Assessment of brain structure and volume reveals neurodevelopmental abnormalities in preterm infants with low-grade intraventricular hemorrhage.

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.

Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

BACKGROUND: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. METHODS: A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. RESULTS: The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. CONCLUSIONS: Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.

Posthemorrhagic hydrocephalus management in patients with necrotizing enterocolitis: a monocentric experience.

PURPOSE: Posthemorrhagic hydrocephalus (PHH) and necrotizing enterocolitis (NEC) are two comorbidities associated with prematurity. The management of patients with both conditions is complex and it is necessary to intercept them to avoid meningitis and multilocular hydrocephalus. METHODS: In a single-center retrospective study, we analyzed 19 patients with NEC and PHH admitted from 2012 to 2022. We evaluated perinatal, imaging, and NEC-related data. We documented shunt obstruction and infection and deaths within 12 months of shunt insertion. RESULTS: We evaluated 19 patients with NEC and PHH. Six cases (31.58%) were male, the median birth weight was 880 g (650-3150), and the median gestational age was 26 weeks (23-38). Transfontanellar ultrasound was performed on 18 patients (94.74%) and Levine classification system was used: 3 cases (15.79%) had a mild Levine index, 11 cases (57.89%) had moderate, and 5 cases (26.32%) were graded as severe. Magnetic resonance showed intraventricular hemorrhage in 14 cases (73.68%) and ventricular dilatation in 15 cases (78.95%). The median age at shunt insertion was 24 days (9-122) and the median length of hospital stay was 120 days (11-316). Sepsis was present in 15 cases (78.95%). NEC-related infection involved the peritoneal shunt in 4 patients and 3 of them had subclinical NEC. At the last follow-up, 6 (31.58%) patients presented with psychomotor delay. No deaths were reported. CONCLUSIONS: Although recognition of subclinical NEC is challenging, the insertion of a ventriculoperitoneal shunt is not recommended in these cases and alternative treatments should be considered to reduce the risk of meningitis and shunt malfunction.

Early onset neonatal thrombocytopenia is associated with severe intraventricular hemorrhage in very preterm infants: A retrospective cohort study.

BACKGROUND: The role of platelet function in the development of intraventricular hemorrhage is still a subject of debate. In this study, we aimed to determine whether there is an association between platelet indices in the first week of life and severity of intraventricular hemorrhage in very preterm infants. MATERIALS AND METHODS: Preterm infants born < 30 weeks of gestation in our hospital were retrospectively evaluated. Platelet parameters, including platelet counts, mean platelet volume, platelet distribution width, and platelet mass were retrieved at two different time points: the initial value on the first day of life and the value closest to the end of the first week of life. The infants were categorized according to the findings of cranial ultrasonography as; no intraventricular hemorrhage, mild or severe intraventricular hemorrhage. RESULTS: Totally, 1051 infants were evaluated. The mean gestational age and birth weight for the entire cohort were 27.9±1.6 weeks and 1058±247 g, respectively. Infants in the severe intraventricular hemorrhage group had significantly lower gestational age (p < 0.001) and birthweight (p < 0.001) compared to other two groups. Furthermore, there were significant differences in platelet count and platelet mass between the groups at two time intervals. However, logistic regression analysis revealed that only platelet count of < 100×109/L on the first postnatal day was independently associated with the severity of intraventricular hemorrhage. CONCLUSION: There is an association between platelet count of < 100×109/L on the first postnatal day and severe intraventricular hemorrhage in very preterm infants.

Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% (n = 78) of the HS epoch versus 32% (n = 137) of the control subjects (P = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Brain Biometry Reveals Impaired Brain Growth in Preterm Neonates with Intraventricular Hemorrhage.

INTRODUCTION: Preterm birth and cerebral hemorrhage have adverse effects on brain development. Alterations in regional brain size on magnetic resonance imaging (MRI) can be assessed using 2D biometrical analysis, an easily applicable technique showing good correlation with 3D brain volumes. METHODS: This retrospective study included 74 preterm neonates with intraventricular hemorrhage (IVH) born <32+0 weeks of gestation between 2011 and 2019. Cerebral MRI was performed at term-equivalent age, and 2D measurement techniques were used for biometrical analysis and compared to normative data of two control groups. Finally, the correlation and association of brain parameters and patterns of impaired brain growth and outcome at 2 and 3 years of age were evaluated. RESULTS: Interhemispheric distance (IHD), the 3rd ventricle, and lateral ventricles presented larger, in contrast, cerebral biparietal width (cBPW), fronto-occipital diameter (FOD), and the length of the corpus callosum were smaller in IVH patients compared to respective controls. The strongest correlations with outcome were observed for the parameters FOD, anteroposterior diameter of the vermis, transverse cerebellar diameter (tCD), corpus callosum, 3rd ventricle, and left ventricular index. Patients with the small FOD, small BPW, and increased IHD pattern reached overall lower outcome scores at follow-up. DISCUSSION: Preterm neonates with IVH showed reduced total brain sizes and enlarged pericerebral spaces compared to neurologically healthy controls. Biometric analysis revealed that several 2D brain parameters as well as different patterns of impaired brain growth were associated with neurodevelopmental impairment in early childhood. These findings may support prediction of long-term outcome and parental counseling in patients with IVH.

Early Vital Sign Differences in Very Low Birth Weight Infants with Severe Intraventricular Hemorrhage.

OBJECTIVE: Severe intraventricular hemorrhage (sIVH, grades 3 and 4) is a serious complication for very low birth weight (VLBW) infants and is often clinically silent requiring screening cranial ultrasound (cUS) for detection. Abnormal vital sign (VS) patterns might serve as biomarkers to identify risk or occurrence of sIVH. STUDY DESIGN: This retrospective study was conducted in VLBW infants admitted to two level-IV neonatal intensive care units (NICUs) between January 2009 and December 2018. Inclusion criteria were: birth weight <1.5 kg and gestational age (GA) <32 weeks, at least 12 hours of systemic oxygen saturation from pulse oximetry (SpO2) data over the first 24 hours and cUS imaging. Infants were categorized as early sIVH (sIVH identified in the first 48 hours), late sIVH (sIVH identified after 48 hours and normal imaging in the first 48 hours), and no IVH. Infants with grades 1 and 2 or unknown timing IVH were excluded. Mean heart rate (HR), SpO2, mean arterial blood pressure (MABP), number of episodes of bradycardia (HR < 100 bpm), and desaturation (SpO2 < 80%) were compared. RESULTS: A total of 639 infants (mean: 27 weeks' gestation) were included (567 no IVH, 34 early sIVH, and 37 late sIVH). In the first 48 hours, those with sIVH had significantly higher HR compared with those with no IVH. Infants with sIVH also had lower mean SpO2 and MABP and more desaturations <80%. No significant differences in VS patterns were identified in early versus late sIVH. Logistic regression identified higher HR and greater number of desaturations <80% as independently associated with sIVH. CONCLUSION: VLBW infants who develop sIVH demonstrate VS differences with significantly lower SpO2 and higher mean HR over the first 48 hours after birth compared with VLBW infants with no IVH. Abnormalities in early VS patterns may be a useful biomarker for sIVH. Whether VS abnormalities predict or simply reflect sIVH remains to be determined. KEY POINTS: · A higher HR in the first 48 hours is seen in infants with severe IVH.. · Infants with sIVH have lower blood pressure in the first 48 hours.. · Infants with sIVH have more oxygen desaturations in the first 48 hours..

Hospital variation in neonatal echocardiography among very preterm infants at US children's hospitals.

OBJECTIVE: Estimate hospital variation in echocardiography (echo) among very preterm infants. STUDY DESIGN: Retrospective cohort study of very preterm (<32 weeks) infants discharged between 2012 and 2019 from US children's hospitals. Echo exposure was identified using daily billing, and hospital variation was estimated after adjustment for illness severity. Variation in very early echo use (<3 days of life) was compared to exposure to treatment of a patent ductus arteriosus (PDA), and other practice patterns. RESULTS: 27,498 subjects across 39 children's hospitals were included. Very early echo use had the greatest hospital variation (3-34%). Increasing very early echo use was not associated with PDA treatment (p = 0.93), but was associated with nitric oxide (p < 0.01) and vasoactive medications (p < 0.01). CONCLUSIONS: Hospital variation in echo use among preterm infants was greatest in the first few days of life and was associated with increasing nitric oxide and vasoactive medication use. The impact of this variation on clinical outcomes is uncertain and warrants further investigation.

Evaluation of a Cranial Ultrasound Screening Protocol for Very Preterm Infants.

OBJECTIVES: Cranial ultrasound (cUS) screening is recommended for preterm neonates born before 32 weeks' gestational age (GA). The primary aim of this study was to determine if both a day 3 and day 8 cUS screening examination is necessary for all neonates. METHODS: A retrospective observational study was performed at a tertiary-level Australian hospital. Frequencies of cranial ultrasound abnormality (CUA) were compared between routine screening performed at postnatal days 3, 8, and 42. Univariate and multivariate analyses of risk factors for intraventricular hemorrhage (IVH) was performed using logistic regression. RESULTS: cUS examinations on 712 neonates born before 32 weeks' GA were included. Neonates were divided into 2 groups: 99 neonates in the 23-25 weeks 6 days GA (group A) and 613 neonates in the 26-31 weeks 6 days GA (group B). All CUA occurred more frequently in group A neonates and in the subset of group B neonates who had defined risk factors. Low-risk group B neonates had lower incidence of CUAs demonstrated on day 8 cUS than high-risk group B neonates, with no significant differences between day 3 and day 8. Logistic regression analysis identified a number of risk factors (vaginal delivery, small for GA, Apgar score <7 at 5 minutes, intubation, patent ductus arteriosus and infection) that were associated with increased frequency of IVH on day 8. In neonates born between 30 and 31 weeks 6 days GA, 35% had a CUA identified. CONCLUSIONS: Low-risk preterm neonates born between 26 and 31 weeks 6 days GA, without complications, could be screened with a single early cUS examination around day 8 without missing substantial abnormality.

Posthemorrhagic ventricular dilatation late intervention threshold and associated brain injury.

OBJECTIVE: To systematically assess white matter injury (WMI) in preterm infants with posthemorrhagic ventricular dilatation (PHVD) using a high-threshold intervention strategy. STUDY DESIGN: This retrospective analysis included 85 preterm infants (≤34 weeks of gestation) with grade 2-3 germinal matrix-intraventricular hemorrhage. Cranial ultrasound (cUS) scans were assessed for WMI and ventricular width and shape. Forty-eight infants developed PHVD, 21 of whom (intervention group) underwent cerebrospinal fluid drainage according to a predefined threshold (ventricular index ≥p97+4 mm or anterior horn width >10 mm, and the presence of frontal horn ballooning). The other 27 infants underwent a conservative approach (non-intervention group). The two PHVD groups were compared regarding ventricular width at two stages: the worst cUS for the non-intervention group (scans showing the largest ventricular measurements) versus pre-intervention cUS in the intervention group, and at term equivalent age. WMI was classified as normal/mild, moderate and severe. RESULTS: The intervention group showed significantly larger ventricular index, anterior horn width and thalamo-occipital diameter than the non-intervention group at the two timepoints. Moderate and severe WMI were more frequent in the infants with PHVD (p<0.001), regardless of management (intervention or conservative management). There was a linear relationship between the severity of PHVD and WMI (p<0.001). CONCLUSIONS: Preterm infants with PHVD who undergo a high-threshold intervention strategy associate an increased risk of WMI.

Optimizing timing and frequency of head ultrasound screening for severe brain injury among preterm infants born <32 weeks' gestation.

OBJECTIVE: To develop a head ultrasound (HUS) screening protocol for infants born <32 weeks gestational age (GA) that accurately identifies severe brain injury (SBI) while minimizing resource use. STUDY DESIGN: Retrospective cohort study of infants born <32 weeks GA, admitted to a level 3 neonatal intensive care unit between 2011 and 2017. Timing and results of each HUS were reviewed. SBI was defined as intraventricular hemorrhage grade ≥3 and/or periventricular leukomalacia. Logistic regression models were used to identify risk factors and evaluate the predictive value of HUS at different time points during hospitalization. RESULTS: Of 651 included infants, 71 (11%) developed SBI. Risk factors for SBI were GA at birth <29 weeks (adjusted odds ratio (aOR) 2.87, 95% confidence interval (CI) 1.50-5.48), vasopressors on admission (aOR 3.08, 95%CI 1.38-6.88) and mechanical ventilation on admission (aOR 2.50, 95%CI 1.33-4.68). Infants were classified into three risk groups based on these risk factors, and combinations of 1-5 HUS time points were evaluated to determine the optimal number and timing of HUS for each group. The optimal number of screening HUS ranged from 1 for low-risk to 2 for high-risk infants. Adopting a screening protocol using the number and timing of HUS optimized by risk group could reduce the total number of HUS performed by 40% and the median number of HUS per infant from 3 (IQR 2-4) to 2 (IQR 1-3) (p < .01). CONCLUSIONS: Implementation of a risk factor-based HUS screening protocol can help reduce resource use while maintaining high sensitivity for detecting SBI.

Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring: a prospective cohort study.

Unstable hemodynamics and prematurity are the main players in intraventricular hemorrhage (IVH) development. Our objective was to study 8 the use of superior vena cava flow (SVCF), left ventricular output (LVO), and right ventricular output (RVO), and anterior cerebral artery (ACA) Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks and birth weight ≤ 1500 g. This prospective cohort study was conducted in 55NICU of Alexandria University maternity hospital. Of 147 enrolled patients, 132 infants born ≤ 32 weeks GA and birth weight ≤ 1500 g were eligible for- the study. One hundred twenty-seven infants completed the study. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVCF, LVO, and RVO using functional echocardiography in the first 24 h after birth. Patients had another two scans on DOL3 and 7 to detect IVH development. Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with OR, 3.16; 95%CI, 1.19-8.39; P = 0.02 and OR, 1.64; 95%Cl, 1.10-2.44; P = 0.02, respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P = 0.025 and 0.023, respectively. Combined use of low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity. CONCLUSIONS: There are strong relations between both low SVCF and high ACA-RI, and IVH development in premature neonates ≤ 32 weeks and birth weight ≤ 1500 g, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVCF. Maternal anemia, patent ductus arteriosus size (mm/kg), and capillary refill time were significantly associated with high ACA-RI. These findings help in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome. TRIAL REGISTRATION: This work was registered in clinical trial.gv no NCT05050032. WHAT IS KNOWN: •Whether SVCF and RI-ACA can predict IVH in preterm neonates is still debatable. WHAT IS NEW: •Low SVC flow and high ACA-RI significantly increased risk of IVH, confirming the role of hypoperfusion-reperfusion cycle in IVH development. The most striking result that combined metrics using the cut-off value of < 41 ml/kg/min for SVCF and > 0.85 for ACA-RI "in the first day of life" can correctly reject the presence of IVH in 98% of patients "during the first week of life."

Imaging of Premature Infants.

According to the World Health Organization (WHO), 15 million babies are born preterm each year. Preterm infants are those born at less than 37 weeks, while extremely and very preterm neonates include those born at 22 to less than 32 weeks gestational age. Infants that fail to make it to term are missing a key part in neurodevelopment, as weeks 24 to 40 are a critical period of brain development. Neonatal brain injury is a crucial predictor for mortality and morbidity in premature and low birth weight (<1500 g) infants. Although the complications associated with preterm birth continue to be the number one cause of death in children under 5, the survival rates are increasing (Volpe, 2019). Despite this, the incidence of comorbidities, such as learning disabilities and visual and hearing problems, is still high. The functional deficits seen in these infants can be contributed to the white matter abnormalities (WMA) that have been found in 50% to 80% of extremely and very preterm neonates. While numerous, the etiology of the neonatal brain injury is essential for determining the mortality and morbidities of the infant, as there is an increased risk for both intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which can be attributed to their lack of cerebrovascular autoregulation and hypoxic events. Neuroimaging plays a key role in detecting and assessing these neurologic injuries that preterm infants are at risk for. It is essential to diagnose these events early on to assess neurologic damage, minimize disease progression, and provide supportive care. Brain MRI and cranial ultrasound (CUS) are both extensively used neuroimaging techniques to assess WMA, and it has become ever more important to determine the best imaging techniques and modalities with the increasing survival rates and high incidence of comorbidities among these infants.

Pulmonary Magnetic Resonance Imaging Replaces Bedside Imaging in Diagnosing Pneumonia in Infants.

Neonatal Bronchopulmonary Bedside Photography (NBBP) evaluates the consumption of lung magnetic resonance imaging as a replacement for bedside imaging in diagnosing infant pneumonia. In premature baby respiratory support, Neonatal Bronchopulmonary (NB) is one of the most dangerous consequences of accurate diagnosis that impact health alternatives once steroids are administered. Infants may experience eating issues and vomit if their condition is bad enough; lower birth weight, younger gestational age, and extensive breathing tube damage are the most frequently established risk factors as a component of a neonatal habitat. This paper introduces the Intelligent Medical Care (IMC) for Neonatal Bronchopulmonary Bedside Photography (NBBP), which enhances various preventive efforts such as prenatal steroid therapy. Because of many prenatal and postnatal variables, growth hormone and diet nutrients influence alveolar and vascular development. For the future prevention of NB, it is more likely that a combination of different therapies working on diverse causal pathways would be beneficial. This research in NBBP-IMC technology that enhances prenatal care medicines are the most excellent and effective treatments for all these neonates throughout the decades. As a result, premature babies at risk for NB may benefit from the findings of this research, which experts anticipate can inspire further studies in the area. The purpose of this paper is to emphasize the work performed to improve respiratory outcomes for babies at risk of NB and to place this work in perspective with relevant research currently being conducted simultaneously.

Elevated cerebrospinal fluid iron and ferritin associated with early severe ventriculomegaly in preterm posthemorrhagic hydrocephalus.

OBJECTIVE: Posthemorrhagic hydrocephalus (PHH) following preterm intraventricular hemorrhage (IVH) is among the most severe sequelae of extreme prematurity and a significant contributor to preterm morbidity and mortality. The authors have previously shown hemoglobin and ferritin to be elevated in the lumbar puncture cerebrospinal fluid (CSF) of neonates with PHH. Herein, they evaluated CSF from serial ventricular taps to determine whether neonates with PHH following severe initial ventriculomegaly had higher initial levels and prolonged clearance of CSF hemoglobin and hemoglobin degradation products compared to those in neonates with PHH following moderate initial ventriculomegaly. METHODS: In this observational cohort study, CSF samples were obtained from serial ventricular taps in premature neonates with severe IVH and subsequent PHH. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein were quantified using ELISA. Ventriculomegaly on cranial imaging was assessed using the frontal occipital horn ratio (FOHR) and was categorized as severe (FOHR > 0.6) or moderate (FOHR ≤ 0.6). RESULTS: Ventricular tap CSF hemoglobin (mean) and ferritin (initial and mean) were higher in neonates with severe versus moderate initial ventriculomegaly. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein decreased in a nonlinear fashion over the weeks following severe IVH. Significantly higher levels of CSF ferritin and total iron were observed in the early weeks following IVH in neonates with severe initial ventriculomegaly than in those with initial moderate ventriculomegaly. CONCLUSIONS: Among preterm neonates with PHH following severe IVH, elevated CSF hemoglobin, ferritin, and iron were associated with more severe early ventricular enlargement (FOHR > 0.6 vs ≤ 0.6 at first ventricular tap).

A predictive clinical model for moderate to severe intraventricular hemorrhage in very low birth weight infants.

IMPORTANCE: Intraventricular hemorrhage (IVH) occurs in 15-45% of all very low birth weight (VLBW) preterm infants. Despite improvements in the perinatal care, the incidence of IVH remains high. As more preterm infants survive, there will be a larger burden of neurodevelopmental abnormalities borne by former preterm infants. OBJECTIVE: The objective of this study was to develop a predictive clinical model of IVH risk within the first few hours of life in an effort to augment perinatal counseling and guide the timing of future targeted therapies aimed at preventing or slowing the progression of disease. DESIGN: This is a prospective observational cohort study of VLBW infants born in the NICU at John's Hopkins Children's Center from 2011 to 2019. The presence and severity of IVH was defined on standard head ultrasound screening (HUS) using the modified Papile classification. Clinical variables were identified as significant using absolute risk regression from a general linear model. The model predictors included clinically meaningful variables that were not collinear. SETTING: This study took place at the Johns Hopkins Children's Center Level IV NICU. PARTICIPANTS: The study sample included VLBW infants treated in the neonatal intensive care unit (NICU) at John's Hopkins Children's Center from 2011 to 2019. A total of 683 infants included in the study had no or grade I IVH, and 115 infants had grades II through IV IVH. Exclusion criteria included admission to the JHH NICU after 24 h of age, BW > 1500 g, and failure to consent. MAIN OUTCOME: The main outcome of this study was the presence of grades II-IV IVH on standard head ultrasound screening using the modified Papile classification [1]. RESULTS: A total of 798 VLBW infants were studied in this cohort and 14.4% had moderate to severe IVH. Fifty four percent of the cohort was black, 33% white, and half of the cohort was male. A higher gestational age, 5-min Apgar score, hematocrit, and platelet count were significantly associated with decreased incidence of IVH in a multi-predictor model (ROC 0.826). CONCLUSION AND RELEVANCE: In the face of continued lack of treatments for IVH, prevention is still a primary goal to avoid long-term developmental sequela. This model can be used for perinatal counseling and may provide important information during the narrow therapeutic window for targeted prevention therapies.

Long-term neurodevelopmental outcome in preterm infants with intraventricular haemorrhage.

BACKGROUND: Intraventricular haemorrhage (IVH) is one of the key risks for long-term neurodevelopmental issues. There remains controversy over the impact low-grade IVH has on the long-term outcome of premature infants. This study describes the long-term neurodevelopmental impact of Grade I and II IVH in former preterm infants in the early school years. METHODS: This is a retrospective cohort analysis from one tertiary neonatal intensive care unit (NICU) in Australia including all infants born at <30 weeks' gestation and admitted to the NICU between 2006 and 2013 with complete ultrasound reports and follow-up results. Results of standardised tests for neurodevelopmental outcomes at 5 and 8 years were compared between infants who suffered mild IVH and infants who had normal head ultrasounds. RESULTS: During the study period, 491 infants <30 weeks gestation were admitted; 275 patients had full follow-up data available. We found no significant difference in examined outcomes at 5- and 8-year follow-up. CONCLUSION: Mild IVH does not affect cognitive, motor and academic outcomes at school age.

Feeding in Preterm Neonates With Antenatal Doppler Abnormalities: A Systematic Review and Meta-Analysis.

OBJECTIVES: In this systematic review and meta-analysis, we attempted to determine the most appropriate feed initiation and advancement practices in preterm neonates with antenatal Doppler abnormalities. METHODS: We included randomized controlled trials comparing different feed initiation and advancement practices in neonates with antenatal Doppler abnormalities. The databases of PubMed, Embase, Cochrane, CINAHL, Scopus, and Google Scholar were searched on February 25, 2022. The risk of bias was assessed using the Risk of Bias tool, version 2. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RevMan 5.4 was used for data analysis. RESULTS: Of the 1499 unique records identified, 7 studies were eligible for inclusion (6 on feed initiation, 1 on feed advancement). Early enteral feeding did not increase NEC stage 2 or more [risk ratio (RR) 1.12, 95% confidence interval (CI) 0.71-1.78; 6 studies, 775 participants] and mortality (RR 0.83, 95% CI 0.47-1.48; 5 studies, 642 participants). A trend was noted towards an increase in feeding intolerance (RR 1.23, 95% CI 0.98-1.56; 5 studies, 715 participants). There was a significant reduction in age at full enteral feeds, duration of total parental nutrition, and rates of hospital-acquired infections. Rapid feed advancement decreased the age at full enteral feeds without affecting other outcomes. The overall certainty of the evidence was rated low. Heterogeneity was not significant. CONCLUSION: There is low-certainty evidence that early feed initiation in preterm neonates with antenatal Doppler abnormalities does not increase rates of NEC and mortality. There is insufficient data on the speed of feed advancement.

Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants.

BACKGROUND: The independent risk for neurodevelopmental impairments attributed to chorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury identified on magnetic resonance imaging at term-equivalent age can be used as a surrogate measure of neurodevelopmental impairments that is less confounded by postdelivery neonatal intensive care unit environmental factors to investigate this relationship more clearly. OBJECTIVE: This study aimed to determine whether preterm infants born with moderate to severe acute histologic chorioamnionitis would have a higher magnetic resonance imaging-determined global brain abnormality score, independent of early premature birth, when compared with preterm infants with no or mild chorioamnionitis. STUDY DESIGN: This was a prospective, multicenter cohort study involving infants born very prematurely ≤32 weeks' gestational age with acute moderate to severe histologic chorioamnionitis, graded using standard histologic criteria. Brain abnormalities were diagnosed and scored using a well-characterized, standardized scoring system captured using a high-resolution 3 Tesla magnetic resonance imaging research magnet. In secondary analyses, total brain volume and 4 magnetic resonance imaging metrics of cortical maturation (cortical surface area, sulcal depth, gyral index, and inner cortical curvature) were calculated using an automated algorithm and correlated with chorioamnionitis. The association of funisitis (any grade) with brain abnormalities was also explored. We investigated if premature birth mediated the relationship between histologic chorioamnionitis and brain abnormality score using mediation analysis. RESULTS: Of 353 very preterm infants, 297 infants had mild or no chorioamnionitis (controls), and 56 were diagnosed with moderate to severe acute histologic chorioamnionitis. The primary outcome brain abnormality score was significantly higher in histologic chorioamnionitis-exposed infants than in the controls (median, 4 vs 7; P<.001). Infants with acute histologic chorioamnionitis had significantly lower brain tissue volume (P=.03) and sulcal depth (P=.04), whereas other morphometric indices did not differ statistically. In the multiple regression analysis, we observed persistent significant relationships between moderate to severe acute histologic chorioamnionitis and brain abnormality scores (ß=2.84; 1.51-4.16; P<.001), total brain volume (P=.03), and sulcal depth (P=.02). Funisitis was also significantly associated with brain abnormality score after adjustment for clinical confounders (P=.005). Mediation analyses demonstrated that 50% of brain abnormalities was an indirect consequence of premature birth, and the remaining 50% was a direct effect of moderate to severe acute histologic chorioamnionitis when compared with preterm infants with no or mild chorioamnionitis exposure. Examining gestational age as a mediator, funisitis did not exert a significant direct effect on brain abnormalities after the significant indirect effects of preterm birth were accounted for. CONCLUSION: Acute histologic chorioamnionitis increases the risk for brain injury and delayed maturation, both directly and indirectly, by inducing premature birth.