[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Risk of hypospadias in newborn infants exposed to valproic acid during the first trimester of pregnancy: a case-control study in Spain.

BACKGROUND: Hypospadias is one of the most frequently occurring genital anomalies described in infants prenatally exposed to valproic acid (VA). However, to our knowledge, only one publication has studied a potential causal relationship between VA and hypospadias, only estimating the unadjusted global risk. Here we present the results of a multivariate case-control study aimed at analysing and quantifying the specific risk of hypospadias in newborn infants exposed to VA during the first trimester of pregnancy. METHODS: The data analysed here were derived from the Spanish Collaborative Study of Congenital Malformations (ECEMC), an ongoing, hospital-based, case-control study and surveillance system in which collaborating paediatricians identify case and control infants. The paediatricians collect the same data for both case and control infants, blinded to information on any prenatal exposure. The information includes 312 items related to many prenatal exposures, including drug exposure, reproductive and family history, and other characteristics. The sample analysed included 2,393 infants with hypospadias and 12,465 male controls. RESULTS: The results showed that the unadjusted risk of hypospadias in infants prenatally exposed to VA was 5.23 (95% CI 2.31, 11.86; p < 0.00001). Once adjusted for 13 potential confounding factors using conditional logistic regression analyses, the value of the risk was of a similar magnitude (odds ratio = 5.71; 95% CI 1.78, 18.36; p = 0.003). In addition, the frequency of hypospadias in the study population was approximately 1.8/1000 births. This allowed us to calculate the specific risk for an infant with hypospadias to be born to an exposed mother, which was 1 child in 97 births to mothers using VA during the first trimester of pregnancy. We consider this information much more useful for risk assessment than the risk value itself. CONCLUSIONS: An alteration of placental gonadotrophic stimulation caused by changes in gonadotropin-releasing hormone release produced by the effects of VA on GABA is a possible pathogenic mechanism. Our results support the relationship between prenatal exposure to VA and hypospadias.

[Adverse effects of selective serotonin reuptake inhibitors use during the third trimester of pregnancy and prevention guidelines]. / Efectos adversos de los inhibidores selectivos de la recaptación de serotonina durante el tercer trimestre de la gestación y guías de prevención.

Selective Serotonin Reuptake Inhibitors (SSRIs) have become the drug of choice for the treatment of depression and have shown to be effective in the treatment for other mental disorders. Recently, several articles have reported about the adverse effects observed in newborns after maternal exposure to these drugs during the last trimester of pregnancy. In this work, a review of literature is presented, regarding the above mentioned adverse effects. Moreover, some guidelines for the rational use of these drugs during the last trimester of pregnancy and for the management of prenatally exposed newborns are provided.

Efectos adversos de los inhibidores selectivos de la recaptación de serotonina durante el tercer trimestre de la gestación y guías de prevención / Side effects of selective serotonin reuptake inhibitors use during the third trimester of pregnancy and guidelines

Los inhibidores selectivos de la recaptación de serotonina (ISRS) se han convertido en el tratamiento de elección de la depresión y han demostrado ser efectivos en el tratamiento de otros trastornos mentales diversos. Últimamente, se han publicado numerosos artículos sobre los efectos adversos observados en el recién nacido tras la utilización materna de estos fármacos durante el último trimestre de la gestación. En este trabajo se realiza una revisión de la bibliografía de dichos efectos adversos y se enumeran unas pautas de actuación para el uso racional de estos fármacos durante la última parte de la gestación, así como para el manejo de los recién nacidos expuestos prenatalmente

Selective Serotonin Reuptake Inhibitors (SSRIs) have become the drug of choice for the treatment of depression and have shown to be effective in the treatment for other mental disorders. Recently, several articles have reported about the adverse effects observed in newborns after maternal exposure to these drugs during the last trimester of pregnancy. In this work, a review of literature is presented, regarding the above mentioned adverse effects. Moreover, some guidelines for the rational use of these drugs during the last trimester of pregnancy and for the management of prenatally exposed newborns are provided

[Antenatal exposure to corticosteroids for fetal lung maturation and its repercussion on weight, length and head circumference in the newborn infant]. / Exposición prenatal a glucocorticoides para acelerar la maduración pulmonar fetal y su repercusión sobre el peso, la talla y el perímetro cefálico del recién nacido.

BACKGROUND AND OBJECTIVE: To study the effects of antenatal corticosteroids treatment to promote fetal lung maturation, on fetal growth, depending on the number of the courses administered. PATIENTS AND METHOD: The study was based on data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), analysing a sample of 29,557 singleton liveborn infants without congenital defects. An stratified analysis by gestational age was performed to compare the weight, length and head circumference at birth, in the exposed and unexposed infants to dexamethasone/betamethasone. To control confounding factors (year of birth, maternal age, gestational age, parity, maternal smoking and/or alcohol consumption, gestational diabetes, non-gestational diabetes and other maternal chronic diseases) we used a general linear model with random effects, being the randomised variable the place of birth. RESULTS: The exposure to more than one course of antenatal corticosteroids resulted in a significant reduction of birth weight, length and head circumference in singleton preterm infants. The birth weight decreased by 22% (p < 0.0001), the length 5% (p = 0.002) and the head circumference 6% (p = 0.0005). The treatment with only one course reduced also significantly the weight and length but not the head circumference. In addition, we observed a significant interaction between the treatment and gestational age at birth indicating that the effect of corticosteroids is stronger in the most premature babies. CONCLUSIONS: In this retrospective analysis, the antenatal exposure to corticosteroids to promote fetal maturation is associated with diminished weight, length and head circumference in the premature newborn infant. This negative effect was greater in those premature babies exposed to multiple courses.

Exposición prenatal a glucocorticoides para acelerar la maduración pulmonar fetal y su repercusión sobre el peso, la talla y el perímetro cefálico del recién nacido / Antenatal exposure to corticosteroids for fetal lung maturation and its repercussion on weight, length and head circumference in the newborn infant

Fundamento y objetivo: Analizar el impacto sobre el crecimiento fetal del tratamiento con glucocorticoides para acelerar la maduración del pulmón fetal, según el número de ciclos administrados. Pacientes y método: Se ha utilizado la base de datos del Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) en una muestra de 29.557 recién nacidos vivos no gemelos sin defectos congénitos. Se compararon, mediante un análisis estratificado por edad gestacional al nacimiento, el peso, la talla y el perímetro cefálico de los expuestos prenatalmente a betametasona o dexametasona con los no expuestos. Para el control de factores de confusión o interacción (año de nacimiento, edad materna, edad gestacional, paridad, consumo de tabaco y/o bebidas alcohólicas, diabetes crónica, diabetes gestacional y otras enfermedades crónicas) se utilizó un modelo lineal general con efectos aleatorios, en el que la variable aleatoria fue el lugar de nacimiento. Resultados: La exposición prenatal a 2 o más ciclos de glucocorticoides comporta una disminución del peso, la talla y el perímetro cefálico en prematuros. Concretamente, en la muestra analizada supone una pérdida del 22% del peso (p < 0,0001), del 5% de la talla (p = 0,002) y del 6% del perímetro cefálico al nacimiento (p = 0,0005). La exposición a un solo ciclo también comporta una pérdida significativa del peso y la talla, aunque no del perímetro cefálico. Asimismo, se ha observado una interacción significativa entre el tratamiento y la edad gestacional, lo cual indica que el impacto de la medicación es más acusado en los más prematuros. Conclusiones: En este análisis retrospectivo la exposición prenatal a glucocorticoides para acelerar la maduración pulmonar fetal se asoció, en los recién nacidos prematuros, a un efecto negativo sobre el peso, la talla y el perímetro cefálico. Este efecto fue más acusado en los prematuros expuestos a más de un ciclo de glucocorticoides

Background and objective: To study the effects of antenatal corticosteroids treatment to promote fetal lung maturation, on fetal growth, depending on the number of the courses administered. Patients and method: The study was based on data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), analysing a sample of 29,557 singleton liveborn infants without congenital defects. An stratified analysis by gestational age was performed to compare the weight, length and head circumference at birth, in the exposed and unexposed infants to dexamethasone/betamethasone. To control confounding factors (year of birth, maternal age, gestational age, parity, maternal smoking and/or alcohol consumption, gestational diabetes, non-gestational diabetes and other maternal chronic diseases) we used a general linear model with random effects, being the randomised variable the place of birth. Results: The exposure to more than one course of antenatal corticosteroids resulted in a significant reduction of birth weight, length and head circumference in singleton preterm infants. The birth weight decreased by 22% (p < 0.0001), the length 5% (p = 0.002) and the head circumference 6% (p = 0.0005). The treatment with only one course reduced also significantly the weight and length but not the head circumference. In addition, we observed a significant interaction between the treatment and gestational age at birth indicating that the effect of corticosteroids is stronger in the most premature babies. Conclusions: In this retrospective analysis, the antenatal exposure to corticosteroids to promote fetal maturation is associated with diminished weight, length and head circumference in the premature newborn infant. This negative effect was greater in those premature babies exposed to multiple courses