Increased BMI has a linear association with late-onset preeclampsia: A population-based study

Autoři: Pierre-Yves Robillard aff001;  Gustaaf Dekker aff003;  Marco Scioscia aff004;  Francesco Bonsante aff001;  Silvia Iacobelli aff001;  Malik Boukerrou aff002;  Thomas C. Hulsey aff006
Působiště autorů: Service de Néonatologie, Centre Hospitalier Universitaire Sud Réunion, Saint-Pierre Cedex, La Réunion, France aff001;  Centre d’Etudes Périnatales Océan Indien (CEPOI), Centre Hospitalier Universitaire Sud Réunion, Saint-Pierre Cedex, La Réunion, France aff002;  Department of Obstetrics & Gynaecology, University of Adelaide, Robinson Institute, Lyell McEwin Hospital, Adelaide, Australia aff003;  Department of Obstetrics and Gynaecology, Policlinico of Abano Terme, Padua, Abano Terme, Italy aff004;  Service de Gynécologie et Obstétrique, Centre Hospitalier Universitaire Sud Réunion, Saint-Pierre Cedex, La Réunion, France aff005;  Department of Epidemiology, School of Public Health, West Virginia University, Morgantown, WV, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223888



To investigate the ongoing controversy on the effect of BMI (body mass index) on EOP (early onset preeclampsia) vs LOP (late onset), especially focusing on diabetes and maternal booking/pre-pregnancy BMI as possible independent variables.


18 year-observational cohort study (2001–2018). The study population consisted of all consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity (ap. 4,300 birth per year, only level 3 maternity in the south of Reunion Island, sole allowed to follow and deliver all preeclampsia cases of the area). History of pregnancies, deliveries and neonatal outcomes have been collected in standardized fashion into an epidemiological perinatal data base.


Chronic hypertension and, history of preeclampsia in multigravidas, were the strongest risk factors for EOP. Primiparity, age over 35 years and BMI ≥ 35 kg/m² were rather associated with LOP. In a multivariate analysis with EOP or LOP as outcome variables compared with controls (normotensive), maternal age and pre-pregnancy BMI were independent risk factors for both EOP and LOP (p < 0.001). However, analyzing by increment of 5 (years of age, kg/m² for BMI) rising maternal ages and incidence of preeclampsia were strictly parallel for EOP and LOP, while increment of BMI was only associated with LOP. Controlling for maternal ages and booking/pre-pregnancy BMI, diabetes was not an independent risk factor neither for EOP or LOP.


Metabolic factors, other than diabetes, associated with pre-pregnancy maternal corpulence are specifically associated with LOP. This may be a direction for future researches on the maternal preeclamptic syndrome. This may explain the discrepancy we are facing nowadays where high-income countries report 90% of their preeclampsia being LOP, while it is only 60–70% in medium-low income countries.

Klíčová slova:

Body mass index – Diabetes mellitus – Gestational diabetes – Hypertensive disorders in pregnancy – Medical risk factors – Obesity – Preeclampsia – Pregnancy


1. Tranquilli AL, Brown MA, Zeeman GG, Dekker G, Sibai BM. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).Pregnancy Hypertens. 2013 Jan;3(1):44–7. doi: 10.1016/j.preghy.2012.11.001 26105740

2. Robillard PY, Dekker G, Chaouat G, Scioscia M, Iacobelli S, Hulsey TC. Historical evolution of ideas on eclampsia/preeclampsia: A proposed optimistic view of preeclampsia. J Reprod Immunol. 2017 Sep;123:72–77. doi: 10.1016/j.jri.2017.09.006 28941881

3. Bartsch E, Medcalf KE, Park AL, Ray JG; High Risk of Pre-eclampsia Identification Group. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016 Apr 19;353:i1753. doi: 10.1136/bmj.i1753 27094586

4. Conde-Agudelo A(1), Belizán JM. Risk factors for pre-eclampsia in a large cohort of Latin American and Caribbean women. BJOG. 2000 Jan;107(1):75–83. 10645865

5. Sibai BM Gordon T, Thom E, Caritis SN, Klebanoff M, McNellis D, Paul RH. Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 1):642–8.

6. O'Brien TE, Ray JG, Chan WS. Maternal body mass index and the risk of preeclampsia: a systematic overview. Epidemiology. 2003;14(3):368–74. doi: 10.1097/00001648-200305000-00020 12859040

7. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol. 2004;103(2):219–24. doi: 10.1097/01.AOG.0000107291.46159.00 14754687

8. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785–99. doi: 10.1016/S0140-6736(05)17987-2 15733721

9. Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381. doi: 10.1136/bmj.l2381 31307997

10. Anderson NH, McCowan LM, Fyfe EM, Chan EH, Taylor RS, Stewart AW, Dekker GA, North RA; SCOPE Consortium. The impact of maternal body mass index on the phenotype of pre-eclampsia: a prospective cohort study. BJOG. 2012 Apr;119(5):589–95. doi: 10.1111/j.1471-0528.2012.03278.x Feb 3. 22304412

11. Robillard PY, Dekker G, Chaouat G, Le Bouteiller P, Scioscia M, Hulsey TC. Preeclampsia and the 20th century: "Le siècle des Lumières". Pregnancy Hypertens. 2018 Jul;13:107–109. doi: 10.1016/j.preghy.2018.05.013 30177035

12. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627–2642. doi: 10.1016/S0140-6736(17)32129-3 29029897

13. Wolfe HM, Zador IE, Gross TL, Martier SS, Sokol RJ. The clinical utility of maternal body mass index in pregnancy.Am J Obstet Gynecol. 1991 May;164(5 Pt 1):1306–10.

14. Jolly M, Sebire N, Harris J, Robinson S, Regan L. The risks associated with pregnancy in women aged 35 years or older. Hum Reprod. 2000 Nov;15(11):2433–7. doi: 10.1093/humrep/15.11.2433 11056148

15. Poorolajal J, Jenabi E. The association between body mass index and preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med. 2016 Nov;29(22):3670–6. doi: 10.3109/14767058.2016.1140738 26762770

16. Santos S, Voerman E, Amiano P, Barros H, Beilin LJ, Bergström A et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts. BJOG. 2019 Jul;126(8):984–995. doi: 10.1111/1471-0528.15661 30786138

17. Weissgerber TL, Mudd LM. Preeclampsia and diabetes. Curr Diab Rep. 2015 Mar;15(3):9. doi: 10.1007/s11892-015-0579-4 25644816

18. Ostlund I, Haglund B, Hanson U. Gestational diabetes and preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2004 Mar 15;113(1):12–6. doi: 10.1016/j.ejogrb.2003.07.001 15036703

19. Bryson CL, Ioannou GN, Rulyak SJ, Critchlow C. Association between gestational diabetes and pregnancy-induced hypertension. Am J Epidemiol. 2003 Dec 15;158(12):1148–53. doi: 10.1093/aje/kwg273 14652299

20. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early-versus late-onset disease. Am J Obstet Gynecol. 2013 Dec;209(6):544.e1-544.e12. doi: 10.1016/j.ajog.2013.08.019 Epub 2013 Aug 22. 23973398

21. Odegård RA(1), Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Risk factors and clinical manifestations of pre-eclampsia. BJOG. 2000 Nov;107(11):1410–6. 11117771

22. Conde-Agudelo A, Belizán JM. Risk factors for pre-eclampsia in a large cohort of Latin American and Caribbean women. BJOG. 2000 Jan;107(1):75–83. 10645865

23. Li L, Rina S, Chen W, Boya L, Jing H, Huixia Y. Incidence and clinical factors of preeclampsia: a population-based study in Beijing, China. 2019 in Press J Clin Hypertension.

24. Bartsch E, Medcalf KE, Park AL, Ray JG; High Risk of Pre-eclampsia Identification Group. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016 Apr 19;353:i1753. doi: 10.1136/bmj.i1753 27094586

25. ) Lien Tran P, Robillard PY, Dumont C, Schweizer C, Omarjee A, Iacobelli S, Boukerrou M. Recurrent or first preeclampsia in multiparae: a case-control study of singleton pregnancies in Reunion Island. Europ J ObstGynecol Reprod Biol. 2019;240:80–86. doi: 10.1016/j.ejogrb.2019.06.013 31234061

26. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005 Mar 12;330(7491):565. doi: 10.1136/bmj.38380.674340.E0 15743856

27. Poon LC, Kametas NA, Chelemen T, Leal A, Nicolaides KH. Maternal risk factors for hypertensive disorders in pregnancy: a multivariate approach. J Hum Hypertens. 2010 Feb;24(2):104–10. doi: 10.1038/jhh.2009.45 19516271

28. Paré E, Parry S, McElrath TF, Pucci D, Newton A, Lim KH. Clinical risk factors for preeclampsia in the 21st century. Obstet Gynecol. 2014 Oct;124(4):763–70. doi: 10.1097/AOG.0000000000000451 25198274

29. Ros HS, Cnattingius S, Lipworth L. Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am J Epidemiol. 1998 Jun 1;147(11):1062–70. doi: 10.1093/oxfordjournals.aje.a009400 9620050

30. Cockell AP, Learmont JG, Smárason AK, Redman CW, Sargent IL, Poston L. Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function. Br J Obstet Gynaecol. 1997 Feb;104(2):235–40. doi: 10.1111/j.1471-0528.1997.tb11052.x 9070146

31. Redman CW, Staff AC.Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. Am J Obstet Gynecol. 2015 Oct;213(4 Suppl):S9.e1, S9-11. doi: 10.1016/j.ajog.2015.08.003 26428507

32. Lely T, Salahuddin S, Holwerda K, Karumanchi A, Rana S. PP016. Circulating lymphangiogenic factors in preeclampsia. Pregnancy Hypertens. 2012 Jul;2(3):249–50. doi: 10.1016/j.preghy.2012.04.127 26105339

33. Hoeller A, Ehrlich L, Golic M, Herse F, Perschel FH, Siwetz M, Henrich W, Dechend R, Huppertz B, Verlohren S. Placental expression of sFlt-1 and PlGF in early preeclampsia vs. early IUGR vs. age-matched healthy pregnancies. Hypertens Pregnancy. 2017 May;36(2):151–160. doi: 10.1080/10641955.2016.1273363 28609172

34. Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol. 2018 Feb;218(2S):S745–S761. doi: 10.1016/j.ajog.2017.11.577 29422210

35. Gans RO, Dekker GA. Preeclampsia—a state of sympathetic overactivity. N Engl J Med. 1997 May 1;336(18):1326; author reply 1327.

36. Bodnar LM, Ness RB, Markovic N, Roberts JM. The risk of preeclampsia rises with increasing prepregnancy body mass index. Ann Epidemiol. 2005 Aug;15(7):475–82. doi: 10.1016/j.annepidem.2004.12.008 16029839

37. Fang R, Dawson A, Lohsoonthorn V, Williams MA. Risk Factors of Early and Late Onset Preeclampsia among Thai Women.Asian Biomed (Res Rev News). 2009 Oct 1;3(5):477–486.

38. Baker AM, Haeri S. Estimating risk factors for development of preeclampsia in teen mothers. Arch Gynecol Obstet. 2012;286(5):1093–6. doi: 10.1007/s00404-012-2418-z 22707291

39. Ornaghi S(1), Tyurmorezova A, Algeri P, Giardini V, Ceruti P, Vertemati E, Vergani P. Influencing factors for late-onset preeclampsia. J Matern Fetal Neonatal Med. 2013 Sep;26(13):1299–302. doi: 10.3109/14767058.2013.783807 23480598

40. Mbah A. K., Kornosky J. L., Kristensen S., et al. Super-obesity and risk for early and late pre-eclampsia. BJOG. 2010;117(8):997–1004. doi: 10.1111/j.1471-0528.2010.02593.x 20482533

41. Grieger JA, Bianco-Miotto T, Grzeskowiak LE, Leemaqz SY, Poston L, McCowan LM et al,Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: A prospective cohort of nulliparous women. PLoS Med. 2018;15(12):e1002710. doi: 10.1371/journal.pmed.1002710 30513077

42. Steegers Eric A. P., Peter von Dadelszen, Duvekot Johannes J., Robert Pijnenborg. Pre-eclampsia. Lancet. 2010;376(9741):631–44. doi: 10.1016/S0140-6736(10)60279-6 20598363

43. Anouk Bokslag, Mirjam van Weissenbruch, Willem Mol Ben, de Groot Christianne J. M. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum Dev. 2016;102:47–50. doi: 10.1016/j.earlhumdev.2016.09.007 27659865

44. Myles Wolf, Hubel Carl A., Chun Lam, et al. Preeclampsia and future cardiovascular disease: potential role of altered angiogenesis and insulin resistance. J Clin Endocrinol Metab. 2004;89(12):6239–43. doi: 10.1210/jc.2004-0548 15579783

45. Seely Ellen W., Solomon Caren G. Insulin resistance and its potential role in pregnancy-induced hypertension. J Clin Endocrinol Metab. 2003;88(6):2393–8. doi: 10.1210/jc.2003-030241 12788833

46. Carpenter Marshall W. Gestational diabetes, pregnancy hypertension, and late vascular disease. Diabetes Care. 2007;30 Suppl 2:S246–250. doi: 10.2337/dc07-s224 17596480

47. Scioscia M. D-chiro inositol phosphoglycans in preeclampsia: Where are we, where are we going? Journal of Reproductive Immunology. 2017;124:1–7. doi: 10.1016/j.jri.2017.09.010 28982033

48. Kerr William G., Francesco Colucci. Inositol phospholipid signaling and the biology of natural killer cells. J Innate Immun. 2011;3(3):249–57. doi: 10.1159/000323920 21422750

49. Scioscia M, Ananth Karumanchi S., Debra Goldman-Wohl, Robillard PY. Endothelial dysfunction and metabolic syndrome in preeclampsia: an alternative viewpoint. Journal of Reproductive Immunology. 2015;108:42–7. doi: 10.1016/j.jri.2015.01.009 25766966

50. Ravi Thadhani, Ecker Jeffrey L., Mutter Walter P., et al. Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia. Hypertension. 2004;43(5):988–92. doi: 10.1161/01.HYP.0000124460.67539.1d 15023932

51. Arkwright P. D., Rademacher T. W., Dwek R. A., Redman C. W. Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. J Clin Invest. 1993;91(6):2744–53. doi: 10.1172/JCI116515 8514882

52. Scioscia M., Siwetz M., Fascilla F., Huppertz B. Placental expression of D-chiro-inositol phosphoglycans in preeclampsia. Placenta. 2012;33(10):882–4. doi: 10.1016/j.placenta.2012.07.007 22835680

53. Phipps Elizabeth A., Ravi Thadhani, Thomas Benzing, Ananth Karumanchi S. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nature Reviews Nephrology. 2019. doi: 10.1038/s41581-019-0119-6 30792480

54. Levine Richard J., Maynard Sharon E., Cong Qian, et al. Circulating Angiogenic Factors and the Risk of Preeclampsia. New England Journal of Medicine. 2004;350(7):672–83. doi: 10.1056/NEJMoa031884 14764923

55. Robillard PY, Dekker G, Iacobelli S, Chaouat G. An essay of reflection: Why does preeclampsia exist in humans, and why are there such huge geographical differences in epidemiology? J Reprod Immunol. 2016 Apr;114:44–7. doi: 10.1016/j.jri.2015.07.001 26253618

56. Robillard PY, Dekker G, Chaouat G, Elliot MG, Scioscia M. High incidence of early onset preeclampsia is probably the rule and not the exception worldwide. 20th anniversary of the reunion workshop. A summary. J Reprod Immunol. 2019 May 31;133:30–36. doi: 10.1016/j.jri.2019.05.003 31176084

57. Mac Gillivray I. Factors predisposing to the development of pre-eclampsia. In: MacGillivray I, editor. Preeclampsia. London: Saunders WB; 1983. p. 23–55.

58. Lindheimer MD, Roberts JM, Cunnigham FG, Chesley L. Introduction, history, controversies and definitions. In: Lindheimer JM, Roberts FG, Cunningham FG, editors. Chesley's hypertensive disorders in pregnancy., Stamford, Connecticut: Appleton and Lange; 1999. p. 3–41

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