Mosaic trisomy 15 and hemihypertrophy.

We report a case of mosaic trisomy 15 with mental retardation, facial dysmorphism, and hemihypertrophy, but no manifestations of Prader-Willi or Angelman syndromes. Mosaic trisomy 15 (11%) was discovered at the amniocentesis. Uniparental disomy for chromosome 15 was excluded by molecular analysis. Post-natal blood karyotype and examination were normal. Mosaic was confirmed on skin fibroblasts, placenta and cord. Evolution was marked by progressive right hemi-hypertrophy, and developmental delay. Our case is the first patient reported with hemihypertrophy associated with mosaic trisomy 15. The relevant literature is reviewed.

[Ethical dilemmas in the perinatal period: guidelines for end-of-life decisions]. / Dilemmes éthiques de la période périnatale: recommandations pour les décisions de fin de vie.

According to several recent surveys, around 50% of the deaths occurring nowadays in French neonatal intensive care units result from a medical decision. This has led French neonatologists to set up guidelines for end-of-life decisions and practice in the perinatal period, which are presented in this paper. It covers definitions, clinical situations, ethical principles, obligations of the medical and nursing staff, and specific conditions where dilemmas occur.

[Withholding and withdrawing treatment in the perinatal period: importance of a coherent attitude between gyneco-obstetricians and pediatricians]. / Décisions de fin de vie dans la période périnatale: la cohérence obstétrico-pédiatrique est primordiale.

According to several recent surveys, 50% of deaths occurring in neonatal intensive care units in France occur subsequent to a medical decision. The French Neonatal Group therefore decided to publish guidelines for practice. These guidelines present: definitions, clinical situations, ethical principles, obligations of the medical and nursing staff, and specific conditions where dilemmas occur. These guidelines focus on the obstetrico-pediatrics relationship.

[The incidence of prescriptions without marketing product license in a neonatal intensive care unit]. / Incidence des prescriptions hors autorisation de mise sur le marché en réanimation néonatale.

UNLABELLED: Most of the drugs prescribed in pediatric units have no product licence. The lack of clinical studies in children and appropriate drug formulations decrease their safety. The lack of a legal framework makes the prescriber insecure. Even if the debate is not recent, few studies have been carried out in this field. The aim of the present study was to evaluate the rate of prescriptions of unlicensed and off-label drugs in a neonatal intensive care unit. PATIENTS AND METHODS: The present study was carried out in our neonatal intensive care unit, from January 12 to February 12, 1998. Forty babies aged 0 to 128 days were included (90% newborns), with a gestational age between 25 to 40 weeks (88% were premature, with a birth weight lower than 1000 g). RESULTS: Two hundred and fifty-seven prescriptions were administered with 55 different types of drugs during this period. Ten percent of the prescribed drugs had no product licence. Sixty-two percent were off-label for premature infants and 64% for newborns: 90% due to age, 9.3% due to dose and 0.7% to method of administration. No therapeutic alternatives to these prescriptions were found among the few available licensed drugs. CONCLUSION: The prescriptions of unlicensed and off-label drugs in neonatal intensive care units are daily and repeated events. The prescribers are usually not aware of the exact status of the drug and do not realize neither he importance of the problem nor the legal and potential consequences. The lack of pediatric clinical studies is to a large extent responsible for the absence of drug registration in pediatrics. The pharmaceutical industry has few incentives to develop the pediatric product licences.

Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results.

OBJECTIVE: Instrumental dead space wash-out can be used to improve carbon dioxide clearance. The aim of this study was to define, using a bench test, an optimal protocol for long-term use, and to assess the efficacy of this technique in neonates. DESIGN: A bench test with an artificial lung model, and an observational prospective study. Dead space wash-out was performed by continuous tracheal gas insufflation (CTGI), via six capillaries molded in the wall of a specially designed endotracheal tube, in 30 preterm neonates with hyaline membrane disease. SETTING: Neonatal intensive care unit of a regional hospital. RESULTS: The bench test study showed that a CTGI flow of 0.5 l/ min had the optimal efficacy-to-side-effect ratio, resulting in a maximal or submaximal efficacy (93 to 100%) without a marked increase in tracheal and CTGI circuit pressures. In the 30 newborns, 15 min of CTGI induced a significant fall in arterial carbon dioxide tension (PaCO2), from 45 +/- 7 to 35 +/- 5 mmHg (p = 0.0001), and in 14 patients allowed a reduction in the gradient between Peack inspirating pressure and positive end-expiratory pressure from 20.8 +/- 4.6 to 14.4 +/- 3.7 cmH2O (p < 0.0001) while keeping the transcutaneous partial pressure of carbon dioxide constant. As predicted by the bench test, the decrease in PaCO2 induced by CTGI correlated well with PaCO2 values before CTGI (r = 0.58, p < 0.002) and with instrumental dead space-to-tidal volume ratio (r = 0.54, p < 0.005). CONCLUSION: CTGI may be a useful adjunct to conventional ventilation in preterm neonates with respiratory disease, enabling an increase in CO2 clearance or a reduction in ventilatory pressure.

Efficacy of dead-space washout in mechanically ventilated premature newborns.

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.

[Psychologic management of extreme prematurity]. / Prise en charge psychique de l'extrême prématurité.

The ongoing progress in neonatal intensive care is modifying the psychic context of prematurity for all the partners, infants as well as parents and physicians. Comfort and prognosis of preterm infants have much improved. Since newborns under 24 weeks of gestational age are now surviving, they spend approximately half the duration of pregnancy out of the maternal uterus. All the psychological issues of such an early separation have to be considered, including the developmental outcome of a sensorial environment which is quite different from the intra-uterine one. Research has been developing in this field. The cooperation between neonatalogists and psychologists has been profitable to parents. Problems linked to the separation, such as difficulty in representing the infant, are no more frequent owing to the attention paid to the mother-child bond and subsequent early contacts. What is forward now is the impact of an hyper technical world of intensive care on the parents, and of the strange aspect of the tiny baby surrounded by engines and tubes. Such an overpresence of reality often results in a reaction of traumatic daziness among parents. The cooperation of the whole staff is necessary for the resumption of an imaginary process of psychic functioning. Finally, the survival of very-low-birth-weight infants confronts the neonatalogists with some delicate ethical questions. Psychiatrists and psychologists might have an important part to play in aiding the profession in its sorting out of these ethical issues.

[Physiopathological approach and antenatal diagnosis of diabetes mellitus insulin resistant: apropos of a case with leprechaunism]. / Approche physiopathologique et diagnostic anténatal du diabète insulinorésistant: à propos d'un cas de lepréchaunisme.

BACKGROUND: Leprechaunism is characterized by severe intrauterine growth retardation, elfin-like face, relatively large hands, feet and genitalia and abnormal skin with hypertrichosis, acanthosis nigricans and low subcutaneous fat. The insulin receptors have multiple defects. CASE REPORT: A boy was born after cesarean section at the 35th week of gestation because of intrauterine growth retardation: weight: 930 g; height: 36 cm; head circumference: 27 cm. He had trigonocephaly, coarse features and hyperkeratosis. Ultrasonography confirmed the presence of a ventricular septal defect detected during pregnancy. Hyperglucosemia (3 g/l) was associated with insulinemia above 350 mU/l; his C-peptide concentration was above 20 ng/ml. The patient was given intravenous insulin, up to 2,500 U/kg/d. He died at the age of 95 days, weighing 1500 g, with persistent hyperglucosemia and cholestasis. Postmortem examination showed adrenal and thymus hypoplasia and hyperplasia of pancreatic islet cells. Molecular biology studies showed that this patient was heterozygotic for two mutations, one in exon 20 inherited from his father, the other in exon 18 inherited from his mother; both mutations are associated with tyrosine-kinase activity of the insulin receptor. These results will be used for antenatal diagnosis in any future pregnancy. CONCLUSION: Molecular biology can indicate specific defects in the insulin receptor. It may also allow antenatal diagnosis in some families.

[Brucellosis in a 3 month-old infant]. / Brucellose chez un nourrisson de 3 mois.

During the course of a bronchiolitis in a 3 month-old child, one blood culture yielded Brucella melitensis. The diagnosis of brucellosis is difficult in infancy because the symptoms are nonspecific and the disease may be mild and self-limited. The child received only breast milk and dietetic preparations. So, the detection in the maternal serum of a significant titer of Brucella agglutinin enabled us to consider the very rare human-to-human transmission from mother to child. Because the efficacy of ceftriaxone assessed by a favorable initial response, and in order to avoid complications due to the use of tetracyclines and cotrimoxazole in infant, our patient was successfully treated with ceftriaxone plus rifampin.

[Spontaneous perforation of the bile ducts]. / Perforation spontanée des voies biliaires.

Spontaneous perforation of the extra-hepatic bile ducts in infancy is rare and of unknown etiology. Its finding at laparotomy in a 2 month-old premature with artificial ventilation allows to underline that the diagnosis may be difficult and may necessitate ultrasonography and even hepatobiliary scintigraphy.

[Clofibrate for the treatment of hyperbilirubinemia in neonates born at term: a double blind controlled study (author's transl)]. / Traitement curatif de l'ictère du nouveau-né à terme par le clofibrate. Essai thérapeutique contrôlé en double aveugle.

A double blind controlled study of the therapeutic effect of clofibrate, an inductor of bilirubin glucuronyl transferase, was performed in neonates born at term and presenting with physiologic jaundice. 47 children were treated with a single oral dose of clofibrate. 46 control children were given corn oil alone. Results show that mean plasma bilirubin levels are significantly lower in the treated group as compared with the control group, from the 16th hour of treatment, if there is no ABO incompatibility. Clofibrate treatment also resulted in a shorter duration of jaundice and a restricted use of phototherapy. No undesirable side-effect was observed.

[Simultaneous assessment of intra-pulmonary right-to-left shunting and of aADCO2 in 5 neonates with refractory hypoxemia (author's transl)]. / L'exploration des hypoxémies réfractaires chez le nouveau-né.

Five neonates with refractory hypoxemia (aortic PO2 less than or equal to 6.7 KPa despite FiO2 = 1 and efficient artificial ventilation) were investigated in order to determine the principal mechanism of hypoxemia. PO2 values were measured (under FiO2 = 1) in a pulmonary vein, the left auricle and the aorta. They were used to distinguish intra-pulmonary shunts from extra-pulmonary shunts (though foramen ovale and/or ductus arteriosus). Simultaneous measurements of PACO2 and PaCO2 were used to assess the percentage of the ventilation output reaching hypoperfused areas. In cases with extra-pulmonary shunt, when this percentage is over 30%, pulmonary hypertension is likely. The use of both methods is useful for selecting those patients who might benefit from tolazoline.

[Hyaline membrane disease in full-term neonates (author's transl)]. / La maladie des membranes hyalines chez le nouveau-né à terme. A propos de 11 cas.

Eleven full term neonates with respiratory distress syndrome resembling hyaline membrane disease (HMD) are reported. Gestational ages awere assessed from the history and by clinical and EEG criteria. The diagnosis of HMD was made when clinical and radiological signs, usually present in premature infants, were found together with an abnormal lecithin/sphingomyelin ratio in the tracheal aspirate during the first 60 hours. In the majority of newborns all organs should be mature after 37 weeks gestation but, development may be delayed. Thus the lungs in the full term infants may occasionally have an immature surfactant system.

[The diagnostic value of the EEG in peri- and intraventricular haemorrhage in the newborn (author's transl)]. / Etude de la valeur diagnostique de l'EEG au cours des hémorragies péri et intraventriculaires du nouveau-né.

EEGs were performed in 39 newborns with intraventricular haemorrhage (IVH) who subsequently died and compared with a series of 37 neonates who did not have an IVH. Abnormalities were more common in the IVHgroup. The most significant findings were the presence of electrical storms and that it was not possible to assess the gestational age. Positive rolandic spikes were not significantly more frequent in the IVH group. None of the EEG changes seem to be specific for IVH, but the presence of any of these in a premature infant makes an IVH highly probable.

[Pulmonary and bone maturation. Study of 36 neonates (author's transl)]. / Maturation pulmonaire et maturation osseuse. Etude chez 36 nouveau-nés.

Pulmonary surfactant deficiency was diagnosed in 36 newborn infants by measuring low L/S ratios in sequential tracheal aspirated samples. A distal femoral epiphysis was seen in knee X-rays in 25 of these 36 infants. It is concluded that fetal pulmonary maturity cannot be judged in utero by the presence of ossific centres at the knee, although there is a statistical correlation between gestational age and maturity of the bones.

[Laboratory diagnosis of hyaline membrane disease and amniotic fluid inhalation. A study of 100 neonates with respiratory distress]. / Diagnostic biologique de la maladie des membranes hyalines et de l'inhalation de liquide amniotique. une étude chez 100 nouveau-nés en déstresse respiratoire.

The aim of this study of 100 newborns with respiratory distress in the first 24 hours was to evaluate the diagnostic reliability of sequential L/S ratio testing of the fluid retrieved through tracheal suctioning in identifying hyaline membrane disease and that of calculating the urinary meconial index (UMI) for the first mictions in identifying amniotic fluid aspiration. The L/S ratio was found to be low (< 2) during the first 3 days in 90% of the cases of hyaline membrane disease; this good correlation shows that the technique employed here can reliably be used to diagnose clinically and radiologically atypical forms of this disease (12%). The UMI was found to be abnormally elevated (> 1) in all the cases of severe meconial aspiration. This result implies that minor or atypical cases or those in which another disorder is associated can be diagnosed by the test. It is therefore proposed that the concurrent use of these two tests would improve the accuracy of the etiological diagnosis of respiratory distress in newborns.