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Possible role of low birth weight in the pathogenesis of primary (essential) hypertension

William J Elliott, MD, PhD
Section Editor
George L Bakris, MD
Deputy Editor
John P Forman, MD, MSc


The pathogenesis of primary (formerly "essential") hypertension remains incompletely understood. Among the factors that have been intensively studied include salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. In the past few years, a number of other factors have been evaluated, including genetics, endothelial dysfunction (as manifested by changes in endothelin and nitric oxide), and low birth weight, frequently accompanying preeclampsia [1].

Although this hypothesis is not universally accepted, the data supporting a role for low birth weight in the development of primary hypertension in adulthood are presented in this topic review. Other factors potentially associated with primary hypertension are reviewed separately. (See "Salt intake, salt restriction, and primary (essential) hypertension" and "Obesity and weight reduction in hypertension" and "Genetic factors in the pathogenesis of hypertension".)


Babies who are small at birth are more likely to have higher blood pressures during adolescence and to be hypertensive as adults [2]. Very low birth weight infants (defined as <1500 g) have even higher blood pressures as adults, as seen in an individual-level meta-analysis of 1571 adults from nine worldwide cohorts [3]. Small for gestational age babies are also more likely to have metabolic abnormalities that have been associated with the later development of hypertension and coronary disease including insulin resistance [4], diabetes mellitus, and hyperlipidemia [5], frequently in association with abdominal (visceral) obesity (eg, the metabolic syndrome).

The effect of low birth weight on adult blood pressure was first described in 1988 [6]. The relationship was confirmed in both men and women using data from the Nurses' Health Study and the Health Professionals Follow-up Study [7,8]. In the Nurses' Health Study, low birth weight accounted for 24 percent of the risk of adult hypertension; 64 percent was attributed to unhealthy lifestyle factors [9]. Multiple surveys of children also show a relation between birth weight and blood pressure but of a lesser degree than in adults [10,11]. An analysis of data from four populations across the entire life span demonstrated that for every one-kilogram-higher birth weight, systolic blood pressure was 5.2 mmHg lower at ages 64 to 71 years but only 1 to 3 mmHg lower in adolescence [12]. The relationship with adult blood pressure may be even more attenuated [2].

Maternal undernutrition has been linked to fetal growth restriction and adult hypertension (and possibly nephrosclerosis) in animal experiments [12-14]. The offspring of female rats given a low-protein diet during pregnancy were smaller and developed higher blood pressures than controls as they matured, even though they were fed a normal diet after birth.

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Literature review current through: Nov 2017. | This topic last updated: Oct 18, 2017.
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  1. Ferreira I, Peeters LL, Stehouwer CD. Preeclampsia and increased blood pressure in the offspring: meta-analysis and critical review of the evidence. J Hypertens 2009; 27:1955.
  2. Davies AA, Smith GD, May MT, Ben-Shlomo Y. Association between birth weight and blood pressure is robust, amplifies with age, and may be underestimated. Hypertension 2006; 48:431.
  3. Hovi P, Vohr B, Ment LR, et al. Blood Pressure in Young Adults Born at Very Low Birth Weight: Adults Born Preterm International Collaboration. Hypertension 2016; 68:880.
  4. Phillips DI, Barker DJ, Hales CN, et al. Thinness at birth and insulin resistance in adult life. Diabetologia 1994; 37:150.
  5. Barker DJ, Hales CN, Fall CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36:62.
  6. Gennser G, Rymark P, Isberg PE. Low birth weight and risk of high blood pressure in adulthood. Br Med J (Clin Res Ed) 1988; 296:1498.
  7. Curhan GC, Chertow GM, Willett WC, et al. Birth weight and adult hypertension and obesity in women. Circulation 1996; 94:1310.
  8. Curhan GC, Willett WC, Rimm EB, et al. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 1996; 94:3246.
  9. Li Y, Ley SH, VanderWeele TJ, et al. Joint association between birth weight at term and later life adherence to a healthy lifestyle with risk of hypertension: a prospective cohort study. BMC Med 2015; 13:175.
  10. Law CM, Shiell AW. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens 1996; 14:935.
  11. Khalsa DD, Beydoun HA, Carmody JB. Prevalence of chronic kidney disease risk factors among low birth weight adolescents. Pediatr Nephrol 2016; 31:1509.
  12. Law CM, de Swiet M, Osmond C, et al. Initiation of hypertension in utero and its amplification throughout life. BMJ 1993; 306:24.
  13. Regina S, Lucas R, Miraglia SM, et al. Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis 2001; 37:467.
  14. Van Abeelen AF, Veenendaal MV, Painter RC, et al. The fetal origins of hypertension: a systematic review and meta-analysis of the evidence from animal experiments of maternal undernutrition. J Hypertens 2012; 30:2255.
  15. Øglaend B, Forman MR, Romundstad PR, et al. Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies. J Hypertens 2009; 27:2051.
  16. Huxley R, Neil A, Collins R. Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Lancet 2002; 360:659.
  17. Filler G, Yasin A, Kesarwani P, et al. Big mother or small baby: which predicts hypertension? J Clin Hypertens (Greenwich) 2011; 13:35.
  18. Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 2006; 69:671.
  19. Hemachandra AH, Klebanoff MA, Furth SL. Racial disparities in the association between birth weight in the term infant and blood pressure at age 7 years: results from the collaborative perinatal project. J Am Soc Nephrol 2006; 17:2576.
  20. Langley-Evans SC. Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. J Hypertens 1997; 15:537.
  21. IJzerman RG, Stehouwer CD, de Geus EJ, et al. Low birth weight is associated with increased sympathetic activity: dependence on genetic factors. Circulation 2003; 108:566.
  22. Hoy WE, Hughson MD, Bertram JF, et al. Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol 2005; 16:2557.
  23. Samuel T, Hoy WE, Douglas-Denton R, et al. Determinants of glomerular volume in different cortical zones of the human kidney. J Am Soc Nephrol 2005; 16:3102.
  24. Bergvall N, Iliadou A, Johansson S, et al. Genetic and shared environmental factors do not confound the association between birth weight and hypertension: a study among Swedish twins. Circulation 2007; 115:2931.
  25. Luyckx VA, Perico N, Somaschini M, et al. A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. Lancet 2017; 390:424.
  26. Low Birth Weight and Nephron Number Working Group. The Impact of Kidney Development on the Life Course: A Consensus Document for Action. Nephron 2017; 136:3.
  27. Lopes AA, Port FK. The low birth weight hypothesis as a plausible explanation for the black/white differences in hypertension, non-insulin-dependent diabetes, and end-stage renal disease. Am J Kidney Dis 1995; 25:350.
  28. Eriksson J, Forsén T, Tuomilehto J, et al. Fetal and childhood growth and hypertension in adult life. Hypertension 2000; 36:790.
  29. Schreuder MF, Nyengaard JR, Fodor M, et al. Glomerular number and function are influenced by spontaneous and induced low birth weight in rats. J Am Soc Nephrol 2005; 16:2913.
  30. Hughson M, Farris AB 3rd, Douglas-Denton R, et al. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 2003; 63:2113.
  31. Schmidt IM, Chellakooty M, Boisen KA, et al. Impaired kidney growth in low-birth-weight children: distinct effects of maturity and weight for gestational age. Kidney Int 2005; 68:731.
  32. Keller G, Zimmer G, Mall G, et al. Nephron number in patients with primary hypertension. N Engl J Med 2003; 348:101.
  33. Schreuder MF, Nauta J. Prenatal programming of nephron number and blood pressure. Kidney Int 2007; 72:265.
  34. de Jong F, Monuteaux MC, van Elburg RM, et al. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension 2012; 59:226.
  35. Keijzer-Veen MG, Kleinveld HA, Lequin MH, et al. Renal function and size at young adult age after intrauterine growth restriction and very premature birth. Am J Kidney Dis 2007; 50:542.
  36. Hughson MD. Low birth weight and kidney function: is there a relationship and is it determined by the intrauterine environment? Am J Kidney Dis 2007; 50:531.
  37. Juonala M, Cheung MM, Sabin MA, et al. Effect of birth weight on life-course blood pressure levels among children born premature: the Cardiovascular Risk in Young Finns Study. J Hypertens 2015; 33:1542.
  38. Singhal A, Lucas A. Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet 2004; 363:1642.
  39. Stettler N, Stallings VA, Troxel AB, et al. Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation 2005; 111:1897.
  40. Ben-Shlomo Y, McCarthy A, Hughes R, et al. Immediate postnatal growth is associated with blood pressure in young adulthood: the Barry Caerphilly Growth Study. Hypertension 2008; 52:638.
  41. Martin RM, Ness AR, Gunnell D, et al. Does breast-feeding in infancy lower blood pressure in childhood? The Avon Longitudinal Study of Parents and Children (ALSPAC). Circulation 2004; 109:1259.
  42. Vohr BR, Allan W, Katz KH, et al. Early predictors of hypertension in prematurely born adolescents. Acta Paediatr 2010; 99:1812.
  43. Thiering E, Brüske I, Kratzsch J, et al. Peak growth velocity in infancy is positively associated with blood pressure in school-aged children. J Hypertens 2012; 30:1114.
  44. Jones A, Charakida M, Falaschetti E, et al. Adipose and height growth through childhood and blood pressure status in a large prospective cohort study. Hypertension 2012; 59:919.