Original Article

Preeclamapsia Preeclampsia Mediates the Association between Advanced Maternal Age and Adverse Pregnancy Outcomes: A Structural Equation Modeling Approach


Background: Advanced maternal age (AMA) is considered a risk factor associated with preeclampsia and adverse pregnancy outcomes. We aimed to assess the mediating role of preeclampsia between AMA and adverse pregnancy outcomes.

Methods: A sample of 14646 pregnant women from the tertiary hospital of Hubei Province, China, during the years 2011-2017 were included in this study. Pregnant women were divided into 4 groups according to their age at delivery. Mediated effect of preeclampsia with relation to AMA and adverse pregnancy outcomes was measured using structural equation modeling.

Results: Women in the highest age group were significantly associated with preterm delivery [RR 1.37 (95% CI 1.24 - 1.49)] and low birth weight [RR 1.28 (95% CI 1.11 - 1.45)] compared with women in the lowest age group. The indirect effect (mediated effect) of AMA on preterm delivery and low birth weight mediated by preeclampsia was [β 0.053 (95% CI: 0.047, 0.060)], and [β 0.045 (95% CI: 0.038, 0.052)], respectively. The estimated mediation proportion of the effect of AMA due to mediated effect of preeclampsia was (35.5%) for preterm delivery and (23.5%) for low birth weight.

Conclusion: Preeclampsia partially mediates the association between AMA and adverse pregnancy outcomes.

1. Goisis A, Remes H, Barclay K, et al (2017). Advanced maternal age and the risk of low birth weight and preterm delivery: a within-family analysis using Finnish pop-ulation registers. Am J Epidemiol, 186(11):1219–1226.
2. Shan D, Qiu PY, Wu YX, et al (2018). Preg-nancy outcomes in women of advanced maternal age: a retrospective cohort study from China. Scientific Reports, 8:12239.
3. Hamilton BE, Martin JA, Osterman MJK, et al (2015). Births: final data for 2014. Natl Vital Stat Rep, 64(12):1–64.
4. Jacobsson B, Ladfors L, Milsom I (2004). Advanced maternal age and adverse peri-natal outcome. Obstet Gynecol, 104:727–33.
5. Waldenstrom U, Cnattingius S, Vixner L, et al (2017). Advanced maternal age increas-es the risk of very preterm birth, irrespec-tive of parity: a population based register study. BJOG, 124(8):1235–1244.
6. Cnattingius S, Forman MR, Berendes HW, et al (1992). Delayed childbearing and risk of adverse perinatal outcome. a popula-tion-based study. JAMA, 268(7):886-90.
7. Almeida NK, Almeida RM, Pedreira CE (2015). Adverse Perinatal outcomes for advanced maternal age: a cross-sectional study of Brazilian births. J Pediatr (Rio J), 91(5):493-8.
8. Koo YJ, Ryu HM, Yang JH, et al (2012). Pregnancy outcomes according to in-creasing maternal age. Taiwan J Obstet Gy-necol, 51(1):60-5.
9. Lamminpaa R, Julkunen KV, Gissler M, et al (2012). Preeclampsia complicated by ad-vanced maternal age: a registry-based study on primiparous women in Finland 1997-2008. BMC Pregnancy Childbirth, 12:47.
10. Londero AP, Rossetti E, Pittini C, et al (2019). Maternal age and the risk of ad-verse pregnancy outcomes: a retrospec-tive cohort study. BMC Pregnancy and Childbirth, 19(261): 2-10.
11. Rasmussen S, Irgens LM (2003). Fetal growth and body proportion in preeclampsia. Obstet Gynecol, 101(3):575-83.
12. Nawsherwan, Khan A, Begum N, et al (2020). Low birth weight, and low pon-deral index mediates the association be-tween preeclampsia, placenta previa, and neonatal mortality. Iran J Public Health, 49(4):654-662.
13. Kang H (2013). The prevention and han-dling of the missing data. Korean J Anesthe-siol, 64(5): 402-406.
14. Hossin MH, Koupil I, Falkstedt D (2019). Early life socioeconomic position and mortality from cardiovascular diseases: an application of causal mediation analysis in the Stockholm Public Health Cohort. BMJ Open, 9:e026258.
15. Hu Lt, Bentler PM (1999). Cutoff criteria for fit indexes in covariance structure analy-sis: conventional criteria versus new alter-natives. Struct Equ Modeling, 6:1–55.
16. Kelly R, Holzman C, Senagore P, et al (2009). Placental vascular pathology find-ings and pathways to preterm delivery. Am J Epidemiol, 170:148–158.
17. Norwitz ER, Caughey AB (2011). Progester-one supplementation and the prevention of preterm birth. Rev Obstet Gynecol, 4(2):60–72.
18. Driul L, Londero AP, Bertozzi S, et al (2010). Pregnancy outcome and neonatal health by mothers aged 40 years and over. JMMS, 1:148-155.
19. Tabcharoen C, Pinjaroen S, Suwanrath C, et al (2009). Pregnancy outcome after age 40 and risk of low birth weight. J Obstet Gynaecol, 29:378-83.
20. Aldous MB, Edmonson MB (1993). Mater-nal age at first childbirth and risk of low birth weight and preterm delivery in Washington State. JAMA, 270(21):2574–7.
21. Althabe F, Moore JL, Gibbons L, et al (2015). Adverse maternal and perinatal outcomes in adolescent pregnancies: The global Network’s maternal newborn health registry study. Reprod Health, 12(2):S8.
22. Alemu T, Umeta M (2015). Prevalence and determinants of small size babies in Ethiopia: Results from in-depth analyses of the Ethiopian Demographic and Health Survey-2011. Fam Med Med Sci Res, 4(171):2.
23. Restrepo-Mendez MC, Lawlor DA, Horta BL, et al (2015). The association of ma-ternal age with birthweight and gestation-al age: a cross-cohort comparison. Paedi-atr Perinat Epidemiol, 29:31-40.
24. Davies EL, Bell JS, Bhattacharya S (2016). Preeclampsia and preterm delivery: A population based case–control study. Hy-pertens Pregnancy, 35(4):510-519.
25. Martius J, Steck T, Oehler M, et al (1998). Risk factors associated with preterm (<37+0 weeks) and early preterm (<32+0 weeks): univariate and multivariate analy-sis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavar-ia. Eur J Obstet Gynecol Reprod Biol, 80(2):183-9.
26. Maiti S, Kanrar P, Karmakar C, et al (2014). Maternal and perinatal outcome in rural Indian women with placenta previa. Br Biomed Bull, 2(4):714-718.
27. Mayo K, Melamed N, Vandenberghe H (2015). The impact of adoption of the in-ternational association of diabetes in pregnancy study group criteria for the screening and diagnosis of gestational di-abetes. Am J Obstet Gynecol, 212(2):224.e1-9.
28. Waldenstrom U, Aasheim V, Nilsen ABV, et al (2014). Adverse pregnancy outcomes related to advanced maternal age com-pared with smoking and being over-weight. Obstet Gynecol, 123 (1) 104-12.
29. Gant NF, Worley RT (1980). Hypertension in pregnancy: Concepts and management. In: Chesley LC (ed) Hypertension in pregnancy. Appleton Century Crofts, New York, 199-204.
IssueVol 49 No 9 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i9.4092
Advanced maternal age; Preeclampsia Adverse pregnancy outcomes Structural equation modeling

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How to Cite
NAWSHERWAN ., MUBARIK S, NABI G, WANG S, FAN C. Preeclamapsia Preeclampsia Mediates the Association between Advanced Maternal Age and Adverse Pregnancy Outcomes: A Structural Equation Modeling Approach. Iran J Public Health. 2020;49(9):1727-1733.