Impact of fetal growth restriction on neurodevelopmental outcome at 2 years for extremely preterm infants: a single institution study.

AIM: We evaluated the impact of fetal growth restriction on neurodevelopmental outcomes at 2 years corrected age for infants born before 27 weeks gestational age. METHOD: Data on infants born before 27 weeks gestational age between 1999 and 2008 (n=463), admitted to a tertiary neonatal unit in Paris, were used to compare neurological outcomes at 2 years for infants with birthweight lower than the 10th centile and birthweight of at least the 10th centile, using intrauterine reference curves. Outcomes were cerebral palsy (CP) and the Brunet-Lézine assessment of cognitive development, which provides age-corrected overall and domain-specific (global and fine motor skills, language and social interaction) developmental quotients. Models were adjusted for perinatal and social factors. RESULTS: Seventy-two percent of infants were discharged alive. Eighty-three percent (n=268) were evaluated at 2 years. Six percent had CP. Fetal growth restriction was not associated with the risk of CP. After adjustment, children with a birthweight lower than the 10th centile had a global developmental quotient 4.7 points lower than those with birthweight of at least the 10th centile (p<0.001); differences were greatest for fine motor and social skills (-4.7, p=0.053 and -7.3, p<0.001 respectively). INTERPRETATION: In extremely preterm children, fetal growth restriction was associated with poorer neurodevelopmental outcomes at 2 years, but not with CP.

Development of a questionnaire to assess the impact on parents of their infant's bronchiolitis hospitalization.

BACKGROUND: Bronchiolitis is a distressing respiratory condition and the most common cause of hospitalization during the first year of life. The hospitalization of an infant is a stressful event for parents and deserves careful consideration. The objective of this work was to develop and validate a self-administered instrument that comprehensively assesses the impact on parents of the hospitalization of their infant for bronchiolitis. METHODS: The Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©) was developed using a literature review and pre-study interviews with both parents and clinicians. For finalization and psychometric validation, it was included in a multicenter, longitudinal, observational study conducted in France. Parents of infants under the age of 1 year and hospitalized for bronchiolitis were asked to complete the questionnaire at hospital discharge, and 3 months after. RESULTS: Seven hundred and seven questionnaires were completed by the parents of the 463 eligible infants. After finalization, based on principal component analyses, the IBHQ included 30 core items allowing the calculation of 7 dimension core scores (Worries and distress; Fear for future; Guilt; Impact on daily organization; Physical impact; Impact on behavior with hospitalized infant; Financial impact), as well as 16 optional items, allowing the calculation of 5 optional dimension scores (Disturbed breastfeeding; Physical reaction of hospitalized infant; Impact on feeding; Impact on behavior with other infants; Siblings' reaction). Internal consistency reliability and construct validity of the IBHQ were satisfactory. The highest impact was observed for "Worries and distress", "Fear for future" and "Impact on daily organization" scores. CONCLUSIONS: The IBHQ is a reliable and valid instrument for assessing the multifaceted impact on parents of the hospitalization of their infant for bronchiolitis.

Unbound bilirubin does not increase during ibuprofen treatment of patent ductus arteriosus in preterm infants.

OBJECTIVE: To determine whether ibuprofen displaces bilirubin from albumin in preterm infants. STUDY DESIGN: A total of 34 preterm neonates (<32 weeks gestation) treated by ibuprofen (10-5-5 mg/kg) were included in this prospective open-label study. Total bilirubin (TB), unbound bilirubin (UB), and ibuprofen concentrations were measured before, 1 hour, and 6 hours after the first dose; before and 1 hour after the second dose; and 72 hours after the beginning of treatment. The infants were screened by auditory brainstem responses and by neurologic examination at term. RESULTS: At baseline, TB, UB, apparent binding affinity of albumin (Ka), and albumin concentrations were 6.0±1.6 mg/dL, 1.9±2.2 µg/dL, 14.1±5.8 L·µmol(-1), and 28.7±2.3 g/L, respectively. Ibuprofen treatment had no effect on TB, UB, or Ka values. No correlation between UB or Ka and ibuprofen concentrations was found. No neurologic symptoms or significant modifications of auditory brainstem responses were observed at term. CONCLUSION: Ibuprofen (10-5-5 mg/kg) did not displace bilirubin in preterm infants with a baseline TB concentration <8.8 mg/dL.

Impact on parents of bronchiolitis hospitalization of full-term, preterm and congenital heart disease infants.

BACKGROUND: The objective of this work was to explore the impact on parents of the bronchiolitis hospitalization of their infant using the Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©). METHODS: Four hundred sixty-three infants aged less than 1 year and hospitalized for bronchiolitis were included in a French observational study during the 2008-2009 season. Parents were asked to complete the IBHQ at hospital discharge and 3 months later. IBHQ scores, ranging from 0 (no impact) to 100 (highest impact), were compared according to gestational age (full-term, 33-36 wGA, ≤ 32 wGA) and the presence of congenital heart disease (CHD). The potential drivers of impact were explored using multivariate linear regressions. RESULTS: The study included 332 full-terms, 71 infants born at 33-36 wGA, and 60 at ≤ 32 wGA; 28 infants had a CHD. At hospital discharge, 9 of the 12 IBHQ mean scores were above 40, indicating a marked impact on parents. Three months later, all mean scores were lower but 5 were still greater than 40. At discharge, the length of hospitalization had a significant effect on IBHQ worries and distress, fear for future, guilt and impact on daily organization scores (p<0.01); the parents' educational level had a significant effect on IBHQ worries and distress, fear for future, impact on daily organization and financial impact scores (p<0.05). The only statistically significant difference found between the parents of preterm and full-term infants was for the physical impact score at discharge (p=0.004). CONCLUSIONS: Bronchiolitis hospitalization has conspicuous emotional, physical and organizational consequences on parents and siblings, which persist 3 months after hospital discharge. The main drivers of the impact were length of hospital stay and parents' educational level, while infants' gestational age or the presence of a CHD had little influence.

Fecal calprotectin: cutoff values for identifying intestinal distress in preterm infants.

This study aimed to determine cutoff levels for fecal calprotectin as a marker of intestinal distress in preterm neonates. A total of 126 infants born at a median gestational age of 33 weeks (range 25.7-35 weeks) were enrolled. Samples (n = 312) were collected weekly from the end of the first week of life until the end of the first month and if any gastrointestinal event occurred. Receiver operating characteristic curves analysis gave cutoff values of 363 microg/g (sensitivity 0.65, specificity 0.82) and 636 microg/g (sensitivity 0.72, specificity 0.95) for the development of mild or severe enteropathy.

Evidence for transmission of Escherichia coli from mother to child in late-onset neonatal infection.

Genetic characterization of non-K1 Escherichia coli strains isolated from a mother and her neonate allowed us to provide evidence of the maternal origin of a late-onset neonatal infection. The use of ante- and peripartum antimicrobial prophylaxis with amoxicillin may have promoted the vertical transmission of this amoxicillin-resistant E. coli from mother to newborn. It allowed us to clarify the natural history of the disease.

Positive slow waves in the EEG of premature infants between 24 and 36 weeks of conceptional age.

OBJECTIVE: The aim of this prospective and longitudinal study was to characterize EEG patterns during the first weeks of life in extremely premature infants. METHODS: Twenty-five extremely premature infants were included and weekly EEG recordings were obtained between 24 and 36 weeks of conceptional age (CA). RESULTS: Central (rolandic) positive slow waves (CPSW) were found to be the most reliable and characteristic pattern. CPSWs were frequent at 24 weeks CA and progressively diminished and disappeared around 34 weeks CA. CPSWs appeared isolated or in sequences, they occurred during periods of continuous or discontinuous EEG activity, during bursts or during intervals of discontinuous activity, and unilaterally or bilaterally. Temporal positive slow waves and theta rhythms occurred less often and did not decrease as a function of CA. In addition, the amount of discontinuity progressively decreased until 36 weeks CA. The duration of bursts stayed constant, while inter-burst intervals decreased as a function of CA. CONCLUSIONS: Central positive slow waves are characteristic features of the EEG in the extremely premature infant. SIGNIFICANCE: The presence of CPSWs and their progressive disappearance until 34 weeks CA may represent a maturational marker in the EEG.

Increased incidence of necrotizing enterocolitis in premature infants born to HIV-positive mothers.

OBJECTIVE: To examine if being born to an HIV-positive mother may increase the risk of necrotizing enterocolitis in premature infants. DESIGN: Case-control study. SETTING: Neonatal unit of a level 3 perinatal centre. METHODS: : Over a period of 8.5 years, all cases of necrotizing enterocolitis occurring in premature infants admitted to the neonatal unit were identified. For each case, two controls were retrospectively chosen that matched for postmenstrual age at birth, intrauterine growth and year of birth. Perinatal characteristics were studied in all infants. MAIN RESULTS: There were 79 cases of necrotizing enterocolitis, which were compared with 158 controls. Using multivariate analysis, multiple pregnancy [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.23-4.25; P = 0.009], abnormal umbilical artery velocity (OR, 2.21; 95% CI, 1.08-4.54; P = 0.030), abnormal fetal heart rate (OR, 2.14; 95% CI, 1.05-4.36; P = 0.036) and HIV-positive mother (OR, 6.63; 95% CI, 1.26-34.8; P = 0.025) were significantly more frequent in fetuses who subsequently developed necrotizing enterocolitis. CONCLUSIONS: This preliminary report suggests an association, not previously reported, between maternal HIV-positive status and an increased risk of necrotizing enterocolitis in premature infants. Despite the limitations of this study, we suggest that premature newborn infants of HIV-positive mothers should be monitored very carefully for a possible increased risk of necrotizing enterocolitis.

Capnography in spontaneously breathing preterm infants with bronchopulmonary dysplasia.

BACKGROUND: In adult patients with chronic obstructive pulmonary disease, there is a gradient between end-tidal carbon dioxide (EtCO(2)) and arterial carbon dioxide pressure (PaCO(2)), and the slope of the ascending phase of the capnogram is decreased due to obstruction. Corresponding data are lacking in infants with bronchopulmonary dysplasia (BPD). OBJECTIVES: To compare PCO(2) -EtCO(2) gradient and capnogram shape in two groups of spontaneously breathing preterm subjects: infants with BPD and infants without respiratory disease (controls). MATERIAL AND METHODS: Capnography was performed at 36 weeks postmenstrual age in 20 infants (12 BPD with oxygen dependency, 8 controls). Respiratory rate and the components of the respiratory cycle were measured. The PCO(2) -EtCO(2) gradient was calculated using EtCO(2) values and simultaneously sampled capillary values (PcCO(2)). Capnograms were compared between groups. RESULTS: In BPD subjects, respiratory rate was increased (60 ± 16 bpm vs 43 ± 16 bpm, P = 0.009); a widened PcCO(2) -EtCO(2) gradient was observed (13 ± 4 mmHg vs 0 ± 7 mmHg, P = 0.0013); the ascending phase of the capnogram was not decreased, whereas the initial inspiratory phase was prolonged (0.32 ± 0.05 vs 0.24 ± 0.04, P = 0.001). CONCLUSIONS: Compared with healthy infants, a higher PcCO(2) -EtCO(2) gradient was observed in infants with BPD, suggesting that ventilation-perfusion mismatch may be present in these infants. The capnogram did not exhibit the characteristic shape of airway obstruction.

A conserved switch in sensory processing prepares developing neocortex for vision.

Developing cortex generates endogenous activity that modulates the formation of functional units, but how this activity is altered to support mature function is poorly understood. Using recordings from the visual cortex of preterm human infants and neonatal rats, we report a "bursting" period of visual responsiveness during which the weak retinal output is amplified by endogenous network oscillations, enabling a primitive form of vision. This period ends shortly before delivery in humans and eye opening in rodents with an abrupt switch to the mature visual response. The switch is causally linked to the emergence of an activated state of continuous cortical activity dependent on the ascending neuromodulatory systems involved in arousal. This switch is sensory system specific but experience independent and also involves maturation of retinal processing. Thus, the early development of visual processing is governed by a conserved, intrinsic program that switches thalamocortical response properties in anticipation of patterned vision.

Detection of carbon dioxide thresholds using low-flow sidestream capnography in ventilated preterm infants.

BACKGROUND: Monitoring CO2 levels in preterm infants receiving mechanical ventilation is designed to avoid the harmful consequences of hypocapnia or hypercapnia. Capnography is of questionable accuracy for monitoring PCO2 in preterm infants. OBJECTIVES: To determine the accuracy of sidestream capnography in ventilated preterm infants by comparing end-tidal carbon dioxide (EtCO2) values to mixed venous carbon dioxide pressure (PvCO2) and to transcutaneous carbon dioxide pressure (TcPCO2). METHODS: Simultaneous recordings of EtCO2, TcPCO2 and PvCO2 in 37 ventilated preterm infants. The PvCO2-EtCO2 gradient was calculated. The Bland-Altman technique and the intra-class correlation coefficient (ICC) were used to assess agreement between methods. The area under the curve (AUC) was calculated. RESULTS: Ninety-nine EtCO2/PvCO2 pairs were studied from 37 preterm infants with a mean gestational age of 27.7 +/- 1.9 weeks and a mean birth weight of 1,003 +/- 331 g. The mean PvCO2-EtCO2 gradient was 11.2 +/- 8.0 mmHg, and the ICC was 0.28. The mean PvCO2-TcPCO2 gradient was 0 +/- 7.8 mmHg, and the ICC was 0.78. AUCs for EtCO2 and TcPCO2 were similar in detecting high or low PvCO2. CONCLUSION: Despite an insufficient correlation between EtCO2 and PvCO2, capnography was able to detect low and high CO2 warning levels with a similar efficacy to that of TcPCO2, and may therefore be of clinical interest.

[Analysis of the concept of risk in a medical teaching program]. / L'analyse de la notion de risque, base d'un enseignement médical.

The concept of risk has acquired an extremely important place in medical care in the course of various social developments. This concept plays a role in the physician-patient relationship, especially as the form in which the physician provides information to the patient; it is also a form of medical knowledge. We propose a cross-sectional medical course module on this concept of risk, intended for medical students; it can be included in module 1 of the curriculum for the national ranking examination. This class enables a new approach to medical care by showing the variety of definitions of risk and facilitating their perception and integration. Through a process that is simultaneously epistemological and practical, it aims to associate the medical knowledge we use every day with the concept of risk and thereby help the students take a critical distance relative to the mass of available knowledge. This approach to medical knowledge through the concept of risk makes the knowledge more operational and more pertinent within the context of individual clinical situations and thus optimizes medical care. Its pedagogical techniques combine standard classroom lectures with workshops involving role-playing in specific scenarios. This original course meets the needs of medical students who are in the process of becoming health care providers--needs related to the analysis and use of available medical knowledge in their clinical practice and to some aspects of the patient-provider relationship.

Neuromotor outcome at 2 years of very preterm infants who were treated with high-frequency oscillatory ventilation or conventional ventilation for neonatal respiratory distress syndrome.

OBJECTIVE: In a previous multicenter, randomized trial, elective use of high-frequency oscillatory ventilation was compared with the use of conventional ventilation in the management of respiratory distress syndrome in preterm infants <30 weeks. No difference in terms of respiratory outcome was observed, but concerns were raised about an increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group. To evaluate outcome, a follow-up study was conducted until a corrected age of 2 years. We report the results concerning neuromotor outcome. METHODS: Outcome was able to be evaluated in 192 of the 212 infants who survived until discharge from the neonatal unit: 97 of 105 infants of the high-frequency group and 95 of 104 infants of the conventional ventilation group. RESULTS: In the infants reviewed, mean birth weight and gestational age were similar in the 2 ventilation groups. As in the overall study population, the following differences were observed between the high-frequency ventilation group and the conventional ventilation group: lower 5-minute Apgar score, fewer surfactant instillations, and a higher incidence of severe intraventricular hemorrhage. At a corrected age of 2 years, 93 of the 97 infants of the high-frequency group and 79 of the 95 infants of the conventional ventilation group did not present any neuromotor disability, whereas 4 infants of the high-frequency group and 16 infants of the conventional ventilation group had cerebral palsy. CONCLUSIONS: Contrary to our initial concern about the increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group, these data suggest that early use of high-frequency ventilation, compared with conventional ventilation, may be associated with a better neuromotor outcome. Because of the small number of patients studied and the absence of any explanation for this finding, we can conclude only that high-frequency oscillatory ventilation is not associated with a poorer neuromotor outcome.