Jean-Claude Fauchère

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children

CD31+CD45RA+RO– lymphocytes contain high numbers of T cell receptor circle (TREC)‐bearing T cells; however, the correlation between CD31+CD4+ lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31+ and CD31– CD4+ lymphocytes in healthy individuals from birth to old age. Sorted CD31+CD45RA+RO– naive CD4+ lymphocytes contained high TREC numbers, whereas CD31+CD45RA–RO+ cells (comprising ⩽5% of CD4+ cells during aging) did not contain TREC. CD31+ overall CD4+ cells remained TREC rich despite an age‐related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31+CD45RA+RO–CD4+ cells exhibited significantly longer telomeres and higher telomerase activity than CD31–CD45RA+RO–CD4+ cells, suggesting that CD31+CD45RA+RO–CD4+ cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4+ as well as naive CD45RA+RO–CD4+ cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5–12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC‐rich lymphocytes essentially in lymphopenic children after HSCT.

The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized, Controlled Trial

OBJECTIVE. Our goal was to investigate the effect of placentofetal transfusion on cerebral oxygenation in preterm infants by near-infrared spectroscopy. SUBJECTS. A total of 39 preterm infants with a median gestational age of 30.4 weeks were randomly assigned to an experiment group (n = 15) and a control group (n = 24). INTERVENTIONS. The delivery of the infants in the experiment group was immediately followed by maternal administration of syntocinon, the infant was placed 15 cm below the placenta, and cord clamping was delayed by 60 to 90 seconds. The infants in the control group were delivered conventionally. At the ages of 4 and 24 hours, cerebral hemoglobin concentrations, cerebral blood volume, and regional tissue oxygenation were measured by near-infrared spectroscopy. RESULTS. Cerebral blood volume was not different between the 2 groups at the age of 4 hours (6.1 vs 5.8 mL/100 g of tissue) nor at the age of 24 hours (6.2 vs 6.2 mL/100 g of tissue). Mean regional tissue oxygenation of the experiment group was higher at the ages of 4 hours (69.9% vs 65.5%) and of 24 hours (71.3% vs 68.1%). CONCLUSION. Delayed clamping of the umbilical cord improves cerebral oxygenation in preterm infants in the first 24 hours.

Methadone maintenance program in pregnancy in a Swiss perinatal center (II): neonatal outcome and social resources

Background:  The aim of the study was to analyze the neonatal impact of a methadone maintenance program in pregnancy, and the social resources of the families involved.

Grief and Post-Traumatic Growth in Parents 2–6 Years after the Death of Their Extremely Premature Baby

Objective: To assess grief and post-traumatic growth in parents 2–6 years after the death of a premature baby (24–26 weeks’ gestation) and to evaluate Pictorial Representation of Illness and Self-Measure (PRISM) in the assessment of bereavement. Method: Fifty-four parents were assessed for their experiences during hospitalization and by questionnaires regarding grief (MTS), post-traumatic growth, affective symptoms and the visual representation of the baby and the self of the parents (PRISM). Results: Even 2–6 years after the loss of their extremely preterm infant the parents still suffer a lot from their bereavement, mothers more so than fathers (Mann-Whitney U test, U = 230.5, p < 0.05). Having another child reduced the level of grief (U = 119.0, p < 0.05). Mothers showed more post-traumatic growth than fathers (U = 140.5, p < 0.001). For all parents a shorter distance between the baby and the self (PRISM) correlated with greater grief (ρ = –0.62, p < 0.001); in multiple regression analysis MTS explained 38% of the SBS-variance. Conclusions: Clinicians should be aware that the death of an extremely premature infant triggers not only a painful long-term process of mourning but also of individual personal growth. Adaptation processes after the death differ depending on gender, with mothers experiencing more intense grief but also more growth than fathers. The modified PRISM test is recommended as a visual, non-verbal and easy-to-use instrument to assess bereavement.

Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland 2011 Revision of the Swiss recommendations

Perinatal care of pregnant women at high risk for preterm delivery and of preterm infants born at the limit of viability (22-26 completed weeks of gestation) requires a multidisciplinary approach by an experienced perinatal team. Limited precision in the determination of both gestational age and foetal weight, as well as biological variability may significantly affect the course of action chosen in individual cases. The decisions that must be taken with the pregnant women and on behalf of the preterm infant in this context are complex and have far-reaching consequences. When counselling pregnant women and their partners, neonatologists and obstetricians should provide them with comprehensive information in a sensitive and supportive way to build a basis of trust. The decisions are developed in a continuing dialogue between all parties involved (physicians, midwives, nursing staff and parents) with the principal aim to find solutions that are in the infants and pregnant womans best interest. Knowledge of current gestational age-specific mortality and morbidity rates and how they are modified by prenatally known prognostic factors (estimated foetal weight, sex, exposure or nonexposure to antenatal corticosteroids, single or multiple births) as well as the application of accepted ethical principles form the basis for responsible decision-making. Communication between all parties involved plays a central role. The members of the interdisciplinary working group suggest that the care of preterm infants with a gestational age between 22 0/7 and 23 6/7 weeks should generally be limited to palliative care. Obstetric interventions for foetal indications such as Caesarean section delivery are usually not indicated. In selected cases, for example, after 23 weeks of pregnancy have been completed and several of the above mentioned prenatally known prognostic factors are favourable or well informed parents insist on the initiation of life-sustaining therapies, active obstetric interventions for foetal indications and provisional intensive care of the neonate may be reasonable. In preterm infants with a gestational age between 24 0/7 and 24 6/7 weeks, it can be difficult to determine whether the burden of obstetric interventions and neonatal intensive care is justified given the limited chances of success of such a therapy. In such cases, the individual constellation of prenatally known factors which impact on prognosis can be helpful in the decision making process with the parents. In preterm infants with a gestational age between 25 0/7 and 25 6/7 weeks, foetal surveillance, obstetric interventions for foetal indications and neonatal intensive care measures are generally indicated. However, if several prenatally known prognostic factors are unfavourable and the parents agree, primary non-intervention and neonatal palliative care can be considered. All pregnant women with threatening preterm delivery or premature rupture of membranes at the limit of viability must be transferred to a perinatal centre with a level III neonatal intensive care unit no later than 23 0/7 weeks of gestation, unless emergency delivery is indicated. An experienced neonatology team should be involved in all deliveries that take place after 23 0/7 weeks of gestation to help to decide together with the parents if the initiation of intensive care measures appears to be appropriate or if preference should be given to palliative care (i.e., primary non-intervention). In doubtful situations, it can be reasonable to initiate intensive care and to admit the preterm infant to a neonatal intensive care unit (i.e., provisional intensive care). The infants clinical evolution and additional discussions with the parents will help to clarify whether the life-sustaining therapies should be continued or withdrawn. Life support is continued as long as there is reasonable hope for survival and the infants burden of intensive care is acceptable. If, on the other hand, the health care team and the parents have to recognise that in the light of a very poor prognosis the burden of the currently used therapies has become disproportionate, intensive care measures are no longer justified and other aspects of care (e.g., relief of pain and suffering) are the new priorities (i.e., redirection of care). If a decision is made to withhold or withdraw life-sustaining therapies, the health care team should focus on comfort care for the dying infant and support for the parents.

End-of-life decisions in delivery room and neonatal intensive care unit.

Background: The increase in neonatal survival in recent decades has been followed by an increase in later disabilities. This has given rise to many new ethical issues. In different countries, efforts are being made to define ethical guidelines regarding withholding or withdrawing intensive care and end‐of‐life decisions in critically ill newborn infants. These guidelines have to be differentiated from ethical decision‐making models which structure the process of decision making for an individual child. Such a framework has been in existence in our clinic for 10 years. Aim: The aims of this study were to evaluate how end‐of‐life decisions are taken in our perinatal centre and to analyse whether these decisions are consistent with our framework for structured ethical decision making.

New multichannel near infrared spectrophotometry system for functional studies of the brain in adults and neonates

We have designed a versatile, multi-channel near-infrared spectrophotometry (NIRS) instrument for the purpose of mapping neuronal activation in the neonatal and adult brain in response to motor, tactile, and visual stimulation. The optical linearity, stability, and high signal to noise ratio (>70 dB) of the instrument were demonstrated using an in vitro validation procedure. In vivo measurements on the adult forearm were also performed. Changes in oxygenation, induced by arterial occlusion of the forearm, were recorded and were shown to compare well with measurements acquired using a conventional NIRS instrument. To demonstrate the capabilities of the instrument, functional measurements in adults and neonates were performed. The instrument exhibited the capability to differentiate with a spatial resolution in the order of cm, local activation patterns associated with a finger tapping sequence.

Near-Infrared Spectroscopy Measurements of Cerebral Oxygenation in Newborns during Immediate Postnatal Adaptation

OBJECTIVE In view of growing concerns regarding the optimal supplementation of oxygen at birth, we measured cerebral oxygenation during the first minutes of life. STUDY DESIGN Using near-infrared spectroscopy, changes in cerebral oxygenated hemoglobin (O(2)Hb), dexoxygenated hemoglobin (HHb), and tissue oxygenation index (TOI) were measured during the first 15 minutes of life in 20 healthy newborn infants delivered at term by elective cesarean section. RESULTS O(2)Hb and TOI increased rapidly within the first minutes of life (median slope for O(2)Hb, 3.4 micromol/L/min; range, 1.4 to 20.6 micromol/L/min; median slope for TOI, 4.2 %/min; range, -0.4 to 27.3%/min), and cerebral HHb decreased (median slope, -4.8 micromol/L/min; range, -0.2 to -20.6 micromol/L/min). O(2)Hb, TOI, and HHb all reached a plateau within 8 minutes. CONCLUSIONS A significant increase in cerebral O(2)Hb and TOI and a significant decrease in HHb occur during immediate adaptation in healthy term newborns, reaching a steady plateau at around 8 minutes after birth.

MicroRNA-96 Directly Inhibits γ-Globin Expression in Human Erythropoiesis

Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (<1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased γ-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation.

Growth, developmental milestones and health problems in the first 2 years in very preterm infants compared with term infants: a population based study

Abstract. The outcome of very preterm infants varies widely from centre to centre and from country to country. The aim of this study was to evaluate growth, developmental milestones and post-discharge morbidity of infants born before 32 weeks of gestation in Switzerland. A questionnaire was sent to the parents of 456 survivors born in 1996. A total of 309 (68%) parents responded and their infants were matched with 309 control infants born at term. At the corrected age of 24 months, the very preterm infants had significantly lower weight (–1.0 z-scores), lower length (–1.23 z-scores), and lower head circumference (–0.64 z-scores). Very preterm infants were reported to eat with a spoon later than those born at term (50% at 7.5 months corrected for prematurity versus 10 months, P<0.001), to drink later out of a cup (50% at 16.5 months versus 13.5 months, P=0.03) and to walk later independently (50% at 14.5 months versus 13.5 months, P=0.04), whereas timing of sitting unsupported was no different (50% at 7.4 months versus 7.2 months, P=0.9). Of very preterm infants, 16% were not able to walk at least three steps unsupported at 18 months after term which puts them at an increased risk for cerebral palsy. Some 35% of very preterm infants had to be readmitted to hospital during the first 24 months compared with 20% of control infants born at term (P<0.05). There was no difference between very preterm and term infants in respect to episodes of fever >38.5°C, episodes of coughing >3 days and treatment with antibiotics. Conclusion: these data based on a national survey allow to quantify growth retardation, developmental delay and post-discharge health problems within the first 2 years in preterm infants born before 320/7 weeks.