Christian Debauche

Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND Ibuprofen is used for treatment and prevention of patent ductus arteriosus in low-birthweight infants. Its effects on regional circulations differ from those of indometacin. Because prophylactic indometacin reduces the frequency of severe intraventricular haemorrhage and patent ductus arteriosus, we aimed to study the efficacy of early ibuprofen in reducing these outcomes in a double-blind, multicentre trial. METHODS Within 6 h after birth, 415 low-birthweight infants (gestational age <31 weeks) were randomly allocated ibuprofen-lysine (10 mg/kg then two doses of 5 mg/kg after 24 h and 48 h) or placebo intravenously. The primary outcome was occurrence of severe intraventricular haemorrhage; secondary outcomes were occurrence of patent ductus arteriosus and possible adverse effects of ibuprofen. Analysis was by intention to treat. FINDINGS 17 (8%) of 205 infants assigned ibuprofen and 18 (9%) of 210 assigned placebo developed severe intraventricular haemorrhage (relative risk 0.97 [95% CI 0.51-1.82]). In 172 (84%) infants of the ibuprofen group, the ductus was closed on day 3 compared with 126 (60%) of the placebo group (relative risk 1.40 [1.23-1.59]). No important differences in other outcomes or side-effects were noted; however, urine production was significantly lower on day 1 and concentration of creatinine in serum was significantly higher on day 3 after ibuprofen. INTERPRETATION Ibuprofen prophylaxis in preterm infants does not reduce the frequency of intraventricular haemorrhage, but does decrease occurrence of patent ductus arteriosus.

Contemporary neonatal outcome following rupture of membranes prior to 25 weeks with prolonged oligohydramnios

BACKGROUND Prolonged oligohydramnios following early preterm prelabour rupture of membranes (PPROM) is traditionally associated with high neonatal mortality and significant risk of pulmonary hypoplasia. However, recent evidence points to an apparent improvement in outcome. AIMS To document current neonatal outcomes following rupture of membranes prior to 25 weeks with severe persistent oligohydramnios and a latency to delivery of at least 14 days. METHODS A retrospective case note analysis over a 28-month period at Saint Luc University Hospital, Brussels. RESULTS From 23 pregnancies that were complicated by PPROM prior to 25 weeks, 15 infants were born after 24 weeks with a latency of more than 14 days and persistent oligohydramnios. Nine infants (60%) had severe respiratory failure and clinical signs compatible with pulmonary hypoplasia. Seven of these infants (78%) responded to high frequency ventilation and inhaled nitric oxide therapy with good clinical outcome but two died from severe respiratory failure. Five infants showed no clinical signs of pulmonary hypoplasia and responded to conventional neonatal management. One of these infants died at 77 days of age of necrotising enterocolitis. One infant was not resuscitated and died within minutes of birth, following prior discussion with the perinatal team and the parents. Survivors in this high-risk group (73%) had low morbidity at the time of discharge. SUMMARY The favourable neonatal survival and morbidity figures are in keeping with recent published evidence. This study confirms improved outcome even amongst the highest risk infants with documented persistent oligohydramnios.

Sporadic In Utero Generalized Edema Caused by Mutations in the Lymphangiogenic Genes VEGFR3 and FOXC2

OBJECTIVES To investigate the genetic causes of idiopathic sporadic prenatal generalized edema. STUDY DESIGN In a series of 12 patients, in whom in utero generalized skin edema or hydrops fetalis had been diagnosed, we screened 3 lymphangiogenic genes, VEGFR3, FOXC2, and SOX18. RESULTS In 3 of the patients, we identified a mutation: 2 in VEGFR3 and 1 in FOXC2. Two of the mutations were de novo and one was either de novo or nonpenetrant inherited. In these patients, the generalized edema resorbed spontaneously, either in utero or after birth. In the 2 individuals with a VEGFR3 mutation, edema remained limited to lower limbs. CONCLUSIONS Mutations in the VEGFR3 and FOXC2 genes account for a subset of patients with unexplained in utero generalized subcutaneous edema and hydrops fetalis without family history of lymphedema. Lymphangiogenic genes should be screened for mutations in sporadic patients diagnosed with fetal edema.

Pulmonary Effects of Prolonged Oligohydramnios following Mid-Trimester Rupture of the Membranes – Antenatal and Postnatal Management

Mid-trimester, preterm prelabour rupture of the membranes (PPROM) with prolonged oligohydramnios remains a challenge for both obstetricians and neonatologists. Although survival rates have improved, morbidity remains common particularly due to pulmonary insufficiency and pulmonary hypertension. The aetiology of abnormal lung development is unknown but may depend critically on pulmonary vascular development. Antenatal evaluation of at-risk foetuses by three-dimensional ultrasound and MRI is possible but the techniques need to be further assessed. Antenatal corticosteroids given in cases of PPROM reduce the incidence of neonatal death, respiratory distress syndrome, intraventricular haemorrhage and necrotising enterocolitis without increasing maternal or neonatal infection. The true risk-benefit ratio of antibiotics, tocolysis and strategies to normalise amniotic fluid volume remains less clear. There is no consensus regarding the optimal ventilation strategy to support infants with pulmonary insufficiency following PPROM, and further work is required to determine whether and which pulmonary vasodilators improve long-term outcome in these infants.

Sonographic evaluation of traumatic spinal cord lesions in the newborn infant

We present a case of spinal cord injury due to birth trauma and assess the value of sonography for diagnosis, lesion characterization, and follow-up. Sonography is a non-invasive and easily reproducible imaging method for examining a ventilated child, and its initial sensitivity is comparable to that of MRI. Sonography is the method of choice for guiding diagnosis in this type of traumatic lesion to the newborn.

Two-year neonatal outcome following PPROM prior to 25 weeks with a prolonged period of oligohydramnios.

BACKGROUND Improved neonatal survival data have been reported following early preterm prelabour rupture of membranes (PPROM) prior to 25 weeks gestation with a prolonged latency to delivery and persistent oligohydramnios. However, data regarding long-term respiratory and neurological morbidity are lacking. AIMS To evaluate the respiratory and neurological outcome data at two years of age in a cohort of infants born following PPROM prior to 25 weeks with a prolonged latency (14 days) to delivery and compare the data to an aged matched group of infants. METHODS Retrospective case note analysis over a 43-month period at Saint Luc University Hospital, Brussels. RESULTS 15 surviving infants born following PPROM were matched to a group of 30 control infants. Although there was no significant difference in the incidence of BPD between the groups (33% vs 27%, p=0.24), the length of hospitalisation, duration of respiratory support and number of hospital readmissions for respiratory indications were all significantly higher for infants born following a prolonged period of oligohydramnios. There were no major anomalies on cranial ultrasound in the PPROM group and Baileys developmental assessment at 20-24 months corrected gestational age showed no difference between the two groups (Mental development index 93.9 vs 94.4 and Psychomotor development index 95.5 vs 95.8 respectively p = ns). CONCLUSION Neurodevelopmental outcome appears encouraging in this cohort although these infants are at high risk of prolonged initial hospitalisation and significant respiratory morbidity in the first two-years of life.

Resolution of fetal tachycardia and hydrops by a single adenosine administration

Fetal tachyarrhythmias is a life-threatening condition that causes congestive heart failure, nonimmune hydrops, and intrauterine death. Adenosine, a safe and effective drug used to terminate atrioventricular reentrant tachycardia, has been injected into the fetus. Serial intravascular injections of low-dose adenosine was successful in one case, reported in letter form (Blanch G, Walkinshaw SA, Walsh K. Cardioversion of fetal tachyarrhythmia with adenosine [letter]. Lancet 1994;344: 1646), despite the risk of repeated funipuncture. In the other case, adenosine injection was efficient but did not prevent intrauterine death. We report a case of immediate and definitive termination of supraventricular tachycardia following a single intravascular administration of adenosine.

Twin-to-twin transfusion syndrome: perinatal outcome and recipient heart disease according to treatment strategy

The aims of the study were to compare perinatal outcome and assess recipient cardiac disease according to treatment strategy (amnioreduction (AR), laser or selective feticide).

Imaging of primary unilateral pulmonary hypoplasia: a case report

BackgroundPulmonary hypoplasia is a rare cause of neonatal dyspnea almost always secondary to other conditions. We report an exceedingly rare case of primary unilateral pulmonary hypoplasia.Results and discussionThis case illustrates the role of prenatal magnetic resonance imaging when this condition is suspected during the fetal life. Combined with ultrasounds, this imaging modality offers a three-dimensional evaluation of the lungs that can be critical for postnatal medical management.

Fetal liver hemangioma and chorioangioma: two unusual cases of severe fetal anemia detected by ultrasonography and its perinatal management.

Severe anemia was diagnosed by cordocentesis in two fetuses, one with a large chorioangioma, the other with a liver hemangioma. Despite the presence of a chronic fetotumoral shunt, both cases were partly treated by a fetal intravascular transfusion, followed by an elective Cesarean section. This ‘predelivery’ management of anemia should improve neonatal morbidity associated with severe hematological and acid‐base balance disorders.