Preterm Birth and its Impact on Renal Health

https://doi.org/10.1016/j.semnephrol.2017.05.002Get rights and content

Summary

Preterm birth occurs in approximately 10% of all births worldwide. Preterm infants have reduced nephron numbers at birth in proportion to gestational age, and are at increased risk of neonatal acute kidney injury as well as higher blood pressure, proteinuria, and chronic kidney disease later in life. Rapid catch-up growth in preterm infants, especially if resulting in obesity, is a risk factor for end-stage kidney disease among children with proteinuric renal disease. Preterm birth, however, is a risk factor not only for the infant because mothers who deliver preterm have an increased risk of having subsequent preterm deliveries as well as hypertension, cardiovascular disease, and renal disease later in life. Preterm birth in a female infant is also a risk factor for her future risk of having a preterm delivery, gestational hypertension, and gestational diabetes, which in turn may impact the development of fetal kidneys and the offspring’s risk of hypertension and renal disease. This intergenerational programming cycle, therefore, perpetuates the risks and consequences of prematurity. Interruption of this cycle may be possible through optimization of maternal nutrition and health as well as careful antenatal care, which may in turn reduce the global burden of hypertension and renal disease in subsequent generations.

Section snippets

preterm birth and Nephron Number

Given the fact that nephron number does not increase after birth, Brenner et al9 hypothesized that individuals born with kidneys with fewer nephrons would be at increased risk for hypertension and renal disease later in life. This paradigm has been termed the nephron number hypothesis. In human beings, nephrogenesis generally continues in utero until the 36th week of gestation, with little evidence of nephrogenesis occurring postnatally in term infants.10 In preterm infants, however, it has

Impact of Post-Natal Factors on Nephron Number

Preterm infants often are small and require hospitalization in the neonatal intensive care unit (NICU) after birth. Preterm birth is a risk factor for neonatal acute kidney injury (AKI). In an autopsy study, postnatal renal failure (serum creatinine level, >2.0 mg/dL) in preterm infants was associated with a reduction in nephron number (Fig. 2).11 Whether the lower nephron number was a risk factor for or the result of AKI, or whether a common external factor, such as antibiotic use, may have

preterm birth and Blood Pressure

A recent meta-analysis comprising 10 studies in 1,738 term and 1,342 preterm individuals born at a mean of 30.2 weeks gestational age found a significant 2.5 mm Hg (95% confidence interval, 1.7-3.3 mm Hg) higher systolic blood pressure among the preterm individuals measured at a mean age of 17.8 years (range, 6.3-22.4 y).24 Although these few millimeters of blood pressure may seem clinically irrelevant at age 17, blood pressure tracks with age and these individuals may develop hypertension

PREMATURITY and Renal Function

The measurement of glomerular filtration rate (GFR) on day 1 of life may be a good surrogate marker for nephron number because renal tubular function is immature and hyperfiltration is unlikely to have begun at this stage. Serum creatinine measurement cannot be used in this period because neonatal creatinine reflects maternal renal function. Amikacin clearance on day 1 of life, used as a measure of neonatal GFR, was found to decrease with decreasing gestational age, suggesting a reduced nephron

Preterm birth and Renal Dysfunction

In the setting of a reduced nephron number, renal function may be maintained at the expense of hyperfiltration. An early clinical sign of hyperfiltration is microalbuminuria, which may progress over time to overt proteinuria, especially in the face of increased functional demand imposed by obesity or further nephron loss. Consistent with this possibility, among 4-year-old children born preterm, albuminuria was found to be higher in both boys and girls who had reached normal height (presumably

Catch-Up Growth and Renal Disease

Early childhood nutrition is important for survival, but also may modify the risks associated with preterm birth and growth restriction.46 Increased weight gain and height have been associated with higher blood pressure in adolescence and young adulthood in those who were born preterm.47, 48 Both prenatal and postnatal growth restriction were associated with a lower GFR in children who were born preterm, the odds of which were reduced with better weight gain during postnatal hospitalization.35,

Preterm Birth and Acute Kidney Injury

Preterm birth, growth restriction, and reduced nephron numbers are important risk factors for neonatal AKI.11, 56, 57 AKI occurs in 12% to 40% of preterm infants and the risk increases with increasing prematurity.56, 57, 58 Variance in AKI incidence may relate to differences in the populations studied, but also may reflect the current lack of standardized definitions of AKI in neonates. Multiple factors likely contribute to the AKI risk after preterm birth, including reduced nephron numbers,

preterm birth and Nephrocalcinosis

Nephrocalcinosis (ie, calcification within the renal parenchyma) occurs in 7% to 64% of very preterm infants or those with birth weights less than 1,500 g.62 The strong correlation of nephrocalcinosis with low gestational age suggests that differential maturation of the renal tubules in the renal cortex and slow rates of urine flow may predispose to calcium oxalate precipitation.62 Medication use such as furosemide, aminoglycosides, and glucocorticoids, as well as nutritional intake, may

Maternal and Intergenerational Risks of preterm birth

Mothers who have one preterm infant are at increased risk for subsequent preterm deliveries (Fig. 3).67 This risk appears to persist despite a reduction in identifiable risk factors for preterm delivery in subsequent pregnancies, suggesting an intrinsic maternal risk.67 Interestingly, mothers who themselves were preterm are at increased risk of having a preterm delivery, and this risk increases inversely with the mother’s own gestational age and with the mother having been SGA.68, 69, 70 This

Conclusions

Preterm birth is common and increasingly is being recognized as an important risk factor for later-life hypertension and renal disease in both infants and their mothers. Growth restriction, in addition to preterm birth, appears to exacerbate these risks. Preterm birth and growth restriction likely are important contributors to the global burden of hypertension and renal disease. A major drawback of studies in preterm individuals to date is that most have been conducted in Caucasian populations.

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