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Meta-Analysis
. 2023 Oct 12;10(10):CD012642.
doi: 10.1002/14651858.CD012642.pub2.

Higher versus lower sodium intake for preterm infants

Natasha Diller  1 , David A Osborn  2 , Pita Birch  3
Affiliations
Meta-Analysis

Higher versus lower sodium intake for preterm infants

Natasha Diller et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

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

Search methods: 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.

Selection criteria: 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.

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

Main results: 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.

Authors' conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

David A Osborn is a Senior Editor for Cochrane Neonatal. However, he was not involved in editorial acceptance or review of this manuscript.

Natasha Diller does not have any interests to disclose at this time.

Pita Birch does not have any interests to disclose at this time.

Figures

1
1
PRISMA flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 1: Mortality (latest time reported up to hospital discharge)
1.2
1.2. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 2: Hyponatraemia (< 130 mmol/L)
1.3
1.3. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
1.4
1.4. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 4: Necrotising enterocolitis
1.5
1.5. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 5: Patent ductus arteriosus
1.6
1.6. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 6: Bronchopulmonary dysplasia (≥ 28 days age)
1.7
1.7. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 7: Intraventricular haemorrhage (any)
1.8
1.8. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 8: Periventricular leukomalacia
1.9
1.9. Analysis
Comparison 1: Early (< 7 days following birth) higher versus lower sodium intake, Outcome 9: Maximal weight loss %
2.1
2.1. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 1: Mortality (latest time reported up to hospital discharge)
2.2
2.2. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 2: Hyponatraemia (< 130 mmol/L)
2.3
2.3. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
2.4
2.4. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 4: Postnatal growth failure (weight < 10th percentile)
2.5
2.5. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 5: Necrotising enterocolitis
2.6
2.6. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 6: Patent ductus arteriosus
2.7
2.7. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 7: Chronic lung disease (36 weeks' PMA)
2.8
2.8. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 8: Maximal weight loss %
2.9
2.9. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 9: Weight gain
2.10
2.10. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 10: Linear growth cm/week
2.11
2.11. Analysis
Comparison 2: Late (≥ 7 days following birth) higher versus lower sodium intake, Outcome 11: Percent weight change from birth to 2 weeks
3.1
3.1. Analysis
Comparison 3: Early and late higher versus lower sodium intake, Outcome 1: Hypernatraemia (≥ 150 mmol/L)
3.2
3.2. Analysis
Comparison 3: Early and late higher versus lower sodium intake, Outcome 2: Weight gain
4.1
4.1. Analysis
Comparison 4: Early (< 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
4.2
4.2. Analysis
Comparison 4: Early (< 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
4.3
4.3. Analysis
Comparison 4: Early (< 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
4.4
4.4. Analysis
Comparison 4: Early (< 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 4: Necrotising enterocolitis
4.5
4.5. Analysis
Comparison 4: Early (< 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 5: Bronchopulmonary dysplasia (≥ 28 days age)
5.1
5.1. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
5.2
5.2. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
5.3
5.3. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
5.4
5.4. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 4: Postnatal growth failure (weight < 10th percentile)
5.5
5.5. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 5: Necrotising enterocolitis
5.6
5.6. Analysis
Comparison 5: Late (≥ 7 days following birth) higher versus lower sodium intake: gestation and birthweight subgroup analysis, Outcome 6: Chronic lung disease (36 weeks' PMA)
6.1
6.1. Analysis
Comparison 6: Early (< 7 days following birth) higher versus lower sodium intake: lower versus high fluid intake subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
6.2
6.2. Analysis
Comparison 6: Early (< 7 days following birth) higher versus lower sodium intake: lower versus high fluid intake subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
6.3
6.3. Analysis
Comparison 6: Early (< 7 days following birth) higher versus lower sodium intake: lower versus high fluid intake subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
6.4
6.4. Analysis
Comparison 6: Early (< 7 days following birth) higher versus lower sodium intake: lower versus high fluid intake subgroup analysis, Outcome 4: Necrotising enterocolitis
6.5
6.5. Analysis
Comparison 6: Early (< 7 days following birth) higher versus lower sodium intake: lower versus high fluid intake subgroup analysis, Outcome 5: Bronchopulmonary dysplasia (≥ 28 days age)
8.1
8.1. Analysis
Comparison 8: Early (< 7 days following birth) higher versus lower sodium intake: stable versus sick infants subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
8.2
8.2. Analysis
Comparison 8: Early (< 7 days following birth) higher versus lower sodium intake: stable versus sick infants subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
8.3
8.3. Analysis
Comparison 8: Early (< 7 days following birth) higher versus lower sodium intake: stable versus sick infants subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
8.4
8.4. Analysis
Comparison 8: Early (< 7 days following birth) higher versus lower sodium intake: stable versus sick infants subgroup analysis, Outcome 4: Necrotising enterocolitis
8.5
8.5. Analysis
Comparison 8: Early (< 7 days following birth) higher versus lower sodium intake: stable versus sick infants subgroup analysis, Outcome 5: Bronchopulmonary dysplasia (≥ 28 days age)
9.1
9.1. Analysis
Comparison 9: Early (< 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
9.2
9.2. Analysis
Comparison 9: Early (< 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
9.3
9.3. Analysis
Comparison 9: Early (< 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
9.4
9.4. Analysis
Comparison 9: Early (< 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 4: Necrotising enterocolitis
9.5
9.5. Analysis
Comparison 9: Early (< 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 5: Bronchopulmonary dysplasia (≥ 28 days age)
10.1
10.1. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
10.2
10.2. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
10.3
10.3. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
10.4
10.4. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 4: Postnatal growth failure (weight < 10th percentile)
10.5
10.5. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 5: Necrotising enterocolitis
10.6
10.6. Analysis
Comparison 10: Late (≥ 7 days following birth) higher versus lower sodium intake: parenteral versus enteral versus parenteral and enteral intake subgroup analysis, Outcome 6: Chronic lung disease (36 weeks' PMA)
11.1
11.1. Analysis
Comparison 11: Early (< 7 days following birth) higher versus lower sodium intake: sensitivity analysis, Outcome 1: Mortality (latest time reported up to hospital discharge)
11.2
11.2. Analysis
Comparison 11: Early (< 7 days following birth) higher versus lower sodium intake: sensitivity analysis, Outcome 2: Hyponatraemia (< 130 mmol/L)
11.3
11.3. Analysis
Comparison 11: Early (< 7 days following birth) higher versus lower sodium intake: sensitivity analysis, Outcome 3: Hypernatraemia (≥ 150 mmol/L)
11.4
11.4. Analysis
Comparison 11: Early (< 7 days following birth) higher versus lower sodium intake: sensitivity analysis, Outcome 4: Necrotising enterocolitis
11.5
11.5. Analysis
Comparison 11: Early (< 7 days following birth) higher versus lower sodium intake: sensitivity analysis, Outcome 5: Bronchopulmonary dysplasia (≥ 28 days age)
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012642

References

References to studies included in this review

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Isemann 2016 {published data only}
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References to studies excluded from this review

Al‐Dahhan 1983 {published data only}
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Lucas 1988 {published data only}
    1. Lucas A, Morley R, Hudson GJ, Bamford MF, Boon A, Crowle P, et al. Early sodium intake and later blood pressure in preterm infants. Archives of Disease in Childhood 1988;63(6):656-7. [DOI: 10.1136/adc.63.6.656] [PMID: ] - DOI - PMC - PubMed
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Prekajski 1998 {published data only}
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References to studies awaiting assessment

Sanchez 2023 {published data only}
    1. Sanchez C, Castillo D, Valdes BD, Castaneda F. Effect of high sodium intake (5 mEq/kg/day) in preterm newborns. Indian Pediatrics 2023;60(1):146-8. - PubMed

References to ongoing studies

CTRI/2019/08/020617 {published data only}
    1. CTRI/2019/08/020617. Effect of early sodium supplementation in postnatal weight gain of preterm babies. https://trialsearchwhoint/Trial2aspx?TrialID=CTRI/2019/08/020617.
NCT03889197 {published data only}
    1. NCT03889197. Physiologic approach to sodium supplementation in premature infants. https://clinicaltrialsgov/show/nct03889197 2019.
NCT04035564 {published data only}
    1. NCT04035564. Early sodium intake in preterm newborns. clinicaltrials.gov/ct2/show/NCT04035564 (first received 29 July 2019). [CENTRAL: CN-01965880]

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