Elvira Rodríguez-Pinilla

Pre‐gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes

Aimsu2003 The aim of the present study was to identify characteristics in women diagnosed with gestational diabetes mellitus (GDM) that could be predictive of congenital malformations in their infants.

Maternal polymorphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes : Is there any relationship between polymorphisms of the folate pathway, maternal homocysteine levels, and the risk for having a child with down syndrome?

This study was aimed at analyzing the effect of mutations in three non‐synonymous SNP genes (677Cu2009>u2009T and 1298Au2009>u2009C of the methylenetetrahydrofolate reductase (MTHFR) gene, and 66Au2009>u2009G in the MTRR gene) on total plasmatic homocysteine (Hcy), in 91 mothers of Down syndrome (DS) infants and 90 control mothers. The comparison of both groups of mothers is a new way to determine if those mutations and their interactions increase the risk for DS. Material came from the case‐control network of the Spanish Collaborative Study of Congenital Malformations (ECEMC).

The safety of calcium channel blockers during pregnancy : A prospective, multicenter, observational study

OBJECTIVEnTo assess the safety of calcium channel blockers during the first trimester of pregnancy.nnnSTUDY DESIGNnA multicenter (n=11), prospective observational study of the European Network of Teratology Information Services (ENTIS). The rate of major birth defects was compared between a cohort of pregnant women exposed to calcium channel blockers during the first trimester (n=299) and a control group not exposed to potential teratogens (n=806).nnnRESULTSnMajor birth defects were not more common in the study group than in the control group. Birth weight was significantly lower in exposed term newborns. There were more preterm infants in the study group than in the control group (23.8% vs. 6.5%). These adverse effects are more likely due to the underlying disease than to the medication.nnnCONCLUSIONnThis study suggests that calcium channel blockers during the first trimester of pregnancy do not represent a major teratogenic risk.

Does single umbilical artery (SUA) predict any type of congenital defect? Clinical-epidemiological analysis of a large consecutive series of malformed infants.

Most studies associating different types of malformations with the presence of a single umbilical artery (SUA) are based on small and selected series. Here, we present the results of a study aimed at identifying the most frequent, and the most specific anomalies related to SUA. We analyzed 19,909 consecutive newborn infants with congenital malformations, from the Spanish Collaborative Study of Congenital Malformations (ECEMC). To estimate the specificity of the relationship of different congenital defects with SUA, we calculated their relative frequencies (RF) by dividing their frequency in infants with SUA by the corresponding frequency in newborn infants without SUA. Using the different levels of the ECEMC coding system, we calculated the RFs in three steps: (a) a group of individual congenital defects, (b) different groups of malformed infants, and (c) each individual malformation by its clinical presentation in some of the studied groups of malformed infants. The defects most specifically associated with SUA were bilateral renal agenesis and imperforate anus, followed by unilateral renal agenesis, and vertebral defects, the RF of which indicated that they were between 7.99 and 9.93 times more frequent among malformed infants with SUA than among malformed infants without SUA. However, these defects were not as frequent in the group of infants with SUA, as cardiovascular anomalies. Regarding the association of SUA in the groups of malformed infants, the most specific groups were body stalk defects and sirenomelia. Finally, we analyzed the association of the individual defects by different groups of malformed infants in order to identify if the individual defects are associated with SUA in any type of clinical presentation, and in relation to some groups of infants with genetic disorders. The results, together with the embryonic development of the umbilical cord, strongly suggest that not all cases of SUA have the same cause, and that all previously suggested mechanisms may be possible but with different frequencies.

Consumo de tabaco durante el embarazo en España: análisis por años, comunidades autónomas y características maternas

Fundamento y objetivo: Desde hace anos se ha venido informado sobre la conveniencia de que las mujeres embarazadas no fumen. Por ello, hemos estudiado si se ha producido alguna variacion en el habito de fumar durante el embarazo en Espana. Sujetos y metodo: Utilizamos datos de 31.056 madres de ninos sin defectos congenitos, procedentes de todas las autonomias, recogidos con la misma metodologia en todo el pais. Se analiza la evolucion del habito de fumar por anos, comunidades autonomas, caracteristicas y otros habitos maternos. Resultados: En los ultimos anos del estudio (1995-2002), el 30,31% de las madres fumo durante el embarazo, con variaciones entre diferentes grupos etnicos. Se observa un incremento secular de la prevalencia de madres fumadoras entre 1978 y 1991, estabilizandose posteriormente en el 27-28%. No se observa una disminucion secular en los analisis por edades maternas, cantidades y autonomias. Solo las madres de mayor nivel de escolaridad muestran un descenso del habito de fumar en 1993, estabilizandose en alrededor del 23%. Las madres con menos de 25 anos son las que mas fuman en todos los anos. Se ha confirmado la estrecha relacion entre el tabaco, el alcohol y otras drogas comentada por otros autores. Conclusiones: Nuestros datos indican que no ha disminuido la prevalencia de mujeres que fuman durante la gestacion ni por anos ni por comunidades, aunque el 19,19% dejo de hacerlo en los primeros meses de embarazo. Ademas, las madres mas fumadoras en todos los anos son las mas jovenes. Estos resultados muestran la necesidad de aumentar la informacion para que las mujeres dejen de fumar antes del embarazo

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

AbstractBackground: 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.n 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 2393 infants with hypospadias and 12 465 male controls.n 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% I 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.n 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.

Análisis de la situación en España sobre el consumo de ácido fólico/folinato cálcico para la prevención de defectos congénitos

Fundamento y objetivo Desde 1992, en los paises desarrollados se ha generalizado la recomendacion de tomar un aporte complementario de acido folico (AF) para prevenir defectos congenitos. En este trabajo analizamos como es la situacion en Espana en los ultimos anos. Pacientes y metodo Utilizamos la informacion sobre las madres de los ninos controles de la base de datos del Estudio Colaborativo Espanol de Malformaciones Congenitas (ECEMC), que constituye una muestra de las mujeres embarazadas de la poblacion general. Analizamos la evolucion temporal del consumo de AF/folinato calcico (FC) (tanto en productos multivitaminicos como en los que se encuentra solo), por las mujeres embarazadas en los ultimos 22 anos, considerando momento de la ingestion de esta vitamina y las dosis utilizadas. Resultados La proporcion de mujeres que ingiere AF/FC durante el primer trimestre del embarazo ha experimentado un importante incremento a lo largo de los ultimos 9 anos, llegando a cerca del 80% en 2002. Sin embargo, solo alrededor del 9% de las mujeres inicio ese aporte desde antes de estar embarazadas. Ademas, las dosis medias diarias utilizadas son muy superiores a las internacionalmente recomendadas para la poblacion general de mujeres que planean un embarazo. Conclusiones En Espana, el consumo de AF/FC para la prevencion de defectos congenitos solo se esta realizando de forma adecuada en una pequena fraccion de la poblacion. Sigue, pues, siendo necesario difundir sus pautas de utilizacion correctas.

Evolución secular y por autonomías de la frecuencia de tratamientos de fertilidad, partos múltiples y cesáreas en España

Fundamento y objetivo Los tratamientos de fertilidad, los partos multiples y las cesareas estan relacionados con la edad materna. Por ello, al haber aumentado esta en Espana, es de esperar que hayan aumentado esas variables. Analizamos su evolucion secular y por edades maternas en todo el pais y por comunidades autonomas. Sujetos y metodo Se ha estudiado una muestra de 30.956 madres de todo el pais cuyos recien nacidos entre 1977 y junio de 2002 no tenian defectos congenitos. Resultados El porcentaje de tratamientos de fertilidad muestra un incremento secular estadisticamente significativo en todas las edades maternas, aunque es superior en mujeres mayores de 34 anos, en las que tambien se ha incrementado la frecuencia de partos multiples (pxa0=xa00,01). Las mismas tendencias se observan por comunidades autonomas, aunque con diferencias entre ellas. En la Comunidad Valenciana se observa la mayor frecuencia de tratamientos de fertilidad, mientras que la mayor edad materna se registra en Aragon. En Galicia la proporcion de partos multiples es de las mas bajas y la de los tratamientos de fertilidad es similar a la de las otras comunidades. El porcentaje de cesareas (globalmente superior al 25%) muestra un incremento progresivo y significativo en todas las edades maternas, y es maximo en las madres mayores de 39 anos. Conclusiones El incremento de la edad materna implica mayor utilizacion de tratamientos de fertilidad, mayor numero de partos multiples y de cesareas. Todas estas variables presentan en Espana variaciones significativas a lo largo del tiempo y entre comunidades autonomas.

Evolución temporal y por comunidades autónomas del consumo de diferentes cantidades de alcohol durante el embarazo

Fundamento y objetivo: Desde que Jones y Smith describieron el sindrome alcoholico fetal (SAF), son muchos los trabajos realizados sobre sus efectos. Se considera la primera causa prevenible de defectos congenitos y deficiencia mental. Se analiza si con el tiempo ha variado el consumo de alcohol entre las mujeres embarazadas de Espana. Sujetos y metodo: Analizamos la evolucion del consumo materno de alcohol en los ultimos 24 anos, por comunidades autonomas y por anos y comunidades. Utilizamos los datos del Estudio Colaborativo Espanol de Malformaciones Congenitas (ECEMC), que corresponden a 1.820.862 recien nacidos, de los que 30.836 nacieron malformados. Se selecciono como controles a un numero similar de ninos no malformados. Establecimos 5 niveles de dosis crecientes de ingestion de alcohol, incluyendo dosis esporadicas y dosis diarias, y tres niveles de escolaridad maternal. Resultados: Se observa una gran concordancia en las tendencias estudiadas entre las madres de los casos y controles. Excepto las dosis muy bajas y muy altas de alcohol, las demas presentan tendencias decrecientes y similares en practicamente todas las comunidades autonomas. Al comparar cada nivel entre las comunidades, las diferencias son significativas. Cuanto menor es la escolaridad de la madre, mayor es la cantidad de alcohol ingerida durante el embarazo. Conclusiones: El conocimiento por parte de las mujeres del efecto del alcohol en el embarazo depende del nivel cultural. La ingestion materna de alcohol es diferente entre las comunidades autonomas, aunque tienen tendencias iguales. El hecho de utilizar datos recogidos con la misma metodologia en todo el pais permite comparar los resultados y evaluar el impacto de campanas de informacion.

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.