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

Abstract

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 m²; 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).

Keywords: Biomarkers; Children; Cystatin C; Kidney function; Meta-analysis; Prematurity.