Impact of Refeeding Syndrome on the Short-Term Clinical Outcomes of Very-Premature Infants.

BACKGROUND: Refeeding syndrome (RFS) is a potentially life-threatening condition that can occur in preterm infants if nutritional support is initiated or increased after a period of starvation or malnutrition. OBJECTIVES: The current study aimed to examine the short-term clinical outcomes of RFS in preterm infants born at ≤32 weeks of gestation. METHODS: Infants with a gestational age of ≤32 weeks and a birth weight of <1500 g who were born and admitted to the level III neonatal intensive care unit and received parenteral nutrition upon admission were retrospectively evaluated. The modified log Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the outcomes of infants. RESULTS: In total, 760 infants met this study's inclusion criteria. Of them, 289 (38%) developed RFS. RFS was significantly associated with a composite outcome of mortality and intraventricular hemorrhage. Based on the multivariate Cox regression analysis adjusted for significant potential confounders, RFS was significantly associated with increased mortality risk, with a hazard ratio for death in infants with RFS being 1.74-fold higher compared to those without RFS. CONCLUSIONS: Preterm infants born at ≤32 weeks of gestation who develop RFS within the first week of life are at increased risk for both intraventricular hemorrhage and mortality. This study underscores the need for standardized clinical approaches for managing RFS in the neonatal intensive care unit to improve outcomes. Future research should establish a unified RFS definition and conduct clinical trials to optimize parenteral nutrition strategies for this vulnerable population.

Association of early dysglycemia with intraventricular hemorrhage and mortality in very low birth weight infants.

To investigate the combined effect of hyperglycemia and hypoglycemia on intraventricular hemorrhage (IVH) and mortality recognizing that previous research has predominantly focused on examining these conditions independently. This study included very preterm infants who were born at King Saud Medical City, a tertiary referral center, and admitted to a level 3 neonatal intensive care unit between January 2020 and January 2024. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber-White) were used to adjust for potential confounding factors. A total of 554 infants met the inclusion criteria. Hyperglycemia and/or hypoglycemia developed in 75.5% (418) patients within the first postnatal week. During the study period, IVH occurred in 28.5% (N = 158), and severe IVH occurred in 13% (72) infants. In addition, 13.7% (76) of infants died during the study period. The multivariate regression revealed an association between the isolated hyperglycemia, combined exposure of hypo- and hyperglycemia, and development of IVH (relative risk [RR], 2.10; 95% confidence interval [CI], 1.36, 3.25; RR, 2.33; 95% CI, 1.34, 4.06, respectively). Severe IVH was significantly associated with isolated hyperglycemia (adjusted relative risk [aRR], 2.46; 95% CI, 1.16, 5.23). Death was associated with combined hypo- and hyperglycemia (adjusted hazardous ratio [aHR], 3.19; 95% CI, 1.23, 8.26).Conclusion: Combined hyper- and hypoglycemia in the first week of life of premature babies increases the risk and severity of IVH and neonatal mortality.

SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants.

The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber−White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid−LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82). SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD) (aRR 0.61; 95% CI 0.46, 0.8) and higher rate of late-onset sepsis compared with intralipid (aRR 1.44; 95% CI 1.22−1.69). SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis­it is a double-edged sword.

Association between acute kidney injury and brain injury on term-equivalent age brain magnetic resonance imaging in very preterm infants.

BACKGROUND: This study aimed to investigate the relationship between acute kidney injury (AKI) in the first 2 weeks of life and brain injury on term-equivalent age magnetic resonance imaging in very preterm infants. METHODS: We included 116 infants with a birth weight of < 1500 g who were born at the King Saud Medical City at ≤ 32 gestational weeks. They were admitted to the neonatal intensive care unit and underwent term-equivalent age and pre-discharge brain magnetic resonance imaging. A negative binomial with generalized linear models and a robust variance estimator (Huber-White) was applied for univariate relative risk analysis. The Kidokoro score was then used to determine the effect of AKI on brain morphology and growth at term-equivalent age. RESULTS: Sixty-eight (64.2%) infants had developed an AKI in the first 2 weeks of life. AKI was significantly associated with cerebellum signal abnormalities, cerebellar volume reduction, and a high total cerebellum score (P = 0.04, P < 0.001, P < 0.001, respectively). CONCLUSIONS: AKI in the first 2 weeks of life is associated with brain insult, especially in the cerebellum. More well-designed studies are required to investigate the association and impact of AKI on the central nervous system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Intravenous Ceftazidime-Avibactam in Extremely Premature Neonates With Carbapenem-Resistant Enterobacteriaceae: Two Case Reports.

The increasing use of carbapenems has contributed to a notable distribution of carbapenem-resistant Enterobacteriaceae (CRE). Recently, the incidence of CRE-associated infections is increasing significantly in NICUs, which pose a grave challenge to clinical treatment. We report 2 cases of IV ceftazidimeavibactam use to treat CRE infections in extremely premature neonates. The first case was diagnosed with bacteraemia and meningitis and the second one was diagnosed with bacteraemia only. Due to the lack of neonatal-specific information for IV ceftazidime-avibactam, the usual pediatric dose (62.5 mg/kg/dose every 8 hours) was used in these patients. Clinical cure occurred in these 2 patients. Although blood cultures became sterile after starting ceftazidime-avibactam in the second case, the patient died, presumably owing to sepsis or various causes, such as prematurity and chronic lung disease. Large and randomized studies are necessary to ensure the safety and efficacy of IV ceftazidime-avibactam for the treatment of neonates with sepsis caused by multidrug resistant organisms.

Association between morphine exposure and impaired brain development on term-equivalent age brain magnetic resonance imaging in very preterm infants.

To investigate the relationship between morphine exposure in the first week of life and brain injury on term-equivalent age magnetic resonance imaging (MRI) in very preterm infants. A retrospective study included 106 infants with a birth weight of < 1500 g who were born at King Saud Medical City at ≤ 32 gestational weeks, were admitted to the neonatal intensive care unit, and underwent term-equivalent age or pre-discharge brain MRI. A univariate analysis in addition to modified log-Poisson regression with a robust variance estimator was applied, and the effect of early morphine exposure and cumulative dose in the first seven days on brain morphology and growth at term-equivalent age was determined using the Kidokoro score. Sixty-eight (64.2%) infants had received morphine in the first week of life (median cumulative dose: 1.68 mg/kg, interquartile range 0.48-2.52 mg/kg). Early initiation of morphine administration was significantly associated with high total white matter (adjusted relative risk [aRR] 1.32, 95% confidence interval [CI] 1.01-1.72) and cerebellum (aRR 1.36, 95% CI 1.03-1.81) scores and a small cerebellar volume (aRR 1.28, 95% CI 1.02-1.61). Morphine exposure in the first week of life was independently associated with white matter and cerebellar injury on term-equivalent age brain MRI in very preterm infants.

Relationship between intraventricular hemorrhage and acute kidney injury in premature infants and its effect on neonatal mortality.

Intraventricular hemorrhage (IVH) and acute kidney injury (AKI) are important neonatal morbidities in premature infants. This study aimed to investigate the relationship between IVH and AKI in premature infants and whether this association affects the incidence of neonatal mortality. Infants [gestational age (GA) ≤ 32 weeks; birth weight (BW) < 1500 g] were retrospectively evaluated in a large tertiary neonatal intensive care unit. Of 710 premature infants, 268 (37.7%) developed AKI. Infants with IVH were more likely to have AKI than those without IVH. Infants with severe IVH had a higher incidence of AKI than infants with mild IVH. Infants younger than 28 weeks with IVH were more likely to have AKI than those without IVH. An association between IVH grades and AKI stages was observed in the overall study population, in infants with GA < 28 weeks, and in infants with GA between 28 and 32 weeks. Mortality was increased 1.5 times in infants with IVH and AKI compared with that in infants with IVH but without AKI. Furthermore, mortality was increased in infants with IVH and AKI compared with infants without IVH or AKI. This study shows a direct relationship between the severity of IVH and the degree of AKI; both IVH and AKI increase the incidence of neonatal mortality.

Ivabradine Monotherapy for the Treatment of Congenital Junctional Ectopic Tachycardia in a Premature Neonate.

Congenital junctional ectopic tachycardia is a rare and special type of supraventricular arrhythmia. Junctional ectopic tachycardia is characterized by persistently elevated heart rates that may cause an impairment in cardiac function. Junctional ectopic tachycardia is considered one of the most difficult-to-treat conditions even with a combination of antiarrhythmic medications. Ivabradine is a novel antiarrhythmic medication used to decrease the heart rate in adults with angina pectoris. We report a first case of a premature neonate with a normal heart structure who developed junctional ectopic tachycardia and was subsequently treated successfully with ivabradine.

The Use of Daptomycin in the Treatment of Persistent Coagulase-Negative Staphylococcal Sepsis in Premature Infants: A Case Series.

OBJECTIVE: Daptomycin is a lipopeptide antibiotic with rapid bactericidal activity against Gram-positive bacteria. Reports regarding the use of daptomycin in infants are still limited. Thus, the objective of this report is to describe the safety and efficacy of daptomycin in premature infants with persistent coagulase-negative staphylococci (CoNS) infection. METHODS: This was a retrospective chart review of 10 premature infants with persistent CoNS infection who received daptomycin therapy between January 2018 and September 2019. Four patients had endocarditis and 1 had bacterial meningitis and infectious endocarditis. The other 5 patients had persistent CoNS bacteraemia only. RESULTS: Daptomycin treatment was successful for 5 patients. The others died owing to multiple factors such as prematurity, sepsis, and chronic lung disease. Adverse drug reactions, including elevation of creatine phosphokinase and/or hepatotoxicity, were noted in 4 patients. CONCLUSIONS: Large and randomized studies are necessary to ensure daptomycin's safety and efficacy for the treatment of infants with persistent sepsis caused by Gram-positive bacteria.

Retrospective study of short-term complications associated with early morphine use in intubated premature infants.

Relieving neonatal pain is essential for the management of premature infants. Morphine is the most frequently used analgesic in neonatal intensive care. Here we report the relationship between early morphine infusion and the composite outcome of intraventricular hemorrhage and/or death in intubated premature infants. Infants (gestational age ≤ 32 weeks and birth weight < 1,500 g) intubated on admission were retrospectively evaluated in a large tertiary neonatal intensive care unit. Modified log-Poisson regression with robust variance estimator and Cox regression was applied to adjust the relative risk for infants' outcomes. Of 420 premature infants, 230 (54.7%) received continuous morphine infusion in the first 72 h. Of these, 153 were < 28 gestational weeks; of the 190 patients who did not receive morphine, 63 were < 28 gestational weeks. The analysis revealed that infants < 28 gestational weeks who received morphine were significantly associated with an increased risk for IVH and/or death [adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.1-1.71)], and mortality (aRR 1.83, 95% CI 1.17-2.89). Moreover, in infants < 28 gestational weeks, survival was low in those infants who were exposed to morphine infusion in the first 72 h (hazard ratio 2.11; 95% CI 1.19-3.73). Early morphine infusion is associated with an increased risk for IVH and/or death; however, further studies are required to verify our findings.