Hercília Guimarães

Dose-related bronchodilator response to aerosolized salbutamol (albuterol) in ventilator-dependent premature infants

We used a placebo-controlled standardized protocol to define the dose-response relationship to the beta-adrenergic bronchodilator salbutamol (albuterol) in 10 ventilator-dependent premature infants at a postnatal age of 13.3 +/- 4.9 days. Passive respiratory system resistance and compliance were measured at baseline and 10 minutes after administration of salbutamol via a metered-dose inhaler and spacer device. Salbutamol caused a significant dose-related response with a 33% mean decrease in respiratory system resistance (p less than 0.05) and a 67% mean increase in respiratory system compliance (p less than 0.001). In seven and six patients, respectively, 100 micrograms of salbutamol caused significant improvement in resistance and compliance; 200 micrograms was required in the remainder, but one patient had no improvement in compliance. Oxygen saturation increased linearly with the increase in compliance. In 7 of the 10 infants, the duration of action of 200 micrograms of salbutamol on the following day was 3 hours. We conclude that bronchodilator treatment may be useful in the management of ventilator-dependent neonates with respiratory distress syndrome.

Inhaled salbutamol and beclomethasone for preventing broncho-pulmonary dysplasia: a randomised double-blind study.

Abstract Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation. We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia (BPD) in ventilator-dependent premature neonates. The study was double-blinded and placebo controlled. We studied 173 infants of less than 31 weeks of gestational age, who needed ventilatory support at the 10th postnatal day. They were randomised to four groups and received either placebo + placebo, placebo + salbutamol, placebo + beclomethasone or beclomethasone + salbutomol, respectively for 28 days. The major criteria for efficacy were: diagnosis of BPD (with score of severity), mortality, duration of ventilatory support and oxygen therapy. The trial groups were similar with respect to age at entry (9.8–10.1 days), gestational age (27.6–27.8 weeks), birth weight and oxygen dependence. We did not observe any significant effect of treatment on survival, diagnosis and severity of BPD, duration of ventilatory support or oxygen therapy. For instance, the odds-ratio (95% confidence interval) for severe or moderate BPD were 1.04 (0.52–2.06) for inhaled beclomethasone and 1.54 (0.78–3.05) for inhaled salbutamol. Conclusion This randomised prospective trial does not support the use of treatment with inhaled beclomethasone, salbutamol or their combination in the prevention of BPD in premature ventilated neonates.

Chorioamnionitis and brain damage in the preterm newborn

Aim. To evaluate the association between histological chorioamnionitis and brain damage (intraventricular hemorrhage and cystic periventricular leukomalacia) in the preterm newborn. Methods. This was a retrospective study on neonates born at less than 34 weeks gestational age, and their respective mothers, at three tertiary medical centers in the north of Portugal, from January 2001 to December 2002. Results. The study included 452 newborns (235 male/217 female; birth weight 1440 (515–2620) grams; gestational age 31 (23–33) weeks), 125 from mothers whose placenta showed signs of chorioamnionitis and 327 from mothers without the condition. The association between histological chorioamnionitis and: (1) intraventricular hemorrhage grades I–IV was OR 1.43 (95% CI 0.49–3.94); (2) intraventricular hemorrhage grades III and IV was OR 2.49 (95% CI 1.20–5.11); (3) cystic periventricular leukomalacia was OR 3.02 (95% CI 1.50–6.07). The association, adjusted for birth weight and gestational age, between chorioamnionitis and: (1) intraventricular hemorrhage grades III and IV was OR 0.94 (95% CI 0.39–2.28); (2) cystic periventricular leukomalacia was OR 1.94 (95% CI 1.03–4.61). The association between histological chorioamnionitis with funisitis and/or vasculitis and: (1) intraventricular hemorrhage grades I to IV was OR 1.27 (95% CI 0.52–3.10); (2) cystic periventricular leukomalacia was OR 2.08 (95% CI 0.72–5.98). Conclusion. This study confirms the association between histological chorioamnionitis and cystic periventricular leukomalacia, but was unable to confirm the association between histological chorioamnionitis and intraventricular hemorrhage.

Policy benchmarking report on neonatal health and social policies in 13 European countries

Background and aim:  Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% ‐ an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states.

Training neonatal skills with simulators

Aim: To compare two different ways of learning (self‐study vs. simulation sessions) the adequate steps to resuscitate a neonate in the 5th year undergraduate medical curriculum.

Follow-up of the survivors of congenital diaphragmatic hernia

INTRODUCTION Survivors of congenital diaphragmatic hernia have increased with the introduction of new treatment modalities and have been reported to experience ongoing medical morbidity until adulthood. AIM To describe the long-term functional impact of congenital diaphragmatic repair on the survivors of a single institution cohort of newborns over a 14-year period. METHODS The follow up medical charts of 39 congenital diaphragmatic hernia survivors treated at a tertiary neonatal intensive care unit, from January 1997 to December 2010, were analyzed. RESULTS The median age at follow up was 70 (4-162) months. Gastrointestinal sequelae were the most common with 12 (30.7%) patients affected by failure to thrive. Chronic lung disease occurred in 5 (12.8%) patients, neurodevelopmental delay in 5 (12.8%), musculoskeletal sequelae in 6 (15.3%), recurrence of hernia in 4 (10.2%) and 2 (7.6%) were deceased. CONCLUSION Congenital diaphragmatic hernia survivors are a group of patients that requires long term periodic follow up in a multidisciplinary setting to provide adequate support and improve their quality of life.

Non-steroid anti-inflammatory drugs in the treatment of patent ductus arteriosus in European newborns

Introduction. Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among very low birth weight infants and must be treated on an individual basis. Non-steroid anti-inflammatory drugs (NSAIDs) have been used in the treatment of PDA. However, no general guidelines have been followed. Aim. To know the European reality on NSAIDs in the treatment of PDA in preterm newborns. Methods. A questionnaire was sent to 24 European Societies of Neonatology and Perinatology to be filled, at least, by two neonatal intensive care units (NICUs) in each country, and to three representatives NICUs in Europe. Results. We received 45 filled forms from 19 countries: 1 (2%) from North, 12 (27%) from East, 6 (13%) from West, and 26 (58%) from South Europe. Intravenous (iv) indomethacin is used in 32 (71%) NICUs (88% use a 30–60 min perfusion), iv ibuprofen in 16 (36%), and oral ibuprofen in 13 (29%). In 45% of NICUs a second course is used; 27% prescribed a third one. Prolonged treatment, 4–6 days, is mentioned by 45% of NICUs, in extremely low birth eight infants and after the failure of 3 courses of treatment. Prophylactic treatment is used in two NICUs, 24% treat no hemodynamically significant PDA, 96% treat with NSAIDs hemodynamically significant PDA and one NICU uses surgical closure as first line treatment. The ibuprofen/indomethacin contra-indications and preferences are similar to the literature. Pedea® is the iv ibuprofen solution used and oral ibuprofen is a solution with 20 mg/ml. The choices are influenced by economical reasons in 22% of NICUs. Conclusion. Our data show a wide variation among NICUs and countries, regarding the use of NSAIDs to treat PDA, and that no general guidelines are followed. Guidelines or recommendations are necessary to standardize treatment of PDA in Europe, in order to give to all newborns identical health care opportunities.

Vitamin A in Prevention of Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) remains one of the most serious challenges in the care of the very preterm infants, affecting approximately one-quarter of infants born <1500g birth weight and 30% <1000g. Oxygen toxicity may contribute to its pathogenesis. Vitamin A concentrations are lower in BPD infants which may result in a reduction of the antioxidant protection. It has been found to up regulate genes necessary for fetal lung growth and increase surfactant production in animal models and is also involved in the modulation of immunological and inflammatory responses by regulation of cytokine production. Retinoic acid plays a key role in lung development improving alveolar septation. Evidence exists that vitamin A supplementation for very low birth weight (VLBW) infants, beyond that routinely given in multivitamin preparations, is associated with a reduction in death or BPD. So, parenteral administration of vitamin A to the newborn is one of the current recommended preventive therapies for BPD (number needed to treat 12; 95% CI:6-94; The information on long-term neurodevelopmental status suggests no evidence of either benefit or harm. Estimates for cerebral palsy range from a number needed to treat of 11 to a number needed to harm of 33. Nowadays, is seems that administration of antenatal vitamin A to the mother in late pregnancy associated with neonatal supplementation can better prevent the development of BPD in areas of endemic vitamin A deficiency. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections, the association of vitamin A prenatal and postnatal, as well as the effectiveness and safety of administered high dose vitamin A in ELBW infants waits evaluation and should be assessed in further trials.

Gastroschisis: preterm or term delivery?

AIM The main objective of this study was to evaluate the association between prematurity and the time to achieve full enteral feeding in newborns with gastroschisis. The second objective was to analyze the associations between length of hospital stay and time to achieve full enteral feeding with mode of delivery, birth weight and surgical procedure. METHODS The medical records of newborns with gastroschisis treated between 1997 and 2007 were reviewed. Two groups were considered: those delivered before 37 weeks (group A) and those delivered after 37 weeks (group B). The variables of gestational age, mode of delivery, birth weight, time to achieve full enteral feeding, length of hospital stay and surgical approach were analyzed and compared between groups. RESULTS Forty-one patients were studied. In Group A, there were 14 patients with a mean birth weight (BW) of 2300 g (range=1680–3000) and a mean gestational age (GA) of 36 weeks (range=34–36). In group B, there were 24 patients with a mean BW of 2700 g (range=1500–3550) and a mean GA of 38 weeks (range=37–39). The mean time to achieve full enteral feeding was 30.1±6.7 days in group A and 17.0±2.5 days in group B (p=0.09) with an OR of 0.82 and a 95% CI of 0.20–3.23 after adjustment for sepsis and BW. No statistical difference was found between low BW (<2500 g), mode of delivery and number of days to achieve full enteral feeding (p=0.34 and p=0.13, respectively). Patients with BW over 2500 g had fewer days in the hospital (22.9±3.1 vs. 35.7±5.7 days; p=0.06). CONCLUSION The results of this study do not support the idea of anticipating the delivery of fetuses with gastroschisis in order to achieve full enteral feeding earlier.

Evolving Indications for the EXIT Procedure: The Usefulness of Combining Ultrasound and Fetal MRI

The EXIT procedure (EX utero Intrapartum Treatment) encompasses a multidisciplinary approach to situations in which airway obstruction is anticipated. Uteroplacental circulation is maintained to avoid neonatal hypoxemia while intubation is attempted. Not only is it useful in congenital diaphragmatic hernia with intrauterine tracheal occlusion, but new indications have been proposed. We present two cases in which EXIT procedure was adopted (huge cervical mass with tracheal compression and a highly vascularized cephalocervical mass) for the same purpose on different grounds. Our two cases stress once more the importance of combining fetal ultrasound and magnetic resonance imaging in the characterization of cervical masses and its usefulness in programming the procedure with a multidisciplinary team.