Extreme Prematurity Research Articles

Identification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome

BackgroundAntenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported.MethodsIn our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.ResultsOur findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.ConclusionsOur results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.

Breastfeeding premature infants affects the microbiota composition of breast milk.

To determine whether and how breast feeding of premature infants influences the human milk (HM) bacterial communities. HM samples before and after breastfeeding were collected from 40 preterm infant mothers at 24-366/7 weeks of gestational age in the neonatal intensive care unit of our hospital. Of these 40 babies, 11 at 24-276/7 weeks of gestational age and 12 at 28-316/7 weeks were grouped into an extremely premature (EPM) group and a very premature (VPM) group, respectively. In addition, 11 with a birth weight (BWT) of 1000 g ≤ BWT < 1500 g were classified as a very low birth weight (VLBW) group and 12 with BWT < 1000 g an extremely low birth weight (ELBW) group. Breast feeding and kangaroo mother care were given once a day for 7 days, from 14 to 21 days of age. The bacterial composition of HM was analyzed using high-throughput sequencing before and after feeding. Linear discriminant analysis effect size of HM samples before and after feeding showed that Bacillus, Prevotella and Fusobacterium were significantly enriched in HM before breastfeeding (P < 0.05). Post-feeding HM for the EPM group showed significant enrichment in Lactobacillales, Streptococcus, Desulfuromonadales, Ruminococcus, Geobacteraceae, Geobacter and Elizabethkingia_meningoseptica (P < 0.05). Bacillus was significantly enriched in the HM for EPM group before feeding (P < 0.05). For mothers with VLBW infants, Bacillus was enriched before feeding, while Lactobacillales was predominant after feeding (P < 0.05). There was a moderate correlation between the diversity of HM bacteria and infant development and immune outcomes. Breastfeeding of preterm infants can significantly affect the bacterial diversity in HM.

A Case of Extremely Premature Baby with Persistent Metabolic Acidosis, Hypoglycemia and Dyselectrolytemia Induced by Liposomal Amphotericin B

Amphotericin B is widely used in the treatment of neonatal invasive fungal disease. Liposomal amphotericin B (LAmB) is now preferred over conventional amphotericin B deoxycholate due to its lower kidney toxicity. However, it is essential to monitor the possible side effects of LAmB when treating extremely premature infants. Herein, we present a case of an extremely premature infant who exhibited persistent metabolic acidosis, hypoglycemia, and dyselectrolytemia after administration of LAmB for a suspected fungal infection.

Disruption of Cerebellar Granular Layer as a Consequence of Germinal Matrix Intraventricular Hemorrhage in Extreme Prematurity: An Acute Direct Mechanism Too?

Cerebellum is an important brain structure for the future development of motor, cognitive, and behavioral abilities in children. This structure undergoes its most significant growth during the third trimester of pregnancy. Prematurity gathers several risk factors for cerebellar impairment and underdevelopment, and among them is ventricular dilatation following germinal matrix intraventricular hemorrhage (GMH-IVH). In this report, we illustrate how this prevalent complication associated with prematurity may induce secondary cerebellar cortical damage. A premature male born by an emergency Caesarean section displayed massive GMH-IVH at brain ultrasound performed after three hours of extrauterine life and died after 18 hours of life, despite maximized vital support. We report a postmortem histopathological specimen of the cerebellar cortex showing the disruption of the external granular layer (EGL) by hemorrhagic content flowing from the supratentorial ventricles into the fourth ventricle and cisterna magna. The expansion of the ventricular system and the presence of blood in the lateral ventricles can cause inflammation and damage to the cerebellar gyri. Experimental models have shown a thinning of the EGL, suggesting that blood surrounding the cerebellum has a harmful action. Additionally, a sudden influx of cerebrospinal fluid from the lateral ventricles may directly contribute to cerebellar damage, indicating that this may be another way in which the cerebellar gyri are impaired during acute severe GMH-IVH. This is the first histopathologically confirmed case of acute disruption in the cerebellar cortex during a GMH-IVH in a premature baby.

Outcomes of Ultrasound or Physical Examination-Indicated Cerclage according to the Degree of Cervical Dilation.

Pregnancy outcomes of individuals receiving cervical cerclage when the cervix is dilated are not well known. We sought to examine preterm birth rates after ultrasound or physical examination-indicated cerclage placement according to the degree of cervical dilation. This was a retrospective cohort study of individuals with singleton pregnancies undergoing ultrasound or physical examination-indicated cerclage before 240/7 weeks of gestation from 2004 to 2018. Individuals were categorized based on the degree of cervical dilation at the time of cerclage. Our primary outcome was preterm delivery at less than 37 weeks of gestation. Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) with 95th confidence intervals (95% CI), controlling for predefined covariates. Of 147 individuals undergoing ultrasound or physical examination-indicated cerclage, 90/147 (61%) had a closed or 0.5 cm dilated cervix at the time of cerclage placement, 45/147 (31%) had a cervical dilation of 1 to 2.5 cm, and 12/147 (8%) had a cervical dilation of 3 to 4 cm at the time of placement. Individuals with a cervical dilation of 1 to 2.5 cm compared with those who had a closed cervix did not have increased odds of preterm delivery (58 vs. 42%; aOR: 1.95; 95% CI: 0.93-4.07). However, individuals with a cervical dilation of 3 to 4 cm compared with individuals who had a closed cervix had significantly increased odds of preterm delivery (75 vs. 42%; aOR: 4.33; 95% CI: 1.05-17.77). The rate of preterm birth increases with increasing cervical dilation at the time of cerclage placement. However, individuals who have a cerclage placed when the cervix is 1 to 2.5 cm can achieve an outcome that is not significantly different from those who had a cerclage placed when the cervix is closed. · Time from cerclage placement to delivery decreases as cervical dilation increases.. · Individuals 1 to 2.5 cm dilated at the time of cerclage can achieve a favorable outcome.. · A cervical dilation of ≥3 cm at cerclage placement was associated with extreme prematurity..

Study of Childbirth with A Single Scar Uterus at the "Major Moussa Diakite" Reference Health Center in Kati, Mali

The management of childbirth in a scarred uterus is one of the most debated subjects in modern obstetrics, due to the considerable increase in caesarean section rates and many other risks of complication such as disunion of the old scar. Objective: To study childbirth with a single scar uterus at the Kati Reference Health Center. Method: This was a prospective cross-sectional study, which ran from 1 January to 31 December 2021. It focused on parturients with a single myometrial scar, a vertex presentation of the foetus, a clinically normal pelvis, a uterine height of less than 36 centimeters, a single foetal pregnancy and an intergenesic interval of more than one year. Results: Out of a total of 2521 deliveries, seventy (70) women met the criteria of our study, or a frequency of 28%. The average age of parturients was 30, with extremes ranging from 18 to 42. Only 20% of our parturients had completed four antenatal consultations. They were carried out in 78.5% of cases by qualified staff. Eight out of ten of our parturients (81.4%) came on their own, and in seven out of ten cases (70.0%) in the active phase of childbirth. Delivery was by natural route in almost seven out of ten cases (65.7%), compared with caesarean section in 34.3% of cases. The indications for caesarean section were dominated by dynamic dystocia (66.7%), followed by failure to engage (12.5%), acute foetal distress (12.5%) and umbilical cord prolapse (8.3%). Previous vaginal delivery prior to caesarean section was associated with a successful uterine test (P=0.019). Maternal complications were haemorrhage due to uterine atony (1 case) and disunion of the old caesarean scar (1 case). We recorded two macerated stillbirths and one case of early neonatal death linked to extreme prematurity, and six cases of neonatal suffering. Conclusion: Childbirth in a scar uterus is a high-risk delivery, and strict adherence to the conditions under which it is carried out is essential to improve the maternal and ....

Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option. This study evaluated the minimum effective dose of prophylactic acetaminophen to close the ductus and assessed the safety and tolerability profile in extremely preterm infants at 23-26 weeks of gestation. A dose finding trial with Bayesian continual reassessment method was performed in a multicenter study with premature infants hospitalized in neonatal intensive care unit. Infants of 23-26 weeks of gestation and post-natal age ≤ 12 h were enrolled. Four intravenous acetaminophen dose levels were predefined. The primary outcome was the ductus arteriosus closing at two consecutive echocardiographies or at day 7. The main secondary objectives included the safety of acetaminophen on hemodynamics and biological hepatic function. A total of 29 patients were analyzed sequentially for the primary analysis with 20 infants assigned to the first dose level followed by 9 infants to the second dose level. No further dose level increase was necessary. The posterior probabilities of success, estimated from the Bayesian logistic model, were 46.1% [95% probability interval (PI), 24.9-63.9] and 67.6% (95% PI, 51.5-77.9) for dose level 1 and 2, respectively. A closing or closed pattern was observed among 19 patients at the end of treatment [65.5% (95% confidence interval (CI), 45.7-82.0)]. No change in alanine aminotransferase values was observed during treatment. A significant decrease in aspartate aminotransferase values was observed with postnatal age. No change in systolic and diastolic blood pressures was observed during treatment. Minimum effective dose to close the ductus was 25 mg/kg loading dose then 10 mg/kg/6 h for 5 days in extremely preterm infants. Acetaminophen was well tolerated in this study following these doses. ClinicalTrials.gov Identifier: NCT04459117.

Leveraging transcriptomics to develop bronchopulmonary dysplasia endotypes: a concept paper

ImpactBronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes.IntroductionBronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease.MethodsAn unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics.ResultsFour BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value < 0.05 after multiple comparison testing. Endotype A consisted of neonates with a higher gestational age and birthweight. Endotypes B-D included neonates between 25 and 26 weeks and a birthweight range of 640 to 940 g. Endotype D appeared to have a protective role against BPD compared to Endotypes B and C (36% vs. 62% vs. 60%, respectively). The most significant pathway focused on T helper 17 cell differentiation.ConclusionBioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD.

Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study

The administration of dexamethasone has been associated with suboptimal neurodevelopment. We aimed to compare the development of extremely premature infants treated or not with alternatives to dexamethasone: betamethasone, hydrocortisone hemisuccinate. This retrospective cohort study included infants born before 29 weeks of gestational age, treated or not with late (day ≥ 7) postnatal steroids (betamethasone, hydrocortisone hemisuccinate). The neurodevelopment outcome was evaluated at 24 months corrected age, after adjustment on comorbidities of extreme prematurity. In order to analyse their overall development, data about growth and respiratory outcomes were collected. Among the 192 infants included, 59 (30.7%) received postnatal steroids. Suboptimal neurodevelopment concerned 37/59 (62.7%) postnatal steroid-treated and 43/133 (38.1%; p = 0.002) untreated infants. However, in multivariable analysis, only severe neonatal morbidity (p = 0.007) and male gender (p = 0.027) were associated with suboptimal neurodevelopment outcome at 24 months. Conclusions: Betamethasone or hydrocortisone hemisuccinate treatment was not an independent risk for suboptimal neurological development, growth and respiratory outcomes assessed at 24 months corrected age in extremely premature infants. Registration number: The study was registered on the ClinicalTrials.gov register: NCT05055193.What is Known:• Late postnatal steroids are used to treat bronchopulmonary dysplasia• Meta-analyses warned against the neurological risk of dexamethasone use during neonatal period. Early or late hydrocortisone hemisuccinate has been evaluated in multiple studies, none of which have reported an adverse effect on neurodevelopment at least to 2 years. Data about the use of betamethasone are scarce.What is New:• The risk of suboptimal neurodevelopment was higher among extremely premature infants who received postnatal steroids when compared to those who did not.• Betamethasone and hydrocortisone hemisuccinate treatment was not an independent risk factor for suboptimal neurodevelopment at 24 months corrected age.

Hydrocephalus in prematurity: does valve choice make a difference?

PurposeExtremely premature neonates diagnosed with post-haemorrhagic hydrocephalus (PHH) are recognised to have particularly poor outcomes. This study assessed the impact of a number of variables on outcomes in this cohort, in particular the choice of shunt valve mechanism.MethodsElectronic case notes were retrospectively reviewed of all premature neonates admitted to our centre for management of hydrocephalus between 2012 and 2021. Data included (i) gestational age, (ii) birth weight, (iii) hydrocephalus aetiology, (iv) surgical intervention, (v) shunt system, (vi) ‘surgical burden’ and (vii) wound failure and infection rate. Data was handled in Microsoft Excel and statistical analysis performed in SPSS v27.0ResultsN = 53 premature hydrocephalic patients were identified (n = 28 (52.8%) female). Median gestational age at birth was 27 weeks (range: 23–36 + 6 weeks), with n = 35 extremely preterm patients and median birth weight of 1.9 kg (range: 0.8–3.6 kg). Total n = 99 programmable valves were implanted (n = 28 (28.3%) de novo, n = 71 (71.2%) revisions); n = 28 (28.3%) underwent n ≥ 1 pressure alterations, after which n = 21 (75%) patients had symptoms improve. In n = 8 patients exchanged from fixed to programmable valves, a mean reduction of 1.9 revisions per patient after exchange was observed (95%CI: 0.36–3.39, p = 0.02). Mean overall shunt survival was 39.5 weeks (95%CI: 30.6–48.5); 33.2 weeks (95%CI: 25.2–41.1) in programmable valves and 35.1 weeks (95%CI: 19.5–50.6) in fixed pressure (p = 0.22) with 12-month survival rates of 25.7% and 24.7%, respectively (p = 0.22). Shorter de novo shunt survival was associated with higher operation count overall (Pearson’s R: − 0.54, 95%CI: − 0.72 to − 0.29, p < 0.01). Wound failure, gestational age and birth weight were significantly associated with shorter de novo shunt survival in a Cox regression proportional hazards model; gestational age had the greatest impact on shunt survival (Exp(B): 0.71, 95%CI: 0.63–0.81, p < 0.01).ConclusionHydrocephalus is especially challenging in extreme prematurity, with a shorter de novo shunt survival associated with higher number of future revisions. Programmable valves provide flexibility with regard to pressure setting, with the potential for fewer shunt revisions in this complex cohort.

Exploring and Supporting Parents' Stories of Loss in the NICU: A Narrative Study.

Death is no stranger to the neonatal intensive care unit (NICU). Extreme prematurity, congenital abnormalities, and other complexities can turn what was hoped to be a very exciting moment in a family's life into one of despair and grief. There are many infants that not only do not survive but also have a medicalized death necessitating complex decision-making, weighing quality versus duration of life. We can learn from the stories of parents who chose palliative care for their children. In this narrative inquiry study, we elicited bereaved parents' stories and reflections on the lives of their children and the care they received in the NICU. From a narrative ethics perspective, their stories speak to normative aspects of parenting, decision-making, and receiving medical care that affect their moral sense-making of their NICU experiences as well as their longer-term living with the loss of their children. Their stories express the importance of having had meaningful time with their children, maintaining direct and frequent communication, acknowledging uncertainty, and emphasizing compassion as methods of providing support to parents as they navigate their bereavement.

Characterizing post-branching nephrogenesis in the neonatal rabbit

Human nephrogenesis ends prior to birth in term infants (34–36 week gestation), with most (60%) nephrons forming in late gestation in two post-branching nephrogenesis (PBN) periods: arcading and lateral branch nephrogenesis. Preterm infants, however, must execute PBN postnatally. Extreme prematurity is associated with low nephron counts. Identifying additional model(s) that undergo PBN postnatally will help support postnatal PBN in preterm infants. The rabbit exhibits longer postnatal nephrogenesis than the mouse but whether it forms nephrons through PBN has not been determined. We performed morphologic and immunohistological assessments of rabbit nephrogenesis from birth (post-conceptual day 31 or 32) to PC49 using H&E and antibodies against SIX1, SIX2, WT1, ZO-1, and JAG1 in the postnatal period. We performed 3D rendering of the nephrogenic niche to assess for PBN, and supplemented the staining with RNAScope to map the expression of Six1, Six2 (nephron progenitors, NPC), and Ret (ureteric bud tip) transcripts to determine the nephrogenic niche postnatal lifespan. Unlike the mouse, rabbit SIX2 disappeared from NPC before SIX1, resembling the human niche. Active nephrogenesis as defined by the presence of SIX1 + naïve NPC/tip population persisted only until PC35–36 (3–5 postnatal days). 3D morphologic assessments of the cortical nephrons identified an elongated tubule with attached glomeruli extending below the UB tip, consistent with PBN arcades, but not with lateral branch nephrogenesis. We conclude that the rabbit shows morphologic and molecular evidence of PBN arcades continuing postnatally for a shorter period than previously thought. The rabbit is the first non-primate expressing SIX1 in the progenitor population. Our findings suggest that studies of arcading in postnatal nephrogenic niche should be performed within the first 5 days of life in the rabbit.

Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm

BackgroundChildren born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term.MethodsOur study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups.ResultsBrain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ.ConclusionsThese findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT.ImpactThe article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy.Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes.While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes.We found no differences in volumetric asymmetry between children born EPT and at term.

CE Workshop 06: The Cumulative Burden of Congenital Heart Disease Across the Lifespan: Implications for Neuropsychologists in Pediatrics Through Geriatrics

Abstract &amp; Learning Objectives:The heart and the brain are inextricably linked across development by overlapping genetic programs and transacting physiologies that exist long before birth and endure throughout the lifespan. Congenital heart disease (CHD) refers to a diverse array of conditions in which structural heart development is atypical. Of the roughly 1 million babies born with CHD each year, some 40,000 are born with a “critical” form of CHD that will require intensive surgical intervention within the first year of life. As recently as the 1980s, children born with some forms of critical CHD did not survive; palliation was their only option. This has changed dramatically over the past 30-40 years. Driven by momentous breakthroughs in medical science and technology, approximately 80-95% of children born with CHD today will reach adulthood.But increased survival is only a part of the CHD story. Indeed, like extreme prematurity, leukemia, and many other previously fatal medical conditions with which neuropsychologists are familiar, increases in longevity among CHD survivors have come with increasing recognition of the many challenging transitions and cumulative medical, neurobehavioral, and psychosocial burdens inherent to “living with CHD.” CHD begins to alter expected brain development in utero with evidence of structural, volumetric, and metabolic differences documented as early as the second or third prenatal trimester. Brain dysmaturation, in turn, increases one’s risk for further acquired brain injury and gives rise to a range of neurobehavioral deficits and psychosocial difficulties that consistently rank among the most salient threats to quality of life among children, adolescents, and adults with CHD.More recently, as survival into adulthood has become increasingly common for individuals with CHD, we have also begun to more fully appreciate the cascading impact and cumulative neuropsychological burden of CHD across the lifespan, which impact a range of long-term outcomes such as educational and occupational attainment, living independently, and risk for dementia.In short, CHD can no longer reasonably be considered a child or pediatric condition, but rather a lifespan condition with the potential to adversely impact neurobehavioral and psychosocial outcomes in different ways and at different times across infancy, childhood, adolescence, and adulthood. Over a series of talks presented by a panel of recognized neuropsychologists and experts in CHD, this symposium aims to review the neuropsychology of CHD across the lifespan and to present an integrative lifespan developmental neuropsychological model of CHD that eschews prevailing “child” vs. “adult” distinctions. Each presentation will address a salient developmental epoch (prenatal-early childhood, school-age/adolescence, and adulthood/geriatric timeframes) and will include a comprehensive review of the extant literature pertaining to relevant neuroanatomical and neurodevelopmental/neuropsychological considerations for individuals with CHD during each epoch. Transitions, of which there are myriad for individuals living with CHD (e.g., from acute inpatient care to stepdown unit care; from inpatient to outpatient settings; from early intervention to the school system; from childhood to adolescence; from adolescence to young adulthood; from pediatric to adult CHD care), will feature prominently throughout the symposium, as will recommendations for competent, developmentally-informed clinical neuropsychological management and intervention planning throughout the lifespan. Upon conclusion of this course, learners will be able to:1.Describe the mechanisms by which congenital heart disease (CHD) impacts brain development and functioning across the lifespan (from infancy to older adulthood).2.Discuss neurodevelopmental/neuropsychological sequelae of CHD for children, adolescents, and adults.3.Explain the role of clinical neuropsychologists in evaluating, supporting, and optimizing the neuropsychological trajectories of individuals with CHD across the lifespan.

Intratracheal Instillation of Budesonide-Surfactant for Prevention of Bronchopulmonary Dysplasia in Extremely Premature Infants.

This study aimed to determine the effect of intratracheal instillation of a budesonide-surfactant combination on the incidence of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely preterm infants. In this retrospective, single-center study, we included extremely preterm infants (<28 weeks' gestation) who received surfactant for respiratory distress in the first 3 days of life. We compared infants who received budesonide-surfactant combination (intervention group: infants born between February 2016 and October 2021) with surfactant alone (control group: infants born from January 2010 through January 2016). The primary outcome was a composite of BPD grade 2 or 3 (as defined by Jensen et al, 2019) or death before 36 weeks' postmenstrual age (PMA). We included 966 extremely preterm infants (528 in the control group and 438 in the intervention group). While the incidence of death/BPD grade 2 or 3 at 36 weeks of PMA was not different between the two groups (66% in the intervention group vs. 63% in the control group; adjusted relative risk [aRR], 0.99; 95% confidence interval [CI], 0.90-1.07; p-value = 0.69), budesonide was associated with a reduction in the primary outcome only in a subgroup of infants with birth weight ≥ 750 grams (36.8 vs. 43.5%, respectively; aRR 0.75; 95% CI, 0.57-0.98). Primary and secondary outcomes did not differ between the two groups within the subgroup of infants weighing <750 grams. In extremely preterm infants, the budesonide-surfactant combination therapy reduced the rates of BPD or death in infants weighing ≥750 grams; however, this beneficial effect was not seen in infants weighing <750 grams. Further investigation of this treatment may be indicated before it is considered a standard approach to management. · Intratracheal budesonide-surfactant therapy reduces BPD in preterm infants weighing ≥750 grams.. · Intratracheal budesonide-surfactant therapy does not affect BPD in preterm infants weighing <750 grams.. · Intratracheal budesonide-surfactant therapy does not affect the mortality rate in preterm infants..

Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study.

Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score < -2. Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0. NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0. · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction..

Stillbirth rates and their determinants in a national maternity hospital in Phnom Penh, Cambodia in 2017–2020: a cross-sectional assessment with a nested case–control study

BackgroundIn Cambodia, stillbirths and their underlying factors have not been systematically studied. This study aimed to assess the proportion and trends in stillbirths between 2017 and 2020 in a large maternity referral hospital in the country and identify their key determinants to inform future prevention efforts.MethodsThis was a retrospective cross-sectional analysis with a nested case–control study of women giving birth at the National Maternal and Child Health Centre (NMCHC) in Phnom Penh, 2017–2020. We calculated percentages of singleton births at ≥ 22 weeks’ gestation resulting in stillbirth and annual stillbirth rates by timing: intrapartum (fresh) or antepartum (macerated). Multivariable logistic regression was used to explore factors associated with stillbirth, where cases were all women who gave birth to a singleton stillborn baby in the 4-year period. One singleton live birth immediately following each case served as an unmatched control. Multiple imputation was used to handle missing data for gestational age.ResultsBetween 2017 and 2020, 3.2% of singleton births ended in stillbirth (938/29,742). The stillbirth rate increased from 24.8 per 1000 births in 2017 to 38.1 per 1000 births in 2020, largely due to an increase in intrapartum stillbirth rates which rose from 18.8 to 27.4 per 1000 births in the same period. The case–control study included 938 cases (stillbirth) and 938 controls (livebirths). Factors independently associated with stillbirth were maternal age ≥ 35 years compared to < 20 years (aOR: 1.82, 95%CI: 1.39, 2.38), extreme (aOR: 3.29, 95%CI: 2.37, 4.55) or moderate (aOR: 2.45, 95%CI: 1.74, 3.46) prematurity compared with full term, and small-for-gestational age (SGA) (aOR: 2.32, 1.71, 3.14) compared to average size-for-age. Breech/transverse births had nearly four times greater odds of stillbirth (aOR: 3.84, 95%CI: 2.78, 5.29), while caesarean section reduced the odds by half compared with vaginal birth (aOR: 0.50, 95%CI: 0.39, 0.64). A history of abnormal vaginal discharge increased odds of stillbirth (aOR: 1.42, 95%CI: 1.11, 1.81) as did a history of stillbirth (aOR: 3.08, 95%CI: 1.5, 6.5).ConclusionsStillbirth prevention in this maternity referral hospital in Cambodia requires strengthening preterm birth detection and management of SGA, intrapartum care, monitoring women with stillbirth history, management of breech births, and further investigation of high-risk referral cases.

Total liquid ventilation in an ovine model of extreme prematurity: a randomized study.

This study aimed at comparing cardiorespiratory stability during total liquid ventilation (TLV)-prior to lung aeration-with conventional mechanical ventilation (CMV) in extremely preterm lambs during the first 6 h of life. 23 lambs (11 females) were born by c-section at 118-120 days of gestational age (term = 147 days) to receive 6 h of TLV or CMV from birth. Lung samples were collected for RNA and histology analyses. The lambs under TLV had higher and more stable arterial oxygen saturation (p = 0.001) and cerebral tissue oxygenation (p = 0.02) than the lambs in the CMV group in the first 10 min of transition to extrauterine life. Although histological assessment of the lungs was similar between the groups, a significant upregulation of IL-1a, IL-6 and IL-8 RNA in the lungs was observed after TLV. Total liquid ventilation allowed for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Refinement of our TLV prototype and ventilation algorithms is underway to address specific challenges in this population, such as minimizing tracheal deformation during the active expiration. Total liquid ventilation allows for remarkably stable transition to extrauterine life in an extremely preterm lamb model. Total liquid ventilation is systematically achievable over the first 6 h of life in the extremely premature lamb model. This study provides additional incentive to pursue further investigation of total liquid ventilation as a transition tool for the most extreme preterm neonates.

Pathogenetic Aspects of Intraventricular Hemorrhages in Extremely Premature Infants

INTRODUCTION: Intraventricular hemorrhage (IVH) is one of the most common types of the brain damage in newborns with extremely low and very low body mass. The main source of IVH in the extremely premature infants is the germinal matrix. This is a subependymal structure of the brain consisting of poorly differentiated, randomly arranged cells, well vascularized with vessels with a poor connective-tissue support. The germinal matrix a key supplier of neurons and glial cells of the brain is unique among the brain regions for its specific rate of angiogenesis and selective vulnerability to hemorrhages during its development. Etiology and pathogenesis of IVH in premature infants are highly multifactorial and have not been fully studied. In this review, the data on the key points of the pathogenesis of IVH in premature infants are generalized.&#x0D; CONCLUSION: IVH is a potentially destructive disease, in the study of which a certain progress has been achieved in elucidating the causes and mechanisms of brain damage. In-depth understanding of the key points of the pathogenesis of intraventricular hemorrhage will permit to choose the optimal management tactics and develop new approaches to prevention and treatment of this pathology.

Factors Predicting Secondary Respiratory Morbidity Following Early-Life Respiratory Syncytial Virus Infections: Population-Based Cohort Study.

The association between early-life respiratory syncytial virus (RSV) infections and later respiratory morbidity is well established. However, there is limited evidence on factors that influence this risk. We examined sociodemographic and perinatal factors associated with later childhood respiratory morbidity requiring secondary care following exposure to a laboratory-confirmed RSV episode in the first 2 years. We used a probabilistically linked whole-of-population-based birth cohort including 252 287 children born in Western Australia between 2000 and 2009 with follow-up to the end of 2012. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of the association of various risk factors with the first respiratory episode for asthma, wheezing, and unspecified acute lower respiratory infection beyond the age of 2 years. The analytic cohort included 4151 children with a confirmed RSV test before age 2 years. The incidence of subsequent respiratory morbidity following early-life RSV infection decreased with child age at outcome (highest incidence in 2-<4-year-olds: 41.8 per 1000 child-years; 95% CI, 37.5-46.6), increased with age at RSV infection (6-<12-month-olds: 23.6/1000 child-years; 95% CI, 19.9-27.8; 12-<24-month-olds: 22.4/1000 child-years; 95% CI, 18.2-22.7) and decreasing gestational age (50.8/1000 child-years; 95% CI, 33.5-77.2 for children born extremely preterm, <28 weeks gestation). Risk factors included age at first RSV episode (6-<12 months: aHR, 1.42; 95% CI, 1.06-1.90), extreme prematurity (<28 weeks: aHR, 2.22; 95% CI, 1.40-3.53), maternal history of asthma (aHR, 1.33; 95% CI, 1.04-1.70), and low socioeconomic index (aHR, 1.76; 95% CI, 1.03-3.00). Our results suggest that in addition to preterm and young infants, children aged 12-<24 months could also be potential target groups for RSV prevention to reduce the burden of later respiratory morbidities associated with RSV.