-
Frontiers in Pediatrics 2023To analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity.
OBJECTIVE
To analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity.
METHODS
Between January 2022 and December 2022, 797 infants were admitted to 25 neonatal intensive care units in Shenzhen with gestational age (GA) < 32 weeks, excluded discharged against medical advice, insufficient information, and congenital malformation, 742 VPIs were included. Comparison of maternal and neonate characteristics, morbidities, survival, and survival without major morbidities between groups used Mann Whitney test and test, multivariate logistic regression was used to analyze of risk factors of survival without major morbidities.
RESULTS
The median GA was 29.86 weeks (interquartile range [IQR], 28.0-31.04), and the median birth weight was 1,250 g (IQR, 900-1,500). Of the 797 VPIs, 721 (90.46%) survived, 53.52% (38 of 71) at 25 weeks' or less GA, 86.78% (105 of 121) at 26 to 27 weeks' GA, 91.34% (211 of 230) at 28 to 29 weeks' GA, 97.86% (367 of 375) at 30 to 31 weeks' GA. The incidences of the major morbidities were moderate-to-severe bronchopulmonary dysplasia,16.52% (113 of 671); severe intraventricular hemorrhage and/or periventricular leukomalacia, 2.49% (17 of 671); severe necrotizing enterocolitis, 2.63% (18 of 671); sepsis, 2.34% (16 of 671); and severe retinopathy of prematurity, 4.55% (27 of 593), 65.79% (450 of 671) survived without major morbidities. After adjustment for GA, birth weight, and 5-min Apgar score, antenatal steroid administration (OR = 2.397), antenatal magnesium sulfate administration (OR = 1.554) were the positivity factors to survival without major morbidity of VPIs, however, surfactant therapy (OR = 0.684,), and delivery room resuscitation (OR = 0.626) that were the negativity factors.
CONCLUSIONS
The present results indicate that survival and the incidence of survival without major morbidities increased with GA. Further, antenatal administration of steroids and magnesium sulfate, surfactant therapy, and delivery room resuscitation were pronounced determinants of survival without morbidities.
PubMed: 38464983
DOI: 10.3389/fped.2023.1298173 -
American Journal of Obstetrics and... Feb 2024Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was...
BACKGROUND
Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated.
OBJECTIVE
This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes.
STUDY DESIGN
We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia.
RESULTS
After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial.
CONCLUSION
In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.
PubMed: 38341166
DOI: 10.1016/j.ajog.2024.02.002 -
Journal of Integrative Neuroscience Jan 2024Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in...
BACKGROUND
Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in pediatric populations worldwide. Although patients with CVI are heterogeneous both in terms of underlying etiology and visual behavioural manifestations, there may be underlying similarities in terms of which white matter pathways are potentially altered. This exploratory study used diffusion tractography to examine potential differences in volume, quantitative anisotropy (QA), as well as mean, axial, and radial diffusivities (mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), respectively) focusing on the dorsal and ventral visual stream pathways in a cohort of young adults with CVI compared to typically sighted and developing controls.
METHODS
High angular resolution diffusion imaging (HARDI) data were acquired in a sample of 10 individuals with a diagnosis of CVI (mean age = 17.3 years, 2.97 standard deviation (SD), range 14-22 years) and 17 controls (mean age = 19.82 years, 3.34 SD, range 15-25 years). The inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), vertical occipital fasciculus (VOF), and the three divisions of the superior longitudinal fasciculus (SLF I, II, and III) were virtually reconstructed and average tract volume (adjusted for intracranial volume), MD, AD, and RD were compared between CVI and control groups. As a secondary analysis, an analysis of variance (ANOVA) was carried out to investigate potential differences based on etiology (i.e., CVI due to periventricular leukomalacia (CVI-PVL) and CVI due to other causes (CVI-nonPVL)).
RESULTS
We observed a large degree of variation within the CVI group, which minimized the overall group differences in tractography outcomes when examining the CVI sample as a unitary group. In our secondary analysis, we observed significant reductions in tract volume in the CVI-PVL group compared to both controls and individuals with CVI due to other causes. We also observed widespread significant increases in QA, MD, and AD in CVI-PVL compared to the control group, with mixed effects in the CVI-nonPVL group.
CONCLUSIONS
These data provide preliminary evidence for aberrant development of key white matter fasciculi implicated in visual perceptual processing skills, which are often impaired to varying degrees in individuals with CVI. The results also indicate that the severity and extent of the white matter changes may be due in part to the underlying cause of the cerebral visual impairments. Additional analyses will need to be done in a larger sample alongside behavioural testing to fully appreciate the relationships between white matter integrity, visual dysfunction, and associated causes in individuals with CVI.
Topics: Child; Young Adult; Humans; Adolescent; Adult; White Matter; Neural Pathways; Diffusion Magnetic Resonance Imaging; Brain Injuries; Vision Disorders; Brain
PubMed: 38287851
DOI: 10.31083/j.jin2301001 -
Children (Basel, Switzerland) Dec 2023Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a...
BACKGROUND
Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care.
AIMS
This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model.
METHODS
Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed.
RESULTS
In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal ( = 173, 77.9%), minor ( = 34, 15.3%), and major sequelae ( = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; value 0.016) and periventricular-intraventricular hemorrhage (OR 5.6; value < 0.004) were associated with major sequelae.
CONCLUSIONS
We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge.
PubMed: 38275433
DOI: 10.3390/children11010012 -
Frontiers in Pharmacology 2023The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks... (Review)
Review
The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial. The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks. We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies. Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality. Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86-0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90-0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000 g, iNO dose of 10 ppm or higher, or treatment duration exceeding 7 days ( < 0.05). Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.
PubMed: 38273818
DOI: 10.3389/fphar.2023.1268795 -
Cold Spring Harbor Molecular Case... Dec 2023Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of Patients with DHP deficiency exhibit a... (Review)
Review
Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in , has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis.
Topics: Humans; Metabolism, Inborn Errors; Genetic Testing; Phenotype; Diphosphonates
PubMed: 38199782
DOI: 10.1101/mcs.a006319 -
European Journal of Pediatrics Apr 2024The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first... (Observational Study)
Observational Study
The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4-30.6) weeks, birthweight 1020 (745-1505) g) were included in the analysis. Median CO was 241 (197-275) mL/kg/min for the adverse outcome and 198 (175-227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03); p = 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02); p = 0.373). CO trajectory did not differ by outcome (p = 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2. Conclusions: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2. What is Known: • Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants. What is New: • Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally. • In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.
Topics: Female; Humans; Infant, Newborn; Birth Weight; Fetal Growth Retardation; Gestational Age; Infant, Extremely Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intracranial Hemorrhages
PubMed: 38189914
DOI: 10.1007/s00431-023-05387-1 -
Biochimica Et Biophysica Acta.... Mar 2024Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic...
Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 × 10, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 × 10, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.
Topics: Infant, Newborn; Child; Pregnancy; Female; Humans; Cerebral Palsy; Infant, Low Birth Weight; Pregnancy Complications; Genotype; HLA-B Antigens
PubMed: 38163449
DOI: 10.1016/j.bbadis.2023.167008 -
Frontiers in Pediatrics 2023Acute intestinal diseases (AID), including necrotizing enterocolitis and spontaneous intestinal perforation, are a group of conditions that typically present in preterm...
INTRODUCTION
Acute intestinal diseases (AID), including necrotizing enterocolitis and spontaneous intestinal perforation, are a group of conditions that typically present in preterm infants, and are associated with an elevated mortality and morbidity rate. The risk factors for these diseases remain largely unknown. The aim of the study is to identify the correlation between twinning and the development of AID.
METHODS
A single-center retrospective case-control study was conducted. We recruited all infants with a diagnosis of AID, confirmed by anatomopathology, recovered in NICU between 2010 and 2020. Considering the rarity of the outcome, 4 matched controls for each subject were randomly chosen from the overall population of newborns. Odds Ratio (OR) and 95% Confidence Interval (CI) were calculated using a conditional logistic regression model and a multivariate model by the creation of a Directed Acyclic Graph (www.dagitty.net).
RESULTS
The study population resulted in 65 cases and 260 controls. The two groups present similar median gestational age and mean birthweight in grams. The cases have a higher frequency of neonatal pathology (defined as at least one of patent ductus arteriosus, early or late sepsis, severe respiratory distress) (84.6% vs. 51.9%), medically assisted procreation (33.8% vs. 18.8%) and periventricular leukomalacia (10.8% vs. 2.7%), and a lower frequency of steroids prophylaxis (67.7% vs. 86.9%). About 50% of cases needed surgery. The OR for the direct effect were difference from one using logistic regression booth without and with repeated measures statements: from 1.14 to 4.21 ( = .019) and from 1.16 to 4.29 ( = .016), respectively.
CONCLUSIONS
Our study suggests that twinning may be a risk factor for the development of AID. Due to the small number of cases observed, further studies on larger populations are needed.
PubMed: 38161432
DOI: 10.3389/fped.2023.1308538 -
Neuroradiology Feb 2024Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite...
PURPOSE
Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL.
METHODS
We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP.
RESULTS
There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect.
CONCLUSION
This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.
Topics: Child; Infant, Newborn; Humans; Cerebral Palsy; Leukomalacia, Periventricular; Glymphatic System; Retrospective Studies; Hand
PubMed: 38129651
DOI: 10.1007/s00234-023-03269-9