[Moderate hypoglycemia in the preterm infant: is it relevant?]. / Les hypoglycémies modérées de l'enfant né prématurément: est-ce vraiment important?

Glucose monitoring and management of hypoglycaemia in preterm infants remain controversial. However, recent animal studies have shown that hypoglycaemia is associated to increased generation of reactive oxygen and nitrogen species, to inhibition of cellular maturation and to apoptosis in brain. Despite potential consequences of hypoglycaemia on brain development in preterm infants, only few studies are available on this topic. Available clinical studies on neurological development of hypoglycaemic preterm infants are not conclusive but suggest detrimental effect of repeated mild hypoglycaemia on brain development. Both experimental and clinical arguments are sufficient to mind to this problem with great awareness. Therefore, routine repeated measurements of blood glucose concentration are necessary and active intervention is proposed if glucose plasma level decreases below 2.5 mmol/l.

Prenatal exposure to cigarettes in infants with obstructive sleep apneas.

OBJECTIVE: To investigate the effect of prenatal smoking on infant respiratory behavior during sleep. METHODS: A questionnaire concerning family habits and infants' history was completed for 550 healthy infants before a 9-hour night polysomnographic study. Because the data for 41 infants were not available for analysis, 509 subjects were studied: 115 were newborns evaluated within 1 week after birth, and 394 were healthy infants admitted at 11 weeks of life (range 5 to 29 weeks) after various research protocols. RESULTS: According to the smoking frequency of the mothers during pregnancy, the subjects were defined as "nonsmokers" (no cigarette smoked during pregnancy; n = 400), "light smokers" (1 to 9 cigarettes per day; n = 37), or "smokers" (10 or more cigarettes per day; n = 72). Compared with nonsmokers and light smokers, "smoking" mothers had a significant increase in the number of episodes of uterine bleeding during the pregnancy. Their infants had lower birth weights and more frequent episodes of profuse sweating during sleep. Infants of smokers also had more frequent and longer obstructive sleep apneas than those of the two other groups. For infants of smokers the relative risk for obstructive apneas was 2.76 (95% confidence interval: 1.63 to 4.69; P = .001). The relation between prenatal smoking and postnatal manifestation of obstructive sleep apneas demonstrated a dose-response pattern. Paternal smoking during pregnancy increased the risk of obstructive apneas only in the infants of smoking mothers, but not in those of the two other groups. Maternal smoking after birth did not add significantly to the risk of obstructive apneas. The effect of smoking was seen in older infants, as well as in the newborn not yet exposed to ambient cigarette smoke. A stepwise logistic regression, using obstructive sleep apneas as the dependent variable identified three significant independent variables: smoking during pregnancy (P = .001), profuse sweating during sleep (P = .001), and birth weight (P = .010). No explanation was found for the effect of prenatal smoking on obstructive sleep apneas. CONCLUSION: Prenatal smoking by mothers correlated with an increase in frequency and length of obstructive apneas and a decrease in birth weight of their infants. The infants were under greater risk for obstructive apnea if both parents smoked. Explanations for our results are unknown to us, but these findings may be of interest in the study of infant breathing behavior and epidemiological characteristics of sudden infant death syndrome.

Anterior fontanelle pressure variations during sleep in healthy infants.

Our aim was to study the intracranial pressure (ICP) variations during sleep normal infants. Using a noninvasive method, ICP was measured continuously during polysomnography in 12 healthy infants aged from 1 to 11 months (median 3.5 months). We analyzed the variations of mean basal ICP, mean basal pulse pressure amplitude and maximal amplitude of both plateau and B-like waves between transient sleep, quiet sleep and rapid eye movement (REM) sleep. Mean ICP, mean pulse pressure amplitude and B-like wave amplitude increased significantly during transient sleep and REM sleep. Plateau waves occurred during transient sleep and especially REM sleep. By contrast, noninvasive ICP recordings were relatively flat during quiet sleep stages 2 and 3. ICP variations and pressure waves seem to be related to cerebrovascular changes associated with sleep. The physiological ICP variations during sleep must be known in order to allow correct interpretation of continuous ICP measurements in infants.

Pyruvate dehydrogenase deficiency: clinical and biochemical diagnosis.

A female neonate with pyruvate dehydrogenase (PDH) deficiency is presented with clinical, radiologic, biochemical, neuropathologic, and molecular genetic data. She was dysmorphic, with a high forehead, lowset ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF and blood. Urinary organic acid profile was compatible with PDH deficiency. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was found within the regulatory phosphorylation site in exon 10. It is postulated that this mutation causes a cerebral form of PDH deficiency. Tissue-specific expression of the disease could be explained by differential X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.

Non-invasive measurement of intracranial pressure in neonates and infants: experience with the Rotterdam teletransducer.

On the basis of an experience of more than 400 recordings, we demonstrate the usefulness of the anterior fontanelle pressure monitoring (AFP) in several clinical conditions. Main indications for AFP monitoring are the evaluation and the differential diagnosis of neonatal encephalopathy and the assessment of infants with enlarged ventricular spaces, ventriculo-peritoneal derivation or increased head growth rate. Further technical progress is needed to permit AFP recordings in infants with small anterior fontanelle and to reduce the time necessary for the AFP measurement and interpretation procedure. We conclude that it is technically possible and clinically helpful to obtain accurate information about ICP and changes in cerebral compliance in a wide range of clinical conditions without the use of invasive techniques.

Anterior fontanelle pressure recording with the Rotterdam transducer: variation of normal parameters with age.

Using a reliable non-invasive technique for ICP monitoring, we realized 93 continuous anterior fontanelle pressure (AFP) recordings in 86 healthy infants aged from 29 to 85 post-conceptional (PC) weeks. For each recording, we calculated the mean and extremes values of AFP, cerebral pulse amplitude, and pressure waves rate and amplitude. We observed the occurrence of plateau-waves of relatively low amplitude and duration in most infants aged of more than 49 PC weeks. We postulate that PW represents a physiological phenomenon which is amplified under pathological conditions. All AFP parameters are correlated to PC age and vary during early infancy according to an ascending sigmoidal relation (this variation may be explained by a connection between several cranio-cerebral characteristics of the young infant). We conclude that the interpretation of AFP recordings must take into account [1] PC age rather than postnatal age, [2] variation of AFP parameters with age, and [3] occurrence of physiological plateau-waves.

[Definition of asphyxia neonatorum and incidence of neurologic and systemic complications in the full-term newborn]. / Définition de l'asphyxie à la naissance et incidence des complications neurologiques et systémiques chez le nouveau-né à terme.

PATIENTS AND METHODS: In a prospective multicentric study, 152 of 10,065 live term births had birth asphyxia, defined by the association of three indicators (fetal distress, depression at birth and metabolic acidosis). RESULTS: The incidence of birth asphyxia was 1.5% of live term births when birth asphyxia was defined by the presence of at least two indicators, and 1% of live term births when birth asphyxia was defined by the association of metabolic acidosis and another indicator. Neurological complications were observed in 66 cases (43%). The incidence of post-asphyxial encephalopathy (PAE) was 5.9/1000 of live term births (mild PAE: 3/1000; moderate PAE: 2.7/1000; severe PAE: 0.2/1000). Systemic complications were observed in 87 patients (57%). Renal injury and coagulopathy were associated with moderate or severe PAE. Respiratory complications (39%), infections (17%) and gastro-intestinal intolerance (15%) often complicated the course. Severe complications were never seen in the absence of significant metabolic acidosis at 30 minutes of life. CONCLUSION: Our study has many implications concerning the diagnosis of birth asphyxia and its complications. A terminology based on clinical observation and arterial pH evaluation is proposed in order to clarify the situation.

[Monitoring of fontanelle pressure in neonates and infants. Evaluation of a new measuring technique, determination of normal values and clinical usefulness]. / Monitorage de la pression fontanellaire chez le nouveau-né et le nourrisson. Evaluation d'une nouvelle technique de mesure, détermination des valeurs normales et utilisation clinique.

The experience with 200 measurements of anterior fontanelle pressure with the Rotterdam Teletransducer in newborns and infants is reported. Statistical analysis of 25 comparative measurements between anterior fontanelle pressure and invasive cerebrospinal fluid pressure showed an excellent correlation (rs = 0.95). Measurements were reproducible and the plot quality allowed visualisation of pulse pressure and pressure waves. Normal values of the anterior fontanelle pressure, pulse pressure amplitude and pressure wave maximal amplitude were established in 15 prematures, 27 term newborns and 10 infants. Anterior fontanelle pressure monitoring was performed in 19 term newborns with post-asphyxial encephalopathy, 18 newborns and infants with hydrocephalus, 8 preterm and term newborns with respiratory distress and 19 patients with subdural haematomas, metabolic diseases, meningitis, subarachnoidal haemorrhage, head trauma, post cardiac arrest encephalopathy and abnormal head growth or bulging fontanelle. Abnormal patterns of anterior fontanelle pressure monitoring were found in moderate or severe neonatal post-asphyxial encephalopathy, evolutive hydrocephalus, subdural haematomas, metabolic diseases with hyperammoniemia and other clinical situations. In contrast, anterior fontanelle pressure monitoring yielded normal values in mild post-asphyxial encephalopathy, arrested hydrocephalus, well functioning ventriculo-peritoneal derivation, and in normal infants with rapid head growth or bulging fontanelle. The Rotterdam Teletransducer provides thus accurate and reproducible values of intracranial pressure. Anterior fontanelle pressure monitoring may be of value in many situations in clinical practice.

Non-invasive measurement of intracranial pressure in the newborn and the infant: the Rotterdam teletransducer.

Knowledge of intracranial pressure may be important in many clinical situations in neonates and young infants. The best way to obtain this information would be a non-traumatic procedure. In order to test the reliability of a new fontanometer, the Rotterdam teletransducer, 25 simultaneous measurements of cerebrospinal fluid (CSF) pressure and anterior fontanelle pressure (AFP) were performed. Mean (SD) difference between CSF pressure and AFP was -0.2 (1.8) mm Hg (95% confidence interval from -0.48 to -0.88 mm Hg). The AFP was also measured in 60 healthy children (15 premature, 30 term newborn babies, and 15 infants). The different aspects of AFP were analysed and normal values computed. These results suggest that the Rotterdam teletransducer gives reliable continuous information about intracranial pressure and can be used in clinical practice. Interpretation of AFP plots must take the influence of postconceptional age and the physiological occurrence of pressure waves into account.

Clinical value of a single postnatal lactate measurement after intrapartum asphyxia.

UNLABELLED: Our aim was to compare the respective values of base deficit and lactate in birth asphyxia. METHODS: Base deficit and lactate levels were measured from radial artery blood samples taken at 30 min of life in 115 term newborns suspected as having been asphyxiated during labour. Both base deficit and lactate levels were compared between patients who further developed moderate or severe encephalopathy and those who experienced no or only mild encephalopathy. Receiver operating characteristics curves and clinical values of both indicators were computed. RESULTS: The correlation between base deficit and lactate was significant (r2 = 0.51, p < 0.0001). Both indicators were significantly associated with neonatal outcome. Lactacidaemia lower than 5 mmol/l and/or base deficit level lower than 10 mEq/l were not followed by neurological complications. Plasma lactate concentration greater than 9 mmol/l was associated with moderate or severe encephalopathy with a sensitivity of 84% and a specificity of 67%. Base deficit and lactate had similar clinical values. CONCLUSIONS: Base deficit and lactate measurements in arterial blood at 30 min of life are equally valuable in assessing the severity of birth asphyxia.

Diagnosis of severe birth asphyxia and early prediction of neonatal neurological outcome in term asphyxiated newborns.

Ten indicators available during the first two hours of life, such as clinical criteria of neonatal distress and postnatal arterial blood gases, were compared with the neonatal neurological course in sixty full term newborns with significant birth asphyxia in order to test their value for the diagnosis and the short-term prognosis of severe birth asphyxia. Birth asphyxia was defined as severe when it was followed by symptoms of moderate or severe post-asphyxial encephalopathy. We calculated a sensitivity lower than fifty percent for clinical criteria such as delay in establishing regular respiration and Apgar scores. It was clear that normal delay in establishing regular respiration and normal Apgar scores do not exclude severe birth asphyxia. Arterial pH and base deficit at thirty minutes of life were found to be the best criteria for the diagnosis of severe birth asphyxia, but lacked positive predictive value. The best predictive tool for the short-term neurological prognosis of birth asphyxia was a single score established at 30 minutes of life and based on the evaluation of consciousness, respiration and neonatal reflexes. Some aspects of the pathophysiology of birth asphyxia and the rationale for treatment of post-asphyxial metabolic acidosis are discussed.

Anterior fontanelle pressure monitoring for the evaluation of asymptomatic infants with increased head growth rate.

We studied non-invasive intracranial pressure monitoring in 20 asymptomatic infants with increased head growth rate. Both basal anterior fontanelle pressure (AFP) traces and occurrence of pressure waves were analysed and compared with normal range values previously established. Eight recordings were classified as pathological; cerebral imaging showed subdural collections or ventricular dilatation in all cases. Five out of these eight infants further developed neurological deficits and/or increase of the ventricular size, and required neurosurgical procedures. Twelve infants had normal AFP traces; six of these had normal cerebral imaging and six showed enlargement of subarachnoid spaces with normal ventricles. All of these 12 patients normalised their head growth rate and remained asymptomatic. This observation suggests that AFP monitoring may be helpful in asymptomatic infants with increased head growth rate to identify a progressive intracranial process and the potential need for a neurosurgical procedure.

Neuropathological findings of a patient with pyruvate dehydrogenase E1 alpha deficiency presenting as a cerebral lactic acidosis.

Neuropathological findings are reported of a 6-month-old female child with a "cerebral" lactic acidosis. A mutation in the pyruvate dehydrogenase (PDH) E1 alpha gene was found. Gross examination of the brain revealed a severe thinning of the cerebral parenchym, a marked hydrocephalus sparing the aqueduct and fourth ventricle, agenesis of the corpus callosum and heterotopic noduli of gray matter in subependymal regions. Microscopical examination showed heterotopic inferior olives, absent pyramids and focal neuroglial overgrowth into meninges. In addition some heterotopia of Purkinje cells and dysplasia of the dentate nuclei were observed. There was a marked vascular proliferation with many thin-walled, congestive vessels in the cerebral and cerebellar white matter, and to a lesser extent in the striatum. To our knowledge these cerebellar and vascular abnormalities have not been reported before in patients with "cerebral" lactic acidosis. The combination of these neuropathological findings might be characteristic for PDH deficiency and more specifically for its E1 alpha subtype. Neuropathological examination could lead to the retrospective diagnosis of PDH E1 alpha deficiency in those cases where biochemical investigations were not or incompletely performed. This may have potential implications for genetic counseling.

Hyperphosphatasemia in early diagnosed infantile GM1 gangliosidosis presenting as transient hydrops fetalis.

The authors report a case of unsuspected fetal storage disorder initially diagnosed by placental examination performed because of a transient ascites at 28 weeks of gestation. At birth mild dysmorphic features and gradual neurological deterioration were observed. Highly elevated alkaline phosphatase levels were repeatedly noticed. Deficiency of beta-galactosidase was documented confirming GM1 gangliosidosis. Previous reports described the placental pathology after positive prenatal diagnoses of lysosomal diseases. In the present case, the postnatal diagnosis was made in view of the placental pathologic findings. Our observation indicates the need for thorough investigations in hydrops fetalis, in search for metabolic diseases.