tretinoin and Respiratory-Distress-Syndrome--Newborn

Congenital diaphragmatic hernia (CDH) is a common cause of severe neonatal respiratory distress. Mortality and morbidity are determined by the amount of pulmonary hypoplasia (PH) that occurs and by the development of therapy-resistant pulmonary hypertension. The pathogenesis and aetiology of CDH and its associated anomalies are still largely unknown despite all research efforts. The pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. PH, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Our understanding of CDH has also been aided by basic research with the use of dietary, teratogen-induced, and knockout models of CDH. These studies indicate that lung hypoplasia may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. Recent data reveal the role of disruption of a retinoid-signalling pathway in the pathogenesis of CDH. Although multifactorial inheritance may best explain most cases of CDH in humans, much has been learned about the genetic factors that play a role in the development of CDH by studies of patients with CDH caused by specific genetic syndromes and chromosome anomalies. More research is warranted to improve our understanding of normal and abnormal lung development in relation to CDH. Such investigations will help in the design of new treatment strategies to improve the natural course or even to prevent this anomaly.

Topics: Abnormalities, Multiple; Animals; Disease Models, Animal; Female; Genetic Association Studies; Gestational Age; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Lung; Mice; Mice, Knockout; Persistent Fetal Circulation Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Distress Syndrome, Newborn; Risk Factors; Tretinoin; Vitamin A

The introduction of treatment with tretinoin (all-trans retinoic acid) and its combination with antineoplastic therapy has improved the outcome of acute promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect of tretinoin and it occurs in about 25% of treated APL patients in the absence of prophylactic measures and is often fatal. Generally, the retinoic acid syndrome is associated with increasing leucocyte counts and is probably caused by the release of several cytokines by maturing blast cells. The retinoic acid syndrome gives a clinical picture of bodyweight gain, respiratory distress, serous effusions and cardiac and renal failure. Adequate prophylaxis, based on the addition to tretinoin of dexamethasone and also, according to most authors, antineoplastic therapy (in case of rapidly increasing leucocyte counts) has decreased the incidence of retinoic acid syndrome to about 15%. Most importantly, these measures have reduced its mortality to about 1% of all treated patients.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Clinical Trials as Topic; Cytokines; Dexamethasone; Heart Failure; Humans; Infant, Newborn; Leukemia, Promyelocytic, Acute; Leukocyte Count; Renal Insufficiency; Respiratory Distress Syndrome, Newborn; Syndrome; Tretinoin; Weight Gain

Topics: Adult; Antineoplastic Agents; Atrial Premature Complexes; Ductus Arteriosus, Patent; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leukemia, Promyelocytic, Acute; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Respiratory Distress Syndrome, Newborn; Treatment Outcome; Tretinoin