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.

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.

Validation of the 34-week gestation as definition of late onset preeclampsia: Testing different cutoffs from 30 to 37 weeks on a population-based cohort of 1700 preeclamptics.

INTRODUCTION: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP) have been differentiated with a cut-point of ≤34 weeks. This classical definition has never been examined with respect to maternal characteristics by different gestational age cut-points. We examined maternal characteristics in a population-based cohort of 1736 preeclamptic deliveries at different gestational age cut-points from 30 to 37 weeks (CO30 to CO37). MATERIAL AND METHODS: Eighteen-year observational population-based historical cohort study (2001-2018). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity. Standardized epidemiological perinatal database. RESULTS: The incidence of EOP was lower in adolescents (1.8% vs 3.5%, odds ratio [OR] 0.50, P = .17). Conversely, the odds of LOP was increased for women over 35, beginning at C030 (OR 1.13, P = .02) and this effect (OR = 1.2) was still detectable at C037 (P = .06). Among primigravid women, the incidence of EOP was lower than LOP (OR ranging from 0.71 to 0.82 for different CO). Conversely, the incidence of LOP was higher (adjusted OR about 2.7 [CO30-CO34] with a rise to 3.3 at CO37 (P < .001). Women with EOP had a lower body mass index (BMI) as compared with LOP at CO34 and CO37. The adjusted OR (per 5 kg/m2 increment) declined from 1.06 to 1.03 from CO30 to C037 in EOP women. Conversely, for LOP, the adjusted odds ratio (aOR) increased from 1.04 to 1.06 from CO30 to CO37 (P < .001). Gestational diabetes mellitus was not associated with LOP at any cut-off (aOR 1.07, NS) but was protective against EOP from CO30 to CO34 (aOR 0.42, 0.61 and 0.73, respectively, P < .001). This protective effect disappeared at CO37. Chronic hypertension and history of preeclampsia were both EOP and LOP risks but with a much stronger effect for EOP (chronic hypertension: aOR 6.0-6.5, history of preeclampsia: aOR 12-17). CONCLUSIONS: The 34th week of gestation appears to provide a reasonable cut-point to differentiate between EOP and LOP. Additional research is needed to better describe the possible differences in the pathophysiology of these different phenotypes.

Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis.

OBJECTIVE: To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis. STUDY DESIGN: All existing randomized controlled trials testing the efficacy of the prophylaxis of early adrenal insufficiency using low-dose hydrocortisone on survival without BPD were considered for inclusion when data were available. The primary outcome was the binary variable survival without BPD at 36 weeks of postmenstrual age. RESULTS: Among 5 eligible studies, 4 randomized controlled trials had individual patient data available (96% of participants identified; n = 982). Early low-dose hydrocortisone treatment for 10-15 days was associated with a significant increase in survival without BPD (OR, 1.45; 95% CI, 1.11-1.90; P = .007; I2 = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I2 = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I2 = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I2 = 31.9%) when hydrocortisone was given in association with indomethacin exposure. The incidence of late-onset sepsis was increased in infants exposed to hydrocortisone (OR, 1.34; 95% CI, 1.02-1.75; P = .04; I2 = 0%), but no adverse effects were reported for either death or 2-year neurodevelopmental outcomes as assessed in an aggregate meta-analysis. CONCLUSIONS: This individual patient data meta-analysis showed that early low-dose hydrocortisone therapy is beneficial for survival without BPD in very preterm 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.

Clear amniotic fluid aspiration syndrome: A novel description of an old entity.

BACKGROUND: Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to characterize the risk factors and outcomes associated with Clear Amniotic Fluid Aspiration Syndrome and 2. to compare the outcomes of Clear Amniotic Fluid Aspiration to Meconium Aspiration. METHODS: This was an observational study over a 22-year period in a single level-3 medical center. Compared were parturient/labor characteristics and neonatal outcomes in cases with suspected Clear Amniotic Fluid Aspiration to cases suspected for Meconium Aspiration. RESULTS: Out of 79,620 term deliveries there were 66,705 (83.8%) clear amniotic fluids and 12,915 (16.2%) meconium stained amniotic fluid (MSAF). Of neonates born with clear amniotic fluid, 166 (0.25%) were diagnosed with Clear Amniotic Fluid Aspiration Syndrome (CAF-AS), while 202 (15.7%) of those born with MSAF, were diagnosed with aspiration syndrome (MSAF-AS). Both conditions had comparable rates of mild manifestation (67.5% vs 69.2%, p = 0.63). Persistent pulmonary hypertension (PPH) occurred 5 times less in CAF-AS than MSAF-AS (4% vs 20%, OR 0.17, P< 0.0001) Both conditions presented similar rates of surfactant without PPH (11.1% vs 13.4%, p = 0.87). There was 1 postnatal death in CAF-AS vs 10 in MSAF. CONCLUSION: CAF-AS were quantitatively quite similar in terms of need of actual active intervention of the neonatologists in the delivery room (166 vs 202, i.e. in terms of numbers of cases and not prevalence) to MSAF-AS.We identified in these cases two major specific causes: hyperkinetic explosive deliveries in multiparas and long-lasting episodes of maternal hypotension due to epidural/spinal anaesthesia during labor. Out of 140 million births per year in the world, it should be of concern that 3 million cases are neglected nowadays. Future studies should evaluate if this CAF-AS should benefit from a more active intervention such as immediate endotracheal suction at birth, this clear fluid being very easy to suction.

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.

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.

Preeclampsia in 2023: Time for preventing early onset- and term preeclampsia: The paramount role of gestational weight gain.

The 2023 goal is to halve the incidence of preeclampsia worldwide to reach 3 million cases per year vs the current approximately 7 million cases. Preventive treatment by low dose aspirin only halves the incidence of early-onset preeclampsia (EOP < 34 weeks gestation) in high-risk women. However, 90% of PE cases are the late onset form (LOP, 34 weeks onward) proportionally associated with increasing maternal pre-pregnancy BMI. In 2018, we published a new method to calculate individualized optimal gestational weight gain based on normal Gaussian distribution of neonatal birthweights (SGA 10%, LGA 10%) and demonstrated that this optimal gestational weight gain (GWG) follows a linear equation suitable for all maternal PRE-pregnancy BMIs (from lean to obesities classes 1-2-3). A similar linear equation has been published recently based on a 2022 US database of 200,000 multiple pregnancies. Subsequently, we demonstrated in a prospective population study that in overweight and obese women who are able to achieve an optimal GWG, the rate of term preeclampsia (> 37 week's gestation) halves. Providing individual app-based calculations of optimal individual GWG, all patients will be aware of their personal weight gain target over the pregnancy. CONCLUSION: Halving the incidence of early-onset- and term preeclampsia worldwide by prevention is now theoretically achievable. Appropriate and timely start of low-dose Aspirin and providing women clear advice on their optimal GWG are they ingredients to achieve this goal.

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.

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.

The blurring boundaries between placental and maternal preeclampsia: a critical appraisal of 1800 consecutive preeclamptic cases.

OBJECTIVES: To present a comprehensive overview of different risk factors for early onset preeclampsia (<34 weeks gestation, EOP) vs. late onset (LOP). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 18.5 year-observational population-based cohort study (2001-2019). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. All consecutive singleton pregnancies (>21 weeks) compared with all preeclamptic pregnancies delivered in the south of Reunion island. MAIN OUTCOME MEASURES: Comparing risk factors between EOP and LOP. RESULTS: Among 1814 singleton preeclamptic pregnancies (600 EOP and 1214 LOP), EOP women were older than LOP 29.5 vs. 28.6 years, p = .009, primigravidas (OR 0.78 [0.63-0.96], p = .02) were prone to LOP. History of preeclampsia (PE) (aOR 12.8 vs. 7.1), chronic hypertension (aOR 6.5 vs. 4.5) had much higher adjusted odds ratios for EOP than for LOP, p < .001. Specific to EOP: coagulopathies (aOR 2.95, p = .04), stimulated pregnancies (aOR 3.9, p = .02). Specific to LOP: renal diseases (aOR 2.0, p = .05) and protective effect for smoking (aOR 0.75, p = .008). EOP women were prone to have a lower BMI. CONCLUSION: "Placental preeclampsia" (defective placentation) being linked to early onset PE (<34 weeks gestation) while "maternal preeclampsia" (maternal cardiovascular predisposition) being typically manifesting as the late form of the disease LOP is not systematically verified. Future researches are needed to propose a more adapted paradigm.Highlights  Risk factors for different preeclampsia phenotypes (early/late); challenging proposed models.

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.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

"Holding-Cuddling" and Sucrose for Pain Relief During Venepuncture in Newborn Infants: A Randomized, Controlled Trial (CÂSA).

Objectives: Oral sucrose is commonly used to provide analgesia to neonates during painful procedures, such as venepuncture. The additional benefits of reducing pain during venepuncture when oral sucrose is combined with nonpharmacological strategies have not been extensively studied. This randomized controlled trial compared the efficacy of oral sucrose with nonnutritive sucking vs. oral sucrose with nonnutritive sucking plus "holding-cuddling" for pain management during venepuncture in term infants from birth to 3 months of life. Methods: Seventy-eight infants were equally randomized to receive 24% oral sucrose with nonnutritive sucking (control group) or 24% oral sucrose with nonnutritive sucking plus "holding-cuddling" (being held in a secure, cuddling position; experimental group) before venepuncture. Behavioral response to pain was measured by the 0-10 ranking scale "acute pain for neonates (APN)" at 30 and 60 s after venepuncture. Results: Within the study sample, APN scores were ≥ 2 for 32/68 (47%) infants. "Holding-cuddling" did not significantly reduce mean APN scores at 30 and 60 s, but the rate of infants experiencing a high pain score (APN ≥ 8) at 60 s after the venepuncture was significantly lower in the experimental group compared to controls [4/34 vs. 12/34 (p = 0.04)]. Conclusions: Venepuncture is a painful procedure in newborn and young infants. The implementation of behavioral strategies in association with oral sucrose may mitigate pain during this procedure. Clinical Trial Registration: This trial was registered at http://clinicaltrials.gov/ (NCT number 02803723).

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.