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

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

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

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

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

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

Interaction between pulmonary vasculature and the patent ductus arteriosus in very premature infants.

BACKGROUND: The benefits of closing the ductus arteriosus in very preterm infants have not been convincingly shown in numerous clinical trials. Because a large untreated ductus arteriosus can cause death from congestive heart failure in infants born at term, we need to explain why this might not occur in premature infants born at <28 weeks' gestation. METHODS: Based on information in the literature, I have commented on the possible relationship between the pulmonary vasculature and the shunt through the patent ductus arteriosus. RESULTS: Many of these infants have bronchopulmonary dysplasia, in which animal and human studies have shown a reduced number of capillaries and small pulmonary arteries as well as reduction in vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1). Both of these import angiogenic factors. Some who do not have bronchopulmonary dysplasia may have a restricted pulmonary vascular bed. CONCLUSIONS: The increased pulmonary vascular resistance in very premature infants may restrict pulmonary blood flow even if the ductus is large, thus reducing the urgency for ductus closure.

Pulmonary hypertension in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications.

The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term "Fetal Inflammatory Response Syndrome" (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur ("rescued by birth"). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.

Assessing Patent Ductus Arteriosus (PDA) Significance on Cardiac Output by Whole-Body Bio-impedance.

We evaluated the effectiveness of a whole-body bioimpedance device (NICaS®, NI Medical, Petach Tikva, Israel) to predict the presence of a hemodynamically significant patent ductus arteriosus (PDA) in premature infants. A total of 36 infants less than 35 week's gestation age and birth weights of less than 1750 g were included in the study. Using the NICaS® device, we obtained whole-body bioimpedance measurements of stroke volume index (SI), cardiac output index (CI) and total peripheral resistance index. A total of 61 measurements were taken together with echocardiograph imaging. The study population was divided into three groups according to the echocardiograph results: group 1-small PDA, group 2-moderate PDA, and group 3-large PDA. Both SI and CI significantly increased from a median value of 22.6 ml/m2 and 3.4 l/min/m2 to 23.8 and 3.7, to 39.8 and 5.4 between groups 1, 2 and 3 respectively. The difference was statistically significant between groups 1 and 3 (P = 0.005 for SI and P = 0.002 for CI) and between groups 2 and 3 (P = 0.037 for SI and P = 0.05 for CI). We found statistically significant differences in SI and CI between infants with large PDAs and infants with no or small and medium PDAs. We suggest that these differences can be used in real time, in addition to echocardiography, in assessing the presence of significant PDAs.

El riñón del niño prematuro: riesgos a largo plazo / The kidney of the premature child: long-term risks

Resumen: El recién nacido prematuro se enfrenta a las condiciones extrauterinas con sistemas aún inmaduros, tanto anatómica como fisiológicamente. El riñón termina de desarrollarse a finales del tercer trimes tre del embarazo, por lo que está especialmente expuesto a alterar su desarrollo normal en caso de nacer en forma prematura. Esta situación puede condicionar, entre otras consecuencias, una menor masa renal funcional y cambios microvasculares que representan un riesgo elevado de hipertensión arterial y daño renal crónico en el largo plazo. En el presente artículo se analiza la evidencia existente actual sobre estos riesgos en los prematuros y se ofrece un esquema de seguimiento de estos niños desde el punto de vista nefrológico.

Abstract: The premature newborn faces extrauterine conditions with some systems still immature, both ana tomically and physiologically. The kidney finishes developing at the end of the third trimester of pregnancy, so it is especially exposed to alter its normal development if preterm birth occurs. This si tuation may condition, among other consequences, a lower functional renal mass and microvascular changes comprising a high risk of chronic kidney disease in the long term and arterial hypertension. This article analyzes the current evidence on these risks in premature infants and offers a nephrology follow-up scheme of these children.

Mechanical Ventilation Duration, Brainstem Development, and Neurodevelopment in Children Born Preterm: A Prospective Cohort Study.

OBJECTIVES: To determine, in children born preterm, the association of mechanical ventilation duration with brainstem development, white matter maturation, and neurodevelopmental outcomes at preschool age. STUDY DESIGN: This prospective cohort study included 144 neonates born at <30 weeks of gestation (75 male, mean gestational age 27.1 weeks, SD 1.6) with regional brainstem volumes automatically segmented on magnetic resonance imaging at term-equivalent age (TEA). The white matter maturation was assessed by diffusion tensor imaging and tract-based spatial statistics. Neurodevelopmental outcomes were assessed at 4.5 years of age using the Movement Assessment Battery for Children, 2nd Edition, and the Wechsler Primary and Preschool Scale of Intelligence, 4th Edition, full-scale IQ. The association between the duration of mechanical ventilation and brainstem development was validated in an independent cohort of children born very preterm. RESULTS: Each additional day of mechanical ventilation predicted lower motor scores (0.5-point decrease in the Movement Assessment Battery for Children, 2nd Edition, score by day of mechanical ventilation, 95% CI -0.6 to -0.3, P < .0001). Prolonged exposure to mechanical ventilation was associated with smaller pons and medulla volumes at TEA in 2 independent cohorts, along with widespread abnormalities in white matter maturation. Pons and medulla volumes at TEA predicted motor outcomes at 4.5 years of age. CONCLUSIONS: In neonates born very preterm, prolonged mechanical ventilation is associated with impaired brainstem development, abnormal white matter maturation, and lower motor scores at preschool age. Further research is needed to better understand the neural pathological mechanisms involved.

The Effect of Earmuffs on Physiological Parameters in Preterm Infants: A Systematic Review.

Noise may cause stress responses such as apnea, hypoxemia, changes in oxygen saturation and augmented oxygen consumption secondary to elevated heart and respiratory rates. Moreover, stress results in increased intracranial pressure, abnormal sleep patterns, hearing impairment, and bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, retardate development and alterations in the neuroendocrine system. Herein, this study aimed to discuss the effects of earmuffs on physiological parameters in preterm infants. The relevant and available peer-reviewed publications from 2012 to 2018 from various databases were analyzed. For the assessment of the studies, the full-text accessible studies were included for analysis. The retrieved documents were analyzed using VOSviewer regarding the geographical distributions of the documents with their numbers and citations, keywords proposed by the researchers. All records with the term "earmuffs OR earmuff" in the "article title, abstract, keywords" were retrieved from different databases. Accordingly, 396 documents containing the word "earmuffs OR earmuff" were recorded. The search was then restricted for publications that contain the words "noise AND nursing AND preterm" in the title and abstracts (TITLE-ABS-KEY (earmuffs OR earmuff)) AND (noise AND nursing AND preterm) (Scopus=390; Web of Science=1, Medline=2; Cochrane=1; Embase=1= Pubmed=1=n=396). After inclusion and exclusion criteria, 7 documents were recorded and then evaluated for the present study. As a conclusion, the effects of earmuffs on physiological parameters of preterm infants have not been clearly understood and reported yet. Along with the present documents, it is not clear that the use of earmuffs reduces stress and provides physiological stability in preterm infants born between approximately 28-32 weeks. The studies with a larger sample size are needed for validation of information reported in the articles analyzed herein.

Oxidative Stress Biomarker Decreased in Preterm Neonates Treated With Kangaroo Mother Care.

OBJECTIVE: Due to physiological and metabolic immaturity, prematurely born infants are at increased risk because of maternal separation in many neonatal intensive care units (NICUs). The stress induced from maternal-infant separation can lead to well-documented short-term physiologic instability and potentially lifelong neurological, sociological, or psychological sequelae. Based on previous studies of kangaroo mother care (KMC) that demonstrated improvement in physiologic parameters, we examined the impact of KMC on physiologic measures of stress (abdominal temperature, heart rate, oxygen saturation, perfusion index, near-infrared spectrometry), oxidative stress, and energy utilization/conservation in preterm infants. METHODS: In this randomized, stratified study of premature neonates, we compared the effects on urinary concentrations of biomarkers of energy utilization and oxidative stress of 1 hr of KMC versus incubator care on Day 3 of life in intervention-group babies (n = 26) and control-group babies (n = 25), respectively. On Day 4, both groups received 1 hr of KMC. Urinary samples were collected 3 hr before and 3 hr after intervention/incubator care on both days. Energy utilization was assessed by measures of adenosine triphosphate (ATP) degradation (i.e., hypoxanthine, xanthine, and uric acid). Oxidative stress was assessed using urinary allantoin. Mixed-models analysis was used to assess differences in purine/allantoin. RESULTS: Mean allantoin levels over Days 3 and 4 were significantly lower in the KMC group than in the control group (p = .026). CONCLUSIONS: Results provide preliminary evidence that KMC reduces neonatal oxidative stress processes and that urinary allantoin could serve as an effective noninvasive marker for future studies.

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia.

We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). However, there is still a paucity of studies providing scientific evidence to guide future updates of BPD severity definitions. Our goal was to validate a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks postmenstrual age (PMA). We hypothesized that this approach improves BPD risk assessment, particularly in extremely premature infants. This is a longitudinal cohort of premature infants (≤32 weeks PMA, n = 188; Washington D.C). We performed receiver operating characteristic analysis to define optimal BPD severity levels using the duration of supplementary O2 as predictor and respiratory hospitalization after discharge as outcome. Internal validation included lung X-ray imaging and phenotypical characterization of BPD severity levels. External validation was conducted in an independent longitudinal cohort of premature infants (≤36 weeks PMA, n = 130; Bogota). We found that incorporating the total number of days requiring O2 (without restricting at 36 weeks PMA) improved the prediction of respiratory outcomes according to BPD severity. In addition, we defined a new severity category (level IV) with prolonged exposure to supplemental O2 (≥120 days) that has the highest risk of respiratory hospitalizations after discharge. We confirmed these findings in our validation cohort using ambulatory determination of O2 requirements. In conclusion, a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks improves risk stratification and should be considered when updating current BPD severity definitions.

A Case of Congenital Anaplastic Large Cell Lymphoma in a Very Preterm Low-Birth Weight Neonate.

A premature infant male was born at 30 weeks' gestation with severe coagulopathy and thrombocytopenia. Over the first days of his life, the patient developed evidence of immune hyperactivation with adenopathy, hepatosplenomegaly, and elevated ferritin. Although the patient met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH), flow cytometric based assays were not consistent with primary HLH. A lymph node and bone marrow biopsy eventually revealed the presence of anaplastic lymphoma kinase+anaplastic large cell lymphoma. To our knowledge, this is the earliest presentation of a lymphoma, and expands the known timeframe of lymphomagenesis.

Postmenstrual age at discharge in premature infants with and without ventilatory pattern instability.

RATIONALE: To determine if ventilatory pattern instability, manifested as periodic breathing (PB) during physiologic challenge testing, affects postmenstrual age (PMA) at discharge. METHODS: Eighty infants underwent challenge testing at 36 weeks PMA. Infants breathing supplemental O2 received a room air challenge (RAC, N = 51); those breathing ambient air underwent a hypoxic challenge test (HCT, N = 29). Infants were assigned one of four ventilatory control phenotypes based on the presence or absence of PB during their test, and if they passed or failed because of hypoxemia during the challenge test. RESULTS: There were no clinical or demographic differences between groups. Infants who passed their challenge testing were, on average, discharged 1.6 weeks sooner than those who failed. The groups of ventilatory control phenotypes differed in PMA at discharge (p = 0.0020), but those with PB were younger by PMA at discharge. CONCLUSIONS: Ventilatory pattern instability did not prolong time to discharge. Passing either challenge was associated with earlier discharge, suggesting these tests might identify infants who can have nasal cannula support removed and be safely discharged sooner. Most of the infants who failed their challenge tests with PB were receiving nasal cannula support. Nasal cannula support may be not only treating hypoxemia due to bronchopulmonary dysplasia (BPD), but also mitigating their ventilatory pattern instability.

[Extremely preterm birth in Sweden - clear progress but remaining challenges]. / Extremt förtidig födelse ­ svåra utmaningar trots stora framsteg - Överlevnaden till 1 års ålder är hög, men allvarlig neonatal sjuklighet är en utmaning.

The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 % in a recent study of extremely preterm infants born at < 27 gestational weeks delivered in Sweden in 2014-2016 and surviving to 1 year of age. Damage to immature organ systems inflicted during the neonatal period causes varying degrees of functional impairment with lasting effects in the growing child. There is an urgent need for evidence-based novel interventions aiming to prevent neonatal morbidity with a subsequent improvement of long-term outcome.

Relationship between pulmonary artery acceleration time and pulmonary artery pressures in infants.

BACKGROUND: Pulmonary artery acceleration time measured by echocardiography inversely correlates with pulmonary artery pressures in adults and children older than 1 year of age. There is a paucity of data investigating this relationship in young children, particularly among preterm infants. OBJECTIVE: To characterize the relationship between pulmonary artery acceleration time (PAAT) and pulmonary artery pressures in infants. DESIGN/METHODS: Patients ≤ 1 year of age at Children's Hospital of Philadelphia between 2011 and 2017 were reviewed. Infants with congenital heart disease were excluded, except those with a patent ductus arteriosus (PDA), atrial septal defect (ASD), or ventricular septal defect (VSD). Linear regression analysis was used to assess the correlation between PAAT measured by echocardiography and systolic pulmonary artery pressure, mean pulmonary artery pressure, and indexed pulmonary vascular resistance from cardiac catheterization. RESULTS: Fifty-seven infants were included, of which 61% were preterm and 49% had a diagnosis of bronchopulmonary dysplasia. The median postmenstrual age and weight at catheterization were 51.1 weeks (IQR 35.8-67.9 weeks) and 4400 g (IQR 3100-6500 g), respectively. Forty-four infants (77%) had a patent ductus arteriosus (PDA). There was a weak inverse correlation between PAAT with mPAP (r = -0.35, P = 0.01), sPAP (r = -0.29, P = 0.03), and PVRi (r = -0.29, P = 0.03). CONCLUSION: There is a weak inverse relationship between PAAT and pulmonary artery pressures. This relationship is less robust in our population of infants with a high incidence of PDAs compared to previous studies in older children. Thus, PAAT may be less clinically meaningful for diagnosing pulmonary arterial hypertension in infants, particularly those with PDAs.

Small for gestational age very preterm infants present a higher risk of developing bronchopulmonary dysplasia.

INTRODUCTION: Several studies assessed the influence of a low birth weight on bronchopulmonary dysplasia (BPD), but not all could find a significant association. Our aim was to assess the association between low birth weight and BPD in preterm infants, prospectively recruited at 11 level III Portuguese neonatal centers. METHODS: Obstetrical and neonatal data on mothers and preterm infants with gestational ages between 24 and 30 weeks, born during 2015 and 2016 after a surveilled pregnancy, were analyzed. Neonates were considered small for gestational age (SGA) when their birthweight was below the 10th centile of Fenton's growth chats and BPD was defined as the dependency for oxygen therapy until 36 weeks of corrected age. Statistical analysis was performed using IBM SPSS® statistics 23 and a p-value <0.05 was considered statistically significant. RESULTS: Out of 614, a total of 494 preterm infants delivered from 410 women were enrolled in the study; 40 (8.0%) infants with SGA criteria. SGA were more often associated with a single pregnancy, had greater use of antenatal corticosteroids, increased prevalence of gestational hypertensive disorders, C-section, rupture of membranes below 18 hours, rate of intubation in the delivery room, use of surfactant treatment, oxygen therapy, mechanical ventilation need, BPD, cystic periventricular leukomalacia, nosocomial sepsis and pneumonia; had lower prevalence of chorioamnionitis, and lower Apgar scores. The multivariate analysis by logistic regression, adjusted for BPD risk factors revealed a significant association between SGA and BPD: OR = 5.2 [CI: 1.46-18.58]; p = 0.01. CONCLUSION: The results of this study increase the scientific evidence that SGA is an independent risk factor for BPD.

Altered neonatal white and gray matter microstructure is associated with neurodevelopmental impairments in very preterm infants with high-grade brain injury.

BACKGROUND: This study examines relationships between neonatal white and gray matter microstructure and neurodevelopment in very preterm (VPT) infants (≤30 weeks gestation) with high-grade brain injury (BI). METHODS: Term-equivalent diffusion tensor magnetic resonance imaging data were obtained in 32 VPT infants with high-grade BI spanning grade III/IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), and cystic periventricular leukomalacia (BI group); 69 VPT infants without high-grade injury (VPT group); and 55 term-born infants. The Bayley-III assessed neurodevelopmental outcomes at age 2 years. RESULTS: BI infants had lower fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC), cingulum, and corpus callosum, and higher mean diffusivity (MD) in the optic radiations and cingulum than VPT infants. PHH was associated with higher MD in the optic radiations and left PLIC, and higher FA in the right caudate. For BI infants, higher MD in the right optic radiation and lower FA in the right cingulum, PLIC, and corpus callosum were related to motor impairments. CONCLUSIONS: BI infants demonstrated altered white and gray matter microstructure in regions affected by injury in a manner dependent upon injury type. PHH infants demonstrated the greatest impairments. Aberrant white matter microstructure was related to motor impairment in BI infants.

Speed of Retinal Vascularization in Retinopathy of Prematurity: Risk and Protective Factors.

OBJECTIVE: The objective was to study the risk and protective factors involved in retinal vascular development of preterm infants with retinopathy of prematurity. METHODS: Between 2000 and 2017, 185 preterm infants were included in the protocol for retinopathy of prematurity. Risk factors associated with speed of retinal vascularization <0.5 disc diameter/week were studied in each of them. RESULTS: The statistically significant variables related to retinal vascular development <0.5 DD/w were intubation days, degree 3 of bronchopulmonary dysplasia, weight gain at 4-6 weeks, avascular temporal area, gestational age, number of transfusions, sepsis, number of risk factors, apnea at birth, presence of ductus arteriosus, and days of continuous positive airway pressure therapy. After the multivariate logistic regression analysis, only three variables were found to be significant: intubation days (p=0.005), degree 3 of bronchopulmonary dysplasia (p=0.022), and weight gain at 4-6 weeks (p=0.031). CONCLUSION: In retinopathy of prematurity, degree 3 of bronchopulmonary dysplasia and intubation days cause delayed retinal vascular development, whereas greater postnatal weight gain favors an appropriate rate of retinal vascularization.