Kidney health outcomes in children born very prematurely compared to full-term counterparts: a systematic review and meta-analysis.

BACKGROUND

Advances in neonatal care have improved survival rates in preterm neonates. However, concerns persist regarding the long-term kidney implications of prematurity. Nephrogenesis is disrupted, particularly in those born very preterm (≤ 32 weeks of gestation), increasing the risk of early kidney dysfunction and hypertension later in life.

OBJECTIVES

This systematic review and meta-analysis aimed to evaluate kidney health outcomes in former very preterm children and adolescents compared to full-term peers.

DATA SOURCES

A systematic literature search was conducted in MEDLINE/PubMed, Scopus, and Web of Science from their earliest available records to October 9, 2024.

STUDY ELIGIBILITY CRITERIA

We included observational studies comparing kidney health parameters between children/adolescents born very preterm (gestational age - GA ≤ 32 weeks) and their full-term counterparts (gestational age > 36 weeks or birth weight > 2000 g) within the age range of 6 to 18 years.

PARTICIPANTS AND INTERVENTIONS

Children and adolescents aged 6-18 years born very preterm were compared to their full-term counterparts. The analyzed kidney function markers included serum Cystatin C, serum creatinine (sCr), estimated glomerular filtration rate (eGFR) based on sCr (Cr-eGFR), and blood pressure (systolic and diastolic, SBP/DBP).

STUDY APPRAISAL AND SYNTHESIS METHODS

The Newcastle-Ottawa Scale was used to assess study quality. The mean difference with 95% confidence intervals was used for continuous outcomes. Statistical significance was set at p < 0.05. Sensitivity, subgroup and meta-regression analyses were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2).

RESULTS

Thirteen studies (16 reports; 2,112 participants) were included. Very preterm children and adolescents had higher serum Cystatin C (0.05 mg/L; 95%CI: 0.02-0.08), lower Cr-eGFR (-11.87 mL/min/1.73 m; 95%CI: -22.44 to -1.31), and higher SBP (1.96 mmHg; 95%CI: 0.21-3.71). Sensitivity analysis confirmed Cystatin C findings but rendered Cr-eGFR and SBP differences non-significant. Subgroup analysis showed a significant GA effect on sCr (p < 0.0001), though the ≥ 28 weeks subgroup included only two studies.

LIMITATIONS

Considerable heterogeneity across studies persisted despite sensitivity and subgroup analyses. The lack of randomized controlled trials and longitudinal studies limits result interpretation, while non-significant meta-regression findings hinder full explanation of heterogeneity. Insufficient data prevented the assessment of additional kidney function parameters.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS

Cystatin C was elevated in very preterm individuals compared to full-term peers, reinforcing its role as an early marker of kidney dysfunction. While differences in Cr-eGFR and SBP lost significance after sensitivity analysis, these markers remain relevant for long-term follow-up in this vulnerable population.

SYSTEMATIC REVIEW REGISTRATION NUMBER

PROSPERO (CRD42024554702).