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.

Gastroschisis Due to Maternal Exposure to Carbimazole in A Term Neonate.

Pregnant women with hyperthyroidism need careful management, which is due to the increased risk of maternal and fetal complications. However, safe and effective therapies for hyperthyroidism during pregnancy remain limited. Carbimazole is an anti-thyroid agent and has been used to treat hyperthyroidism. Gastroschisis is a congenital severe abdominal birth defect of the fetus but its etiology remains unclear. Here, we present a case of a female term neonate who developed gastroschisis after being exposed to carbimazole in uteroduring the first and half of the second trimester.

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.

Early initiation of broad-spectrum antibiotics in premature infants.

BACKGROUND: Neonatal sepsis remains one of the main reasons for mortality among premature infants, and the early initiation of empirical broad-spectrum antibiotics could increase the risk of complications, including late-onset sepsis. This study aimed to investigate the complications related to the use of empirical broad-spectrum antibiotics in the first week of life. METHODS: A retrospective study of 365 neonates with gestational age ≤32 weeks and birth weight <1500 g who survived and had no confirmed sepsis in the first week of life from July 2015 to June 2018 was performed in a large tertiary Neonatal Intensive Care Unit. The primary outcome of this study was the incidence of a composite outcome consisting of late-onset sepsis, necrotizing enterocolitis, and mortality. The secondary outcomes were the incidences of late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and infant mortality. RESULTS: Of the 365 premature infants, 75 (20.5%) received broad-spectrum antibiotics. Multivariate regression analysis revealed that administration of broad-spectrum antibiotics in infants was independently associated with adverse outcomes. The composite outcome (late-onset sepsis, necrotizing enterocolitis, and death) had an odds ratio of 3.03 with 95% confidence interval of 1.41-6.49. CONCLUSIONS: Administration of empirical broad-spectrum antibiotics in the first week of life is associated with severe adverse outcomes. Thus, the restricted use of broad-spectrum antibiotics in the first week of life is recommended.

High alanine aminotransaminase associated with daptomycin use in a premature infant.

Daptomycin is a cyclic lipopeptide antibiotic, a fermented product derived from Streptomyces roseosporus that is active against gram-positive bacteria. We report on a premature infant who developed hepatotoxicity as an adverse drug reaction after the administration of daptomycin 6 mg per kg per dose every 12 h. The patient had an unexpectedly sharp rise of alanine aminotransaminase, prothrombin time and international normalised ratio on the second day following daptomycin administration. This case illustrates a previously unrecognised adverse drug effect associated with daptomycin use in infants.

Safety and efficacy of colistin and fluoroquinolone in neonatal persistent late-onset sepsis.

Growing resistance of microorganisms to antibiotics for the treatment of late-onset sepsis (LOS) in premature infants has led physicians to use antibiotics that are not well studied in neonatal populations. We aimed to determine the efficacy and safety of colistin and fluoroquinolone for the treatment of persistent LOS. We retrospectively reviewed infants with gram-negative LOS, who received either colistin or fluoroquinolone therapy, to determine if there was a significant difference in kidney and liver function tests and electrolyte levels before, during, and at the end of the treatment. Infants who received colistin and fluoroquinolone had 17 and 34 positive cultures with gram-negative organisms, respectively. Multi-drug resistant organisms were more common in infants who received colistin than in those who received fluoroquinolone. Microbiological clearance was found to be higher in infants treated with fluoroquinolone than in those treated with colistin. In both the groups, the median levels of kidney and liver function tests and electrolytes showed a significant increase during the treatment. The prescription of colistin and fluoroquinolones should be reserved for cases with no other safe and effective alternatives.

Risk factors for intraventricular hemorrhage in premature infants in the central region of Saudi Arabia.

BACKGROUND: Intraventricular hemorrhage (IVH) is a serious complication of premature (<32 weeks) deliveries, especially in very-low-birth-weight (VLBW; <1500 g) neonates. Infants developing severe IVH are more prone to long-term developmental disabilities. Although 62%-79% of women in Saudi Arabia receive antenatal steroids, IVH incidence remains high. We analyzed the risk factors for IVH in preterm VLBW neonates in the central region of Saudi Arabia. METHODS: We included premature infants with IVH (n = 108) and gestational age- and birth weight-matched control group infants (n = 108) admitted to our neonatal intensive care unit. Cases were divided into mild (grades I and II; n = 56) and severe (grades III and IV; n = 52) IVH groups. Association of IVH with risk factors in the first week of life was investigated. RESULTS: The following risk factors were associated with severe IVH: lack of antenatal steroid administration (P < .001), pulmonary hemorrhage (P = .023), inotrope use (P = .032), neonatal hydrocortisone administration (P = .001), and patent ductus arteriosus (PDA) (P = .005). Multivariable logistic regression analysis revealed the following to be significant: lack of antenatal dexamethasone (adjusted odds ratio [aOR]: 0.219, 95% confidence interval [95% CI] 0.087-0.546), neonatal hydrocortisone administration (aOR: 3.519, 95% CI 1.204-10.281), and PDA (aOR: 2.718, 95% CI 1.024-7.210). Low hematocrit in the first 3 days of life was significantly associated with severe IVH (all P < .01). CONCLUSIONS: Failure to receive antenatal dexamethasone, PDA, hydrocortisone administration for neonatal hypotension, and low hematocrit in the first 3 days of life was associated with severe IVH in VLBW neonates. Clinicians and healthcare policy makers should consider these factors during decision-making.

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.

Safety and Efficacy of Daptomycin in Neonates with Coagulase-Negative Staphylococci: Case Series Analysis.

There has been an increase in the prevalence of gram-positive bacteremia in neonates in the last two decades. However, as a consequence of better care, there has been an increase in the survival of premature neonates. Coagulase-negative staphylococci (CoNS) is the most prevalent bacteria, responsible for up to 60% of late-onset sepsis (LOS). Daptomycin, a lipopeptide antimicrobial agent, is active against CoNS. This was an observational, retrospective case series study carried out in the Pediatric Hospital of King Saud Medical City, Riyadh, Saudi Arabia. The medical records of 21 neonates, aged 0-28 days, who were treated in Neonatal Intensive Care Unit (NICU) with intravenous daptomycin as monotherapy or combination therapy for at least 4 days for proven gram-positive infection between June 2019 to July 2020, were included. The median gestational and chronological age were 27 weeks and 5 days, respectively. The most frequent diagnosis in neonates was infective endocarditis (42.9%). Of the 21 patients who received daptomycin therapy, 13 (62%) recovered and 8 died. The clinical cure rate was higher in Staphylococcus hominis (100%) and in patients who received 6 mg/kg/dose twice daily (62.5%). The mean of aspartate aminotransferase significantly elevated after starting daptomycin (p = 0.048). However, no muscular or neurological toxicity of daptomycin was documented in any of the cases. Overall, daptomycin was well tolerated, even with long-term treatment.

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.

Antenatal care of mothers and morbidity and mortality disparities among preterm Saudi and non-Saudi infants less than or equal to 32 weeks' gestation.

BACKGROUND: Premature non-Saudi infants comprise a significant proportion of neonatal intensive care unit admissions in Saudi Arabia. Any differences in antenatal care of mothers and neonatal outcomes compared with premature Saudi infants are unreported. OBJECTIVE: Assess antenatal care of mothers and neonatal outcomes among premature Saudi and non-Saudi infants, and investigate possible reasons for disparities. DESIGN: Retrospective cohort study. SETTING: Tertiary care center in Riyadh. PATIENTS AND METHODS: All neonates of gestational age ≤32 weeks and birthweight <1500 g admitted from 2015 to 2019 were included. MAIN OUTCOME MEASURES: Antenatal care of mothers and rates of neonatal mortality and morbidity in premature Saudi and non-Saudi infants. SAMPLE SIZE: 755 premature infants, 437 (57.9%) Saudi, 318 (42.1%) non-Saudi. RESULTS: Saudi mothers received more antenatal steroids and were more likely to have gestational diabetes mellitus (P=.01 and .03, respectively). Non-Saudi mothers were more likely to have pregnancy-induced hypertension (P=.01). Non-Saudi infants had significantly higher rates of intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, bronchopulmonary dysplasia and necrotizing enterocolitis compared with Saudi infants (P=.03, <.001, .04, .002, and <.001, respectively). There were no significant differences in mortality rate, early-onset sepsis, and late-onset sepsis between Saudi and non-Saudi infants (P=.81, .81, and .12, respectively). CONCLUSIONS: Disparities exist in the antenatal care of Saudi and non-Saudi women and in the neonatal morbidities of their premature infants. There was no difference in the neonatal mortality rate. More quality improvement initiatives are required to reduce differences in antenatal and neonatal outcomes. LIMITATIONS: Retrospective, socioeconomic disparities not identified. CONFLICT OF INTEREST: None.

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.

A Neonatal Unit Experience with Empiric Antibiotics for Late-onset Neonatal Sepsis: A Retrospective Study.

Neonatal sepsis remains a major cause of morbidity and mortality and warrants the immediate start of appropriate empiric treatment. Thus, this study compared the effectiveness of the 2 antibiotic regimens (cloxacillin-amikacin or cefotaxime-ampicillin) among neonates with late-onset neonatal sepsis. METHODS: We conducted a retrospective cohort study comparing mortality between 2 treatment cohorts of very low birth weight neonates with late-onset sepsis, who had received amikacin-cloxacillin or cefotaxime-ampicillin between January 2014 and December 2017. There were 27 neonates in each treatment arm after 1:1 propensity score matching. Univariate analyses (Chi-square and independent t tests, where appropriate) were performed to determine the association between variables. We determined the hazard ratio for all-cause mortality using the Cox regression model. RESULTS: We identified a total of 132 neonates from the hospital's record. We included 27 neonates each in the amikacin-cloxacillin and cefotaxime-ampicillin groups. Intraventricular hemorrhage, necrotizing enterocolitis, birth weight, and gestational age were significantly associated with mortality (P < 0.05). The risk of mortality was significantly higher in neonates receiving empiric cefotaxime and ampicillin than those receiving amikacin and cloxacillin (hazard ratio: 2.91, 95% confidence interval: 1.17-7.30, P = 0.023). CONCLUSIONS: In our center, amikacin-cloxacillin combination therapy was associated with lower mortality in very low birth weight neonates with late-onset sepsis compared with cefotaxime-ampicillin therapy.

The consequences of prolonged duration of antibiotics in premature infants with suspected sepsis in a large tertiary referral hospital: a retrospective cohort study.

OBJECTIVE: To assess whether there is any association between prolonged duration of the first course of empirical antibiotic treatment for suspected neonatal sepsis and other factors including comorbidities, interventions, and adverse outcomes. BACKGROUND: Neonatal sepsis is one of the main reasons of mortality among premature infants in Neonatal Intensive Care Unit (NICU). Therefore, commencing antibiotics treatment on admission plays a crucial role in reducing the complications of neonatal sepsis, however the arbitrary use of antibiotics holds many serious complications. In our study we investigated the complications of prolonged use of antibiotics in treating suspected early onset of sepsis. STUDY DESIGN: This is a retrospective cohort study of infants of gestational age 32 weeks or less and with birth weight of 1500 g or less along with suspected neonatal sepsis admitted to our neonatal intensive care unit from July 2015 to June 2017. The study outcome measures were the association between the antibiotic treatment duration and maternal factors, gender, adverse outcomes, developmental factors, comorbid conditions, early-onset sepsis, and late-onset sepsis. RESULTS: Of 295 premature infants, late-onset sepsis was associated with the duration of early empiric antibiotic use (n = 54/295), where 50 (92.6%) infants with LOS received the antibiotic treatment for more than 5 days (P < .001). Approximately 91.2% of those receiving the prolonged treatment had a positive blood culture result. Necrotizing enterocolitis was more prevalent in those with long duration of antibiotic treatment (95.1%). Among patients with the comorbid conditions patent ductus arteriosus (n = 123/295), intraventricular hemorrhage (n = 73/295), and periventricular leukomalacia (n = 25/295), 100 (81.3%), 60 (82.2%), and 21 (84%) of them, respectively, received prolonged treatment. CONCLUSION: Prolonged administration of empiric antibiotics to infants with very low birth weight along with sterile cultures is associated with the adverse outcomes late-onset sepsis and necrotizing enterocolitis. However, no association with other adverse outcomes, namely, candidiasis or maternal factors, was found.

A New IVH Scoring System Based on Laterality Enhances Prediction of Neurodevelopmental Outcomes at 3 Years Age in Premature Infants.

Objective To compare the new intraventricular hemorrhage (IVH) Abdi score to the Papile grading system of IVH for prediction of composite outcome of death or neurodevelopmental impairment (NDI). Methods In a cohort study, all preterm infants with IVH who were born ≤1,250 g and/or ≤ 28 weeks of gestation at birth were prospectively followed up in our neonatal follow-up clinic. All cranial ultrasounds of the included infants were reviewed by neuroradiologists who were blinded to the clinical data and neurodevelopmental outcomes. Cranial ultrasounds were graded according to the Papile scoring system and by calculation of the Abdi score. Results A total of 183 preterm infants met inclusion and exclusion criteria. Of these, 80 (44%) had the composite primary outcome of death or NDI (51 died, 29 survived with NDI). The area under receiver operating characteristic curve for predicting death or NDI was 0.87 (95% confidence interval [CI]: 0.81-0.93) for Abdi score and 0.85 (95% CI: 0.79-0.91) for Papile grading (p = 0.04). Abdi scores had higher specificity than Papile grade II at Abdi score 5 (63.9 vs. 39.2%; p < 0.001) and Abdi score 6 (73.2 vs. 39.2%; p < 0.001). Conclusion Abdi scores seem to be more specific than Papile grading system in predicting death or NDI by 3 years' corrected age.