Context: Lung ultrasonography (LUS) is increasingly used to identify various neonatal respiratory disorders. There is emerging evidence that it can identify infants with significant lung disease who need surfactant treatment or mechanical ventilation. Objective: To systematically review the accuracy of LUS in determining the need for surfactant treatment or mechanical ventilation in infants with respiratory distress treated with nasal continuous positive airway pressure (NCPAP). Methods: Database search include EMBASE, Medline, CINAHL and Cochrane central from inception until 17 October 2018. Included is diagnostic accuracy studies reporting LUS evaluating surfactant therapy/mechanical ventilation. Two authors extracted data independently and assessed quality. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to determine the methodological quality. Results: Six studies involving 485 infants included in the review. Three studies used LUS score, two used type 1 lung profile, and one used high-risk LUS to evaluate the outcome. The pooled sensitivity and specificity at LUS score cut-off >5–6 was 88% (95% CI 80% to 93%) and 82% (95% CI 74% to 89%), respectively. Infants with LUS score >5–6 were at significantly increased risk of surfactant treatment compared with infants with LUS score <5–6 (relative risk=7.51; 95% CI 4.16 to 13.58; two studies; participants=189; I²=0%). The diagnostic accuracy of type 1 lung profile was better in younger preterm infants (sensitivity 88.9%, specificity 100%) compared with late preterm and term infants (sensitivity 100%, specificity 28%). Conclusions: LUS, particularly LUS score, can be used accurately to determine the need for surfactant replacement treatment or mechanical ventilation in infants with respiratory distress treated with NCPAP support. The accuracy is better in younger preterm infants compared with late preterm and term infants. PROSPERO registration number: CRD42018115135.

Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are acquired brain injuries in neonates born before 37 weeks’ gestation. Severe IVH (sIVH), often referred to as IVH with ventricular distension or periventricular hemorrhagic infarction, occurs in 7.7% of very preterm infants (gestational age <32 weeks) and 16.2% of extremely preterm infants (gestational age <28 weeks).¹ Cystic PVL (cPVL), a type of brain injury characterized by necrosis of white matter near the lateral ventricles, occurs in 6.1% of extremely preterm infants.² Both sIVH and cPVL, which are collectively recognized as severe brain injury, are detrimental to long-term neurodevelopmental outcomes,³ and interventions to reduce their risk in preterm neonates are of utmost importance in neonatal medicine.

Background: Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods: Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results: Six RCTs (EPO=5 and darbepoetin α=1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47–1.19, LOE−low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49–1.32, LOE−low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27–0.80, LOE−moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28–0.85, LOE−moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53–0.92, LOE−moderate). Conclusion: EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation.

Prematurity and hypoxic-ischemic encephalopathy (HIE) represent critical concerns in neonatal health, posing significant risks to the well-being of newborns. Prematurity affects approximately 1 in 10 births globally,¹ whereas HIE affects 1.6 per 1000 live births in high-income countries and 12.1 per 1000 in low- or middle-income countries.² Interventions to mitigate the risk of morbidities linked to prematurity and HIE are limited,³ leaving affected infants at an elevated risk of neurodevelopmental complications that adversely affect motor skills and cognitive abilities. While various neurodevelopmental concerns exist, cognitive impairment and cerebral palsy stand out as primary concerns, affecting approximately 16.9% and 6.9% of very preterm infants, respectively.⁴ Early detection of these complications is recommended because prompt identification allows for timely intervention, promoting optimal motor and cognitive development in infants.⁵

Context: The association between small for gestational age (SGA) and retinopathy of prematurity (ROP) is unclear. Objective: A systematic review and meta-analysis was conducted to evaluate the association between ROP and SGA in preterm infants <37 weeks’ gestational age (GA) admitted to neonatal intensive care unit. Methods: Medline, PubMed, Web of Science and Cochrane Central databases were searched from inception through 15 January 2019. Studies reporting outcomes based on SGA as the primary exposure variable were included. Data were extracted independently by two coauthors. Modified Newcastle-Ottawa scale was used for risk of bias assessment. Results: Database search yielded 536 records (Medline=152, PubMed=171, Web of Science=144 and Cochrane Central=69). Twenty-one studies evaluating 190 946 infants were included. SGA was associated with significantly higher odds of any stage of ROP on unadjusted analysis (unadjusted OR (uOR) 1.55; 95% CI 1.22 to 1.98; 10 studies) but not on adjusted analysis (adjusted OR (aOR) 2.16; 95% CI 0.66 to 7.11; 3 studies). SGA was associated with significantly higher odds of severe ROP (aOR 1.92; 95% CI 1.57 to 2.34; nine studies). SGA was also significantly associated with higher odds of treated ROP (aOR 1.39; 95% CI 1.18 to 1.65; three studies). In subgroup analysis of infants <29 weeks’ GA, SGA was significantly associated with increased odds of ROP (uOR 1.64; 95% CI 1.19 to 2.26; two studies), severe ROP (aOR 1.61; 95% CI 1.23 to 2.10; four studies) and treated ROP (aOR 1.37; 95% CI 1.16 to 1.62; two studies). Conclusion: SGA was associated with increased odds of any stage of ROP, severe ROP and treated ROP in preterm infants. Neonatologists should incorporate SGA into the risk assessment during ROP evaluation and while providing counselling to the families of preterm SGA infants. ROP screening guidelines should look into the frequency of follow-up examination in SGA infants in aim to offer early detection and treatment.