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.

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.

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.

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.

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.

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.

Prescription of Aminoglycosides in 23 French Neonatal Intensive Care Units.

Background: Aminoglycosides are the most prescribed antibiotics in neonatal intensive care units (NICU). Reducing exposure to antibiotics in the NICU is highly desirable, particularly through benchmarking methods. Methods: Description of aminoglycosides prescriptions in 23 French NICU using the same computerized system over a 4-year period (2017-2020). A benchmarking program of antibiotics prescription was associated. Results: The population included 53,818 patients. Exposition rates to gentamicin and amikacin were 31.7% (n = 17,049) and 9.1% (n = 4894), respectively. Among neonates exposed to gentamicin, 90.4% of gentamicin and 77.6% of amikacin treatments were started within the 1st week of life. Among neonates exposed to amikacin, 77.6% started amikacin within the 1st week. The average daily dose of gentamicin at first prescription increased over the study period from 3.9 in 2017 to 4.4 mg/kg/d in 2020 (p < 0.0001). Conversely, the corresponding amikacin daily doses decreased from 13.0 in 2017 to 12.3 mg/kg/d in 2020 (p = 0.001). The time interval between the first 2 doses of gentamicin was mainly distributed in 3 values during the first week of life: 49.4% at 24 h, 26.4% at 36 h, and 22.9% at 48 h. At first amikacin prescription, the time interval was distributed in 4 categories: 48% at 24 h, 4.1% at 30 h, 8.5% at 36 h, and 37.1% at 48 h. As compared to literature guidelines, the rates of overdose and underdose in gentamicin (1.5% and 2.7%) and amikacin (0.3% and 1.0%). They significantly decreased for gentamicin over the study period. In multivariate analysis, the factors significantly associated with GENT overdose were the year of admission, prematurity, length of stay, and duration of the treatment. Conclusion: This prescription strategy ensured a low rate of overdose and underdose, and some benefits of the benchmarking program is suggested.

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.

Antibiotics Prescription Over Three Years in a French Benchmarking Network of 23 Level 3 Neonatal Wards.

Introduction: Prescribing antibiotics to newborns is challenging, as excess antibiotics are a risk factor for increased morbidity and mortality. The objective of this study was to describe the evolution of antibiotic exposure over three years in a large network of level 3 neonatal wards where each center is informed yearly of its own results and the results of other centers and has full autonomy to improve its performance. Patients and Methods: This is a prospective, observational study of antibiotics prescriptions over the 2017-2019 period in a network of 23 French level 3 neonatal wards. The network relied on an internal benchmarking program based on a computerized prescription ordering system. Among others, antibiotics exposure, treatment duration, and antibiotics spectrum index were analyzed. Results: The population consisted of 39,971 neonates (51.5% preterm), 44.3% of which were treated with antibiotics. Of the treated patients, 78.5% started their first antibiotic treatment in the first three days of life. Antibiotic exposure rate significantly declined from 2017 to 2019 (from 46.8% to 42.8%, p < 0.0001); this decline was significant in groups with gestational age >26 weeks, but not in the group with extremely low gestational age <27 weeks. Gentamicin, cefotaxime, amoxicillin (ampicillin), vancomycin, and amikacin were the antibiotics most prescribed. The lower the gestational age, the higher the exposure for cefotaxime, vancomycin, and amikacin. Compared to 2017, cefotaxime exposure in 2019 declined by 12.6%, but the change was only significant in the gestational age group of 32-36 weeks (17.4%) and at term (20.3%). The triple combination of antibiotics in the first three days decreased by 28.8% from 2017 to 2019, and this was significant in each gestational age group. During the study, the delayed ending of antibiotics in unconfirmed early-onset neonatal infection increased from 9.6% to 11.9%. Conclusion: This study showed that a strategy characterized by the collection of information via a computerized order-entry system, analysis of the results by a steering committee representative of all neonatal wards, and complete autonomy of neonatal wards in the choice of prescription modalities, is associated with a significant reduction in the use of antibiotics in newborns with gestational age greater than 26 weeks.

The burden to be second twin: a population-based study of 2686 twins: (2124 dichorionic). Proposal of the concept of mobility.

Objectives: To identify if there is a specific neonatal morbidity/mortality among second twins relative to first twins.Study design: A 17-year (2001-2017) population-based observational cohort of all twin newborns born in the South of Reunion island after 21 weeks.Results: Among 1062 dichorionic (DTP) and 281 monochorionic twin pregnancies (2686 newborns), twin 2 have a doubled risk to be in breech presentation and a bad Apgar at 1 mn (≤6) in vaginal deliveries. Specific to dichorionic pregnancies, twin 2 were lighter by 50-60 g than twin 1, had higher rates of intrauterine growth retardation (IUGR), OR 1.33, p = .007, a doubled risk to have congenital abnormalities OR 2.1, p = .006.Conclusion: In dichorionic twin pregnancies, second twins having a doubled prevalence of severe congenital abnormalities are not completely elucidated and deserves further research. (1) We propose that twin 2 presenting higher risks of being IUGR and much higher risks of severe malformations suggest that during pregnancy, the less mobile of the two twins is "relegated" to the back of the uterus. (2) For interventions in the delivery room, systematically the most experimented neonatologist should plan to manage the second twin because significantly twin 2 presents higher problems than twin 1.

Characteristics of prescription in 29 Level 3 Neonatal Wards over a 2-year period (2017-2018). An inventory for future research.

OBJECTIVES: The primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW. MATERIAL AND METHODS: The research is a two-year observational cohort study (2017-2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse. RESULTS: The study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (p<0.0001). In addition, 69.2% of the 351 different combinations of an medication INN and a route of administration have no indication for the first month of life according to the French SmPC. Ninety-five percent of premature infants with GA less than 32 weeks received at least one medication not cited in SmPC. CONCLUSION: Neonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

An observational study using eye tracking to assess resident and senior anesthetists' situation awareness and visual perception in postpartum hemorrhage high fidelity simulation.

BACKGROUND: The postpartum hemorrhage (PPH) is the leading cause of maternal mortality in the world. Human factors and especially situation awareness has primarily responsibility to explain suboptimal cares. Based on eye tracking and behavior analysis in high fidelity simulation of PPH management, the goal of this study is to identify perceptual and cognitive key parameters of the expertise. METHODS: Two groups of fifteen anesthetists (residents and experienced anesthetists) watched the beginning of a severe simulated PPH management. During this first experimental phase, situation awareness was assessed using SAGAT (Situation Awareness Global Assessment Technique) questionnaire and visual behavior was analyzed with eye tracking. In the continuity of the video sequence, they have to step in the PPH situation and to provide care to the simulated patient. Performance of cares was evaluated and self-assessed as well as cognitive load. RESULTS: No statistical difference between the residents and experienced anesthetists was observed on performance of simulated PPH management. The mean expected practice score was 76.9 ± 13.9%). Assessment of situation awareness (65 ± 7%), cognitive load (74.4 ± 11.3%) and theoretical knowledge of PPH (52.4 ± 3.5%) were also not statistically different between the two groups. Only results of self-assessed performance (respectively 66.1 ± 16.6 and 47.0 ± 20.8 for experts and residents) and eye-tracking data revealed that experts tended to get accurate evaluation of their performance and to monitor more the blood loss of the patient. Experts have in average 8.28% more fixating points than Novices and gazed the blood loss region longer (865 ms ± 439 vs. 717 ms ± 362). CONCLUSIONS: This study pointed out the limits of classical assessment of performance, and human factors based on questionnaires to identify expertise in simulated PPH care. A neuroscientific approach with new technology like eye tracking could provide new objective and more sensitive insights on human factors in simulated medical emergency situations.

Low Renal Oxygen Saturation at Near-Infrared Spectroscopy on the First Day of Life Is Associated with Developing Acute Kidney Injury in Very Preterm Infants.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in preterm infants, and the identification of early markers of renal hypoperfusion is a chief challenge in neonatal intensive care units. OBJECTIVES: To describe the association between early markers of cardiovascular function and renal perfusion with AKI occurrence in a cohort of preterm infants < 32 weeks' gestation. METHODS: 128 infants were prospectively included from birth to discharge. During the first day of life, we assessed cardiovascular function, systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (rSO2) using near-infrared spectroscopy (NIRS). These measures were analyzed in relation to developing AKI and serum creatinine (SCr) peak from day 2 to 7 of life. RESULTS: 12 of 128 infants presented with AKI (9.4%). SCr peak was 155.3 ± 30.2 µmol/L in infants with AKI versus 82.0 ± 16.5 in non-AKI infants (p < 0.001). Among all measures of cardiovascular function and renal perfusion, low mean cerebral and renal rSO2 during the first day of life and a low resistive index at renal artery Doppler were significantly associated with developing AKI. After adjustment for possible confounding factors, low renal rSO2 on the first day of life remained associated with a high SCr peak from day 2 to 7 of life. CONCLUSION: Low renal rSO2 values during the first day of life correlate with developing AKI in preterm infants < 32 weeks' gestation. NIRS monitoring of renal function during adaptation seems promising, and its very early use after birth to detect kidney hemodynamic dysfunction deserves further investigations.

Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study.

Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared. Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates. Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12-24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably). Results: The study included 130 infants of median gestational age 28 weeks (range, 24-41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8-77.6%), 78.5% (95% CI, 67.8-86.9%), 48.5% (95% CI, 30.8-66.5%), 84.9% (95% CI, 74.6-92.2%), 2.7 (95% CI, 1.6-4.9), and 0.5 (95% CI, 0.3-0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70-97.41%), PPV (72.22%; 95% CI, 46.52-90.30%) and LR+ (6.17, 95% CI, 2.67-28.44), but had low specificity (48.15%; 95% CI, 28.67-68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03-90.72%), NPV (91.3%; 95% CI, 82.38-96.32%) and LR- (0.29; 95% CI, 0.12-0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055). Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

Linear association between maternal age and spontaneous breech presentation in singleton pregnancies after 32 weeks gestation.

PURPOSE: To investigate the association between maternal age and spontaneous breech presentation. MATERIAL AND METHODS: Fifteen-year observational study over (2001-2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion's maternity. The only single exclusion criterion was uterine malformations (N = 123) women. RESULTS: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001. CONCLUSION: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent).

Early optimal parenteral nutrition and metabolic acidosis in very preterm infants.

BACKGROUND: It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN) on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN. METHODS: This observational study described the acid-base profile of very preterm infants (≤29 week's gestation) receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3) nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate). The outcome measure to assess metabolic acidosis was the base excess (BE). RESULTS: 161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d) and lipids (2.8 ± 1.4 g/kg/d) during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3); -6.4 ± 3.4 (group 2); -5.1 ± 3.0 (group 1)]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes. DISCUSSION: Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation) displayed greater acidotic disequilibrium and a higher need of bicarbonate.

Low Plasma Protein Levels at Birth Are Associated with Poor Cardiovascular Adaptation and Serious Adverse Outcome in Infants with Gestational Age <32 Weeks: The ProHémie Study.

BACKGROUND: Retrospective studies suggest that early hypoproteinemia has prognostic value for adverse outcome in preemies, but the underlying pathophysiology is unknown. We hypothesized that the prognostic relevance of hypoproteinemia could be related to its association with impaired cardiovascular function and organ perfusion during transition. OBJECTIVES: To describe the plasma protein status and the measures of cardiovascular function according to the outcome in infants <32 weeks' gestation. METHODS: One hundred and twenty-eight infants were prospectively included from birth to discharge. During the first 24 h of life, we assessed the cardiovascular function and systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (cRSO2, rRSO2) using near-infrared spectroscopy. These measures were analyzed in relationship to hypoproteinemia (total plasma protein level <40 g/L at 12 h of life) and severe adverse outcome (death or survival with severe neurological injury). RESULTS: Hypoproteinemia was associated with a higher risk of a severe adverse outcome after adjustment of confounding variables (adjusted OR = 6.8; 95% CI 1.3-34). Compared to normoproteinemic infants and after adjustment for gestational age, hypoproteinemic ones had more significantly: hypotension (7 vs. 13%, p = 0.03), abnormal capillary refilling time (20 vs. 36%, p < 0.001), abnormal renal blood flow (resistive index 0.78 ± 0.11 vs. 0.85 ± 0.09, p = 0.04), lower rRSO2 (82.9 ± 9.2 vs. 73.6 ± 10.5%, p = 0.04), and lower systemic vascular resistance (0.155 ± 0.058 vs. 0.108 ± 0.037 mm Hg/L/kg; p = 0.04). The cRSO2 patterns were significantly decreased in infants with severe adverse outcome and independent from protein status. CONCLUSION: Hypoproteinemia is associated with impaired cardiovascular function. Further studies are required to elucidate the interplay between changes in protein levels, postnatal hemodynamics and clinical outcome.

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.