An educational programme in neonatal intensive care units (SEPREVEN): a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed. METHODS: In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609. FINDINGS: Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65 830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048). INTERPRETATION: A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates. FUNDING: Solidarity and Health Ministry, France.

Clinical Value of Serial Quantitative Analysis of Cytomegalovirus DNA in Blood and Saliva Over the First 24 Months of Life in Congenital Infection: The French Cymepedia Cohort.

OBJECTIVE: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first 2 years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications. STUDY DESIGN: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for 2 years. Whole blood and saliva were collected at inclusion and months 4 and 12, and saliva at months 18 and 24. Real-time CMV polymerase chain reaction (PCR) was performed, results expressed as log10 IU/mL in blood and in copies per milliliter in saliva. RESULTS: Viral load in saliva progressively decreased from 7.5 log10 at birth to 3.3 log10 at month 24. CMV PCR in saliva was positive in 100% and 96% of infants at 6 and 12 months, respectively. In the first month of life, neonatal saliva viral load of less than 5 log10 was related to a late CMV transplacental passage. Detection in blood was positive in 92% of neonates (147/159) in the first month of life. No viral load threshold values in blood or saliva could be associated with a high risk of sequelae. Neonatal blood viral load of less than 3 log10 IU/mL had a 100% negative predictive value for long-term sequelae. CONCLUSIONS: Viral loads in blood and saliva by CMV PCR testing in congenital infection fall over the first 24 months. In this study of infants affected mainly after primary maternal infection during pregnancy, all salivary samples were positive in the first 6 months of life and sequelae were not seen in infants with neonatal blood viral load of less than 3 log10 IU/mL.

Very preterm infants displayed similar imitation skills to full-term infants at term equivalent age.

AIM: Very preterm infants are exposed to an atypical environment that could alter their developmental trajectory. We aimed to examine neonatal imitation, a foundation of social cognition, in very preterm and full-term infants. METHODS: In Strasbourg, France, between 2015 and 2018, we prospectively investigated the development of imitation skills. Very preterm (27 to 33 weeks of gestational age, n = 20) and full-term infants (n = 20) were enrolled using four gestures: tongue protrusion, mouth opening, sequential finger movements and hand movements. All testing were performed in infants at term-equivalent age. Two independent and blinded observers coded the behaviour of each infant on video recording. Facial expressions or hand movements, similar to the one presented, were quantified and classified according to their timing. RESULTS: A total of 37 out of 40 infants imitated at least one gesture. The very preterm and term infants did not differ in the presence of imitation or its timing for the four gestures tested. The very preterm infants displayed more imitation abilities for sequential finger movement. Tongue protrusion and sequential finger movement were the particularly strong imitated gesture in both groups. CONCLUSION: These findings are the first to show similar neonatal imitation in term and very preterm infants. Our results may support early parent-infant social interactions.

Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.

BACKGROUND: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. METHODS: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. RESULTS: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001). CONCLUSIONS: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

Observational study found that even small variations in light can wake up very preterm infants in a neonatal intensive care unit.

AIM: This prospective observational study evaluated the behavioural responses of very preterm infants to spontaneous light variations. METHODS: We measured spontaneous light variations in the incubators of 27 very preterm infants, with a median gestational age of 28 weeks (range 26-31 weeks), over 10 hours. All of them had been admitted to the neonatal care unit of the Strasbourg University Hospital, France, between April 2008 and July 2009. Two independent raters examined changes in the infants' behavioural states using video recordings. The percentage of awakenings was recorded when there were light variations and during control periods with no changes. RESULTS: We analysed 275 periods following light variations and 275 control periods. The overall percentage of awakenings was greater during periods following a change in light than during control periods (16.3% vs 11%, p = 0.03). The extent of light protection affected the percentage of awakenings. In mild light protection, there were more awakenings following changes in light than in control periods (25.6% vs 6.7%, p = 0.01). This difference was not found in high light protection. CONCLUSION: Very preterm infants can be woken up by small variations in light, when the light protection in their incubator is insufficient.

Simultaneous primary invasive cutaneous aspergillosis in two preterm twins: case report and review of the literature.

BACKGROUND: Primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. Newborns of very low birth weight present a high risk for this type of infection due to an immaturity of the cutaneous barrier and of the immune system. CASE PRESENTATION: We describe here a case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two male preterm bichorionic biamniotic twins (A & B) were born at a general hospital by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were transferred to our hospital where they receive surfactant, antibiotics and hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical region. The spectrum of antibiotic therapy was broadened and fluconazole was added. The umbilical catheters of the two twins were removed and replaced by epicutaneo-cava venous catheters and the cultures were positive for Aspergillus fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and the incubators were changed. The serum galactomannan was also positive for both twins. At day 10, yellowish lesions appeared in the abdominal region in twin B. He died on day 18 following complications related to his prematurity. Concerning the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B was stopped 1 week later, with a relay by econazole (cream). His condition improved and on day 66 he was transferred for follow-up at the general hospital where he was born. CONCLUSION: The source of contamination by A. fumigatus was not identified, but other similar cases from the literature include construction work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin fragility of preterm newborns is an excellent potential entry point for environmental fungal infections. These cases highlight the importance of suspecting primary cutaneous aspergillosis in extremely low birth weight neonates with rapidly progressive necrotic lesions.

Very preterm infants can detect small variations in light levels in incubators.

AIM: This prospective observational study was designed to improve our understanding of the responses of very preterm infants to light level variations in incubators and to evaluate what determined those reactions. METHODS: The physiological responses of 27 very preterm infants were analysed following variations in the light level environments of their incubators over 10 hours. Heart and respiratory rates, systemic oxygen saturation and regional cerebral oxygen saturations were recorded using near-infrared spectroscopy, and the variation of each parameter was analysed. RESULTS: We analysed 332 light level changes. Heart rate increased by 3.8 beats per minute (range -2.6 to 12.6), respiratory rate by six cycles per minute (-1.5 to 26) and regional cerebral oxygen saturation by 1.1% (-0.5% to 3.9%) (p < 0.05 each) when delta lux was over 50. Only respiratory rate decreased significantly, by -8.4 cycles per minute (-28 to -0.4), when delta lux was 50 or lower (p < 0.05). The initial level of illumination altered the very preterm infants' responses, with higher reactivity for higher ambient light levels. CONCLUSION: Very preterm infants reacted to moderate variations in illumination in their incubator, within recommended ranges of light levels, suggesting that they may detect even small light level variations.

Neural tube defects: the experience of the registry of congenital malformations of Alsace, France, 1995-2009.

CONTEXT AND OBJECTIVE: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). METHODS: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. RESULTS: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). CONCLUSION: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

Supraclavicular ultrasound-guided catheterization of the subclavian vein in pediatric and neonatal ICUs: a feasibility study.

OBJECTIVES: To assess the feasibility of ultrasound-guided supraclavicular catheterization of the subclavian vein in pediatric and neonatal ICU. DESIGN: Retrospective cohort. SETTING: Ten-bed pediatric medicosurgical ICU and 15-bed neonatal ICU. PATIENTS: Children and newborns undergoing supraclavicular ultrasound-guided subclavian vein catheterization from March 2010 to September 2010. MEASUREMENTS: The placement of central venous catheter in ICU was carried out either by one of the experts in ultrasound-guided puncture of the unit or by a novice completely supervised by the expert. The success and the early complications were recorded. A comparison between novice and expert operators was also made. RESULTS: Forty-two catheters were placed in 40 children. The median age and median weight were, respectively, 6.5 months and 6.5 kg. The success rate was 97.6% (one failure) and the early complication rate was 4.7% (one pneumothorax and one arterial puncture); 61% of children breathed spontaneously during the catheter placement. No significant difference was found between expert and novice operators. CONCLUSIONS: Supraclavicular ultrasound-guided catheterization of the subclavian vein in pediatric and neonatal ICU seems to be a promising technique in the context of emergency. It is safe, reliable, with few early complications. Furthermore, it does not compromise the airways of the patient owing to the low level of sedation needed for its placement.

Moderate acoustic changes can disrupt the sleep of very preterm infants in their incubators.

AIM: To evaluate the impact of moderate noise on the sleep of very early preterm infants (VPI). METHODS: Observational study of 26 VPI of 26-31 weeks' gestation, with prospective measurements of sound pressure level and concomitant video records. Sound peaks were identified and classified according to their signal-to-noise ratio (SNR) above background noise. Prechtl's arousal states during sound peaks were assessed by two observers blinded to the purpose of the study. Changes in sleep/arousal states following sound peaks were compared with spontaneous changes during randomly selected periods without sound peaks. RESULTS: We identified 598 isolated sound peaks (5 ≤ SNR < 10 decibel slow response A (dBA), n = 518; 10 ≤ SNR < 15 dBA, n = 80) during sleep. Awakenings were observed during 33.8% (95% CI, 24-43.7%) of exposures to sound peaks of 5-10 dBA SNR and 39.7% (95% CI, 26-53.3%) of exposures to sound peaks of SNR 10-15 dBA, but only 11.7% (95% CI, 6.2-17.1%) of control periods. The proportions of awakenings following sound peaks were higher than the proportions of arousals during control periods (p < 0.005). CONCLUSIONS: Moderate acoustic changes can disrupt the sleep of VPI, and efficient sound abatement measures are needed.

Safety and effectiveness of skin-to-skin contact in the NICU to support neurodevelopment in vulnerable preterm infants.

Skin-to-skin contact (SSC) is a cornerstone of neurodevelopmentally supportive and family-oriented care for very low-birth-weight preterm infants (VPIs). However, performing SSC with unstable and/or ventilated VPIs remains challenging for caregiving teams and/or controversial in the literature. We first aimed to assess the safety and effectiveness of SSC with vulnerable VPIs in a neonatal intensive care unit over 12 months. Our second aim was to evaluate the impact of the respiratory support (intubation or not) and of the infant's weight (above or below 1000 g) on the effects of SSC. Vital signs, body temperature, and oxygen requirement data were prospectively recorded by each infant's nurse before (baseline), during (3 time points), and after their first or first 2 SSC episodes. We compared the variations of each parameter from baseline (analysis of variance for repeated measures with post hoc analysis when appropriate). We studied 141 SSCs in 96 VPIs of 28 (24-33) weeks' gestational age, at 12 (0-55) days of postnatal age, and at a postmenstrual age of 30.5 (±1.5) weeks. During SSC, there were statistically significant increases in oxygen saturation (Sao2) (P < .001) with decreases in oxygen requirement (P = .043), a decrease in heart rate toward stability (P < .01) but a transient and moderate decrease in mean axillary temperature following the transfer from bed to mother (P < .05). Apneas/bradycardias requiring minor intervention occurred in 19 (13%) SSCs, without need for SSC termination. These variations were similar for intubated newborns (18%) as compared with newborns on nasal continuous positive airway pressure (52%) or breathing room air (30%). However, ventilated infants exhibited a significant increase in transcutaneous partial pressure of carbon dioxide (TcPco2) (P = .01), although remaining in a clinically acceptable range, and a greater decrease in oxygen requirements during SSC (P < .001) than nonventilated infants. Skin-to-skin contact in the neonatal intensive care unit seems safe and effective even in ventilated VPIs. Recording physiologic data of infants before, during, and after SCC provides data needed to secure changes of practice in SCC.

Adequacy of sedation analgesia to support the comfort of neonates undergoing therapeutic hypothermia and its impact on short-term neonatal outcomes.

Objectives: We aimed to evaluate (1) whether sedation analgesia (SA) used during therapeutic hypothermia (TH) was efficient to support the wellbeing of neonates with hypoxic-ischemic encephalopathy, (2) the SA level and its adjustment to clinical pain scores, and (3) the impact of inadequate SA on short-term neonatal outcomes evaluated at discharge. Methods: This was an observational retrospective study performed between 2011 and 2018 in two level III centers in Alsace, France. We analyzed the wellbeing of infants by using the COMFORT-Behavior (COMFORT-B) clinical score and SA level during TH, according to which we classified infants into four groups: those with excess SA, adequate SA, lack of SA, and variability of SA. We analyzed the variations in doses of SA and their justification. We also determined the impact of inadequate SA on neonatal outcomes at discharge by multivariate analyses with multinomial regression, with adequate SA as the reference. Results: A total of 110 patients were included, 89 from Strasbourg university hospital and 21 from Mulhouse hospital. The COMFORT-B score was assessed 95.5% of the time. Lack of SA was mainly found on the first day of TH (15/110, 14%). In all, 62 of 110 (57%) infants were in excess of SA over the entire duration of TH. Most dose variations were related to clinical pain scores. Inadequate SA was associated with negative short-term consequences. Infants with excess of SA had a longer duration of mechanical ventilation [mean ratio 1.46, 95% confidence interval (CI), 1.13-1.89, p = 0.005] and higher incidence of abnormal neurological examination at discharge (odds ratio 2.61, 95% CI, 1.10-6.18, p = 0.029) than infants with adequate SA. Discussion: Adequate SA was not easy to achieve during TH. Close and regular monitoring of SA level may help achieve adequate SA. Excess of SA can be harmful for newborns with hypoxic-ischemic encephalopathy who are undergoing TH.

Infants born very preterm react to variations of the acoustic environment in their incubator from a minimum signal-to-noise ratio threshold of 5 to 10 dBA.

INTRODUCTION: Very early preterm infants (VPIs) are exposed to unpredictable noise in neonatal intensive care units. Their ability to perceive moderate acoustic environmental changes has not been fully investigated. RESULTS: Physiological values of the 598 isolated sound peaks (SPs) that were 5-10 and 10-15 dB slow-response A (dBA) above background noise levels and that occurred during infants' sleep varied significantly, indicating that VPIs detect them. Exposure to 10-15 dBA SPs during active sleep significantly increased mean heart rate and decreased mean respiratory rate and mean systemic and cerebral oxygen saturations relative to baseline. DISCUSSION: VPIs are sensitive to changes in their nosocomial acoustic environment, with a minimal signal-to-noise ratio (SNR) threshold of 5-10 dBA. These acoustic changes can alter their well-being. METHODS: In this observational study, we evaluated their differential auditory sensitivity to sound-pressure level (SPL) increments below 70-75 dBA equivalent continuous level in their incubators. Environmental (SPL and audio recording), physiological, cerebral, and behavioral data were prospectively collected over 10 h in 26 VPIs (GA 28 (26-31) wk). SPs emerging from background noise levels were identified and newborns' arousal states at the time of SPs were determined. Changes in parameters were compared over 5-s periods between baseline and the 40 s following the SPs depending on their SNR thresholds above background noise.

Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics.

UNLABELLED: Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. CONCLUSION: Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.

Exploring the olfactory environment of premature newborns: a French survey of health care and cleaning products used in neonatal units.

AIM: To assess the main determinants of the newborn's nosocomial olfactory environment. METHODS: An electronic questionnaire was sent to 99 neonatal units in France. Senior nurses and/or physicians described the nature and use of skin care products (e.g. umbilical cord and skin disinfectants, adhesive removers), lubrications used for tubes positioning, disinfectants used to clean materials, hand hygiene products (e.g. alcohol-based hand rubs, soaps) and newborns' bath. RESULTS: Nine groups of products and 76 distinct commercial preparations were identified. Depending on their level of respiratory support, preterm newborns were estimated to be exposed to nosocomial odours (NO) an average of 1320-1800 times during their first month of life. During their whole hospital stay, newborns of 28 and 32 weeks of gestational age could be exposed to NOs products an average of 3448 and 2024 times, respectively. The use of these products varied among medical centres. Newborns were most frequently exposed to the odour of aqueous alcoholic solutions. CONCLUSIONS: Vulnerable preterm infants are daily exposed to multiple NOs most of them be considered as irritant for the nose. Minimizing infants' exposure to them would be beneficial. Future studies should describe the exact olfactory properties of the products considered essential for infant care and should assess their effects on the infant's well-being and development.

Raine syndrome: expanding the radiological spectrum.

We describe ante- and postnatal imaging of a 1-year-old otherwise healthy girl with Raine syndrome. She presented with neonatal respiratory distress related to a pyriform aperture stenosis, which was diagnosed on CT. Signs of chondrodysplasia punctata, sagittal vertebral clefting and intervertebral disc and renal calcifications were also found on imaging. This new case confirms that Raine syndrome is not always lethal. The overlapping imaging signs with chondrodysplasia punctata and the disseminated calcifications give new insights into its pathophysiology.

Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program.

Introduction: Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation. Objectives: The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center. Methods: All EPIs (<28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated. Results: We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (all p < 0.01). In addition, the first SSC was performed earlier (p = 0.03) and lasted longer (p < 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p = 0.02) and the time from birth to first extubation (p = 0.02), and an increase of weight gain at discharge (p = 0.02). Conclusion: NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.

Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

A severe case of Frank-ter Haar syndrome and literature review: Further delineation of the phenotypical spectrum.

Frank-ter Haar syndrome (FTHS) is a rare autosomal recessive syndrome resulting from mutations in the SH3PXD2B gene involved in the formation of podosomes and invadopodia which have a role in extracellular matrix remodelling and cell migration. FTHS is characterized by facial dysmorphism, megalocornea, inconstant glaucoma, variable developmental delay, skeletal and cardiac anomalies. To date, 40 patients have been reported in the literature with a clinical diagnosis of FTHS, only 20 patients having identified mutations. We present a review of these 20 reported patients and describe a patient born to non-consanguineous parents, with intrauterine growth retardation, hypotonia, congenital glaucoma, caudal appendix, scoliosis, camptodactyly, ventricular septal defect, thin corpus callosum and craniofacial features suggestive of FTHS. Clinical evolution resulted in buphthalmos worsening, coarsening of the facial features and respiratory failure leading to death at 4,5 months. Diagnosis was confirmed by the identification of a previously known homozygous mutation c.969delG, p.(Arg324Glyfs*19) in SH3PXD2B. This is the first description of very severe phenotype with lethal respiratory impairment in FTHS. Since very few patients are described in the literature, and 2 out of the 3 patients carrying the c.969delG mutation had a favourable clinical course, more cases are needed to better characterize the phenotype and understand the natural history of this syndrome. Furthermore, we hypothesize that the alteration of podosomes function could lead to a reduction of the extracellular matrix degradation and accumulation of the latter in the extracellular space, which might explain the coarsening of the facial features and the severe refractory glaucoma.