Version May 2024
INTRODUCTION — 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]. Some of these (particularly hypertension and low birth weight) may be confounded by socioeconomic status [2].
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 and hypertension".)
●(See "Overweight, obesity, and weight reduction in hypertension".)
●(See "Genetic factors in the pathogenesis of hypertension".)
BIRTH WEIGHT AND BLOOD PRESSURE — Babies who are small at birth are more likely to have higher blood pressures during adolescence and to be hypertensive as adults [3]. This phenomenon may be exaggerated for gestational (as distinct from primary) hypertension in females born with very low birth weights [4]. 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 [5]. 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 [6], diabetes mellitus, and hyperlipidemia [7], 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 [8]. The relationship was confirmed in both males and females using data from the Nurses' Health Study and the Health Professionals Follow-up Study [9,10], as well as in other cohorts [11]. 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 [12].
Multiple surveys of children also show a relation between birth weight and blood pressure but of a lesser degree than in adults [13,14]. 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 [15]. The relationship with adult blood pressure may be even more attenuated [3].
Maternal undernutrition has been linked to fetal growth restriction and adult hypertension (and possibly nephrosclerosis) in animal experiments [15-17]. 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.
Blood pressures in children are more closely correlated to the blood pressure in the mother than the father [13]. Although this may in part relate to X-linked genes, the prenatal environment is clearly more strongly related to the mother. Furthermore, higher blood pressure in the mother partly reflects her own fetal experience, which in turn influences the intrauterine environment that she provides for her children, thereby creating a vicious cycle [18].
Despite the above findings, which provided an estimate that a one-kilogram-higher birth weight is associated with a 5.2 mmHg lower systolic blood pressure in adult life, a systematic review of 55 studies suggests a much less impressive association [19]. After appropriate statistical adjustments, the estimate was a 0.6 mmHg lower blood pressure per one-kg-higher birth weight. The authors conclude, "Claims of a strong inverse association between birth weight and subsequent blood pressure may chiefly reflect the impact of random error, selective emphasis of particular results, and inappropriate adjustment for current weight and for confounding factors. These findings suggest that birth weight is of little relevance to blood pressure levels in later life." Support for this conclusion comes from a large cohort study in which higher newborn and maternal weight were stronger predictors of adult blood pressure than low birth weight [20].
In addition, the association is less clear among African Americans. The few studies that directly compared the relationship in this group between birth weight and, subsequently, the development of hypertension have reported conflicting results [21,22]. However, only a limited number of individuals have thus far been evaluated.
Possible mechanisms — A number of hypotheses have been proposed to explain the possible association between low birth weight and subsequent hypertension [23-30]. The most logical hypothesis that is well supported by both experimental and clinical evidence is "congenital oligonephropathy," which suggests that impaired intrauterine growth leads to impaired kidney development [26,27]. The decrease in the number of nephrons results in compensatory hypertrophy in the nephrons present; the associated intraglomerular hypertension can then lead, over a period of years, to glomerular sclerosis and the development of hypertension similar to that seen with nephron loss in chronic kidney failure [31,32]. (See "Secondary factors and progression of chronic kidney disease".)
Experimental support for this hypothesis includes the observations that rats with induced intrauterine growth retardation have offspring with markedly fewer nephrons, and these rats develop progressive glomerular sclerosis as adults [33]. The kidneys of low birth weight human infants have also been shown to be small with reduced numbers of glomeruli, a finding that may increase the risk of developing kidney disease [34-36]. The most direct confirmation is the finding that, at autopsy, 10 White patients with hypertension had significantly fewer glomeruli per kidney than 10 matched normotensive controls [37].
However, the association between low nephron number and the development of hypertension may not exist for African Americans. An autopsy study of 62 African American and 60 White individuals showed that, whereas the average number of glomeruli was lower for White patients with hypertension compared with White patients without hypertension, there was no difference in the number of glomeruli between African American patients with and without hypertension [21]. The conclusive determination of an association between nephron number and hypertension will ultimately require large prospective studies using optimal radiographic techniques [38].
PRETERM BIRTH — Prematurity may also increase the risk of hypertension via decreased glomerulogenesis independent of birth weight [39-41]. A meta-analysis of 10 studies including 3083 individuals from eight countries reported the association of prematurity with adolescent or adult blood pressure (measured at an average age of 18 years) [39]. Those who were born premature had modestly but significantly higher systolic blood pressures (by 2.5 mmHg), regardless of weight. After restricting to the five highest quality studies, the average difference in systolic blood pressure was more pronounced (3.8 mmHg higher among those born premature).
However, other data (including those from the Adults Born Preterm International Collaboration [5]) suggest that prematurity is not associated with higher adult blood pressure unless it is also accompanied by lower birth weight. In a study of 1756 Finnish children followed for 31 years, systolic pressure (measured at a mean age of 41 years) among those born premature and small for gestational age was 7 mmHg higher than both those born at term and those born premature but with an appropriate gestational weight [42]. Blood pressure was identical among those born at term and those born premature with an appropriate gestational weight.
POSTNATAL WEIGHT GAIN — Despite evidence supporting a role of low birth weight in adult hypertension, its contribution may be quantitatively small. The rapid postnatal "catch-up" in body weight that such infants typically undergo may contribute to a greater extent [43,44].
It is possible that overfeeding during the first few weeks after birth programs the infant for later obesity, insulin resistance, and endothelial dysfunction, which, in turn may result in diabetes, hypertension, and coronary disease [45,46]. Observations regarding the beneficial effects of breast feeding on subsequent blood pressure lend further support to this hypothesis since breast milk usually results in slower early growth due to its lower caloric content and lower initial volume [47]. It is also possible that postnatal weight gain could affect adult blood pressure via other mechanisms since a significant association between weight gain velocity in the early years and blood pressure in young adulthood has been described that is independent of adult adiposity [46,48-50].
SUMMARY
●Low birth weight as well as prematurity independent of birth weight may contribute to the development of primary (formerly "essential") hypertension in adulthood. (See 'Birth weight and blood pressure' above and 'Preterm birth' above.)
●A leading hypothesis to explain this is that impaired kidney development results in compensatory hypertrophy and intraglomerular hypertension, which lead to glomerular sclerosis. (See 'Possible mechanisms' above.)
●The contribution of low birth weight may be quantitatively small; it is possible that the rapid postnatal "catch-up" in body weight contributes to a greater extent. A possible mechanism is that overfeeding during the first few weeks after birth may program the infant for later obesity, insulin resistance, and endothelial dysfunction, causing diabetes, hypertension, and coronary disease. (See 'Postnatal weight gain' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman M Kaplan, MD (deceased), who contributed to an earlier version of this topic review.
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