Guy Moriette

The Effect of Epoetin-beta (recombinant-human-erythropoietin) On the Need for Transfusion in Very-low-birth-weight Infants

BACKGROUND Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

Congenital chylothorax with hydrops: postnatal care and outcome following antenatal diagnosis

We consecutively managed 25 cases of fetal chylothorax with hydrops (pleuroamniotic shunting in 20/25 cases). Three of the 16 liveborn infants died before day 5 from malformations (n = 1) or complications of antenatal origin (n= 2). Eleven of the 13 survivors were treated in our unit. Four infants whose chylothorax had resolved before birth following antenatal shunting were delivered at term, and had no respiratory disease. Seven infants, whose chylothorax persisted, were delivered prematurely and required intensive respiratory care (with mechanical ventilation for a median duration of 34 days). The 11 infants were maintained on total parenteral nutrition for a median duration of 31 days. They were discharged home after complete clinical recovery at a median age of 64 days. Antenatal pleuroamniotic shunting may improve the prognosis of congenital chylothorax with hydrops. Chylothorax persisting at birth resolves progressively with medical management. Congenital chylothorax, critical care, non‐immunologic fetal hydrops, pleuroamnotic shunting, preterm newborn

12 GASTRO-ESOPHAGEAL REFLUX AND APNEA IN PREMATURELY BORN INFANTS, DURING WAKEFULNESS AND SLEEP

Apnea of infancy may be caused by gastro-esophageal reflux (GER). We tested the hypothesis that GER may similarly account for cases of persistence after term, of apnea of prematurity (AOP), which usually ceases before. 20 prematurely born infants (CA 31.6±2.8 wks) were selected because they still had apneas of duration ≥ 10s, or regurgitations, at 38.9±1.7 wks of post conceptional age (mean ± SD). GER was identified using esophageal pH monitoring. Recordings of chest and abdominal movements and of nasal airflow enabled apneas to be classified as central (CA), obstructive and mixed (OMA). Wakefulness (W), active sleep (AS) and quiet sleep (QS) were identified using EEG and assessment of eye movements.Results GER occured in the 20 subjects, in W and AS more frequently (p<0.02) than in QS (n of events : 2.77±1.97;2.79±1.99 and 1.46±2.01 per 100 min). OMA (n=113) were predominant. They occured more in AS than in QS (p<0.01). OMA did not occur more during than without GER ; and their number was not correlated with that of GER or with its duration.Conclusion In prematurely born infants with persisting AOP, GER occurs frequently in wakefulness and in AS. Usually, it is not the direct cause of apneas.

Functional Residual Capacity and Sleep States in the Premature Newborn

Functional residual capacity (FRC) variations in relation to sleep state changes were studied in 11 premature infants with birth weights of 1.68 +/- 0.48 kg and gestational ages of 32.7 +/- 2.2 weeks (mean +/- SD). Helium dilution was used to measure FRC, and sleep states were identified using neurophysiologic criteria. No significant difference in FRC could be demonstrated between data collected during active sleep (AS) and quiet sleep. However a relationship was shown between AS and paradoxical breathing (p less than 0.02) and between AS and irregular breathing (p less than 0.05). Several factors are discussed which might explain the discrepancy between the present data in premature infants and the previously published data in term infants. (1) Neurophysiologic identification of sleep states does not include breathing pattern whereas behavioral identification does. It is therefore possible that lung volume changes are related to breathing pattern changes and not to sleep state changes per se. (2) Maturational changes may occur among the mechanisms which control FRC, leading to a progressive stabilisation of FRC, the variation of which could become related to sleep state changes.

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 <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.

Pulmonary Functional Outcome at One Year of Age in Infants Treated with Natural Porcine Surfactant at Birth

This prospective study was designed to assess pulmonary function (functional residual capacity, FRC; dynamic lung compliance, CLdyn; and total pulmonary resistance, RL) at 1 year of corrected age in infants with neonatal respiratory distress syndrome treated with natural porcine surfactant (Curosurf) (n = 13), as compared to nontreated control infants (n = 9). Values from 21 healthy infants of similar age served as reference. We found similar pulmonary dysfunction (decreased CLdyn, elevated RL) in both patient groups. These results suggest that surfactant replacement therapy does not affect pulmonary function at 1 year of age in infants who survive respiratory distress syndrome.

Heliox® Tolerance in Spontaneously Breathing Neonates with Bronchopulmonary Dysplasia

The use of a gas mixture in which helium is substituted for nitrogen allows a decrease in pulmonary resistances and in resistive work of breathing. This treatment might allow a reduction in energy expenditure in infants with bronchopulmonary dysplasia (BPD) and spare calories for growth. In a preliminary study designed to assess tolerance to Heliox®, 4 infants with BPD and 4 controls were studied firstly when breathing air and secondly when breathing Heliox®, at 10, 20 and 30 min exposure (T10, T20, T30). The following parameters were recorded: respiratory and cardiac rates, room (RT) and skin temperatures (ST) and transcutaneous (Tc) blood gases. When breathing air, TcPO2 was normal in the two groups (mean ± SEM: 70 ± 4 mm Hg in BPD vs. 78 ±4 in controls). TcPCO2 was higher in the BPD group (41 ± 2 vs. 35 ± 1 mm Hg in controls; p = 0.028). Spontaneously breathing Heliox had immediate consequences such as wakening, crying, decrease in ST and hypoxia. Hypoxia was more serious and more rapid in the BPD group. At the 10-min exposure, mean TcPO2 was 39 ± 4 mm Hg in BPD vs. 69 ± 7 in controls (p = 0.042). Hypoxia was immediatly corrected when breathing room air. TcPCO2 was unchanged in both groups.

Necrotizing Enterocolitis in Full-Term Newborns

During a 17-month period, 19 full-term newborn infants were hospitalized for necrotizing enterocolitis (NEC). 10 of these infants had no apparent risk factors. Only 7 suffered acute fetal distress. 16 of the 19 infants were born in the same hospital. Toxicological and bacteriological investigations of possible cause revealed no specific agent. Virological analysis of 8 stool samples revealed the presence of corona virus in 5 of the 8.

Prospective Randomized Multicenter Comparison of High-Frequency Oscillatory Ventilation (HFOV) and Conventional Ventilation (CV) in Preterm Infants <30 Weeks Gestational Age (GA) with RDS

Prospective Randomized Multicenter Comparison of High-Frequency Oscillatory Ventilation (HFOV) and Conventional Ventilation (CV) in Preterm Infants <30 Weeks Gestational Age (GA) with RDS

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.