Betametasona fosfato para la prevención de Síndrome de Dificultad Respiratoria (SDR) del recién nacido de pretérmino / Betamethasone phosphate for the prevention of Respiratory Distress Syndrome (RDS) in the preterm newborn

RESUMEN Introducción: El estándar para inducción de madurez pulmonar en fetos con riesgo de nacer prematuramente es la administración de 12 mg de betametasona acetato/fosfato por dos veces espaciada cada 24 horas. El uso establecido en algunos hospitales públicos en Chile es con dos dosis de 12 mg betametasona fosfato aunque no existen estudios publicados sólo con betametasona fosfato sobre la incidencia de Síndrome de Distress Respiratorio (SDR). Objetivo: Evaluar efecto de betametasona en su forma fosfato como tratamiento antenatal para inducción de madurez fetal pulmonar en la incidencia SDR debido a membrana hialina en prematuros menores de 34 semanas de edad gestacional. Comparar el efecto de betametasona fosfato con el efecto publicado de betametasona acetato/fosfato. Material y método: Análisis de incidencia de SDR en prematuros nacidos en Hospital Padre Hurtado entre 24+0 y 34+0 semanas que recibieron betametasona fosfato para madurez pulmonar y aquellos que no la recibieron. Resultados: De 1.265 neonatos estudiados, 722 completaron dos dosis (57,5%); 436 sólo una dosis (34,5%) y 107 (8,5%) no recibieron corticoides antenatales. La incidencia de SDR debido a membrana hialina en el grupo con dos dosis fue 8,7%, una dosis 25,3% y 32,7% en los no tratados (p<0,001). Para SDR severo las incidencias fueron 6,7%, 12,6% y 16,8% respectivamente (p<0,001). Conclusiones: Inducción de madurez fetal pulmonar con betametasona fosfato en dos dosis de 12 mg IM separadas por 24 horas otorga una reducción significativa de incidencia de SDR semejante a la publicada con betametasona acetato/fosfato en iguales dosis.

ABSTRACT The standard for induction of lung maturity in fetuses at risk of being born prematurely is the administration of 12 mg of betamethasone acetate/phosphate two doses separated by 24 hours. The established use in some public hospitals in Chile is with two doses of 12 mg betamethasone phosphate although there are no studies published with betamethasone phosphate alone on the incidence of respiratory distress syndrome (RDS). Objective: To evaluate the effect of betamethasone in its phosphate form as antenatal treatment for the induction of fetal lung maturity in the incidence of RDS due to hyaline membrane in preterm infants less than 34 weeks of gestational age. To compare the effect of betamethasone phosphate with the published effect of betamethasone acetate/phosphate. Material and method: Analysis of the incidence of RDS in preterm infants born at Hospital Padre Hurtado between 24 + 0 and 34 + 0 weeks who received betamethasone phosphate for lung maturity and those who did not receive it. Results: Of 1,265 infants studied, 722 completed two doses (57.5%); 436 only one dose (34.5%) and 107 (8.5%) did not receive antenatal corticosteroids. The incidence of RDS due to hyaline membrane in the group with two doses was 8.7%, one dose 25.3% and 32.7% in the untreated ones (p <0.001). For severe RDS, incidences were 6.7%, 12.6% and 16.8% respectively (p <0.001). Conclusions: Induction of fetal lung maturity with betamethasone phosphate in two doses of 12 mg IM separated by 24 hours gives a significant reduction in the incidence of RDS similar to that published with betamethasone acetate/phosphate in equal doses.

[Risk factors on the occurrence and prognosis of neonatal hyaline membrane disease].

OBJECTIVE: To identify risk factors with related to the occurrence and prognosis of neonatal hyaline membrane disease (HMD) and to develop effective measures to prevent and treat the disease. METHODS: A case control (1 : 4 paired) study was undertaken, with 62 neonates with HMD as a case group paired with 248 sick neonates without HMD and respiratory disorders as a control group. The controls were matched with the cases by admission time (+/- 7 d), birth weight (+/- 200 g) and gestational age (+/- 3 d). All of the patients came from the neonatal intensive care unit (NICU) in the West China Second University Hospital from June 2008 to January 2009. Conditional logistic regression analysis was performed to identify risk factors associated with the development and prognosis of HMD. RESULTS: Fetal distress, placenta previa, preeclampsia, placental abruption, maternal diabetes, and multiple births were identified as risk factors associated with the development of HMD, with an OR 10.459, 9.382, 8.884, 7.817, 7.727, and 7.217, respectively (P < 0.05). The Cochran Armitage trend test showed that the mortality of HMD decreased with the increase of gestational age and birth weight (P < 0.05). The mortality of HMD increased significantly in the patients with complication such as pulmonary hemorrhage, respiratory failure, neonatal asphyxia, and gastrointestinal hemorrhage (P < 0.05). CONCLUSION: Prevention of premature birth and treatment with high risk pregnancy and complications can reduce the mortality of HMD.

[Short-term respiratory outcome of late preterm newborn in a center of level III]. / Devenir respiratoire à court terme d'une population d'enfants nés à 34, 35 et 36 SA dans une maternité de niveau III.

The rate of infants born at 34-36 weeks gestation has increased over the last 10 years. These babies are at higher risk of morbidity and mortality than full-term infants. At present, prenatal steroids are given until 34 weeks. The purpose of this study was to present the epidemiologic data of the late preterm infants and look for respiratory distress risk factors. This is a descriptive, single-center study including 59, 55 and 72 children born at 34, 35 and 36 weeks gestation, respectively, in a level III center in 2005 and 2006 for babies born at 34 weeks and in 2006 for the babies born at 35 and 36 weeks. Of the mothers who delivered at 34 and 35 weeks, 63% and 49%, respectively, had a morbidity. The cesarean-section delivery rate before labor was 36% for the infants born at 34 weeks and 25% for the infants born at 35 weeks. Prenatal steroids were used for 57% of the mothers who delivered at 34 weeks and for 27% of the mothers who delivered at 35 weeks. In the population of the babies born at 34 weeks, a mean delay between the last dose of steroid and delivery was 18.9 days. Of the infants born at 34, 35 and 36 weeks, 27%, 18% and 8% suffered from respiratory distress. The mechanical ventilation rate was 8.5% and 5.5% for the infants born at 34 and 35 weeks' gestation. Surfactant was given to all infants born at 34 weeks who were intubated. Twenty percent of the 34-week-gestation infants and 12.7% of the 35-week-gestation infants required mechanical ventilation or noninvasive continuous positive airway pressure. Respiratory distress was mainly caused by respiratory distress syndrome or transient tachypnea of the newborn. There were no cases of meconium aspiration syndrome. There was 1 case of infection and 2 cases of pneumothorax. One-third of the infants born at 34-35 weeks were admitted to the neonatal intensive care unit. The number dropped to 11% at 36 weeks' gestation. The gestational age was the only significant risk factor for respiratory distress. There was a strong tendency of the respiratory distress rate to decrease in the babies whose mothers had received steroids (odds ratio = 0.39, p = 0.06).

[Induction of fetal lung maturation in the prevention of hyaline membrane disease: the connection with neonatal sepsis]. / Induzione della maturazione polmonare fetale nella profilassi della malattia da membrane ialine e sepsi neonatale.

BACKGROUND: The aim of this study was to evaluate the effect of antenatal maternal corticosteroid treatment on the frequency of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. METHODS: A nonrandomized analysis was performed on 189 neonates of 24-34 weeks' gestation who were born at the Department of Obstetrics and Gynecology, University of Udine, between January 2000 to December 2001. The neonates were subdivided into 3 groups: 1) 143 neonates received 2 doses of corticosteroids in a 24-hour interval and repeated after 10 days; 2) 26 neonates received 2 doses; 3) 20 neonates did not receive any treatment. Data were analysed with the Fisher exact test. p<0.05 was considered significant. RESULTS: The incidence of respiratory distress syndrome (RDS), neonatal mortality and intraventricular hemorrhage was respectively 43.4%, 3.2 % and 6.3 %. The rate of early-onset neonatal sepsis was 4.9% in the 1st group, 3.9% in the 2nd group and 5% in the 3rd group. There were no significant differences in the early-onset neonatal sepsis and the antenatal corticosteroids treatment. CONCLUSIONS: The single or the multiple courses of antenatal steroids did not apparently increase neonatal sepsis in patients with preterm delivery.

[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. / Apport de la corticothérapie anténatale dans la prévention de la maladie des membranes hyalines chez le prematuré. Etude prospective randomisée.

OBJECTIVE: The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population. SUBJECTS AND METHODS: Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist. RESULTS: 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars. CONCLUSION: Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.

[Perinatal corticosteroid therapy: modalities, efficacy, consequences]. / Corticothérapie périnatale: modalités, efficacité, conséquences.

During perinatal period, corticosteroid treatment has two major indications: first antenatally to improve fetal maturity and then to treat postnatal bronchopulmonary dysplasia. Antenatal corticosteroid treatment is widely proved to be efficient in reducing hyaline membrane disease and perinatal mortality incidence. Moreover, it has positive effects on intraventricular hemorrhage incidence, on hemodynamic failure, on persistent patent ductus arteriosus and on necrotizing enterocolitis. Side-effects are few and mild considering expected benefits and they usually occurs after multiple courses. Contra-indications are rare. Bronchopulmonary dysplasia comes with early, important and prolonged inflammatory processes. Corticotherapy allows decreasing significantly length of mechanical ventilation and oxygenotherapy among ventilated premature infants diagnosed with bronchopulmonary dysplasia. In the meantime, acute side-effects are frequent and benefits on mortality rate and long term outcome are not obvious. Main concern remains on possible long-term deleterious consequences on growth, lung and central nervous system development. In this field, clinical data are still insufficient as animal experimentation data promote caution and search for a minimal efficient therapeutic pathway.

Effects of early treatment with rSP-C surfactant on oxygenation and histology in rats with acute lung injury.

Surfactant treatment in patients with acute respiratory distress syndrome (ARDS) may be a promising treatment strategy. The aim of this study was to investigate whether addition of a recombinant surfactant protein C (rSP-C) to a plain phospholipid (PL) surfactant (PL surfactant) can result in activity comparable to commercially available surfactant preparations (Alveofact and bLES) which contain surfactant protein B and C. In this investigation dose-response comparisons of four surfactants were performed in an animal model of ARDS induced by total lung lavage. The surfactants were given shortly (;10 min) after the last lavage. The effects of surfactant treatment were compared with respect to improve oxygenation and to prevent histopathological changes, such as hyaline membrane formation. The surfactants were compared to lavaged, untreated controls. The surfactants were administered at doses of 25, 50 and 100 mg total amount of phospholipids/kg body weight. At 120 min after early treatment, all three doses of rSP-C surfactant showed statistically significant higher improvements in oxygenation than PL surfactant. This improvement was comparable to bLES and superior to Alveofact. The rSP-C surfactant showed the most prominent effect on preventing hyaline membrane formation. It was again superior to PL surfactant and comparable to bLES. It is concluded that addition of rSP-C enhances the activity of a pure PL surfactant. The rSP-C surfactant showed comparable or even superior activity to bovine-derived surfactant preparations containing both, SP-B and SP-C.

Increased survival in low birth weight neonates given prophylactic surfactant.

OBJECTIVE: To compare the effectiveness of a prophylactic surfactant treatment strategy (PRO) to the effectiveness of a rescue (RESC) surfactant treatment strategy in patients at high risk for developing hyaline membrane disease (HMD). STUDY DESIGN: We analyzed data from a retrospective cohort consisting of all patients admitted to the neonatal intensive care units at the centers participating in the recently completed Infasurf-Survanta Comparative Trial. To be in the cohort, a patient had to be admitted during the trial, be <48 hours of age on admission, have a gestational age of <30 weeks, have a birth weight of 501 to 1250 gm, and be free of congenital anomalies. Twelve centers participated in this study. They contributed 1097 patients of whom 381 were treated with a PRO strategy. RESULTS: Survival was significantly higher in the PRO-strategy patients (84% vs 72%, p < 0.05) as was survival without oxygen requirement at a postconceptional age of 36 weeks (60% vs 46%, p < 0.05). In addition, the patients with PRO had a lower prevalence of grade III and IV intraventricular hemorrhage (IVH, 9% vs 14%, p < 0.05). All analyses were controlled for birth weight and type of study center. CONCLUSION: These data support the conclusion that using a PRO treatment strategy results in improved survival in patients at risk for developing HMD. A PRO treatment strategy may also decrease the likelihood of developing a severe IVH.

Meta-analyses of surfactant replacement therapy of infants with birth weights less than 2000 grams.

OBJECTIVES: We conducted a meta-analysis of surfactant replacement therapy to determine (1) the efficacy of surfactant therapy in the reduction of short-term morbidity and long-term outcome in terms of bronchopulmonary dysplasia (BPD) and mortality; (2) whether there are differences in efficacy between modified natural surfactant and synthetic surfactant; (3) the effectiveness of prophylactic surfactant therapy; and (4) whether there are differences in efficacy between the prophylactic approach and the rescue strategy. STUDY DESIGN: We included studies in which infants with birth weights between 500 and 1500 gm were eligible. Studies were grouped into the following categories: (1) rescue therapy with modified natural surfactant; (2) rescue therapy with synthetic surfactant; (3) prophylaxis with modified natural surfactant; (4) prophylaxis with synthetic surfactant; (5) prophylaxis versus rescue studies; (6) modified natural surfactant versus Exosurf (Burroughs-Wellcome Co., Research Triangle Park, NC) studies. The relative risk ratios, corrected for study size, were calculated for the outcome variables (pneumothorax, incidence of BPD, survival, survival without BPD, prevention of hyaline membrane disease [HMD], and intraventricular hemorrhage [IVH]). RESULTS AND CONCLUSION: Surfactant therapy is efficacious in reducing the risk for pneumothorax and increasing the chance for survival without BPD. Synthetic surfactant is not efficacious in the prevention of HMD. Modified natural surfactant is more effective in reducing the risk of pneumothorax and increasing the chance for survival without BPD than is synthetic surfactant. These data do not support the use of either synthetic or modified natural surfactant for routine prophylaxis.

Gestational age can predict the need for prophylaxis with surfactant therapy.

Controversy exists as to whether prophylactic or rescue therapy with surfactant should be used in infants born at less than 30 weeks gestation. We developed the hypothesis that gestational age can be used to predict a need for prophylactic surfactant therapy. We designed this retrospective study to determine whether there was a gestational age below which one could accurately predict the need for prophylactic surfactant therapy in almost all infants and limit unnecessary treatment of infants. We conducted a retrospective study of infants born at 23-34 weeks' gestation to determine the frequency with which surfactant therapy was used in a rescue strategy at each gestational age, and to ascertain the sensitivity, specificity, and predictive values of gestational age as a predictor of the use of surfactant therapy. There was a significant inverse correlation between gestational age and the proportion of infants treated with surfactant (r = -0.923, p < 0.001). A gestational age cut-off of 26 completed weeks' had a positive predictive value of 85% and a specificity of 96% for the need for surfactant therapy. We conclude that gestational age can be used to predict a need for surfactant therapy in premature infants. At our institution, the failure to attain 26 completed weeks' gestation will accurately predict the need for surfactant therapy and will result in unnecessary treatment of very few infants. We suggest that each institution caring for very low birth weight infants should examine its population to determine the gestational age at which they can accurately predict the need for prophylaxis with surfactant therapy.

[Prenatal corticotherapy and acceleration of fetal maturation. II. Results of clinical applications]. / Corticothérapie anténatale et accélération de la maturation foetale. II. Résultats des applications cliniques.

Numerous subsequent controlled trials and recent meta-analysis have confirmed the efficiency of antenatal glucocorticoid therapy in reducing both the incidence of respiratory distress syndrome (RDS) and perinatal mortality. Moreover, antenatal glucocorticoid administration reduces the odds of several severe complications relating to immaturity: intraventricular hemorrhage (IVH), ductus arteriosus patency, necrotising enterocolitis, and hemodynamic failure. Exogenous surfactant therapy has not ruled out the benefits of corticosteroids: on the contrary, a synergic effect is obtained when both antenatal and postnatal therapeutic approaches are combined. Very premature infants may also take advantage of the hormonal treatment: in this population, RDS occurrence, IVH incidence and perinatal mortality are also reduced. Unfortunately, despite convincing evidence, the incidence of antenatal steroids therapy has not yet achieved the optimal and desirable level. Obstetricians and pediatricians must be encouraged to ensure high maternal exposure to steroids when preterm delivery is likely to occur.

Surfactante artificial, su uso en recién nacidos prematuros / Artificial pulmonary surfactant: its use in premature newborm

El síndrome de dificultad respiratoria (SDR) neonatal o Enfermedad de Membrana Hialina (EMH), continúa siendo una de las principales causas de mortalidad entre los recién nacidos prematuros. El tratamiento convencional de esta enfermedad es estrictamente sintomático y de sostén, para permitir al paciente llegar hasta el momento en que es capaz de sintetizar su propio material surfactante. Consiste en asegurar un ambiente térmico adecuado, aportes hidroelectrolíticos suficientes y asistencia respiratoria. En las últimas décadas ha comenzado a desarrollarse en forma exitosa un tratamiento más racional y específico, dirigido a tratar la causa primaria de la enfermedad. Ya que la falta de surfactante durante los primeros 2 ó 3 días del naciemiento es la causa del problema, se implementó una terapéutica de reemplazo. Las modalidades utilizadas hasta la fecha pueden reunirse en dos, una como tratamiento de pacientes afectados y otra como profilaxis en el momento del nacimiento en prematuros con alto riesgo de desarrollar la enfermedad (AU)

Prematuridade: aspectos obstétricos e perinatais / Prematurity: obstetric and perinatal aspects

Foram avaliadas, retrospectivamente, 359 gestaçoes assistidas na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto-USP, no período de janeiro a dezembro de 1991. A incidência de pré-termo neste período foi de 11,4 por cento, tendo o parto ocorrido, mais freqüentemente, nas idades entre a 34( e 36( semana gestacional (58 por cento). A assistência pré-natal ocorreu em 87 por cento dos casos, sendo 20 por cento no HCFMRP-USP. Natimortalidade e prematuridade foram as intercorrências mais freqüentes detectadas em gestaçoes anteriores; enquanto que, no decorrer da gestaçao analisada, a intercorrência mais comum foi a amniorrexe prematura, seguida da patologia hipertensiva e da infecçao do trato urinário. A tocólise foi utilizada em 14 por cento das vezes e a corticoterapia mostrou-se efetiva na reduçao das taxas de membrana hialina na idade gestacional entre a 31( e a 34( semana. A operaçao cesariana foi a principal forma de resoluçao das gestaçoes (56 por cento) e a principal indicaçao foi o sofrimento fetal agudo. Em aproximadamente 61 por cento dos casos, os RN, mostraram-se adequados para a idade gestacional correspondente e, na maioria das vezes, tinham o peso compreendido entre 1501-25OOg (55 por cento). Estudando-se as condiçoes de nascimento dos RN, observou-se que 56 por cento deles mostraram-se vigorosos na análise dos índices de Apgar no primeiro minuto e 82 por cento no quinto minuto de vida. A icterícia foi a intercorrência neonatal mais freqüente (32 por cento), seguida da anóxia grave (ll por cento) e da membrana hialina (9 por cento). Quando se avaliou o tempo de internamente, verificou-se que a maioria permanecia no berçário entre 3-10 dias, e que na idade igual ou inferior a 28 semanas o obituário foi de 95 por cento, ocorrendo desde poucos minutos até dois dias de vida. Depreende-se que o pré-termo ainda continua apresentando altos índices de morbimortalidade, apesar da evoluçao médica, e que deve ser assistido por uma equipe especializada, com o intuito de entender e minimizar os danos decorrentes da imaturidade funcional.