Objective: Postnatal tissue accretion in preterm infants differs from those in utero, affecting body composition (BC) and lifelong morbidity. Length normalized BC data allows infants with different body lengths to be compared and followed longitudinally. This study aims to analyze BC of preterm and term infants during the first six months of life. Methods: The BC data, measured using dual energy X-ray absorptiometry, of 389 preterm and 132 term infants from four longitudinal studies were combined. Fat-mass/length² (FMI) and fat-free mass/length² (FFMI) for postmenstrual age were calculated after reaching full enteral feeding, at term and two further time points up to six months corrected age. Results: Median FMI (preterm) increased from 0.4 kg/m² at 30 weeks to 2.5, 4.3, and 4.8 kg/m² compared to 1.7, 4.7, and 6 kg/m² in term infants at 40, 52, and 64 weeks, respectively. Median FFMI (preterm) increased from 8.5 kg/m² (30 weeks) to 11.4 kg/m² (45 weeks) and remained constant thereafter, whereas term FFMI remained constant at 11 kg/m² throughout the tested time points. Conclusion: The study provides a large dataset of length normalized BC indices. Followed longitudinally, term and preterm infants differ considerably during early infancy in the pattern of change in FMI and FFMI for age.

Hypoxic-ischemic encephalopathy (HIE) is a manifestation of perinatal asphyxial insult that continues to evolve over days to weeks following the initial injury. Therapeutic hypothermia has demonstrated that a proportion of this secondary brain injury may indeed be preventable. However, therapeutic hypothermia has also altered the prognostic utility of many bedside tools that are commonly used as predictors of long-term neurodevelopmental outcome in HIE. Clinicians are often confronted with uncertainty when assessing the prognosis of infants with HIE. Improved understanding of the implications and limitations of individual investigations may inform clinical decisions and allow for timely intervention. This review summarizes the predictive value of currently available prognostic markers in HIE infants in the therapeutic hypothermia era, including clinical, biochemical, neurophysiological, physiological, and neuroimaging predictors. ^* These authors contributed equally to the manuscript.

Aim: Safe limits of arterial partial pressure of carbon dioxide (PaCO₂) and acidosis in premature infants are not well defined. Both respiratory and systemic illness along with center-specific ventilation strategies contribute to PaCO₂ fluctuations and acid–base imbalances during the critical time period of first 72 h of life. This study evaluated the association between early blood gas parameters and intraventricular hemorrhage (IVH) in preterm infants. Methods: This retrospective observational study included neonates with a gestational age (GA) of ≤29 wks, who had at least 7 blood gas analysis done within the first 72 h of life. By adjusting for known variables that predispose to IVH, multivariable logistic regression analysis was used to study the association of PaCO₂ and acid–base measures with the risk of IVH. Results: Between 2013–2016, among 272 neonates who met inclusion criteria and were assessed for IVH on cranial ultrasound within first week of life, 101 neonates [mean GA of 25 ± 1.5 wks] had IVH and 171 neonates [mean GA of 25 ± 1.6 wks] had normal scans. After adjustment for confounding variables, higher values of maximum lactate (OR = 1.18, 95% CI = 1.1–1.3, p < .0001) and maximum base deficit (OR = 1.19, 95% CI = 1.1–1.2, p < .0001) within 72 h of life increased the likelihood of any grade of IVH. However, time-weighted average PaCO₂, maximum and minimum PaCO₂ had no statistically significant effect on the risk of IVH. The relationship remained unchanged even when moderate–severe IVH was considered as the primary outcome. Conclusion: Severe metabolic acidosis rather than hypo/hypercapnia during the first 72 h of life was associated with higher odds of IVH in infants born at ≤29 wks of gestation. Future studies determining levels of PaCO₂ that is safe for premature brain would need to control for the metabolic component of acidosis.

Background: Continuous video electroencephalographic (EEG) (cvEEG) monitoring is emerging as the standard of care for diagnosis and management of neonatal seizures. However, cvEEG is labor-intensive and the need to initiate and interpret studies on a 24-hour basis is a major limitation. Purpose: This study aims at establishing consistency in monitoring of newborns admitted to 2 different neonatal intensive care units (NICUs) managed by the same neurocritical care team. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues, and identify amplitude-integrated EEG abnormalities. Guidelines, checklists, and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. A cohort of 100 infants with moderate to severe hypoxic-ischemic encephalopathy before and after the training program was compared. Results: During the study period, 192 cvEEGs were obtained. The time to initiate brain monitoring decreased by 31.5 hours posttraining; this, in turn, led to an increase in electrographic seizure detection (20% before vs 34% after), decrease in seizure clinical misdiagnosis (65% before and 36% after), and reduction in antiseizure medication burden. Implications for Practice: Training experienced NICU nurses to set up, start, and monitor cvEEGs can decrease the time to initiate cvEEGs, which may lead to better seizure diagnosis and management. Implications for Research: Further understanding of practice bundles for best supporting infants at risk and being treated for seizures needs to be evaluated for integration into practice. Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Background: Therapeutic hypothermia (TH) is a widely practiced neuroprotective strategy for neonates with hypoxic-ischemic encephalopathy. Induced hypothermia is associated with shivering, cold pain, agitation, and distress. Objective: This scoping review determines the breadth of research undertaken for pain and stress management in neonates undergoing hypothermia therapy, the pharmacokinetics of analgesic and sedative medications during hypothermia and the effect of such medication on short- and long-term neurological outcomes. Methods: We searched the following online databases namely, (i) MEDLINE, (ii) Web of Science, (iii) Cochrane Library, (iv) Scopus, (v) CINAHL, and (vi) EMBASE to identify published original articles between January 2005 and December 2022. We included only English full-text articles on neonates treated with TH and reported the sedation/analgesia strategy used. We excluded articles that reported TH on transport or extracorporeal membrane oxygenation, did not report the intervention strategies for sedation/analgesia, and reported hypoxic-ischemic encephalopathy in which hypothermia was not applied. Results: The eligible publications (n = 97) included cohort studies (n = 72), non-randomized experimental studies (n = 2), pharmacokinetic studies (n = 4), dose escalation feasibility trial (n = 1), cross-sectional surveys (n = 5), and randomized control trials (n = 13). Neonatal Pain, Agitation, and Sedation Scale (NPASS) is the most frequently used pain assessment tool in this cohort. The most frequently used pharmacological agents are opioids (Morphine, Fentanyl), benzodiazepine (Midazolam) and Alpha2 agonists (Dexmedetomidine). The proportion of neonates receiving routine sedation-analgesia during TH is center-specific and varies from 40–100% worldwide. TH alters most drugs’ metabolic rate and clearance, except for Midazolam. Dexmedetomidine has additional benefits of thermal tolerance, neuroprotection, faster recovery, and less likelihood of seizures. There is a wide inter-individual variability in serum drug levels due to the impact of temperature, end-organ dysfunction, postnatal age, and body weight on drug metabolism. Conclusions: No multidimensional pain scale has been tested for reliability and construct validity in hypothermic encephalopathic neonates. There is an increasing trend towards using routine sedation/analgesia during TH worldwide. Wide variability in the type of medication used, administration (bolus versus infusion), and dose ranges used emphasizes the urgent need for standardized practice recommendations and guidelines. There is insufficient data on the long-term neurological outcomes of exposure to these medications, adjusted for underlying brain injury and severity of encephalopathy. Future studies will need to develop framework tools to enable precise control of sedation/analgesia drug exposure customized to individual patient needs.

This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18–24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte–hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18–24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates [GA 25.8 (1.7) weeks, birthweight 885 (232) g], prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24–25 + 6 weeks, 26–27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI [OR 0.99 (95% CI 0.85–1.2)]. Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood.