Background and Objective: The effects of neonatal hypoglycemia on the developing brain are well known, resulting in poor neurological outcomes. We aimed to perform an updated meta-analysis on neonatal hypoglycemia, the severity of hypoglycemia, and the associated neurodevelopmental outcomes from infancy to adulthood. Methods: A systematic literature search was conducted from inception until March 2024, using the PubMed, CINAHL, Embase, and the CENTRAL databases. Randomized/quasi-randomized trials and observational studies that evaluated at least one of the pre-specified outcomes were included. A random-effects model meta-analysis was performed to yield the pooled OR and its 95% CI for each outcome due to the expected heterogeneity in the studies. The study findings were reported as per the PRISMA guidelines. Neurodevelopmental impairment (NDI), cognitive impairment, and visual-motor or visual impairment were the primary outcomes. Results: A total of 17 studies (19 publications) were included in the final analysis. NDI, as defined by authors, was significantly higher in early- (OR = 1.16; 95% CI = 1.11–1.43) and mid-childhood (OR = 3.67; 95%CI = 1.07–12.2) in infants with neonatal hypoglycemia. ‘Any cognitive impairment’ was significantly more common in infants with neonatal hypoglycemia (OR = 2.12; 95%CI = 1.79–2.52). Visual-motor impairment (OR = 3.33; 95%CI = 1.14–9.72) and executive dysfunction (OR = 1.99; 95%CI = 1.36–2.91) were also more common in the hypoglycemic group. No difference in the incidence of epilepsy, motor impairment, emotional-behavioral problems, or hearing impairment were noted. Certainty of evidence was adjudged as ‘low’ to ‘very low’ for most outcomes. The severity of hypoglycemia was studied at different intervals, with NDI more common with a blood glucose interval between 20 and 34 mg/dL (1.1–1.9 mmol/L). Conclusions: Low-quality evidence from large observational studies finds a significant association with hypoglycemia in the early neonatal period and long-term neurodevelopmental problems. Additional studies with long enough follow-up are paramount to determine the cut-off concentration and to quantify the impact beyond the infancy period.

Neonatal shock presents a complex clinical challenge and is one of the leading causes of mortality. Traditionally, neonatal shock is equated to hypotension, and therapeutics are often initiated based on low blood pressure (BP) values alone. This fails to address the underlying goal of optimizing the tissue perfusion resulting in both over- and under-treatment of neonatal shock. Also, what defines a normal BP in neonates is still a contentious topic. Further, the most appropriate way of measuring BP in neonates with shock is still debated. Shock secondary to transient circulatory instability and patent ductus arteriosus, conditions that are unique to preterm neonates, have not been researched adequately. Treatment of myocardial dysfunction secondary to perinatal asphyxia, a leading cause of neonatal mortality, is still a conundrum. Quite similarly, there are only a handful of controlled trials evaluating therapeutics in some of the other commonly encountered conditions, namely, septic shock and hypoperfusion secondary to pulmonary hypertension. Even the universally practiced intervention of volume expansion with crystalloid boluses in shock is not backed by high-certainty evidence in neonates. Though the diagnostic modalities of functional echocardiography and near-infrared spectroscopy have aided greatly in the management of neonatal shock in recent years, these have not been proven to be associated with improved critical clinical outcomes such as mortality and major brain injury. To conclude, neonatologists often rely on limited evidence, mostly anecdotal, when treating neonatal shock. This review critically examines the current evidence with respect to various aspects of neonatal shock with an objective to identify the lacunae in the literature that may fuel future research, eventually paving the way to efficacious, safe and evidence-based clinical practice.

Background: The role of less invasive surfactant administration (LISA) using a thin catheter in the management of meconium aspiration syndrome (MAS) is unclear. Study design: A retrospective study of infants with MAS admitted between January 2016 and December 2023. Relevant characteristics and outcomes were compared between a group of infants receiving surfactant in conjunction with mechanical ventilation (MV) via an endotracheal tube (ETT-surf) and receiving LISA. Infants intubated at birth were excluded. Results: Of the 113 infants admitted on continuous positive airway pressure (CPAP), 61 did not receive surfactant, 26 belonged to the ETT-surf group and 26 to the LISA group. Compared with the ETT-surf, a higher proportion of infants in the LISA group were exposed to chorioamnionitis and received a lower median fraction of inspired oxygen at birth and before surfactant therapy. Notably, infants in the LISA group had a lower need for MV (100 vs 23%, p<0.001), inhaled nitric oxide (iNO) (46% vs 12%, p=0.01) and a shorter median duration of hospital stay (14 vs 24 days, p=0.04). A subgroup analysis of infants with hypoxic respiratory failure on admission showed lower need for MV and duration of hospital stay with the LISA group compared with the ETT-surf group. Conclusions: LISA was associated with a lower need for MV, iNO and a shorter duration of hospital stay in a select group of infants with MAS. Further prospective studies are necessary to evaluate the role of LISA in MAS.

Background: In October 2018, a respiratory care protocol (RCP) including less invasive surfactant administration (LISA), was introduced for preterm infants admitted on continuous positive airway pressure (CPAP). Study Design: We compared respiratory care practices and outcomes of ≥ 35‐week gestational age (GA) infants between a pre‐RCP (Jan 2016 to September 2018) and a post‐RCP cohort (Oct 2018 to Dec 2021). Infants requiring < 24 h of CPAP and diagnosed with meconium aspiration syndrome were excluded. Results: Of the 260 infants meeting inclusion criteria, 126 belonged to the pre‐RCP and 134 to post‐RCP cohort. Compared to pre‐RCP, a lower proportion of infants in the post‐RCP received CPAP on admission but a higher proportion received surfactant therapy (8% vs 22%, p < 0.001). Notably, surfactant therapy was associated with lower FiO ₂ requirement for 24 h and respiratory severity score for 48 h in the post‐RCP cohort. However, there was no difference in any of the outcomes such as the need for mechanical ventilation, incidence of pneumothorax and length of hospital stay between two cohorts. Conclusions: Implementing an RCP increased surfactant use with associated improvement in oxygenation but did not improve outcomes. Further studies are necessary to evaluate the role of LISA in ≥ 35‐week GA infants.

Background: Neonatal myocytes rely predominantly on glycolytic metabolism for survival during hypoxic conditions. During asphyxia, metabolic pathway dysregulation impairs cardiac myocyte contractility. Co-administration of dextrose and insulin may help restore metabolic homeostasis and improve cardiac function. Methods: Following blinded randomization and instrumentation, near-term lambs (138–140 days gestational age) were asphyxiated by umbilical cord occlusion until complete cardiac arrest, followed by 7 min of continued arrest to model severe asphyxia. Return of spontaneous circulation (ROSC) was defined as heart rate ≥ 100 beats per minute (bpm) and diastolic blood pressure ≥ 20 mmHg. Results: The incidence of ROSC was 3/6 in the control group compared to 5/5 in the experimental group receiving dextrose–insulin therapy, although this difference did not reach statistical significance. Conclusions: In this proof-of-concept study using a near-term ovine model of prolonged asphyxial cardiac arrest, dextrose and insulin co-administered with epinephrine were associated with improved ROSC rates although could be an association. Larger studies are needed to confirm these findings and evaluate clinical translation

Background Magnesium sulphate is widely used in antenatal mothers for various indications such as neuroprotection, tocolysis and preeclampsia. Some studies suggest that there is alteration in intestinal motility and blood flow in preterm neonates as a result of exposure to Magnesium sulphate. Objective To evaluate the effect of antenatal magnesium Sulphate (MgSO ₄ ) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants. Search strategy PubMed, CINAHL, Embase, and CENTRAL were searched through up to November 2022. Data collection and Analysis Two authors independently conducted data extraction. A random-effects model meta-analysis was performed. All included studies were assessed for methodological quality using appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence. Main Results A total of thirty-eight observational and six RCTs involving 51,466 preterm infants were included. There were no increased odds of stage ≥2 NEC, (n= 50,727, OR:1.0; 95% CI: 0.89-1.12, I ² - 7%), SIP ( n= 34,186, OR: 1.22, 95% CI: 0.94-1.58, I ² -30% ), feed intolerance (n= 414, OR: 1.06, 95% CI: 0.64-1.76, I ² -12%) in infants exposed to antenatal MgSO ₄ . On the contrary, the incidence of surgical NEC was significantly lower in MgSO ₄ exposure infants (n= 29,506 OR:0.74; 95% CI: 0.62-0.90, ARR: 0.47%). Studies assessing the effect on GI-related mortality were sparse to make any conceivable conclusion. GRADE certainty of findings were ‘very low’. Conclusion Antenatal MgSO ₄ did not increase the incidence of gastrointestinal-related morbidities or mortality in preterm infants.