A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.

Outcomes of neonates born through meconium-stained amniotic fluid pre and post 2015 NRP guideline implementation.

A shift in the Neonatal Resuscitation Program (NRP) guidelines occurred in 2015 from routine intubation and endotracheal suctioning of all meconium-stained non-vigorous infants towards less aggressive interventions based on response to initial resuscitation. This study aims to examine the impact of this change on outcomes of non-vigorous infants born through meconium-stained amniotic fluid at a level III academic NICU encompassing years before and after the change in guideline. This single-center retrospective study compared NICU therapies and clinical outcomes of 117 non-vigorous newborns pre-guideline implementation to 106 non-vigorous newborns post-guideline implementation. Nearly two thirds of infants in the pre-guideline cohort received endotracheal suctioning with recovery of meconium compared to less than a third of infants in the post-guideline cohort (p<0.01). Though a higher proportion of the pre-guideline cohort were admitted to the NICU for respiratory issues compared to the post-guideline cohort, the two groups did not differ significantly with regard to morbidity and therapies. Despite a marked reduction in rates of intubation and endotracheal suctioning, there is no difference in outcomes between pre-guideline implementation vs post-guideline implementation in non-vigorous meconium-stained infants, supporting the recent NRP guideline change and highlighting the benefit of expectant management.

Neonatal Nurse Practitioner Use of Ultrasonography to Verify Umbilical Venous Catheter Placement in the Neonatal Intensive Care Unit.

BACKGROUND: Literature dating back to 1982 supports the use of ultrasound to confirm UVC position as a more reliable method compared to x-ray. The use of ultrasound to confirm UVC position remains infrequent in the NICU. PURPOSE: To determine the feasibility of training an NNP in the acquisition and interpretation of a parasternal short-axis (PSAX) image of the heart to confirm UVC position. METHODS: A retrospective review of 48 charts evaluated descriptive data using standard technique of an x-ray to confirm UVC placement. An NNP was trained to acquire and interpret a parasternal short-axis (PSAX) cardiac view by a pediatric cardiologist. The NNP independently and prospectively evaluated 21 neonates and determined whether the UVC was in satisfactory or unsatisfactory position. The same image was blindly over-read by the pediatric cardiologist. Agreement between the NNP and pediatric cardiologist interpretations as well as the pediatric cardiologist and radiologist interpretations was evaluated using the κ-test. RESULTS: Initial pediatric cardiology interpretation of UVC position showed the UVC to be malpositioned in 66% of neonates (n = 14). NNP and pediatric cardiology interpretations in UVC position had 86% agreement (κ-0.667). Pediatric cardiology (ultrasound) and radiology interpretations (x-ray) in UVC position had 86% agreement (κ-0.69). IMPLICATIONS FOR PRACTICE: It is feasible to train NNPs to perform and accurately interpret a single PSAX ultrasound image to determine satisfactory UVC position. IMPLICATIONS FOR RESEARCH: Increasing the use of ultrasound to determine satisfactory position of UVCs in the NICU can reduce unnecessary exposure to ionizing radiation in neonates.

Congenital pulmonary lymphangiectasia: an unusual presentation of nonimmune hydrops in a preterm infant.

Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung. CPL can present antenatally as nonimmune hydrops with pleural effusions, which are frequently associated with polyhydraminos. CPL presents in the neonatal period with severe respiratory distress and can be complicated by chylothorax. Diagnosis is difficult, as radiographic findings are nonspecific. Lung biopsy is indicated in some severe cases to diagnose CPL. The majority of infants with this condition rarely survive the neonatal period and are often diagnosed at autopsy. The final diagnosis is confirmed histologically by lung biopsy or at postmortem. We report a rare case of CPL in a preterm female infant presenting with severe nonimmune Hydrops fetalis who survived the neonatal period, and report clinical follow-up to early childhood.

Effects of protein/nonprotein caloric intake on parenteral nutrition associated cholestasis in premature infants weighing 600-1000 grams.

BACKGROUND: Parenteral nutrition-associated cholestasis (PNAC) has historically been a significant cause of morbidity and mortality in neonates undergoing parenteral feeding. Studies examining the causes of cholestasis in the PN-dependent neonate have produced a wide range of data, with some conflicting results. Increased protein/nonprotein calorie ratios, increased glucose concentrations, and increased lipid concentrations have all been implicated as possible causes of PNAC. However, these studies were done in the pre-TrophAmine (neonatal-specific amino acid parenteral nutrition [PN] formulation) era. With the introduction of TrophAmine, infants are now receiving higher concentrations of protein, often being advanced rapidly even when nonprotein calories may not be sufficiently advanced to meet the infants' caloric needs. To the best of our knowledge, no studies have been conducted to evaluate the protein/nonprotein calorie ratio as a cause of PNAC in the TrophAmine era. METHODS: A retrospective chart review of 25 cholestatic and 25 noncholestatic PN-dependent premature neonates was conducted. All neonates weighed between 600 and 1000 g. Cholestasis was defined as a serum total bilirubin (TB) >or=2.0 mg/dL, with a serum direct bilirubin (DB) >or=20% of the TB. Neonates with major congenital anomalies or who underwent major surgery were excluded. PN macronutrient compositions were analyzed to examine if the different amounts of protein concentrations and protein/nonprotein calorie ratios played a role in the development of PNAC. Statistical analysis was performed using Student's t-tests. p Values < .05 were considered statistically significant. RESULTS: All measured nutrition parameters did not differ significantly between the cholestatic and noncholestatic groups. Protein intake, the protein/nonprotein calorie ratio, and renal function as evaluated by blood urea nitrogen (BUN) and creatinine did not differ between the 2 study groups. The only parameters that differed significantly between the groups were the duration of PN therapy and length of hospital stay. CONCLUSIONS: Protein to nonprotein calorie ratio was not an etiology in the development of cholestasis in infants (600-1000 g) receiving PN. Renal function elicited not to have an impact on cholestasis status of these infants. Therefore, providing adequate protein calories should not be limited in this patient population, as suggested by previous studies in the pre-TrophAmine era. We found that increased duration of PN therapy and increased length of hospital stay were associated with PNAC.

Continuing care of NICU graduates.

After a prolonged and complicated hospital stay, the NICU graduate enters the world with unique and complex medical problems. A well-coordinated multidisciplinary approach is essential in the follow-up care of these infants. The crucial issues for the pediatrician who cares for these infants are assisting in the catch-up growth and the ongoing healing process with good nutritional supplementation, while preventing further problems by detecting and treating illness early. Timely inclusion of other appropriate health care personnel and facilities in the care may be crucial and rewarding. The role of the pediatrician in helping these infants attain their full physical, neurodevelopmental, emotional, and psychosocial potential by providing optimal care is invaluable. With appropriate support most NICU graduates will become productive and well-adjusted adults. The pediatrician plays a major role in completing this process and contributes to the eventual success of the neonatal intensive care that these infants are subjected to at the very beginning of their lives.