Analysis of congenital hearing loss after neonatal hearing screening.

Introduction: Neonates undergo neonatal hearing screening to detect congenital hearing loss at an early stage. Once confirmed, it is necessary to perform an etiological workup to start appropriate treatment. The study objective was to assess the different etiologies, risk factors, and hearing results of infants with permanent hearing loss and to evaluate the efficacy and consequences of the different screening devices over the last 21 years. Methods: We conducted a single-center retrospective cohort analysis for all neonatal hearing screening program referrals and performed an etiological workup in case of confirmed hearing loss. We analyzed the evolution of the etiological protocols based on these results. Results: The governmental neonatal hearing screening program referred 545 infants to our center. Hearing loss was confirmed in 362 (66.4%) infants and an audiological workup was performed in 458 (84%) cases. 133 (24.4%) infants were diagnosed with permanent hearing loss. Ninety infants (56 bilateral and 34 unilateral) had sensorineural hearing loss, and the degree was predominantly moderate or profound. The most common etiology in bilateral sensorineural hearing loss was a genetic etiology (32.1%), and in unilateral sensorineural hearing loss, an anatomical abnormality (26.5%). Familial history of hearing loss was the most frequently encountered risk factor. Conclusion: There is a significant number of false positives after the neonatal hearing screening. Permanent hearing loss is found only in a limited number of infants. During the 21 years of this study, we noticed an increase in etiological diagnoses, especially genetic causes, due to more advanced techniques. Genetic causes and anatomical abnormalities are the most common etiology of bilateral and unilateral sensorineural hearing loss, respectively, but a portion remains unknown after extensive examinations.

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.

BACKGROUND: Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain. METHODS: In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points. RESULTS: A total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], -7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups. CONCLUSIONS: Expectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.).

Belgian Consensus Recommendations to Prevent Vitamin K Deficiency Bleeding in the Term and Preterm Infant.

Neonatal vitamin K prophylaxis is essential to prevent vitamin K deficiency bleeding (VKDB) with a clear benefit compared to placebo. Various routes (intramuscular (IM), oral, intravenous (IV)) and dosing regimens were explored. A literature review was conducted to compare vitamin K regimens on VKDB incidence. Simultaneously, information on practices was collected from Belgian pediatric and neonatal departments. Based on the review and these practices, a consensus was developed and voted on by all co-authors and heads of pediatric departments. Today, practices vary. In line with literature, the advised prophylactic regimen is 1 or 2 mg IM vitamin K once at birth. In the case of parental refusal, healthcare providers should inform parents of the slightly inferior alternative (2 mg oral vitamin K at birth, followed by 1 or 2 mg oral weekly for 3 months when breastfed). We recommend 1 mg IM in preterm <32 weeks, and the same alternative in the case of parental refusal. When IM is perceived impossible in preterm <32 weeks, 0.5 mg IV once is recommended, with a single additional IM 1 mg dose when IV lipids are discontinued. This recommendation is a step towards harmonizing vitamin K prophylaxis in all newborns.

Multi-centre, randomised non-inferiority trial of early treatment versus expectant management of patent ductus arteriosus in preterm infants (the BeNeDuctus trial): statistical analysis plan.

BACKGROUND: Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy. METHODS/DESIGN: The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24-72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data. TRIAL REGISTRATION: ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.

Current respiratory support practices in premature infants: an observational study.

This study aims to describe longitudinally the current invasive and non-invasive ventilation practices in premature infants in a single neonatal intensive care unit (NICU). It´s a retrospective chart review including 682 babies born at gestational age ≤35 weeks, admitted to the NICU at Erasme Hospital, between 1st of January 2001 and 31st of December 2011, the different ventilatory support used were analyzed. This population was stratified depending on gestational age and the recruitment period on 3 groups. All infants born <28 weeks of GA (group 1) needed some kind of respiratory support of which 22% non-invasive. Among babies born after 28 to 31 weeks (group 2), 10.2% didn´t need any ventilatory support and 42% needed a non-invasive respiratory support. In neonates from 32 to 35 weeks of GA (group 3) respiratory support was needed in 34.9%, 65% of which was non-invasive. The median duration of endotracheal ventilation was: 6, 1 and 2 days, and of non-invasive support: 41, 17 and 2 days in group 1, 2 and 3 respectively. One single premature baby could pass along the first weeks through all modes. In premature infants whose respiratory support was needed, the median age at the end of support was remarkably constant at 33 - 34 weeks of corrected age. We conclude that is an important diversity and a significant complementarity between modes of respiratory support for premature infants. Invasive ventilation decreased significantly for group 2, but is still remarkably long for group 1.

Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial.

OBJECTIVES: Most studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO. METHODS: A 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life. RESULTS: A total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes. CONCLUSIONS: iNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants.

Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants.

The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was -1.12 g/day (90% CI: [-2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of -2.52 g/day (90% CI: [-4.23; -0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.

Very Preterm Infants with Technological Dependence at Home: Impact on Resource Use and Family.

OBJECTIVE: To examine the impact of medical complexity among very preterm infants on health care resource use, family, and neurodevelopmental outcomes at 18 months' corrected age. METHODS: This observational cohort study of Canadian infants born < 29 weeks' gestational age in 2009-2011 compared infants with and those without medical complexity defined as discharged home with assistive medical technology. Health care resource use and family outcomes were collected. Children were assessed for cerebral palsy, deafness, blindness, and developmental delay at 18 months. Logistic regression analysis was performed for group comparisons. RESULTS: Overall, 466/2,337 infants (20%) needed assistive medical technology at home including oxygen (79%), gavage feeding (21%), gastrostomy or ileostomy (20%), CPAP (5%), and tracheostomy (3%). Children with medical complexity were more likely to be re-hospitalized (OR 3.6, 95% CI 3.0-4.5) and to require ≥2 outpatient services (OR 4.4, 95% CI 3.5-5.6). Employment of both parents at 18 months was also less frequent in those with medical complexity compared to those without medical complexity (52 vs. 60%, p < 0.01). Thirty percent of children with medical complexity had significant neurodevelopmental impairment compared to 13% of those without medical complexity (p < 0.01). Lower gestational age, lower birth weight, bronchopulmonary dysplasia, sepsis, and surgical necrotizing enterocolitis were associated with a risk of medical complexity. CONCLUSION: Medical complexity is common following very preterm birth and has a significant impact on health care use as well as family employment and is more often associated with neurodevelopmental disabilities. Efforts should be deployed to facilitate care coordination upon hospital discharge and to support families of preterm children with medical complexity.

Laboratory validation and field usability assessment of a point-of-care test for serum bilirubin levels in neonates in a tropical setting.

Background: Screening and monitoring serum bilirubin (SBR) in neonates is crucial to prevent neonatal hyperbilirubinemia (NH)-associated morbidity and mortality worldwide. A lack of resources is often a barrier for measuring SBR in developing countries. Reliable, cost-effective, easy to use point-of-care (POC) SBR tests are needed. This study aimed to evaluate the technical accuracy and usability of the Bilistick System (BS), a new bilirubin POC test, in a tropical setting. Methods: This was a mixed-methods study, including laboratory validation of the BS, direct observation of technical procedures as performed by the midwives and midwives' assessment of the device's easiness of use through focus group discussions (FGD) and a self-administered questionnaire. The study was conducted in a field clinic of the Shoklo Malaria Research Unit along the Thailand-Myanmar border between January and December 2017. Results: A total of 173 samples were tested at a median age of 4 days. BS generated an error message-providing no SBR readout-in 48.6% of the tests performed. For the tests that yielded a result, the correlation coefficient (95% CI) between BS and routine laboratory bilirubinometer SBR was 0.87 (0.77-0.93). The accuracy decreased with increasing haematocrit and at higher humidity (≥75%). Direct observation of the operators using the device and analysis of the focus group discussions and questionnaires indicated that the BS was considered easy to use and required limited training. Conclusions: This evaluation showed that the BS, in its current formulation, does not provide reliable results for measuring SBR in a tropical, low-resource setting  but has acceptable usability features.

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BACKGROUND: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. METHODS: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. DISCUSSION: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. TRIAL REGISTRATION: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .

Application of NPE in the assessment of a patent ductus arteriosus.

In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term outcomes, with a paucity of data on the correct diagnostic and pathophysiological assessment of the patent ductus arteriosus (PDA) in association with long-term outcomes. Echocardiography is the selected method of choice for detecting a PDA, assessing the impact on the preterm circulation and monitoring treatment response. PDA in a preterm infant can result in pulmonary overcirculation and systemic hypoperfusion, Therefore, echocardiographic assessment should include evaluation of PDA characteristics, indices of pulmonary overcirculation with left heart loading conditions, and indices of systemic hypoperfusion. In this review, we provide an evidence-based overview of the current and emerging ultrasound measurements available to identify and monitor a PDA in the preterm infant. We offer indications and limitations for using Neonatologist Performed Echocardiography to optimize the management of a neonate with a PDA.

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.

Assessment of continuous pain in newborns admitted to NICUs in 18 European countries.

AIM: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown. METHODS: A prospective cohort study in 243 neonatal intensive care units (NICUs) from 18 European countries recorded the frequency of pain assessments, use of mechanical ventilation, sedation, analgesia or neuromuscular blockade for each neonate for up to 28 days after NICU admission. RESULTS: Only 2113 of 6648 (31.8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46.0%), noninvasive ventilation (NiV, 35.0%) and no ventilation (NoV, 20.1%) groups (p < 0.001). Daily assessments for continuous pain occurred in only 10.4% of all neonates (TrV: 14.0%, NiV: 10.7%, NoV: 7.6%; p < 0.001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions and surgical admissions (all p < 0.01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anaesthetics (O-SH-GA) (all p < 0.001), or surgery (p = 0.028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1.60, p < 0.001) and NiV groups (OR:1.40, p < 0.001). CONCLUSION: Assessments of continuous pain occurred in less than one-third of NICU admissions and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.

Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study.

BACKGROUND: Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries. METHODS: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745. FINDINGS: From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35.0 weeks (SD 4.6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p<0.0001). In the participating NICUs, the median use of sedation or analgesia was 89.3% (70.0-100) for neonates in the TV group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of 2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in the TV group were given neuromuscular blockers, which were administered as continuous infusions to 146 (7%) of these neonates. Pain assessments were recorded in 1250 (58%) of 2138, 672 (45%) of 1493, and 916 (30%) of 3017 neonates in the TV, NIV, and SV groups, respectively (p<0.0001). In the univariate analysis, neonates given O-SH-GA in the TV group needed a longer duration of TV than did those who were not given O-SH-GA (mean 136.2 h [SD 173.1] vs 39.8 h [94.7] h; p<0.0001). Multivariable and propensity score analyses confirmed this association (p<0.0001). INTERPRETATION: Wide variations in sedation and analgesia practices occur between NICUs and countries. Widespread use of O-SH-GA in intubated neonates might prolong their need for mechanical ventilation, but further research is needed to investigate the therapeutic and adverse effects of O-SH-GA in neonates, and to develop new and safe approaches for sedation and analgesia. FUNDING: European Community's Seventh Framework Programme.

Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia?

UNLABELLED: Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2 ) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials. CONCLUSION: SpO2 of 85-89% can increase mortality and 91-95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87-94% or 88-94%, may be safer.

Two-year outcomes of a randomized controlled trial of inhaled nitric oxide in premature infants.

BACKGROUND AND OBJECTIVES: The European Union Nitric Oxide trial was designed to assess the potential benefits of inhaled nitric oxide (iNO) compared with placebo in infants with respiratory failure. This follow-up study evaluated respiratory, neurodevelopmental, and other outcomes for infants entered into the European Union Nitric Oxide trial to age 2 years. METHODS: In a multicenter, randomized, double-blind study, preterm infants born at <29 weeks' gestation with moderate respiratory failure were allocated to receive iNO (5 ppm) or placebo for 7 to 21 days. Subjects underwent assessments at 1 and 2 years corrected for prematurity. RESULTS: At 36 weeks' postmenstrual age, 696 of 792 infants were alive; 4 in the iNO arm subsequently died before age 2 years compared with 7 in the control arm. We evaluated 95% of the survivors at 12 months and 90% at 2 years. In the iNO arm, 244 of 363 (67.2%) infants had survived without disability at age 2 years compared with 270 of 374 (72.2%) who received placebo (P = .094). Mean (SD) cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) were 94 (13) in the iNO group and 95 (14) in the placebo group; in the iNO group, 19% scored <85 and 9.5% developed cerebral palsy compared with 13.3% and 9%, respectively. There were no significant differences in hospitalizations overall or due to respiratory illness in use of home oxygen therapy or respiratory medications, in growth, or in other health outcomes. CONCLUSIONS: At 2 years of age, low-dose (5 ppm) iNO started early (<24 hours after birth) for a median of 20 days did not affect neurodevelopmental or other health outcomes.

Language development at 2 years is correlated to brain microstructure in the left superior temporal gyrus at term equivalent age: a diffusion tensor imaging study.

This study aims at testing the hypothesis that neurodevelopmental abilities at age 2 years are related with local brain microstructure of preterm infants at term equivalent age. Forty-one preterm infants underwent brain MRI with diffusion tensor imaging sequences to measure mean diffusivity (MD), fractional anisotropy (FA), longitudinal and transverse diffusivity (λ// and λ[perpendicular]) at term equivalent age. Neurodevelopment was assessed at 2 years corrected age using the Bayley III scale. A voxel-based analysis approach, statistical parametric mapping (SPM8), was used to correlate changes of the Bayley III scores with the regional distribution of MD, FA, λ// and λ[perpendicular]. We found that language abilities are negatively correlated to MD, λ// and λ[perpendicular] in the left superior temporal gyrus in preterm infants. These findings suggest that higher MD, λ// and λ[perpendicular] values at term-equivalent age in the left superior temporal gyrus are associated with poorer language scores in later childhood. Consequently, it highlights the key role of the left superior temporal gyrus for the development of language abilities in children. Further studies are needed to assess on an individual basis and on the long term the prognostic value of brain DTI at term equivalent age for the development of language.

Paracetamol to induce ductus arteriosus closure: is it valid?

There remains a need for alternative medical treatments for patent ductus arteriosus (PDA) closure in extreme preterm neonates because of therapeutic failure and adverse effects associated with non-selective cyclo-oxygenase inhibitors. Reports of an association between paracetamol exposure and PDA closure in a limited number of extreme preterm neonates have been published. However, causality cannot be taken for granted because a link between the current knowledge of the clinical pharmacology of paracetamol and (patho)physiology of ductal closure is not known. In contrast to non-selective cyclo-oxygenase inhibitors, paracetamol has limited effects at peripheral sites, is a poor antithrombotic and anti-inflammatory drug and exerts its effects primarily within the central nervous system. Although paracetamol appears an effective and safe analgesic in term and near term neonates, its effectiveness and safety for PDA closure are uncertain because the drug is administered in high doses and there remain a limited number of observations in this specific subpopulation so far. Prospective comparative trials are reasonable and are urgently needed to establish both the effectiveness and safety data of paracetamol when used for this indication.