Receptor-interacting protein kinase-3 (RIPK3): a new biomarker for necrotising enterocolitis in preterm infants.

OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.

New and old lessons from a devastating case of neonatal E coli meningitis.

BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

Necrotizing enterocolitis in premature infants at different gestation ages.

OBJECTIVE: Aim: To compare X-ray signs in different gestational and body weight groups of patients with NEC. PATIENTS AND METHODS: Materials and Methods: We conducted a retrospective study, enrolling 52 preterm newborns with symptoms of NEC regardless of onset time, who underwent treatment at Neonatal Intensive Care Units in Municipal Non-commercial enterprise "City Children Hospital №2", Odesa. The patients were split into 3 clinical groups: very preterm newborns (VPN), moderately preterm newborns (MPN), and moderately preterm newborns with intrauterine growth restriction (MPN+IUGR). RESULTS: Results: In the VPN group NEC was diagnosed at stage II (58,82±12,30) % and III (41,18±12,30) % by Bell MJ, р>0,05. In the group MPN+IUGR, NEC stage II (33,33±14,21) % and stage III (66,66 ±14,21) %, р>0,05, were equally observed. In the MPN group, NEC was diagnosed at stage I (41,67±10,28) % and II (58,33±10,28) %, р>0,05, without prevalence of any. Also only localized forms were observed. In VPN, we observed localized forms in most cases, while diffuse forms were diagnosed in (11,76±8,05) % cases, р<0,05. In the MPN+IUGR group, we found diffuse form of the NEC in half of the cases - (50,00±15,08) %. In the VPN and MPN+IUGR groups, NEC developed at 13,23±0,39 and 14,33±1,19 days, respectively. However, in MPN without IUGR, NEC developed at 17,75±0,55 days, significantly later than in the MPN+IUGR group, р<0,05. CONCLUSION: Conclusions: We have described distinct features of NEC in MPN with IUGR. Compared to MPN without IUGR, NEC had more severe course and earlier manifestation in such neonates.

Analysis of similarities and differences between transient symptomatic zinc deficiency and acrodermatitis enteropathica in children: a case report of a Chinese Yi-ethnic infant.

BACKGROUND: Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging. CASE PRESENTATION: Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient's blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence. CONCLUSIONS: The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.

Machine learning-based analysis for prediction of surgical necrotizing enterocolitis in very low birth weight infants using perinatal factors: a nationwide cohort study.

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction.    Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data.

Urinary tract infections in very premature neonates: the definition dilemma.

BACKGROUND AND OBJECTIVES: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines. METHODS: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI. RESULTS: Most episodes were Possible UTI (87%). Symptoms of UTIs and pathogens varied based on the definition category. A positive urinalysis was obtained in 25%. Possible UTI episodes grew 2 organisms in 62% of cases and <50,000 CFU/mL in 62% of cases. CONCLUSION: Characteristics of UTIs in VPTNs vary based on the definition category and case definitions used by clinicians differ from that of established pediatric guidelines.

Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

Screening for functional gastrointestinal disorders in preterm infants up to 12 months of corrected age: a prospective cohort study.

Functional gastrointestinal disorders (FGIDs) are characterized by a variety of symptoms that are frequently age-dependent, chronic, or recurrent and are not explained by structural or biochemical abnormalities. There are studies in the literature reporting different results regarding the relationship between prematurity and FGIDs. The main objective of this study was to compare the frequency of FGIDs between preterm and term infants. The secondary objective was to evaluate whether there was any association between neonatal characteristics and development of FGIDs. A multicenter prospective cohort study that included preterm infants born before 37 weeks of gestation and healthy term infants was carried out. At 1, 2, 4, 6, 9, and 12 months of age, infants were assessed for the presence of FGIDs using the Rome IV criteria. In preterm infants, an additional follow-up visit was made at 12 months corrected age. 134 preterm and 104 term infants were enrolled in the study. Infantile colic, rumination syndrome, functional constipation, and infant dyschezia were more common in preterm infants. Incidence of other FGIDs (infant regurgitation, functional diarrhea and cyclic vomiting syndrome) were similar among preterm and term infants. Preterm infants who are exclusively breastfeed in the first 6 months of life have a lower incidence of infantile colic (18.8% vs 52.1%, p = 0.025). In terms of chronological age, FGIDs symptoms started later in preterm infants; this difference was statistically significant for infantile colic and regurgitation (median age 2 months vs 1 month, p < 0.001).   Conclusions: Preterm infants have a higher prevalence of FGIDs compared with term controls. Therefore, especially if they have gastrointestinal complaints, they should be screened for FGIDs. Possibly due to maturational differences, the time of occurrence of FGIDs may differ in preterm infants. Infantile colic incidence decreases with exclusive breastfeeding. What is Known: • The functional gastrointestinal disorders are a very common in infancy. • Data on preterm infants with FGIDs are currently very limited. What is New: • Preterm infants have a higher incidence of infantile colic, rumination syndrome, functional constipation and infant dyschezia when compared to term infants. • Preterm infants who are exclusively breastfed during the first 6 months of life experience a lower incidence of infantile colic.

Electrical Cardiometry during transition and short-term outcome in very preterm infants: a prospective observational study.

The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4-30.6) weeks, birthweight 1020 (745-1505) g) were included in the analysis. Median CO was 241 (197-275) mL/kg/min for the adverse outcome and 198 (175-227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03); p = 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02); p = 0.373). CO trajectory did not differ by outcome (p = 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2.          Conclusions: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2. What is Known: • Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants. What is New: • Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally. • In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.

Evaluation of the "Neonatal Sequential Organ Failure Assessment" to Predict Mortality in Late-Onset Sepsis in Very Preterm Infants.

INTRODUCTION: We aimed to evaluate the use of "Neonatal Sequential Organ Failure Assessment" (nSOFA) scoring in predicting mortality, to compare the accuracy of nSOFA scores at different time points in very preterm infants with late-onset sepsis (LOS), and to investigate other possible parameters that would improve the prediction. METHODS: This single-center, retrospective study included preterm infants born atS<32 weeks' gestation with culture-proven LOS. The nSOFA scores of non-fatal and fatal episodes were compared at nine time points. RESULTS: Of 120 culture-proven LOS episodes in 106 infants, 90 (75%) episodes were non-fatal and 30 (25%) episodes were fatal. The mean birth weight (BW) of the infants who died was lower than that of survivors (p=0.038). In the fatal LOS episodes, median nSOFA scores were higher at all time points measured before sepsis evaluation, at the time of evaluation, and at all time points measured after the evaluation (p<0.001). nSOFA scores before death and at 48 hours were higher in the fatal episodes (p<0.001). At the time of sepsis assessment, nSOFA score>4 was associated with a 7- to 16-fold increased risk of mortality. Adjustment for BW, lymphocyte and monocyte counts increased the risk to 9- to 18-fold. CONCLUSION: This study demonstrated that the use of nSOFA to predict mortality and morbidity in extremely preterm infants seems feasible. The scoring system could be improved by evaluating the other parameters.

Cerebellar injury in preterm infants less than 28 weeks gestational age.

BACKGROUND: Cerebellar injury is one of the perinatal complications in preterm infants. Recent studies have highlighted the effect of perinatal complications on neurological morbidity. We investigated the perinatal risk factors and morbidity for cerebellar injury in extremely premature infants. METHODS: This retrospective cohort study included 285 infants born between April 2009 and December 2020 at gestational age <28 weeks at our institution. The infants were divided into two groups based on magnetic resonance imaging findings: those with and without cerebellar injury. We performed a statistical analysis of the perinatal background and short-term morbidity of the two groups. RESULTS: Significant differences (p < 0.05) were observed between the groups with respect to the perinatal background, especially gestational weeks, birthweight, and hemoglobin values at birth. In the short-term morbidity, significant differences (p < 0.05) were observed in the incidence of respiratory distress syndrome, chronic lung disease, hydrocephalus, severe intraventricular hemorrhage (IVH), and cerebellar hemorrhage. Extensive cerebellar lesions, such as cerebellar agenesis or global cerebellar hypoplasia, accounted for 11 of the 22 cases of cerebellar injury; seven of the 11 cases had severe IVH in addition to cerebellar hemorrhage. CONCLUSIONS: Gestational age was significantly lower in the cerebellar injury group. The combination of severe IVH and cerebellar hemorrhage may promote cerebellar injury.

Diaphragmatic muscle function in term and preterm infants.

We aimed to assess the determinants of diaphragmatic function in term and preterm infants. 149 infants (56 term; 93 preterm, of whom 14 were diagnosed with bronchopulmonary dysplasia-BPD) were studied before discharge. Diaphragmatic function was assessed by measurement of the maximum transdiaphragmatic pressure (Pdimax)-a measure of diaphragmatic strength, and the pressure-time index of the diaphragm (PTIdi)-a measure of the load-to-capacity ratio of the diaphragm. The Pdimax was higher in term than preterm infants without BPD (90.1 ± 16.3 vs 81.1 ± 11.8 cmH2O; P = 0.001). Term-born infants also had lower PTIdi compared to preterms without BPD (0.052 ± 0.014 vs 0.060 ± 0.017; P = 0.006). In term and preterm infants without BPD, GA was the most significant predictor of Pdimax and PTIdi, independently of the duration of mechanical ventilation and oxygen support. In infants with GA < 32 weeks (n = 30), the Pdimax was higher in infants without BPD compared to those with BPD (76.1 ± 11.1 vs 65.2 ± 11.9 cmH2O; P = 0.015). Preterms without BPD also had lower PTIdi compared to those with BPD (0.069 ± 0.016 vs 0.109 ± 0.017; P < 0.001). In this subgroup, GA was the only significant independent determinant of Pdimax, while BPD and the GA were significant determinants of the PTIdi.  Conclusions: Preterm infants present lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. In very preterm infants, BPD may further aggravate diaphragmatic function. What is Known: • The diaphragm of preterm infants has limited capacity to undertake the work of breathing effectively. • The maximum transdiaphragmatic pressure (a measure of diaphragmatic strength) and the pressure-time index of the diaphragm (a measure of the load-to-capacity ratio of the muscle) have not been extensively assessed in small infants. What is New: • Preterm infants have lower diaphragmatic strength and impaired ability to sustain the generated force over time, which renders them prone to diaphragmatic fatigue. • In very preterm infants, bronchopulmonary dysplasia may further impair diaphragmatic function.

Major Surgery, Brain Injury, and Neurodevelopmental Outcomes in Very Preterm Infants.

OBJECTIVES: We determined whether (1) major surgery is associated with an increased risk for brain injury and adverse neurodevelopment and (2) brain injury modifies associations between major surgery and neurodevelopment in very preterm infants. METHODS: Prospectively enrolled infants across 3 tertiary neonatal intensive care units underwent early-life and/or term-equivalent age MRI to detect moderate-severe brain injury. Eighteen-month neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development, third edition. Multivariable logistic and linear regressions were used to determine associations of major surgery with brain injury and neurodevelopment, adjusting for clinical confounders. RESULTS: There were 294 infants in this study. Major surgery was associated with brain injury (odds ratio 2.54, 95% CI 1.12-5.75, p = 0.03) and poorer motor outcomes (ß = -7.92, 95% CI -12.21 to -3.64, p < 0.001), adjusting for clinical confounders. Brain injury x major surgery interaction significantly predicted motor scores (p = 0.04): Lowest motor scores were in infants who required major surgery and had brain injury. DISCUSSION: There is an increased risk for brain injury and adverse motor outcomes in very preterm infants who require major surgery, which may be a marker of clinical illness severity. Routine brain MRI to detect brain injury and close neurodevelopmental surveillance should be considered in this subgroup of infants.

Symptomatic Postnatal Cytomegalovirus Infection in Less than 32-Week Preterm Infants: 13-Year Retrospective Multicenter Case-Control Study.

INTRODUCTION: Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation. METHODS: We used data from the Neonatal Intensive Care Units' (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants <32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant. RESULTS: Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7-4.5) and spend 25.2 days more in hospital (95% CI: 15.2-35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (<28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment. CONCLUSION: Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants.

Spontaneous resolution of post-hemorrhagic ventricular dilatation in preterm newborns and neurodevelopment.

BACKGROUND: We investigated the temporal evolution of post-hemorrhagic ventricular dilatation (PHVD) and compared neurodevelopmental impairments (NDI) in newborns with (Group 1) spontaneous resolution of PHVD, (Group 2) persistent PHVD without neurosurgical intervention, and (Group 3) progressive PHVD receiving neurosurgical intervention. METHODS: A multicenter retrospective cohort study of newborns born at ≤34 weeks with PHVD (ventricular index [VI] >97th centile for gestational age and anterior horn width [AHW] >6 mm) from 2012 to 2020. Severe NDI was defined as global developmental delay or cerebral palsy GMFCS III-V at 18 months. RESULTS: Of 88 survivors with PHVD, 39% had a spontaneous resolution, 17% had persistent PHVD without intervention, and 44% had progressive PHVD receiving intervention. The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8-32.3) and between PHVD diagnosis and first neurosurgical intervention was 12.0 days (IQR 7.0-22.0). Group 1 had smaller median maximal VI (1.8, 3.4, 11.1 mm above p97; p < 0.001) and AHW (7.2, 10.8, 20.3 mm; p < 0.001) than Groups 2 and 3. Neurodevelopmental outcome data were available for 82% of survivors. Group 1 had reduced severe NDI compared to Group 3 (15% vs 66%; p < 0.001). CONCLUSION: Newborns with PHVD without spontaneous resolution are at higher risk for impairments despite neurosurgical interventions, which may be due to larger ventricular dilatation. IMPACT: The natural evolution of post-hemorrhagic ventricular dilatation (PHVD) and developmental implications of spontaneous resolution are not well established. In this study, approximately one in three newborns with PHVD experienced spontaneous resolution and this subset of newborns had reduced rates of neurodevelopmental impairments. More prominent ventricular dilatation was associated with reduced rates of spontaneous resolution and increased rates of severe neurodevelopmental impairment among newborns with PHVD. Understanding clinically relevant time points in the evolution of PHVD and predictors of spontaneous resolution may help inform the discussion around the optimal timing for intervention and allow for more precise prognostication in this population.

Association of Cystic Periventricular Leukomalacia and Postnatal Epilepsy in Very Preterm Infants.

INTRODUCTION: Cystic periventricular leukomalacia (PVL) is the most common white matter injury and a common cause of cerebral palsy in preterm infants. Postnatal epilepsy may occur after cystic PVL, but their causal relationship remains uncertain. Our aim was to validate the contribution of cystic PVL to postnatal epilepsy in very preterm infants and demonstrate their seizure characteristics. METHODS: This prospective cohort study enrolled 1,342 preterm infants (birth weight <1,500 g and gestational age <32 weeks) from 2003 to 2015. Cystic PVL was diagnosed by serial cerebral ultrasound, and other comorbidities were recorded during hospitalization. Neurological developments and consequences, including epilepsy, were serially accessed until the age of 5. RESULTS: A total of 976 preterm infants completed a 5-year neurological follow-up; 47 (4.8%) had cystic PVL. Preterm infants with cystic PVL were commonly associated with other comorbidities, including necrotizing enterocolitis stage III, neonatal seizures, and intraventricular hemorrhage during hospitalization. At age 5, 14 of the 47 (29.8%) preterm infants with cystic PVL had postnatal epilepsy. After adjusting for gender, gestational age, and three common comorbidities, cystic PVL was an independent risk factor for postnatal epilepsy (adjust OR: 16.2; 95% CI: 6.8-38.4; p < 0.001). Postnatal epilepsy after cystic PVL was commonly the generalized type (13 of 14, 92.9%), not intractable and most occurred after 1 year of age. DISCUSSION/CONCLUSION: Cystic PVL would independently lead to postnatal epilepsy. Preterm infants with cystic PVL are at risk of postnatal epilepsy after age 1 in addition to cerebral palsy.

Impact of Transfer for Surgical Management of Preterm Necrotising Enterocolitis or Focal Intestinal Perforation.

OBJECTIVE: To compare outcomes after surgically managed necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in infants <32 weeks requiring transfer to or presenting in a single surgical centre. DESIGN: Retrospective review of transferred and inborn NEC or FIP, from January 2013 to December 2020. PATIENTS: 107 transfers with possible NEC or FIP contributed 92 cases (final diagnoses NEC (75) and FIP (17)); 113 inborn cases: NEC (84) and FIP (29). RESULTS: In infants with a final diagnosis of NEC, medical management after transfer was as common as when inborn (41% TC vs 54% p = 0.12). Unadjusted all-cause mortality was lower in inborn NEC (19% vs 27%) and FIP (10% vs 29%). In infants undergoing surgery unadjusted mortality attributable to NEC or FIP was lower if inborn (21% vs 41% NEC, 7% vs 24% FIP). In regression analysis of surgically treated infants, being transferred was associated with increased all-cause mortality (OR 2.55 (1.03-6.79)) and mortality attributable to NEC or FIP (OR 4.89 (1.80-14.97)). CONCLUSIONS: These data require replication, but if confirmed, suggest that focusing care for infants at highest risk of developing NEC or FIP in a NICU with on-site surgical expertise may improve outcomes.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).