Evaluation of the effect of intraventricular haemorrhage on cerebral perfusion in preterm neonates using three-dimensional pseudo-continuous arterial spin labelling.

BACKGROUND: Intraventricular haemorrhage (IVH) often arises as a cerebral complication directly related to preterm birth. The impaired autoregulation of cerebral blood flow is closely associated with IVH in preterm neonates. Three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) is a noninvasive magnetic resonance imaging (MRI) technique used for evaluating cerebral perfusion. OBJECTIVE: This study aimed to compare cerebral blood flow values among three distinct groups using 3D-pCASL: preterm neonates with and without IVH and preterm neonates at term-equivalent age. MATERIALS AND METHODS: A total of 101 preterm neonates who underwent conventional MRI and 3D-pCASL were included in this study. These neonates were categorised into three groups: 12 preterm neonates with IVH, 52 preterm neonates without IVH, and 37 healthy neonates at term-equivalent age. Cerebral blood flow measurements were obtained from six brain regions of interest (ROIs)-the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus-in the right and left hemispheres. RESULTS: The cerebral blood flow values measured in all ROIs of preterm neonates with IVH were significantly lower than those of neonates at term-equivalent age (all P<0.05). Additionally, the cerebral blood flow in the temporal lobe was lower in preterm neonates without IVH than in neonates at term-equivalent age (16.87±5.01 vs. 19.76±5.47 ml/100 g/min, P=0.012). Furthermore, a noteworthy positive correlation was observed between post-menstrual age and cerebral blood flow in the temporal lobe (P=0.037), basal ganglia (P=0.010), and thalamus (P=0.010). CONCLUSION: The quantitative cerebral blood flow values, as measured by 3D-pCASL, highlighted that preterm neonates with IVH had decreased cerebral perfusion. This finding underscores the potential of 3D-pCASL as a technique for evaluating the developmental aspects of the brain in preterm neonates.

Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

A neonatal neuroNICU collaborative approach to neuromonitoring of posthemorrhagic ventricular dilation in preterm infants.

Morbidity and mortality in prematurely born infants have significantly improved due to advancement in perinatal care, development of NeuroNICU collaborative multidisciplinary approaches, and evidence-based management protocols that have resulted from a better understanding of perinatal risk factors and neuroprotective treatments. In premature infants with intraventricular hemorrhage (IVH), the detrimental secondary effect of posthemorrhagic ventricular dilation (PHVD) on the neurodevelopmental outcome can be mitigated by surgical intervention, though management varies considerably across institutions. Any benefit derived from the use of neuromonitoring to optimize surgical timing and technique stands to improve neurodevelopmental outcome. In this review, we summarize (1) the approaches to surgical management of PHVD in preterm infants and outcome data; (2) neuromonitoring modalities and the effect of neurosurgical intervention on this data; (3) our resultant protocol for the monitoring and management of PHVD. In particular, our protocol incorporates cerebral near-infrared spectroscopy (NIRS) and transcranial doppler ultrasound (TCD) to better understand cerebral physiology and to enable the hypothesis-driven study of the management of PHVD. IMPACT: Review of the published literature concerning the use of near-infrared spectroscopy (NIRS) and a cerebral Doppler ultrasound to study the effect of cerebrospinal fluid drainage on infants with posthemorrhagic ventricular dilation. Presentation of our institution's evidence-based protocol for the use of NIRS and cerebral Doppler ultrasound to study the optimal neurosurgical treatment of posthemorrhagic ventricular dilation, an as yet inadequately studied area.

Late Pre-term Infants with Severe Bronchiolitis and Risk of Asthma by Age 5 Years.

In a prospective, multicenter cohort of infants hospitalized with bronchiolitis, we found infants born late pre-term (ie, gestational age of 34-36.9 weeks) had 35% higher odds of having asthma by age 5 years compared with infants born at full-term.

Hourly Kinetics of Critical Organ Dysfunction in Extremely Preterm Infants.

Rationale: Use of severity of illness scores to classify patients for clinical care and research is common outside of the neonatal ICU. Extremely premature (<29 weeks' gestation) infants with extremely low birth weight (<1,000 g) experience significant mortality and develop severe pathology during the protracted birth hospitalization. Objectives: To measure at high resolution the changes in organ dysfunction that occur from birth to death or discharge home by gestational age and time, and among extremely preterm infants with and without clinically meaningful outcomes using the neonatal sequential organ failure assessment score. Methods: A single-center, retrospective, observational cohort study of inborn, extremely preterm infants with extremely low birth weight admitted between January 2012 and January 2020. Neonatal sequential organ failure assessment scores were calculated every hour for every patient from admission until death or discharge. Measurements and Main Results: Longitudinal, granular scores from 436 infants demonstrated early and sustained discrimination of those who died versus those who survived to discharge. The discrimination for mortality by the maximum score was excellent (area under curve, 0.91; 95% confidence intervals, 0.88-0.94). Among survivors with and without adverse outcomes, most score variation occurred at the patient level. The weekly average score over the first 28 days was associated with the sum of adverse outcomes at discharge. Conclusions: The neonatal sequential organ failure assessment score discriminates between survival and nonsurvival on the first day of life. The major contributor to score variation occurred at the patient level. There was a direct association between scores and major adverse outcomes, including death.

Behavioral and brain morphological analysis of non-inflammatory and inflammatory rat models of preterm brain injury.

Investigations using preclinical models of preterm birth have much contributed, together with human neuropathological studies, for advances in our understanding of preterm brain injury. Here, we evaluated whether the neurodevelopmental and behavioral consequences of preterm birth induced by a non-inflammatory model of preterm birth using mifepristone would differ from those after inflammatory prenatal transient hypoxia-ischemia (TSHI) model. Pregnant Wistar rats were either injected with mifepristone, and pups were delivered on embryonic day 21 (ED21 group), or laparotomized on the 18th day of gestation for 60 min of uterine arteries occlusion. Rat pups were tested postnatally for characterization of developmental milestones and, after weaning, they were behaviorally tested for anxiety and for spatial learning and memory. One month later, brains were processed for quantification of doublecortin (DCX)- and neuropeptide Y (NPY)-immunoreactive cells, and cholinergic varicosities in the hippocampus. ED21 rats did not differ from controls with respect to neonatal developmental milestones, anxiety, learning and memory functions, and neurochemical parameters. Conversely, in TSHI rats the development of neonatal reflexes was delayed, the levels of anxiety were reduced, and spatial learning and memory was impaired; in the hippocampus, the total number of DCX and NPY cells was increased, and the density of cholinergic varicosities was reduced. With these results we suggest that a preterm birth, in a non-inflammatory prenatal environment, does not significantly change neonatal development and adult neurologic outcome. On other hand, prenatal hypoxia and ischemia (inflammation) modifies developmental trajectory, learning and memory, neurogenesis, and NPY GABAergic and cholinergic brain systems.

Association between postnatal growth and neurodevelopmental impairment by sex at 2 years of corrected age in a multi-national cohort of very preterm children.

BACKGROUND & AIMS: Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort. METHODS: Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex. RESULTS: Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18-2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12-2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76-1.22) and 1.12 (0.90-1.40) respectively. CONCLUSION: EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies.

Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.

OBJECTIVE: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. MATERIALS AND METHODS: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. RESULTS: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. CONCLUSION: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.

Estimated Survival and Major Comorbidities of Very Preterm Infants Discharged Against Medical Advice vs Treated With Intensive Care in China.

Importance: A significant proportion of very preterm infants (<32 weeks' gestation) are discharged against medical advice (DAMA) from neonatal intensive care units in China. There is minimal information available on the potential outcomes of providing complete care before discharge in these infants. Objective: To describe potential neonatal outcomes of DAMA in very preterm infants if they receive complete care based on estimates derived from a group of propensity score-matched infants who are not DAMA. Design, Setting, and Participants: This cohort study enrolled all infants born at between 24 and 31 weeks' gestation from May 1, 2015, to April 30, 2018, and admitted to 25 tertiary neonatal intensive care units across China within 7 days of birth. A multilevel mixed-effects logistic regression model was constructed to estimate the propensity score for the likelihood of DAMA for each infant. Infants who were not DAMA were then matched to DAMA infants with the closest propensity score on a 1:1 ratio by using a nearest neighbor greedy matching algorithm without replacement. Incidences of neonatal outcomes were then calculated among the matched non-DAMA infants to simulate the outcomes of DAMA infants. Statistical analyses were performed from August 16, 2020, to September 26, 2020. Exposures: Discharge against medical advice, which was defined as termination of treatment and discharge before the treating physicians recommended discharge. Main Outcomes and Measures: Survival and survival without major morbidity. Results: The study enrolled a total of 14 083 infants (8141 boys [57.8%]) with a median gestational age of 30.1 weeks (interquartile range [IQR], 29.0-31.1 weeks) and a median birth weight of 1400 g (IQR, 1170-1600 g). Overall, 1876 of 14 083 very preterm infants (13.3%; 95% CI, 12.8%-13.9%) were DAMA, of whom 1367 of 1876 (72.9%; 95% CI, 70.8%-74.8%) required intensive care on discharge. A total of 1473 DAMA infants were successfully matched to 1473 non-DAMA infants. Overall, 1211 of 1473 matched non-DAMA infants (82.2%; 95% CI, 80.2%-84.1%) survived to discharge. The survival rates were 68.3% (95% CI, 62.4%-73.7%) for infants at 26 to 27 weeks' gestation, 84.1% (95% CI, 80.7%-87.0%) for infants 28 to 29 weeks' gestation, and 92.4% (95% CI, 90.0%-94.2%) for infants at 30 to 31 weeks' gestation. A total of 872 of 1473 matched non-DAMA infants (59.2%; 95% CI, 56.7%-61.7%) survived without any major morbidity. Conclusions and Relevance: The results of this cohort study suggest that very preterm infants who are DAMA from neonatal intensive care units may have intact survival if complete care is provided. Efforts to reduce DAMA may be associated with improved outcomes of very preterm infants in China.

Pulmonary Function Tests in Very Low Birth Weight Infants Screened for Pulmonary Hypertension: A Pilot Study.

OBJECTIVE: To compare pulmonary function tests (PFTs), specifically respiratory system resistance (Rrs) and compliance (Crs), in very low birth weight (VLBW) infants with and without pulmonary hypertension. STUDY DESIGN: Infants were included who underwent PFTs at 34-38 weeks postmenstrual age (PMA) as part of our pulmonary hypertension screening guidelines for infants born at ≤1500 g requiring respiratory support at ≥34 weeks PMA. One pediatric cardiologist reviewed and estimated right ventricular or pulmonary arterial pressure and defined pulmonary hypertension as an estimated pulmonary arterial pressure or right ventricular pressure greater than one-half the systemic pressure. Rrs and Crs were measured with the single breath occlusion technique and functional residual capacity with the nitrogen washout method according to standardized criteria. RESULTS: Twelve VLBW infants with pulmonary hypertension and 39 without pulmonary hypertension were studied. Those with pulmonary hypertension had significantly lower birth weight and a trend toward a lower gestational age. There were no other demographic differences between the groups. The infants with pulmonary hypertension had significantly higher Rrs (119 vs 78 cmH2O/L/s; adjusted P = .012) and significantly lower Crs/kg (0.71 vs 0.92 mL/cmH2O/kg; P = .04). CONCLUSIONS: In this pilot study of VLBW infants screened for pulmonary hypertension at 34-38 weeks PMA, those with pulmonary hypertension had significantly increased Rrs and decreased Crs compared with those without pulmonary hypertension. Additional studies are needed to further phenotype infants with evolving BPD and pulmonary hypertension.

Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage.

BACKGROUND: Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury. OBJECTIVE: The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH. METHODS: This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age. RESULTS: A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026. CONCLUSIONS: Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH. TRIAL REGISTRATION: The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).

Early bradycardia detection and therapeutic interventions in preterm infant monitoring.

In very preterm infants, cardio-respiratory events and associated hypoxemia occurring during early postnatal life have been associated with risks of retinopathy, growth alteration and neurodevelopment impairment. These events are commonly detected by continuous cardio-respiratory monitoring in neonatal intensive care units (NICU), through the associated bradycardia. NICU nurse interventions are mainly triggered by these alarms. In this work, we acquired data from 52 preterm infants during NICU monitoring, in order to propose an early bradycardia detector which is based on a decentralized fusion of three detectors. The main objective is to improve automatic detection under real-life conditions without altering performance with respect to that of a monitor commonly used in NICU. We used heart rate lower than 80 bpm during at least 10 sec to define bradycardia. With this definition we observed a high rate of false alarms (64%) in real-life and that 29% of the relevant alarms were not followed by manual interventions. Concerning the proposed detection method, when compared to current monitors, it provided a significant decrease of the detection delay of 2.9 seconds, without alteration of the sensitivity (97.6% vs 95.2%) and false alarm rate (63.7% vs 64.1%). We expect that such an early detection will improve the response of the newborn to the intervention and allow for the development of new automatic therapeutic strategies which could complement manual intervention and decrease the sepsis risk.

Novel Method of Calculating Pulse Pressure Variation to Predict Fluid Responsiveness to Transfusion in Very Low Birth Weight Infants.

A novel technique was used to calculate pulse pressure variation. The algorithm reliably predicted fluid responsiveness to transfusion, with a receiver operating characteristic area under the curve of 0.89. This technique may assist clinicians in the management of fluids and vasoactive medications for premature infants.

Neurodevelopmental outcome and early rehabilitation of premature babies - is it needed in the first 2 years of life?

INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the neurodevelopmental outcomes of extremely premature babies at the age of 2 years, and to determine whether rehabilitation was carried out during this period. An additional aim was to determine the relationship between the use of rehabilitation and the degree of prematurity, asphyxia, birth weight, and the result of brain ultrasound. MATERIAL AND METHODS: The study included 87 premature babies born between 24-31 weeks of pregnancy. A rehabilitation specialist assessed the neurodevelopmental outcomes of the children aged 2 years. Based on the documentation, the frequency of rehabilitation and its dependence on prematurity, asphyxia, birth weight and ultrasound results were analyzed. RESULTS: Correct neurodevelopmental outcome in children aged 2 years was found in 57 (65%) children, of whom 40 (46%) did not undergo rehabilitation. Incorrect development was observed in a group of 30 children - 12 patients were diagnosed with CP (14%), and 18 (21%) had 'red flags' of development milestones, they underwent rehabilitation. There was no statistically significant relationship between the degree of prematurity, perinatal asphyxia, birth weight and rehabilitation in the first 2 years of life. Abnormal ultrasound results were more common in rehabilitated children (n = 25; 53%) than in children without rehabilitation (n = 10; 25%), p = 0.008. CONCLUSIONS: Correct neurodevelopmental outcome at the age of 2 reached two-thirds of extreme prematurities, most of which did not need rehabilitation during this period. According to the authors' knowledge, this is the first study to show the percentage of premature babies who in the first 2 years of life did not require rehabilitation and achieved normal development.

The predictive value of 'red flags' as milestones of psychomotor development of premature babies - preliminary study.

INTRODUCTION: Premature babies are a special group at risk of persistent brain damage caused by diseases, the most serious of which are cerebral palsy(CP), autism spectrum disorders (ASD) and mental retardation, among others. These conditions may occur concurrently, but appear more often as separate disease syndromes in the same group of at-risk children. Long-term observation of psychomotor development by an interdisciplinary medical team closely cooperating with parents is necessary. It is important to detect the risk of developing these diseases as soon as possible in all development spheres. MATERIAL AND METHODS: The research was conducted to demonstrate the prognostic value of 'red flags' of developmental milestones and the ability to detect early signs of risk of developing CP and ASD in extremely premature babies. In this preliminary study, 42 preterm babies, born after less than 32 weeks pregnancy participated. RESULTS: The occurrence of 'red flags'in the spheres: gross motor, fine motor and cognitive at 9 months was strongly associated with their presence at 24 months. The sensitivity and specificity were: gross motor - 0.91 (95% CI: 0.59, 1.00) and 0.94 (95% CI: 0.79, 0.99); fine motor - 0.83 (95% CI 0.36-1.00) and 1.00 (95% CI: 0.90-1.00); cognitive - 1.00 (0.40, 1.00) and 0.97 (0.86, 1.00). Other spheres had lower sensitivity but high specificity. CONCLUSIONS: The conclusion is that the 'red flags'at the 9 months milestones already predict the normal or developmental delay of premature babies, and predict the risk of CP and ASD. Due to the availability and lack of the need for specialized and costly training, it is worth considering their use in everyday life medical practice.

Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates.

Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.

Prematurity and postnatal alterations in intermittent hypoxaemia.

Intermittent hypoxaemia (IH) events are well described in extremely preterm infants, but the occurrence of IH patterns in more mature preterm infants remains unclear. The objective of this study was to characterise the effect of gestational age on early postnatal patterns of IH in extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<34 weeks) preterm infants. As expected, extremely preterm infants had a significantly higher frequency of IH events of longer durations and greater time with hypoxaemia versus very and moderately preterm infants. In addition, the postnatal decrease in IH duration was comparable in the very and moderately preterm infants. This progression of IH events should assist clinicians and families in managing expectations for resolution of IH events during early postnatal life.