Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

INTRODUCTION: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). METHODS: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. RESULTS: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008-0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01-0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31-47.04; p = 0.024). CONCLUSION: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review.

OBJECTIVES: To summarize evidence regarding microbial dysbiosis of the airway associated with bronchopulmonary dysplasia (BPD) and to explore heterogeneity among studies. STUDY DESIGN: We included studies that evaluated the airway microbiome in preterm infants who developed BPD using culture-independent molecular techniques and reported alpha- and beta-diversity metrics and microbial profiles. RESULTS: The 6 included studies had substantial clinical and methodological heterogeneity. Most studies reported the presence of an airway microbiome early after birth and an evolution in the first weeks of life with increasing bacterial loads. The early airway microbiome was dominated by Staphylococcus and Ureaplasma spp. Two studies reported differences in alpha- and beta- diversity indices in preterm infants with BPD compared with those who did not develop BPD. Increased microbial community turnover, changes in the relative abundance of Proteobacteria and Firmicutes, and decreased Lactobacilli were reported with BPD progression. Most included infants were born by cesarean delivery, and a majority were exposed to postnatal antibiotics. No data regarding feeding human milk or correlations with the development of gut microbiota (gut-lung axis) were available. CONCLUSIONS: Microbial dysbiosis may be associated with BPD progression and severity, and further study of microbiome optimization in preterm infants at risk for BPD is warranted.

Pre-cannulation lung biopsy shortens ECMO course.

We describe the clinical course of an infant with respiratory failure who underwent lung biopsy prior to cannulation for undergoing extracorporeal membrane oxygenation (ECMO). Pathology revealed alveolar capillary dysplasia, and ECMO was discontinued. Rapid diagnosis allowed for closure and saved resources. We recommend considering early biopsy in infants with atypical pulmonary hypertension.

The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with perinatal inflammatory triggers. Methods targeting bacterial rRNA may improve detection of microbial colonization in premature infants. We hypothesize that respiratory microbiota differs between preterm infants who develop BPD and those unaffected and correlates with inflammatory mediator concentrations. METHODS: Twenty-five infants, born at ≤32 wk of gestation and intubated in the first 24 h, were enrolled. Tracheal aspirates were obtained at intubation and on days 3, 7, and 28. Bacterial DNA was extracted, and 16S rRNA genes were amplified and sequenced. Concentrations of interleukins (IL-1ß, IL-6, IL-8, IL-10, and IL-12), tumor necrosis factor-α, interferon-γ, lipopolysaccharide (LPS), and lipoteichoic acid (LTA) were measured. Chorioamnionitis was diagnosed by histology. BPD was defined as an oxygen requirement at 36 wk postmenstrual age. RESULTS: Acinetobacter was the predominant genus in the airways of all infants at birth. Ten infants developed BPD and showed reduced bacterial diversity at birth. No differences were detected in bacterial diversity, cytokines, LPS, and LTA from infants with and without exposure to chorioamnionitis. CONCLUSION: The airways of premature infants are not sterile at birth. Reduced diversity of the microbiome may be an important factor in the development of BPD and is not associated with differences in inflammatory mediators.

Case Report: The Medical and Surgical Management of an Infant With Extreme Prematurity and Fetus-In-Fetu.

Fetus-in-fetu (FIF) is a rare congenital anomaly where a parasitic twin is within the body of a host twin. FIF is reported to occur in 1:500,000 live births. Herein, we report the first case of the medical and surgical treatment of a FIF patient who was born with extreme prematurity at 25-weeks gestation. With the multi-disciplinary coordination of neonatology, surgery, and interventional radiology, the patient was able to achieve a window of medical stability 4 weeks after birth. A decision was made at that time to proceed with an intra-abdominal and perineal resection of the FIF. The FIF was successfully resected and the patient was able to recover from the operation, with eventual discharge from the NICU. In conclusion, extreme prematurity and FIF may be amenable to surgical resection and a multi-disciplinary approach is crucial to achieve the desired outcome.

Mortality trends in neonatal ECMO for pulmonary hypoplasia: A review of the Extracorporeal Life Support Organization database from 1981 to 2016.

BACKGROUND: The purpose of this review is to provide ECMO outcome data for medical personnel who counsel families of patients with pulmonary hypoplasia (PH), often secondary to renal abnormalities. We report diagnoses and outcomes associated with PH in neonates that were treated with ECMO over the past 35 years. METHODS: Retrospective cohort study using the ELSO database for neonates born between 1981 and 2016 with a primary or secondary diagnosis of PH. Five patient groups were created based on ICD-9 codes. Mortality rates were compared and trends over time were investigated. RESULTS: Thirty-three percent of the 1385 patients survived to discharge. Congenital diaphragmatic hernia (CDH) patients had significantly higher mortality than PH patients secondary to renal dysplasia (p < 0.001). Mortality decreased significantly over time for all groups (p < 0.001). The proportion of patients alive at discharge increased over time for CDH patients (p < 0.001), whereas survival decreased for patients with PH secondary to renal dysplasia (p = 0.012). CONCLUSIONS: Neonates with PH that require ECMO have high mortality rates, which have generally decreased over the past 35 years; however, mortality for neonates with PH secondary to renal dysplasia continues to increase. We speculate that the apparent rise in mortality for these patients is because of changes in patient selection subsequent to improvements in non-ECMO ventilatory support. LEVEL OF EVIDENCE: II.

Newborn with Perinatal Naphthalene Toxicity after Maternal Ingestion of Mothballs during Pregnancy.

Maternal ingestion of naphthalene-containing mothballs is an uncommon cause of perinatal toxicity. Naphthalene toxicity is associated with methemoglobinemia, hypotension, hemolytic anemia, and hyperbilirubinemia, as well as other hepatic, renal, and respiratory complications. Naphthalene exposure is a common cause of toxicity in older children, but is rarely described in neonates. The neonatal cases described in the literature focus primarily on maternal inhalation as opposed to ingestion. We present a case of perinatal toxicity due to repeated maternal ingestion of naphthalene-containing mothballs during pregnancy. The patient presented with methemoglobinemia, hypotension, hemolytic anemia, and hyperbilirubinemia. Sepsis or pulmonary hypertension were the initial working diagnoses, as the mother did not provide the history of ingestion until after the patient's clinical status worsened. This case highlights the importance of obtaining a thorough maternal history and considering maternal ingestion when the etiology of symptoms is not clear.

Improved feeding tolerance and growth are linked to increased gut microbial community diversity in very-low-birth-weight infants fed mother's own milk compared with donor breast milk.

BACKGROUND: Mother's own milk (MOM) is protective against gut microbiota alterations associated with necrotizing enterocolitis (NEC) and feeding intolerance among preterm infants. It is unclear whether this benefit is preserved with donor milk (DM) feeding. OBJECTIVE: We aimed to compare microbiota development, growth, and feeding tolerance in very-low-birth-weight (VLBW) infants fed an exclusively human milk diet of primarily MOM or DM. METHODS: One hundred and twenty-five VLBW infants born at Texas Children's Hospital were enrolled and grouped into cohorts based on percentage of MOM and DM in enteral feeds. Feeds were fortified with DM-derived fortifier per unit protocol. Weekly stool samples were collected for 6 wk for microbiota analysis [16S ribosomal RNA (rRNA) sequencing]. A research nurse obtained weekly anthropometrics. Clinical outcomes were compared via Wilcoxon's rank-sum test and Fisher's exact test, as well as multivariate analysis. RESULTS: The DM cohort (n = 43) received on average 14% mothers' milk compared with 91% for the MOM cohort (n = 74). Diversity of gut microbiota across all time points (n = 546) combined was increased in MOM infants (P < 0.001). By 4 and 6 wk of life, microbiota in MOM infants contained increased abundance of Bifidobacterium (P = 0.02) and Bacteroides (P = 0.04), whereas DM-fed infants had increased abundance of Staphylococcus (P = 0.02). MOM-fed infants experienced a 60% reduction in feeding intolerance (P = 0.03 by multivariate analysis) compared with DM-fed infants. MOM-fed infants had greater weight gain than DM-fed infants. CONCLUSIONS: Compared with DM-fed infants, MOM-fed infants have increased gut microbial community diversity at the phylum and genus levels by 4 and 6 wk of life, as well as better feeding tolerance. MOM-fed infants had superior growth. The incidence of NEC and other gastrointestinal morbidity is low among VLBW infants fed an exclusively human milk diet including DM-derived fortifier. This trial was registered at clinicaltrials.gov as NCT02573779.

Predictive value of oxygenation index for outcomes in left-sided congenital diaphragmatic hernia.

BACKGROUND & OBJECTIVES: Congenital Diaphragmatic Hernia (CDH) is associated with significant morbidity and mortality. This study compares the efficacy of the highest oxygenation index in the first 48 h (HiOI) versus current prenatal indices to predict survival and morbidity. METHODS: Medical records of 50 prenatally diagnosed, isolated, left-sided CDH patients treated from January 2011 to April 2016 were reviewed. Data abstracted included HiOI, lung to head ratio (LHR), observed to expected total fetal lung volume (O/E TFLV), percent liver herniation (%LH), 6 month survival, respiratory support at discharge, ventilator days and length of stay. Data were analyzed using parametric and nonparametric tests and regression analyses as appropriate. RESULTS: HiOI was associated with significantly increased LOS (p<0.001), respiratory support at discharge (p<0.001), greater ventilator days (p=0.001) and higher odds of death (p=0.004) with risk of death increasing by 5% for every one-unit increase in OI. HiOI was statistically a better predictor of LOS than O/E TFLV (p=0.007) and %LH (p=0.02). CONCLUSIONS: In isolated, left-sided CDH patients, HiOI is associated with higher mortality, greater length of stay, more ventilator days and increased respiratory support at discharge. HiOI is a better predictor of length of stay than O/E TFLV and %LH. TYPE OF STUDY: Retrospective Study LEVEL OF EVIDENCE: II.