9.5)256 (9.8)
      Past drinker196 (16.2)386 (15.2)314 (14.6)379 (14.6)0.83
      Current drinker892 (73.7)1913 (75.2)1636 (76.0)1966 (75.6)
      Recreational physical activity, mean (SD), MET-hours/week12.9 (13.0)13.4 (13.0)14.4 (14.0)14.3 (13.6)<0.001
      Healthy eating index score, mean (SD)69.3 (10.1)69.5 (10.1)70.3 (9.8)70.2 (9.7)0.003
      Body mass index, kg/m2
      Normal weight429 (35.5)1027 (40.8)884 (41.6)1050 (40.8)
      Overweight491 (40.6)968 (38.4)785 (37.0)988 (38.4)0.02
      Obese289 (23.9)523 (20.8)454 (21.4)533 (20.7)
      Burnham depression scale score ≥0.0669 (5.8)130 (5.2)100 (4.7)131 (5.1)0.61
      History of major morbidities
      Coronary heart disease92 (7.6)208 (8.1)179 (8.3)239 (9.1)0.35
      Stroke93 (7.6)167 (6.5)167 (7.7)177 (6.8)0.32
      Cancer290 (23.8)665 (26.0)559 (25.8)699 (26.7)0.29
      Diabetes188 (15.4)402 (15.7)334 (15.4)376 (14.4)0.57
      Hip fracture103 (8.5)201 (7.9)171 (7.9)213 (8.2)0.92
      ≥1 disease579 (47.5)1272 (49.7)1108 (51.2)1320 (50.5)0.20
      Self-rated health
      Excellent228 (18.9)499 (19.7)471 (21.9)525 (20.3)
      Very good581 (48.1)1217 (48.0)1061 (49.3)1287 (49.7)0.007
      Good348 (28.8)717 (28.3)571 (26.5)705 (27.2)
      Fair/poor50 (4.1)104 (4.1)50 (2.3)75 (2.9)
      Data are presented as no. (%), unless otherwise indicated.
      Among this cohort of women ages 65–79 years at baseline, maternal age was not associated with healthy survival to age 90 or death before age 90, adjusting for age, race/ethnicity, study component, education, income, marital status, smoking, alcohol consumption, diet quality, BMI, depressive symptoms, physical activity, and self-rated health (Table 3). Maternal age was not linearly associated with healthy survival to age 90 or death before age 90.
      Table 3Associations of parental ages at childbirth with aging outcomes, Women’s Health Initiative.
      Healthy survival to age 90 vs. usual survival to age 90
      Healthy survival defined as: survival to age 90 without major morbidities (coronary heart disease, stroke, cancer, diabetes, or hip fracture) or mobility disability.
      Death before age 90 vs. usual survival to age 90
      No. survived to age 90 with healthy aging/total (%)Multivariable-adjusted
      Multivariable model adjusted for adjusted for age, race/ethnicity, study component (Observational Study or Clinical Trial), education, income, marital status, smoking, alcohol consumption, diet quality, body mass index, depressive symptoms, physical activity, and self-rated health.
      P-values for trend (maternal age): 0.26 (healthy survival); 0.67 (death); P-values for trend (paternal age): 0.87 (healthy survival); 0.65 (death).
      OR (95% CI)
      No. died before age 90/total (%)Multivariable-adjusted
      Multivariable model adjusted for adjusted for age, race/ethnicity, study component (Observational Study or Clinical Trial), education, income, marital status, smoking, alcohol consumption, diet quality, body mass index, depressive symptoms, physical activity, and self-rated health.
      P-values for trend (maternal age): 0.26 (healthy survival); 0.67 (death); P-values for trend (paternal age): 0.87 (healthy survival); 0.65 (death).
      OR (95% CI)
      Maternal age at childbirth, years
      <25969/2833 (34.2)1.09 (0.96-1.24)208/2833 (7.3)0.90 (0.71-1.14)
      25-29920/2809 (32.8)1.00216/2809 (7.7)1.00
      30-34600/1795 (33.4)1.00 (0.87-1.16)151/1795 (8.4)1.13 (0.88-1.46)
      ≥35460/1396 (33.0)1.02 (0.87-1.19)98/1396 (7.0)0.88 (0.66-1.18)
      Paternal age at childbirth, years
      <25420/1218 (34.5)1.15 (0.97-1.37)96/1218 (7.9)0.94 (0.69-1.29)
      25-29863/2558 (33.7)1.14 (0.99-1.30)186/2558 (7.3)0.87 (0.68-1.13)
      30-34690/2163 (31.9)1.00173/2163 (8.0)1.00
      ≥35885/2614 (33.9)1.15 (1.00-1.32)193/2614 (7.4)0.95 (0.74-1.22)
      CI, confidence interval; OR, odds ratio.
      a Healthy survival defined as: survival to age 90 without major morbidities (coronary heart disease, stroke, cancer, diabetes, or hip fracture) or mobility disability.
      b Multivariable model adjusted for adjusted for age, race/ethnicity, study component (Observational Study or Clinical Trial), education, income, marital status, smoking, alcohol consumption, diet quality, body mass index, depressive symptoms, physical activity, and self-rated health.
      c P-values for trend (maternal age): 0.26 (healthy survival); 0.67 (death); P-values for trend (paternal age): 0.87 (healthy survival); 0.65 (death).
      Women born to fathers aged ≥35 compared with 30–34 years had higher odds (OR, 1.15; 95% CI, 1.00–1.32) of healthy compared with usual survival to age 90 in the multivariable model (Table 3). Younger paternal age categories were not associated with healthy survival, and no linear association was observed. Paternal age was not associated with death before age 90, and a linear association was not observed among this cohort of older women.
      There were no appreciable changes in findings after adjustment for maternal age in models for paternal age or vice versa; further, there was no interaction between parental ages. Findings were also similar after adjusting for number of brothers and sisters (data not shown). Using an alternative definition of mobility disability, findings for maternal age were similar (data not shown), and being born to a father aged ≥35 compared with 30–34 years at childbirth remained associated with higher odds of healthy compared with usual survival (OR, 1.19; 95% CI, 1.04,1.36).

      4. Discussion

      In a large, national study of postmenopausal women ages 65–79 years at study entry, those who were born to fathers aged ≥35 compared with 30–34 years at their births had higher odds of survival to age 90 without major morbidities or mobility disability, independent of age, race/ethnicity, socioeconomic status (SES), lifestyle behaviors, BMI, family size, and health-related factors. There was no association between a woman’s mother’s age at her birth and healthy survival to age 90, and parental ages were not associated with death before age 90 in this cohort of older women.
      Associations of parental ages with childhood and adulthood health outcomes among offspring have been mixed, and few studies have examined aging outcomes, such as exceptional longevity or healthy aging [
      • D’Onofrio B.M.
      • Rickert M.E.
      • Frans E.
      • Kuja-Halkola R.
      • Almqvist C.
      • Sjolander A.
      • Larsson H.
      • Lichtenstein P.
      Paternal age at childbearing and offspring psychiatric and academic morbidity.
      ,
      • Carslake D.
      • Tynelius P.
      • van den Berg G.
      • Davey Smith G.
      • Rasmussen F.
      Associations of parental age with health and social factors in adult offspring methodological pitfalls and possibilities.
      ,
      • Gavrilov L.A.
      • Gavrilova N.S.
      Biodemography of exceptional longevity: early-life and mid-life predictors of human longevity.
      ,
      • Hubbard R.E.
      • Andrew M.K.
      • Rockwood K.
      Effect of parental age at birth on the accumulation of deficits, frailty and survival in older adults.
      ,
      • Savage T.
      • Derraik J.
      • Miles H.
      • Mouat F.
      • Hofman P.L.
      • Cutfield W.S.
      Increasing maternal age is associated with taller stature and reduced abdominal fat in their children.
      ,
      • Myrskyla M.
      • Fenelon A.
      Maternal age and offspring adult health: evidence from the Health and Retirement Study.
      ,
      • Myrskyla M.
      • Elo I.T.
      • Kohler I.V.
      • Martikainen P.
      The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.
      ,
      • Hviid M.M.
      • Skovlund C.V.
      • Morch L.S.
      • Lidegaard O.
      Maternal age and child morbidity: a Danish national cohort study.
      ,
      • Lu Y.
      • Ma H.
      • Sullivan-Halley J.
      • Henderson K.D.
      • Chang E.T.
      • Clarke C.A.
      • Neuhausen S.L.
      • West D.W.
      • Bernstein L.
      • Wang S.S.
      Parents’ age at birth and risk of adult-onset hematologic malignancies among female teachers in California.
      ,
      • Robine J.M.
      • Cournil A.
      • Henon N.
      • Allard M.
      Have centenarians had younger parents than others?.
      ,
      • Eriksen W.
      • Sundet J.M.
      • Tambs K.
      Paternal age at birth and the risk of obesity in young adulthood: a register-based birth cohort study of Norwegian males.
      ,
      • Khandwala Y.
      • Baker V.L.
      • Shaw G.M.
      • Stevenson D.K.
      • Lu Y.
      • Eisenberg M.L.
      Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population-based cohort study.
      ,
      • Hurley E.G.
      • DeFranco E.A.
      Influence of paternal age on perinatal outcomes.
      ]. A prospective study among >5000 adults ages 65 years and older observed no associations of parental ages with mortality or frailty in old age among sons or daughters [
      • Hubbard R.E.
      • Andrew M.K.
      • Rockwood K.
      Effect of parental age at birth on the accumulation of deficits, frailty and survival in older adults.
      ]. However, that study did not examine survival to an advanced age (i.e., longevity) or use a composite definition of healthy aging as we did in our study. Previous studies have observed no differences in paternal age between children of centenarians and controls [
      • Gavrilov L.A.
      • Gavrilova N.S.
      Biodemography of exceptional longevity: early-life and mid-life predictors of human longevity.
      ,
      • Robine J.M.
      • Cournil A.
      • Henon N.
      • Allard M.
      Have centenarians had younger parents than others?.
      ]; however, these studies relied upon use of historical or registry-based data and did not conduct prospective studies among large cohorts of participants.
      Parental age has been linked to both negative and positive health outcomes among offspring. In the Health and Retirement study, there were U-shaped associations of maternal age with mortality, self-rated heath, obesity, and number of chronic diseases, with worse outcomes for ages <25 and >35 compared with 25–34 years [
      • Myrskyla M.
      • Fenelon A.
      Maternal age and offspring adult health: evidence from the Health and Retirement Study.
      ]; however, paternal age was not examined. Other studies have observed associations of older maternal age with offspring childhood morbidity [
      • Hviid M.M.
      • Skovlund C.V.
      • Morch L.S.
      • Lidegaard O.
      Maternal age and child morbidity: a Danish national cohort study.
      ], higher adult BMI [
      • Carslake D.
      • Tynelius P.
      • van den Berg G.
      • Davey Smith G.
      • Rasmussen F.
      Associations of parental age with health and social factors in adult offspring methodological pitfalls and possibilities.
      ], and higher adult blood pressure [
      • Carslake D.
      • Tynelius P.
      • van den Berg G.
      • Davey Smith G.
      • Rasmussen F.
      Associations of parental age with health and social factors in adult offspring methodological pitfalls and possibilities.
      ], as well as positive outcomes including reduced abdominal fat and improved insulin sensitivity among children [
      • Savage T.
      • Derraik J.
      • Miles H.
      • Mouat F.
      • Hofman P.L.
      • Cutfield W.S.
      Increasing maternal age is associated with taller stature and reduced abdominal fat in their children.
      ]. Older paternal age has been associated with increased risk of non-Hodgkin’s Lymphoma among women [
      • Lu Y.
      • Ma H.
      • Sullivan-Halley J.
      • Henderson K.D.
      • Chang E.T.
      • Clarke C.A.
      • Neuhausen S.L.
      • West D.W.
      • Bernstein L.
      • Wang S.S.
      Parents’ age at birth and risk of adult-onset hematologic malignancies among female teachers in California.
      ], obesity in adulthood [
      • Eriksen W.
      • Sundet J.M.
      • Tambs K.
      Paternal age at birth and the risk of obesity in young adulthood: a register-based birth cohort study of Norwegian males.
      ], psychiatric morbidities in childhood and adolescence [
      • D’Onofrio B.M.
      • Rickert M.E.
      • Frans E.
      • Kuja-Halkola R.
      • Almqvist C.
      • Sjolander A.
      • Larsson H.
      • Lichtenstein P.
      Paternal age at childbearing and offspring psychiatric and academic morbidity.
      ], and mortality [
      • Myrskyla M.
      • Elo I.T.
      • Kohler I.V.
      • Martikainen P.
      The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.
      ]. Furthermore, older paternal age has been associated with increased risk of low birthweight and premature birth in some studies [
      • Khandwala Y.
      • Baker V.L.
      • Shaw G.M.
      • Stevenson D.K.
      • Lu Y.
      • Eisenberg M.L.
      Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population-based cohort study.
      ], whereas others have observed no associations of paternal age with adverse birth outcomes [
      • Hurley E.G.
      • DeFranco E.A.
      Influence of paternal age on perinatal outcomes.
      ].
      Unlike other studies, we examined an older, healthier cohort of women ages 65–79 years at baseline who had already survived many earlier negative outcomes that may be associated with delayed parental age. It is possible that older paternal age may be associated with adverse health outcomes earlier in life and also with healthy survival later in life, conditional upon survival to a benchmark such as 65 years. Further studies following women from ages younger than 65 years are needed to confirm these observations.
      Previous studies have reported associations of older paternal age with longer offspring telomere length, supporting a potential biological mechanism for our findings [
      • Prescott J.
      • Du M.
      • Wong J.Y.
      • Han J.
      • De Vivo I.
      Paternal age at birth is associated with offspring leukocyte telomere length in the Nurses’ Health Study.
      ,
      • De Meyer T.
      • Rietzschel E.R.
      • Buyzere M.L.
      • De Bacquer D.
      • Van Criekinge W.
      • De Becker G.G.
      • Gillebert T.C.
      • Van Oostveldt P.
      • Bekaert S.
      Asklepios Investigators Paternal age at birth is an important determinant of offspring telomere length.
      ]. For example, in the Nurses’ Health Study, older paternal, but not maternal, age was associated with longer offspring telomere length after controlling for confounders including age and childhood SES among women [
      • Prescott J.
      • Du M.
      • Wong J.Y.
      • Han J.
      • De Vivo I.
      Paternal age at birth is associated with offspring leukocyte telomere length in the Nurses’ Health Study.
      ]. Shortened telomere length is associated with reduced longevity, chronic diseases, and functional limitations, suggesting that telomere length might be a mediator in the association of paternal age with healthy aging [
      • Wentzensen I.M.
      • Mirabello L.
      • Pfeiffer R.M.
      • Savage S.A.
      The association of telomere length and cancer: a meta-analysis.
      ,
      • Haycock P.C.
      • Heydon E.E.
      • Kaptoge S.
      • Butterworth A.S.
      • Thompson A.
      • Willeit P.
      Leukocyte telomere length and risk of cardiovascular disease: a systematic review and meta-analysis.
      ,
      • Zhao J.
      • Miao K.
      • Wang H.
      • Ding H.
      • Wang D.W.
      Association between telomere length and type 2 diabetes mellitus: a meta-analysis.
      ,
      • Cawthon R.M.
      • Smith K.R.
      • O’Brien E.
      • Sivatchenko A.
      • Kerber R.A.
      Association between telomere length in blood and mortality in people aged 60 years or older.
      ,
      • Rojas M.
      • Nilsson A.
      • Ponsot E.
      • Brummer R.J.
      • Fairweather-Tait S.
      • Jennings A.
      • de Groot L.C.P.G.M.
      • Berendsen A.
      • Pietruszka B.
      • Madej D.
      • Caumon E.
      • Meunier N.
      • Malpuech-Brugere C.
      • Guidarelli G.
      • Santoro A.
      • Franceschi C.
      • Kadi F.
      Short telomere length is related to limitations in physical function in elderly European adults.
      ]. However, we lacked adequate telomere measurements in our study population, and further studies are needed to evaluate any potential links between paternal age, telomere length, and aging outcomes.
      The association of older paternal age with healthy aging may also be partly explained by residual confounding due to childhood SES. Education, employment, and wealth improve as age increases; therefore, children of older fathers tend to have greater access to economic resources [
      • Liu Y.
      • Zhi M.
      • Li X.
      Parental age and characteristics of the offspring.
      ]. We did not have information on childhood SES (e.g., father’s occupation), which is associated with health outcomes in adulthood [
      • Cohen S.
      • Janicki-Deverts D.
      • Chen E.
      • Matthews K.A.
      Childhood socioeconomic status and adult health.
      ]. However, SES in childhood predicts SES later in life, such that older adults with higher incomes had parents who were financially well-off [
      • Luo Y.
      • Waite L.J.
      The impact of childhood and adult SES on physical, mental, and cognitive well-being in later life.
      ]. Because our findings were independent of SES later in life, it is possible that SES throughout the life course does not fully explain our findings.
      Our study has several limitations. Parental age was not collected at the baseline visit but later during the WHI Extension Study. Therefore, our study population consisted of an older cohort of women who lived long enough and agreed to participate in the Extension Study and complete the questionnaire evaluating parental ages. The number of women who survived to age 90 was thus lower than that who died before age 90. Women who enrolled for additional follow-up in the WHI were more likely to be white, educated, and healthier at baseline. We did not include cognitive status in our definition of healthy aging, because cognitive data were not regularly collected among WHI participants. We also did not have information on birth order. Strengths include a long follow-up period and examination of a diverse cohort of women who survived into advanced ages with information on major chronic diseases and disabilities. There are limited prospective cohorts with information on parental ages and follow-up into late ages to evaluate healthy aging.
      Growing numbers of men and women are choosing to postpone parenthood to later ages. Accordingly, understanding the implications of later parental age on the aging of future generations should be a priority for future research. Specifically, it will be important to determine whether parental age is a surrogate for factors such as SES throughout the life course that are associated with aging.

      Funding

      This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [contracts HHSN268201100046C , HHSN268201100001C , HHSN268201100002C , HHSN268201100003C , HHSN268201100004C , and HHSN271201100004C ].
      The National Heart, Lung, and Blood Institute has representation on the Women’s Health Initiative Steering Committee, which governed the design and conduct of the study, the interpretation of the data, and preparation and approval of manuscripts.

      Ethics statement

      All participants provided written informed consent, and institutional review board approval was received by all participating institutions.

      Provenance and peer review

      This article has undergone peer review.

      Research data (data sharing and collaboration)

      There are no linked research data sets for this paper. Individuals who wish to analyze data from the Women’s Health Initiative (WHI) are required to have paper proposals approved by the WHI Publications and Presentations Committee.

      CRediT authorship contribution statement

      Aladdin H. Shadyab: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - original draft, Writing - review & editing. JoAnn E. Manson: Investigation, Writing - review & editing. Wenjun Li: Methodology, Investigation, Writing - review & editing. Margery Gass: Investigation, Writing - review & editing. Robert L. Brunner: Investigation, Writing - review & editing. Michelle J. Naughton: Investigation, Writing - review & editing. Brad Cannell: Investigation, Writing - review & editing. Barbara V. Howard: Investigation, Writing - review & editing. Andrea Z. LaCroix: Conceptualization, Investigation, Methodology, Project administration, Supervision, Writing - review & editing.

      Declaration of Competing Interest

      The authors declare that they have no conflict of interest.

      Acknowledgements

      We would like to acknowledge the following Women’s Health Initiative Investigators:
      Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller.
      Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg.
      Investigators and Academic Centers: (Brigham and Women's Hospital, Harvard Medical
      School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University,
      Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA)
      Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University
      of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY)
      Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher;
      (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh,
      Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem,NC)
      Sally Shumaker.

      Appendix A. Supplementary data

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