Caffeine and kidney function at two years in former extremely low gestational age neonates

Abstract

Background: Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months.

Methods: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation.

Primary outcomes: 'reduced eGFR' <90 ml/min/1.73 m², 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used.

Results: 598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m² (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25).

Conclusions: Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status.

Impact: In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

Fig. 1. Consort diagram.

Of 941 participants enrolled in the original trial, 598 subjects had a 22–26-month corrected age follow-up visit with at least one kidney metric obtained. The figure details participants who did not meet the inclusion criteria and the number who had specific kidney metrics obtained. eGFR estimated Glomerular Filtration Rate). Created with BioRender.com.

Fig. 2. 22–26 month corrected gestational age kidney outcomes.

This histogram depicts frequencies of specific kidney outcomes by gestational age category. The x-axis displays the categories of kidney outcomes while the y axis is percent total of gestational age categories represented by the different bars with key beneath.

Fig. 3. Last caffeine administration by post menstrual age.

This boxplot depicts the timing of caffeine discontinuation. The x-axis is the postmenstrual age of caffeine discontinuation, and the y axis is gestational age at birth.

Fig. 4. Post menstrual age at caffeine discontinuation stratified by bronchopulmonary dysplasia status and follow-up at 22–26 months corrected gestational age.

This histogram depicts frequencies of the timing of caffeine discontinuation based on follow-up status and bronchopulmonary dysplasia (BPD) status. Each of the 4 panes represents a combination of those two possibilities: Follow-up with BPD, follow-up without BPD, no follow-up with BPD, and no follow-up without BPD. The x-axis is the postmenstrual age, and the y axis is number of study subjects.