Higher versus lower sodium intake for preterm infants

Infants born preterm are at increased risk of early hypernatraemia (above-normal blood sodium levels) and late hyponatraemia (below-normal blood sodium levels). There are concerns that imbalances of sodium intake may impact neonatal morbidities, growth and developmental outcomes.

To determine the effects of higher versus lower sodium supplementation in preterm infants.

We searched CENTRAL in February 2023; and MEDLINE, Embase and trials registries in March and April 2022. We checked reference lists of included studies and systematic reviews where subject matter related to the intervention or population examined in this review. We compared early (< 7 days following birth), late (≥ 7 days following birth), and early and late sodium supplementation, separately.

We included randomised, quasi-randomised or cluster-randomised controlled trials that compared nutritional supplementation that included higher versus lower sodium supplementation in parenteral or enteral intake, or both. Eligible participants were preterm infants born before 37 weeks' gestational age or with a birth weight less than 2500 grams, or both. We excluded studies that had prespecified differential water intakes between groups.

Two review authors independently assessed eligibility and risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence.

We included nine studies in total. However, we were unable to extract data from one study (20 infants); some studies contributed to more than one comparison. Eight studies (241 infants) were available for quantitative meta-analysis. Four studies (103 infants) compared early higher versus lower sodium intake, and four studies (138 infants) compared late higher versus lower sodium intake. Two studies (103 infants) compared intermediate sodium supplementation (≥ 3 mmol/kg/day to < 5 mmol/kg/day) versus no supplementation, and two studies (52 infants) compared higher sodium supplementation (≥ 5 mmol/kg/day) versus no supplementation. We assessed only two studies (63 infants) as low risk of bias. Early (less than seven days following birth) higher versus lower sodium intake Early higher versus lower sodium intake may not affect mortality (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.38 to 2.72; I² = 0%; 3 studies, 83 infants; low-certainty evidence). Neurodevelopmental follow-up was not reported. Early higher versus lower sodium intake may lead to a similar incidence of hyponatraemia < 130 mmol/L (RR 0.68, 95% CI 0.40 to 1.13; I² = 0%; 3 studies, 83 infants; low-certainty evidence) but an increased incidence of hypernatraemia ≥ 150 mmol/L (RR 1.62, 95% CI 1.00 to 2.65; I² = 0%; 4 studies, 103 infants; risk difference (RD) 0.17, 95% CI 0.01 to 0.34; number needed to treat for an additional harmful outcome 6, 95% CI 3 to 100; low-certainty evidence). Postnatal growth failure was not reported. The evidence is uncertain for an effect on necrotising enterocolitis (RR 4.60, 95% CI 0.23 to 90.84; 1 study, 46 infants; very low-certainty evidence). Chronic lung disease at 36 weeks was not reported. Late (seven days or more following birth) higher versus lower sodium intake Late higher versus lower sodium intake may not affect mortality (RR 0.13, 95% CI 0.01 to 2.20; 1 study, 49 infants; very low-certainty evidence). Neurodevelopmental follow-up was not reported. Late higher versus lower sodium intake may reduce the incidence of hyponatraemia < 130 mmol/L (RR 0.13, 95% CI 0.03 to 0.50; I² = 0%; 2 studies, 69 infants; RD -0.42, 95% CI -0.59 to -0.24; number needed to treat for an additional beneficial outcome 2, 95% CI 2 to 4; low-certainty evidence). The evidence is uncertain for an effect on hypernatraemia ≥ 150 mmol/L (RR 7.88, 95% CI 0.43 to 144.81; I² = 0%; 2 studies, 69 infants; very low-certainty evidence). A single small study reported that later higher versus lower sodium intake may reduce the incidence of postnatal growth failure (RR 0.25, 95% CI 0.09 to 0.69; 1 study; 29 infants; low-certainty evidence). The evidence is uncertain for an effect on necrotising enterocolitis (RR 0.07, 95% CI 0.00 to 1.25; 1 study, 49 infants; very low-certainty evidence) and chronic lung disease (RR 2.03, 95% CI 0.80 to 5.20; 1 study, 49 infants; very low-certainty evidence). Early and late (day 1 to 28 after birth) higher versus lower sodium intake for preterm infants Early and late higher versus lower sodium intake may not have an effect on hypernatraemia ≥ 150 mmol/L (RR 2.50, 95% CI 0.63 to 10.00; 1 study, 20 infants; very low-certainty evidence). No other outcomes were reported.

Early (< 7 days following birth) higher sodium supplementation may result in an increased incidence of hypernatraemia and may result in a similar incidence of hyponatraemia compared to lower supplementation. We are uncertain if there are any effects on mortality or neonatal morbidity. Growth and longer-term development outcomes were largely unreported in trials of early sodium supplementation. Late (≥ 7 days following birth) higher sodium supplementation may reduce the incidence of hyponatraemia. We are uncertain if late higher intake affects the incidence of hypernatraemia compared to lower supplementation. Late higher sodium intake may reduce postnatal growth failure. We are uncertain if late higher sodium intake affects mortality, other neonatal morbidities or longer-term development. We are uncertain if early and late higher versus lower sodium supplementation affects outcomes.