A new individualized prognostic approach to the management of women at risk of extreme preterm birth in France: Effect on neonatal outcome.

INTRODUCTION: After discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. METHODS: A before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks+6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. RESULTS: The study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22-23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. CONCLUSION: Implementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage.

[Perinatal care for extremely preterm infants. Considerations of the "risks in pregnancy" department]. / Prise en charge de la prématurité extrême. Réflexions du département hospitalo-universitaire (DHU) « risques et grossesse ¼.

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.

Early individualised parenteral nutrition for preterm infants.

Considerable effort should be made to optimise parenteral nutrition of preterm infants in order to limit the development of postnatal growth restriction. A monocentric before-and-after study design was used to determine the effects of computerising parenteral nutrition ordering on the composition of parenteral nutrition (PN) solutions and early clinical outcomes of preterm infants born < or =28 weeks of gestation. Parenteral protein intake during the first week of life and parenteral lipid, glucose and energy intakes during the first and second week of life were significantly higher in infants assessed after the introduction of computerised parenteral nutrition ordering. This led to a significant reduction in the cumulative energy deficit over the first 28 days of life and to an improvement in both early growth and pulmonary outcome. Computerising the PN ordering process improves the nutrient content of the PN solutions and early postnatal outcome.

[Management of neonatal seizures]. / Conduite à tenir en cas de "convulsions" néonatales.

The aim of this review is to focus on the nosological classification of neonatal "convulsions", to precise the underlying aetiologies and the prognosis, and to propose diagnostic and therapeutical approach. Seizures may be epileptic or not, they may be occasional, part of an epilepsy syndrome or associated to a metabolic disease. Electroencephalography plays a central role; it enables to confirm the epileptic nature of the ictal events, it allows to evaluate the prognosis and to guide the treatment decision, and sometimes may help in the etiological diagnosis. Work up should include cerebral imaging (MRI) completed by other exams according to the diagnostic hypothesis. It is essential to go as far as possible in the etiological work-up not to attribute convulsions to an occasional event as HIE in which criteria remain very strict, when convulsions could be due to genetic origin or to maternal pathology. Treatment decision should comprise different ways: treatment of the underlying cause, of the eventual associated pathologies, maintenance of vital functions and antiepileptic treatment. Phenobarbitone remains the first line drug in occasional seizures, and second line drugs for which further studies are needed both for immediate and long-term secondary effects. Besides occasional seizures epilepsy syndromes and metabolic diseases remain exceptional. Nevertheless recognition of these conditions allows to establish the prognosis and to start immediately with an appropriate and specific medication depending on the epilepsy syndrome and can contribute to a prenatal diagnosis. It is important to recognize the inborn errors of metabolism because emergency appropriate treatment is required. Prognosis which is generally bad is essentially related to the underlying aetiology and probably to the duration of the active period of seizures.

Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.

BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants.

Radiological analysis of hyaline membrane disease after exogenous surfactant treatment.

BACKGROUND: Exogenous surfactant treatment of hyaline membrane disease is known to modify the pattern of radiological changes on the chest radiograph. OBJECTIVES: To analyse and attempt to explain the radiological changes observed after exogenous surfactant treatment. Materials and methods. Thirty-nine premature infants with typical hyaline membrane disease. RESULTS: Transient asymmetrical clearing with better aeration of the right lung in the absence of malposition of the tip of the endotracheal tube was observed in nine cases (23 %). This asymmetry was patchy in one case. It was due to a complication of mechanical ventilation in three cases [pneumothorax (n = 2) and pneumomediastinum (n = 1)]. In the other six cases, asymmetrical clearing could be related to the anatomical position of the right main bronchus, which facilitates distribution of surfactant to the right lung. However, the course of these premature infants was similar to that of infants with symmetrical chest radiological findings after treatment. CONCLUSIONS: Asymmetrical clearing of chest radiographs, sometimes patchy, after surfactant treatment requires exclusion of pneumothorax or infection but has no influence on clinical outcome.

Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.

The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.

Delivery of uncomplicated triplet pregnancies: is the vaginal route safer? A case-control study.

OBJECTIVE: Our purpose was to evaluate the safety of vaginal delivery of triplets. STUDY DESIGN: A retrospective case-control study on 69 consecutive triplet pregnancies delivered in the same institution between 1981 and 1992. Vaginal delivery was attempted in 23 otherwise uncomplicated triplet pregnancies, which form the study group. They were compared with 23 controls undergoing routine cesarean section and matched for gestational age at birth. Maternal hospital stay, neonatal mortality, hospitalization in the neonatal intensive care unit, and 5-minute Apgar scores were compared by means of paired t tests. RESULTS: In the vaginal delivery group there was one neonatal death related to prematurity (32 weeks) after intrapartum cesarean section for failure to progress. However, neonatal mortality was not significantly increased in comparison with controls (1 of 69 vs 0). In the study group Apgar scores were significantly higher (9.5 vs 8.4) and hospitalization in the neonatal care intensive unit was significantly shorter (6 vs 18 days) than in the cesarean section group (p < or = 0.002). CONCLUSION: In carefully selected cases vaginal delivery of triplets may be safe.

Myasthenia gravis with polyhydramnios in the fetus of an asymptomatic mother.

Transient myasthenia gravis was observed in an infant whose mother had no signs of neuro-muscular disease. The case presented with severe polyhdramnios at 31 weeks. Sonographic and invasive work-up showed only an absence of fetal swallowing. At birth, the infant had severe muscle weakness and respiratory distress. He had high titres of anti-acetylcholine receptor (anti-AChR) antibodies of maternal origin. Anti-AChR antibodies were also found in stored samples of fetal serum and amniotic fluid. To our knowledge, this is the first case of neonatal myasthenia gravis for which neither past nor present evidence of disease could be obtained in the mother. Anti-AChR antibody testing should be considered in cases of unexplained polyhydramnios.

Use of preestablished criteria for deciding on extubation in the very low birthweight newborn. Preliminary analysis of a randomized study.

The duration of mechanical ventilation (MV) in very low birthweight infants can sometimes be very prolonged, even in the absence of any respiratory disease. To avoid this, we have developed a double-blind study protocol of the concomitant use of caffeine and doxapram or caffeine and placebo as an aid to early weaning from MV. This protocol necessitated the definition of very precise ventilatory criteria for extubation. Even before the double-blind code has been broken, we can note that the duration of ventilation was very significantly reduced (p < 0.001) from 27.5 days (median; range 1-99) in infants of the retrospective study group to 4 days (median: range 1-34) in the prospective study group (extubation according to strict criteria). This reduction in duration of MV cannot be explained by a difference in the severity of the initial pathology, or by the treatment of some of the infants with doxapram (the difference would not be so marked), but, probably, to the definition of strict criteria concerning extubation.

[Neonatal cervical cord compression by a staphylococcal abscess]. / Compression médullaire cervicale néonatale par abcès staphylococcique.

In a small for date premature newborn infant, septicemia caused by Staphylococcus aureus was observed on day 16. In spite of an appropriate antimicrobial therapy, proteins of inflammation serum levels remained elevated for 2 weeks. The occurrence of cervical cord compression which could be related to a staphylococcal abscess explained the persisting inflammatory process. After puncturing of the abscess, immobilization and prolonged antibiotic treatment, outcome was favorable. This case demonstrates the difficulty of preventing abscesses related to staphylococcal septicemias and reports a very unusual site of abscess which could be well localized using MRI.

Gastroesophageal reflux and apnea in prematurely born infants during wakefulness and sleep.

The hypothesis that acid gastroesophageal reflux may be responsible for the persistence of apnea was tested on 20 prematurely born infants, at a median conceptional age of 38.7 weeks. Gastroesophageal reflux was identified using distal esophageal pH monitoring. Apneas of durations greater than 10 seconds were identified and classified as either central or obstructive and mixed, using recordings of respiration. Wakefulness, active sleep, and quiet sleep were identified using electroencephalography and by assessing eye movements. Of 134 episodes of acid gastroesophageal reflux in the 20 subjects, more occurred during wakefulness and during active sleep than during quiet sleep. A total of 139 apneas, predominantly of the obstructive and mixed type, occurred. No relationship could, however, be demonstrated, in this rather small number of patients, between the occurrence of gastroesophageal reflux and that of apneas.

Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists.

A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.

[Treatment of severe hyaline membrane disease with a single-dose of natural exogenous surfactant of porcine origin. A randomized trial: immediate effects and outcome at 28 days of life]. / Traitement de formes sévères de la maladie des membranes hyalines par une dose unique d'un surfactant exogène naturel d'origine porcine. Un essai randomisé: effets immédiats et devenir à 28 jours de vie.

The results obtained with porcine surfactant (Curosurf) administration for the treatment of hyaline membrane disease (HMD) are reported. Thirty premature infants weighing 700 to 2,000 g with severe HMD (mechanical ventilation and oxygen requirement (FiO2) greater than 60% were randomly allocated at 2 to 15 hours postnatal age. Eight of the 30 patients included in this group participated in a multicenter european trial. The fifteen infants with mean gestational age (GA) of 29.5 weeks included in the treatment group (T), were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group (C). Infants in the T group showed an immediate, dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour. This significant improvement in favor of T group (p less than 0.005) persisted for 2 days when control infants began to recover. This improvement in oxygenation allowed a significant decrease of FiO2 (p less than 0.005) and mean airway pressure (p less than 0.01) in the T group within 1 hour and up till the second day. Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified. However the tendency was towards decreased respiratory morbidity. The discussion will consider the value of multiple doses.

[Cardiopulmonary adaptation to birth]. / Adaptation cardiopulmonaire à la naissance.

The cardio-pulmonary situation of the foetus is very special; certain changes occurring at the end of pregnancy make preparations for extra-uterine life. In the foetus, the two ventricles eject different outputs to the systemic and pulmonary circulation, these communicate between each other by the ductus arteriosus and the foramen ovale. The pulmonary output is very small on account of the high pulmonary resistance. The lungs do not participate in gas exchange (ensured by the placenta) they secrete a liquid maintaining airway distension; the synthesis of surfactant, whose role will be vital after birth, begins at the end of the second trimester of pregnancy. Dramatic changes occur at birth. The two ventricles now function in series, the shunts between the two circulations are shut. The lowering of the pulmonary vascular resistance, the aeration of the lungs, the formation of the functional residual capacity and the appearance of a regular and rhythmic respiration now enable the new born to ensure its own gas exchange.