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BackgroundIncreasing numbers of UK women have overweight or obese body mass index scores when they become pregnant, or gain excessive weight in pregnancy, increasing their risk of adverse outcomes. Failure to manage postnatal weight is linked to smoking, non-healthy dietary choices, lack of regular exercise and poorer longer-term health. Women living in areas of higher social deprivation are more likely to experience weight management problems postnatally.ObjectivesThe objectives were to assess the feasibility of conducting a definitive randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of lifestyle information and access to a commercial weight management group focusing on self-monitoring, goal-setting and motivation to achieve dietary change commencing 8–16 weeks postnatally to achieve and maintain weight management and positive lifestyle behaviour.DesignThe design was a randomised two-arm feasibility trial with a nested mixed-methods process evaluation.SettingThe setting was a single centre in an inner city setting in the south of England.ParticipantsParticipants were women with body mass index scores of > 25 kg/m2at antenatal ‘booking’ and women with normal body mass index scores (18.0–24.9 kg/m2) at antenatal booking who developed excessive gestational weight gain as assessed at 36 weeks’ gestation.Main outcome measuresRecruitment, retention, acceptability of trial processes and identification of relevant economic data were the feasibility objectives. The proposed primary outcome was difference between groups in weight at 12 months postnatally, expressed as percentage weight change and weight loss from antenatal booking. Other proposed outcomes included assessment of diet, physical activity, smoking, alcohol consumption, body image, maternal esteem, mental health, infant feeding and NHS costs.ResultsMost objectives were achieved. A total of 193 women were recruited, 98 allocated to the intervention arm and 95 to the control arm. High follow-up rates (> 80%) were achieved to 12 months. There was an 8.8% difference in weight loss at 12 months between women allocated to the intervention arm and women allocated to the control arm (13.0% vs. 4.2%, respectively;p = 0.062); 47% of women in the intervention arm attended at least one weight management session, with low risk of contamination between arms. The greatest benefit was among women who attended ≥ 10 sessions. Barriers to attending sessions included capability, opportunity and motivation issues. Data collection tools were appropriate to support economic evaluation in a definitive trial, and economic modelling is feasible to quantify resource impacts and outcomes not directly measurable within a trial.LimitationsThe trial recruited from only one site. It was not possible to recruit women with normal body mass index scores who developed excessive pregnancy weight gain.ConclusionsIt was feasible to recruit and retain women with overweight or obese body mass index scores at antenatal booking to a trial comparing postnatal weight management plus standard care with standard care only and collect relevant data to assess outcomes. Approaches to recruit women with normal body mass index scores who gain excessive gestational weight need to be considered. Commercial weight management groups could support women’s weight management as assessed at 12 months postnatally, with probable greater benefit from attending ≥ 10 sessions. Process evaluation findings highlighted the importance of providing more information about the intervention on trial allocation, extended duration of time to commence sessions following birth and extended number of sessions offered to enhance uptake and retention. Results support the conduct of a future randomised controlled trial.Trial registrationCurrent Controlled Trials ISRCTN39186148.FundingThis project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full inPublic Health Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information.

Background In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

ObjectivesTo understand the barriers and facilitators to uptake and retention of postnatal women randomised to a commercial group weight management intervention using the COM-B (capability, opportunity, motivation and behaviour) behaviour change model.DesignConcurrent mixed-methods (qualitative dominant) process evaluation nested within a feasibility randomised controlled trial, comprising questionnaires and interviews at 6 and 12 months postbirth.SettingOne National Health Service maternity unit in an inner city area in the south of England.Participants98 postnatal women with body mass indices>25 kg/m2(overweight/obese) at pregnancy commencement.InterventionTwelve-week Slimming World (SW) commercial group weight management programme, commencing anytime from 8 to 16 weeks postnatally.Primary and secondary outcome measuresData regarding uptake and retention from questionnaires and interviews conducted 6 and 12 months postbirth analysed thematically and mapped to the COM-B model.ResultsBarriers to SW uptake mostly concerned opportunity issues (eg, lack of time or childcare support) though some women also lacked motivation, not feeling that weight reduction was a priority, and a few cited capability issues such as lacking confidence. Weight loss aspirations were also a key factor explaining retention, as were social opportunity issues, particularly in relation to factors such as the extent of group identity and relationship with the group consultant; and physical opportunity such as perceived support from and fit with family lifestyle. In addition, barriers relating to beliefs and expectations about the SW programme were identified, including concerns regarding compatibility with breastfeeding and importance of exercise. Women’s understanding of the SW approach, and capability to implement into their lifestyles, appeared related to level of attendance (dose–response effect).ConclusionsUptake and retention in commercial weight management programmes may be enhanced by applying behaviour change techniques to address the barriers impacting on women’s perceived capability, motivation and opportunity to participate.Trial registration numberNCT39186148.

Paramedics have been regulated in the UK since 2003. Analysis shows that the profession has had consistently higher rates of self-referral to its regulator compared with other health and care professions. Between 2013 and 2016, the percentage of paramedics who self-referred averaged 50% of all cases, compared with 6% across all other health professions regulated by the Health and Care Professions Council (HCPC) and 10% across social workers in England. This article reports on possible reasons underlying this trend. Using a mixed-methods approach including a literature review, interviews, focus groups and case analysis, the study identified a number of possible contributory factors. These included pressurised work environments, variable guidance and support from employers, and work cultures of fear and conflict. The evolving nature of the profession was also cited. The research found that there was a cohort of cases that appeared inappropriate—where the referral was for a matter that did not require reporting. Actions are being taken to reduce such self-referrals to avoid the emotional distress and resource implications for those involved.

Background Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease. Methods Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses. Results The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM-receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer's, Parkinson's and Huntington's disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression. Conclusions Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

Objective: To examine the gene expression regarding pulmonary vascular disease in experimental bronchopulmonary dysplasia in young mice. Premature delivery puts babies at risk of severe complications. Bronchopulmonary dysplasia (BPD) is a common complication of premature birth leading to lifelong affection of pulmonary function. BPD is recognized as a disease of arrested alveolar development. The disease process is not fully described and no complete cure or prevention is known. The focus of interest in the search for treatment and prevention of BPD has traditionally been at airspace level; however, the pulmonary vasculature is increasingly acknowledged in the pathology of BPD. The aim of the investigation was to study the gene expression in lungs with BPD with regards to pulmonary vascular disease (PVD). Methods: We employed a murine model of hyperoxia-induced BPD and gene expression microarray technique to determine the mRNA expression in lung tissue from young mice. We combined gene expression pathway analysis and analyzed the biological function of multiple single gene transcripts from lung homogenate to study the PVD relevant gene expression. Results: There were n = 117 significantly differentially regulated genes related to PVD through down-regulation of contractile elements, up- and down-regulation of factors involved in vascular tone and tissue-specific genes. Several genes also allowed for pinpointing gene expression differences to the pulmonary vasculature. The gene Nppa coding for a natriuretic peptide, a potent vasodilator, was significantly down-regulated and there was a significant up-regulation of Pde1a (phosphodiesterase 1A), Ptger3 (prostaglandin e receptor 3), and Ptgs1 (prostaglandin-endoperoxide synthase one). Conclusion: The pulmonary vasculature is affected by the arrest of secondary alveolarization as seen by differentially regulated genes involved in vascular tone and pulmonary vasculature suggesting BPD is not purely an airspace disease. Clues to prevention and treatment may lie in the pulmonary vascular system.

Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Objectives To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost‐effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post‐birth. Design Two‐arm feasibility trial, with nested mixed‐methods process evaluation. Setting Inner‐city unit, south England. Population Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5–24.9 kg/m2) identified with excessive gestational weight gain at 36 weeks of gestation. Methods Randomised to standard care plus commercial weight management sessions commencing 8–16 weeks postnatally or standard care only. Main outcomes Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. Results In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. Conclusion It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out‐of‐trial costs and benefits in a future trial. A definitive trial is an important next step. Tweetable abstract A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

Background: Bronchopulmonary dysplasia (BPD) is a common cause of abrupted lung development after preterm birth. BPD may lead to increased rehospitalization, more severe and frequent respiratory infections, and life-long reduced lung function. The gene regulation in lungs with BPD is complex, with various genetic and epigenetic factors involved. Objectives: The aim of this study was to examine the regulatory relation between gene expression and the epigenome (DNA methylation) relevant for the immune system after hyperoxia followed by a recovery period in air using a mouse model of BPD. Methods: Newborn mice pups were subjected to an immediate hyperoxic condition from birth and kept at 85% O2 levels for 14 days followed by a 14-day period in room air. Next, mice lung tissue was used for RNA and DNA extraction with subsequent microarray-based assessment of lung transcriptome and supplementary methylome analysis. Results:The immune system-related transcriptomeregulation was affected in mouse lungs after hyperoxia. A high proportion of genes relevant in the immune system exhibited significant expression alterations, e.g., B cell-specific genes central to the cytokine-cytokine receptor interaction, the PI3K-AKT, and the B cell receptor signaling pathways. The findings were accompanied by significant DNA hypermethylation observed in the PI3K-AKT pathway and immune system-relevant genes. Conclusions: Oxygen damage could be partly responsible for the increased susceptibility and abnormal response to respiratory viruses and infections seen in premature babies with BPD through dysregulated genes.

Background Immature immune systems predispose very low birth weight (VLBW) neonates to systemic infections in early life. Defective inflammasome function may increase a neonate's susceptibility to late-onset sepsis (LOS). Methods Blood samples were taken on the 5th day of life (DOL) for all VLBW neonates (non-LOS and before-LOS groups; n=76), and within 24 hours of sepsis onset (LOS group; n=39). Monocyte (MO) subsets and intracellular interleukin-1β (IL-1β) expression were analysed using flow cytometry. Inflammasome function, defined as level of IL-1β and interleukin-18 (IL-18) was measured with enzyme-linked immunosorbent assay. IRA B cells were reported as a fraction of all B cells. Results Stimulation of classical MO in non-LOS cells demonstrated a higher expression of intracellular IL-1β in comparison to MO from before-LOS group. Serum from the LOS group revealed a higher level of IL-18. Stimulation of mononuclear cultures from samples taken during LOS resulted in significantly increased supernatant level of IL-1β and IL-18 in comparison to samples taken on 5th DOL. No changes in the levels of IRA B cells were detected with the onset of sepsis. Conclusions We did not observe a difference in the functioning of the inflammasome within monocytes taken on 5th DOL from premature VLBW neonates. Furthermore, there was no observable change in the IRA B cells of the septic and non-septic groups. The decreased expression of intracellular IL-1β within classical MO of the before-LOS group may be an independent risk factor for LOS development.

Inflammasomes regulate activation of caspase-1, which cleaves and activates interleukin (IL)-1β and IL-18, the cytokines that trigger pro-inflammatory and antimicrobial responses. There is very little known about inflammasome function in the subsets of monocytes (MO) isolated from preterm neonates born extremely and very prematurely.A group of 76 very low birth weight patients without early-onset sepsis was divided into extremely preterm (28 gestational week) or very preterm (28-32 gestational week) neonates. The first blood sample was collected on the 5th day of life (5th DOL) to analyse MO subsets as well as the intracellular IL-1β expression and supernatant concentration of IL-1β and IL-18. Secondary blood samples were collected within 24h of late-onset sepsis (LOS) development and analysed as above.On the 5th DOL, the extremely preterm neonates were characterized by a significantly higher absolute count of MO, in particular in the classical and intermediate subsets, as compared to the very preterm group. The counts of the intermediate and non-classical MO subsets increased during LOS in all neonates. We did not observe significant differences in the intracellular IL-1β expression between the analysed groups. Furthermore, the levels of the analysed cytokines in the MO supernatants were comparable between the extremely and very preterm neonates on the 5th DOL. Finally, a higher level of IL-18 was observed in the supernatant of the extremely preterm group during LOS.During LOS, extremely preterm neonates excrete a higher level of IL-18 cytokines compared to very preterm neonates. Further studies are required to determine whether this observation is a result of a higher count of the circulating MO or is a true reflection of increased inflammasome function in this particular group of newborns.

Premature infants represent one of the groups with increased risk for metabolic syndrome. Our study is the first one to evaluate irisin and visfatin levels, associated with the metabolic syndrome, both in blood of preterm and full-term infants, as well as in the breastmilk of their mothers. A total of 72 newborns was enrolled in the study, including 53 very low birth weight preterm infants and a control group of 19 term infants. The levels of irisin and visfatin were determined by a commercial enzyme-linked immunoabsorbent assay both in the baby serum and maternal milk twice, first during the 1st week of life and then 4 weeks later. Preterm infants had significantly lower serum irisin levels compared to the term infants. Overall, serum irisin level during the 1st week of life was positively correlated with several anthropometric measurements at birth, as well as during 5th weeks of age. In contrast, serum visfatin levels during 5th week of life were negatively correlated with z-scores of birth weight, weight and head circumference during 5th week of age. We found a strong negative correlation between serum irisin and serum visfatin levels at both analyzed time points. The level of milk visfatin was significantly higher in the mothers of the preterm group during 5th week of life. In conclusion, our results provide further evidence that irisin and visfatin may play physiologic roles in development of both preterm and full-term newborns during their first month after birth. Observed differences in irisin and visfatin serum and breastmilk concentrations during the earliest stages of life may contribute to development of catch up growth, but also, they might eventually lead to a higher risk for metabolic syndrome in prematurely born children in later years.

Purpose Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease. Methods The cord and peripheral blood of neonates (≤30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (PMA), respectively. Blood samples were retrospectively subdivided into ROP(+) and ROP(-) groups, according to the development of ROP. Results The quantitative analysis of plasma proteome at both time points revealed 30 protein abundance changes between ROP(+) and ROP(-) groups. After standardization to gestational age, children who developed ROP were characterized by an increased C3 complement component and fibrinogen level at both analyzed time points. Conclusions Higher levels of the complement C3 component and fibrinogen, present in the cord blood and persistent to 36 PMA, may indicate a chronic low-grade systemic inflammation and hypercoagulable state that may play a role in the development of ROP.

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome.

Background: The long-term impact of prematurity on cardiac structure and function has not yet been fully discovered. Objectives: To assess long-term cardiac complications in the regional cohort of extremely low birth weight (ELBW) children born in 2002-2004. Material and Methods: Eighty-one children born as ELBW infants (91% of the available cohort) with a median birth weight of 890 g (25-75th percentile: 760-950) were evaluated at the mean age of 6.7 years. The control group included 40 children born full-term, selected from one general practice in the district. Echocardiography and 24-hour ambulatory blood pressure measurements (ABPM) were performed. The primary outcome variable was the presence of cardiac complications such as left ventricular hypertrophy (LVH), diastolic dysfunction or systolic dysfunction. Results: LVH was diagnosed in 4/81 ELBW children and 2/40 control children (p = 1.0). Concentric remodeling was detected in 8 (10%) subjects from the ELBW group and in 2 (5%) from the control group (p = 0.49). There were no patients with diastolic or systolic dysfunction in either group. After having expressed the results of M-mode echocardiography as z-scores for body surface area (BSA), statistically significant differences were observed for right-ventricle dimension in diastole (-1.49 ± 1.25 vs. -0.31 ± 0.91; p < 0.001), LV inner dimension in diastole (-0.53 ± 1.26 vs. 0.13 ± 0.94; p = 0.01) and left atrium (-0.93 ± 1.07 vs. -0.15 ± 1.02; p < 0.01). Heart rate (HR) was significantly faster in ELBW children (92.9 ± 8.4 vs. 86.7 ± 7.4 bpm; p = 0.01 adjusted for BSA) and they also had significantly higher night-time blood pressure [mean (z-score): 1.15 vs. 0.2; p = 0.02] without nocturnal dipping (night-time dipping Conclusions: No differences were found between the groups in the occurrence of cardiac complications. Ex-preterm ELBW children at age 6 may have a faster HR, smaller cardiac dimensions on echocardiography and higher nocturnal blood pressure. The clinical relevance of these findings is unknown.

We assessed the long-term renal complications in a regional cohort of extremely low birth weight (ELBW) children born in 2002–2004. The study group, comprising 78 children born as ELBW infants (88% of the available cohort), was evaluated with measurement of serum cystatin C, urinary albumin excretion, renal ultrasound, and 24-h ambulatory blood pressure measurements. The control group included 38 children born full-term selected from one general practice in the district. Study patients were evaluated at a mean age of 6.7 years, and had a median birthweight of 890 g (25th–75th percentile: 760–950 g) and a median gestational age of 27 weeks (25th–75th percentile: 26–29 weeks). Mean serum cystatin C levels were significantly higher (0.64 vs. 0.59 mg/l; p = 0.01) in the ELBW group. Hypertension was diagnosed in 8/78 ELBW and 2/38 of the control children (p = 0.5). Microalbuminuria (>20 mg/g of creatinine) was detected only in five ELBW children (p = 0.17). The mean renal volume was significantly lower in the ELBW group (absolute kidney volume 81 ml vs. 113 ml; p

Introduction: Neuroblastoma (NB), Hirschsprung disease (HSCR), Congenital Central Hypoventilation Syndrome (CCHS), clinically referred as the NB-HSCR-CCHS cluster, is genetic disorders linked to mutations in the PHOX2B gene on chromosome 4p12. Specific aim: The specific aim of this project is to define the PHOX2B gene mutations as the genomic basis for the clinical manifestations of the NB-HSCR-CCHS cluster. Patient: A one day old male patient presented to the JUMC neonatal ICU due to abdominal distention, vomiting, and severe apneic episodes. With the preliminary diagnosis of the NB-HSCR-CCHS, the blood and tissue samples were acquired from the child, as well as from the child’s parents. All procedures were pursued in accordance with the Declaration of Helsinki, with the patient’s Guardian Informed Consent and the approval from the Institutional Review Board. Genetic/genomic methods: Karyotyping was analyzed based upon Giemsa banding. The patient’s genomic DNA was extracted from peripheral blood and amplified by polymerase chain reaction. Direct microfluidic Sanger sequencing was performed on the genomic DNA amplicons. These procedures were pursued in addition to the routine clinical examinations and tests. Results: G-banding showed the normal 46 XY karyotype. However, genomic sequencing revealed a novel, heterozygous deletion (8 nucleotides (c.699-706, del8) in exon 3 of the PHOX2B gene on chromosome 4. This led to the frame-shift mutation and malfunctioning gene expression product. Conclusion: Herein, we report a novel PHOX2B gene mutation in the patient diagnosed with the NB-HSCRCCHS cluster. The resulting gene expression product may be a contributor to the clinical manifestations of these genetic disorders. It adds to the library of the mutations linked to this syndrome. Consequently, we suggest that screening for the PHOX2B mutations becomes an integral part of genetic counseling, prenatal screening, and preparing supportive therapy upon delivery.