Need for Gastrostomy Tube in Periviable Infants.

OBJECTIVE: We sought to identify clinical and demographic factors associated with gastrostomy tube (g-tube) placement in periviable infants. STUDY DESIGN: We conducted a single-center retrospective cohort study of live-born infants between 22 and 25 weeks' gestation. Infants not actively resuscitated and those with congenital anomalies were excluded from analysis. RESULTS: Of the 243 infants included, 158 survived until discharge. Of those that survived to discharge, 35 required g-tube prior to discharge. Maternal race/ethnicity (p = 0.006), intraventricular hemorrhage (p = 0.013), periventricular leukomalacia (p = 0.003), bronchopulmonary dysplasia (BPD; p ≤ 0.001), and singleton gestation (p = 0.009) were associated with need for gastrostomy. In a multivariable logistic regression, maternal Black race (Odds Ratio [OR] 2.88; 95% confidence interval [CI] 1.11-7.47; p = 0.029), singleton gestation (OR 3.99; 95% CI 1.28-12.4; p = 0.017) and BPD (zero g-tube placement in the no BPD arm; p ≤ 0.001) were associated with need for g-tube. CONCLUSION: A high percentage of periviable infants surviving until discharge require g-tube at our institution. In this single-center retrospective study, we noted that maternal Black race, singleton gestation, and BPD were associated with increased risk for g-tube placement in infants born between 22 and 25 weeks' gestation. The finding of increased risk with maternal Black race is consistent with previous reports of racial/ethnic disparities in preterm morbidities. Additional studies examining factors associated with successful achievement of oral feedings in preterm infants are necessary and will inform future efforts to advance equity in newborn health. KEY POINTS: · BPD, singleton birth, and Black race are associated with need for g-tube in periviable infants.. · Severe intraventricular hemorrhage is associated with increased mortality or g-tube placement in periviable infants.. · Further investigation into the relationship between maternal race and g-tube placement is warranted..

Risk of birth defects in pregnant persons with sleep-disordered breathing during pregnancy.

INTRODUCTION: As many as one in four pregnant women may experience sleep-disordered breathing (SDB) during pregnancy. The same sequelae of SDB, such as insulin resistance and inflammation, have been implicated in the development of certain birth defects. METHODS: This is a secondary analysis of the SDB substudy of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be study, which included 2106 participants who had a sufficiency sleep study at two visits at different time points in pregnancy. SDB was based on a self-administered home sleep apnea test with data scored by trained, blinded research polysomnologists. SDB was defined as an apnea-hypopnea index (AHI) ≥5. The primary outcome of this analysis was any of the 45 non-chromosomal birth defects included in the National Birth Defects Prevention Network Annual Report. RESULTS: In this cohort, the overall rate of birth defects was 3.1%. The prevalence was similar between those without SDB (3.0%) and those with only mid-pregnancy SDB (3.4%), but was higher in those with early-pregnancy SDB (6.7%). After adjusting for maternal age, chronic hypertension, pregestational diabetes, and body mass index (BMI), there were no statistically significant differences in the risk of birth defects by subject SDB status. CONCLUSIONS: Further studies to evaluate the effect of prepregnancy and early-pregnancy SDB on the fetus, as well as the risk of specific birth defects and neonatal outcomes in those with an objectively measured diagnosis of SDB, are still needed.

Association between Sleep Disordered Breathing and Neonatal Outcomes in Nulliparous Individuals.

OBJECTIVE: Our objective was to determine whether objectively measured sleep-disordered breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals. STUDY DESIGN: Secondary analysis of the nuMom2b sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early (6-15 weeks' gestation) and mid-pregnancy (22-31 weeks' gestation). SDB was defined as an apnea-hypopnea index ≥5 events/h at either time point. The primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age, seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into (1) early pregnancy SDB (6-15 weeks' gestation), (2) new onset mid-pregnancy SDB (22-31 weeks' gestation), and (3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CIs) representing the association. RESULTS: Among 2,106 participants, 3% (n = 75) had early pregnancy SDB and 5.7% (n = 119) developed new-onset mid-pregnancy SDB. The incidence of the primary outcome was higher in the offspring of individuals with early (29.3%) and new onset mid-pregnancy SDB (30.3%) compared with individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, and body mass index, new onset mid-pregnancy SDB conferred increased risk (RR = 1.43, 95% CI: 1.05, 1.94), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome. CONCLUSION: New onset, mid-pregnancy SDB is independently associated with neonatal morbidity. KEY POINTS: · Sleep disordered breathing (SDB) is a common condition impacting pregnancy with known maternal risks.. · Objectively defined SDB in pregnancy was associated with a composite of adverse neonatal outcomes.. · New onset SDB in mid pregnancy conferred statistically significant increased risk..

Group B Streptococcus Drives Major Transcriptomic Changes in the Colonic Epithelium.

Group B Streptococcus (GBS) is a leading cause of infant sepsis worldwide. Colonization of the gastrointestinal tract is a critical precursor to late-onset disease in exposed newborns. Neonatal susceptibility to GBS intestinal translocation stems from intestinal immaturity; however, the mechanisms by which GBS exploits the immature host remain unclear. ß-hemolysin/cytolysin (ßH/C) is a highly conserved toxin produced by GBS capable of disrupting epithelial barriers. However, its role in the pathogenesis of late-onset GBS disease is unknown. Our aim was to determine the contribution of ßH/C to intestinal colonization and translocation to extraintestinal tissues. Using our established mouse model of late-onset GBS disease, we exposed animals to GBS COH-1 (WT), a ßH/C-deficient mutant (KO), or vehicle control (phosphate-buffered saline [PBS]) via gavage. Blood, spleen, brain, and intestines were harvested 4 days post-exposure for determination of bacterial burden and isolation of intestinal epithelial cells. RNA sequencing was used to examine the transcriptomes of host cells followed by gene ontology enrichment and KEGG pathway analysis. A separate cohort of animals was followed longitudinally to compare colonization kinetics and mortality between WT and KO groups. We demonstrate that dissemination to extraintestinal tissues occurred only in the WT exposed animals. We observed major transcriptomic changes in the colons of colonized animals, but not in the small intestines. We noted differential expression of genes that indicated the role of ßH/C in altering epithelial barrier structure and immune response signaling. Overall, our results demonstrate an important role of ßH/C in the pathogenesis of late-onset GBS disease.

Vaginal carriage of Haemophilus influenzae in a non-pregnant reproductive-age population.

BACKGROUND: Haemophilus influenzae (Hi) is an emerging cause of early onset neonatal sepsis, but mechanisms of transmission are not well understood. We aimed to determine the prevalence of vaginal carriage of Hi in reproductive age women and to examine behavioral and demographic characteristics associated with its carriage. METHODS: We performed a secondary analysis of stored vaginal lavage specimens from a prospective cohort study of nonpregnant reproductive-age women. After extraction of bacterial genomic DNA, samples were tested for the presence of the gene encoding Haemophilus protein d (hpd) by quantitative real-time polymerase chain reaction (PCR) using validated primers and probe. PCR for the V3-V4 region of the 16 S rRNA gene (positive control) assessed sample quality. Samples with cycle threshold (CT) value < 35 were defined as positive. Sanger sequencing confirmed the presence of hpd. Behavioral and demographic characteristics associated with vaginal carriage of Hi were examined. RESULTS: 415 samples were available. 315 (75.9%) had sufficient bacterial DNA and were included. 14 (4.4%) were positive for hpd. There were no demographic or behavioral differences between the women with Hi vaginal carriage and those without. There was no difference in history of bacterial vaginosis, vaginal microbiome community state type, or presence of Group B Streptococcus in women with and without vaginal carriage of Hi. CONCLUSION: Hi was present in vaginal lavage specimens of 4.4% of this cohort. Hi presence was unrelated to clinical or demographic characteristics, though the relatively small number of positive samples may have limited power to detect such differences.

Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy.

Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin ß-hemolysin/cytolysin (ß-h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of ß-h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through ß-h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a ß-h/c-deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that ß-h/c-producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge.

What's new in the management of neonatal early-onset sepsis?

The expert guidelines highlighted in this review provide an evidence-based framework for approaching at-risk infants and allow for a more limited and standardised approach to antibiotic use. While these guidelines have significantly reduced antibiotic utilisation worldwide, optimally each unit would individualise their approach to early onset sepsis (EOS) based on the neonatal population they serve and available resources. As advancements in EOS research continue and limitations with sepsis prediction tools are addressed, it is inevitable that our risk stratification and management guidelines will become more precise.

Systematic Review of Literature Examining Bacterial Urinary Tract Infections in Diabetes.

This systematic review addresses the central research question, "what is known from the published, peer-reviewed literature about the impact of diabetes on the risk of bacterial urinary tract infections (UTI)?" We examine the results from laboratory studies where researchers have successfully adapted mouse models of diabetes to study the pathophysiology of ascending UTI. These studies have identified molecular and cellular effectors shaping immune defenses against infection of the diabetic urinary tract. In addition, we present evidence from clinical studies that in addition to diabetes, female gender, increased age, and diabetes-associated hyperglycemia, glycosuria, and immune impairment are important risk factors which further increase the risk of UTI in diabetic individuals. Clinical studies also show that the uropathogenic genera causing UTI are largely similar between diabetic and nondiabetic individuals, although diabetes significantly increases risk of UTI by drug-resistant uropathogenic bacteria.

Toward the development of a protein-based group B Streptococcus vaccine.

Clinical trials of protein-based vaccines to prevent Group B streptococcal infections are underway. In this issue of Cell Reports Medicine, Pawlowski et al.1 provide an extensive characterization of the immune response generated by the recently tested GBS-NN vaccine.

Effects of Inhaled Iloprost for the Management of Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVE: The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: We conducted a retrospective chart review of 30 patients with PPHN from January 2014 to November 2018, who did not respond to inhaled nitric oxide (iNO) alone and received inhaled iloprost. Twenty-two patients met the inclusion criteria and eight patients were excluded from the study (complex cardiac disease and extreme prematurity). Patients were categorized as responders or nonresponders (patients who required extracorporeal membrane oxygenation or died). Oxygenation index, mean airway pressure (MAP), and arterial partial pressure of oxygen (PaO2) were recorded. RESULTS: Among a total of 22 patients who were included in the study, 10 were classified as nonresponders as they required either extracorporeal membrane oxygenation or died. Gestational age and gender did not differ between responders and nonresponders. The median PaO2 was lower (37 vs. 42 mm Hg; p < 0.05) and median MAP was higher (20 vs. 17 cm H2O; p < 0.02) in nonresponders compared with responders just prior to initiating iloprost. Iloprost responders had a significant increase in median PaO2 and decrease in median oxygenation index in the 24 hours after initiating treatment (p < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. CONCLUSION: Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. KEY POINTS: · Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN.. · Inhaled iloprost is generally well tolerated in newborns with PPHN.. · There is a need for prospective randomized controlled trials to further ascertain the benefits of using inhaled iloprost..

Equity for women in medicine-neonatologists identify issues.

OBJECTIVE: Inequity between genders with regards to leadership achievement, compensation, scholarly productivity, and grant funding exist among physicians. This study explores whether similar inequities exist among board certified neonatologists within the USA. STUDY DESIGN: A voluntary anonymous survey was distributed to 3575 members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine with 560 respondents (15.7% response rate). The survey contained questions assessing clinician characteristics, work environment, compensation, professional productivity, and social factors. Statistical analysis was done using JMP Pro 15.0.0 by SAS. RESULTS: Female neonatologists, compared to male peers, were less likely to hold leadership positions (OR 0.36, p = 0.005), received lower compensation by an average of $34,916 or 12.47% (p < 0.001), and had 6.71 fewer primary authored publications (p = 0.025) after adjusting for several confounding factors. CONCLUSION: Gender remains a significant independent factor influencing leadership attainment, compensation, and academic productivity in this cohort of neonatologists.

Characteristics of Hospitalized Children With SARS-CoV-2 in the New York City Metropolitan Area.

OBJECTIVES: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0-21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support. RESULTS: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care (P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002). CONCLUSIONS: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care.

The Impact of Circulating Antibody on Group B Streptococcus Intestinal Colonization and Invasive Disease.

Gastrointestinal (GI) colonization with group B Streptococcus (GBS) is an important precursor to late-onset (LO) disease in infants. The host-pathogen interactions that mediate progression to invasive disease remain unknown due, in part, to a paucity of robust model systems. Passively acquired maternal GBS-specific antibodies protect newborns from early-onset disease, yet their impact on GI colonization and LO disease is unexplored. Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease, and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12 and 14 days, respectively. We defined LO disease as >7 days of life in the perinatal model. We studied the impact of maternal immunization using a whole-cell GBS vaccine on the duration of intestinal colonization and progression to invasive disease after postnatal GBS exposure in offspring. Animals exhibit sustained GI colonization following both perinatal and postnatal exposure to GBS, with 21% and 27%, respectively, developing invasive disease. Intestinal colonization with GBS induces an endogenous IgG response within 20 days of exposure. Maternal vaccination with whole-cell GBS induces production of GBS-specific IgG in dams that is vertically transmitted to their offspring but does not decrease the duration of GBS intestinal colonization or reduce LO mortality following postnatal GBS exposure. Both perinatal and postnatal murine models of GBS acquisition closely recapitulate the human disease state, in which GBS colonizes the intestine and causes LO disease. We demonstrate both endogenous production of anti-GBS IgG in juvenile mice and vertical transfer of antibodies to offspring following maternal vaccination. These models serve as a platform to study critical host-pathogen interactions that mediate LO GBS disease.

Group B streptococcal transmission rates as determined by PCR.

Background Group B Streptococcus (GBS) is a common cause of neonatal sepsis. GBS colonization of the newborn gastrointestinal tract (GIT) may be a critical precursor for late-onset infection. Assessment of the rate of neonatal GBS intestinal colonization has generally relied upon culture-based methods. We used polymerase chain reaction (PCR) and culture to determine the rate of GBS transmission to neonates. We hypothesized that PCR may enhance the detection of neonatal GBS colonization of the GIT, and that the rate will be higher when evaluated with PCR as compared to culture. Methods This was a cross-sectional study, in which mothers who were positive for GBS on routine screening and their healthy infants were eligible for recruitment. Newborn stool was collected after 24 h of life and before hospital discharge, and stored at -80°C for culture and PCR targeting the GBS-specific surface immunogenic protein (sip) gene. Results A total of 94 mother-infant pairs were enrolled; of these pairs, stool was collected from 83 infants. Based on PCR, the overall GBS transmission rate was 3.6% (3/83). The transmission rate was 2.4% (1/41) among vaginal deliveries and 4.8% (2/42) among cesarean deliveries. The results of culture-based transmission detection were identical. Conclusion These results indicate that the rate of GBS transmission is low and that detection may not be enhanced by PCR methods.

Hyponatremic Seizures and Adrenal Hypoplasia Congenita in a Neonate with Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) in neonates may occur as an isolated finding, in association with other anomalies, or as part of a genetic syndrome. We report the first case of an infant with CDH who presented with hyponatremic seizures due to adrenal hypoplasia congenita (AHC). The patient underwent repair of CDH defect. After an uncomplicated postoperative course while on discharge planning, he developed a seizure episode associated with severe hyponatremia and hyperkalemia. Extensive diagnostic workup revealed an NR0B1 gene variant confirming the diagnosis of X-linked AHC. The patient was eventually discharged home on hydrocortisone, fludrocortisone, and salt supplements. There are a few case reports of adrenal insufficiency in neonates with CDH, manifesting with symptoms before and immediately after reparative surgery. Clinical presentation of our patient was unique in manifesting as neonatal seizure secondary to severe hyponatremia after a stable postoperative phase. The patient's electrolytes and hemodynamic status remained stable before, during, and after surgery for CDH. This case underlines the importance of taking detailed family history and continued vigilance for signs and symptoms of adrenal insufficiency in infants with repaired CDH by pediatricians and intensivists.