Neonatal end-of-life decision-making almost 20 years after the EURONIC study: A French survey.

Nearly 20 years ago the EURONIC study reported that French neonatologists sometimes deemed it legitimate to terminate the lives of newborn infants when the prognosis appeared extremely poor. Parents were not always informed of these decisions. Major change has occurred since then and is described herein. MATERIAL AND METHODS: A survey was conducted in the Île-de-France region, from 1 January to 31 January 2016. Professionals from 15 neonatal intensive care units (NICUs) were invited to complete a questionnaire. RESULTS: A total of 702 questionnaires were collected and 670 responses were analyzed. Knowledge of the law differed according to professional status, with 71% of MDs (medical staff, MS), compared with 28% of nonmedical staff (NMS) declaring that they had good knowledge of the law. Most MDs and NMS believed that withholding or withdrawing life-sustaining treatments (WWLST) could be decided and implemented after a delay. Half of them thought that WWLST would always result in death. Although required by law, a consulting MD attended the collegial meeting required before deciding on WWLST in only half of the cases. Parents were almost always informed of the decision thereafter by the physician in charge of their infant. The most frequent disagreement with parents was observed when WWLST was the option selected. In this case, most professionals suggested postponing WWLST, continuing intensive care and dialogue with parents, aiming at a final shared decision. Major differences were observed between NICUs with regard to the withdrawal of artificial nutrition and hydration. Finally, 14% of MDs declared that infant active terminations of life still occurred in their NICU. Major differences concern WWLST and active termination of life, whose meaning has been partly modified since 2001. CONCLUSION: Several major changes were observed in this survey: (1) treatment withdrawal decisions are made today in agreement with the law; (2) parents' information and involvement in the decision process have profoundly changed; (3) active termination of life (euthanasia) very rarely occurs; only at the end of a process in accordance with ethical principles and within the law is this decision made.

[How to decide with precision, justice, and equity? Reflections on decision-making in the context of extreme prematurity. Part two: moving toward making the best possible decision: defining conditions for putting decisions into practice]. / Comment décider avec justesse, justice et équité? Réflexion sur la décision en situation d'extrême prématurité. Deuxième partie: comment tendre vers une décision optimale? Définition des conditions d'exercice de la décision.

Extreme premature child's long-term prognostic is getting better and better known, and if a resuscitation procedure is possible at birth, it won't guarantee survival or a survival free of disability. Incertitude toward individual prognosis and outcome for those children remains considerable. In this field, we are at the frontier of medical knowledge and the answer to the question, "how to decide the ante and postnatal care" is crucial. This work is focused on this problematic of decision-making in the context of extreme prematurity. It attempts to deconstruct this concept and to explicit its stakes. Thus, with the support of the medical sources and of philosophical debates, we tried to build a decision-making procedure that complies with the ethical requirements of medical care, accuracy, justice and equity. This decision-making procedure is primarily concerned with the singularity of each decision situation and it intends to link it closely to the notions of rationality and responsibility.

[How to decide with precision, justice, and equity? Reflections on decision-making in the context of extreme prematurity. Part one: the problematics of decision-making in the context of extreme prematurity]. / Comment décider avec justesse, justice et équité? Réflexion sur la décision en situation d'extrême prématurité. Première partie: problématique de la décision dans le contexte de la prématurité extrême.

Extreme premature child's long-term prognostic is getting better and better known, and if a resuscitation procedure is possible at birth, it won't guarantee survival or a survival free of disability. Incertitude toward individual prognosis and outcome for those childs remains considerable. In this field, we are at the frontier of medical knowledge and the answer to the question, "how to decide the ante and postnatal care?" is crucial. This work is focused on this problematic of decision making in the context of extreme prematurity. It attempts to deconstruct this concept and to explicit its stakes. Thus, with the support of the medical sources and of philosophical debates, we tried to build a decision-making procedure that complies with the ethical requirements of medical care, accuracy, justice and equity. This decision-making procedure is primarily concerned with the singularity of each decision situation and it intends to link it closely to the notions of rationality and responsibility.

[Palliative care for newborn infants with congenital malformations or genetic abnormalities]. / Démarche palliative chez le nouveau-né atteint de malformations ou d'anomalies génétiques sévères.

The choice of palliative care can be made today in the perinatal period, as it can be made in children and adults. Palliative care, rather than curative treatment, may be considered in three clinical situations: babies born at the limits of viability, withholding/withdrawing treatments in the NICU, and babies with severe malformations of genetic abnormalities identified during pregnancy. Only the last situation is addressed hereafter. In newborn infants as in older patients, palliative care aims at taking care of the baby and at providing comfort and well-being. The presence of human beings by the newborn infant, most importantly the parents and family, is of utmost importance. The available time should not be used only for care and medical treatments. Sufficient time should be kept for the parents to interact with the baby and for human presence and warmth. The best interests of the newborn infant are the main element for guiding appropriate care. Before birth, the choice of palliative care for newborn infants requires successive steps: (1) establishing a diagnosis of malformation(s) or genetic abnormalities; (2) making a prognosis and ruling out intensive treatments at birth and thereafter; (3) giving the parents appropriate information; (4) assisting the pregnant woman in deciding to continue pregnancy while excluding intensive treatment of the newborn baby; (5) dialoguing with parents about the expected duration of the baby's life and the related uncertainty; (6) planning of palliative care to be implemented at birth; (7) preparing a plan with the parents for discharging the infant from the hospital and for taking care of him over a long time, when it is deemed possible that the baby may live for more than a few days.

[Lung protective strategies for premature infants]. / Stratégies de protection pulmonaire chez les prématurés.

Despite many advances in perinatal medicine, bronchopulmonary dysplasia still frequently occurs in very premature infants. The very fragile lungs of these infants therefore have to be protected from birth. The protective strategies consist in applying positive expiratory pressure immediately, and using exogenous surfactant in a prophylactic or early use approach. The recent, variable flow, continuous positive airway pressure (CPAP) systems are very efficient and may allow to avoid tracheal intubation, or to facilitate weaning. When mechanical ventilation has to be used, high peak pressure and/or high tidal volume have to be avoided in order to prevent volutrauma. Accepting not to normalize PCO(2) contributes to it. High frequency oscillatory ventilation, which actually does not prevent bronchopulmonary dysplasia, is an extremely efficient ventilatory support technique for severe respiratory failure. Postnatal gluco-corticoid use reduces the rate of bronchopulmonary dysplasia at 36 weeks, but also results in an increased incidence of long-term neurological handicaps. In our experience, using these treatments can be avoided. Maternal transfer to a level three perinatal center, associated with the adequate use of theses lung protective strategies following very premature birth enable the less unfavorable results to be obtained.

Impact of delayed repair and elective high-frequency oscillatory ventilation on survival of antenatally diagnosed congenital diaphragmatic hernia: first application of these strategies in the more "severe" subgroup of antenatally diagnosed newborns.

OBJECTIVE: a) To analyze the influence of a new management strategy on the outcome of neonates with antenatally diagnosed congenital diaphragmatic hernia (CDH); b) to determine early prognosis respiratory factors with the new strategy. DESIGN: Retrospective study. SETTING: Level III perinatal center. PATIENTS AND METHOD: Between 1985 and 1997, 51 consecutive neonates with antenatally diagnosed CDH were admitted to our level III neonatal intensive care unit. Before 1992 (period 1; n = 19), we used conventional mechanical ventilation and early surgery requiring transfer. Since 1992 (period 2; n = 32), we prospectively tested a new approach including (a) systematically use of high-frequency oscillatory ventilation (HFOV) regardless of the initial clinical severity, (b) delayed surgery following stabilization requiring transfer to a different surgical unit, but (c) no transfer of unstable patients with surgery under HFOV in our neonatal intensive care unit (n = 10). The two cohorts were comparable in terms of potential ante and postnatal prognostic indicators. RESULTS: Survival was improved with the new strategy: 21/32 (66%) vs. 5/19 (26%); P < 0.02. This improvement between periods 1 and 2 was due to a decrease in both preoperative and postoperative deaths in the later period. The better survival during period 2 was associated with the appearance of very late deaths, frequent pleural effusions, and the survival of more severe forms having evolved to a chronic respiratory insufficiency. Survivors were ventilated for longer time with longer duration of oxygen supplementation. The best oxygenation index (OI), alveolar arterial difference and oscillation amplitude (P/P) during the first 24 h, but not the best PaCO2, were the most reliable prognostic indicators during period 2. An OI < or = 10 with a P/P < or = 55 cmH2O was associated with a very good prognosis (94% survival). CONCLUSIONS: The prognosis of antenatally diagnosed CDH was improved by systematic HFOV on admission, no systematic transfer, and delayed surgery. This improvement is associated with modification of postnatal outcome.

Estimation of inspiratory pressure drop in neonatal and pediatric endotracheal tubes.

Endotracheal tubes (ETTs) constitute a resistive extra load for intubated patients. The ETT pressure drop (DeltaP(ETT)) is usually described by empirical equations that are specific to one ETT only. Our laboratory previously showed that, in adult ETTs, DeltaP(ETT) is given by the Blasius formula (F. Lofaso, B. Louis, L. Brochard, A. Harf, and D. Isabey. Am. Rev. Respir. Dis. 146: 974-979, 1992). Here, we also propose a general formulation for neonatal and pediatric ETTs on the basis of adimensional analysis of the pressure-flow relationship. Pressure and flow were directly measured in seven ETTs (internal diameter: 2.5-7.0 mm). The measured pressure drop was compared with the predicted drop given by general laws for a curved tube. In neonatal ETTs (2.5-3.5 mm) the flow regime is laminar. The DeltaP(ETT) can be estimated by the Ito formula, which replaces Poiseuille's law for curved tubes. For pediatric ETTs (4.0-7.0 mm), DeltaP(ETT) depends on the following flow regime: for laminar flow, it must be calculated by the Ito formula, and for turbulent flow, by the Blasius formula. Both formulas allow for ETT geometry and gas properties.

Long-term pulmonary functional outcome of bronchopulmonary dysplasia and premature birth.

Pulmonary function and exercise tolerance were evaluated in late childhood in two groups of prematurely born children: one group with bronchopulmonary dysplasia (BPD) [n = 15; gestational age at birth (GA): 29.6 +/- 2.8 weeks; birth weight (BW): 1,367 +/- 548 g; age at test: 7.9 +/- 0.6 years], and a second group without significant neonatal lung disease [pre-term (PT)] (n = 9; GA: 30.3 +/- 1.7 weeks; BW: 1,440 +/- 376 g; age at test: 7.8 +/- 0.22 years). The results were compared with a control group of children of similar ages and heights, born at term [term born (TB)]. We observed that total lung resistance (RL) was significantly higher in BPD (11 +/- 3 cmH2O/L/s), and in PT (9 +/- 2) than in TB [5 +/- 1; (P < 0.001 and P < 0.05, respectively)]. In BPD RL was higher than in PT (P < 0.05). Dynamic lung compliance (CLdyn) was decreased in BPD (43 +/- 11 mL/cmH2O) and in PT (56 +/- 17) compared with TB (76 +/- 20) (P < 0.001 and P < 0.05), and also in BPD compared with PT (P < 0.05). Forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were lower in BPD (1.07 +/- 0.15 L and 72 +/- 7%) than in PT (1.29 +/- 0.23 L, and 80 +/- 7%) (P < 0.05). Exercise tests were performed in six boys with BPD. The ratio between minute ventilation at maximal workload (VEmax) and the predicted value of maximal voluntary ventilation (MVV) was elevated in the six BPD boys tested, compared with five boys of Group 2 and five TB boys (87 +/- 15% vs. 62 +/- 14% and 65 +/- 13%) (P < 0.05). We conclude that: 1) prematurity and BPD is followed by long-term airway obstruction and a mild degree of exercise intolerance and; 2) premature birth without BPD may be followed by a milder degree of airway obstruction in childhood than in infants who developed BPD during the neonatal period.

Pulmonary function in infancy and in childhood following mechanical ventilation in the neonatal period.

Pulmonary function was evaluated in both infancy and childhood in the same 19 prematurely born infants, who required mechanical ventilation (MV) during the neonatal period. Results of our patients were compared with those of control subjects. Upon first evaluation, we found that lung resistance (RL) was significantly elevated (24.85 +/- 6.06 vs. 17.77 +/- 2.39 cmH2O/L/s; P less than 0.01). The mean value of dynamic lung compliance (CLdyn) was low, but the difference compared to controls did not reach significance. From infancy to childhood, elevated RL persisted (9.33 +/- 2.51 vs. 6.52 +/- 1.52 cm H2O/L/s; P less than 0.01), and the decrease of CLdyn became significant (46.86 +/- 12.84 vs. 59.34 +/- 15.68 mL/cmH2O; P less than 0.05). In addition, maximum flow at functional residual capacity was significantly decreased (0.824 +/- 0.284 vs. 1.215 +/- 0.358 L/s; P less than 0.01); whereas pulmonary diffusing capacity for carbon monoxide was similar in the patients (7.62 +/- 2.16 mL/min/mm Hg) and in the controls (8.38 +/- 1.6). Pulmonary dysfunction following premature birth, respiratory distress, and prolonged MV may not resolve from infancy to childhood.

Inspiratory work of breathing in ventilated preterm infants.

In ventilated newborns, part of the inspiratory work of breathing (WOB) may be due to the inspiratory efforts preceding inspiratory ventilator flow. This study was designed to quantify the contribution of these efforts to WOB. WOB was evaluated in six intubated preterm infants ventilated by the Dräger Babylog 8000. The ventilatory modes studied were intermittent mandatory ventilation (IMV), continuous positive airway pressure (CPAP), and assist-control ventilation at 10 (ACV10) and 15 (ACV15) cmH2O peak pressure. Mouth flow (V) and esophageal pressure (Pe) were recorded, and WOB was estimate from the area delineated by the esophageal pressure-volume curve, where volume is the time integral of V. Calculation of WOB started either at the onset of the infant's inspiratory flow (WOBi), or at the beginning of the infant's inspiratory muscle efforts, detected on Pe and confirmed on the V tracing (WOBm). WOBm was found to be significantly higher than WOBi under all ventilatory conditions studied. The difference in work of breathing (delta W) between WOBm and WOBi did not depend on the type of ventilatory mode. When delta W was related to WOBm, it amounted to about 30% of WOBm in IMV and CPAP, and 60% in ACV (P < 0.05, ACV15 vs. IMV). These results suggest that, in preterm infants connected to a ventilator, inspiratory efforts preceding flow inspiration might account for a large fraction of the inspiratory work of breathing.

Pulmonary function at 1 year of age in survivors of neonatal respiratory distress: a multivariate analysis of factors associated with sequelae.

We studied pulmonary function 1 year after neonatal respiratory distress (RD) in 54 infants who had been treated at birth in the same neonatal intensive care unit. RD was related to hyaline membrane disease in 36 cases (group I) and to other causes in 18 cases (group II). Compared with predicted values, dynamic lung compliance (CL) was lower (less than -2 SD) and total pulmonary resistance (RL) was higher (+2 SD) in 18 (33%) and 12 (22%) infants, respectively. The relationships between these functional abnormalities at 1 year of age and the characteristics of the neonatal respiratory disease were assessed using a multifactorial analysis (multiple correspondences analysis). We found that elevated RL (greater than +2 SD) at 1 year of age was very significantly related with hyaline membrane disease, involving both high rate of positive pressure ventilation and prolonged intubation, and with the presence of both tachypnea and abnormal chest X rays at the time of discharge. Compared with elevated RL, the relationships between low CL (less than -2 SD) and the same neonatal characteristics were less significant; in particular, there was no strong link between low CL and hyaline membrane disease. Finally, birth before 30 weeks gestation was an index of severity.

Corticosteroids and chronic lung disease in extremely immature infants: a dilemma.

What is the balance of benefits and risks of dexamethasone in extremely immature infants? The answer remains unclear. We feel that the risks of "early" treatment outweigh the benefits, because many infants who would not develop CLD will be treated. Treatment between day 7 and day 14 seems more appropriate to us, as it focuses on infants with a high risk of developing CLD. However, the lungs may be already somewhat damaged when starting treatment, whose expected benefit is a shortened duration of mechanical ventilation and a decreased incidence of CLD. The risks for growth and brain development are not clearly assessed. Both 7-day courses and pulse therapy are effective, but no comparison of these 2 schedules has been published. We therefore do not know whether pulse therapy provides the same benefits as 7-day courses with fewer risks for growth or cardiomyopathy.

[Erythropoietin and anemia in premature infants]. / Erythropoïétine et anémie du prématuré.

Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many premature infants receive multiple blood transfusions. To reduce the number of those transfusions, treatment with EPO and iron supplementation is routinely used in premature infants. Even if the efficacy of this treatment is demonstrated, the results are not so good in the very low birth weight infants or very small gestational age infants and the need of transfusion is still important. This is due for a large part to blood loss in these very small infants. But there are also other explanations. Thus the pharmacokinetics of EPO is different in premature infants and newborn than in adults. Best dose, best way of administration (i.v. or subcutaneous), best number of injections per week are not already known. Further study has to be done to achieve a better use and efficacy of this treatment.

[Conjoined omphalopagous twins separated at fifteen days of age]. / Jumelles conjointes omphalopages séparées à 15 jours de vie.

BACKGROUND: Conjoined (siamese) twins represent a rare situation which may occur in 1 of every 50,000 births. A prenatal diagnosis usually leads to stopping pregnancy. We report a case with successful surgical separation at the age of 15 days. CASE REPORT: Ultrasonographic examination at 20 weeks of gestation showed omphalopagus siamese joined at the abdomen from the xiphoid process to the umbilicus. Conjoined structures included liver. There was a multicystic right kidney in one twin, without other malformation. Karyotype was normal, 46XX. The mother refused interruption of her pregnancy. Both girls were born by cesarean section. Angiography, magnetic resonance imaging and intravenous urography confirmed the ultrasound examination. There was no cross circulation into the liver and the gastrointestinal tract was not conjoined. The twins were separated at 15 days of age with right heminephrectomy of the multicystic kidney. The girls are now 16 months old and are in very good health. CONCLUSION: Prognosis of siamese twins depends on the nature of joined structures and presence of malformations. Ultrasonographic examination during pregnancy shows the possibility of surgical separation, which is performed by a double anesthetic and surgical pediatric team. Preoperative investigations must include MRI.

[Acute retinopathy of prematurity following oxygen therapy: current concepts (author's transl)]. / Données actuelles sur la rétinopathie aiguë du prématuré sous oxygénothérapie.

Five cases of retinopathy of prematurity have been observed among 1,750 premature infants at the Florence Geller Center in Cochin-Port-Royal--C.H.U. over a period of four years. In all cases, arterial PaO2 was more than 100 mmHg at least once. In the two worst cases, oxygen therapy given only during the first had been hours of life. The authors insist on the dangers of oxygen overdose immediately after birth or during transport to a Premature Infants Center. Laser photocoagulation was employed in four eyes: 2 with regression, 1 with cicatrisation, 1 with fibroplasia. Retinopathy of prematurity remains a danger in France, even if it is not as frequent as in the U.S.A. or Japan. Indirect ophthalmoscopy is essential for diagnosis and fluorography very useful to determine prognosis and treatment.

[Prenatal risk evaluation, parent information and mode of delivery]. / Evaluation des risques en anténatal, information des parents et prise en charge de l'accouchement.

Perinatal networks, antenatal administration of glucosteroids, postnatal administration of surfactant, and new techniques for mechanical ventilation, have considerably improved the prognosis of extremely preterm infants. Such recent progress in perinatology had enabled neonatologists to provide intensive care for infants born after 24 and 28 weeks of gestation. This practice raises serious medical and ethical issues. The optimal mode of delivery of such newborns is not well established mainly because available studies are retrospective and subjected to biases. Moreover, perinatologists are implicated in the continuing discussion on ethical issues that modify clinical practices.

[Extremely preterm infants: resuscitation criteria in the delivery room and dialogue with parents before birth]. / Critères de réanimation des prématurissimes en salle de naissance: quel discours en anténatal?

The resuscitation of extremely preterm infants presents complex medical, social and ethical issues for the families and the health professionals. The principle of a systematic resuscitation "temporary intensive care" does not prohibit the question of a limit in terms of gestational age and birth weight. In France, a do not resuscitate order (comfort care alone) is appropriate for newborns weighing less than 500g and/or with a gestational age of less than 24 weeks' since the mortality is nearly 100%. The survival of infants born at 24 weeks' gestational age remains low with significant risks of chronic medical problems and neurodevelopmental disabilities. The decisions regarding the extent of resuscitative efforts depend on antenatal factors, condition of the neonate at birth and the parental opinion. Before the delivery, parents should receive appropriate information about survival and risks of adverse long-term outcome. The physician should follow the parents' desires whenever the parents' decision would not obviously violate the infants' best interests. However, they must be informed that decisions about neonatal management made before the delivery can have to be changed in the delivery room, depending on the condition of the neonate at birth. At 25 weeks of gestational age, the prognosis is better and the resuscitation should be more intensive.

[Repetition of corticoid treatment for fetal lung maturation: clinical and experimental scientific data]. / Répétition des cures de corticoïdes pour maturation pulmonaire foetale: données scientifiques cliniques et expérimentales.

Before 34 weeks, one course of antenatal corticosteroids significantly decreases neonatal mortality and morbidity. Courses are repeated every week, because of their alleged loss of efficiency after 7 days, although the relative benefits and risks of repeated courses are poorly known. Data from the literature suggest that improvement in lung function after repeated courses depends on the reduction of the treatment/birth interval and not on the rise in the cumulative dose. These benefits must be balanced against the risk of decreased birth weight induced by repeated courses. Because of their effect on fetal growth, weekly courses of corticosteroids should no longer be given systematically. In clinical practice, pregnancies at high risk of preterm delivery must be reassessed every week before prescribing a new course. Both better understanding of treatment duration of corticosteroids and randomized controlled trials comparing one and multiple courses are needed to improve antenatal management of neonatal respiratory stress syndrome.

[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.