Danièle Vermeylen

Nitrated plasma albumin as a marker of nitrative stress and neonatal encephalopathy in perinatal asphyxia

Reactive nitrogen species (RNS) have been shown to play a major role in the pathophysiology of hypoxic-ischemic cerebral injury. Using a novel sensitive ELISA allowing the quantification of nitrated albumin (nitroalbumin) in plasma, we tested the hypothesis that perinatal asphyxia increases nitrating RNS generation by verifying whether the concentration of one of its target proteins is correlated with the clinical outcome. We assayed nitroalbumin in 114 plasma samples collected during the first hour, at day 1, and at day 4 of life from 48 term newborns suffering from perinatal asphyxia and correlated this marker with neurological and systemic neonatal outcomes. Nitroalbumin levels at day 1, but not at days 0 and 4, were significantly increased in patients who developed moderate or severe encephalopathy compared to those who had a normal neurological evolution or developed mild encephalopathy (median: 14.4 ng/ml versus 7.3 ng/ml, respectively). In contrast, nitroalbumin concentration at day 1 was not associated with systemic complications. First-hour and fourth-day nitroalbumin concentrations did not differ with respect to the neonatal neurological course. At day 0, nitroalbumin levels also correlated with circulating leukocytes. We conclude that plasma nitroalbumin seems to be a specific marker of neurological injury after perinatal asphyxia and may serve as a secondary end-point in neuroprotective clinical trials.

Cellular immune responses of preterm infants after vaccination with whole-cell or acellular pertussis vaccines.

ABSTRACT Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants against Bordetella pertussis according to their chronological age. However, as specific T-cell responses also are involved in the protection against B. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa; n = 24) or a whole-cell (Pw; n = 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-γ) response to the B. pertussis antigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-γ secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.

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.

High-frequency ventilation and conventional mechanical ventilation in newborn babies with respiratory distress syndrome: A prospective, randomized trial

ObjectiveMorbidity and mortality remain high amongst babies ventilated for a respiratory distress syndrome (RDS). Whether newly developed ventilators allowing high frequency ventilation such as high frequency flow interrupted ventilation (HFFIV) could decrease the morbidity and the mortality was investigated in a randomized study.DesignPreterm babies weighing ≤1800g suffering from RDS and ventilated by conventional mechanical ventilation (CMV) were randomized to be further ventilated either by CMV (group CMV) or by HFFIV (group HFFIV) when peak inspiratory pressure (PIP) on CMV was ≥20cmH2O.SettingThe study was undertaken in the neonatal intensive care unit of the Erasmus Hospital.Patients24 patients entered into the investigation and were randomized but 2 patients were removed from the study because the switch over to HFFIV failed. Eight of the 12 CMV patients and 5 of the 10 HFFIV patients completed the study.Measurements and resultsClinical variables, blood gas analysis and ventilatory variables were looked at. There were no differences in mortality, in incidence of air leaks and pulmonary complications or in blood gas analysis. Bronchopulmonary dysplasia was not decreased by the use of HFFIV.ConclusionIt is concluded that HFFIV is safe although it offers no concrete advantages over CMV when applied as we did in a low pressure approach.

Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

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.

Detection and evaluation of fetal goitre by ultrasound

Antenatal diagnosis of fetal goitre has been reported rarely. Once detected, however, it is important to evaluate fetal thyroid function so early treatment can be initiated if necessary. In reporting three new cases, the authors analyse the various methods of evaluation. The normal sequence of appearance of the various epiphyseal ossification centres is an indirect illustration of thyroid function and can be followed by ultrasound. Direct evaluation of hormone levels through cord blood sampling under sonographic guidance is a complementary method in doubtful cases. The mechanisms predisposing to the development of fetal goitres and the possible implications of these findings are also discussed.

Long-term follow up of a case of severe congenital chloride diarrhoea

A patient with congenital chloride diarrhoea (CCD) is reported. The diagnosis on the 5th day of life was based on the watery stools with characteristic ionic composition. The neonate presented with abdominal distension necessitating laparotomy on day 1, followed by transverse colostomy on day 3, owing to persistent abdominal swelling. Total parenteral nutrition (from 1 to 3 months) followed by an enteral semielemental diet (from 3 to 5 months) was required to reduce the quantity of stools and to obtain a satisfactory nutritional state. The colostomy was closed at 16 months. Growth, psychomotor development and renal function are normal at 6 years. Criteria for therapeutic evaluation are discussed.

Decreased spontaneous arousability in preterm newborns with impaired neurological outcome

Preterm newborns are at high risk of neurological injury. In this population, we investigated the link between neurological complications and sleep architecture. At term‐corrected gestational age, we studied retrospectively the polysomnography of 45 preterm infants born at < 28 weeks or weighting < 1 kg. These infants were followed‐up by a neuropaediatrician (median age at last follow‐up 50.4 months). Two groups of children were constituted: a group without neurological disorder and a second group with at least one of the following: cerebral palsy, language or mental retardation, visual or hearing disability or attention disorder. A Multiple Indicators and Multiple Causes model assessed the relationship between the neurological outcome and two sleep components: spontaneous arousability [number of awakenings and movements per hour of quiet sleep (QS) and active sleep] and QS characteristics (median duration of QS cycles and percentage of QS over total sleep time). Twenty‐six infants had an impaired neurological outcome. There were no statistical differences between the two groups regarding clinical characteristics. Compared to preterm neonates with normal neurological outcome, those with impaired outcomes had a lower spontaneous arousability; i.e. 0.7 (0.5–1) times less awakenings and movements per hour of QS and 0.9 (0.8–1) times less per hour of active sleep than infants with normal outcomes (P = 0.05). The differences in QS characteristics did not reach statistical significance. These findings suggested that, in preterm infants, perinatal neurological injuries could be associated with an abnormal sleep architecture characterized by altered spontaneous arousability.

Sonographic demonstration of a congenital laryngeal cyst

A premature 34 week old female newborn infant of atriplet pregnancy was admitted in the neonatal unit withmoderate axial hypotonia. A few hours later, she wasfound to be suffering from respiratory distress and stridor.Clinical examination revealed a premature hypotonicbaby with respiratory retraction of suprasternal and infra-sternal soft tissue, stridor, and regurgitation. The abdomenwas slightly distended. Chest radiograph and arterialblood gas determination showed normal results, and alaryngeal abnormality was suspected.Cervical ultrasonography showed a cystic mass 12 mmin diameter at the right aryepiglottic fold, displacing theglottis toward the left side (Fig. 1). No flow was detectedwith Doppler ultrasonography. The ultrasonographicfindings suggested the diagnosis of aryepiglottic cyst.Limited endoscopic marsupialization was performedbut with transient clinical improvement. Ultrasonographyrevealed persistence or recurrence of the cyst, and a sec-ondary complete removal of the cyst was performed endo-scopically (Fig. 2). Microscopic examination revealed amucinous cyst. No recurrence was detected on sono-graphic follow-up, and deviation of the glottis wasreduced. The infant is now 32 months old and is com-pletely asymptomatic. On an ultrasonogram, the glottis isno longer deviated (Fig. 3).