Gasping in Dying Children: Health Care Professionals' Feelings and Knowledge.

Purpose: To assess the feelings and knowledge of health care professionals (HCPs) about gasping in dying patients in neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). Methods: A 9-item questionnaire addressed to 488 HCPs (physicians, nurses, and nursing assistants) of 2 NICUs and 2 PICUs. Questions were about HCPs' feelings when confronted with gasping, their knowledge, and their opinions on what to tell family members. Results: Responses were obtained from 248 staff members. Of the respondents, 43% felt that gasping was painful to the patient and most felt that witnessing gasps was distressing for the parents, and 77% reported being distressed by witnessing gasps. Conclusions: Efforts are needed to educate HCPs about the physiology of gasping, to help them to cope with gasping, and to give better support to parents.

Immaturity of Oculomotor Capabilities During a Reading Task in Children Born Prematurely: An Eye Tracker Study.

To our knowledge, there are no studies recording the reading eye movements of children born prematurely. We examined the oculomotor patterns during reading of 23 children born prematurely (M age = 7.8, SD = 0.2 years) to compare them with those from two groups of children born at full-term who were matched for chronological age or reading age, respectively. We found the oculomotor reading pattern in children who were preterm to be similar to that of children who were full-term and matched for reading age; this shared pattern was characterized by longer duration of fixations, frequent prosaccades of smaller amplitude and several backward saccades. In contrast, when these two groups were compared to full-term children matched for chronological age, the latter group showed significantly shorter duration of fixations, less frequent saccades and larger amplitude prosaccades. Thus, the oculomotor pattern we observed in 7-year-old children who were either preterm or reading-delayed, relative to their age-matched peers, reflected delayed development of brain areas involved in reading-related eye movements.

Immature brain structures were associated with poorer eye movement performance at 8 years of age in preterm born children.

AIM: Eye movements have rarely been explored in preterm born children. The aim of this study was to compare horizontal eye movements in children born preterm and full term when they reached 8 years of age. METHODS: Eye movements were recorded in 24 preterm born children (18 boys) and 26 matched controls (19 boys), recruited by a French hospital, using an eye tracker. This identified different types of visually guided saccades, namely step, gap, overlap and antisaccades and pursuit eye movements. The saccades task measured the latency and the percentage of anticipatory and express saccades and errors. The pursuit task measured the gain and percentage of intrusive saccades. RESULTS: This study confirmed that children born at 24-28 weeks of gestation demonstrated a global deficit in inhibitory processes compared to children born full term. The saccades were less precise in the preterm group, anticipatory and express saccades were elevated and there was a high occurrence of intrusive saccades during pursuit movements. CONCLUSION: These findings suggest that preterm born children have immature brain structures, particularly the parietal and frontal cortexes that are responsible for both saccade and pursuit performance. These could have been the cause of the abnormal inhibitory control measured in this study.

Treatment outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues.

This study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2%), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines.

Thoracoscopy Versus Thoracotomy in the Repair of Esophageal Atresia with Distal Tracheoesophageal Fistula.

Background/Objective: Thoracoscopic repair of esophageal atresia (EA) is gaining popularity, but it is a highly technically demanding procedure. The aim of our study is to evaluate our outcomes in the management of type C EA comparing the thoracoscopic and the open (thoracotomy) approaches. Methods: This is a retrospective bicentric study of two major pediatric surgery centers, reviewing all the patients operated for EA with distal tracheoesophageal fistula. Only patients who underwent primary anastomosis were included. From 2008 to 2018, 187 patients were included. Results: Forty-seven patients were operated thoracoscopically (TS group) and 140 by the open approach (TT group). Mean gestational age was 38 ± 2.4 weeks in TS group and 36.4 ± 3.3 weeks in TT group (P = .005) with a mean birth weight of 2785 ± 654 g and 2404.9 ± 651 g in TS and TT groups, respectively (P = .003). The mean operative time was 127.6 ± 35 minutes in TS group and 105.7 ± 23 minutes in TT group (P = .0005). The mean postoperative ventilation time and the mean length of stay were significantly shorter in the thoracoscopic group (P = .004 and P < .0001, respectively). The incidence of anastomotic leak was 8.9% in TS group versus 16.4% in TT group (P = .33). Anastomotic stenosis occurred in 33.3% of TS group and in 22.4% of TT group (P = .17). Conclusions: Surgical outcome of thoracoscopic repair of EA is comparable to the open repair with no higher complication rate with the expected skeletal and cosmetic benefits. However, possible bias regarding prematurity, weight at surgery, and associated anomalies must be taken into consideration.

Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

OBJECTIVE: Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. DESIGN: Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). SETTING: Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. PATIENTS: Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. INTERVENTION: Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day. MAIN OUTCOME MEASURES: Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation. RESULTS: Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24). CONCLUSIONS: Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among neonates. Both gestational and postnatal ages account for these differences but their differential impact on omeprazole doses remains to be determined.

Fetal growth restriction is worse than extreme prematurity for the developing lung.

BACKGROUND: Perinatal lung growth is highly vulnerable to inflammation and intrauterine growth restriction (IUGR), two major risk factors for chronic lung disease (CLD) in preterm neonates. However, the balance between extremely low gestational age (ELGA) and IUGR in very preterm infants as risk factors for CLD and co-morbidities remains poorly explored. OBJECTIVES: This single-center study aims to compare neonatal morbidity (including CLD) and mortality among ELGA infants with normal birth weight (ELGA-AGA), very preterm infants with IUGR <3rd percentile (VLGA-IUGR) and very preterm infants with a birth weight appropriate for gestational age (VLGA-AGA), matched with VLGA-IUGR infants. METHODS: Selected characteristics of the perinatal and neonatal periods were recorded and retrospectively compared among the three groups. Infants with major congenital anomalies were excluded. The diagnosis of CLD was based on whether the infant was receiving supplemental oxygen and/or non-invasive ventilation at a postmenstrual age of 36 weeks. RESULTS: We found that, despite a median difference of 3 weeks in gestational age at birth between VLGA-IUGR and ELGA-AGA infants, neonatal mortality was 35% higher in neonates who had experienced fetal growth restriction, and that VLGA- IUGR was five times more predictive of CLD than was ELGA-AGA. These differences persisted after adjustment for confounding factors such as antenatal steroids, gender and respiratory distress syndrome. CONCLUSIONS: This study reports that VLGA-IUGR infants are at higher risk of neonatal mortality and CLD than both ELGA-AGA and VLGA-AGA infants.

Necrotizing enterocolitis (NEC) and the risk of intestinal stricture: the value of C-reactive protein.

Necrotizing enterocolitis (NEC) is a severe complication frequently seen during the neonatal period associated with high mortality rate and severe and prolonged morbidity including Post-NEC intestinal stricture. The aim of this study is to define the incidence and risk factors of these post-NEC strictures, in order to better orient their medicosurgical care. Sixty cases of NEC were retrospectively reviewed from a single tertiary center with identical treatment protocols throughout the period under study, including systematic X-ray contrast study. This study reports a high rate of post-NEC intestinal stricture (n = 27/48; 57% of survivors), either in cases treated surgically (91%) and after the medical treatment of NEC (47%). A colonic localization of the strictures was more frequent in medically-treated patients than in those with NEC treated surgically (87% vs. 50%). The length of the strictures was significantly shorter in case of NEC treated medically. No deaths were attributable to the presence of post-NEC stricture. The mean hospitalization time in NICU and the median age at discontinuation of parenteral nutrition were longer in the group with stricture, but this difference was not significant. The median age at discharge was significantly higher in the group with stricture (p = 0.02). The occurrence of post-NEC stricture was significantly associated with the presence of parietal signs of inflammation and thrombopenia (<100 000 platelets/mm(3)). The mean maximum CRP concentration during acute phase was significantly higher in infants who developed stricture (p<0.001), as was the mean duration of the elevation of CRP levels (p<0.001). The negative predictive value of CRP levels continually <10 mg/dL for the appearance of stricture was 100% in our study. In conclusion, this retrospective and monocentric study demonstrates the correlation between the intensity of the inflammatory syndrome and the risk of secondary intestinal stricture, when systematic contrast study is performed following NEC.

A long-term competent chimeric immune system in a dizygotic dichorionic twin.

We present here a rare case that involved the long-term coexistence of 2 mature, functional, and equilibrated immune systems in a single child after fetofetal transfusion between dizygotic twins. A dichorionic diamniotic pregnancy complicated by twin anemia-polycythemia sequence resulted in the demise of 1 twin. The detection of abnormal vessels on the dichorionic plate strongly suggested the existence of functional vascular anastomoses leading to blood chimerism in the survivor. Genetic, phenotypic, and immunologic analyses at 2 years revealed chimeric lymphoid and myeloid cells in the surviving twin, although no tissue mosaicism was detected, which indicates that early transfusion led to mutual immune tolerance.

De novo RYR1 heterozygous mutation (I4898T) causing lethal core-rod myopathy in twins.

"Core-rod myopathy" is a rare congenital myopathy characterized by the presence of "cores" and "rods" in distinct locations in the same or different muscle fibres. This association is linked currently to mutations in RYR1, NEB and ACTA1 genes. We report identical twins who presented with polyhydramnios and loss of fetal motility during pregnancy; hypotonia, arthrogryposis and swallowing impairment at birth; need of immediate respiratory support and death at 27 and 50 days of life. Muscle biopsies, performed at 27 days of life in twin 1 and at 49 days in twin 2, showed the presence of separate cores and rods in the muscle fibres, both at light and electron microscopy. The molecular analysis showed a heterozygous de novo mutation (Ile4898Thr) of the RYR1 gene. The molecular study of ACTA1, TMP2 and TMP3 genes did not show abnormalities. This is the first report of a lethal form of congenital "core-rod myopathy". The mutation Ile4898Thr has been previously described in central core disease but not in core-rod myopathy. The report enlarges the phenotypic spectrum of "core-rod myopathy" and highlights the morphological variability associated to special RYR1 mutations.

Congenital malaria in neonates: two case reports and review of the literature.

UNLABELLED: Congenital malaria is uncommon in nonendemic countries. We describe two cases involving neonates hospitalized with fever, anaemia and thrombocytopaenia. Thick and thin blood smears were positive for Plasmodium vivax (P. vivax) and P. ovale, respectively. These two cases were discussed regarding the literature and potential implications of HIV coinfection in the mother. CONCLUSION: Consistent data in the literature suggest that peripheral blood films should be performed in HIV-positive women who travelled to an endemic area or with a history of malaria prior to gestation. With today's travelling patterns, congenital malaria should be considered as an important differential diagnosis of neonatal sepsis.

Cytomegalovirus infection as a possible underlying factor in neonatal surgical conditions.

BACKGROUND: The seroprevalence of cytomegalovirus (CMV) in France is about 38%. Fetal contamination during pregnancy is 40%. We report a series of gastrointestinal conditions associated with CMV in neonates. PATIENTS AND METHOD: This is a retrospective study on neonates operated on for gastrointestinal conditions in our institution between January 1998 and December 2002. Only children with suspected CMV infection (characteristic nuclear inclusions) on pathologic examination were reviewed. We analyzed the age of onset, the clinical and radiologic presentation, and the serologic findings in mother and child. RESULTS: The study included 3 boys and 2 girls. The average gestational age was 34.4 weeks (range, 28-39 weeks) and the average birth weight was 2364 g (range, 790-3580 g). Two infants had necrotizing enterocolitis, 2 had pathologic condition related to Meckel's diverticulum (volvulus and perforation, respectively), and 1 had distal ileal atresia. All surgical specimens showed characteristic CMV nuclear inclusions. Maternal serologic studies were positive for CMV in only 1 case with CMV IgM detected in serum. Two babies had a positive serological finding for CMV with detection of CMV IgM, and 2 had CMV isolated on urinary viral culture (one had both). CONCLUSION: Cytomegalovirus is a viral agent that may be involved in surgical pathology in neonates. To confirm the causal relationship between CMV and these pathologic findings, a large-scale longitudinal prospective screening of CMV in neonates with intestinal conditions should be performed.

Treatment failure of nosocomial pertussis infection in a very-low-birth-weight neonate.

We describe a case of nosocomial maternal transmission of Bordetella pertussis to a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates and in parents with clinical signs of pertussis and suggests that standard treatment may not be appropriate for VLBW neonates.

CARD15/NOD2 is not a predisposing factor for necrotizing enterocolitis.

Multiple factors are incriminated in the etiopathogeny of necrotizing enterocolitis (NEC) in premature infants, including oral feeding, vascular abnormalities, increase in pro-inflammatory cytokines, and inappropriate response of the intestinal barrier to bacterial microflora. CARD15/NOD2 is a gene recently recognized as important in the innate response to gut flora and is involved in Crohn's disease susceptibility. We thus tested its putative role in NEC. Ten children (seven boys and three girls) suffering from NEC who were admitted to Robert Debré hospital between 1999 and 2002 were retrospectively included in the study. Genetic screening of the 11 constant exons and the exon-intron junctions of CARD15/NOD2 by direct sequencing revealed no novel mutations of that gene in NEC patients. Furthermore, the three main mutations of CARD15/NOD2 (R702W, G908R, and 1007fs) associated with susceptibility to Crohn's disease were not found in these patients. Our results suggest that CARD15/NOD2 does not play a major role in genetic susceptibility to NEC.

Drug administration errors and their determinants in pediatric in-patients.

OBJECTIVE: . To quantify the type and frequency of drug administration errors to pediatric in-patients and to identify associated factors. DESIGN: Prospective direct-observation study of drug administration errors from April 2002 to March 2003. SETTING: Four clinical units in a pediatric teaching hospital. STUDY PARTICIPANTS: Twelve observers accompanied nurses giving medications and witnessed the preparation and administration of all drugs to all patients on all weekday mornings. INTERVENTION: None. MAIN OUTCOME MEASURE: Discrepancies between physicians' orders and actual drug administration. RESULTS: During the 1719 observed administrations to 336 patients by 485 nurses, 538 administration errors were detected, involving timing (36%), route (19%), dosage (15%), unordered drug (10%), or form (8% form). These errors occurred for 467 (27%) of the 1719 administrations. Intravenous drugs (OR = 0.28; CI = 0.16-0.49; versus miscellaneous) were associated with fewer errors. Error rates were higher for cardiovascular (OR = 3.38; CI = 1.24-9.27; versus miscellaneous) and central nervous system drugs (OR = 2.65; CI = 1.06-6.59; versus miscellaneous); unspecified dispensing system (OR = 2.06; CI = 1.29-3.29; versus store in the unit); non-intravenous non-oral administration (OR = 4.44; CI = 1.81-10.88; versus oral administration); preparation by the pharmacy (OR = 1.66; CI = 1.10-2.51); and administration by a hospital pool nurse, temporary staffing agency nurse, or nurse intern (OR = 1.67; CI = 1.04-2.68; versus registered full-time nurse). Each additional management procedure in the patient increased the risk of error (OR = 1.22; CI = 1.01-1.48). CONCLUSIONS: The risk factors identified in our study should prove useful for designing preventive strategies, thereby improving the quality of care.