Neonatal Aerodigestive Disorders: Epidemiology and Economic Burden.

Aerodigestive disorders, those affecting the upper and lower airway or upper gastrointestinal tract, are interrelated anatomically during fetal development and functionally after birth. Successful respiration and feeding requires careful coordination to promote effective swallowing and prevent aspiration. I describe the epidemiology, including the prevalence of the most common aerodigestive disorders. The ability of an infant to feed by mouth at discharge, without a surgically placed feeding tube, is an important neurodevelopmental marker. Therefore, aerodigestive disorders have a high potential for lifelong morbidities and health care expenditures. When available, published research on related medical costs for these disorders is provided.

Positive pressure ventilation coaching during neonatal bag-mask ventilation: A simulation-based pilot study.

BACKGROUND: Positive pressure ventilation (PPV) is the most important procedure during neonatal resuscitation. Providing effective PPV seems easy. However, performing the procedure correctly is extremely challenging. Airway obstruction and face mask large leaks are common. It is estimated that two-thirds of continued neonatal respiratory depression after the time of birth is caused by ineffective or improperly provided PPV. Finding methods to improve PPV performance are critically needed. Performance coaching is a simple and easy method of improving performing in procedural skills, and has been used previously to optimize compression technique. We performed the simulation-based pilot study to evaluate the impact of PPV coaching during neonatal bag-mask ventilation. METHODS: Randomized cross-over study of nurses performing PPV on a SMART Newborn Resuscitation Training System with, and without, coaching. The PPV coach provided real-time feedback on chest rise, mask hold, and ventilation rate. The SMART system captured data on peak inspiratory pressure (PIP), tidal volume (Vt), mask leak, and ventilation rate. Data were analyzed by a blinded reviewer. RESULTS: PPV coaching resulted in more appropriate PIPs (34 cmH2O, IQR 32-38 vs. 36 cmH2O, IQR 28-37; P < 0.001), lower Vt (4.7 ml/kg, IQR 4-8 vs. 5.5 ml/kg, IQR 4-13; P < 0.001), and less mask leak (39% leak, IQR 21-70 vs. 45%, IQR 22-98; P = 0.005). There was no difference in respiratory rate (P = 0.93). CONCLUSIONS: Coaching improved PPV performance in this simulation-based pilot study. Further research on PPV coaching during neonatal resuscitation is warranted.

Outcomes of infants born near term.

Most research on outcomes of preterm birth has centred on babies born at <32 weeks gestation and at highest risk of mortality and serious morbidity. Recent years have seen a dramatic increase in studies focusing on late preterm infants (34-36 weeks gestation). Early epidemiological studies demonstrated increased risks of mortality and adverse neonatal outcomes in this group, prompting further investigations. These increased risks have been confirmed and more recent studies have also included babies born at 37-38 weeks, now defined as 'early-term' births. It now seems that it is inappropriate to consider term and preterm as a dichotomy; gestational age rather represents a continuum in which risk and severity of adverse outcomes increase with decreasing gestational age, but where measurable effects can be detected even very close to full term. In this review, we summarise current evidence for the outcomes of infants born at late preterm and early-term gestations.

Spectrographic cry analysis in newborns with profound hearing loss and perinatal high-risk newborns.

BACKGROUND: Crying is the first neurophysiological demonstration of the newborn. The acoustic analysis of crying episodes can provide useful information in the early diagnosis of several pathologies. METHODS: We carried out a spectrographic cry analysis of 40 infants with several diseases such as neonatal asphyxia, breathing disorders, deafness and neurological disorders. Statistical t-test was used in order to compare means of fundamental frequencies (F0) of cries among pathologies, as well as contingency tables for qualitative variables and melodic form. RESULTS: No significant differences of F0 were found by applying the t-test among pathologies. Time of inspiration in breathing disorders is higher compared with other groups. Infants with deafness and neurological disorders present poor melodic forms. Qualitative analysis revealed more often glottal roll and vibrato. CONCLUSIONS: Cry analysis is clinically useful for early detection of diseases in newborns as a result of alterations in the central nervous system that are reflected in phonoarticulatory and respiratory functions for sound emission.

Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial.

OBJECTIVES: To determine the effectiveness of corticosteroids in reducing respiratory disorders in infants born at 34-36 weeks' gestation. Design Randomised triple blind clinical trial. Setting A large tertiary teaching hospital in northeast of Brazil. Participants Women at 34-36 weeks of pregnancy at risk of imminent premature delivery. Interventions Betamethasone 12 mg or placebo intramuscularly for two consecutive days. Main outcomes measures Primary outcome was the incidence of respiratory disorders (respiratory distress syndrome and transient tachypnoea of the newborn). Secondary outcomes included the need for ventilatory support, neonatal morbidity, and duration of stay in hospital. RESULTS: 320 women were randomised, 163 of whom were assigned to the treatment group and 157 to the controls. Final analysis included 143 and 130 infants, respectively. The rate of respiratory distress syndrome was low (two (1.4%) in the corticosteroid group; one (0.8%) in the placebo group; P = 0.54), while the rate of transient tachypnoea was high in both groups (34 (24%) v 29 (22%); P = 0.77). There was no reduction in the risk of respiratory morbidity with corticosteroid use even after adjustment for subgroups of gestational age (34-34(+6) weeks, 35-35(+6) weeks, and ≥ 36 weeks). The adjusted risk of respiratory morbidity was 1.12 (95% confidence interval 0.74 to 1.70). The need for ventilatory support was around 20% in both groups. There was no difference in neonatal morbidity (88 (62%) v 93 (72%); P = 0.08) or in the duration of stay in hospital between the two groups (5.12 v 5.22 days; P = 0.87). Phototherapy for jaundice was required less often in babies whose mothers received corticosteroids (risk ratio 0.63, 0.44 to 0.91). CONCLUSIONS: Antenatal treatment with corticosteroids at 34-36 weeks of pregnancy does not reduce the incidence of respiratory disorders in newborn infants. Trial registration Clinical Trials NCT00675246.

[The paediatric roots of chronic obstructive pulmonary disease]. / Racines pédiatriques de la bronchopneumopathie chronique obstructive.

Early disturbances in pulmonary development seem to favour the occurrence of the functional impairments observed in COPD. In utero exposure to maternal smoking is the most commonly documented antenatal factor. Early life events such as the bronchopulmonary dysplasia are responsible for hypoalveolisation. The effects of passive smoking during childhood are prolonged into adulthood. The role of viral respiratory infections in early childhood remains a subject for debate. Finally the role of genes implied in pulmonary development both pre and post natally is beginning to be recognized. The decline of the respiratory function that occurs in adulthood leads then more rapidly to the functional criteria of COPD, particularly in the event of active smoking. There thus exist epidemiological and fundamental arguments, which support the idea that the COPD has at least, in part, a paediatric origin.

[Ventilatory care]. / L'assistenza ventilatoria.

Mechanical ventilation is considered a supportive, nontherapeutic technology used to perform the work of breathing for patients who are unable to do so on their own. In neonatology, mechanical ventilation is often used for premature neonates who are unable to sustain ventilation because of reduced functional residual capacity due to surfactant deficiency. Mechanical ventilation is thus an attempt to mimic the respiratory system's physiological function of gas exchange until the respiratory system reaches maturation. In pediatrics, mechanical ventilation is rarely used for acute respiratory distress syndrome as shown by Dahlem et al. in 2003 who found that only 9.9% of cases of respiratory failure in PICU was caused by ARDS. For this reason, ventilatory techniques in PICU are very heterogenous from the assisted to the most aggressive controlled modes associated with ventilator maneuvers. There are no specific guidelines for the use of mechanical ventilation in children and the low number of infants with ARDS in PICU makes it difficult to run randomized controlled trials in this population. Thus the algorithms are based on the results of either adult or neonatal studies. The advantage of extrapolating data from the neonatal evidence relates mainly to the prevention of ventilator induced lung injury (e.g., CPAP, HFOV, NIV, permissive hypercapnia, surfattant), of which neonatologists are particularly expert.

Selected neonatal outcomes in dizygotic twins after IVF versus non-IVF pregnancies.

OBJECTIVE: To compare neonatal outcome among twins conceived after in vitro fertilisation (IVF) with that of spontaneously conceived twins. DESIGN: Comparison of different-sex (dizygotic) twins born after IVF with non-IVF dizygotic twins. SETTING: National health registers in Sweden. POPULATION: All births in Sweden during the period 1982-2007. METHODS: We studied gestational duration, lowest birthweight and birthweight difference in the twin pair, presence of one or two twins with a respiratory complication, and with jaundice in one or both twins. Risk estimates were calculated as odds ratios with adjustments for year of birth, maternal age, parity and smoking in pregnancy. MAIN OUTCOME MEASURES: Gestational duration, birth weight, respiratory complications, jaundice. RESULTS: We studied 1545 pairs of dizygotic twins born after IVF, and 8675 pairs of dizygotic twins where IVF was not known to have occurred. The risk for preterm delivery before 32 weeks of gestation was significantly increased among dizygotic twin pairs born after IVF compared with non-IVF dizygotic twin pairs. No significant difference in low birthweight or birthweight difference within twin pairs was seen. There was an increased occurrence of twin pairs with respiratory problems or jaundice, but only the latter diagnosis occurred in a statistically significant excess. CONCLUSIONS: The study confirms recent findings that IVF is associated with an increased risk for some neonatal complications, not only among singletons but also among twins.

Prenatal diagnosis of episodic tachypnea in an infant with OFD VI.

Episodic tachypnea is a typical neonatal presentation of Joubert syndrome, but may also occur in infants with other anomalies of the cerebellar vermis. Even though fetuses at risk for Joubert syndrome are usually closely followed by ultrasound, this respiratory pattern has only once been described prenatally. We describe a patient who presented prenatally with posterior meningocele, Dandy-Walker cyst, and four limb polydactyly on ultrasound. Amniocentesis showed a normal male karyotype and normal 7DHC. At 31 weeks, episodic fetal tachypnea was noted on ultrasound. The working diagnosis was Joubert syndrome or oro-facio-digital syndrome type VI (OFD VI). At birth, in addition to the findings noted prenatally, he had multiple nodules of his tongue, a Y-shaped metacarpal and micropenis. His respiratory pattern was notable for alternating tachypnea and apnea with respiratory rates up to 200 followed by apnea and bradycardia. Magnetic resonance image showed Dandy-Walker with massive 4th ventricle, complete absence of the cerebellar vermis, hypoplastic brainstem, and small meningocele. Development is profoundly delayed and he remains ventilator dependent. Both the previously described Joubert patient with prenatally recognized tachypnea, and our patient are atypical for Joubert syndrome since they have polydactyly (which occurs in only 8% of Joubert patients) and hamartomas of the tongue (which occur in 2%). Despite the tongue hamartomas, these patients are not entirely typical for OFD VI, since their polydactyly is postaxial. The observation of prenatal tachypnea in these two patients, but not in typical Joubert patients, suggests they have either a variant of OFD VI or a new Joubert or OFD-like syndrome.

A genetic reason for male excess in infant respiratory mortality?

UNLABELLED: Male infants have a 50% higher risk of death from respiratory diseases and a number of congenital heart diseases that can lead to cerebral hypoxia. The most important of these diseases are infant respiratory distress syndrome and sudden infant death syndrome. CONCLUSION: The mechanism behind the excess peri-mortality rate in male infants is not known. A genetic factor leading to reduced tolerance to hypoxia is possible.

Genetics and early disturbances of breathing control.

Early disturbances in breathing control, including apneas of prematurity and apparently life-threatening events, account for some cases of sudden infant death syndrome and for a rare disorder called congenital central hypoventilation syndrome (CCHS). Data suggesting a genetic basis for CCHS have been obtained. Recently, we found heterozygous de novo mutations of the PHOX2B gene in 18 of 29 individuals with CCHS. Most mutations consisted of five to nine alanine expansions within a 20-residue polyalanine tract, probably resulting from nonhomologous recombination. Other mutations, generally inherited from one of the parents, in the coding regions of genes involved in the endothelin and RET signaling pathways and in the brain-derived-neurotrophic factor (BDNF) gene have been found in a few CCHS patients. Interestingly, all these genes are involved in the development of neural crest cells. Targeted disruption of these genes in mice has provided information on the pathophysiological mechanisms underlying CCHS. Despite the identification of these genes involved in breathing control, none of the genetically engineered mice developed to date replicate the full human CCHS respiratory phenotype. Recent insights into the genetic basis for CCHS may shed light on the genetics of other early disturbances in breathing control, such as apnea of prematurity and sudden infant death syndrome.

Successful treatment of acute promyelocytic leukaemia during pregnancy.

A case is reported of a pregnant 16-year-old-woman diagnosed with Acute promyelocytic leukaemia (APL) at 25 weeks gestation and treated with all-trans retinoic acid (ATRA) (45 mg/m2) for 25 days in combination with chemotherapy. She achieved a complete cytogenetic and molecular remission. Clinical course was complicated, with an intracerebral bleed, respiratory failure requiring ventilation and prolonged pancytopenia following initial chemotherapy. A live female infant was born at 28 weeks gestation who survived to discharge with significant pulmonary complications. She remains oxygen dependent at 6 months of age. ATRA has been used from the 3rd week of gestation, but fetal malformations are common during the first trimester. In contrast it seems to be safe in the second and third trimesters with regard to teratogenesis but can cause other side-effects. Most successful outcomes in treatment of APL during pregnancy are seen after treatment with ATRA and delivery of the baby at as late a stage as possible. Pregnancies terminated before remission has been obtained or those treated in the first trimester have a poor maternal outcome.

Abnormalities of the chemical control of breathing: Clinical correlates in infants and children.

Abnormalities of the chemical control of breathing may go unrecognized and lead to life-threatening events, especially during sleep. Tests to assess chemical control in vivo have not yet been standardized, and their results may be difficult to interpret. Non-invasive monitoring of gas exchange and polysomnography are essential to assess the severity of hypoventilation and the extent to which it is dependent on the state of alertness. One has to be aware that some patients may have increased vulnerability to stress, and that mild infections may trigger acute hypoventilation. To date, no pharmacological approaches have proved effective in the long-term. Therefore, the management of infants and children with abnormal chemical control of breathing includes ventilatory support during sleep and diaphragmatic pacing during wakefulness, if necessary. Further research is needed to improve our understanding of the mechanisms controlling chemosensitivity and of the developmental plasticity of chemosensitivity during infancy and childhood. Genetic influences, as well as environmental factors in utero or during early infancy, may contribute to abnormal chemical control of breathing during infancy and childhood.

[Prevalence of Chlamydia trachomatis in newborn infants with respiratory problems]. / Prevalencia de Chlamydia trachomatis en recién nacidos con dificultad respiratoria.

The prevalence of C. trachomatis in neonates with respiratory distress was studied after 24 h of birth, nine patients were positive for C. trachomatis culture (12.9%). The chest radiographs showed six with hyaline membrane disease and two with pneumonia. One patient with treatment of ventilation mechanics developed bronchopulmonary dysplasia and was C. trachomatis positive in a second cell culture. Of the nine patients with C. trachomatis, eight were neonates preterm with low weight to the birth and with leukocytosis. Six patients were delivered by cesarean section. These results suggest that C. trachomatis can participate in an important way in the development of the distress respiratory in infants preterm.

[Total anomalous pulmonary venous drainage. Description of a case]. / Deflusso venoso polmonare anomalo totale. Descrizione di un caso.

A case of total anomalous pulmonary venous drainage (TAPVD) is reported, which according to Darling classification corresponded to infradiaphragmatic type (type III) and is associated to pulmonary arterial thrombosis and infarctions. It's emphasized the need of an accurate dissection of cardiovascular system in perinatal necropsies, specially in cases of sudden infant death. By an appropriate dissection, cardiovascular malformations can be recognized. Moreover, it's explained the pathogenesis of pulmonary arterial thrombosis and infarctions.

Exogenous surfactant therapy in non-respiratory distress syndrome.

There is clinical evidence of the benefit of exogenous surfactant therapy to certain neonates with severe respiratory failure, diaphragmatic hernia, pneumonia and meconium aspiration syndrome. There still remain, however, important unanswered questions regarding, for example, optimum dosage and method of administration; appropriate randomized trials must be undertaken.