Preterm Birth and its Impact on Renal Health☆
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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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Cited by (63)
Exposure of preterm neonates to toxic metals during their stay in the Neonatal Intensive Care Unit and its impact on neurodevelopment at 2 months of age
2023, Journal of Trace Elements in Medicine and BiologyPopulation pharmacokinetic modeling of caffeine in preterm infants with apnea of prematurity: New findings from concomitant erythromycin and AHR genetic polymorphisms
2022, Pharmacological ResearchCitation Excerpt :The model established by Gao et al. [18] incorporated the SCR, and the authors concluded that TDM of caffeine in preterm infants with renal insufficiency is necessary. However, many studies have confirmed that SCR is not a reliable surrogate for estimating the renal function of premature infants [71–74], because SCR levels are affected by the tubular resorption of creatinine by the immature kidney, variations in muscle mass, abnormalities in protein catabolism, patient fluid status, total body fluid loss, and intravascular volume contraction [71,72]. Therefore, it is currently recommended to use indicators (e.g., CYSC) as a substitute for SCR in the evaluation of neonatal renal function [71,74].
The transition to parenthood in obstetrics: enhancing prenatal care for 2-generation impact
2022, American Journal of Obstetrics and Gynecology MFMCitation Excerpt :Annually, 10% of US births are preterm birth (PTB; <37 weeks of gestation), with nearly 400,000 births affected68 and recent data showing rates rising.69 PTB is associated with a future risk of poor mental health outcomes.70 It is estimated that 40% of children born prematurely will experience compromised neurodevelopment, with effects on social, emotional, and physical health.71
Management of Extreme Prematurity (Manuscript for Seminars in Pediatric Surgery)
2022, Seminars in Pediatric SurgeryCitation Excerpt :Table 1 summarizes the observations in each phase with appropriate guidelines for management. Prematurity, along with perinatal and postnatal stressors placed on the developing kidneys, has both short- and long-term implications.85 Reduced nephron endowment, maladaptation, and exposures such as hypoxemia, infection, hypovolemia and nephrotoxic medications increase the risk of acute kidney injury (AKI).
Prenatal urinary concentrations of phenols and risk of preterm birth: exploring windows of vulnerability
2021, Fertility and Sterility
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