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European Journal of Pediatrics Oct 2023This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes...
This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain. Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors. What is Known: • Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes. • Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation). What is New: • The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment. • Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Fetal Growth Retardation; Infant, Premature; Cohort Studies; Retrospective Studies; Umbilical Arteries; Gestational Age; Ultrasonography, Prenatal
PubMed: 37490110
DOI: 10.1007/s00431-023-05104-y -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120).
METHODS
This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety.
RESULTS
A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups.
CONCLUSIONS
BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet.
TRIAL REGISTRATION
http://www.
CLINICALTRIALS
gov: NCT03085277.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Animals; Cattle; Infant, Premature; Colostrum; Dietary Supplements; Milk, Human; Infant, Very Low Birth Weight; Infant, Premature, Diseases; Fetal Growth Retardation; Enterocolitis, Necrotizing
PubMed: 37437359
DOI: 10.1016/j.clnu.2023.06.024 -
Neurobiology of Disease Aug 2023Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe... (Review)
Review
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.
Topics: Humans; Ischemic Stroke; Oligodendroglia; Myelin Sheath; Central Nervous System; Stroke
PubMed: 37321419
DOI: 10.1016/j.nbd.2023.106200 -
European Journal of Clinical Nutrition Aug 2023This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion.
METHODS
This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups.
RESULTS
No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05).
CONCLUSIONS
The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.
Topics: Infant, Newborn; Humans; Infant, Premature; Prospective Studies; Fat Emulsions, Intravenous; Soybean Oil; Olive Oil; Fish Oils; Cholestasis; Triglycerides; Bilirubin; Infant, Very Low Birth Weight
PubMed: 37138099
DOI: 10.1038/s41430-023-01288-6 -
Pediatrics and Neonatology Nov 2023The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain...
BACKGROUND
The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants.
METHODS
All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of <1 year were excluded. Chromosomal abnormalities, brain anomalies, severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and hypoxic ischemic encephalopathy (HIE) were considered to be risk factors.
RESULTS
Epilepsy occurred in 21/526 (4.0%) VLBW infants. Chromosomal abnormalities, brain anomalies, severe IVH, cystic PVL, HIE, neonatal seizures, advanced maternal age, maternal diabetes mellitus, no administration of antenatal corticosteroids, and low Apgar scores at 1 and 5 min were associated with a risk of epilepsy. The median time to epilepsy onset was 8 months (range: 0-59 months), and the onset occurred within 2 years in 15/21 patients (71.4%) and within 4 years in 18/21 patients (85.7%). VLBW infants with risk factors developed epilepsy earlier and at a significantly higher rate than those without risk factors. Among infants who had risk factors and who developed epilepsy, 86.7% did so within 2 years of age, compared to 33.3% of those who developed epilepsy but did not have risk factors.
CONCLUSION
These findings regarding factors associated with a risk of development of epilepsy and temporal feature of epilepsy may contribute to the development of monitoring and treatment protocols for epilepsy in VLBW infants.
Topics: Infant, Newborn; Infant; Humans; Female; Pregnancy; Infant, Very Low Birth Weight; Leukomalacia, Periventricular; Infant, Newborn, Diseases; Risk Factors; Cerebral Hemorrhage; Epilepsy; Brain Diseases; Chromosome Aberrations; Birth Weight
PubMed: 37117074
DOI: 10.1016/j.pedneo.2022.12.019 -
The Journal of Maternal-fetal &... Dec 2023Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated...
BACKGROUND
Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects.
OBJECTIVES
We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls.
METHODS
Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry.
RESULTS
LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants.
CONCLUSION
Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.
Topics: Adult; Infant; Infant, Newborn; Humans; Infant, Premature; Neutrophils; Monocytes; Protein C; Toll-Like Receptor 4; Lipopolysaccharides
PubMed: 36935364
DOI: 10.1080/14767058.2023.2183467 -
Journal of Perinatal Medicine Jul 2023Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage...
Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage encompasses very different aetiological entities that result in an insult to the developing brain and does not differentiate between the onset, cause and severity of this insult. Hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage, periventricular leukomalacia and perinatal stroke are often listed as the major aetiologies of perinatal brain damage. They differ by type and timing of injury, neuropathological and imaging findings and their clinical picture. Along the timeline of neurodevelopment , there appears to be a specific "window of vulnerability" for each type of injury, but clinical overlap does exist. In the past, peripartum acute hypoxia was believed to be the major, if not the only, cause of perinatal brain damage, but intrauterine inflammation, prematurity, chronic hypoxia/growth retardation and genetic abnormalities appear to be at least equally important contributors.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Obstetricians; Brain Injuries; Brain; Hypoxia-Ischemia, Brain; Hypoxia; Infant, Newborn, Diseases
PubMed: 36853861
DOI: 10.1515/jpm-2022-0523 -
Archives of Disease in Childhood. Fetal... Sep 2023To evaluate epidemiology and outcomes among very preterm infants (<32 weeks' gestation) with culture-positive and culture-negative late-onset sepsis (LOS).
OBJECTIVE
To evaluate epidemiology and outcomes among very preterm infants (<32 weeks' gestation) with culture-positive and culture-negative late-onset sepsis (LOS).
DESIGN
Cohort study using a nationwide, population-based registry.
SETTING
21 neonatal units in Norway.
PARTICIPANTS
All very preterm infants born 1 January 2009-31 December 2018 and admitted to a neonatal unit.
MAIN OUTCOME MEASURES
Incidences, pathogen distribution, LOS-attributable mortality and associated morbidity at discharge.
RESULTS
Among 5296 very preterm infants, we identified 582 culture-positive LOS episodes in 493 infants (incidence 9.3%) and 282 culture-negative LOS episodes in 282 infants (incidence 5.3%). Extremely preterm infants (<28 weeks' gestation) had highest incidences of culture-positive (21.6%) and culture-negative (11.1%) LOS. The major causative pathogens were coagulase-negative staphylococci (49%), (15%), group B streptococci (10%) and (8%). We observed increased odds of severe bronchopulmonary dysplasia (BPD) associated with both culture-positive (adjusted OR (aOR) 1.7; 95% CI 1.3 to 2.2) and culture-negative (aOR 1.6; 95% CI 1.3 to 2.6) LOS. Only culture-positive LOS was associated with increased odds of cystic periventricular leukomalacia (cPVL) (aOR 2.2; 95% CI 1.4 to 3.4) and severe retinopathy of prematurity (ROP) (aOR 1.8; 95% CI 1.2 to 2.8). Culture-positive LOS-attributable mortality was 6.3%, higher in Gram-negative (15.8%) compared with Gram-positive (4.1%) LOS, p=0.009. Among extremely preterm infants, survival rates increased from 75.2% in 2009-2013 to 81.0% in 2014-2018, p=0.005. In the same period culture-positive LOS rates increased from 17.1% to 25.6%, p<0.001.
CONCLUSIONS
LOS contributes to a significant burden of disease in very preterm infants and is associated with increased odds of severe BPD, cPVL and severe ROP.
Topics: Infant; Female; Infant, Newborn; Humans; Cohort Studies; Intensive Care Units, Neonatal; Infant, Premature, Diseases; Sepsis; Infant, Extremely Premature; Gestational Age; Bronchopulmonary Dysplasia; Retinopathy of Prematurity; Leukomalacia, Periventricular; Fetal Growth Retardation
PubMed: 36732047
DOI: 10.1136/archdischild-2022-324977 -
Journal of Perinatal Medicine Jul 2023Cerebral palsy, the most common disability in childhood, is a devastating non-progressive ailment of the infants' brain with lifelong sequelae, e.g., spastic paresis,... (Review)
Review
Cerebral palsy, the most common disability in childhood, is a devastating non-progressive ailment of the infants' brain with lifelong sequelae, e.g., spastic paresis, chronic pain, inability to walk, intellectual disability, behavioral disorders, for which there is no cure at present. CP may develop after pediatric brain damage caused, e.g., by hypoxic-ischemia, periventricular leukomalacia, intracranial hemorrhage, hypoxic-ischemic encephalopathy, trauma, stroke, and infection. About 17 million people worldwide live with cerebral palsy as a result of pediatric brain damage. This reflects both the magnitude of the personal, medical, and socioeconomic global burden of this brain disorder and the overt unmet therapeutic needs of the pediatric population. This review will focus on recent preclinical, clinical, and regulatory developments in cell therapy for infantile cerebral palsy by transplantation of cord blood derived mononuclear cells from bench to bedside. The body of evidence suggests that cord blood cell therapy of cerebral palsy in the autologous setting is feasible, effective, and safe, however, adequately powered phase 3 trials are overdue.
Topics: Infant, Newborn; Humans; Child; Cerebral Palsy; Brain; Stem Cells; Brain Injuries; Leukomalacia, Periventricular; Hypoxia-Ischemia, Brain
PubMed: 36503655
DOI: 10.1515/jpm-2022-0505 -
American Journal of Perinatology May 2024Data from the academic medical centers in the United States showing improvements in survival of periviable infants born at 22 to 24 weeks GA may not be nationally...
OBJECTIVE
Data from the academic medical centers in the United States showing improvements in survival of periviable infants born at 22 to 24 weeks GA may not be nationally representative since a substantial proportion of preterm infants are cared for in community hospital-based neonatal intensive care units. Our objective was to examine the national trends in survival and other short-term outcomes among preterm infants born at ≤24 weeks gestational age (GA) in the United States from 2009 to 2018.
STUDY DESIGN
This was a retrospective, repeated cross-sectional analysis of the National Inpatient Sample for preterm infants ≤24 weeks GA. The primary outcome was the trends in survival to discharge. Secondary outcomes were the trends in the composite outcome of death or one or more major morbidity (bronchopulmonary dysplasia, necrotizing enterocolitis stage ≥2, periventricular leukomalacia, severe intraventricular hemorrhage, and severe retinopathy of prematurity). The Cochran-Armitage trend test was used for trend analysis. -Value <0.05 was considered significant.
RESULTS
Among 71,854 infants born at ≤24 weeks GA, 34,251 (47.6%) survived less than 1 day and were excluded. Almost 93% of those who survived <1 day were of ≤23 weeks GA. Among the 37,603 infants included in the study cohort, 48.1% were born at 24 weeks GA. Survival to discharge at GA ≤ 23 weeks increased from 29.6% in 2009 to 41.7% in 2018 ( < 0.001), while survival to discharge at GA 24 weeks increased from 58.3 to 65.9% ( < 0.001). There was a significant decline in the secondary outcomes among all the periviable infants who survived ≥1 day of life.
CONCLUSION
Survival to discharge among preterm infants ≤24 weeks GA significantly increased, while death or major morbidities significantly decreased from 2009 to 2018. The postdischarge survival, health care resource use, and long neurodevelopmental outcomes of these infants need further investigation.
KEY POINTS
· Survival increased significantly in infants ≤24 weeks GA in the United States from 2009 to 2018.. · Death or major morbidity in infants ≤24 weeks GA decreased significantly from 2009 to 2018.. · Death or surgical procedures including tracheostomy, VP shunt placement, and PDA surgical closure in infants <=24 weeks GA decreased significantly from 2009 to 2018..
Topics: Humans; Infant, Newborn; United States; Retrospective Studies; Female; Male; Infant, Extremely Premature; Cross-Sectional Studies; Gestational Age; Infant Mortality; Infant, Premature, Diseases; Infant; Bronchopulmonary Dysplasia; Enterocolitis, Necrotizing; Intensive Care Units, Neonatal; Fetal Viability; Retinopathy of Prematurity
PubMed: 35523408
DOI: 10.1055/a-1845-2526