Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Maternal cardiovascular disorders before and during pregnancy and offspring cardiovascular risk across the life course

Abstract

Obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia are highly prevalent among women of reproductive age and contribute to complications in >30% of pregnancies in Western countries. An accumulating body of evidence suggests that these cardiovascular disorders in women, occurring before and during their pregnancy, can affect the development of the structure, physiology and function of cardiovascular organ systems at different stages during embryonic and fetal development. These developmental adaptations might, in addition to genetics and sociodemographic and lifestyle factors, increase the susceptibility of the offspring to cardiovascular disease throughout the life course. In this Review, we discuss current knowledge of the influence of maternal cardiovascular disorders, occurring before and during pregnancy, on offspring cardiovascular development, dysfunction and disease from embryonic life until adulthood. We discuss findings from contemporary, large-scale, observational studies that provide insights into specific critical periods, evidence for causality and potential underlying mechanisms. Furthermore, we focus on priorities for future research, including defining optimal cardiovascular and reproductive health in women and men before their pregnancy and identifying specific embryonic, placental and fetal molecular developmental adaptations from early pregnancy onwards. Together, these approaches will help stop the intergenerational cycle of cardiovascular disease.

Key points

  • Obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia are highly prevalent among women of reproductive age and complicate >30% of pregnancies in Western countries.

  • Maternal cardiovascular disorders before and during pregnancy seem to contribute to embryonic and fetal cardiovascular developmental adaptations that predispose to an increased risk of cardiovascular dysfunction and disease in the offspring throughout their life course.

  • The development of cardiovascular diseases seems to be the result of cumulative effects of cardiovascular adaptations occurring across the life course, and preconception, early pregnancy and infancy seem to be specific critical periods in early life related to future risk of cardiovascular disease.

  • Future research needs to focus on identifying specific cardiovascular health parameters in both women and men from preconception onwards that are associated with cardiovascular health and disease in offspring, and the mechanisms underlying these associations; use of innovative imaging techniques to study cardiovascular development from embryonic life onwards, novel ‘omics’ approaches to identify functional adaptations, and strong collaborations between cohorts studies worldwide offer opportunities to address these research issues.

  • The use of innovative imaging techniques to study cardiovascular development from embryonic life onwards as well as novel omics approaches to identify functional adaptations and to interpret findings from cohort studies offer opportunities to address these research issues.

  • Novel preventative strategies focused on improving cardiovascular health in men and women from preconception onwards might lead to better cardiovascular health in future generations and stop the intergenerational cycle of cardiovascular risk transmission.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Cardiovascular development and disease from preconception onwards.
Fig. 2: Potential mechanisms involved in the association between maternal cardiovascular health and cardiovascular dysfunction and disease in the offspring.
Fig. 3: 3D ultrasonography and virtual reality approaches to assess embryonic development.

Similar content being viewed by others

References

  1. Lloyd-Jones, D. M. et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic impact goal through 2020 and beyond. Circulation 121, 586–613 (2010).

    Article  PubMed  Google Scholar 

  2. Gluckman, P. D. et al. Effect of in utero and early-life conditions on adult health and disease. N. Engl. J. Med. 359, 61–73 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lloyd-Jones, D. M. et al. Status of cardiovascular health in US adults and children using the American Heart Association’s New “Life’s Essential 8” Metrics: prevalence estimates from the National Health and Nutrition Examination Survey (NHANES), 2013 through 2018. Circulation 146, 822–835 (2022).

    Article  CAS  PubMed  Google Scholar 

  4. Curhan, G. C. et al. Birth weight and adult hypertension and obesity in women. Circulation 94, 1310–1315 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Curhan, G. C. et al. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 94, 3246–3250 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Barker, D. J. et al. Trajectories of growth among children who have coronary events as adults. N. Engl. J. Med. 353, 1802–1809 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Robbins, C. L. et al. Screening low-income women of reproductive age for cardiovascular disease risk factors. J. Womens Health 22, 314–321 (2013).

    Article  Google Scholar 

  8. Deputy, N. P. et al. Gestational weight gain — United States, 2012 and 2013. Morb. Mortal. Wkly. Rep. 64, 1215–1220 (2015).

    Article  Google Scholar 

  9. Flegal, K. M. et al. Trends in obesity among adults in the United States, 2005 to 2014. JAMA 315, 2284–2291 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Ford, N. D. et al. Hypertensive disorders in pregnancy and mortality at delivery hospitalization — United States, 2017–2019. MMWR Morb. Mortal. Wkly. Rep. 71, 585–591 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Brown, H. L. 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 137, e843–e852 (2018).

    Article  PubMed  Google Scholar 

  12. Ramlakhan, K. P., Johnson, M. R. & Roos-Hesselink, J. W. Pregnancy and cardiovascular disease. Nat. Rev. Cardiol. 17, 718–731 (2020).

    Article  PubMed  Google Scholar 

  13. Gaillard, R. Maternal obesity during pregnancy and cardiovascular development and disease in the offspring. Eur. J. Epidemiol. 30, 1141–1152 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Burton, G. J. et al. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 30, 473–482 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Juhola, J. et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J. Pediatr. 159, 584–590 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Chen, X. & Wang, Y. Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regression analysis. Circulation 117, 3171–3180 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Reilly, J. J. & Kelly, J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int. J. Obes. 35, 891–898 (2011).

    Article  CAS  Google Scholar 

  18. Franks, P. W. et al. Childhood obesity, other cardiovascular risk factors, and premature death. N. Engl. J. Med. 362, 485–493 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Stothard, K. J. et al. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA 301, 636–650 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Voerman, E. et al. Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: an individual participant data meta-analysis. PLoS Med. 16, e1002744 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Eitmann, S. et al. Maternal overnutrition elevates offspring’s blood pressure — a systematic review and meta-analysis. Paediatr. Perinat. Epidemiol. 36, 276–287 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kankowski, L. et al. The impact of maternal obesity on offspring cardiovascular health: a systematic literature review. Front. Endocrinol. 13, 868441 (2022).

    Article  Google Scholar 

  23. Reynolds, R. M. et al. Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years. BMJ 347, f4539 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lahti-Pulkkinen, M. et al. Consequences of being overweight or obese during pregnancy on diabetes in the offspring: a record linkage study in Aberdeen, Scotland. Diabetologia 62, 1412–1419 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain During Pregnancy: Reexamining the Guidelines (eds Rasmussen, K.M. & Yaktine, A.L.) (National Academies Press US, 2009).

  26. LifeCycle Project-Maternal Obesity and Childhood Outcomes Study Group; et al. Association of gestational weight gain with adverse maternal and infant outcomes. JAMA 321, 1702–1715 (2019).

    Article  PubMed Central  Google Scholar 

  27. Eitmann, S. et al. Maternal overnutrition impairs offspring’s insulin sensitivity: a systematic review and meta-analysis. Matern. Child. Nutr. 16, e13031 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hochner, H. et al. Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-up Study. Circulation 125, 1381–1389 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mamun, A. A. et al. Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study. Circulation 119, 1720–1727 (2009).

    Article  PubMed  Google Scholar 

  30. Reynolds, R. M. et al. Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood. J. Clin. Endocrinol. Metab. 95, 5365–5369 (2010).

    Article  CAS  PubMed  Google Scholar 

  31. Tequeanes, A. L. et al. Maternal anthropometry is associated with the body mass index and waist:height ratio of offspring at 23 years of age. J. Nutr. 139, 750–754 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Khedagi, A. M. & Bello, N. A. Hypertensive disorders of pregnancy. Cardiol. Clin. 39, 77–90 (2021).

    Article  PubMed  Google Scholar 

  33. Auger, N., Fraser, W. D., Healy-Profitos, J. & Arbour, L. Association between preeclampsia and congenital heart defects. JAMA 314, 1588–1598 (2015).

    Article  CAS  PubMed  Google Scholar 

  34. Liu, S. et al. Association between maternal chronic conditions and congenital heart defects: a population-based cohort study. Circulation 128, 583–589 (2013).

    Article  PubMed  Google Scholar 

  35. Patro Golab, B. et al. Influence of maternal obesity on the association between common pregnancy complications and risk of childhood obesity: an individual participant data meta-analysis. Lancet Child. Adolesc. Health 2, 812–821 (2018).

    Article  PubMed  Google Scholar 

  36. Yu, H. et al. Association between hypertensive disorders during pregnancy and elevated blood pressure in offspring: a systematic review and meta-analysis. J. Clin. Hypertens. 24, 1397–1404 (2022).

    Article  Google Scholar 

  37. Rice, M. M. et al. Pregnancy-associated hypertension and offspring cardiometabolic health. Obstet. Gynecol. 131, 313–321 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Geelhoed, J. J. et al. Preeclampsia and gestational hypertension are associated with childhood blood pressure independently of family adiposity measures: the Avon longitudinal study of parents and children. Circulation 122, 1192–1199 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Andraweera, P. H. & Lassi, Z. S. Cardiovascular risk factors in offspring of preeclamptic pregnancies-systematic review and meta-analysis. J. Pediatr. 208, 104–113.e6 (2019).

    Article  PubMed  Google Scholar 

  40. Wiertsema, C. J. et al. Childhood blood pressure, carotid intima media thickness, and distensibility after in utero exposure to gestational hypertensive disorders. J. Am. Heart Assoc. 11, e023163 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kuciene, R. & Dulskiene, V. Associations of maternal gestational hypertension with high blood pressure and overweight/obesity in their adolescent offspring: a retrospective cohort study. Sci. Rep. 12, 3800 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Huang, C. et al. Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: a national population-based cohort study. PLoS Med. 18, e1003805 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kajantie, E. et al. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke 40, 1176–1180 (2009).

    Article  PubMed  Google Scholar 

  44. Zhang, T. N. et al. Risks of specific congenital anomalies in offspring of women with diabetes: a systematic review and meta-analysis of population-based studies including over 80 million births. PLoS Med. 19, e1003900 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Oyen, N. et al. Prepregnancy diabetes and offspring risk of congenital heart disease: a nationwide cohort study. Circulation 133, 2243–2253 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kawasaki, M. et al. Obesity and abnormal glucose tolerance in offspring of diabetic mothers: a systematic review and meta-analysis. PLoS One 13, e0190676 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Pathirana, M. M. et al. Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis. J. Dev. Orig. Health Dis. 11, 599–616 (2020).

    Article  PubMed  Google Scholar 

  48. Yu, Y. et al. Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up. BMJ 367, l6398 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Napoli, C. et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J. Clin. Invest. 100, 2680–2690 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Napoli, C. et al. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: fate of early lesions in children (FELIC) study. Lancet 354, 1234–1241 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Cacciatore, F. et al. Maternal hypercholesterolaemia during pregnancy affects severity of myocardial infarction in young adults. Eur. J. Prev. Cardiol. 29, 758–765 (2022).

    Article  PubMed  Google Scholar 

  52. Gaillard, R. et al. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R study. Hypertension 63, 683–691 (2014).

    Article  CAS  PubMed  Google Scholar 

  53. Santos, S. et al. Maternal body mass index, gestational weight gain, and childhood abdominal, pericardial, and liver fat assessed by magnetic resonance imaging. Int. J. Obes. 43, 581–593 (2019).

    Article  Google Scholar 

  54. Ay, L. et al. Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R study. BJOG 116, 953–963 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Geurtsen, M. L. et al. High maternal early-pregnancy blood glucose levels are associated with altered fetal growth and increased risk of adverse birth outcomes. Diabetologia 62, 1880–1890 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Geurtsen, M. L. et al. Maternal early-pregnancy glucose concentrations and liver fat among school-age children. Hepatology 74, 1902–1913 (2021).

    Article  CAS  PubMed  Google Scholar 

  57. Wahab, R. J. et al. Associations of maternal glycemia in the first half of pregnancy with alterations in cardiac structure and function in childhood. Diabetes Care 43, 2272–2280 (2020).

    Article  PubMed  Google Scholar 

  58. Wahab, R. J. et al. Maternal glucose concentrations in early pregnancy and cardiometabolic risk factors in childhood. Obesity 28, 985–993 (2020).

    Article  CAS  PubMed  Google Scholar 

  59. Miliku, K. et al. Associations of maternal and paternal blood pressure patterns and hypertensive disorders during pregnancy with childhood blood pressure. J. Am. Heart Assoc. 5, e003884 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Yesil, G. D. et al. Influence of maternal gestational hypertensive disorders on microvasculature in school-age children: the Generation R study. Am. J. Epidemiol. 184, 605–615 (2016).

    Article  PubMed  Google Scholar 

  61. Josefson, J. L. et al. The joint associations of maternal BMI and glycemia with childhood adiposity. J. Clin. Endocrinol. Metab. 105, 2177–2188 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Scholtens, D. M. et al. Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal glycemia and childhood glucose metabolism. Diabetes Care 42, 381–392 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Taylor, K. et al. Effect of maternal prepregnancy/early-pregnancy body mass index and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study. J. Am. Heart Assoc. 10, e020051 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Rutkowski, R. E. et al. Proportion of critical congenital heart defects attributable to unhealthy prepregnancy body mass index among women with live births in Florida, 2005-2016. Birth Defects Res. 113, 1285–1298 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Helle, E. I. T. et al. First trimester plasma glucose values in women without diabetes are associated with risk for congenital heart disease in offspring. J. Pediatr. 195, 275–278 (2018).

    Article  CAS  PubMed  Google Scholar 

  66. Priest, J. R. et al. Maternal midpregnancy glucose levels and risk of congenital heart disease in offspring. JAMA Pediatr. 169, 1112–1116 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Andraweera, P. H. et al. Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease. J. Dev. Orig. Health Dis. 11, 235–242 (2020).

    Article  CAS  PubMed  Google Scholar 

  68. Burton, G. J. et al. Placental origins of chronic disease. Physiol. Rev. 96, 1509–1565 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Smith, G. D. & Ebrahim, S. Mendelian randomization: prospects, potentials, and limitations. Int. J. Epidemiol. 33, 30–42 (2004).

    Article  PubMed  Google Scholar 

  70. Tyrrell, J. et al. Genetic evidence for causal relationships between maternal obesity-related traits and birth weight. JAMA 315, 1129–1140 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Warrington, N. M. et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat. Genet. 51, 804–814 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang, G. et al. Investigating a potential causal relationship between maternal blood pressure during pregnancy and future offspring cardiometabolic health. Hypertension 79, 170–177 (2022).

    Article  CAS  PubMed  Google Scholar 

  73. Bond, T. A. et al. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores. BMC Med. 20, 34 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Frisell, T. et al. Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23, 713–720 (2012).

    Article  PubMed  Google Scholar 

  75. Kral, J. G. et al. Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics 118, e1644-9 (2006).

    Article  PubMed  Google Scholar 

  76. Lawlor, D. A. et al. Does maternal weight gain in pregnancy have long-term effects on offspring adiposity? A sibling study in a prospective cohort of 146,894 men from 136,050 families. Am. J. Clin. Nutr. 94, 142–148 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ludwig, D. S. et al. Pregnancy weight gain and childhood body weight: a within-family comparison. PLoS Med. 10, e1001521 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Smith, J. et al. Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity. J. Clin. Endocrinol. Metab. 94, 4275–4283 (2009).

    Article  CAS  PubMed  Google Scholar 

  79. Razaz, N. et al. Maternal obesity and risk of cardiovascular diseases in offspring: a population-based cohort and sibling-controlled study. Lancet Diabetes Endocrinol. 8, 572–581 (2020).

    Article  PubMed  Google Scholar 

  80. Patro, B. et al. Maternal and paternal body mass index and offspring obesity: a systematic review. Ann. Nutr. Metab. 63, 32–41 (2013).

    Article  CAS  PubMed  Google Scholar 

  81. Gaillard, R. et al. Lifestyle intervention strategies in early life to improve pregnancy outcomes and long-term health of offspring: a narrative review. J. Dev. Orig. Health Dis. 10, 314–321 (2019).

    Article  PubMed  Google Scholar 

  82. Landon, M. B. et al. Mild gestational diabetes mellitus and long-term child health. Diabetes Care 38, 445–452 (2015).

    Article  PubMed  Google Scholar 

  83. Louise, J. et al. The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials. BMC Med. 19, 128 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Heijmans, B. T. et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105, 17046–17049 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Roseboom, T. J. et al. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas 70, 141–145 (2011).

    Article  PubMed  Google Scholar 

  86. Gaillard, R. et al. Maternal weight gain in different periods of pregnancy and childhood cardio-metabolic outcomes. The Generation R study. Int. J. Obes. 39, 677–685 (2015).

    Article  CAS  Google Scholar 

  87. Fraser, A. et al. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 121, 2557–2564 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Karachaliou, M. et al. Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood. Am. J. Obstet. Gynecol. 212, 502.e1-14 (2015).

    Article  PubMed  Google Scholar 

  89. Vidakovic, A. J. et al. Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R study. Am. J. Clin. Nutr. 103, 1017–1025 (2016).

    Article  CAS  PubMed  Google Scholar 

  90. Stephenson, J. et al. Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health. Lancet 391, 1830–1841 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Fleming, T. P. et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet 391, 1842–1852 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Black, R. E. et al. Health and development from preconception to 20 years of age and human capital. Lancet 399, 1730–1740 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Vogelezang, S. et al. Associations of fetal and infant weight change with general, visceral, and organ adiposity at school age. JAMA Netw. Open. 2, e192843 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Leunissen, R. W. et al. Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 301, 2234–2242 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Jaddoe, V. W. et al. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study. BMJ 348, g14 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Bedzhov, I. et al. Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130538 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Li, L., Lu, X. & Dean, J. The maternal to zygotic transition in mammals. Mol. Asp. Med. 34, 919–938 (2013).

    Article  Google Scholar 

  98. Nicholas, L. M. et al. The early origins of obesity and insulin resistance: timing, programming and mechanisms. Int. J. Obes. 40, 229–238 (2016).

    Article  CAS  Google Scholar 

  99. Fleming, T. P. et al. Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health. Reprod. Fertil. Dev. 27, 684–692 (2015).

    Article  CAS  PubMed  Google Scholar 

  100. Wyman, A. et al. One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinology 149, 466–469 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Ruebel, M. L. et al. Obesity modulates inflammation and lipid metabolism oocyte gene expression: a single-cell transcriptome perspective. J. Clin. Endocrinol. Metab. 102, 2029–2038 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Leary, C. et al. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum. Reprod. 30, 122–132 (2015).

    Article  PubMed  Google Scholar 

  103. Mook-Kanamori, D. O. et al. Risk factors and outcomes associated with first-trimester fetal growth restriction. JAMA 303, 527–534 (2010).

    Article  CAS  PubMed  Google Scholar 

  104. Martyn, C. N. et al. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet 350, 953–955 (1997).

    Article  CAS  PubMed  Google Scholar 

  105. Gaillard, R. et al. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the Generation R study. Circulation 128, 2202–2210 (2013).

    Article  PubMed  Google Scholar 

  106. Verburg, B. O. et al. Fetal hemodynamic adaptive changes related to intrauterine growth: the Generation R study. Circulation 117, 649–659 (2008).

    Article  PubMed  Google Scholar 

  107. Llurba, E. et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur. Heart J. 35, 701–707 (2014).

    Article  CAS  PubMed  Google Scholar 

  108. Llurba, E. et al. Maternal serum placental growth factor at 11-13 weeks’ gestation and fetal cardiac defects. Ultrasound Obstet. Gynecol. 42, 169–174 (2013).

    Article  CAS  PubMed  Google Scholar 

  109. Bongers-Karmaoui, M. N. et al. Associations of maternal angiogenic factors during pregnancy with childhood carotid intima-media thickness and blood pressure. Atherosclerosis 338, 46–54 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Bongers-Karmaoui, M. N. et al. Associations of maternal angiogenic factors during pregnancy with alterations in cardiac development in childhood at 10 years of age. Am. Heart J. 247, 100–111 (2022).

    Article  CAS  PubMed  Google Scholar 

  111. Gishti, O. et al. Influence of maternal angiogenic factors during pregnancy on microvascular structure in school-age children. Hypertension 65, 722–728 (2015).

    Article  CAS  PubMed  Google Scholar 

  112. Gishti, O. et al. Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children. J. Clin. Endocrinol. Metab. 99, 2557–2566 (2014).

    Article  CAS  PubMed  Google Scholar 

  113. Hanson, M. A. et al. DOHaD — the challenge of translating the science to policy. J. Dev. Orig. Health Dis. 10, 263–267 (2019).

    Article  CAS  PubMed  Google Scholar 

  114. Sermondade, N. et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum. Reprod. Update 19, 221–231 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Guo, D. et al. The impact of BMI on sperm parameters and the metabolite changes of seminal plasma concomitantly. Oncotarget 8, 48619–48634 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Raad, G. et al. Paternal obesity: how bad is it for sperm quality and progeny health? Basic Clin. Androl. 27, 20 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Bakos, H. W. et al. Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil. Steril. 95, 1700–1704 (2017).

    Article  Google Scholar 

  118. Bromfield, J. J. et al. Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc. Natl Acad. Sci. USA 111, 2200–2205 (2021).

    Article  Google Scholar 

  119. Jaddoe, V. W. V. et al. The LifeCycle Project–EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents. Eur. J. Epidemiol. 35, 709–724 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Wiertsema, C. J. et al. First trimester fetal proportion volumetric measurements using a virtual reality approach. Prenat. Diagn. 41, 868–876 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Wiertsema, C. J. et al. Innovative approach for first-trimester fetal organ volume measurements using a virtual reality system: the Generation R Next study. J. Obstet. Gynaecol. Res. 48, 599–609 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Reus, A. D. et al. Early pregnancy placental bed and fetal vascular volume measurements using 3-D virtual reality. Ultrasound Med. Biol. 40, 1796–1803 (2014).

    Article  PubMed  Google Scholar 

  123. Felix, J. F. et al. Cohort profile: pregnancy and childhood epigenetics (PACE) consortium. Int. J. Epidemiol. 47, 22–23u (2018).

    Article  PubMed  Google Scholar 

  124. Drury, S. et al. Cell-free fetal DNA testing for prenatal diagnosis. Adv. Clin. Chem. 76, 1–35 (2016).

    Article  CAS  PubMed  Google Scholar 

  125. Steinberger et al. Cardiovascular health promotion in children: challenges and opportunities for 2020 and beyond: a scientific statement from the American Heart Association. Circulation 134, e236–e255 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  126. WHO. Obesity https://www.who.int/health-topics/obesity/ (2023).

  127. Tranquilli, A. L. et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 4, 97–104 (2014).

    Article  CAS  PubMed  Google Scholar 

  128. WHO. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. https://apps.who.int/iris/handle/10665/85975 (2013).

  129. Zhou, T. et al. Prevalence and trends in gestational diabetes mellitus among women in the United States, 2006–2017: a population-based study. Front. Endocrinol. 13, 868094 (2022).

    Article  Google Scholar 

  130. WHO. The Global Health Observatory https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3236 (2023).

Download references

Acknowledgements

R.G. received funding from the Dutch Diabetes Foundation (grant number 2017.81.002), the Netherlands Organization for Health Research and Development (NWO, ZonMW 543003109; NWO, ZonMw 09150172110034); EU Horizon 2020 research and innovation programme under the ERA-NET Cofund action (grant number 727565), EndObesity (ZonMW 529051026). V.W.V.J received a grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw 05430052110007) and a European Research Council Consolidator Grant (ERC-2014-CoG-648916).

Author information

Authors and Affiliations

Authors

Contributions

R.G. researched data and discussed the content of the article. R.G. and V.W.V.J wrote and reviewed the manuscript before submission.

Corresponding author

Correspondence to Romy Gaillard.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Cardiology thanks Tamar Wainstock, Emily Harville and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gaillard, R., Jaddoe, V.W.V. Maternal cardiovascular disorders before and during pregnancy and offspring cardiovascular risk across the life course. Nat Rev Cardiol 20, 617–630 (2023). https://doi.org/10.1038/s41569-023-00869-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-023-00869-z

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing