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Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = −0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

•Fetuses with ATM who receive ≥2 IUTs have resolution of hydrops with near-term birth and a short hospital stay.•Children with ATM who received ≥2 IUTs have normal neurodevelopment; earlier transfusions correlate with higher scores.

A 36-week, 5-day-old boy was born through uncomplicated vaginal delivery to a healthy, 36-year-old G7P4 mother. His resuscitation included tactile warmth, drying, and stimulation, and his Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. He was small for gestational age with a birth weight of 2100 g (0.16 percentile). His course was unremarkable with normal behavior and breastfeeding for approximately 40 hours of life.

Objectives: To investigate racial/ethnic differences in rehospitalization and mortality rates among premature infants over the first year of life. Study design: A retrospective cohort study of infants born in California from 2011 to 2017 (n= 3,448,707) abstracted from a California Office of Statewide Health Planning and Development database. Unadjusted Kaplan–Meier tables and logistic regression controlling for health and sociodemographic characteristics were used to predict outcomes by race/ethnicity. Results: Compared to White infants, Hispanic and Black early preterm infants were more likely to be readmitted; Black late/moderate preterm (LMPT) infants were more likely to be readmitted and to die after discharge; Hispanic and Black early preterm infants with BPD were more likely to be readmitted; Black LMPT infants with RDS were more likely to be readmitted and die after discharge. Conclusions: Racial/ethnic disparities in readmission and mortality rates exist for premature infants across several co-morbidities. Future studies are needed to improve equitability of outcomes.

IMPORTANCE: Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm. OBJECTIVE: To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks’ gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months’ corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors. MAIN OUTCOMES AND MEASURES: Punctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months’ CA. RESULTS: Of 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, −2.2; 95% CI, −5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, −3.0; 95% CI, −6.4 to 0.4). CONCLUSIONS AND RELEVANCE: Histologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months’ CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.

Introduction:COL4A1/A2 mutations affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a potential cause of intracranial hemorrhage across the lifespan. We aim to describe fetal MRI findings and clinical outcomes in seven cases of fetal intraparenchymal hemorrhage (IPH) associated with COL4A1/A2 mutations.Methods:Subjects with COL4A1/A2 mutations were identified from a retrospective single-center cohort study of fetal IPH identified on fetal brain MRI between 1998-2021. Imaging findings were reviewed by two pediatric neuroradiologists, and clinical data were collected from electronic medical records.Results:Among the seven subjects with fetal IPH and COL4A1/A2 mutations, fetal MRI was performed at median gestational age (GA) 29 weeks (range 22-36 weeks) and demonstrated supratentorial IPH in 7/7 with variable size of hemorrhage, including 4/7 with multifocal hemorrhage (Figure 1).Four fetuses were liveborn at median GA 39 weeks (range 33-42 weeks); three pregnancies were terminated. Postnatal imaging revealed recurrent IPH in 1/4 cases, but no cases had recurrent IPH after the neonatal period. None of the seven cases had known family history of COL4A1/A2 or IPH; genetic testing revealed 5/7 with COL4A1 mutation, 1/7 with COL4A2 mutation, and 1/7 with 13q34 deletion with associated loss of COL4A1 and COL4A2 genes. Clinical follow-up data was available for the four liveborn cases through ≥12 months; three had mild hemiplegic cerebral palsy and one had severe spastic quadriplegia. None required CSF diversion, none had epilepsy, and one had visual impairment.Conclusions:Our series suggests that COL4A1/A2 mutations can present as fetal IPH with a wide range of phenotypes ranging from unifocal to multifocal IPH without additional systemic involvement, and that prenatal imaging severity may be associated with early clinical outcomes. COL4A1/A2 testing should be considered in all cases of prenatal IPH, regardless of severity.

(Abstracted from JAMA Pediatr2018;172(6):534–541)Acute chorioamnionitis refers to the neutrophilic inflammation of the placental tissues thought to result from an ascending bacterial infection. It is considered a major factor associated with preterm birth and has been estimated to occur in 40% to 80% of preterm deliveries.

AbstractPreterm newborns are highly susceptible to brain injury. White matter injury is among the dominant patterns of brain injury in preterm newborns. The purpose of this review is to discuss the pathogenesis, diagnosis, management, and prevention of white matter injury in premature newborns. The long-term outcome of white matter injury in children born prematurely is also addressed.

Background:Anesthesia in early childhood is associated with adverse neurodevelopmental outcome; however, it is not known if age at exposure affects the risk of adverse outcome. Our objective was to evaluate the association of the number and timing of anesthetic exposures for surgery with cognitive outcome in a cohort of premature newborns.Methods:A cohort study of exposure to anesthesia for surgery in premature newborns (<33?wk gestation) prospectively evaluated with neonatal magnetic resonance imaging (MRI) and neurodevelopmental testing at 3–6 y was employed. Exposure to anesthesia for surgery was classified as before term-equivalent age (TEA, <42?wk postmenstrual age) or after (=42?wk). Multivariate regression was performed to analyze the association of composite IQ scores with the number of surgeries before and after TEA.Results:Among 137 newborns, 25 (18.2%) had one surgery before TEA and 18 (13.1%) had =2 surgeries. Two or more surgeries before TEA were associated with significantly reduced composite IQ scores at 4.6?±?0.6 y after adjusting for gestational age and illness severity. Neither the number of surgeries after TEA nor sedation for MRI was associated with cognitive outcome.Conclusions:More than one surgery prior to TEA is independently associated with impaired cognitive performance in premature newborns.

Background:Brain injury in term neonatal hypoxic–ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE.Methods:A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures.Results:Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P = 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P = 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns.Conclusion:In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.

A Correction to this paper has been published: https://doi.org/10.1038/s41372-021-01004-x