Lipid levels after childbirth and association with number of children: A population-based cohort study

Autoři: Aleksandra Pirnat aff001;  Lisa A. DeRoo aff001;  Rolv Skjærven aff002;  Nils-Halvdan Morken aff003
Působiště autorů: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway aff001;  Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway aff002;  Department of Clinical Science, University of Bergen, Bergen, Norway aff003;  Department of Obstetrics and Gynecology, Haukeland University Hospital, University of Bergen, Bergen, Norway aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Low parity women are at increased risk of cardiovascular mortality. Unfavourable lipid profiles have been found in one-child mothers years before they conceive. However, it remains unclear whether unfavourable lipid profiles are evident in these women also after their first birth. The aim was to estimate post-pregnancy lipid levels in one-child mothers compared to mothers with two or more children and to assess these lipid’s associations with number of children.


We used data on 32 618 parous women (4 490 one-child mothers and 28 128 women with ≥2 children) examined after first childbirth as part of Cohort of Norway (1994–2003) with linked data on reproduction and number of children from the Medical Birth Registry of Norway (1967–2008). Odds ratios (ORs) with 95% confidence intervals (CIs) for one lifetime pregnancy (vs. ≥2 pregnancies) by lipid quintiles were obtained by logistic regression and adjusted for age at examination, year of first birth, body mass index, oral contraceptive use, smoking and educational level.


Compared to women with the lowest quintiles, ORs for one lifetime pregnancy for the highest quintiles of LDL and total cholesterol were 1.30 (95%CI: 1.14–1.45) and 1.43 (95%CI: 1.27–1.61), respectively. Sensitivity analysis (women <40 years) showed no appreciable change in our results. In stratified analyses, estimates were slightly stronger in overweight/obese, physically inactive and women with self-perceived bad health.


Mean lipid levels measured after childbirth in women with one child were significantly higher compared to mothers with two or more children and were associated with higher probability of having only one child. These findings corroborate an association between serum lipid levels and one lifetime pregnancy (as a feature of subfecundity), emphasizing that these particular women may be a specific predetermined risk group for cardiovascular related disease and death.

Klíčová slova:

Birth – Body Mass Index – Cardiovascular diseases – Cholesterol – Lipid profiles – Lipids – Pregnancy – Oral contraceptive therapy


1. Brown HL, Warner JJ, Gianos E, Gulati M, Hill AJ, Hollier LM, et al. Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists. Circulation. 2018;137: e843–e852 doi: 10.1161/CIR.0000000000000582 29748185

2. Halland F, Morken NH, DeRoo LA, Klungsøyr K, Wilcox AJ, Skjærven R. Association of Women's Reproductive History With Long-term Mortality and Effect of Socioeconomic Factors. Obstet Gynecol. 2015;126: 1181–7. doi: 10.1097/AOG.0000000000001155 26551179

3. Lewis CE, Funkhouser E, Raczynski JM, Sidney S, Bild DE, Howard BV. Adverse effect of pregnancy on high density lipoprotein (HDL) cholesterol in young adult women. The CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol.1996;144: 247–54. doi: 10.1093/oxfordjournals.aje.a008919 8686693

4. Parikh NI, Cnattingius S, Mittleman MA, Ludvigsson JF, Ingelsson E. Subfertility and risk of later life maternal cardiovascular disease. Hum Reprod. 2012;27: 568–575. doi: 10.1093/humrep/der400 22131387

5. Skjaerven R, Wilcox AJ, Klungsøyr K, Irgens LM, Vikse BE, Vatten LJ, et al. Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study. BMJ 2012;345:e7677. doi: 10.1136/bmj.e7677 23186909

6. Grundy E, Kravdal O. Reproductive history and mortality in late middle age among Norwegian men and women. Am J Epidemiol. 2008;167: 271–279. doi: 10.1093/aje/kwm295 18000019

7. Li W, Ruan W, Lu Z, Wang D. Parity and risk of maternal cardiovascular disease: A dose-response meta-analysis of cohort studies. Eur J Prev Cardiol. 2018;19: 2047487318818265.

8. Schisterman EF, Mumford SL, Browne RW, Barr DB, Chen Z, Louis GM. Lipid concentrations and couple fecundity: the LIFE study. J Clin Endocrinol Metab. 2014;99: 2786–2794. doi: 10.1210/jc.2013-3936 24846535

9. Pugh SJ, Schisterman EF, Browne RW, Lynch AM, Mumford SL, Perkins NJ, et al. Preconception maternal lipoprotein levels in relation to fecundability. Hum Reprod. 2017;32: 1055–1063. doi: 10.1093/humrep/dex052 28333301

10. Miettinen HE, Rayburn H, Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice. J Clin Invest. 2001;108:1717–1722. doi: 10.1172/JCI13288 11733567

11. Lobaccaro JM, Gallot, Lumbroso S, Mouzat K. Liver X Receptors and female reproduction: when cholesterol meets fertility! J Endocrinol Invest. 2013;36:55–60. doi: 10.3275/8765 23211426

12. Cardozo E, Pavone ME, Hirshfeld-Cytron JE. Metabolic syndrome and oocyte quality. Trends Endocrinol Metab. 2011;22: 103–109. doi: 10.1016/j.tem.2010.12.002 21277789

13. Fujimoto VY, Kane JP, Ishida BY, Bloom MS, Browne RW. High- density lipoprotein metabolism and the human embryo. Hum Reprod Update. 2010;16: 20–38. doi: 10.1093/humupd/dmp029 19700490

14. Grummer R R, Carroll DJ. A review of lipoprotein cholesterol metabolism: importance to ovarian function. J Anim Sci. 1988;66: 3160–3173. doi: 10.2527/jas1988.66123160x 3068221

15. Mouzat K, Baron S, Marceau G, Caira F, Sapin V, Volle DH, et al. Emerging roles for LXRs and LRH-1 in female reproduction. Mol Cell Endocrinol. 2013;368: 47–58. doi: 10.1016/j.mce.2012.06.009 22750099

16. Browne RW, Bloom MS, Shelly WB, Ocque AJ, Huddleston HG, Fujimoto VY. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF. J Assist Reprod Genet. 2009;26:5 57–560.

17. Gautier T, Becker S, Drouineaud V, Ménétrier F, Sagot P, Nofer JR, et al. Human luteinized granulosa cells secrete apoB100-containing lipoproteins. J Lipid Res. 2010;51: 2245–2252. doi: 10.1194/jlr.M005181 20407020

18. Von Wald T, Monisova Y, Hacker MR, Yoo SW, Penzias AS, Reindollar RR, et al. Age-related variations in follicular apolipoproteins may influence human oocyte maturation and fertility potential. Fertil Steril. 2010;93: 2354–2361. doi: 10.1016/j.fertnstert.2008.12.129 19230882

19. Kim K, Bloom MS, Browne RW, Bell EM, Yucel RM, Fujimoto VY. Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients. J Assist Reprod Genet. 2017;34: 1–10.

20. Markovitz AR, Haug EB, Horn J, Fraser A, Macdonald-Wallis C, Tilling K, et al. Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway. J Lipid Res. 2018;59: 2403–2412. doi: 10.1194/jlr.P085720 30314998

21. Gunderson EP, Lewis CE, Murtaugh MA, Quesenberry CP, Smith West D, Sidney S. Long-term plasma lipid changes associated with a first birth: the Coronary Artery Risk Development in Young Adults study. Am J Epidemiol. 2004;159: 1028–39. doi: 10.1093/aje/kwh146 15155287

22. Agrinier N, Cournot M, Dallongeville J, Arveiler D, Ducimetière P, Ruidavets JB,et al. Menopause and modifiable coronary heart disease risk factors: a population based study. Maturitas. 2010;65: 237–43. doi: 10.1016/j.maturitas.2009.11.023 20031345

23. Derby CA, Crawford SL, Pasternak RC, Sowers M, Sternfeld B, Matthews KA. Lipid changes during the menopause transition in relation to age and weight: the Study of Women's Health Across the Nation. Am J Epidemiol. 2009;169: 1352–61. doi: 10.1093/aje/kwp043 19357323

24. Gunderson EP, Schreiber G, Striegel-Moore R, Hudes M, Daniels S, Biro FM, et al. Pregnancy during adolescence has lasting adverse effects on blood lipids: a 10-year longitudinal study of black and white females. J Clin Lipidol. 2012;6: 139–49. doi: 10.1016/j.jacl.2011.12.004 22385547

25. Pirnat A, DeRoo L, Skjaerven R, Morken NH. Women’s pre-pregnancy lipid levels and number of children. BMJ Open. 2018;8: e021188. doi: 10.1136/bmjopen-2017-021188 29986867

26. Naess O, Sogaard AJ, Arnesen E, Beckstrom AC, Bjertness E, Engeland A, et al. Cohort profile: cohort of Norway (CONOR). Int J Epidemiol. 2008;37: 481–485. doi: 10.1093/ije/dym217 17984119

27. Irgens LM. The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years. Acta Obstet Gynecol Scand. 2000;79: 435–439. 10857866

28. Holmen J, Midthjell K, Kruger Ø, Langhammer A, Holmen TL, Bratberg GH, et al. The Nord-Trøndelag Health Study 1995–97 (HUNT 2): Objectives, contents, methods and participation. Norsk Epidemiologi. 2003;13: 19–32.

29. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18: 499–502. 4337382

30. Enkhmaa B, Prakash N, Berglund L. Non-HDL-C levels and residual cardiovascular risk: Do population-specific precision approaches offer any advantages? Atherosclerosis. 2018; 274: 230–231. doi: 10.1016/j.atherosclerosis.2018.05.010 29764695

31. Porta MS, Greenland S, Hernan M, Silva I.dS, Last JM, International Epidemiological Association. A dictionary of epidemiology. 6th ed. Oxford University Press, Oxford. 2014.

32. Last JM., International Epidemiological Association. A dictionary of epidemiology. 4th ed. Oxford University Press, New York. p76. 2001.

33. VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med. 2017;167: 268–274. doi: 10.7326/M16-2607 28693043

34. Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol. 2009;15: 54(25).

35. Kurabayashi T, Mizunuma H, Kubota T, Hayashi K. Ovarian infertility is associated with cardiovascular disease risk factors in later life: A Japanese cross-sectional study. Maturitas. 2016;83: 33–9. doi: 10.1016/j.maturitas.2015.08.015 26417693

36. Hubert HB, Eaker ED, Garrison RJ, Castelli WP. Life-style correlates of risk factor change in young adults: an eight-year study of coronary heart disease risk factors in the Framingham offspring. Am J Epidemiol. 1987;125: 812–31. doi: 10.1093/oxfordjournals.aje.a114598 3565356

37. Mankuta D, Elami-Suzin M, Elhayani A, Vinker S. Lipid profile in consecutive pregnancies. Lipids Health Dis. 2010; 9: 58. doi: 10.1186/1476-511X-9-58 20525387

38. Descamps OS, Bruniaux M, Guilmot PF, Tonglet R, Heller FR. Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children. J Lipid Res. 2005;46: 2405–14. doi: 10.1194/jlr.M500223-JLR200 16106048

39. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113: 898–918. doi: 10.1161/CIRCULATIONAHA.106.171016 16380542

40. Ertunc M.E, Hotamisligil GS. Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res. 2016;57: 2099–2114. doi: 10.1194/jlr.R066514 27330055

41. Cole CB, Nikpay M, Lau P, Stewart AF, Davies RW, Wells GA, et al. Adiposity significantly modifies genetic risk for dyslipidemia. J Lipid Res.2014;55: 2416–22. doi: 10.1194/jlr.P052522 25225679

42. Mavaddat N, Parker RA, Sanderson S, Mant J, Kinmonth AL. Relationship of self-rated health with fatal and non-fatal outcomes in cardiovascular disease: a systematic review and meta-analysis. PLoS One. 2014;9: e103509. doi: 10.1371/journal.pone.0103509 25076041

43. Sjaarda L, Mumford S, Connell MT, Kim K, Hill MJ, Perkins N, et al. Increased androgen, anti-mullerian hormone and neonatal outcomes in fertile women without PCOS. Fert Ster. 2018;110: 9e.

44. Tani S, Matsumoto M, Nagao K, Hirayama A. Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size. J Cardiol. 2014;63: 60–8. doi: 10.1016/j.jjcc.2013.06.018 24016623

45. Bassuk SS, Manson JE. Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol (1985). 2005;99: 1193–204.

46. Egeland GM, Klungsøyr K, Øyen N, Tell GS, Næss Ø, Skjærven R. Preconception Cardiovascular Risk Factor Differences Between Gestational Hypertension and Preeclampsia: Cohort Norway Study. Hypertension. 2016;67: 1173–80. doi: 10.1161/HYPERTENSIONAHA.116.07099 27113053

47. Fukami K, Koike K, Hirota K, Yoshikawa H, Miyake A. Perimenopausal changes in serum lipids and lipoproteins: a 7-year longitudinal study. Maturitas. 1995;22: 193–7. doi: 10.1016/0378-5122(95)00927-d 8746876

48. Pai JK, Manson JE. Acceleration of cardiovascular risk during the late menopausal transition. Menopause. 2013;20: 1–2. doi: 10.1097/gme.0b013e318278e9b4 23266836

49. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298: 299–308. doi: 10.1001/jama.298.3.299 17635890

50. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298: 309–1 doi: 10.1001/jama.298.3.309 17635891

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden