Administración precoz de eritropoyetina en el prematuro extremo, ¿factor de riesgo de la retinopatía del prematuro? / Early administration of erythropoietin in the extreme premature, a risk factor for retinopathy of prematurity?

Introducción: La eritropoyetina (EPO) estimula la angiogénesis y podría favorecer la retinopatía del prematuro (ROP). El objetivo fue determinar si la EPO más hierro (Fe) administrada a partir del quinto día de vida era un factor de riesgo independiente para el desarrollo de ROP y su gravedad. Pacientes y métodos: 718 prematuros supervivientes con peso al nacer (PN) ≤1.500g o edad gestacional (EG) ≤32 semanas (y 6 días), ingresados entre 2001 y 2008. Los objetivos de SaO2 durante estos años fueron mantenerla entre el 88 y el 93%. El tratamiento con EPO se inició a los 5–7 días de vida, a 250UI/kg/3 veces a la semana vía subcutánea, asociada a Fe 5–6mg/kg/día, hasta las 34 semanas de edad corregida o el alta. Resultados: 493 prematuros (68,7%) no presentaron ROP, 139 (19,4%) tuvieron una ROP grado 1, 50 (7,0%) una grado 2 y 36 (5,0%) una grado 3. 27 precisaron láser. Una mayor gravedad de la ROP se asoció con menor PN y EG, más patología neonatal y mayor agresividad terapéutica (duración de la oxigenoterapia o ventiloterapia, número de transfusiones de hematíes). Los factores de riesgo asociados de manera independiente y significativa con la presencia de cualquier estadio de ROP fueron: menor PN, ausencia de cesárea, administración de EPO y necesidad de transfusión de hematíes. La administración de EPO aumentó 2,4 veces el riesgo de ROP, pero la influencia de la EPO sólo se observó en la aparición de ROP grado 1 (odds ratio: 5,50). Conclusiones: La administración de EPO+Fe se asocia y quizás favorece la aparición de ROP grado 1 (AU)

Introduction: Erythropoietin (EPO) stimulates angiogenesis and may favour the appearance of retinopathy of prematurity (ROP). The objective was to determine if EPO+Fe administered from the 5th day of life could be an independent risk factor for ROP appearance and its severity. Patients and method: The study included 718 preterm newborns with a birth weight ≤1,500g or a gestational age ≤32 weeks (and 6 days), admitted between 2001 and 2008. During these years, the target SaO2 was between 88% and 93%. EPO treatment began at 5–7 days of life, with a dose of 250 UI/Kg, 3 times a week, subcutaneously, together with Fe, 5–6mg/kg/day, both until 34 weeks of corrected age or discharge. Results: A total of 493 preterms (68.7%) did not have ROP, 139 (19.4%) had a grade 1 ROP, 50 (7.0%) a grade 2 ROP and 36 (5.0%) a grade 3 ROP. Laser therapy was required by 27 severe ROP was associated with lower birth weight and gestational age, more neonatal morbidity and a more aggressive treatment (duration of oxygen supplements or mechanical ventilation, number of blood transfusions). Risk factors independently and significantly associated with any ROP grade were: lower birth weight, no caesarean section, EPO administration and need for blood transfusion. EPO administration increased the risk of ROP by 2.4, but this only happened in case of grade 1 ROP (OR: 5.50). Conclusions: EPO+Fe administration is associated and perhaps stimulates the appearance of grade 1 ROP (AU)

[Early administration of erythropoietin in the extreme premature, a risk factor for retinopathy of prematurity?]. / Administración precoz de eritropoyetina en el prematuro extremo, ¿factor de riesgo de la retinopatía del prematuro?

INTRODUCTION: Erythropoietin (EPO) stimulates angiogenesis and may favour the appearance of retinopathy of prematurity (ROP). The objective was to determine if EPO+Fe administered from the 5th day of life could be an independent risk factor for ROP appearance and its severity. PATIENTS AND METHOD: The study included 718 preterm newborns with a birth weight ≤1,500g or a gestational age ≤32 weeks (and 6 days), admitted between 2001 and 2008. During these years, the target SaO2 was between 88% and 93%. EPO treatment began at 5-7 days of life, with a dose of 250 UI/Kg, 3 times a week, subcutaneously, together with Fe, 5-6mg/kg/day, both until 34 weeks of corrected age or discharge. RESULTS: A total of 493 preterms (68.7%) did not have ROP, 139 (19.4%) had a grade 1 ROP, 50 (7.0%) a grade 2 ROP and 36 (5.0%) a grade 3 ROP. Laser therapy was required by 27 severe ROP was associated with lower birth weight and gestational age, more neonatal morbidity and a more aggressive treatment (duration of oxygen supplements or mechanical ventilation, number of blood transfusions). Risk factors independently and significantly associated with any ROP grade were: lower birth weight, no caesarean section, EPO administration and need for blood transfusion. EPO administration increased the risk of ROP by 2.4, but this only happened in case of grade 1 ROP (OR: 5.50). CONCLUSIONS: EPO+Fe administration is associated and perhaps stimulates the appearance of grade 1 ROP.

Attempt to normalize simulated exhaled nitric oxide according to ventilatory settings.

BACKGROUND: Simulated exhaled nitric oxide (eNO) depends on ventilatory settings used in different experimental conditions. OBJECTIVES: To normalize the simulated minute exhaled nitric oxide according to different ventilatory settings. WORKING HYPOTHESIS: Different ventilatory settings influence the concentrations of exhaled nitric oxide and these results can be normalized. METHODOLOGY AND STUDY DESIGN: We used a rubber lung model (50 ml) with an orifice through which a 3 mm endotracheal tube was introduced. The NO, which simulated that of endogenous production, was delivered through the base of the lung using a unidirectional rotameter and obtaining a concentration of around 25 ppb. The sample of gas was recorded through a 6 F arterial catheter introduced into the endotracheal tube to its tip. The ventilator used was a Babylog 8000. Air delivered was compressed and filtered and had an NO content of under 0.3 ppb. The NO level assessed was the plateau value given by the software of the Sievers NOA apparatus. Each experiment involved sampling during 1 min, three times. Normalization was done using a multiple cubic regression formula. RESULTS: An increase in respiratory frequency or in peak of inspiratory pressure were accompanied by a decrease in eNO (ppb). Minute volume was adjusted for the percentage of leakage given by the ventilator. Normalization was obtained analyzing 518 respirations with different ventilatory settings. The coefficient of variation fell from 15.5% to 0.27%. Validation of the normalization formula was performed in other three groups (320, 372, and 372 respirations) with different simulated NO concentrations (25, 16, and 50 ppb), resulting in reduction of the coefficient of variation from 42.7% to 9.3%, from 42.3% to 10.6% and from 45.2% to 9.6%, respectively. CONCLUSIONS: Normalization of simulated minute eNO according to ventilatory settings is possible using the equipment and experimental set-up reported. Extrapolation to patients is not possible without constraints.

Nutrición agresiva del recién nacido de bajo peso extremo / Aggressive nutrition of the extreme low weight newborn

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Efficacy of three treatment schedules in severe meconium aspiration syndrome.

AIM: To compare three different schedules in severe meconium aspiration syndrome (MAS) treatment: standard, bronchoalveolar lavage (BAL) with diluted surfactant, and diluted surfactant BAL plus a single early dexamethasone dose. METHODS: Twenty-four full-term newborns with severe MAS (needing mechanical ventilation and with oxygenation index > or = 15) were divided into three groups: group I (historical control group; n = 6) treated with standard therapy; group II (n = 7) treated in the first hours of life with one BAL using diluted surfactant (beractant 5 mg/mL) in a volume of 15 mL/kg in four aliquots; and group III (n = 11) treated with one diluted surfactant BAL and a previous single dose of intravenous dexamethasone (0.5 mg/kg). RESULTS: At 12 h, groups II and III showed a significant improvement in oxygenation index (OI) compared with group I (14.7% and 27.0% vs -19.6% respectively; p = 0.012). Group III also showed a significantly lower OI than group I at 24 h (63.6% vs -27.9%) and at 48 h (87.1% vs 49.6%). Group III, in comparison to group I, showed a lower FiO2 requirement at 12 h (0.66 vs 1), at 24 h (0.4 vs 0.87) and at 48 h (0.35 vs 0.67), and a decrease in the number of days of inhaled nitric oxide administration, mechanical ventilation, oxygen therapy and hospitalisation period. All patients from groups II and III survived and none developed pneumothorax or respiratory infections. CONCLUSION: Diluted surfactant BAL in the first hours of life combined with an intravenous single dose of dexamethasone may be an effective treatment for severe MAS.

[Neonatal convulsions and subarachnoid hemorrhage after in utero exposure to paroxetine]. / Convulsiones y hemorragia subaracnoidea tras exposición a paroxetina in utero.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are often used as antidepressants in pregnant women. SSRIs do not appear to increase the teratogenic risk when used in their recommended doses. However, not enough information is available at this time about the risk of toxicity and complications in newborns, after mother treatment with SSRI during the third trimester of pregnancy. We are limited to the existing reports that describe newborns with symptoms due to hyperserotoninemia or withdrawal. CASE REPORT: One newborn whose mother had been treated with paroxetine 20 mg/day during pregnancy, presented convulsions and subarachnoid haemorrhage in the first six hours of life. The newborn did not present symptoms of hypoxic ischaemic encephalopathy, withdrawal syndrome, infection, metabolic alterations, cerebral malformations or coagulopaties. DISCUSSION: The most probable etiology is that the paroxetine could decrease the seizure threshold, taking place the first seizure during delivery. The difficult fetal extraction would have provoked the subarachnoid haemorrhage in a patient with an impaired haemostatic function due to a depletion of platelet serotonin and may also contribute the increased vascular fragility due to paroxetine and reported in adults or in animals. CONCLUSION: Neonatal convulsions and subarachnoid haemorrhage may occur after paroxetine treatment in the third trimester of pregnancy. An accurate follow up of these newborns in the firsts days of life is strongly recommended.

[Blood ammonia and transaminases in full term infants suffering from perinatal asphyxia]. / Amoniaco y transaminasas en sangre en el recién nacido a término afectado de asfixia perinatal.

AIMS: To find hepatic markers of perinatal asphyxia. PATIENTS AND METHODS: Variations in blood ammonia during the first week of life and in transaminase in serum during the first 48 hours were analysed in four groups of newly born infants (NBI): Group I or control, in which 65 NBI were included, with suspected unconfirmed infection and no other pathologies; Group II, made up of 15 NBI with loss of foetal well being (LFW) with no posterior neurological clinical features; Group III, consisting of 27 NBI with LFW criteria and mild hypoxic ischemic encephalopathy (HIE); and Group IV, with 25 NBI with LFW criteria and mild HIE according to Amiel s criteria. RESULTS: The average blood ammonia values in full term infants remain steady during the first week of life (87.66 21.69 mg/dL), as occurs in infants with LFW but without HIE (89.08 24.69 mg/dL) and in those with mild HIE (89.08 20.75 mg/dL). In moderate HIE, the blood ammonia level rises until the third day (108.55 7.04 mg/dL) and then drops back to the initial values (p= 0.0045). When grouped by days, these values show significant differences (p= 0.04), with higher values in Group IV. The NBI with HIE presented higher levels of transaminases, especially of AST (GOT) (p= 0.000001), and this increase is proportional to its gravity. No relation was found between values of blood ammonia and transaminases. CONCLUSIONS: Both blood ammonia and transaminases can be considered to be perinatal asphyxia markers.

Encefalopatía neonatal grave, secundaria a episodio vasovagal prolongado en una gestante de 31 semanas / Severe neonatal encephalopathy, secondary to a prolonged vasovagal episode in a woman 31 weeks pregnant

Introducción. El síncope vasovagal es poco frecuente en la segunda mitad de la gestación, aunque en este período resulta frecuente el síndrome de hipotensión supina. En estos episodios, la hipotensión marcada puede dificultar el flujo uteroplacentario. Caso clínico. Gestante de 31,5 semanas que presenta pérdida de conciencia de 15 minutos al adoptar la bipedestación. A las 24 horas, al percibir disminución de movimientos fetales, se practica registro cardiotocográfico, que evidencia patrón patológico y perfil biofísico fetal, mediante ecografía, en el cual se observa hipotonía fetal marcada y ausencia de movimientos. Se practica cesárea urgente y se produce nacimiento de feto, varón de 1.810 g, Apgar 5/6 que requiere intubación y ventilación por dificultad respiratoria y con hipotonía generalizada con ausencia de reflejos. En los días siguientes desarrolla hipertonía de base y fallece a los 18 días de vida. En la necropsia se observa lesión encefálica grave de tipo isquémico. Exploraciones complementarias maternas, negativas. Conclusión. La encefalopatía prenatal grave secundaria a síncope vasovagal materno es una entidad muy poco frecuente, de la cual no hemos encontrado otros casos en la literatura. La prolongada duración del episodio hipotensivo, junto con la prematuridad que comporta escasa regulación del flujo cerebral, pudieron contribuir a la gran afectación del sistema nervioso central (AU)

[Usefulness of erythropoietin in the treatment of anemia of prematurity. Influence of birth weight]. / Utilidad de la eritropoyetina en el tratamiento de la anemia de la prematuridad. Influencia del peso de nacimiento.

OBJECTIVE: Our objective was to analyze the utility of treatment with erythropoietin (EPO) plus iron in decreasing the need of late transfusions and reaching hematocrit > or = 32% in preterm infants of < or = 32 weeks of gestation. PATIENTS AND METHODS: Between March 1996 and October 1998, preterm infants of one unit were considered as the control group, while another group in another unit in the same hospital were treated with EPO (250 U/Kg, 3 times a week, subcutaneously) from day 7 of life until 37 weeks 37 post-conception. Oral iron was added to treatment one week later (5 mg/Kg, and increased in order to keep ferritin levels > 100 ng/ml). More strict transfusion criteria were established. Weights were stratified in < 1,000 g, 1,000-1,249 g and > or = 1,250 g. RESULTS: Blood losses during the first 2 weeks were higher in the control group and that was probably the reason for the increased number of transfusions during the first 10 days of life. Late transfusions decreased in the EPO treated group (p < 0.0003). This was significant after the 3rd week and in the 1,000-1,249 g weight group. The EPO-treated group showed lower hematocrit < or = 32% (p < 0.001). When EPO-treated infants were separately analyzed it was clear that late transfusions were more frequent in infants that were smaller, more immature and sicker and with higher blood losses. The reticulocyte count increase was similar in both groups of late transfused vs. Not transfused EPO-treated infants, being higher at 4 weeks after EPO was started (30/1000). EPO and ferritin values were always higher in late transfused EPO-treated infants than in non-transfused infants. CONCLUSIONS: The EPO plus iron treated group of preterm infants had a 40% decrease in the need for late transfusions in comparison with the control group. The best results were obtained in the 1000-1249 g group of preterm infants.