Download PDF
Am J Perinatol
DOI: 10.1055/a-2576-4082
Original Article

Joint Effect of Body Mass Index and Obstructive Sleep Apnea on Preeclampsia Risk

Nana A. Mensah 
1   Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
2   Department of Public Health, Brigham Young University, Provo, Utah
,
Michael J. Fassett
3   Department of Obstetrics & Gynecology, Kaiser Permanente West Los Angeles Medical Center, California
4   Department of Clinical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California
,
Morgan R. Peltier
5   Department of Psychiatry and Behavioral Health, Jersey Shore University Medical Center, Neptune, New Jersey
6   Department of Psychiatry and Behavioral Health, Hackensack Meridian School of Medicine, Nutley, New Jersey
,
Jiaxiao Shi
1   Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
,
Vicki Y. Chiu
1   Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
,
Nehaa Khadkha
1   Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
,
Darios Getahun 
1   Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
7   Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California
› Author Affiliations Funding This work was supported by the Kaiser Community Benefit Funds. D.G. has received unrelated research support from the NIH/NICHD, Garfield Memorial Fund, Hologic Inc., CDC, and Johnson & Johnson. M.J.F. has received unrelated research support from the Garfield Memorial Fund, Hologic Inc., and Johnson & Johnson.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective

Preeclampsia remains one of the leading causes of perinatal mortality worldwide. Little is known about the modifiable risk factors that can be identified and addressed early in pregnancy to reduce the risk of preeclampsia and its associated adverse outcomes. We sought to determine if there is a synergistic effect of prepregnancy body-mass index and obstructive sleep apnea (OSA) on the risk of preeclampsia.

Study Design

We conducted a retrospective cohort study of singleton pregnancies delivered in Kaiser Permanente Southern California hospitals between January 1, 2010, and December 31, 2020 (n = 342,349). Preeclampsia and sleep apnea were ascertained using clinical diagnosis codes. Body mass index (BMI) in kg/m2 measured during prenatal care visits was categorized as normal (18.5–24.9), overweight (25–29.9), and obese (≥30). Multivariable logistic regression was used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI).

Results

Compared with normal weight in pregnancy, overweight (aRR : 1.6; 95% CI: 1.5, 1.7) and obese BMI (aRR: 2.5; 95% CI: 2.4, 2.6) were associated with an increased risk of preeclampsia. Independent of prepregnancy body-mass index, a pregnancy with OSA was associated with an increased risk of preeclampsia (aRR: 2.2; 95% CI: 1.8, 2.6). Compared with normal weight without the diagnosis of OSA in a pregnancy, overweight (aRR: 4.6; 95% CI: 2.9, 7.4) and obese BMI (aRR: 3.8; 95% CI: 3.2, 4.6) with the diagnosis of OSA were associated with an increased risk of preeclampsia.

Conclusion

OSA and elevated body-mass index have an independent and additive relationship with preeclampsia. Overweight women at risk of preeclampsia should be advised of a higher likelihood of developing preeclampsia when both conditions occur together and may benefit from close monitoring and early interventions for these modifiable risk factors.

Key Points

  • There is a dose-dependent association between BMI and the risk of preeclampsia.

  • Coexistent obesity and OSA resulted in a stronger risk for preeclampsia.

  • The combined effect of obesity and OSA on preeclampsia risk is additive rather than synergistic.

Keywords

obesity - body mass index - obstructive sleep apnea - preeclampsia - joint effect

Supplementary Material



Publication History

Received: 26 November 2024

Accepted: 06 April 2025

Accepted Manuscript online:
07 April 2025

Article published online:
06 May 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on hypertension in pregnancy. Obstet Gynecol 2013; 122 (05) 1122-1131
    Search in Google Scholar
  • 2 Jung E, Romero R, Yeo L. et al. The etiology of preeclampsia. Am J Obstet Gynecol 2022; 226 (2S): S844-S866
    Search in Google Scholar
  • 3 Rana S, Lemoine E, Granger JP, Karumanchi SA. . Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019; 124 (07) 1094-1112
    Search in Google Scholar
  • 4 Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347: f6564
    Search in Google Scholar
  • 5 Centers for Disease Control and Prevention. Pregnancy Mortality Surverillane System. Causes of Pregnancy Related Deaths. Novemeber 14, 2024 . Accessed March 17, 2025 at: https://www.cdc.gov/maternal-mortality/php/pregnancy-mortality-surveillance/?CDC_AAref_Val=https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm
    Search in Google Scholar
  • 6 Alonso-Ventura V, Li Y, Pasupuleti V, Roman YM, Hernandez AV, Pérez-López FR. Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis. Metabolism 2020; 102: 154012
    Search in Google Scholar
  • 7 Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol 2013; 28 (01) 1-19
    Search in Google Scholar
  • 8 Khosla K, Heimberger S, Nieman KM. et al. Long-term cardiovascular disease risk in women after hypertensive disorders of pregnancy: recent advances in hypertension. Hypertension 2021; 78 (04) 927-935
    Search in Google Scholar
  • 9 Getahun D, Fassett MJ, Peltier MR. et al. Association of perinatal risk factors with autism spectrum disorder. Am J Perinatol 2017; 34 (03) 295-304
    Search in Google Scholar
  • 10 Getahun D, Rhoads GG, Demissie K. et al. In utero exposure to ischemic-hypoxic conditions and attention-deficit/hyperactivity disorder. Pediatrics 2013; 131 (01) e53-e61
    Search in Google Scholar
  • 11 Stevens W, Shih T, Incerti D. et al. Short-term costs of preeclampsia to the United States health care system. Am J Obstet Gynecol 2017; 217 (03) 237-248.e16
    Search in Google Scholar
  • 12 Croke L. Gestational hypertension and preeclampsia: a practice bulletin from ACOG. Am Fam Physician 2019; 100 (10) 649-650
    Search in Google Scholar
  • 13 Garovic VD, Dechend R, Easterling T. et al; American Heart Association Council on Hypertension; Council on the Kidney in Cardiovascular Disease, Kidney in Heart Disease Science Committee; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Stroke Council. Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association. Hypertension 2022; 79 (02) e21-e41
    Search in Google Scholar
  • 14 Tong S, Kaitu'u-Lino TJ, Hastie R, Brownfoot F, Cluver C, Hannan N. Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. Am J Obstet Gynecol 2022; 226 (2S): S1157-S1170
    Search in Google Scholar
  • 15 Paré E, Parry S, McElrath TF, Pucci D, Newton A, Lim K-H. Clinical risk factors for preeclampsia in the 21st century. Obstet Gynecol 2014; 124 (04) 763-770
    Search in Google Scholar
  • 16 Motedayen M, Rafiei M, Rezaei Tavirani M, Sayehmiri K, Dousti M. The relationship between body mass index and preeclampsia: a systematic review and meta-analysis. Int J Reprod Biomed 2019; 17 (07) 463-472
    Search in Google Scholar
  • 17 Poorolajal J, Jenabi E. The association between body mass index and preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med 2016; 29 (22) 3670-3676
    Search in Google Scholar
  • 18 Wang Z, Wang P, Liu H. et al. Maternal adiposity as an independent risk factor for pre-eclampsia: a meta-analysis of prospective cohort studies. Obes Rev 2013; 14 (06) 508-521
    Search in Google Scholar
  • 19 Dong Z, Xu X, Wang C, Cartledge S, Maddison R, Shariful Islam SM. Association of overweight and obesity with obstructive sleep apnoea: a systematic review and meta-analysis. Obes Med 2020; 17: 100185
    Search in Google Scholar
  • 20 Jaimchariyatam N, Na-Rungsri K, Tungsanga S, Lertmaharit S, Lohsoonthorn V, Totienchai S. Obstructive sleep apnea as a risk factor for preeclampsia-eclampsia. Sleep Breath 2019; 23 (02) 687-693
    Search in Google Scholar
  • 21 Keshavarzi F, Mehdizadeh S, Khazaie H, Ghadami MR. Objective assessment of obstructive sleep apnea in normal pregnant and preeclamptic women. Hypertens Pregnancy 2018; 37 (03) 154-159
    Search in Google Scholar
  • 22 Lungeanu-Juravle L, Patrascu N, Deleanu OC, Cinteza M. The role of obstructive sleep apnea in developing gestational hypertension and preeclampsia. Maedica (Buchar) 2016; 11 (04) 330-333
    Search in Google Scholar
  • 23 Center for Disease Control and Prevention. . Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion. Defining Adult Overweight & Obesity. Adult Body Mass Index. March 19, 2024 . Accessed March 4, 2025 at: https://www.cdc.gov/bmi/adult-calculator/bmi-categories.html?CDC_AAref_Val=https://www.cdc.gov/obesity/basics/adult-defining.html
  • 24 Getahun D, Rhoads GG, Fassett MJ. et al. Accuracy of reporting maternal and infant perinatal service system coding and clinical utilization coding. J Med Stat Inform 2013; 1: 3
    Search in Google Scholar
  • 25 Keenan BT, Kirchner HL, Veatch OJ. et al. Multisite validation of a simple electronic health record algorithm for identifying diagnosed obstructive sleep apnea. J Clin Sleep Med 2020; 16 (02) 175-183
    Search in Google Scholar
  • 26 Bodnar LM, Catov JM, Klebanoff MA, Ness RB, Roberts JM. Prepregnancy body mass index and the occurrence of severe hypertensive disorders of pregnancy. Epidemiology 2007; 18 (02) 234-239
    Search in Google Scholar
  • 27 Bodnar LM, Ness RB, Markovic N, Roberts JM. The risk of preeclampsia rises with increasing prepregnancy body mass index. Ann Epidemiol 2005; 15 (07) 475-482
    Search in Google Scholar
  • 28 He X-J, Dai RX, Hu C-L. Maternal prepregnancy overweight and obesity and the risk of preeclampsia: a meta-analysis of cohort studies. Obes Res Clin Pract 2020; 14 (01) 27-33
    Search in Google Scholar
  • 29 Robillard P-Y, Dekker G, Scioscia M. et al. Increased BMI has a linear association with late-onset preeclampsia: a population-based study. PLoS One 2019; 14 (10) e0223888
    Search in Google Scholar
  • 30 Ness RB, Sibai BM. Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol 2006; 195 (01) 40-49
    Search in Google Scholar
  • 31 Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999; 180 (2 Pt 1): 499-506
    Search in Google Scholar
  • 32 Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet 2001; 357 (9249) 53-56
    Search in Google Scholar
  • 33 Louis JM, Auckley D, Sokol RJ, Mercer BM. Maternal and neonatal morbidities associated with obstructive sleep apnea complicating pregnancy. Am J Obstet Gynecol 2010; 202 (03) 261.e1-261.e5
    Search in Google Scholar
  • 34 Passarella E, Czuzoj-Shulman N, Abenhaim HA. Maternal and fetal outcomes in pregnancies with obstructive sleep apnea. J Perinat Med 2021; 49 (09) 1064-1070
    Search in Google Scholar
  • 35 Thangaratinam S, Rogozińska E, Jolly K. et al. Interventions to reduce or prevent obesity in pregnant women: a systematic review. NIHR Health Technology Assessment programme: Executive Summaries. Southhapmptom (UK): NIHR Journals Library; 2012
    Search in Google Scholar
  • 36 Dominguez JE, Krystal AD, Habib AS. Obstructive sleep apnea in pregnant women: a review of pregnancy outcomes and an approach to management. Anesth Analg 2018; 127 (05) 1167-1177
    Search in Google Scholar
  • 37 Dominguez JE, Street L, Louis J. Management of obstructive sleep apnea in pregnancy. Obstet Gynecol Clin North Am 2018; 45 (02) 233-247
    Search in Google Scholar
  • 38 Venkata C, Venkateshiah SB. Sleep-disordered breathing during pregnancy. J Am Board Fam Med 2009; 22 (02) 158-168
    Search in Google Scholar
  • 39 Koebnick C, Langer-Gould AM, Gould MK. et al. Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data. Perm J 2012; 16 (03) 37-41
    Search in Google Scholar
  • 40 Lee Y-C, Chang Y-C, Tseng L-W. et al. Continuous positive airway pressure treatment and hypertensive adverse outcomes in pregnancy: a systematic review and meta-analysis. JAMA Netw Open 2024; 7 (08) e2427557-e2427557
    Search in Google Scholar