2017 French health authority guidelines for neonates at risk of early-onset sepsis: Adherence and barriers in a tertiary hospital.

The objective of this study was to evaluate the adherence to the French Health Authority's 2017 guidelines concerning early-onset sepsis (EOS) in neonates. This 6-month prospective observational study was conducted in 2020 in a tertiary hospital maternity unit. Neonates were classified according to their risk of EOS and the level of appropriate surveillance was analyzed. The risk of EOS was determined for 69.9% of the 1024 included neonates. Of the 123 neonates with a moderate or high risk of EOS, the optimal clinical surveillance was 88%. Even in a tertiary hospital, with training of caregivers, adherence to guidelines was incomplete. Some corrective measures are suggested and should be applied to enhance the adherence.

[Revelation of the circumstances of the accident vascular arterial ischemic brain in at term or near-term and referral]. / Circonstances de révélation de l'accident vasculaire cérébral ischémique artériel chez le nouveau-né à terme ou proche du terme et orientation des patients.

The neonatal arterial ischemic stroke is an emergency. Recurrent focal seizures, generally occurring in the first 24-72 hours after birth, are the commonest first clinical signs. When neonatal arterial ischemic stroke is suspected, optimal initial management involves careful supportive care including treatment of clinical and frequent or prolonged subclinical seizures, correction of the possible metabolic disorders and their prevention. Contrary to hypoxic ischemic encephalopathy, therapeutic hypothermia is not indicated. This newborn requires emergent transfer to a neonatal intensive care unit for the confirmation of the diagnosis by means of a specialized neonatal transport team.

[Neonatal hyperthyroidism: A sometimes challenging diagnosis]. / L'hyperthyroïdie néonatale : un diagnostic parfois difficile.

Graves disease complicates two pregnancies out of 1000 and when it is known before pregnancy, it warrants careful monitoring of the fetus and the newborn. We report on a case of neonatal hyperthyroidism, which revealed a previously unknown maternal thyroid disease. In this situation, neonatal signs can be misinterpreted, delaying the diagnosis. Neonatal hyperthyroidism is, however, a therapeutic emergency because of the risk of cardiac and neurological complications. The neonatologist must identify thyroid disease in the absence of a maternal history in order to promptly start therapy.

[Neonatal arterial ischemic stroke: Review of the current guidelines]. / Accidents vasculaires cérébraux ischémiques artériels néonatals : synthèse des recommandations.

Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended.

Mammary herpes: a little known mode of neonatal herpes contamination.

Neonatal herpes is a severe disease. We report a case with a fatal outcome, whose transmission was linked to mammary herpes. The lack of early diagnosis delayed appropriate therapeutic management. The purpose of this report is to alert clinicians to this potential mode of transmission.

Influence of hypothermia on the prognostic value of early EEG in full-term neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: To determine the prognostic value of early electroencephalograms (EEG) in full-term neonates suffering from hypoxic ischemic encephalopathy (HIE) exposed to whole-body hypothermia (cooled group), compared to neonates treated conventionally (control group). METHODS: The study included all term neonates born at Grenoble Hospital between 2000 and 2006 with symptoms of HIE. The first two EEGs were reviewed retrospectively and classified according to current electrophysiological criteria. In the cooled group, EEGs were recorded with a mean body temperature of 33°C. Neurological outcome was correlated with EEG pattern. RESULTS: An EEG inactive or paroxysmal pattern was associated with death in 60% of the controls, while all survivors had neurological sequels. In the cooled group, this EEG pattern was only predictive of death in 40% while survivors had normal examination at 1 year of age. Mild abnormalities on the first EEG correlated with a good prognosis in both groups. The second EEG had a high predictive value, particularly in the cooled group. Persistence of inactivity at 3 days after birth was always associated with death. CONCLUSIONS: After HIE, the first two EEGs are good prognostic indicators, also in the cooled group. Strong discontinuity in the EEG observed on the first hours after hypothermia induction can be associated with a good outcome. SIGNIFICANCE: Early Stage 4 EEGs recorded during the hypothermia may not always indicate a poor prognosis in HIE.

[Are mydriatic eyedrops dangerous for pre-term infants?]. / Les collyres mydriatiques sont-ils dangereux chez le nouveau-né prématuré ?

The funduscopic examination is essential in neonatology to screen for retinopathy in the pre-term infant. Mydriatic eyedrops, which are used for this examination, are known to induce digestive side effects. We present a case of necrotizing enterocolitis developing in a pre-term infant as a complication of mydriatics. This infant was a girl born at 28 weeks gestation and 5 days, with Down's syndrome, who died on the 44th day of life, due to necrotizing enterocolitis, after instillation of 1 drop of atropine 0.3% in each eye. The chronology of events, the application method, and the clinical symptoms of atropine impregnation argue in favor of a causal relationship between atropine and necrotizing enterocolitis. The review of the literature made on the basis of this observation shows that side effects of mydriatic eyedrops are frequent in pre-term infants and raise the question of atropine hypersensitivity in pre-term infants with Down's syndrome.

Novel mutations in pyridoxine-dependent epilepsy.

PURPOSE: Pyridoxine-Dependent Epilepsy (PDE) is a rare autosomal recessive disease with neonatal seizures resistant to conventional anti-epileptic drugs. This metabolic disease has to be diagnosed early and treated to improve outcome. We report on two new mutations that open new prenatal prospects and suggest a new diagnostic procedure. CASE REPORT: We describe PDE in a neonate carrying two novel mutations in the ALDH7A1 gene: c.[852_856delCTTAG] + [1230C > A]; p.[(Phe410Leu)] + p.[(Leu285CysfsX26)]. This case also illustrates that diagnosis could have been made without any pyridoxine withdrawal, thanks to the measurement of biomarkers. The patient was successfully treated with pyridoxine supplementation and currently shows normal neurological development.

[Assessment of a hypothermia protocol implementation for hypoxic-ischemic encephalopathy in term newborns]. / Évaluation d'un protocole de prise en charge de l'encéphalopathie anoxo-ischémique du nouveau-né par hypothermie.

BACKGROUND: A whole-body hypothermia protocol for term infants with hypoxic-ischemic encephalopathy (HIE) was implemented in our network in May 2004. The main objective of this study was to assess the feasibility of the protocol. The impact on the outcome was also assessed. METHODS: Monocentric retrospective study of all term infants admitted for HIE after the implementation of the protocol. The feasibility of the protocol was evaluated by its observance during the first 72 h. The neurodevelopmental outcome at 12 months of age of this population was compared with a historical control group. RESULTS: Twenty-five children were included. The protocol was not correctly applied for 8 children. The target temperature (33-34°C) was not reached for 3 infants. Four infants were admitted after 6h of age. In 1 infant, HIE was not diagnosed at admission. In the 17 patients with a good protocol observance, rectal temperature fell to the target temperature on average at 6.4h of age. The long-term follow-up rate was improved after the implementation of the protocol (100 % versus 92 % before protocol implementation). Death or neurodevelopmental disability occurred in 40 % during the protocol period versus 87 % before protocol implementation (p<0.01). CONCLUSIONS: The main limiting factor for implementation of whole-body hypothermia in infants with HIE is admission delay. The follow-up and the rate of death or disability in infants with HIE improved after implementing the protocol.

[Pseudo-"isolated" intestinal perforation in a very low birth weight infant: exceptional presentation of Hirschsprung's disease]. / Perforation intestinale du grand prématuré en apparence "isolée": mode de révélation exceptionnel de la maladie de Hirschsprung.

Intestinal perforations in preterm newborn are characterized with high morbidity and mortality rates. They often are associated with necrotizing enterocolitis and seldom correspond to idiopathic spontaneous intestinal perforation. Perforations upstream of an intestinal organic obstruction (atresia), or of a functionnal obstruction (meconium-ileus, Hirschsprung disease) have been considered to be rare in preterm newborns. We report a case of caecal perforation with a pneumoperitoneum which occurred at 5 days of life, in a 28-week gestational age infant, that was treated by cecostomy. There were no signs of necrotizing enterocolitis. At 43 days of life, the preoperative contrast enema study revealed a left colon transition zone, suggesting a Hirschsprung disease, which was confirmed by rectal biopsies. Transanal pull-through was performed. There were no postoperative complication. This case demonstrates that an isolated intestinal perforation in very preterm newborn can reveal a Hirschsprung disease, especially if it occurs in the caecum.

[Subcutaneous fat necrosis in the newborn: a risk for severe hypercalcemia]. / Cytostéatonécrose néonatale: attention à l'hypercalcémie sévère.

Hypercalcemia associated with subcutaneous fat necrosis (SCN) is a well known but rare event in the newborn. A newborn infant with a history of SCN was admitted because of anorexia, adynamia, polyuria and polydipsia at 6 weeks of age. Serum calcium was markedly increased on admission, while it was normal on the first day of life. Evolution was favourable after treatment including isotonic saline solution, furosemide, corticosteroids, calcitonin and a low calcium and vitamin D diet. Hypercalcemia was severe enough to potentially induces fatal complications in this case. Neonates who develop skin lesions consistent with SCN should be followed-up for possible onset of hypercalcemia and treated in due time. The treatment of hypercalcemia in SCN is reviewed.

[Ruptured mycotic aneurysm with hemoperitoneum: an unusual septic complication of umbilical arterial catheter]. / Anévrisme mycotique rompu avec hémopéritoine: complication septique inhabituelle d'un cathéter artériel ombilical.

Arterial aneurysms are rare in infants and are usually associated with cardiovascular malformations or connective tissue disorders. Mycotic aneurysms of the aorta or its major branches have been described in newborn infants with septicemia originating from an indwelling umbilical artery catheter. We report a case of a newborn infant with a mycotic aneurysm complicated by massive hemoperitoneum. Surgical treatment allowed a complete recovery. Newborn infants with Staphylococcus aureus bacteremia in the context of a current or recent umbilical artery catheterisation should be followed up closely to detect arterial aneurysms.

[Septic shock due to congenital disseminated toxoplasmosis?]. / Toxoplasmose congénitale disséminée responsable d'un choc septique?

Congenital toxoplasmosis secondary to maternal primary infection acquired late during pregnancy is generally asymptomatic at birth. We report a case of a newborn infant whose mother had been infected between the 27th and the 33rd week of gestation. No treatment had been given during gestation. The infant had a disseminated form of toxoplasmosis with hepatosplenomegaly, pneumonitis, purpura, hepatitis. On the third day of life, he developed shock. The patient died early despite therapy. Septic shock is unusual in congenital toxoplasmosis, although it has been described in immunocompromised patients, notably in patients infected with the human immunodeficiency virus.

Chronic oxygen dependency in infants born at less than 32 weeks' gestation: incidence and risk factors.

OBJECTIVE: To assess incidence and clinical risk factors of chronic oxygen dependency (COD) among survivors who were born at or before 31 weeks' gestation. METHODS: This prospective, multicenter study enrolled 802 infants who were born at or before 31 weeks' gestation and admitted to 8 level III neonatal intensive care units in northern and eastern France from January 1 through December 31, 1997. Need for oxygen to maintain oxygen saturation between 92% and 96% was assessed at 28 days of life and at 36 and 42 weeks' postconceptional age (PCA). Stepwise logistic regression analysis was used to identify the incidence of COD and the risk factors related to its occurrence. RESULTS: The mortality rate was 14%. Antenatal corticotherapy was administered to 51% of patients, surfactant therapy to 76% of the ventilated patients, and high-frequency oscillatory ventilation at day 1 to 32%. At 28 days and 36 and 42 weeks' PCA, respectively, 25%, 15%, and 6% of survivors had COD. After adjustment for intercenter variations, we identified the significant risk factors for COD at these dates: a low gestational age, a high score on the Clinical Risk Index for Infants, intrauterine growth restriction, and surfactant treatment. CONCLUSION: COD incidence was high at 28 days of life but decreased dramatically by 42 weeks' PCA. This study confirmed previously reported risk factors and underlined the importance of intrauterine growth restriction and the Clinical Risk Index for Infants as significant risk factors.

[Withdrawal syndromes of newborns of pregnant drug abusers maintained under methadone or high-dose buprenorphine: 246 cases]. / Syndromes de sevrage des nouveau-nés de mères toxicomanes substituées par la méthadone ou la buprénorphine haut dosage.

UNLABELLED: Perinatal prognosis of pregnant drug abusers is better with intensive prenatal care and substitution maintenance programs. There is a large body of data in the literature on methadone (MTD), but very little on high-dose buprenorphine (HDB). The objective of this study was to compare 2 groups of pregnant women maintained on MTD or HDB for perinatal events. STUDY DESIGN: Prospective multicentric study; all neonates (NN) whose mothers has been maintained during pregnancy on MTD or HDB were included by 34 French perinatal centers with specialized staff for care of these pregnant drug abusers. RESULTS: Two hundred and forty-six pregnant women were included: 93 (38%) MTD and 153 (62%) HDB. Social and perinatal data, prenatal care and factors correlated with poor prenatal care are reported. Forty-six percent of the pregnant women had good prenatal care; 88% had peridural analgesia; mean birthweight=2838g; mean gestational age=38.7 weeks; prematurity<37 weeks=13; intra-uterine growth retardation=32%. Sixty-five percent neonates had withdrawal neonatal syndrome (WNNS) at a mean age of beginning at H40, mean highest Lipsitz score was 8.2 at H78. Half of the neonates with WNNS received treatment, mainly with morphine chlorhydrate. Neonatal mortality was 0/246. Discharge of the neonates was 60% with their father and their mother, and 32% with their mother alone; 4% were placed in foster homes by judicial decision. The only statistically significant differences between the MTD and HDB groups were: maintenance program was more frequently initiated before this pregnancy for the HDB vs MTD group (p<0.03); MTD maintenance was more often supervised by maintenance specialized centers and HDB by general practitioners (p<0.001); prematurity was 18% for MTD group vs 9% for HDB group (p<0.04); mean age of maximum Lipsitz score was H92 for MTD group vs H70 for HDB group (p<0.001). CONCLUSIONS: The perinatal medical and social prognosis of these 246 pregnant drug abusers and of their neonates appeared to be improved by the specialized prenatal care, comparatively with literature data. Perinatal impact of substitution program during pregnancy would be similar with MTD or HDB.

Effects of inhaled nitric oxide on gas exchange and acute lung injury in premature lambs with moderate hyaline membrane disease.

OBJECTIVE: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). METHODS: Fifteen moderately premature lambs (128 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. RESULTS: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41+/-0.96 vs. 5.46+/-1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09+/-1.51 in the NO-treated group vs. 4.08+/-1.93 in the control group; P<0.05). CONCLUSIONS: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated.

[Constitutional deficiency of pulmonary surfactant protein B: clinical presentation, histologic and molecular diagnosis]. / Déficit constitutionnel en protéine B du surfactant pulmonaire: présentation clinique, diagnostic histologique et moléculaire.

We report a female full-term infant with fatal respiratory failure of early onset due to inherited SP-B deficiency. Lung biopsy was performed at 18 days after birth, with histopathological characterization indicating congenital alveolar proteinosis. Immunohistochemical studies of lung tissue revealed the absence of SP-B and the presence of intra-alveolar SP-A normal quantities. Analysis of genomic DNA showed homozygosity for the 121ins2 mutation of the SFTPB gene. The infant died 21 days after birth. Both parents were heterozygotes for the mutation. Chorionic villus sampling was performed at the first trimester of the following pregnancy. Restriction analysis of amplified fetal DNA, studies of microsatellite segregation and direct sequencing led to the diagnosis of homozygosity for the parental wild-type allele. The diagnosis of congenital SP-B deficiency should be suspected whenever an early and acute respiratory failure in a term or near-term infant does not resolve after five days of age: diagnostic confirmation can be easily and rapidly obtained with the analysis of genomic DNA and immunohistochemical characterization of lung tissue.

[Cerebral agyria-pachygyria in a child with Werdnig-Hoffmann disease]. / Agyrie-pachygyrie cérébrale chez un enfant atteint d'une maladie de Werdnig-Hoffmann.

Werdnig-Hoffmann disease refers to the severe infantile form of anterior horn cell degeneration. We report an association between Werdnig-Hoffmann disease and agyria-pachygyria. Examples of anterior horn cell disease with lesions in the central nervous system (notably thalamus and cerebellum) have been considered unusual "variants" of Werdnig-Hoffmann disease. This association between Werdnig-Hoffmann disease and agyria-pachygyria has, to our knowledge, never been described.