The utility of the fronto-temporal horn ratio on cranial ultrasound in premature newborns: a ventriculomegaly marker.

BACKGROUND: The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a marker of ventriculomegaly on cranial ultrasound (CUS) in premature newborns and the relation to white matter injury (WMI) and cerebral palsy (CP). METHODS: This is a retrospective study of newborns admitted between 2011 and 2014. Inclusion criteria were: (1) gestation <29 weeks, (2) birth weight ≤1500 g, (3) referred within 7 days of life, (4) at least two CUS preformed, (5) brain magnetic resonance imaging (MRI) at term age-equivalent. Intraventricular hemorrhage (IVH) grade was identified and FTHR was measured on all CUS. WMI on MRI was evaluated through (1) injury score (Kidokoro 2013) and (2) fractional anisotropy (FA) on the MRI diffusion tensor imaging. CP was estimated using the gross motor function classification system (GMFCS). RESULTS: One hundred neonates met the inclusion criteria: 37 with no IVH, 36 with IVH grade 1-2, and 27 with IVH grade 3-4. The FTHR cut-point of 0.51 had the highest sensitivity and specificity for moderate-to-severe WMI. In the IVH grade 3-4 group, the elevated FTHR correlated with lower FA and higher GMFCS. CONCLUSIONS: FTHR is a useful quantitative biomarker of ventriculomegaly in preterm newborns. It may help standardize ventricular measurement and direct intervention. IMPACT: The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population.

High-Frequency Positive Pressure Ventilation as Primary Rescue Strategy for Patients with Congenital Diaphragmatic Hernia: A Comparison to High-Frequency Oscillatory Ventilation.

OBJECTIVE: The aim of this article was to evaluate high-frequency positive pressure ventilation (HFPPV) compared with high-frequency oscillatory ventilation (HFOV) as a rescue ventilation strategy for patients with congenital diaphragmatic hernia (CDH). HFPPV is a pressure-controlled conventional ventilation method utilizing high respiratory rate and low positive end-expiratory pressure. STUDY DESIGN: Seventy-seven patients diagnosed with CDH from January 2005 to September 2019 who were treated with stepwise progression from HFPPV to HFOV versus only HFOV were included. Fisher's exact test and the Kruskal-Wallis test were used to compare outcomes. RESULTS: Patients treated with HFPPV + HFOV had higher survival to discharge (80 vs. 50%, p = 0.007) and to surgical intervention (95.6 vs. 68.8%, p = 0.003), with average age at repair 2 days earlier (p = 0.004). Need for extracorporeal membrane oxygenation (p = 0.490), inhaled nitric oxide (p = 0.585), supplemental oxygen (p = 0.341), and pulmonary hypertension medications (p = 0.381) were similar. CONCLUSION: In CDH patients who fail respiratory support with conventional ventilation, HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effects. KEY POINTS: · HFPPV may be used as an intermediary mode of rescue ventilation prior to HFOV without adverse effect.. · HFPPV is more widely available and can mitigate the limitations faced when using HFOV.. · HFPPV allows for intra- or interhospital transfer of neonates with CDH..

Placental programming of neuropsychiatric disease.

The placenta is vital for fetal growth, and compromised function is associated with abnormal development, especially of the brain. Linking placental function to brain development is a new field we have dubbed neuroplacentology. Approximately 380,000 infants in the United States each year abruptly lose placental support upon premature birth, and more than 10% of pregnancies are affected by more insidious placental dysfunction such as preeclampsia or infection. Abnormal fetal brain development or injury can lead to life-long neurological impairments, including psychiatric disorders. The majority of research connecting placental compromise to fetal brain injury has focused on gas exchange or nutritional programming, neglecting the placenta's essential neuroendocrine role. We will review the current evidence that placental dysfunction, particularly endocrine dysfunction, secretion of pro-inflammatory cytokines, or barrier breakdown may place many thousands of fetuses at risk for life-long neurodevelopmental impairments each year. Understanding how specific placental factors shape brain development and increase the risk for later psychiatric disorders, including autism, attention deficit disorder, and schizophrenia, paves the way for novel treatment strategies to maintain the normal developmental milieu and protect from further injury.

Ventricular shape evaluation on early ultrasound predicts post-hemorrhagic hydrocephalus.

BACKGROUND: To compare the ability of ventricular morphology on cranial ultrasound (CUS) versus standard clinical variables to predict the need for temporizing cerebrospinal fluid drainage in newborns with intraventricular hemorrhage (IVH). METHOD: This is a retrospective study of newborns (gestational age <29 weeks) diagnosed with IVH. Clinical variables known to increase the risk for post-hemorrhagic hydrocephalus were collected. The first CUS with IVH was identified and a slice in the coronal plane was selected. The frontal horns of the lateral ventricles were manually segmented. Automated quantitative morphological features were extracted from both lateral ventricles. Predictive models of the need of temporizing intervention were compared. RESULTS: Sixty-two newborns met inclusion criteria. Fifteen out of the 62 had a temporizing intervention. The morphological features had a better accuracy predicting temporizing interventions when compared to clinical variables: 0.94 versus 0.85, respectively; p < 0.01 for both. By considering both morphological and clinical variables, our method predicts the need of temporizing intervention with positive and negative predictive values of 0.83 and 1, respectively, and accuracy of 0.97. CONCLUSION: Early cranial ultrasound-based quantitative ventricular evaluation in premature newborns can predict the eventual use of a temporizing intervention to treat post-hemorrhagic hydrocephalus. This may be helpful for early monitoring and treatment.

Classification of Preterm Birth With Placental Correlates.

Premature birth lacks a widely accepted classification that unites features of the clinical presentation with placental pathology. To further explore associations between the clinical categories of preterm birth and placental histology, 109 infants with gestational age <34 weeks and birth weight <2000 g were selected and, based on electronic records, were classified into preterm birth categories of preterm labor, prelabor premature rupture of membranes, preeclampsia, indicated preterm birth for maternal factors (other than preeclampsia), indicated preterm birth for fetal factors, and the clinical diagnosis of abruption. Corresponding placentas were analyzed for gross and microscopic variables, with findings grouped into categories of amniotic fluid infection, lymphocytic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Placental features of maternal vascular malperfusion were pervasive in all preterm birth categories and were commonly associated with amniotic fluid infection and lymphocytic inflammation. Features of maternal vascular malperfusion were significantly associated with preterm birth due to preeclampsia, and amniotic fluid infection was highly associated with prelabor preterm rupture of membranes. Findings of lymphocytic inflammation were significantly increased in cases of abruption. Laminar decidual necrosis was present in all cases of abruption. Placentas from multiple gestations had significantly less histologic findings compared to singletons. Given that 75% of placentas demonstrated at least 1 feature of maternal vascular malperfusion despite different clinical presentations, seemingly different pathologies such as ascending amniotic fluid infection or lymphocytic inflammation may be mechanistically related to processes established early in pregnancy. The concept of "uterine ischemia" may be too simplistic to account for all of the changes attributed to maternal vascular malperfusion in the preterm placenta.

Controversies in preterm brain injury.

In this review, we highlight critical unresolved questions in the etiology and mechanisms causing preterm brain injury. Involvement of neurons, glia, endogenous factors and exogenous exposures is considered. The structural and functional correlates of interrupted development and injury in the premature brain are under active investigation, with the hope that the cellular and molecular mechanisms underlying developmental abnormalities in the human preterm brain can be understood, prevented or repaired.

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic.

Importance: Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. Objective: To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. Design, Setting, and Participants: Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. Exposures: Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. Results: The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). Conclusions and Relevance: In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Lack of placental neurosteroid alters cortical development and female somatosensory function.

Placental endocrine function is essential to fetal brain development. Placental hormones include neurosteroids such as allopregnanolone (ALLO), a regulator of neurodevelopmental processes via positive allosteric modulation of the GABAA receptor (GABAA-R). Using a mouse model (plKO) in which the gene encoding the ALLO synthesis enzyme is specifically deleted in trophoblasts, we previously showed that placental ALLO insufficiency alters cerebellar white matter development and leads to male-specific autistic-like behavior. We now demonstrate that the lack of placental ALLO causes female-predominant alterations of cortical development and function. Placental ALLO insufficiency disrupts cell proliferation in the primary somatosensory cortex (S1) in a sex-linked manner. Early changes are seen in plKO embryos of both sexes, but persist primarily in female offspring after birth. Adolescent plKO females show significant reduction in pyramidal neuron density, as well as somatosensory behavioral deficits as compared with plKO males and control littermates. Assessment of layer-specific markers in human postmortem cortices suggests that preterm infants may also have female-biased abnormalities in cortical layer specification as compared with term infants. This study establishes a novel and fundamental link between placental function and sex-linked long-term neurological outcomes, emphasizing the importance of the growing field of neuroplacentology.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection.

Importance: Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown. Objective: To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. Design, Setting, and Participants: A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses. Exposures: Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. Main Outcomes and Measures: Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. Results: Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance: In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.

Neonatal medical admission in a term and late-preterm cohort exposed to magnesium sulfate.

OBJECTIVE: The purpose of this study was to estimate neonatal intensive care unit and special care unit (NICU) admission rates and care needs among term and late-preterm neonates who are exposed to antenatal magnesium sulfate. STUDY DESIGN: We conducted a retrospective cohort study of all singleton neonates of ≥35 weeks' gestation who were exposed immediately antenatally to magnesium sulfate for maternal eclampsia prophylaxis (August 2006 through July 2008). RESULTS: Fifty-one of 242 neonates (21.1%) who, at ≥35 weeks' gestation, had been exposed to antenatal magnesium sulfate were admitted to the NICU. NICU admission was associated in a dose-dependent fashion with total hours and mean dose of magnesium: >12 hours exposure, odds ratio, 2.81 (95% confidence interval, 1.31-6.03); >30 g exposure, odds ratio, 2.59 (95% confidence interval, 1.22-5.51). Infants in NICU who were diagnosed with hypermagnesemia required fluid or nutritional support more frequently (91.3% vs 39.3%; P < .001) than those without hypermagnesemia. CONCLUSION: Antenatal magnesium sulfate exposure is associated with NICU admission among term and late-preterm neonates in a dose-dependent fashion. Fluid and nutritional assistance commonly are needed in this cohort.

Sex-specific cognitive deficits and regional brain volume loss in mice exposed to chronic, sublethal hypoxia.

Male sex is an independent risk factor for long-term neurologic deficits in human preterm infants. Using a chronic, sublethal hypoxia (CSH) mouse model of preterm brain injury, we recently demonstrated acute brain volume loss with an increased male susceptibility to hippocampal volume loss and hypomyelination. We now characterize the long-term, sex-specific effects of CSH on cognition and brain growth. Neonatal mice were treated with CSH for 8 d, raised in normoxia thereafter and underwent behavioral testing at 6 wk of age. Behavioral assays sensitive to hippocampal function were chosen. CSH-treated males had impairments in associative learning, spatial memory, and long-term social memory compared with control males. In contrast, CSH-treated females were less impaired. Persistent reductions in hippocampal and cerebellar volumes were found in adult CSH-treated males, whereas regional brain volumes in adult CSH-treated females were indistinguishable from controls. Similar to human preterm infants, males exposed to hypoxia are especially vulnerable to short-term and long-term deficits in cognition and brain growth.

Preterm Birth Alters the Maturation of the GABAergic System in the Human Prefrontal Cortex.

Developmental changes in GABAergic and glutamatergic systems during frontal lobe development have been hypothesized to play a key role in neurodevelopmental disorders seen in children born very preterm or at/with low birth weight, but the associated cellular changes have not yet been identified. Here we studied the molecular development of the GABAergic system specifically in the dorsolateral prefrontal cortex, a region that has been implicated in neurodevelopmental and psychiatric disorders. The maturation state of the GABAergic system in this region was assessed in human post-mortem brain samples, from term infants ranging in age from 0 to 8 months (n = 17 male, 9 female). Gene expression was measured for 47 GABAergic genes and used to calculate a maturation index. This maturation index was significantly more dynamic in male than female infants. To evaluate the impact of premature birth on the GABAergic system development, samples from 1-month-old term (n = 9 male, 4 female) and 1-month corrected-age very preterm (n = 8 male, 6 female) infants, were compared using the same gene list and methodology. The maturation index for the GABAergic system was significantly lower (-50%, p < 0.05) in male preterm infants, with major alterations in genes linked to GABAergic function in astrocytes, suggesting astrocytic GABAergic developmental changes as a new cellular mechanism underlying preterm brain injury.

A new pipeline for clinico-pathological and molecular placental research utilizing FFPE tissues.

The placenta is at the core of many pregnancy pathologies, but we have limited knowledge about placental function because of two key research barriers: 1) lack of guidelines for sample collection and pathologic diagnosis; and 2) limited tools are available for molecular analysis of stored placental samples. We aimed to create a searchable, population-based placental database of pathologic diagnoses, and to validate molecular methods for gene expression studies of matching formalin fixed paraffin embedded (FFPE) placental blocks. Our database has over 1000 pregnancies coded for clinical diagnosis with corresponding FFPE blocks that are available for gene expression studies. RNA harvested from FFPE tissues is of sufficient quality for downstream applications. We successfully used this pipeline to identify FFPE placenta from term and preterm pregnancies, and compared their gene expression. The establishment of this platform, which links clinicopathological data and molecular gene expression, will increase our understanding of obstetrical diseases.

Placental pathology and intraventricular hemorrhage in preterm and small for gestational age infants.

OBJECTIVE: The aim of this study was to examine the relationship between chorioamnionitis and vascular malperfusion on placental pathology and intraventricular hemorrhage (IVH) in premature and small for gestational age (SGA) infants. STUDY DESIGN: A retrospective analysis of 263 infants ≤34 weeks gestation or ≤1800 g and their mothers was conducted by chart review for placental pathology and clinical data from 2014 to 2018. Unadjusted and adjusted odds ratios (OR) for the association of placental pathology with IVH were calculated. RESULT: Unadjusted OR showed an association between acute chorioamnionitis and IVH, but logistic regression analysis showed a non-significant adjusted OR between acute or chronic chorioamnionitis with IVH. Maternal vascular malperfusion was significantly associated with increased IVH when controlling for confounders. CONCLUSION: Placental maternal vascular malperfusion is associated with the development of IVH in premature and SGA infants when controlling for other confounders.

Placental response to maternal SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.

Placental endocrine function shapes cerebellar development and social behavior.

Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABAAR) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO's synthetic enzyme (akr1c14) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABAAR agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.

Outcomes of Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection at a Large Medical Center in New York City.

Importance: Limited data on vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and health outcomes of neonates born to mothers with symptomatic or asymptomatic coronavirus disease 2019 (COVID-19) are available. Studies are needed to inform evidence-based infection prevention and control (IP&C) policies. Objective: To describe the outcomes of neonates born to mothers with perinatal SARS-CoV-2 infection and the IP&C practices associated with these outcomes. Design, Setting, and Participants: This retrospective cohort analysis reviewed the medical records for maternal and newborn data for all 101 neonates born to 100 mothers positive for or with suspected SARS-CoV-2 infection from March 13 to April 24, 2020. Testing for SARS-CoV-2 was performed using Cobas (Roche Diagnostics) or Xpert Xpress (Cepheid) assays. Newborns were admitted to well-baby nurseries (WBNs) (82 infants) and neonatal intensive care units (NICUs) (19 infants) in 2 affiliate hospitals at a large academic medical center in New York, New York. Newborns from the WBNs roomed-in with their mothers, who were required to wear masks. Direct breastfeeding after appropriate hygiene was encouraged. Exposures: Perinatal exposure to maternal asymptomatic/mild vs severe/critical COVID-19. Main Outcomes and Measures: The primary outcome was newborn SARS-CoV-2 testing results. Maternal COVID-19 status was classified as asymptomatic/mildly symptomatic vs severe/critical. Newborn characteristics and clinical courses were compared across maternal COVID-19 severity. Results: In total, 141 tests were obtained from 101 newborns (54 girls [53.5%]) on 0 to 25 days of life (DOL-0 to DOL-25) (median, DOL-1; interquartile range [IQR], DOL-1 to DOL-3). Two newborns had indeterminate test results, indicative of low viral load (2.0%; 95% CI, 0.2%-7.0%); 1 newborn never underwent retesting but remained well on follow-up, and the other had negative results on retesting. Maternal severe/critical COVID-19 was associated with newborns born approximately 1 week earlier (median gestational age, 37.9 [IQR, 37.1-38.4] vs 39.1 [IQR, 38.3-40.2] weeks; P = .02) and at increased risk of requiring phototherapy (3 of 10 [30.0%] vs 6 of 91 [7.0%]; P = .04) compared with newborns of mothers with asymptomatic/mild COVID-19. Fifty-five newborns were followed up in a new COVID-19 Newborn Follow-up Clinic at DOL-3 to DOL-10 and remained well. Twenty of these newborns plus 3 newborns followed up elsewhere had 32 nonroutine encounters documented at DOL-3 to DOL-25, and none had evidence of SARS-CoV-2 infection, including 6 with negative retesting results. Conclusions and Relevance: No clinical evidence of vertical transmission was identified in 101 newborns of mothers positive for or with suspected SARS-CoV-2 infection, despite most newborns rooming-in and direct breastfeeding practices.

Ultrasound-Based Phenotyping of Lateral Ventricles to Predict Hydrocephalus Outcome in Premature Neonates.

OBJECTIVE: Prediction of post-hemorrhagic hydrocephalus (PHH) outcome-i.e., whether it requires intervention or not-in premature neonates using cranial ultrasound (CUS) images is challenging. In this paper, we present a novel fully-automatic method to perform phenotyping of the brain lateral ventricles and predict PHH outcome from CUS. METHODS: Our method consists of two parts: ventricle quantification followed by prediction of PHH outcome. First, cranial bounding box and brain interhemispheric fissure are detected to determine the anatomical position of ventricles and correct the cranium rotation. Then, lateral ventricles are extracted using a new deep learning-based method by incorporating the convolutional neural network into a probabilistic atlas-based weighted loss function and an image-specific adaption. PHH outcome is predicted using a support vector machine classifier trained using ventricular morphological phenotypes and clinical information. RESULTS: Experiments demonstrated that our method achieves accurate ventricle segmentation results with an average Dice similarity coefficient of 0.86, as well as very good PHH outcome prediction with accuracy of 0.91. CONCLUSION: Automatic CUS-based ventricular phenotyping in premature newborns could objectively and accurately predict the progression to severe PHH. SIGNIFICANCE: Early prediction of severe PHH development in premature newborns could potentially advance criteria for diagnosis and offer an opportunity for early interventions to improve outcome.

Care of the COVID-19 exposed complex newborn infant.

As we confront COVID-19, the global public health emergency of our times, new knowledge is emerging that, combined with information from prior epidemics, can provide insights on how to manage this threat in specific patient populations. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), both caused by coronaviruses, caused serious respiratory illness in pregnant women that resulted in adverse perinatal outcomes. Thus far, COVID-19 appears to follow a mild course in the vast majority of pregnant women. A significant proportion of pregnant women appear to be asymptomatic carriers of SARS-CoV-2. However, there is limited information on how COVID-19 impacts the fetus and whether vertical transmission occurs. While these knowledge gaps are addressed, it is important to recognize the highly efficient transmission characteristics of SARS-C0V-2 and its potential for causing serious disease in vulnerable individuals, including health care workers. This review provides perspectives from a single center in New York City, the epicenter of the pandemic within the United States. It offers an overview of the preparations required for deliveries of newborns of mothers with COVID-19 and the management of neonates with particular emphasis on those born with complex issues.