Abstract
We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.
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References
Academy of Medical Sciences Working Group (2007) Identifying the environmental causes of disease: How should we decide what to believe and when to take action?. Academy of Medical Sciences, London
Alan Guttmacher Institute. (2010). U.S. teenage pregnancy statistics: National and state trends and trends by race and ethnicity. New York
Allison PD (2009) Fixed effects regression models. Sage, Washington DC
Astolfi P, Zonta LA (1999) Risks of preterm delivery and association with maternal age, birth order, and fetal gender. Hum Reprod 14(11):2891–2894. doi:10.1093/humrep/14.11.2891
Bacci S, Bartolucci F, Chiavarini M, Minelli L, Pieroni L (2014) Differences in birthweight outcomes: a longitudinal study based on siblings. Int J Environ Res Public Health 11(6):6472–6484. doi:10.3390/ijerph110606472
Baker JL, Olsen LW, Sorensen TIA (2008) Weight at birth and all-cause mortality in adulthood. Epidemiology 19(2):197–203. doi:10.1097/EDE.0b013e31816339c6
Balasch J, Gratacos E (2012) Delayed childbearing: effects on fertility and the outcome of pregnancy. Curr Opin Obstet Gynecol 24(3):187–193. doi:10.1097/GCO.0b013e3283517908
Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS (2002) Cognitive and behavioral outcomes of school-aged children who were born preterm—a meta-analysis. JAMA 288(6):728–737. doi:10.1001/jama.288.6.728
Blennow M, Ewald U, Fritz T, Holmgren PA, Jeppsson A, Lindberg E, Grp E (2009) One-year survival of extremely preterm infants after active perinatal care in Sweden. JAMA 301(21):2225–2233
Bureau of Labor Statistics, U. S. D. o. L., and National Institute for Child Health and Human Development. (2012). Children of the NLSY79, 1979–2010. from Produced and distributed by the Center for Human Resource Research, The Ohio State University
Carolan M (2013) Maternal age ≥ 45 years and maternal and perinatal outcomes: a review of the evidence. Midwifery 29(5):479–489. doi:10.1016/j.midw.2012.04.001
Class QA, Rickert ME, Langstrom N, Lichtenstein P, D’Onofrio BM (2014a) Birth weight, physical morbidity, and mortality: a population-based sibling-comparison study. Am J Epidemiol 179:550–558
Class QA, Rickert ME, Larsson H, Lichtenstein P, D’Onofrio BM (2014b) Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison. Br J Psychiatry 205(5):355–361. doi:10.1192/bjp.bp.113.143693
Cnattingius S, Forman MR, Berendes HW, Isotalo L (1992) Delayed childbearing and risk of adverse perinatal outcome: a population-based study. JAMA 268(7):886–890
Coley RL, Chase-Lansdale PL (1998) Adolescent pregnancy and parenthood: recent evidence and future directions. Am Psychol 53(2):152–166. doi:10.1037/0003-066x.53.2.152
Coyne CA, D’Onofrio BM (2012) Some (but not much) progress toward understanding teenage childbearing: A reveiew of research from the past decade. In: Benson JB (ed) Advances in child development and behavior, vol 42. Academic Press, California, pp 113–152
Crump C, Winkleby MA, Sundquist K, Sundquist J (2010) Preterm birth and psychiatric medication prescription in young adulthood: a Swedish national cohort study. Int J Epidemiol 39(6):1522–1530. doi:10.1093/ije/dyq103
Crump C, Sundquist K, Sundquist J, Winkleby M (2011) Gestational age at birth and mortality in young adulthood. JAMA 306(11):1233–1240. doi:10.1001/jama.2011.1331
D’Onofrio BM, Goodnight JA, Van Hulle CA, Rodgers JL, Rathouz PJ, Waldman ID, Lahey BB (2009) Maternal age at childbirth and offspring disruptive behaviors: testing the causal hypothesis. J Child Psychol Psychiatry 50(8):1018–1028. doi:10.1111/j.1469-7610.2009.02068.x
D’Onofrio BM, Class QA, Rickert ME, Larsson H, Langstrom N, Lichtenstein P (2013a) Preterm birth and mortality and morbidity a population-based quasi-experimental study. JAMA Psychiatry 70(11):1231–1240. doi:10.1001/jamapsychiatry.2013.2107
D’Onofrio BM, Lahey BB, Turkheimer E, Lichtenstein P (2013b) The critical need for family-based, quasi-experimental research in integrating genetic and social science research. Am J Public Health 103:S46–S55
Duncan GJ (2012) Give us this day our daily breadth. Child Dev 83(1):6–15. doi:10.1111/j.1467-8624.2011.01679.x
Elliott DS, Huizinga D (1983) Social-class and delinquent-behavior in a national youth panel—1976–1980. Criminology 21(2):149–177. doi:10.1111/j.1745-9125.1983.tb00256.x
Freese J (2008) Genetics and the social science explanation of individual outcomes. Am J Sociol 114:S1–S35
Gauderman WJ, Witte JS, Thomas DC (1999) Family-based association studies. J Natl Cancer Inst Monogr 26:31–37
Geronimus AT, Korenman S (1993) Maternal youth or family background—on the health disadvantages of infants with teenage mothers. Am J Epidemiol 137(2):213–225
Geronimus AT, Korenman S, Hillemeier MM (1994) Does young maternal age adversely affect child-development: evidence from cousin comparisons in the United-States. Popul Dev Rev 20(3):585–609. doi:10.2307/2137602
Gibbs CM, Wendt A, Peters S, Hogue CJ (2012) The impact of early age at first childbirth on maternal and infant health. Paediatr Perinat Epidemiol 26:259–284. doi:10.1111/j.1365-3016.2012.01290.x
Hedges LV, Olkin I (2014) Statistical method for meta-analysis. Academic press, New York
Hedges LV, Vevea JL (1998) Fixed-and random-effects models in meta-analysis. Psychol Methods 3(4):486
Jaffee S, Caspi A, Moffitt TE, Belsky J, Silva P (2001) Why are children born to teen mothers at risk for adverse outcomes in young adulthood? Results from a 20-year longitudinal study. Dev Psychopathol 13(2):377–397. doi:10.1017/s0954579401002103
Kendler KS (2005) Psychiatric genetics: a methodologic critique. Am J Psychiatry 162(1):3–11. doi:10.1176/appi.ajp.162.1.3
Knopik VS (2009) Maternal smoking during pregnancy and child outcomes: real or spurious effect? Dev Neuropsychol 34(1):1–36. doi:10.1080/87565640802564366
Mathiasen R, Hansen BM, Anderson AMN, Greisen G (2009) Socio-economic achievements of individuals born very preterm at the age of 27 to 29 years: a nationwide cohort study. Dev Med Child Neurol 51(11):901–908. doi:10.1111/j.1469-8749.2009.03331.x
Mersky JP, Reynolds AJ (2007) Predictors of early childbearing: evidence from the Chicago longitudinal study. Child Youth Serv Rev 29(1):35–52. doi:10.1016/j.childyouth.2006.03.009
Mitchell BF, Taggart MJ (2009) Are animal models relevant to key aspects of human parturition? Am J Physiol-Regul Integr Comp Physiol 297(3):R525–R545. doi:10.1152/ajpregu.00153.2009
Newburn-Cook CV, Onyskiw JE (2005) Is older maternal age a risk factor for preterm birth and fetal growth restriction? A systematic review. Health Care Women Int 26(9):852–875. doi:10.1080/07399330500230912
Nilsen ABV, Waldenstrom U, Hjelmsted A, Rasmussen S, Schytt E (2012) Characteristics of women who are pregnant with their first baby at an advanced age. Acta Obstet Gynecol Scand 91(3):353. doi:10.1111/j.1600-0412.2011.01335.x
Odibo AO, Nelson D, Stamilio DM, Sehdev HM, Macones GA (2006) Advanced maternal age is an independent risk factor for intrauterine growth restriction. Am J Perinatol 23(5):325–328. doi:10.1055/s-2006-947164
Randloff LA (1977) The CES-D scale: a self report depression scale for research in the general population. Appl Psychol Meas 1:385–401
Rodgers JL, Bard DE, Miller WB (2007) Multivariate Cholesky models of human female fertility patterns in the NLSY. Behav Genet 37(2):345–361. doi:10.1007/s10519-006-9137-9
Rosenzweig MR, Wolpin KI (1995) Sisters, siblings, and mothers: the effects of teenage childbearing on birth outcomes in a dynamic family context. Econometrica 63(2):303–326. doi:10.2307/2951628
Rutter M (2007) Proceeding from observed correlation to causal inference: the use of natural experiments. Perspect Psychol Sci 2:377–395
Rutter M, Pickles A, Murray R, Eaves L (2001) Testing hypotheses on specific environmental causal effects on behavior. Psychol Bull 127(3):291–324. doi:10.1037//0033-2909.127.3.291
Susser E, Eide MG, Begg M (2010) Invited commentary: the use of sibship studies to detect familial confounding. Am J Epidemiol 172(5):537–539. doi:10.1093/aje/kwq196
Swamy GK, Edwards S, Gelfand A, James SA, Miranda ML (2012) Maternal age, birth order, and race: differential effects on birthweight. J Epidemiol Community Health 66(2):136–142. doi:10.1136/jech.2009.088567
Turley RNL (2003) Are children of young mothers disadvantaged because of their mother’s age or family background? Child Dev 74(2):465–474
Acknowledgments
This work was supported by a National Science Foundation Graduate Research Fellowship (Grand No. 1342962) awarded to the first author, the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (Grant No. 340-2013-5867), and the National Institute of Child Health and Human Development (HD061817). This study was approved by the Institutional Review Board at Indiana University and the Karolinska Institute.
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Ayesha C. Sujan, Martin E. Rickert, Quetzal A. Class, Claire A. Coyne, Paul Lichtenstein, Catarina Almqvist, Henrik Larsson, Arvid Sjölander, Benjamin B. Lahey, Carol van Hulle, Irwin Waldman, A. Sara Öberg, and Brian M. D’Onofrio declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
Appendices
Appendix 1
In order to test carry-over effects, we fit a model that controlled for maternal age at first childbirth and birth order in a subsample of the data that excluded first-born offspring. We compared the results from this model to Model 1, the population model, which only controlled for birth order (see Figs. 3 and 4). In general, the analyses controlling for maternal age at first childbirth (see Table 3 and the second column of Figs. 3 and 4) were consistent with the results in the main text. The models showed a similar pattern of results for the association between MAC and GA, suggesting that differences in GA among offspring were not due to when a woman had her first child. Furthermore, the models showed similar results for the association between older MAC and BWGA. However, including maternal age at first childbirth as a covariate slightly attenuated the association between younger MAC and BWGA, suggesting that maternal age at first childbirth may partially account for the observed population-wide association between younger MAC and BWGA.
Appendix 2
We did not include offspring year of birth as a covariate in the main analyses because differences in offspring year of birth would be almost perfectly correlated with differences in MAC in the sibling comparison models. Thus, in order to test whether associations may be due to birth cohort effects (i.e., changes in society that have occurred over time) we fit population models that controlled for offspring year of birth. The population-wide models with (see Table 4 and the second column of Figs. 5 and 6) and without (see the first column of Figs. 5 and 6) year of birth included as a covariate yielded the same pattern of results, suggesting that birth cohort effects did not bias our interpretation of the results in the main text.
Appendix 3
We re-ran the adjusted population models (Model 2) and the sibling comparison models (Model 4) in the Swedish sample, leaving out paternal covariates to examine the role of measured paternal characteristics (see Figs. 7 and 8 for population models and Figs. 9 and 10 for sibling comparison models). The model provided us with some insight into the possible confounding roles of measured paternal factors, which we did not have access to in the US sample. The models without paternal covariates (see Table 5 and column two of Figs. 7, 8, 9, 10) showed the same patterns of findings as the models with paternal covariates (see column one of Figs. 7, 8, 9, 10), suggesting that measured paternal characteristics did not account for the results in the Swedish analyses.
Appendix 4
Because GA and birth weight are correlated with birth order we fit a cousin comparison models restricted to the subsample of first-born individuals in the Swedish dataset (see Figs. 11 and 12) to assess whether birth order may have influenced the main results. The first-born cousin comparisons (see Table 6 and column two of Figs. 11 and 12) showed the same patterns of findings as the main analyses full-cousin comparisons (Model 3; see column one of Figs. 11 and 12), suggesting that our main results were not due to birth order effects.
Appendix 5
To examine the clinical significance of the finding further, in the Swedish sample we re-ran models used in the main analyses to predict the log-odds of PTB (see Table 7 and Fig. 13) and found that the results were consistent with the GA findings from the main analyses. The results suggested the observed population-wide association between early MAC and increased risk for PTB was confounded by familial factors. However, the association between advanced MAC and increased risk for PTB was observed in all models, thus, providing support for an association between advanced MAC and increased risk for PTB, independent of measured covariates and unmeasured shared familial factors.
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Sujan, A.C., Rickert, M.E., Class, Q.A. et al. A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes. Behav Genet 46, 431–456 (2016). https://doi.org/10.1007/s10519-015-9748-0
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DOI: https://doi.org/10.1007/s10519-015-9748-0