A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates.

BACKGROUND: Sucrose has been demonstrated to provide analgesia for minor painful procedures in infants. However, results of trials investigating other sweet solutions for neonatal pain relief have not yet been synthesized. OBJECTIVE: To establish the efficacy of nonsucrose sweet-tasting solutions for pain relief during painful procedures in neonates. METHOD: The present article is a systematic review and meta-analyses of the literature. Standard methods of the Cochrane Neonatal Collaborative Review Group were used. Literature searches were reviewed for randomized controlled trials investigating the use of sweet solutions, except sucrose, for procedural pain management in neonates. Outcomes assessed included validated pain measures and behavioural and physiological indicators. RESULTS: Thirty-eight studies (3785 neonates) were included, 35 of which investigated glucose. Heel lancing was performed in 21/38 studies and venipuncture in 11/38 studies. A 3.6-point reduction in Premature Infant Pain Profile scores during heel lances was observed in studies comparing 20% to 30% glucose with no intervention (two studies, 124 neonates; mean difference -3.6 [95% CI -4.6 to -2.6]; P<0.001; I2=54%). A significant reduction in the incidence of cry after venipuncture for infants receiving 25% to 30% glucose versus water or no intervention was observed (three studies, 130 infants; risk difference -0.18 [95% CI -0.31 to -0.05]; P=0.008, number needed to treat = 6 [95% CI 3 to 20]; I2=63%). CONCLUSIONS: The present systematic review and meta-analyses demonstrate that glucose reduces pain scores and crying during single heel lances and venipunctures. Results indicate that 20% to 30% glucose solutions have analgesic effects and can be recommended as an alternative to sucrose for procedural pain reduction in healthy term and preterm neonates.

Treatment of patent ductus arteriosus and neonatal mortality/morbidities: adjustment for treatment selection bias.

OBJECTIVE: To examine the association between treatment for patent ductus arteriosus (PDA) and neonatal outcomes in preterm infants, after adjustment for treatment selection bias. STUDY DESIGN: Secondary analyses were conducted using data collected by the Canadian Neonatal Network for neonates born at a gestational age ≤ 32 weeks and admitted to neonatal intensive care units in Canada between 2004 and 2008. Infants who had PDA and survived beyond 72 hours were included in multivariable logistic regression analyses that compared mortality or any severe neonatal morbidity (intraventricular hemorrhage grades ≥ 3, retinopathy of prematurity stages ≥ 3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥ 2) between treatment groups (conservative management, indomethacin only, surgical ligation only, or both indomethacin and ligation). Propensity scores (PS) were estimated for each pair of treatment comparisons, and used in PS-adjusted and PS-matched analyses. RESULTS: Among 3556 eligible infants with a diagnosis of PDA, 577 (16%) were conservatively managed, 2026 (57%) received indomethacin only, 327 (9%) underwent ligation only, and 626 (18%) were treated with both indomethacin and ligation. All multivariable and PS-based analyses detected significantly higher mortality/morbidities for surgically ligated infants, irrespective of prior indomethacin treatment (OR ranged from 1.25-2.35) compared with infants managed conservatively or those who received only indomethacin. No significant differences were detected between infants treated with only indomethacin and those managed conservatively. CONCLUSIONS: Surgical ligation of PDA in preterm neonates was associated with increased neonatal mortality/morbidity in all analyses adjusted for measured confounders that attempt to account for treatment selection bias.

Male/female differences in indomethacin effects in preterm infants.

To test whether indomethacin prophylaxis has sex-mediated effects on severe intraventricular hemorrhage (grade III and IV) and on long-term outcomes in extremely-low-birth-weight infants. A secondary analysis was performed in the entire "Trial of Indomethacin Prophylaxis in Preterms study" cohort. The results suggest a weak differential treatment effect of indomethacin by sex.

Improved outcomes of outborn preterm infants if admitted to perinatal centers versus freestanding pediatric hospitals.

OBJECTIVES: To examine whether admission hospital type (13 perinatal centers vs 4 freestanding pediatric hospitals) was associated with differences in risk and illness severity adjusted mortality and morbidity among outborn preterm infants. STUDY DESIGN: Records of singleton outborn infants < or =32 weeks' gestational age (n = 605) admitted to 17 tertiary level neonatal intensive care units participating in the Canadian Neonatal Network for the period 1996 to 1997 were examined. RESULTS: Outborn infants admitted to freestanding pediatric hospitals were at higher risk of death (adjusted odds ratio [AOR], 2.25; 95% confidence interval [CI], 1.20, 4.20), nosocomial infection (AOR, 2.48; 95% CI, 1.64, 3.73), and oxygen dependency at 28 days of age (AOR, 1.77; 95% CI, 1.14, 2.75) when compared with outborn infants admitted to perinatal centers. CONCLUSIONS: After adjustment for perinatal risks and admission illness severity, outborn infants had better outcomes if they were admitted to perinatal centers compared with freestanding pediatric hospitals.

The Newborn Individualized Developmental Care and Assessment Program is not supported by meta-analyses of the data.

OBJECTIVES: To systematically review the effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) as compared with conventional care to improve long-term neurodevelopmental outcomes or short-term medical and neurodevelopmental outcomes in preterm and/or low birth weight infants. STUDY DESIGN: With the use of standard systematic review methodology, all randomized, controlled trials (RCTs) and prospective cohort studies evaluating in-hospital developmental care based on the framework of NIDCAP in preterm and/or low birth weight infants were identified. The quality of the RCTs was assessed. Meta-analyses were performed by using relative risk and risk difference for dichotomous data and weighted mean difference for continuous data with 95% confidence intervals. RESULTS: Five RCTs (n = 136) and 3 phase-lag cohort studies (n = 185) met inclusion criteria. School-age neurodevelopmental outcomes after NIDCAP have not been reported. Meta-analyses of medical outcomes showed a statistically significant benefit of NIDCAP on requirement for supplemental oxygen. Neurodevelopmental outcome was improved at 9 or 12 months but not at 2 years. CONCLUSIONS: There is insufficient evidence to support the NIDCAP to improve medical and neurodevelopmental outcomes of preterm infants.