The French Society of Neonatology's proposals for neonatal end-of-life decision-making.

BACKGROUND: Opinions and practice regarding end-of-life decisions in neonatal medicine show considerable variations between countries. A recent change of the legal framework, together with an ongoing debate among French neonatologists, led the French Society of Neonatology to reconsider and update its previous recommendations. OBJECTIVES: To propose a set of recommendations on the ethical principles to be respected in the making and application of end-of-life decisions. METHODS: A multidisciplinary working group on ethical issues in perinatal medicine composed of neonatologists, obstetricians and ethicists. RESULTS: Withholding or withdrawing life-sustaining treatment may be acceptable, and unreasonable therapeutic obstinacy is condemned. This implies that the child's best interests must always be the central consideration. Although the parents must be involved in the decision process so that they form an alliance with the healthcare team, and a collegial approach is of utmost importance, any crucial decision affecting the patient's life calls for individual medical responsibility. Because every newborn is rightfully an integral member of a human family, his or her dignity must be preserved. The goal of palliative care is to preserve the quality of a life, also at its end. The intention underlying an act has to be analyzed perceptively. Euthanasia, i.e. to perform an act with the deliberate intention to cause or hasten a patient's death, is legally and morally forbidden. Conversely, to withhold or withdraw a life-sustaining treatment can be justified when the intention is to cease opposing, in an unreasonable manner, the natural course of a disease. CONCLUSIONS: This statement provides the principles identified by French neonatologists on which to base their decisions concerning the ending of life. Arguments are set forth, discussed and compared with international statements and previously published considerations.

[Very premature births: Dilemmas and management. Part 1. Outcome of infants born before 28 weeks of postmenstrual age, and definition of a gray zone]. / Naissances très prématurées : dilemmes et propositions de prise en charge. Première partie : pronostic des naissances avant 28 semaines, identification d'une zone grise.

With very preterm deliveries, the decision to institute intensive care, or, alternatively, to start palliative care and let the baby die, is extremely difficult, and involves complex ethical issues. The introduction of intensive care may result in long-term survival of many infants without severe disabilities, but it may also result in the survival of severely disabled infants. Conversely, the decision to withhold resuscitation and/or intensive care at birth, which is an option at the margin of viability, implies allowing babies to die, although some of them would have developed normally if they had received resuscitation and/or intensive care. Withholding intensive care at birth does not mean withholding care but rather providing palliative care to prevent pain and suffering during the time period preceding death. The likelihood of survival without significant disabilities decreases as gestational age at birth decreases. In addition to gestational age, other factors greatly influence the prognosis. Indeed, for a given gestational age, higher birth weight, singleton birth, female sex, exposure to prenatal corticosteroids, and birth in a tertiary center are favorable factors. Considering gestational age, there is a gray zone that corresponds to major prognostic uncertainty and therefore to a major problem in making a "good" decision. In France today, the gray zone corresponds to deliveries at 24 and 25 weeks of postmenstrual age. In general, babies born above the gray zone (26 weeks of postmenstrual age and later) should receive resuscitation and/or full intensive care. Below 24 weeks, palliative care is the only option offered in France at the present time. Decisions within the gray zone will be addressed in the 2nd part of this work.

[Very premature births: Dilemmas and management. Second part: Ethical aspects and recommendations]. / Naissances très prématurées : dilemmes et propositions de prise en charge. Seconde partie : enjeux éthiques, principes de prise en charge et recommandations.

In the first part of this work, the outcome following very premature birth was assessed. This enabled a gray zone to be defined, with inherent major prognostic uncertainty. In France today, the gray zone corresponds to deliveries occurring at 24 and 25 weeks of postmenstrual age. The management of births occurring below and above the gray zone was described. Withholding intensive care at birth for babies born below or within the gray zone does not mean withholding care but rather providing palliative care to prevent pain and suffering during the time period preceding death. Given the high level of uncertainty, making good decisions within the gray zone is problematic. Decisions should be based on the infant's best interests. Decisions should be reached with the parents, who are entitled to receive clear and comprehensive information. Possible decisions to withhold intensive care should be made following the procedures described in the French law of April 2005. Guidelines, based on gestational age and the other prognostic elements, are proposed to the parents before birth. They are applied in an individualized fashion, in order to take into account the individual features of each case. At 25 weeks, resuscitation and/or full intensive care are usually proposed, unless unfavorable factors, such as severe growth restriction, are associated. A senior neonatologist will attend the delivery and will make decisions based on both the baby's condition at birth and the parents' wishes. At 24 weeks, in the absence of unfavorable associated factors, the parents' wishes should be followed in deciding between initiating full intensive care or palliative care. Below 24 weeks, palliative care is the only option to be offered in France at the present time.

[Implementing palliative care for newborns in various care settings. Part 3 of "Palliative care in the neonatal period"]. / La mise en oeuvre pratique des soins palliatifs dans les différents lieux de soins : 3(e) partie des réflexions et propositions autour des soins palliatifs en période néonatale.

Palliative care in newborns may take place in the delivery room and then continued either in maternity wards or in the neonatal unit. For babies developing a chronic condition, going home may be advantageous. The population concerned includes babies born with a severe intractable congenital malformation and certain extremely preterm newborn babies at the limits of viability. Care procedures as well as withholding and withdrawing treatments are reviewed.

[Palliative care in the neonatal period. Part one: general considerations]. / Réflexions et propositions autour des soins palliatifs en période néonatale : 1(re) partie considérations générales.

In France, the law dated 22 April 2005 required that all practitioners offer palliative care to patients as an alternative to unreasonable obstinacy. The practical development of palliative care during the neonatal period is not easy, even though obstetricians and neonatologists have always been aware of the ethical necessity of comfort in the dying newborn. The decision leading to palliative care begins with the recognition of patent or potential unreasonable obstinacy, followed by withdrawing treatment and technical support, and finally a palliative care plan is drawn up with the medical team and the parents.

[The eastern Paris perinatal network (2008-2010). Defining the target population and assessing health needs]. / Le réseau périnatal de l'Est parisien (2008-2010). Définition de la population concernée pour évaluer les besoins à couvrir par le réseau.

BACKGROUND: Since the 1990s, governmental plans in France have imposed the regionalization of perinatal care to improve both safety and quality of care. The Eastern Paris Perinatal Network is under construction in health area 75-2, which includes the 11th, 12th, 13th and 20th arrondissements of Paris. A major issue is ensuring that the network can meet the needs of its target population. The objective is to define the network's target population of mothers and newborns. METHODS: We designed a matrix to help assess these needs and identify the data required to define the network's population. Four principal data sources were analyzed: the National Statistics and Economic Studies Institute (Insee) data, annual health facility activity data, national medical informatics program data, and 8th-day health certificates. RESULTS: The network's target population varies according to the precise perinatal period and the planning stage. For the conception period, it includes the general population and specifically all women of childbearing age (15-49 years). The health area included 672,000 inhabitants in 2006, 29% of them are women of childbearing age. The proportion of people born outside France and who are of foreign nationality ranges, according to arrondissement, from 13.2 to 20.0%; the mean for the Paris metropolitan area is 14.7%. Approximately 16,500 women gave birth in 2007, at nine obstetric facility sites in the health area (five level I, three level II, and one type III); only 41.46% of them resided in the health area. Approximately 2500 women living in the health area gave birth at a facility outside the area. The population likely to be covered by the network is thus estimated at approximately 19,000 women. CONCLUSION: A network must simultaneously take into account the local resident population and the population using its health care system. In an urban area such as Paris, where the health care supply is dense, it is essential for policy planning process to define the contours of the target population of a health network.

Visual neurophysiological dysfunction in infants exposed to hydroxychloroquine in utero.

AIM: Hydroxychloroquine therapy during pregnancy is thought to be safe for foetuses. Normal visual function has been showed on clinical grounds in infants exposed in utero to hydroxychloroquine, but there are few visual neurophysiological data. Our study was designed to assess retina and visual pathways using electroretinogram and visual evoked potentials in a series of infants born to mothers treated by hydroxychloroquine for connective tissue diseases. METHODS: Twenty-one infants (3-7 months of age) were consecutively examined between June 2002 and May 2007. Full-field electroretinogram was recorded by contact lens electrodes and visual evoked potentials were recorded by occipital surface electrodes using flash stimulation in mesopic condition. Analysis was focused on the amplitudes and latencies of the a- and b-waves of electroretinogram and the latency of the P(100) component of visual evoked potentials. RESULTS: Electroretinogram abnormalities were detected in six infants, associated with delayed visual evoked potentials in four of them. CONCLUSION: Early electroretinogram and visual evoked potentials testing evidenced neurophysiological visual disturbances in a subset of infants born to mothers treated by hydroxychloroquine. Systematic clinical and neurophysiological vision testing during childhood is needed to detect possible consequences of antenatal exposure to hydroxychloroquine.

[Newborn infants supported by extracorporeal membrane oxygenation: survival and clinical outcome]. / Survie et devenir clinique des nouveau-nés mis en assistance respiratoire extracorporelle.

OBJECTIVES: To assess the prognosis of newborn infants with refractory hypoxemia who required extracorporeal membrane oxygenation (ECMO). METHODS: Eighty-nine newborn infants treated by ECMO during more than 24 hours over a 8-year period (1996-2003) were included in this observational cohort study with a 9-month and 24-month evaluation. RESULTS: Respiratory failure mainly resulted from meconium aspiration syndrome (MAS, 43%), congenital diaphragmatic hernia (CDH, 15%) and sepsis (15%). Overall survival at hospital discharge was 67%. Infants with MAS had the best survival rate (82%) and those with CDH had the worst (46%). Of the remaining 60 survivors, 53% remained oxygen dependent at 28 days and 33% at 45 days. At the age of 2 years, only 1 infant remained oxygen dependent (but did not required oxygen at 3 years) and only 3 infants had significant neurodevelopmental problems. CDH group was associated with a prolonged duration in supplementary oxygen (P<0.001) and a prolonged duration for tube feeding (P=0.01) as compared with other diagnoses. Regarding neurologic outcome, CDH infants had the poorer neurological acquisition rate at 9 months but a very good evolution by the time of the 24-month evaluation. CONCLUSIONS: Morbidity in ECMO survivors is low considering the severity of illness in the newborn period, mainly related to pulmonary and feeding dysfunctions during the first months, in particular for the CDH group. Outcome at the age of 2 years of CDH infants is most often favourable regarding growth and neurodevelopmental evolution.

[Determinants of diphemanil methylsulfate (Prantal) utilization: a survey of practice in the French neonatal and intensive care units]. / Enquête française sur l'utilisation du diphémanil méthylsulfate (Prantal) dans les unités de néonatologie.

UNLABELLED: Diphemanil methylsulfate (Prantal) is a quaternary ammonium with parasympathicolytic properties. It is used in premature and term neonates with bradycardias related to vagal hyper reflectivity (HRV). OBJECTIVES: To assess the use of Prantal in the French neonatal and intensive care units: its indications, its modalities of use, its side effects and the number of patients treated during 1 year (2004) in France. METHODS: A questionnaire was electronically sent to all neonatology units and all neonatal intensive care units in France. RESULTS: Among 202 units, 121 (60%) answered the questionnaire. Prantal was reported to be used in 51 (42.1%) units. Among them, 38 (31.4%) actually treated 169 patients in 2004 with a mean number of patients treated by unit of 4. The diagnostic of HRV was supported by: a history of malaise (84.3%), bradycardia (94.1%), oculocardiac reflex (74.5%), cardiac Holter (76.4%), cardiorespirographic recording (19.6%), esophageal pHmetry (35.2%) and esophageal fibroscopy (21.5%). The mean starting dosing was 4.7 mg/kg/d, the mean maximal dosing was 9 mg/kg/d and the mean daily intakes were initially 2.3 and secondary 2.9. Prantal dosing was adjusted to weight in 54.9%, every month in 85.7%. Treatment was stopped at the mean post-natal age of 6 months, mostly in a progressive manner and without monitoring help. CONCLUSION: Prantal was seldom used in 2004 in France for different reasons: HRV is an uncertain entity, the efficacy of Prantal has not been validated and atropinic side effects can be encountered.

[Perinatal consequences of maternal connective tissue diseases: a prospective study of 73 cases]. / Conséquences périnatales des connectivites maternelles: étude prospective de 73 cas.

AIM: To describe a group of newborns born from mothers with connective tissue diseases, to determine their perinatal characteristics and the neonatal morbidity, and to assess the possible role of drugs received by mothers on the obstetrical and neonatal morbidity. PATIENTS AND METHODS: During a 34-month period, newborns born from mothers with connective tissue diseases and followed in a single center were prospectively included in the study. In all cases, maternal treatments (i.e. hydroxychloroquine and/or prednisone) were continued during pregnancy. RESULTS: Among the 73 included infants, 18 (25%) were born before 37 weeks of gestation and 3 (4%) were small for gestational age. A neonatal lupus syndrome with facial rash and thrombopenia was observed in 1 case. No neonatal congenital heart block was observed and maternal treatment did not significantly influence the mean PR or QT intervals. Four infants had minor congenital abnormalities and 3 had feto-maternal infection. CONCLUSION: These data show that perinatal morbidity is lower than that previously published. We postulate that a strict follow-up during pregnancy may have played a significant positive role in these results.

[Apnea of prematurity: risk factors and ambulatory treatment with caffeine citrate]. / Apnées tardives du prématuré: facteurs de risque, traitement ambulatoire par citrate de caféine.

INTRODUCTION: Apnea of prematurity develop during the first days of life and usually resolve by the time the infant reaches 36-37 weeks postmenstrual age. In a few cases, they persist beyond term, especially in infants delivered at the youngest gestational ages (24-28 GA), and require specific care. In our unit, those preterm babies are discharged home with caffeine citrate treatment. Discontinuing the treatment is performed in hospital when they achieve a postmenstrual age of at least 42 weeks. OBJECTIVE: To identify predictive factors of persistent apnea in preterm babies. MATERIAL AND METHODS: Retrospective study comparing a population of 41 preterm infants discharged with treatment to 123 preterm babies discharged without treatment to identify predictors of persistent apnea. RESULTS: Factors significantly associated were: birth weight<1500 g, initial hypotension, gastroesophageal reflux, need for continuous positive airway pressure and multiparity. At home, no infant died and no adverse effect was reported by parents. CONCLUSION: Persistent apnea can be responsible for prolonged hospitalization. Risk factors can be identified in some children. Discharging with treatment can be an alternative to their hospitalization.

[Caffeine citrate utilization for treatment of apnea in French neonatal units]. / Utilisation du citrate de caféine pour le traitement des apnées idiopathiques du prématuré dans les équipes Françaises de médecine néonatale.

UNLABELLED: Caffeine citrate is commonly used for prophylaxis and treatment of apnea in preterm babies. OBJECTIVE: To evaluate the use of caffeine citrate in french neonatal units. MATERIALS AND METHODS: Postal survey in 100 neonatal units. RESULTS: Answers were obtained from 81 units. Sixty-three units use systematic prophylactic treatment and the threshold of gestationnal age (weeks gestation) for this systematic treatment is 32 weeks. Caffeine citrate is administered as a loading dose of 20 mg/kg followed by a maintenance dose of 5 mg/kg in 95% of the units. Discontinuing the treatment occurs between 33 and 35 weeks in 37% of the units and between 35 and 37 weeks in 53%. Two third of neonatologits describe recurrent apnea beyond 37 weeks, with the need to continue treatment. Fourteen units sometimes discharge babies at home with ambulatory caffeine citrate treatment and discontinue treatment by 42 to 46 weeks'gestation. A mean duration of 5 days without apnea is required before discharge. CONCLUSION: French teams respect "recommendations" concerning doses and duration without apnea before discharge. Indication of treatment, threshold for systematic treatment, duration of treatment and ambulatory treatment differ among teams.

[Use of diazepam in the treatment of opioid neonatal abstinence syndrome]. / Traitement par le diazépam du syndrome de sevrage néonatal aux opiacés (23 cas).

INTRODUCTION: The fetal opiate exposure presents many risks for the newborn. One of the most important is the neonatal abstinence syndrome that associates neurological and digestive signs. In some cases the vital prognosis can be involved. The evaluation of the syndrome's severity is based on certificated scales. The mortality has been reduced by the improved management of these neonates. Diamorphine, phenobarbital, chlorpromazine and diazepam are the most currently used. However, there is no consensus on the treatment. The data concerning the treatment are controversial, especially for the use of diazepam. The aim of our study was to describe the effects of diazepam obtained in three different centers and to compare our results to those of the literature. POPULATION AND METHODS: Twenty-three neonates were included. They were all hospitalized for abstinence syndrome and treated by diazepam. The Finnegan scale was used to evaluate the symptom's severity and the effects of the diazepam. The principal evaluation criteria were the duration of treatment and hospitalization, the timing in recovery of birth weight and the percentage of birth weight loss. RESULTS: The average treatment duration was 7 days, the average hospitalization duration was 18 days, the birth weight was recovered at 10 days of life and the percentage of loss of birth weight was 6.5%. Diazepam treatment failed in only one case. No case of intense dehydration occurred. CONCLUSION: Due to the retrospective design of the study, the diazepam could not be compared to other drugs. Nevertheless, it argues against the "anti-diazepam" attitude. A controlled randomised prospective study is needed to evaluated the optimal therapeutic strategy.

[Analgesic effects of Emla cream and saccharose solution for subcutaneous injections in preterm newborns: a prospective study of 265 injections]. / Effet analgésique de la crème Emla, du saccharose et de leur association pour les injections sous-cutanées chez le nouveau-né prématuré: étude prospective de 265 injections.

OBJECTIVE: To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants. METHODS: Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS). RESULTS: Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation. CONCLUSION: This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO.

[Congenital toxoplasmosis: a new case of infection during pregnancy in an previously immunized and immunocompetent woman]. / Toxoplasmose congénitale: un nouveau cas d'infection pendant la grossesse chez une femme antérieurement immunisée et immunocompétente.

UNLABELLED: Congenital toxoplasmosis is a potentially serious infection which usually affects infants born to non immune women. CASE REPORT: Our case report focuses on a baby born to a normally immunocompetent woman previously immunized against toxoplasmosis. To our knowledge only three similar cases have been published until now. CONCLUSION: We conclude that in front of a patient neonatal congenital infection picture, toxoplasmosis cannot be excluded on the ground of maternal immunity status and must be quickly investigated, given the emergency of appropriate treatment.

[Neonatal resuscitation in the delivery room: educational process and evaluation]. / Réanimation du nouveau-né en salle de naissance : démarche pédagogique et évaluation.

Based upon a three necessities basis: public health, biological and medico-legal, this article presents the state of the art about teaching neonatal resuscitation in the delivery room. The educational process is present worldwide; main experiences are described. Evaluation of these actions varies in the literature. We analyze the evaluation of the process of the trained professionals, their satisfaction, the changes in their practices, their theoretical and practical levels, and the impact on newborns' health. We propose a few measures to make official this kind of teaching in France, with a certificate for instructors and trained professionals.