Maternal and neonatal outcomes associated with illness severity of maternal COVID-19.

BACKGROUND: Several reports demonstrated that perinatal SARS-CoV-2 has significant impact on maternal and neonatal health outcomes. However, the relationship between severity of maternal illness with outcomes remains less clear. METHODS: This is a single-center retrospective cohort study of mother/infant dyads with positive maternal test for SARS-CoV-2 between 14 days prior and 3 days after delivery from 3/30/2020 to 12/28/2021. RESULTS: Among 538 mothers, those with moderate/severe/critical illness were more likely to undergo induction, receive oxygen, mechanical ventilation or ECMO. Mortality was significantly higher among the mothers with severe illness than asymptomatic and those with mild illness (6% vs 0% and 0%, respectively, P < 0.05). Neonates born to mothers with moderate/severe/critical illness were more likely to be preterm with lower birth weight, and to be admitted to the NICU (P < 0.05) but not to be small for gestational age. Mild maternal illness was only associated with NICU admission for isolation precaution and decreased rate of breastfeeding. CONCLUSIONS: Maternal illness severity was significantly associated with prematurity and several adverse maternal and neonatal outcomes.

Mortality among infants with evolving bronchopulmonary dysplasia increases with major surgery and with pulmonary hypertension.

OBJECTIVE: To assess whether mortality in patients with evolving bronchopulmonary dysplasia (BPD, defined as ⩾28 days of oxygen exposure with lung disease) is independently associated with pulmonary arterial hypertension (PAH) and surgery. STUDY DESIGN: Single institution retrospective birth cohort of preterm infants with gestational age (GA) 230/7 to 366/7 weeks, and evolving BPD delivered between 2001 and 2014. Surgery was classified as minor or major using published criteria. Mortality was analyzed by stepwise logistic regression analysis. RESULTS: Among 577 patients with evolving BPD, 33 (6%) died prior to discharge. Mortality decreased with GA (adjusted odds ratio (aOR): 0.69; 95% confidence interval (CI): 0.55, 0.87), birth weight Z-score (aOR: 0.69, 95% CI: 0.47, 0.996) and increased with PAH (aOR: 30, 95% CI: 2.1, 415), major surgery (aOR; 2.8, 95% CI: 1.3, 6.3), and PAH and surgery (aOR: 10.3, 95% CI: 2.5, 42.1). CONCLUSION: Among preterm patients with evolving BPD, PAH and surgery are independently associated with mortality.

Severe intraventricular hemorrhage and withdrawal of support in preterm infants.

OBJECTIVE: The objective of the study was to determine whether withdrawal of support in severe 'intraventricular hemorrhage' (IVH), that is, IVH grade 3 and periventricular hemorrhagic infarction (PVHI), has decreased after publication of studies that show improved prognosis and to examine cranial ultrasonograms, including PVHI territories defined by Bassan. STUDY DESIGN: Retrospective cohort of preterm infants from 23 0/7 to 28 6/7 weeks' gestation in 1993 to 2013. RESULTS: Among the 1755 infants, 1494 had no bleed, germinal matrix hemorrhage (GMH) or IVH grade 2, 137 had grade 3 IVH and 124 had PVHI. The odds of withdrawal of support, adjusted for severity of GMH-IVH and baseline variables, did not decrease after publications showing better prognosis. Among 82 patients who died with PVHI, 76 had life support withdrawn, including 34 without another contributing cause of death. The median number of PVHI territories involved was three. CONCLUSION: Withdrawal of support adjusted for severity of GMH-IVH did not significantly change after publications showing better prognosis.

The association of congenital heart disease with necrotizing enterocolitis in preterm infants: a birth cohort study.

OBJECTIVE: To test the hypothesis that congenital heart disease (CHD) in preterm infants with severe CHD (cyanotic or left-sided obstructive lesions, or congestive heart failure) is independently associated with necrotizing enterocolitis (NEC, stage II or greater). STUDY DESIGN: Single-institution retrospective birth cohort of preterm infants with gestational age 23(0/7) to 34(6/7) weeks delivered between 1 January 2002 and 31 December 2011, excluding infants who received comfort care. Patients were classified into severe CHD, mild CHD and control groups. RESULTS: Among 4678 infants, 170 (3.6%) had CHD and 118 (2.5%) developed NEC. The risk for NEC increased with severe CHD (adjusted relative risk (RR)=3.72; 95% confidence interval (CI)=1.37 to 10.10) but not with mild CHD (RR=0.65; CI=0.27 to 1.55). CONCLUSION: In this cohort, severe but not mild CHD was independently associated with increased risk for NEC. This finding, if confirmed by other studies, may help identify patients at risk for NEC.

Hypomagnesemia secondary to cerebrospinal fluid losses in a patient with congenital hydrocephalus.

We describe a newborn infant with massive congenital hydrocephalus, presenting with hypomagnesemia secondary to magnesium losses through cerebrospinal fluid (CSF) aspirations. Hypomagnesemia due to CSF losses has not been described in pediatric literature.

Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding.

OBJECTIVE: The objective of this prospective, observational study was to test the hypothesis that tissue oxygenation in the splanchnic bed compared with tissue oxygenation in the cerebral circulation changes after feeding in preterm neonates who are tolerating full bolus orogastric feeds. STUDY DESIGN: Clinically stable premature neonates with postmenstrual age between 32 and 35(6/7) weeks who were tolerating full bolus feedings were studied before feeding and 1 h after feeding using near-infrared spectroscopy. The ratio of oxygenated to reduced hemoglobin (tissue oxygenation index, TOI) in the splanchnic circulation bed was divided by the TOI in the cerebral circulation, thereby yielding the cerebro-splanchnic oxygenation ratio (CSOR). We compared TOI and CSOR before and after feeding. As the changes in TOI and CSOR had non-Gaussian distribution, nonparametric statistics were used. RESULT: Among 32 infants, CSOR increased significantly after feeding (median difference 0.08; range -0.48, +0.58; P=0.011), whereas pulse oximetry did not change significantly (P=0.600). The change in CSOR with feeding was associated with a significant increase in splanchnic TOI (preprandial median 43.8, range 25.2-68.4 vs postprandial 47.5, range 25.8-70.8; P=0.013), without any significant change in brain TOI (preprandial median 64.9, range 44.5-75.4 vs postprandial 58.9, range 42.2-72.3; P=0.153). CONCLUSION: This study indicates that CSOR and splanchnic TOI, but not brain TOI, increase significantly after feeding in stable preterm infants who are tolerating full orogastric feeds.

Diuretics for respiratory distress syndrome in preterm infants.

BACKGROUND: Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. OBJECTIVES: The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) were searched using the following keywords: and . These searches were updated in April 2003 and March 2007. In addition, the abstract books of the American Thoracic Society and Society for Pediatric Research were searched. A MEDLINE and CENTRAL search was conducted in March 2007 using the keyword "Respiratory Distress Syndrome" alone, to make sure to find studies medications recently classified as diuretics, such as theophylline. SELECTION CRITERIA: Trials were included in which preterm infants with RDS and less than 5 days of age were randomly allocated to diuretic administration. Of those trials, studies were only included in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postmenstrual age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: The standard method for the Cochrane Collaboration, which is described in the Cochrane Collaboration Handbook, was used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven studies met inclusion criteria. Six studies using furosemide were done before the current era of prenatal steroids, surfactant and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. In one recent study, theophylline had no long-term benefits. Theophylline significantly decreased the risk of oligoanuria and transiently increased renal function, but did not significantly affect renal function at discharge or other outcomes. AUTHORS' CONCLUSIONS: There are no data to support routine administration of furosemide in preterm infants with RDS. Elective administration of furosemide to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia or developing a symptomatic patent ductus arteriosus. There are not enough data to support routine administration of low-dose theophylline in preterm infants with RDS.

Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates.

BACKGROUND: L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity, and acidifies the solution, thereby increasing calcium and phosphate solubility, and potentially improving bone mineralization. OBJECTIVES: To determine the effects of supplementing parenteral nutrition with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE (1966-December 2005), EMBASE (1974-December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and recent abstracts (until December 2005) from the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were searched. SELECTION CRITERIA: All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed. Predetermined outcome variables included growth, nitrogen retention, mortality, morbidity secondary to oxidation injury, bone accretion, acidosis, liver disease, and cysteine levels. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD). MAIN RESULTS: Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (< or = 1000 grams). PRIMARY OUTCOMES: Growth was not significantly affected by cysteine supplementation (evaluated in one quasi-randomized trial) or by N-acetylcysteine supplementation (evaluated in one RCT). Nitrogen retention was significantly increased by cysteine supplementation (studied in four trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants). SECONDARY OUTCOMES: Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH. No data were available on other outcomes. AUTHORS' CONCLUSIONS: Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance.However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants. A large RCT would be required to assess whether routine prolonged cysteine supplementation of cysteine-free PN affects growth and short and long-term neonatal outcomes in very low birth weight infants.

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: { or } and , limited to and limited to or . We searched MEDLINE (1966 - 1998), EMBASE (1974 - 1998) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006). In addition, we hand searched several abstract books of national and international American and European Societies. The search of MEDLINE and of CENTRAL was last updated in March 2006. SELECTION CRITERIA: For the purpose of this analysis, we included trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included need for ventilator support, chronic lung disease, mortality and other important clinical outcomes. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies that met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. AUTHORS' CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Frequency analysis of air and skin temperature in neonates in servo-controlled incubators.

OBJECTIVE: To test a new system designed for digital recording of skin and air temperature, thereby allowing analysis of cyclic changes in temperature in neonates in servo-controlled incubators. METHODS: Analysis of cyclic changes of serial skin and air temperature in asymptomatic infants in servo-controlled incubators adjusting heat output to the patient's temperature. RESULTS: In nine asymptomatic neonates ranging from 25 to 40 weeks of gestational age, analysis showed peaks of coherence (squared correlation) between skin and air temperature measurements at periods ranging between 1.5 and 3 h. CONCLUSION: We have established a new system to study cyclic changes in skin and air temperature in neonates in servo-controlled incubators. The analysis of this pilot study suggests that the most important changes in skin and air temperature in asymptomatic neonates occur at a periodicity of 1.5 to 3 h, which is similar to that previously described for neonatal temperature. Additional data are required to determine whether this new system may be useful in neonatal care.

Diffuse basal ganglia or thalamus hyperechogenicity in preterm infants.

OBJECTIVE: To determine the incidence and factors associated with diffuse basal ganglia or thalamus hyperechogenicity (BGTH) in preterm infants. STUDY DESIGN: (1) Review of serial neurosonograms among neonates with gestational age (GA) <34 weeks born at Weiler Hospital during a 21-month period; (2) Color Doppler flow imaging; (3) Case-control study using GA group-matched controls; and (4) Blind reading of CT scans or MRIs in patients with BGTH. RESULTS: Among 289 infants, 24 (8.3%) had diffuse BGTH. Color Doppler flow imaging was normal in nine patients. The incidence of diffuse BGTH was inversely related to GA (P<0.01). Logistic regression (n=96) showed that diffuse BGTH was significantly associated with requirement of high-frequency oscillation (HFO) (P=0.031), severe intraventricular hemorrhage (IVH) (P=0.004), hypotension requiring vasopressors (P=0.040), hypoglycemia (P=0.031) and male gender (P=0.014). Most patients with diffuse BGTH had normal basal ganglia and thalamus on CT/MRI, one had a hemorrhage, and one had an ischemic infarction. CONCLUSIONS: In our series, diffuse BGTH occurred in 8.3%, and was associated with factors similar to those previously reported. In contrast, several series have reported almost exclusively linear or punctuate hyperechoic foci, corresponding to hyperechogenicity of the lenticulostriate vessels. Our data provide further evidence to suggest that diffuse BGTH and hyperechogenicity of the lenticulostriate vessels are two different entities. Additional studies are required to determine the long-term significance of diffuse BGTH.

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants.

BACKGROUND: Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in side effects. OBJECTIVES: The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants. SEARCH STRATEGY: We searched MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library, 2003, Issue 1, and personal files for clinical trials assessing vitamin E in preterm infants. SELECTION CRITERIA: We selected trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly increased hemoglobin concentration by a small amount. Vitamin E significantly reduced the risk of germinal matrix/intraventricular hemorrhage and increased the risk of sepsis; however, heterogeneity limits the strength of these latter two inferences. Vitamin E did not significantly affect other morbidity or mortality. In VLBW infants, vitamin E supplementation significantly increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses showed (1) an association between intravenous, high-dose vitamin E supplementation and increased risk of sepsis and of parenchymal cerebral hemorrhage; (2) an association between vitamin E supplementation by other than the intravenous route and reduced risk of germinal matrix-intraventricular hemorrhage and of severe intraventricular hemorrhage; and (3) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined. REVIEWER'S CONCLUSIONS: Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants.

BACKGROUND: Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in side effects. OBJECTIVES: The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants. SEARCH STRATEGY: We searched MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library, 2003, Issue 1, and personal files for clinical trials assessing vitamin E in preterm infants. SELECTION CRITERIA: We selected trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly reduced the risk of germinal/intraventricular hemorrhage (typical relative risk [RR] 0.85, 95% confidence interval [CI] 0.73, 0.99), increased the risk of sepsis (typical RR 1.52, CI 1.13, 2.04) and increased hemoglobin concentration by a small amount, but did not significantly affect mortality and other morbidity. In VLBW infants, vitamin E supplementation increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses in VLBW infants showed (1) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined; and (2) an association between intravenous, high-dose administration of vitamin E and increased risk of sepsis. REVIEWER'S CONCLUSIONS: Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.

Successful perinatal management of hydrops fetalis due to hemolytic disease associated with D-- maternal phenotype.

We report the successful management of a case of hemolytic disease and hydrops fetalis secondary to anti Rh 17 antibodies in a woman with the rare D-- phenotype. We discuss the efficacy of intravenous immunoglobulins in treating hemolytic disease of the newborn infant.

Dopamine versus no treatment to prevent renal dysfunction in indomethacin-treated preterm newborn infants.

BACKGROUND: Indomethacin therapy for closure of patent ductus arteriosus frequently causes oliguria, and occasionally more serious renal dysfunction. Low dose dopamine has been suggested as a means for preventing this side effect. PRIMARY OBJECTIVE: To determine whether dopamine therapy may prevent indomethacin-mediated deterioration in renal function in the preterm newborn infant without serious adverse effects. SECONDARY OBJECTIVE: To assess the effects of dopamine on the above variables in two subgroups: (1) patients given indomethacin as prophylaxis of intraventricular hemorrhage, and (2) patients given indomethacin as treatment of patent ductus arteriosus SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group (CNRG) were used. We searched MEDLINE (1966-2001) using PubMed as the search engine, EMBASE (1974-2001) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (Issue 3, 2001). In addition we contacted the principal investigators if necessary to ascertain the required information. SELECTION CRITERIA: Randomized or quasi-randomized studies of the effects of dopamine on urine output, glomerular filtration rate, fluid balance or incidence of renal failure, in preterm newborn infants receiving indomethacin. The comparison group should have received no dopamine. DATA COLLECTION AND ANALYSIS: We used the standard methods of the Cochrane Collaboration and those of the CNRG. The primary outcomes of interest were: mortality before discharge; intraventricular hemorrhage, grade three or four; cystic periventricular leukomalacia; renal failure (either oliguria, defined as a urine output less than 1 ml/kg/hour or an elevation in creatinine by more than 40 micromoles/L); failure to close the ductus arteriosus; need for surgical PDA ligation. For categorical outcomes, we calculated typical estimates for relative risk and risk difference. For continuous outcomes the weighted mean difference (WMD) was calculated. Fixed effect models were assumed for meta-analysis. MAIN RESULTS: Three studies were found (total number randomized patients, 75) which fulfilled the entry criteria for this review. All were single center trials which enrolled NICU patients receiving indomethacin for symptomatic patent ductus arteriosus. There are no (or only partial) results for effects of dopamine on several of the primary outcomes, including death before discharge, serious intraventricular hemorrhage, cystic periventricular leukomalacia, or renal failure. There has been inadequate investigation of the effects of dopamine on cerebral perfusion or cardiac output, or GI complications, or endocrine toxicity. Dopamine improved urine output [WMD 0.68 ml/kg/hour (95% CI 0.22, 1.44)], but there was no evidence of effect on serum creatinine (WMD 2.04 micromoles/liter, CI -17.90, 21.97) or the incidence of oliguria (urine output < 1 ml/kg/hour) (RR 0.73, CI 0.35, 1.54). There was no evidence of effect of dopamine on the frequency of failure to close the ductus arteriosus (RR 1.11, CI 0.56, 2.19). REVIEWER'S CONCLUSIONS: There is no evidence from randomized trials to support the use of dopamine to prevent renal dysfunction in indomethacin-treated preterm infants.