Defining necrotizing enterocolitis: current difficulties and future opportunities.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in hospitalized infants. First classified through Bell staging in 1978, a number of additional definitions of NEC have been proposed in the subsequent decades. In this review, we summarize eight current definitions of NEC, and explore similarities and differences in clinical signs and radiographic features included within these definitions, as well as their limitations. We highlight the importance of a global consensus on defining NEC to improve NEC research and outcomes, incorporating input from participants at an international NEC conference. We also highlight the important role of patient-families in helping to redefine NEC.

Challenges in diagnosing necrotizing enterocolitis.

One of the many challenges with necrotizing enterocolitis (NEC) remains our inability to make an accurate diagnosis of NEC. The lack of a unifying cause and multiple variations in presentations lead to great uncertainty with NEC. Separating out the needs of the researcher wanting to define NEC from the clinician and patient family's perspectives who want an accurate diagnosis for NEC is important. The need to augment and/or replace the outdated modified Bell staging criteria is crucial to improving NEC management. Emerging literature suggests that genetic susceptibility and stool microbiota signatures may help identify preterm infants at increased risk of the disease. Ongoing studies using single or multi-omic approaches may help to characterize biomarkers that will aid in the prediction or early diagnosis of NEC, as well as differentiate other causes of severe bowel injury. Bowel ultrasound shows promise in improving our diagnostic accuracy for NEC but has been slow in adoption. Patient family perspectives are key in accelerating our efforts to integrate newer diagnostic methods into practice.

Hypoxic-ischemic enterocolitis: a proposal of a new terminology for early NEC or NEC-like disease in preterm infants, a single-center prospective observational study.

We aimed to investigate the role of hypoxia-ischemia in the pathophysiology of early NEC/NEC like disease (ENEC) and classic NEC/NEC like disease (CNEC) in preterm infants. In this pilot study, preterm infants who developed the clinical symptoms and signs of NEC/NEC like disease were divided into two groups as early (≤ 7 days, ENEC) or late (> 7 days, CNEC) groups. Beside clinical variables, serum L-lactate, endothelin-1 (ET-1), platelet activating factor (PAF), and intestinal fatty acid binding protein (I-FABP) levels were measured from umbilical/peripheric venous blood in the first hour of life and during the clinical presentation in all groups. A total of 86 preterm infants were enrolled in the study. In the ENEC group, the incidences of fetal umbilical artery Doppler velocimetry abnormalities, IUGR, and delayed passage of first meconium were higher. In addition, mean levels of L-lactate, ET-1, PAF, and I-FABP were higher in the first hour of life.Conclusion: Our study firstly showed that the dominant pathophysiological factor of ENEC is prenatal hypoxic-ischemic event where intestinal injury and inflammation begin in-utero and become clinically apparent in the first week of life. Therefore, we propose a new term "Hypoxic-Ischemic Enterocolitis (HIEnt)" for the definition of ENEC in preterm infants with prenatal hemodynamic disturbances and IUGR. This new sight can provide individualized preventive and therapeutic strategies for preterm infants.What is Known:• The pathophysiology of early necrotizing enterocolitis (NEC) or NEC-like disease which is seen in the first week of life seems different than classic necrotizing enterocolitis (CNEC) which is always seen after the first week of life.What is New:• This study suggests that perinatal hypoxic-ischemic process with inflammation is the point of origin of fetal intestinal injury leading to ENEC.• We propose a new term "Hypoxic-Ischemic Enterocolitis (HIEnt)" for the definition and differentiation of this unique clinical entity.

Intraventricular hemorrhage and posthemorrhagic hydrocephalus in preterm infants: diagnosis, classification, and treatment options.

PURPOSE: Intraventricular hemorrhage is the most important adverse neurologic event for preterm and very low weight birth infants in the neonatal period. This pathology can lead to various delays in motor, language, and cognition development. The aim of this article is to give an overview of the knowledge in diagnosis, classification, and treatment options of this pathology. METHOD: A systematic review has been made. RESULTS: The cranial ultrasound can be used to identify the hemorrhage and grade it according to the modified Papile grading system. There is no standardized protocol of intervention as there are controversial results on which of the temporizing neurosurgical procedures is best and about the appropriate parameters to consider a conversion to ventriculoperitoneal shunt. However, it has been established that the most important prognosis factor is the involvement and damage of the white matter. CONCLUSION: More evidence is required to create a standardized protocol that can ensure the best possible outcome for these patients.

A Lung Ultrasound Severity Score Predicts Chronic Lung Disease in Preterm Infants.

OBJECTIVE: To test the hypothesis that a lung ultrasound severity score (LUSsc) can predict the development of chronic lung disease (CLD) in preterm neonates. STUDY DESIGN: Preterm infants <30 weeks' gestational age were enrolled in this study. Lung ultrasound (LUS) was performed between 1 and 9 postnatal weeks. All ultrasound studies were done assessing three lung zones on each lung. Each zone was given a score between 0 and 3. A receiver operating characteristic curve was constructed to assess the ability of LUSsc to predict CLD. RESULTS: We studied 27 infants at a median (interquartile range [IQR]) gestational age and birth weight of 26 weeks (25-29) and 780 g (530-1,045), respectively. Median (IQR) postnatal age at the time of LUS studies was 5 (2-8) weeks. Fourteen infants who developed CLD underwent 34 studies. Thirteen infants without CLD underwent 30 studies. Those who developed CLD had a higher LUSsc than those who did not (median [IQR] of scores: 9 [6-12] vs. 3 [1-4], p < 0.0001). An LUSsc cutoff of 6 has a sensitivity and specificity of 76 and 97% and positive and negative predictive values of 95 and 82%, respectively. Adding gestational age < 27 weeks improved sensitivity and specificity to 86 and 98% and positive and negative predictive values to 97 and 88%. CONCLUSION: LUSsc between 2 and 8 weeks can predict development of CLD in preterm neonates.

Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.

BACKGROUND: Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage. OBJECTIVE: We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation. STUDY DESIGN: The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome. RESULTS: The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio, 3.4; 95% confidence interval, 1.1-10.2]). Premature rupture of membranes did not significantly increase the risk. CONCLUSION: Relationships between the causes of preterm birth and intraventricular hemorrhage were limited to specific and rare cases involving acute hypoxia-ischemia and/or inflammation. While the emergent nature of placental abruption would challenge any attempts to optimize management, the prenatal care offered during preterm labor could be improved.

Management Outcome of Severe Laryngomalacia at Queen Sirikit National Institute Child Health.

Background: Outcomes of the different management in severe laryngomalacia (LM) have not been evaluated. Objective: To identify the management practices and to evaluate the outcomes in patient with severe LM. Material and Method: The medical records of LM at Queen Sirikit National Institute Child Health between January2007 and December 2012 were retrospectively reviewed. Results: Severe LM 69.8% (30/43) were found in patients diagnosed with LM. Type B (complete collapse) at 46.67% were the most common finding. Decision of management were made individually based on consideration of disease severity and comorbidity. The outcomes after management were evaluated by pre- and post-symptoms score. Post-symptoms scores were statistically significant better than pre-symptom score in all management (observation p<0.001, laser supraglottoplasty p = 0.003, and tracheotomy p = 0.001). Conclusion: Our management in severe LM include: observation, laser supraglottoplasty, and tracheostomy. The overall post-management outcome were satisfactory but the present study was limited to relatively small number of patients.

Short- and Long-Term Outcomes for Extremely Preterm Infants.

Prematurity is the leading cause of infant mortality worldwide. In developed countries, extremely preterm infants contribute disproportionately to both neonatal and infant mortality. Survival of this high-risk population has incrementally improved in recent years. Despite these improvements, approximately one in four extremely preterm infants dies during the birth hospitalization. Among those who survive, respiratory and other morbidities are common, although their effect on quality of life is variable. In addition, long-term neurodevelopmental impairment is a large concern for patients, clinicians, and families. However, the interplay of multiple factors contributes to neurodevelopmental impairment, with measures that change over time and outcomes that can be difficult to define and predict. Understanding outcomes of extremely preterm infants can help better counsel families regarding antenatal and postnatal care and guide strategies to improve survival without morbidity. This review summarizes recent evidence to provide an overview into the short- and long-term outcomes for extremely preterm infants.

Argenta clinical classification of deformational plagiocephaly.

INTRODUCTION: A stratification system is useful in deformational plagiocephaly (DP) to help categorize patients and reproduce a consistent treatment strategy. The Argenta classification is a clinical 5-point scale for unilateral DP and 3-point scale for central DP (CDP). METHODS: A retrospective review was completed for patients with DP and classified using the Argenta clinical classification by plastic surgeons at a tertiary medical center over a 12-year period. RESULTS: In the 4483 patients, type III was the most prevalent DP type (42%) followed by II, IV, I, and V. Within CDP, VIB was the most common (6%) followed by VIA and VIC. Right-sided DP (56.8%) was more common than left-sided (28.3%) and bilateral (20.4%) (P < 0.0001). For treatment, 89.8% used molding helmet therapy, 9.3% used positioning only, and 0.4% used sock hat. Helmet use increased with increasing type to 98% with type V. In CDP, there was a significant increase in helmet use between VIA and VIB, but helmet use decreased in VIC. There was a higher rate of positioning only in types I, II, and VIA, which diminished as severity increased. Deformational plagiocephaly corrected to type I or 0 in 83.5% of the patients with the highest correction rate in type I (90.7%). Mean age of correction was 11.4 months and time to correction was 5.7 months. Both significantly increased with severity of type in the patients with DP but not in those with CDP. CONCLUSIONS: The Argenta classification scale allows reliable evaluation for cranial deformities and may help predict the optimal type duration of treatment.

Pyloric atresia in the neonate.

Bowel obstruction is a common cause for admission into the NICU, but pyloric atresia (PA) is a very rare cause of bowel obstruction. This article illustrates the development of the fetal gastrointestinal tract, most specifically the stomach and pylorus. Pathophysiology, typing, and treatment of PA are also explored. Presented are two cases of PA that occurred in a Level III NICU one month apart. Management of this condition is surgical in nature. Long-term prognosis is usually excellent because this defect is often isolated.

Predictive and concurrent validity of standardized neurodevelopmental examinations by the Griffiths scales and Bayley scales of infant development II.

Standardized examinations of preterm infants are used to identify candidates for early intervention. We aimed to assess the predictive power and concurrent validity of the mental development index of the Bayley scales of infant development II (Bayley MDI) and the Griffiths scales developmental quotient (Griffiths DQ) in healthy term and preterm infants <1500 g birth weight without major perinatal complications.137 Infants (89 term, 48 preterm) were examined by both tests at a corrected age of 6, 12, and 22 months, and 114 went on to undergo Bayley assessments at 39 months.There were significant correlations between Bayley and Griffiths results at 6, 12, and 22 months (r=0.530, 0.714, and 0.833, respectively, p<0.001) but Bland Altman plots revealed major systematic bias at 6 months (Griffiths>Bayley, mean differences 14.3±9.8) and 22 months (Bayley>Griffiths, mean difference 5.2±13.9) and wide 95% limits of agreement at 6, 12 and 22 months (35.9%, 40.0%, and 52.4%, respectively). The agreement for a presumptive diagnosis of developmental impairment in the group of preterm infants between Bayley examinations obtained at 39 months corrected age (reference) and previous examinations was poor at 6, 12, and 22 months for both Bayley and Griffiths (Cohen's kappa for Griffiths: 0.225, 0.192, 0.369; for Bayley: 0.121, 0.316, 0.369, respectively).Caution should be exercised when interpreting results from standardized neurodevelopmental examinations obtained during the first 2 years of life in comparatively well preterm infants.

Neonatal outcomes in spontaneous versus obstetrically indicated late preterm births in a nova scotia population.

OBJECTIVE: To examine the indications for late preterm delivery in Nova Scotia and to compare the short-term outcomes by type of labour (spontaneous, induced, none). METHODS: We conducted a population-based retrospective cohort study of late preterm births (34+0 to 36+6 weeks' gestation) between 1988 and 2009 using the Nova Scotia Atlee Perinatal Database. The association between labour type and neonatal outcomes was examined with logistic regression to estimate odds ratios with 95% confidence intervals. RESULTS: Of the 10 315 late preterm births, 6228 followed spontaneous labour, 2338 followed induction of labour, and 1689 followed Caesarean section with no labour. Babies born following induction were at higher risk of developing hyperbilirubinemia (OR 1.14; 95% CI 1.03 to 1.27) and needing total parenteral nutrition (OR 1.52; 95% CI 1.15 to 1.99) than those born spontaneously. Those born without labour were at higher risk of needing resuscitation (OR 2.43; 95% CI 1.84 to 3.21) and total parenteral nutrition (OR 2.54; 95% CI 1.93 to 3.33) and developing transient tachypnea of the newborn (OR 1.43; 95% CI 1.10 to 1.85), hypoglycemia (OR 1.97; 95% CI 1.63 to 2.39), respiratory distress syndrome (OR 2.33; 95% CI 1.89 to 2.88), necrotizing enterocolitis (OR 3.20; 95% CI 1.07 to 9.53), and apneic spells (OR 1.29; 95% CI 1.05 to 1.59). When adjusted for maternal and fetal factors, odd ratios were only slightly attenuated. CONCLUSION: Among late preterm babies, those born by Caesarean section without labour are at increased risk of many adverse outcomes, while those born following induction of labour are at increased risk of few of the outcomes studied. Maternal and fetal factors other than those for which adjustment was made may contribute to the differences in outcome by labour type.

NCI classification of thrombocytopenia in extremely preterm neonates and its association with mortality and morbidity.

BACKGROUND: Thrombocytopenia (TP) is a common finding among preterm neonates and has been associated with mortality and morbidities. Yet, there is no consistent classification for neonatal TP. TP in adults has recently been graded by the National Cancer Institute (NCI) Common Toxicity Criteria and has been shown to predict clinical outcomes. OBJECTIVE: To use the NCI classification for TP in preterm neonates and elucidate its association with clinical outcomes. METHODS: Retrospective chart review was done on neonates born at gestational age (GA) ≤28 weeks and survived for ≥7 days. TP was classified as per NCI guidelines at 7 days and 28 days of age and their association with mortality, major morbidities and hospital length of stay (LOS) were investigated. RESULTS: A total of 286 patients were included in the study with a mean GA of 26.3±1.5 weeks and birth weight of 899±215 g. NCI TP grades at 7 days were significantly (P<0.001) associated with mortality, LOS, intraventricular hemorrhage and Gram negative infections. In addition to these outcomes, necrotizing enterocolitis, Gram positive and fungal infections were also significantly associated with NCI TP grades at 28 days. CONCLUSIONS: Classification of TP using the NCI criteria in extreme preterm neonates is clinically applicable. This grading system of platelet counts is significantly associated with mortality, morbidity and LOS in preterm neonates.

[Diagnostic endoscopy of the nasal cavity and nasopharynx in premature newborn infants].

Disturbed nasal breathing in the children always was a topical socio-medical problem and has remained such up to now. The objective of the present investigation was to estimate the potential of modern endoscopic techniques for diagnostics of disturbed nasal breathing in the premature infants and to develop therapeutic measures aimed at the prevention of destructive changes in the nose during therapy with the use of continuous positive airway pressure (CPAP). The study included 43 children ranging in the age from 1 month to 2 years (24 boys and 19 girls). All the newborn babies were transferred to the department of resuscitation and intensive therapy for the urgent treatment including respiratory support with the use of the CPAP technique. The endoscopic surveillance made it possible to exactly determine the causes responsible for the disturbances of nasal breathing in the children who survived the critical conditions, to estimate the anatomical and functional conditions of the nasopharyngeal structures, and to develop therapeutic and preventive measures to protect the nose from further destructive changes.

A systematic review of the definitions and prevalence of feeding intolerance in preterm infants.

BACKGROUND & AIMS: Feeding intolerance (FI) is a common phenomenon experienced in preterm infants in neonatal intensive care units, as well as being a focus of many research studies into feeding methods, particularly in relation to comorbidities. There is no widely accepted definition of FI. This systematic review aimed to explore the range of definitions used for FI and provide an estimate of the prevalence amongst preterm infants. METHODS: Searches were completed on MEDLINE (includes the Cochrane library), Embase, PsycInfo, CINAHL, NHS Evidence and Web of Science. Inclusion criteria; preterm infants in neonatal units, a clear definition of FI, >10 patients and be available in English language. Case reports were excluded. RESULTS: One hundred studies were included. Definitions of FI were inconsistent. Studies were grouped according to definition used into: Group A - measuring gastric residual volume (GRV) only; group B - GRV and abdominal distension (AD); group C - GRV, AD and gastrointestinal symptoms (GI) which included any of vomiting, bilious vomiting and blood in stool; group D- GRV and GI; group E - AD and GI; group F - GI only and group G - any other elements used. Meta-analysis demonstrated that prevalence of FI between groups varied from 15 to 30% with an overall prevalence of 27% (95% confidence interval 23-31%). Group A had the highest prevalence. Review of time to full enteral feed was performed (37 studies) which demonstrated a range of 11.3-18.3 days depending on which FI definition used. DISCUSSION: Definitions of FI in research are inconsistent, a similar finding to that seen in studies in both paediatric and adult critical care populations. The difficulty of defining FI in the preterm population is the concern regarding necrotising enterocolitis, with some studies using an overlap in their definitions, despite differing pathophysiology and management. Due to the heterogeneity of data obtained in this review regarding definitions used, further robust research is required in order to conclude which elements which should be used to define FI in this population. PROSPERO NUMBER: CRD42019155596. Registered November 2019.

Association of maternal diabetes mellitus with preterm infant outcomes: a systematic review and meta-analysis.

CONTEXT: The association between maternal diabetes and outcomes of infants who are born preterm is unclear. OBJECTIVE: To perform a systematic review and meta-analysis of clinical studies exploring the association between maternal diabetes and preterm infant outcomes. METHODS: Medline, PubMed and Cumulative Index of Nursing and Allied Health Literature databases were searched without language restriction from 1 January 2000 until 19 August 2019. Studies examining preterm infants <37 weeks gestational age and reporting prespecified outcomes of this review based on maternal diabetes as primary exposure variable were included. RESULTS: Of 7956 records identified through database searches, 9 studies were included in the study. No significant association was found between maternal diabetes and in-hospital mortality (adjusted RR (aRR) 0.90 (95% CI 0.73 to 1.11); 6 studies; participants=1 191 226; I2=83%). Similarly, no significant association was found between maternal diabetes and bronchopulmonary dysplasia (aRR 1.00 (95% CI 0.92 to 1.07); 4 studies; participants=107 902; I2=0%), intraventricular haemorrhage or cystic periventricular leukomalacia (aRR 0.91 (95% CI 0.80 to 1.03); 3 studies; participants=115 050; I2=0%), necrotising enterocolitis (aRR 1.13 (95% CI 0.90 to 1.42); 5 studies; participants=142 579; I2=56%) and retinopathy of prematurity (ROP) (aRR 1.17 (95% CI 0.85 to 1.61); 5 studies; participants=126 672; I2=84). A sensitivity analysis where low risk of bias studies were included in the meta-analyses showed similar results; however, the heterogeneity was lower for in-hospital mortality and ROP. CONCLUSION: Maternal diabetes was not associated with in-hospital mortality and severe neonatal morbidities in preterm infants. Future studies should explore the association between the severity of maternal diabetes with preterm infant outcomes.

Continued improvement in morbidity reduction in extremely premature infants.

OBJECTIVE: Provide a progress report updating our long-term quality improvement collaboration focused on major morbidity reduction in extremely premature infants 23-27 weeks. METHODS: 10 Vermont Oxford Network (VON) neonatal intensive care units (NICUs) (the POD) sustained a structured alliance: (A) face-to-face meetings, site visits and teleconferences, (B) transparent process and outcomes sharing, (C) utilisation of evidence-based potentially better practice toolkits, (D) family integration and (E) benchmarking via a composite mortality-morbidity score (Benefit Metric). Morbidity-specific toolkits were employed variably by each NICU according to local priorities. The eight major VON morbidities and the risk-adjusted Benefit Metric were compared in two epochs 2010-2013 versus 2014-2018. RESULTS: 5888 infants, mean (SD) gestational age 25.8 (1.4) weeks, were tracked. The POD Benefit Metric significantly improved (p=0.03) and remained superior to the aggregate VON both epochs (p<0.001). Four POD morbidities significantly improved through 2018 - chronic lung disease (48%-40%), discharge weight <10th percentile (32%-22%), any late infection (19%-17%) and periventricular leukomalacia (4%-2%). In epoch 2, 34% of survivors had none of the eight major morbidities, while 36% had just one. Mortality did not change. CONCLUSIONS: Inter-NICU collaboration, process and outcomes sharing and potentially better practice toolkits sustain improvement in 23-27 week morbidity rates, notably chronic lung disease, extrauterine growth restriction and the lowest zero-or-one major morbidity rate reported by a quality improvement collaboration. Unrevealed biological and cultural variables affect morbidity rates, countless remain unmeasured, thus duplication to other quality improvement groups is challenging. Understanding intensive care as innumerable interactions and constant flux that defy convenient linear constructs is fundamental.

Severe intraventricular hemorrhage in preterm infants: comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage.

Grade 3 intraventricular hemorrhage (IVH) (without parenchymal involvement) and grade 4 IVH (with parenchymal involvement) are often combined into description of a single entity, usually "severe" IVH, despite different long-term neurodevelopmental outcome. Although risk factors for severe IVH have already been well described, it is not known if these risk factors and associated short-term neonatal morbidities are different for grade 3 and grade 4 IVH, and indeed, this clustering of grade 3 and grade 4 IVH into severe IVH precludes further delineation of the potential risk and protective factors that can be altered to reduce the incidence of grade 4 IVH, which is presumably associated with worse outcome compared with grade 3 IVH. We sought to characterize and compare commonly cited risk factors and associated short-term neonatal morbidities between grade 3 and grade 4 IVH in very low-birth-weight (VLBW) infants. We performed a retrospective review of VLBW (birth weight < 1500 g) infants with severe IVH born between January 2001 and March 2007. Fifty-nine (10.5%) of 562 infants surviving beyond 3 days of age had severe IVH as recorded on routine cranial sonography during the first 7 to 10 days of life, 28 had grade 3, and 31 had grade 4 IVH. Infants with grade 4 IVH were younger [gestational age (weeks), grade 4 IVH versus grade 3 IVH: 25.5 +/- 1.7 versus 26.7 +/- 1.7, p = 0.02) and weighed less at birth [birth weight (g), grade 4 IVH versus grade 3 IVH: 860 +/- 214 versus 1007 +/- 253, p = 0.03) compared with infants with grade 3 IVH. Other commonly cited clinical factors that alter the risk for severe IVH, including mode of delivery, pregnancy-induced hypertension, premature and/or prolonged rupture of membranes, maternal fever, maternal bleeding, prenatal steroid administration, maternal magnesium sulfate therapy, 1-minute and 5-minute Apgar scores, need for delivery room resuscitation (epinephrine and chest compressions), surfactant therapy, presence of refractory hypotension, evidence of early onset culture-proven sepsis, use of high-frequency ventilation, presence of pneumothorax, and hemodynamically significant patent ductus arteriosus, were similar between infants with grade 3 and grade 4 IVH. Carbon dioxide tensions (minimum PaC (2), maximum PaCO(2), mean PaCO(2), standard deviation of PaCO(2), and coefficient of variation of PaCO (2)) in infants receiving mechanical ventilation during first 3 postnatal days were also not statistically dissimilar. To determine the variables differentiating grade 3 from grade 4 IVH in the study population, logistic regression analysis confirmed only the independent association of gestational age (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.5 to 0.9, P = 0.012) and maternal magnesium sulfate therapy (OR 0.3, 95% CI 0.07 to 0.9, P = 0.04) with the development of grade 4 IVH. Short-term neonatal morbidities were also similar between infants with grade 3 and grade 4 IVH. Among VLBW infants, the risk of a grade 4 versus grade 3 IVH increases with declining gestational age, but does not appear to be related to other commonly cited clinical factors. This information may be useful for prognostication and may improve the quality of parental counseling.

Outcome of extremely low birth weight survivors at school age: the influence of perinatal parameters on neurodevelopment.

Extremely low birth weight (ELBW) is associated with impaired neurodevelopmental outcome in infancy. Information on the long-term cognitive and neurological consequences of ELBW is scarce. We aimed to identify the perinatal and neonatal factors of ELBW infants associated with adverse cognitive and neurological outcome at school age. A regional cohort of 135 ELBW infants born between 1993 and 1998 was prospectively evaluated at 3, 6, 12, and 18 months postmenstrual age and at yearly intervals up to age 10 years. The comprehensive follow-up programme for high-risk infants included neurological examinations and psychometric evaluations. According to the overall results of these tests, children were classified as either being normal or having minor or major impairment. At a mean age of 8.4 (SD: 1.6) years, 43% of children had survived without any impairment. Minor impairment was diagnosed in 39% and major impairment in 18% of assessed children. The proportion of disabled school children rose with decreasing gestational age. The following neonatal complications were significant risk factors for developing major or minor impairment at school age: an increase in head circumference < 6 mm per week (OR 4.0, 95% CI: 1.1-14.8), parenteral nutrition > or = 6 weeks (OR 2.5, 95% CI: 1.1-6.0), and mechanical ventilation > 14 days (OR 2.3, 95% CI: 1.0-5.1). High-grade intraventricular haemorrhage (IVH) and/or PVL (OR 13.3, 95% CI: 4.0-44.9), neonatal seizures (OR 5.2, 95% CI: 1.2-22.4) and bowel perforation, and/or necrotizing enterocolitis (OR 4.4, 95% CI: 1.1-17.0) were significant risk factors for developing major impairment. In spite of the relatively large proportion of normal children, ELBW remains an important risk factor for neurodevelopmental impairment at school age. Thus, measures to prevent complications such as necrotizing enterocolitis, cerebral haemorrhage, and undernutrition remain important goals for neonatal intensive care.

Causative factors in cerebral palsy.

Causative factors in cerebral palsy (CP) vary to some degree according to gestational age group and clinical CP subtype. Such catastrophes of birth as placental abruption, cord prolapse, and uterine rupture sharply heighten risk of CP. These conditions are fortunately uncommon, and are sometimes not survived; individually and collectively they account for only a small proportion of CP. Among other factors associated with increased risk of CP are prematurity, intrauterine exposure to infection or maternal fever in labor, ischemic stroke, congenital malformations, atypical intrauterine growth (restricted or excessive for gestational age), and complications of multiple gestations. Although any 1 factor, if severe, may be sufficient to cause CP, more often it is the presence of multiple risk factors that overwhelms defense mechanisms and leads to CP. The contribution of genetic vulnerabilities that interact with environmental stressors is an emerging aspect of our understanding of causative factors in CP.