Urinary protein to creatinine ratio during the first month of life in very preterm infants-a prospective cohort study (PROTIPREMA).

BACKGROUND: Preterm infants have physiological proteinuria and values of urine protein to creatinine ratio (UPr/Cr) are higher compared to full-term infants during the first week of life. Few investigations explored the changes of proteinuria in very preterm infants (VPI, ≤ 31 weeks of gestation) older than a week, and it is unclear whether high and persistent proteinuria is associated with kidney injury in this population. This study aimed to (1) observe the changes of UPr/Cr during the first month of life in VPI and (2) describe clinical and biological variables associated with the changes of UPr/Cr. METHODS: Spot urine samples for UPr/Cr were collected on the first day of life (DOL1) and then on DOL2-3, DOL5-6, second week of life (WOL2), WOL3, and WOL4 in VPI cared for in a third-level NICU. We tested the relationship of UPr/Cr with perinatal variables and diseases. RESULTS: A total of 1140 urine samples were obtained for 190 infants. UPr/Cr values (mg/mmol) (median with interquartile) at DOL1, DOL2, DOL3, WOL2, WOL3, and WOL4 were, respectively, 191 (114-399), 226 (152-319), 225 (156-350), 282 (200-488), 308 (188-576), and 325 (175-664). At the multivariate analysis, lower gestational age (GA) and increasing postnatal age were the only variables significantly associated with higher UPr/Cr values (p < 0.001). There was wide intra- and interindividual variability in UPr/Cr, especially in infants with higher GA and clinical stability. CONCLUSIONS: In VPI, UPr/Cr is higher at lower GA and increases with advancing postnatal age. High persistent proteinuria is not associated with clinical and biological variables reflecting kidney injury during the first month of life. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact of SARS-CoV-2 infection on risk of prematurity, birthweight and obstetric complications: A multivariate analysis from a nationwide, population-based retrospective cohort study.

OBJECTIVE: To determine the impact of maternal coronavirus disease 2019 (COVID-19) on prematurity, birthweight and obstetric complications. DESIGN: Nationwide, population-based retrospective cohort study. SETTING: National Programme de Médicalisation des Systèmes d'Information database in France. POPULATION: All single births from March to December 2020: 510 387 deliveries, including 2927 (0.6%) with confirmed COVID-19 in the mother and/or the newborn. METHODS: The group with COVID-19 was compared with the group without COVID-19 using the chi-square test or Fisher's exact test, and the Student's t test or Mann-Whitney U test. Logistic regressions were used to study the effect of COVID-19 on the risk of prematurity or macrosomia (birthweight ≥4500 g). MAIN OUTCOME MEASURES: Prematurity less than 37, less than 28, 28-31, or 32-36 weeks of gestation; birthweight; obstetric complications. RESULTS: In singleton pregnancies, COVID-19 was associated with obstetric complications such as hypertension (2.8% versus 2.0%, p < 0.01), pre-eclampsia (3.6% versus 2.0%, p < 0.01), diabetes (18.8% versus 14.4%, p < 0.01) and caesarean delivery (26.8% versus 19.7%, p < 0.01). Among pregnant women with COVID-19, there was more prematurity between 28 and 31 weeks of gestation (1.3% versus 0.6%, p < 0.01) and between 32 and 36 weeks of gestation (7.7% versus 4.3%, p < 0.01), and more macrosomia (1.0% versus 0.7%, p = 0.04), but there was no difference in small-for-gestational-age newborns (6.3% versus 8.7%, p = 0.15). Logistic regression analysis for prematurity showed an adjusted odds ratio (aOR) of 1.77 (95% CI 1.55-2.01) for COVID-19. For macrosomia, COVID-19 resulted in non-significant aOR of 1.38 (95% CI 0.95-2.00). CONCLUSIONS: COVID-19 is a risk factor for prematurity, even after adjustment for other risk factors. TWEETABLE ABSTRACT: The risk of prematurity is twice as high in women with COVID-19 after adjustment for factors usually associated with prematurity.

Drug exposure for PDA closure in France: a prospective, cohort-based, analysis.

PURPOSE: To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation. METHODS: A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was "a medically treated PDA," defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure. RESULTS: The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72-0.90), paracetamol as the first-line treatment (0.32; 0.15-0.68), and pharmacological treatment before 48 h of life (0.63; 0.43-0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p < 0.0001). CONCLUSION: Drug utilization patterns in infants with PDA vary among centers. Pharmacoepidemiology studies can provide new information on factors associated with PDA refractory to medical treatment.

Gestational age and 1-year hospital admission or mortality: a nation-wide population-based study.

BACKGROUND: Describe the 1-year hospitalization and in-hospital mortality rates, in infants born after 31 weeks of gestational age (GA). METHODS: This nation-wide population-based study used the French medico-administrative database to assess the following outcomes in singleton live-born infants (32-43 weeks) without congenital anomalies (year 2011): neonatal hospitalization (day of life 1 - 28), post-neonatal hospitalization (day of life 29 - 365), and 1-year in-hospital mortality rates. Marginal models and negative binomial regressions were used. RESULTS: The study included 696,698 live-born babies. The neonatal hospitalization rate was 9.8%. Up to 40 weeks, the lower the GA, the higher the hospitalization rate and the greater the likelihood of requiring the highest level of neonatal care (both p < 0.001). The relative risk adjusted for sex and pregnancy-related diseases (aRR) reached 21.1 (95% confidence interval [CI]: 19.2-23.3) at 32 weeks. The post-neonatal hospitalization rate was 12.1%. The raw rates for post-neonatal hospitalization fell significantly from 32 - 40 and increased at 43 weeks and this persisted after adjustment (aRR = 3.6 [95% CI: 3.3-3.9] at 32 and 1.5 [95% CI: 1.1-1.9] at 43 compared to 40 weeks). The main causes of post-neonatal hospitalization were bronchiolitis (17.2%), gastroenteritis (10.4%) ENT diseases (5.4%) and accidents (6.2%). The in-hospital mortality rate was 0.85‰, with a significant decrease (p < 0.001) according to GA at birth (aRR = 3.8 [95% CI: 2.4-5.8] at 32 and 6.6 [95% CI: 2.1-20.9] at 43, compared to 40 weeks. CONCLUSION: There's a continuous change in outcome in hospitalized infants born above 31 weeks. Birth at 40 weeks gestation is associated with the lowest 1-year morbidity and mortality.

A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants.

Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regimens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimize the dosing regimen. An opportunistic sampling strategy combined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimize the dose. The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two-compartment model with first-order elimination. The median values for clearance and the volume of distribution at steady state were 0.12 liter/h/kg of body weight and 0.64 liter/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age (PNA) had significant impacts on cefotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%. We determined the population pharmacokinetics of cefotaxime and established a model-based dosing regimen to optimize treatment for neonates and young infants.

Nutrition practice, compliance to guidelines and postnatal growth in moderately premature babies: the NUTRIQUAL French survey.

BACKGROUND: The nutritional care provided to moderately premature babies is poorly studied. For a large cohort of such babies, we aimed to describe: nutrition practice intentions, comparison of the intended with the actual practice, compliance of actual practice to current nutrition guidelines, and postnatal growth. METHODS: A questionnaire was sent out to 29 neonatal intensive care units in France, in order to address practice intentions. In the same units, retrospective patient's data were collected to assess actual practice, compliance to nutrition guidelines and infant postnatal growth. The cumulative nutritional deficit during the two first weeks of life was calculated and variables associated with ΔZ-score for weight at 36 weeks postconceptional age/discharge (ΔZ-score(w) 36PCA/DC) were analysed by multivariate linear regression. RESULTS: 276 infants born 30 to 33 weeks of gestation were studied. Among them, 76% received parenteral nutrition on central venous line after birth. On day of life 1 (DOL1), 93% of infants had parenteral amino acids (AA), at an intake ≥ 1.5 g/kg in 27% of cases. Lipids were started at ≤ DOL2 in 47% of infants. There was a divergence between the intended and the actual practice for both AA and lipids intake. The AA and energy cumulative deficit (DOL1 to DOL14) were respectively 10.9 ± 8.3 g/kg and 483 ± 181 kcal/kg. Weight Z-score (mean ± SD) significantly decreased from birth (-0.17 ± 0.88) to 36 weeks PCA/DC (-1.00 ± 0.82) (p < 0.0001), and the extra-uterine growth retardation (EUGR) rate at 36 weeks PCA/DC was 24.2%. Independent variables associated with ΔZ-score(w) 36PCA/DC were AA cumulative intake and DOL of full enteral feeding. CONCLUSIONS: Nutrition intake was not in compliance with recommendations, and the rate of EUGR was considerable in this cohort. Efforts are needed to improve adherence to nutrition guidelines and growth outcome of moderately preterm infants.

Diuretic drug utilization in neonates: a French prescription database analysis.

Background: The use of diuretics is extremely common in infants cared for in neonatal wards, despite the lack of proven efficacy for many conditions. The main objective of this study was to assess the rate of diuretics exposure in a multicenter French cohort. The secondary objectives were to describe the evolution of this exposure over time, the indications, the prescription practices, and the exposure rates among centers. Methods: An observational study was conducted in 40 Level 3 French neonatal intensive care units using the same computerized order-entry system. Neonates hospitalized between January 2017 to December 2021 with a corrected age between 24 and 44 weeks of gestation at admission were eligible. Results: A total of 86,032 patients were included. The exposure rate was 8.5%, more specifically 29.4% for children born at < 32 weeks of gestation and 3.7% for neonates born at term. There was no significant variation over the study period, but the exposure ranged from 2.4% to 26.5% depending on the center. The main drugs prescribed were furosemide, spironolactone and dopamine with a diuretic purpose. The main indications were "fluid retention," and to a lesser extent "bronchopulmonary dysplasia" and "post-transfusion." For furosemide, the first exposure occurred in mean at 16.5 (±17.8) days of life, mean duration of exposure was 6.2 (±9.5) days, and the cumulative dose was in mean 10.7 (23.9) mg/kg. Conclusion: Diuretic prescription practices vary between centers. The administration of these drugs is often non-evidence based, doses and duration of treatment easily exceed toxic thresholds.

Successful control of a Methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit: a retrospective, before-after study.

BACKGROUND: Aim of this study was to provide a detailed description of a Methicillin-resistant Staphylococcus aureus (MRSA) outbreak management strategy in the neonatal intensive care unit of a university hospital. METHODS: This was a retrospective, "before-after" study, over two consecutive 18-month periods. The outbreak management strategy was performed by a multidisciplinary team and included: extensive healthcare workers (HCW) involvement, education, continuous hand-hygiene training and active MRSA colonization surveillance. The actions implemented were identified based on an anonymous, voluntary, reporting system, carried out among all the HCW, and regular audit and feedback were provided to the nursing staff. The main measured outcome was the rate of MRSA infections before and after the implementation of the outbreak management strategy. Piecewise linear Poisson regression was performed and the model adjusted for confounding variables. The secondary outcome was the rate of laboratory-confirmed bloodstream infections before and after the outbreak management strategy. The rates of MRSA colonization, implementation of proposed actions, observed compliance for hand-hygiene and insertion/care of central lines were also recorded during the second period. RESULTS: 1015 newborns were included. The rate of MRSA infections throughout the two periods fell from 3.5 to 0.7 cases per 1000 patient-days (p=0.0005). The piecewise Poisson regression analysis adjusted for confounding variables showed a significant decrease in the MRSA infection rate after the outbreak management strategy (p=0.046). A significant decrease in positive laboratory confirmed blood cultures was observed over the two periods (160 vs 83; p<0.0001). A significant decline in the MRSA colonization rate occurred over the second period (p=0.001); 93% of the proposed actions were implemented. The compliance rate for hand-hygiene and insertion/care of central lines was respectively 95.9% and 62%. CONCLUSIONS: The implementation of multiple, simultaneous, evidence-based management strategies is effective for controlling nosocomial infections. Outbreak management strategies may benefit from tools improving the communication between the institutional and scientific leadership and the ground-level staff. These measures can help to identify individualized solutions addressing specific unit needs.

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.

Routine probiotic use in very preterm infants: retrospective comparison of two cohorts.

OBJECTIVE: Evidence supports the efficacy of probiotics in reducing necrotizing enterocolitis (NEC) in very low-birth-weight infants, although concerns remain with regard to their routine use. Since 2008 in our neonatal intensive care unit, a low dose of probiotics (unique strain) is administered as standard of care in all preterm babies born at 24 to 31 weeks' gestation. This study reports outcomes in infants receiving probiotic cohort (PC) compared with the historical cohort. DESIGN: Treatment with Lactobacillus rhamnosus Lcr35 (Lcr Restituo) (2 × 108 colony-forming units/12 h) was started early after birth and intention to treat was up to 36 weeks' gestation. The main outcome was definite NEC. Secondary outcomes were mortality, late-onset sepsis (LOS), cholestasis, isolated rectal bleeding (IRB), and time to reach full enteral feeding (FEF). RESULTS: A total of 1130 patients were included. No adverse effects were observed. Infants in PC presented a reduced rate of NEC (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.07 to 0.58), mortality (OR 0.46; 95% CI 0.21 to 1.00), and LOS (OR 0.60; 95% CI 0.40 to 0.89) and achieved FEF significantly earlier. IRB was significantly reduced among infants receiving the complete scheduled treatment. CONCLUSION: Administration of Lcr Restituo was well tolerated and associated with lower mortality and morbidities in this cohort. Our results provide evidence in support of the hypothesis that this probiotic may reduce IRB.

Postnatal corticosteroid exposure in very preterm infants: A French cohort study.

Background: Postnatal corticosteroids (PC) are widely used in very preterm infants. International reports and national multicenter trials describe a marked variability across countries and inter-sites, in the use of PC. Few information is available on therapeutic indications and prescription characteristics of PC. Aim: The main objective of this study was to describe the exposure to PC in a large cohort of preterm infants born at less than 32 weeks of gestation, according to the prescription data of 41 tertiary-care NICUs in France. Secondary objectives were to describe therapeutic indications, day of life (DOL) of the first exposure, route of administration, duration, cumulative dose for each drug, and differences in exposure rates across centers. Methods: We conducted a prospective observational cohort analysis from January 2017 to December 2021, in 41 French tertiary-care NICUs using the same computerized order-entry system. Results: In total, 13,913 infants [birth weight 1144.8 (±365.6) g] were included. Among them, 3633 (26.1%) were exposed to PC, 21.8% by systemic and 10.1% by inhaled route. Within the study population, 1,992 infants (14.3%) received the first corticosteroid treatment in the first week of life and 1641 (11.8%) after DOL 7. The more frequent indications were prevention and/or treatment of bronchopulmonary dysplasia, and arterial hypotension. Hydrocortisone was the more often prescribed molecule. For systemic PC the first exposure occurred in mean at DOL 9.4 (±13.5), mean duration of treatment was 10.3 (±14.3) days, and the cumulative dose (expressed as the equivalent dose of hydrocortisone) was in median [IQR] 9.0 [5.5-28.8] mg/kg. For inhaled PC, the first exposure occurred in mean at DOL 34.1 (±19.7), and mean duration of treatment 28.5 (±24.4) days. The exposure rate ranged from a minimum of 5% to a maximum of 56% among centers, and significantly increased over the study period (p < 0.0001). Conclusion: In this French cohort of very preterm infants, around one patient out to five was exposed to PC during hospital stay in the NICU. The exposure occurred early, starting from the first week of life. Exposure rate widely varied among centers. Pharmacoepidemiology studies are useful to increase knowledge on corticosteroid utilization patterns in preterm infants.

Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study.

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs). Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0-10 mg/kg/d), duration of exposure, and cumulative dose. Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p < 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate. Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants.

Antenatal factors associated with perinatal arterial ischemic stroke.

BACKGROUND AND PURPOSE: Perinatal arterial ischemic stroke (PAIS) is a common cause of hemiplegic cerebral palsy in children. The diagnosis of PAIS is based on cerebral imaging. The objective of our study was to determine prenatal risk factors associated with PAIS. METHODS: A retrospective case-control study was nested in the whole population of Burgundy, France, from January 2000 to December 2007. Case patients were confirmed by review of brain imaging and medical records. Three control subjects per case were randomly selected from the study population by sex, term, place, and year of birth. RESULTS: PAIS was confirmed in 32 patients and its incidence was one per 4400 live births. In comparison to control subjects, clinical conditions significantly associated to cases were gestational diabetes (16.1% versus 4.2%; P=0.04), fetal heart rate abnormalities (35.5% versus 10.9%; P=0.001), and meconium-stained liquor (40% versus 12%; P<0.001). At the limit of statistical significance were found maternal smoking before (39.3% versus 22.9%; P=0.08) and during pregnancy (32.1% versus 16.7%; P=0.07), cord abnormalities (29% versus 14.1%; P=0.06), and cesarean delivery (28.1% versus 14.6%; P=0.08). In the multivariate analysis, maternal smoking during pregnancy (OR, 3.1; 95% CI, 1.1-8.8; P=0.04) was the only risk factor significantly associated with PAIS. CONCLUSIONS: This study is the first to identify maternal smoking during pregnancy as an independent prenatal risk factor of PAIS. Additional prospective studies are needed to confirm this result and to investigate the role of maternal smoking in fetal and neonatal thrombogenesis.

Early chloride intake does not parallel that of sodium in extremely-low-birth-weight infants and may impair neonatal outcomes.

BACKGROUND AND OBJECTIVE: Accurate data on the optimal chloride (Cl) intake in premature infants are scarce. The aim of the present study was to describe Cl intakes in the first 10 days of life and to assess the relations between high Cl intakes and corrected serum Cl level or markers of severe acidosis in infants <28 weeks' gestation. METHODS: Retrospective cohort study including all of the infants <28 weeks admitted to the neonatal intensive care unit during a 3-year period and cared for from birth until day 10 or more. RESULTS: Fifty-six infants were included. Cumulative total Cl intakes reached 9.6 ± 3.7 mmol/kg at day 3 and 49.2 ± 13.5 mmol/kg at day 10. Inadvertent intakes (from intravenous fluids other than parenteral nutrition) represented on average 70% of total Cl intakes in the first 3 days. Difference between Cl and sodium intakes reached 7.8 ± 4.8 mmol/kg at day 10 and mainly originated from parenteral nutrition. By multivariate analysis, cumulative Cl intake >10 mmol/kg during the first 3 days was an independent risk factor of base excess <-10 mmol/L. Cumulative Cl intake >45 mmol/kg during the first 10 days was an independent risk factor of corrected chloremia >115 mmol/L and of base excess <-10 mmol/L. CONCLUSIONS: Cumulative Cl intake >10 mmol/kg during the first 3 days (ie, 3.3 mmol · kg (-1) · day(-1) on average) and >45 mmol/kg during the first 10 days (ie, 4.5 mmol · kg (-1) · day(-1) on average) may have unwanted metabolic consequences and should be avoided. Imbalance between electrolytes provided by the parenteral nutrition solution need to be detected and corrected.

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.

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020.

Objectives: No consensus exists about the doses of analgesics, sedatives, anesthetics, and paralytics used in critically ill neonates. Large-scale, detailed pharmacoepidemiologic studies of prescription practices are a prerequisite to future research. This study aimed to describe the detailed prescriptions of these drug classes in neonates hospitalized in neonatal intensive care units (NICU) from computerized prescription records and to compare prescriptions by gestational age. Materials and Methods: We included all neonates requiring intensive care in 30 French level III units from 2014 through 2020 with a computerized prescription for an analgesic, sedative, anesthetic, or paralytic agent. We described frequencies of prescription, methods of administration, concomitant drug prescriptions, and dosing regimen, and compared them across gestational ages. Results: Among 65,555 neonates, 29,340 (44.8%) were prescribed at least one analgesic (acetaminophen in 37.2% and opioids in 17.8%), sedative (9.8%), anesthetic (8.5%), and/or paralytic agent (1%). Among preterm infants born before 28 weeks, 3,771/4,283 (88.0%) were prescribed at least one of these agents: 69.7% opioids, 41.2% sedatives, 32.5% anesthetics, and 5.8% paralytics. The most frequently prescribed agents were sufentanil (in 10.3% of neonates) and morphine (in 8.0% of neonates) for opioids, midazolam (9.3%) for sedatives, ketamine (5.7%) and propofol (3.3%) for anesthetics. In most neonates, opioids and sedatives were prescribed as continuous infusion, whereas anesthetics were prescribed as single doses. Opioids, sedatives and paralytics were mostly prescribed in association with another agent. Doses varied significantly by gestational age but within a limited range. Gestational age was inversely related to the frequency, cumulative dose and duration of prescriptions. For example, morphine prescriptions showed median (IQR) cumulative doses of 2601 (848-6750) vs. 934 (434-2679) µg/kg and median (IQR) durations of 7 (3-15) vs. 3 (2-5) days in infants born <28 vs. ≥ 37 weeks of gestation, respectively (p-value<0.001). Conclusion: The prescriptions of analgesic, sedative, anesthetic, or paralytic agent were frequent and often combined in the NICU. Lower gestational age was associated with higher frequencies, longer durations and higher cumulative doses of these prescriptions. Dose-finding studies to determine individualized dosing regimens and studies on long-term neurodevelopmental outcome according to received cumulative doses are required.

A clinic-biological score for diagnosing early-onset neonatal infection in critically ill preterm infants.

OBJECTIVE: To identify the best combination of serum cytokines and clinical parameters to diagnose rapidly early-onset neonatal infection (EONI) in critically ill preterm infants. At birth, most critically ill neonates are receiving broad-spectrum antibiotics pending bacterial culture results, because distinguishing infected from noninfected infants at birth is difficult. DESIGN: Prospective study. SETTING: Neonatal intensive care unit in a tertiary care hospital. PATIENTS: Two hundred thirteen infants, born before 33 wks' gestation, admitted to the neonatal intensive care unit within 6 hrs of life with a presumptive diagnosis of EONI. INTERVENTION: A presumptive diagnosis of EONI was associated with a 300-µL blood sample to measure six cytokine (interleukin [IL]-1ß, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α) concentrations, using the cytometric bead array technique. MEASUREMENTS AND MAIN RESULTS: Of the 213 infants included, 31 had a definite or possible EONI and 182 were not infected. Concentrations of IL-6, IL-8, and IL-10 were significantly increased in infected neonates, in comparison with infants without EONI. In contrast, IL-1ß, IL-12, and tumor necrosis factor-α concentrations were not. Logistic regression analyses were performed to construct multivariate predictive models that could distinguish infected from noninfected infants at birth. A clinical score was based on three parameters independently associated with EONI (i.e., interval of >12 hrs between the membranes rupture and delivery, prenatal maternal colonization and mechanical ventilation at birth). This score was compared with scores including clinical parameters and serum cytokines, alone or in combination. The best predictive model combined the three clinical parameters, IL-6 (positive threshold, 300 pg/mL) and IL-8 (positive threshold, 300 pg/mL) concentrations. CONCLUSION: A predictive model combining serum IL-6 and IL-8 measurements and selected clinical variables could distinguish infected from noninfected preterm infants at birth and should help the clinician in reducing or shortening the unnecessary use of antibiotics.

[Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention]. / Toxoplasmose congénitale : comparaison randomisée de stratégies de prévention des rétinochoroïdites.

In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children.