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International Journal of Pediatrics &... Dec 2022This study aimed to investigate the association between admission hypothermia (AH), neonatal mortality and major neonatal morbidities in preterm infants <33 weeks'...
OBJECTIVE
This study aimed to investigate the association between admission hypothermia (AH), neonatal mortality and major neonatal morbidities in preterm infants <33 weeks' gestation. An additional aim of the study was to examine changes in the prevalence of admission hypothermia after the initiation of a thermoregulation quality improvement (QI) project.
METHOD
This is a retrospective cohort study of preterm infants < 33 weeks' gestation born at King AbdulAziz Medical City Riyadh (KAMC-R) between January 2017 to December 2020.
RESULTS
Eight-hundred infants were born during the study period. Four hundred and one infants (50.1%) had an admission temperature of <36.5 °C and a further 399 (49.9%) had an admission temperature of >36.5 °C. The mortality before discharge was 15.7% in infants with AH compared to 4.8% among those with an admission temperature above 36.5 °C. This remained statistically significant after adjustments for gestational age and maternal PET status on a multivariate analysis ( = .001, OR 2.7,95%CI 1.5-4.7). The need for mechanical ventilation ( = .005) and incidence of surgical NEC ( = .030) were significantly different between the two temperature groups. Mean (SD) admission temperature increased from 36.3 °C to 36.6 °C following the thermoregulation intervention program ( <.001). Admission temperature <36 °C is associated with higher mortality in the first week ( = .001, OR 3.3,95% CI (1.7-6.6)) and increased incidence of cystic PVL ( = .04, OR 2.1, CI (1.03-4.3)).
CONCLUSION
Preterm infants with AH suffered higher mortality and greater neonatal morbidities.
PubMed: 36937323
DOI: 10.1016/j.ijpam.2022.12.001 -
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 -
Research Square Feb 2023Germinal Matrix Hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and...
Germinal Matrix Hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and subsequent neurocognitive deficits. We demonstrate vascular expression of the adhesion molecule P-selectin after GMH and investigate a strategy to specifically target complement inhibition to sites of P-selectin expression to mitigate the pathological sequelae of GMH. We prepared two fusion proteins consisting of different anti-P-selectin single chain antibodies (scFv's) linked to the complement inhibitor Crry. One scFv targeting vehicle (2.12scFv) blocked the binding of P-selectin to its PSGL-1 ligand expressed on leukocytes, whereas the other targeting vehicle (2.3scFv) bound P-selectin without blocking ligand binding. Post-natal mice on day 4 (P4) were subjected to collagenase induced-intraventricular hemorrhage and treated with 2.3Psel-Crry, 2.12Psel-Crry, or vehicle. Compared to vehicle treatment, 2.3Psel-Crry treatment after induction of GMH resulted in reduced lesion size and mortality, reduced hydrocephalus development, and improved neurological deficit measurements in adolescence. In contrast, 2.12Psel-Crry treatment resulted in worse outcomes compared to vehicle. Improved outcomes with 2.3Psel-Crry were accompanied by decreased P-selectin expression, and decreased complement activation and microgliosis. Microglia from 2.3Psel-Crry treated mice displayed a ramified morphology, similar to naïve mice, whereas microglia in vehicle treated animals displayed a more ameboid morphology that is associated with a more activated status. Consistent with these morphological characteristics, there was increased microglial internalization of complement deposits in vehicle compared to 2.3Psel-Crry treated animals, reminiscent of aberrant C3-dependent microglial phagocytosis that occurs in other (adult) types of brain injury. Also, following systemic injection, 2.3Psel-Crry specifically targeted to the post-GMH brain. Likely accounting for the unexpected finding that 2.12Psel-Crry worsens outcome following GMH was the finding that this construct interfered with coagulation in this hemorrhagic condition, and specifically with heterotypic platelet-leukocyte aggregation, which express P-selectin and PSGL-1, respectively. GMH induces expression of P-selectin, the targeting of which with a complement inhibitor protects against pathogenic sequelae of GMH. A dual functioning construct with both P-selectin and complement blocking activity interferes with coagulation and worsens outcomes following GMH, but has potential for treatment of conditions that incorporate pathological thrombotic events, such as ischemic stroke.
PubMed: 36909595
DOI: 10.21203/rs.3.rs-2617965/v1 -
Frontiers in Pediatrics 2023Retinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The...
BACKGROUND
Retinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The purpose of our study was to analyze the association between the use of probiotics and retinopathy of prematurity.
METHODS
This study retrospectively collected clinical data of premature infants with gestational age <32 weeks and birth weight <1500 g admitted to the neonatal intensive care unit from January 1, 2019 to December 31, 2021 in Suzhou Municipal Hospital, China. Demographic and clinical data of the inclusion population were collected. The outcome was the occurrence of ROP. The chi-square test was used to compare categorical variables, while the t-test and the nonparametric Mann-Whitney U rank-sum test were used for continuous variables. Univariate and multivariate logistic regression were used to analyze the relationship between probiotics and ROP.
RESULTS
A total of 443 preterm infants met the inclusion criteria, of which 264 didn't receive probiotics and 179 were supplemented with probiotics. There were 121 newborns with ROP in the included population. The results of univariate analysis showed that the preterm infants with and without probiotics were significantly different in the gestational age, the birth weight, the one-minute Apgar score, the oxygen inhalation time, the acceptance rate of invasive mechanical ventilation, the prevalence of bronchopulmonary dysplasia, ROP and severe intraventricular hemorrhage and periventricular leukomalacia ( < 0.05). Unadjusted univariate logistic regression model result showed that probiotics (OR 0.383, 95% CI 0.240∼0.611) were the factors affecting ROP in preterm infants ( < 0.01). Multivariate logistic regression result (OR 0.575, 95% CI 0.333∼0.994) was consistent with univariate analysis ( < 0.05).
CONCLUSION
This study showed that probiotic was associated with a reduced risk of ROP in preterm infants with gestational age of <32 weeks and birth weight of <1500 g, but more large-scale prospective studies are still needed.
PubMed: 36896406
DOI: 10.3389/fped.2023.1055992 -
Frontiers in Pediatrics 2023Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse...
Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.
INTRODUCTION
Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants.
METHODS
This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates.
RESULTS
The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death.
CONCLUSION
NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.
PubMed: 36896404
DOI: 10.3389/fped.2023.1098971 -
Frontiers in Neurology 2023Brain injury is the main factor affecting the development and prognosis of the nervous system in premature infants. Early diagnosis and treatment are of great... (Review)
Review
Brain injury is the main factor affecting the development and prognosis of the nervous system in premature infants. Early diagnosis and treatment are of great significance in reducing mortality and disability and improving the prognosis of premature infants. Craniocerebral ultrasound has become an important medical imaging method for evaluating the brain structure of premature infants due to its advantages of being non-invasive, cheap, simple, and bedside dynamic monitoring since it was applied to neonatal clinical practice. This article reviews the application of brain ultrasound to common brain injuries in premature infants.
PubMed: 36860577
DOI: 10.3389/fneur.2023.1095280 -
Ultrasound in Obstetrics & Gynecology :... Mar 2023To develop and validate an index predictive of adverse perinatal outcome (APO) in pregnancies meeting the consensus-based criteria for fetal growth restriction (FGR)...
OBJECTIVES
To develop and validate an index predictive of adverse perinatal outcome (APO) in pregnancies meeting the consensus-based criteria for fetal growth restriction (FGR) endorsed by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG).
METHODS
This was a retrospective analysis of consecutive singleton non-anomalous gestations meeting the ISUOG-endorsed criteria for FGR at a single tertiary care center from November 2010 to August 2020. The dataset was divided randomly into a development set (two-thirds) and a validation set (one-third). The primary composite APO comprised one or more of: perinatal demise, Grade III-IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), seizures, hypoxic ischemic encephalopathy (HIE), necrotizing enterocolitis (NEC), sepsis, bronchopulmonary dysplasia (BPD) and length of stay in the neonatal intensive care unit (NICU) > 7 days. Regression analysis incorporated clinical factors readily available at the time of FGR diagnosis. The sum of β coefficient-based weights yielded an index score, the performance of which was assessed in the validation set. Score cut-offs were selected to identify 'high-risk' and 'low-risk' ranges for which positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios were calculated.
RESULTS
Of the 875 consecutive pregnancies that met the criteria for FGR and were included in the study cohort, 405 (46%) were complicated by one or more components of the composite APO, including 54 (6%) perinatal deaths, 22 (3%) neonates with Grade III-IV IVH and/or PVL, nine (1%) with seizures and/or HIE, 91 (10%) with BPD, 57 (7%) with sepsis, 21 (2%) with NEC, and 361 (41%) who remained in the NICU > 7 days. In addition, 270 (31%) pregnancies were delivered by Cesarean section for non-reassuring fetal status, 43 (5%) were admitted to the NICU for < 7 days, 79 (9%) had 5-min Apgar score < 7, 125/631 (20%) had a cord gas pH ≤ 7.1 and 35/631 (6%) had a base excess ≥ 12 mmol/L. The predictive index we developed included seven factors available at the time of FGR diagnosis: hypertensive disorder of pregnancy (HDP) (+8 points), chronic hypertension without HDP (+4 points), gestational age ≤ 32 weeks (+5 points), absent or reversed end-diastolic flow in the umbilical artery (+8 points), prepregnancy body mass index ≥ 35 kg/m (+3 points), isolated abdominal circumference < 3 percentile (-4 points) and non-Hispanic black race (-2 points). The bias-corrected bootstrapped (1000 replicates) area under the receiver-operating-characteristics curve (AUC) of the predictive index for composite APO in the validation group was 0.88 (95% CI, 0.84-0.92), which was similar to that in the development group (AUC, 0.86 (95% CI, 0.82-0.89); P = 0.34). In the total cohort, 40% of pregnancies had a low-risk index score (≤ 2), associated with a NPV of 85% (95% CI, 81-88%) and a LR- of 0.21 (95% CI, 0.16-0.27), and 23% had a high-risk index score (≥ 10), associated with a PPV of 96% (95% CI, 93-98%) and a LR+ of 27.36 (95% CI, 14.33-52.23). Of the remaining pregnancies that had an intermediate-risk score, 50% were complicated by composite APO.
CONCLUSION
An easy-to-use index incorporating seven clinical factors readily available at the time of FGR diagnosis is predictive of APO and may prove useful in counseling and management of pregnancies meeting the ISUOG-endorsed criteria for FGR. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Humans; Female; Infant, Newborn; Infant; Fetal Growth Retardation; Cesarean Section; Retrospective Studies; Obstetrics; Apgar Score; Bronchopulmonary Dysplasia
PubMed: 36856169
DOI: 10.1002/uog.26044 -
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 -
Turkish Journal of Ophthalmology Feb 2023To evaluate the behavioral characteristics of infants with cerebral visual impairment (CVI) in response to visual stimuli and the frequency of these features.
OBJECTIVES
To evaluate the behavioral characteristics of infants with cerebral visual impairment (CVI) in response to visual stimuli and the frequency of these features.
MATERIALS AND METHODS
In this retrospective study, 32 infants aged 8-37 months who were referred to the low vision unit in 2019-2021 and diagnosed with CVI based on their demographic characteristics, systemic findings, and standard and functional visual examinations were evaluated. The frequency of ten behavioral characteristics exhibited by infants with CVI in response to visual stimuli as defined by Roman-Lantzy was examined in the patients.
RESULTS
The mean age was 23.46±11.45 months, the mean birth weight was 2,550±944 g, and the mean gestational age at birth was 35.39±4.68 weeks. There was hypoxic-ischemic encephalopathy in 22%, prematurity in 59%, periventricular leukomalacia in 16%, cerebral palsy in 25%, epilepsy in 50%, and strabismus in 68.7% of the patients. Color preference for fixation was observed in 40% and visual field preference was observed in 46% of the patients. The most preferred color was red (69%) and the most preferred visual field was right visual field (47%). Difficulty with distance viewing was observed in 84% of patients, visual latency in 72%, need for movement in 69%, absence of visually guided reach in 69%, difficulty with visual complexity in 66%, difficulty with visual novelty in 50%, light-gazing/nonpurposeful gaze in 50%, and atypical visual reflexes in 47%. There was no fixation in 25% of the patients.
CONCLUSION
Behavioral characteristics in response to visual stimuli were observed in most infants with CVI. Knowing and recognizing these characteristic features by ophthalmologists will assist in early diagnosis, referral to visual habilitation, and planning habilitation techniques. These characteristic features are important in order to not miss this critical period in which the brain is still plastic and good responses to visual habilitation can be obtained.
Topics: Infant, Newborn; Humans; Infant; Child, Preschool; Retrospective Studies; Vision, Low; Birth Weight; Gestational Age; Ophthalmologists
PubMed: 36847612
DOI: 10.4274/tjo.galenos.2022.14296 -
Children (Basel, Switzerland) Jan 2023Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of...
Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of corrected age in this vulnerable population. VLBW infants, who were assessed at two years of corrected age using the Bayley Scale of Infant Development, third edition, were included using a population-based cohort database. Language delay was defined as mild to moderate if the composite score was between 70 and 85 and severe if the score was < 70. Multivariable logistic regression analysis was used to identify the perinatal risk factors associated with language delay. The study comprised 3797 VLBW preterm infants; 678 (18%) had a mild to moderate delay and 235 (6%) had a severe delay. After adjusting for confounding factors, low maternal education level, low maternal socioeconomic status, extremely low birth weight, male sex, and severe intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (PVL) were found to be significantly associated with both mild to moderate and severe delays. Resuscitation at delivery, necrotizing enterocolitis, and patent ductus arteriosus requiring ligation showed significant associations with severe delay. The strongest factors predicting both mild to moderate and severe language delays were the male sex and severe IVH and/or cystic PVL; thus, early targeted intervention is warranted in these populations.
PubMed: 36832318
DOI: 10.3390/children10020189