Local protocol helped to deliver vitamin D levels more accurately in preterm infants.

AIM: This study retrospectively evaluated the effectiveness and safety of a local hospital protocol of vitamin D supplementation for preterm infants, which was modified in 2016. METHODS: We focussed on 99 preterm infants born before 31 weeks of gestation and admitted to the neonatal intensive care unit at the Femme Mere Enfant Hospital, Bron, France, from 1 January to 31 December 2018. Calcium and urinary calcium were measured, and 25-hydroxy vitamin D (25(OH)D) levels were monitored monthly and supplementation was adjusted, with 50-120 nmol/L considered normal. The results are presented as medians and interquartile ranges. RESULTS: The infants were enrolled at a gestational age of 28.0 [26.9-29.1] weeks and birth weight of 960 [800-1160] g. When they were discharged at 37.3 [35.2-39.8] weeks, the overall 25(OH)D level was 98 [79-140] nmol/L: 4% had low levels, 63% had normal levels and 33% had high levels. Vitamin D supplementation was withdrawn for 60% more than one month before discharge. Rickets or fractures were not reported. CONCLUSION: The modified protocol limited underdosing and significant overdosing, but moderate hypervitaminosis D was still frequent. Urgent studies are needed to determine the optimal supplementation and clinical impact of 25(OH)D on comorbidities in preterm infants.

Review: Neonatal dialysis is technically feasible but ethical and global issues need to be addressed.

AIM: Our aim was to look at the technical, ethical and global issues related to neonatal dialysis. METHODS: We performed a PubMed research on manuscripts published from March 2010 to March 2020 and retrospectively reviewed all neonates who received dialysis in our French paediatric and neonatal intensive care units from April 2009 to March 2019. RESULTS: Dialysis is performed on neonates with pre-existing renal diseases, acute kidney injuries or inborn errors of metabolism. It is required in 0.5%-1% of neonates admitted to the neonatal intensive care units. Peritoneal dialysis and extracorporeal blood purification are both feasible, with more complications, but the results are close to those obtained in older infants, at least in children without multi-organ dysfunction. Novel haemodialysis machines are being evaluated. Ethical issues are a major concern. Multidisciplinary teams should consider associated comorbidities, risks of permanent end-stage renal disease and provide parents with full and neutral information. These should drive decisions about whether dialysis is in child's best interests. CONCLUSION: Neonatal dialysis is technically feasible, but ethically challenging, and short-term and long-term data remain limited. Prospective studies and dialysis registries would improve global management and quality of life of these patients at risk of chronic kidney disease.

Estimated Fetal Radiation Dose From 18 F-FDG PET/CT During the Second and Third Trimesters of Pregnancy.

PURPOSE: Data published in the literature concerning the doses received by fetuses exposed to a 18 F-FDG PET are reassuring but were obtained from small and heterogeneous cohorts, and very few data are available concerning the fetal dose received after exposure to both PET and CT. The present study aimed to estimate the fetal dose received following a PET/CT exposure using methods that include anthropomorphic phantoms of pregnant women applied on a large cohort. PATIENTS AND METHODS: This retrospective multicenter study included 18 pregnant patients in the second and third trimesters. For PET exposure, the fetal volume and mean concentration of radioactivity in the fetus were measured by manually drawing regions of interest. Those data, combined with the time-integrated activities of the fetus and the mother's organs, were entered into the OLINDA/EXM software 2.0 to assess the fetal dose due to PET exposure. To estimate the fetal dose received due to CT exposure, 2 softwares were used: CT-Expo (based on geometric phantom models of nonpregnant patients) and VirtualDose (using pregnant patient phantoms). RESULTS: The fetal dose exposure for PET/CT examination in the second trimester ranged from 5.7 to 15.8 mGy using CT-Expo (mean, 11.6 mGy) and from 5.1 to 11.6 mGy using VirtualDose (mean, 8.6 mGy). In the third trimester, it ranged from 7.9 to 16.6 mGy using CT-Expo (mean, 10.7 mGy) and from 6.1 to 10.7 mGy using VirtualDose (mean, 7.6 mGy). CONCLUSIONS: The estimated fetal doses were in the same range of those previously published and are well below the threshold for deterministic effects. Pregnancy does not constitute an absolute contraindication for a clinically justified hybrid 18 F-FDG PET/CT.

Neurodevelopmental Outcome at Two Years for Preterm Infants With Intraventricular Hemorrhage: A Case-Control Study.

BACKGROUND: High-grade intraventricular hemorrhage (IVH), including grade III and grade IV IVH, is known to impact neurodevelopmental outcome of preterm infants, but prognosis remains difficult to establish due to confounding factors and significant variations in the reported outcomes. The aim of this study was to compare the neurodevelopmental outcome of preterm infants with or without severe IVH. METHODS: A retrospective case-control study was conducted including preterm infants with gestational age <32 weeks hospitalized between 2009 and 2017 in a level III neonatal intensive care unit. This study included 73 cases with high-grade IVH and 73 controls who were matched to cases, based on the same gestational age, birth weight, sex, and year of birth. The neurodevelopmental outcome was compared at two years of age corrected for prematurity between cases and controls. Neurodevelopmental impairment was defined as cerebral palsy, hearing deficiency, visual impairment, or developmental delay. Multivariate analysis was used to identify whether high-grade IVH was an independent risk factor for neurodevelopmental impairment. RESULTS: In univariate analysis, high-grade IVH was associated with death or poor neurodevelopmental outcome at two years of age corrected for prematurity (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.93 to 57.8; P < 0.001), and this association remained significant after adjusting for confounding factors including neonatal infection and bronchopulmonary dysplasia in multivariate analysis (OR, 8.71; 95% CI, 2.48 to 38.09; P = 0.002). CONCLUSIONS: This study highlights the impact of high-grade IVH as an independent risk factor of poor neurodevelopmental outcomes in very preterm infants and suggests that early interventions could improve the prognosis of these infants.

Disinfection of incubators in neonatal intensive care units: impact of steam pulverization on bacterial colonization.

BACKGROUND: In neonatal intensive care units (NICUs), neonates requiring medical care after birth, including very vulnerable preterm infants, are housed in incubators. Previous studies have reported that the standard chemical disinfection measures used to disinfect these incubators are insufficient to eradicate contaminating bacteria, leading to a worrying infectious risk for preterm neonates. This study aimed to evaluate the efficacy of a disinfection method based on steam pulverization to eradicate the persistent bacterial contamination in such incubators. METHODS: In a tertiary NICU, 20 incubators were monitored qualitatively for bacterial contamination at five different sites (the rubber grommet, the left door handles, the temperature adjustment button, the mattress and the scale) using a culture method at three times: before and after steam pulverization then 24 h after turning on and housing a new neonate. Clinical data of neonates housed in each incubator were retrieved from the medical records to identify potential occurrence of late onset sepsis (LOS). RESULTS: Just after steam pulverization, only two incubators were free from bacteria. Before disinfection 87% of all the samples were contaminated compared to 61% after disinfection. After 24 h, the proportion of contaminated samples reached 85%. Mattresses and scales were the most frequently contaminated incubator sites with respectively 90% and 80% positive samples after disinfection compared to 100% and 90% before disinfection. Coagulase-negative staphylococci, Enterococcus, Enterobacteria and Bacillus resisted disinfection and were identified on respectively 90%, 20%, 5% and 45% of incubators just after disinfection. Three preterm neonates developed LOS after being housed in a disinfected incubator but the bacterial species involved have not been identified in their incubator after disinfection. In two cases, the bacterium had been isolated from the mattress 24 h after housing the infected patient. CONCLUSION: Steam pulverization is not sufficient to eradicate bacterial contamination of incubators. These results highlight the urgent need for an effective disinfection method, especially for mattresses that are in constant contact with patients. In parallel, new incubator designs and mattress protections must be developed.

Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study.

Despite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units, a reliable diagnosis remains difficult. This prospective, multicenter cohort study aimed to identify biomarkers early to rule out the diagnosis of LOS in 230 neonates ≥7 days of life with signs of suspected LOS. Blood levels of eleven protein biomarkers (PCT, IL-10, IL-6, NGAL, IP-10, PTX3, CD14, LBP, IL-27, gelsolin, and calprotectin) were measured. Patients received standard of care blinded to biomarker results, and an independent adjudication committee blinded to biomarker results assigned each patient to either infected, not infected, or unclassified groups. Performances of biomarkers were assessed considering a sensitivity of at least 0.898. The adjudication committee classified 22% of patients as infected and all of these received antibiotics. A total of 27% of the not infected group also received antibiotics. The best biomarkers alone were IL-6, IL-10, and NGAL with an area under the curve (95% confidence interval) of 0.864 (0.798-0.929), 0.845 (0.777-0.914), and 0.829 (0.760-0.898), respectively. The best combinations of up to four biomarkers were PCT/IL-10, PTX3/NGAL, and PTX3/NGAL/gelsolin. The best models of biomarkers could have identified not infected patients early on and avoided up to 64% of unjustified antibiotics. At the onset of clinical suspicion of LOS, additional biomarkers could help the clinician in identifying non-infected patients.

Reference values for the external genitalia of full-term and pre-term female neonates.

BACKGROUND AND OBJECTIVES: Identifying virilisation of the genitalia in female newborns early during the neonatal period is important to diagnose pathologies. However, there is no clear threshold for clitoromegaly or for the anogenital ratio. The objective of this study was to define reference values for the external genitalia of full-term and pre-term female neonates. DESIGN: This was a prospective study of all females born in the study centre between May 2014 and July 2016. Clitoral length and anogenital ratio were measured in 619 newborns with a gestational age of 24+2 to 41+3 weeks during their first 3 days of life. Associations between the values at day 3 and gestational age, birth weight and other newborn characteristics were examined by linear regression. RESULTS: The mean clitoral length at day 3 of life was 3.69±1.53 mm (n=551; 95th percentile, 6.5 mm; maximum, 8 mm), and the mean anogenital ratio was 0.42±0.09 (95th percentile, 0.58). There was no significant variation with gestational age or birth weight, and no significant difference between the results at day 0 and day 3. CONCLUSION: These results suggest that clitoromegaly can be defined as a clitoral length >6.5 mm. Values ≥8 mm should prompt further investigations. An anogenital ratio >0.6 should be considered a sign of virilisation. Since clitoral size does not vary with gestational age or birth weight, clitoromegaly should not be attributed to prematurity.

Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR).

INTRODUCTION: Apnoea affects 85% of premature infants under 34 weeks of age and would be an important risk factor for subsequent neuropsychological disorders. Currently, premature children with life-threatening apnoeas receive stimulants such as methylxanthines (mainly, caffeine) or doxapram (an analeptic unlicensed in children under 15). However, these products have undesirable effects (hyperarousal, irritability, sleep disorders, tachycardia) and are not always effective because apnoea does persist in some premature newborns. Previous studies have indicated that odorant stimulation, a non-invasive intervention, may stimulate the respiratory rhythm. The objective of the present protocol is to reduce the occurrence of apnoeic episodes in premature newborns by controlled odorant stimulation added to current pharmacological treatments. METHODS AND ANALYSIS: The project is a randomised open-label Latin-square trial with independent evaluation of the main endpoint. It will include 60 preterm neonates from two university hospital neonatal intensive care units over 2 years (2021-2023). Each newborn will receive no (S0), sham (S1) or real olfactory stimulation (S2) in random order. During S2, three distinct odorants (mint, grapefruit and vanilla) will be delivered successively, in puffs, over 24 hours. Mint and grapefruit odours stimulate the main and the trigeminal olfactory pathways, whereas vanilla odour stimulates only the main olfactory pathway. A statistical analysis will compare the incidence of apnoeic episodes during S1 versus S2 using a mixed effects Poisson model. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Île-de-France XI (# 2017-AO13-50-53). The results will be disseminated through various scientific meetings, specialised peer-reviewed journals and, whenever possible, posted on appropriate public websites. TRIAL REGISTRATION NUMBER: NCT02851979; Pre-results.

Role of Endoscopic Third Ventriculostomy in the Management of Myelomeningocele-Related Hydrocephalus: A Retrospective Study in a Single French Institution.

INTRODUCTION: Treatment of hydrocephalus related to myelomeningocele (MM) is debated. Endoscopic third ventriculostomy (ETV) has been proposed with contrasting results. We report our experience in the management of hydrocephalus related to MM and the advantages of ETV. MATERIAL AND METHODS: From 1994 to 2012, we treated 97 patients with MM. Seventy patients developed a hydrocephalus needing a surgical treatment. Three types of procedures were used: ETV with concomitant choroid plexus coagulation (CPC), ETV with concomitant ventriculoperitoneal shunt (VPS), or VPS. RESULTS: Thirty-two patients had an ETV with CPC, 20 patients had an ETV and a concomitant VPS, and 18 patients had a VPS. No perioperative complications were reported. Fifty-two patients underwent an ETV. The overall success rate of ETV was approximately 70%. DISCUSSION: VPS in patients with MM leads to complications. Two common arguments are reported against ETV. The first is the variability of the anatomy of the ventricle leading to possible operative complications. The second is the immaturity of the Pacchioni granulations. For us, the modified anatomy does not prevent performing ETV. Regarding the issue of cerebrospinal fluid absorption in failed ETV, the adjunction of a shunt helps to control hydrocephalus until the maturation of the Pacchioni system. CONCLUSIONS: Preoperative imaging helps the surgical decision to predict in which patients the ETV can be realized without risks. ETV in patients with MM is a secure procedure with low rates of failure and no mortality, and it reduces the rate of shunt implantation.