Síndrome de Jacobsen (deleción parcial 11q) asociado a trombocitosis: presentación de un caso y revisión de la literatura científica / Jacobsen syndrome (partial 11q deletion) associated to thrombocytosis: report of a case and literature review

Introducción: El síndrome de Jacobsen se debe a una deleción parcial del brazo largo del cromosoma 11. En un 85% de los casos, la deleción ocurre de novo. Los signos más comunes incluyen retraso en el crecimiento pre/posnatal, retraso psicomotor y malformaciones, así como una dismorfia facial característica. Con frecuencia, desde el nacimiento existe una función plaquetaria anormal, una trombocitopenia o una pancitopenia. Aproximadamente un 20% de los pacientes fallece durante los 2 primeros años de vida. Caso clínico: Recién nacida a término, sin antecedentes familiares de interés, que presenta un fenotipo peculiar (pabellones auriculares pequeños, de implantación baja, puente nasal ancho, hipertelorismo, fisuras palpebrales inclinadas hacia abajo, boca «en carpa», microrretrognatia), fisura palatina, lesiones de aspecto petequial en tórax y muslo derecho, asociado a himen imperforado. Cariotipo 46,XX,del(11)(q14.1q23.3)dn, el estudio de ambos progenitores fue normal. Desde las 2 semanas de vida, la niña presentó una importante trombocitosis, con nula adquisición de los ítems madurativos. La paciente falleció a los 3 meses de vida, tras un accidente cerebrovascular hemorrágico espontáneo. Conclusiones: Las manifestaciones clínicas se relacionan con el tamaño de la deleción. Generalmente, el punto de rotura se localiza en 11q23.3. Entre las alteraciones hematológicas, la más frecuente es la trombopenia, aunque no fue así en esta paciente, que presentaba una trombocitosis. Esto parece deberse a que cuando la deleción afecta a la banda 11q24 se produce la pérdida del gen FLI-1, entre otros genes, que desempeñan un papel fundamental en la megacariopoyesis (AU)

Introduction: Jacobsen syndrome is due to partial deletion of the long arm of chromosome11. A de novo deletion occurs in 85% of cases. Most common signs include pre- and postnatal growth retardation, psychomotor delay, malformations and characteristic facial dysmorphism. Abnormal platelet function thrombocytopenia or pancytopenia are frequent from birth. Approximately, 20% of patients die during the first 2 years of life. Case report: Newborn female born at term, without any family history of congenital anomalies, presenting with peculiar phenotype (small and low-set ears, broad nasal bridge, hypertelorism, downslanting palpebral fissures, micro-retrognathia), carp-like mouth, cleft palate, petechial-like lesion in thorax and right thigh, associated to imperforate hymen. Karyotype 46,XX,del(11)(q14.1q23.3)dn, being normal for both her parents. Since the age of 2 weeks she had a marked thrombocytosis, with no acquisition of developmental milestones. The patient died at 3 months after a spontaneous hemorrhagic cerebral-vascular accident. Conclusions: Clinical manifestations of the syndrome are related to the size of the deletion. Generally, the breakpoint is located at 11q23.3. Among the hematological alterations the most frequent one is thrombopenia, unlike our patient, who had thrombocytosis. This seems to be due to the loss of FLI-1, among other genes with a key role in megakaryopoiesis, when the deletion affects the band 11q24 (AU)

Frecuencias de defectos congénitos al nacimiento en España y su comportamiento temporal y por comunidades autónomas. Causas de las variaciones de las frecuencias / Birth frequency of congenital defects in Spain, their time distribution and by Autonomous Communities. Causes of the variations in frequency

Se presenta una revisión de los principales aspectos derivados del estudio de la frecuencia de los defectos congénitos, explicando la importancia y utilidad de ese conocimiento, e ilustrándola con diversos ejemplos basados en el análisis de los datos del Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC). De dicho análisis se deduce que la frecuencia global de recién nacidos con defectos congénitos en España ha venido disminuyendo a lo largo del tiempo para muchos defectos. Ese descenso es consecuencia, fundamentalmente, del impacto de las interrupciones voluntarias del embarazo (IVE) tras la detección de alteraciones en el feto. No obstante, otros factores, como el mejor cuidado de los embarazos, la planificación de los mismos, y el aumento de la cultura sanitaria de la población, podrían estar teniendo algún efecto, aunque mucho menos patente que el derivado de la realización de IVE. Esa disminución de la frecuencia no ha sido uniforme en todas las CC.AA. Por otra parte, hay ciertos defectos para los que se ha registrado un incremento secular, derivado de la mejora y uso generalizado de las técnicas diagnósticas, tanto prenatales como postnatales. Por otra parte, se ha observado que la diversificación étnica en nuestro país, resultante de la inmigración, está teniendo también cierto impacto sobre la frecuencia de recién nacidos con defectos congénitos en España. Esos grupos de población minoritarios, en general, junto con diferencias en las frecuencias de ciertas mutaciones de genes recesivos, tienen unas condiciones socio-sanitarias que determinan un mayor riesgo para defectos congénitos. Todos estos aspectos son importantes y han de ser tenidos en cuenta a la hora de diseñar los planes de prevención de estas patologías (AU)

A review is presented of the main aspects arising from the study of the frequency of congenital defects, explaining the importance and use of this knowledge, and illustrating it with different examples based on the analysis of data from the ECEMC (Estudio Colaborativo Español de Malformaciones Congénitas) (Spanish Collaborative Study of Congenital Malformations). From this analysis it was observed that the overall frequency of newborns with congenital defects in Spain has been decreasing gradually for many defects. This drop is mainly a result of voluntary termination of pregnancy (TOP) after the detection of foetal abnormalities. However, other factors, such as the improved care of pregnant women and pregnancy planning, plus the increase in the health culture of the population, could also be having some effect, although a lot less obvious than that due to TOP. This decrease in frequency has not been uniform in all the Autonomous Communities. On the other hand, there are certain defects that have shown a secular increase, arising from the improvement and general use of both prenatal and post-natal diagnostic techniques. Furthermore, it has been observed that the ethnical diversification in our country, resulting from immigration, is also having a certain impact on the frequency of newborns with congenital abnormalities in Spain. These minority population groups, in general, along with the differences in the frequency of certain recessive gene mutations, have socio-health conditions that lead to a higher risk of congenital defects. All these aspects are important and have to be taken into account when designing prevention plans for these diseases (AU)

[Characteristics of neonates with and without a single umbilical artery. Analysis of two consecutive series of neonates with and without congenital defects]. / Características de los neonatos con y sin arteria umbilical única. Análisis de dos series consecutivas de recién nacidos con y sin defectos congénitos.

BACKGROUND AND OBJECTIVE: The implications of the presence of a single umbilical artery (SUA) are unknown. Although most articles are based on selected samples, they suggest a relationship between SUA and malformations. Consequently, prenatal detection of SUA causes concern, since there are no definitive guidelines that can be followed after identification of this abnormality. The objective of this study was to comparatively analyze SUA in two series of consecutive births, with and without congenital defects. PATIENTS AND METHODS: A total of 19,909 cases and 19,148 controls from the Registry of the Spanish Collaborative Study on Congenital Malformations were studied. The variables analyzed were sex, birth weight, length, occipito-frontal circumference, gestational age, prematurity, delivery by caesarean section, umbilical cord length, placental weight, survival at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations included relative frequency, odds ratios (OR) and 95 % confidence intervals, the chi-square test, Fisher's p-value, and Student's t-test. RESULTS: SUA was found in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures showed secular variation due to improvements in prenatal diagnosis and interruption of some pregnancies. When cases with and without SUA were compared, those with SUA had lower values of somatometry at birth, umbilical cord length and gestational age and had a higher risk for oligohydramnios, polyhydramnios, caesarean section, and death in the first 72 hours. Among controls, the only differences were a shorter umbilical cord and a higher frequency of oligohydramnios among infants with SUA. CONCLUSIONS: The results suggest that certain malformations associated with SUA could cause some of the differences among cases. Shortening of the umbilical cord and oligohydramnios could be related to SUA, as these abnormalities were found in both cases and controls. Comparison of cases and controls suggests that the etiopathogenesis of SUA could differ in the two groups.

Características de los neonatos con y sin arteria umbilical única. Análisis de dos series consecutivas de recién nacidos con y sin defectos congénitos / Characteristics of neonates with and without a single umbilical artery. Analysis of two consecutive series of neonates with and without congenital defects

Antecedentes y objetivo Se desconocen las implicaciones de la presencia de arteria umbilical única (AUU). Aunque la mayoría de los trabajos utilizan muestras seleccionadas, sugieren una relación entre la AUU y malformaciones. Esto supone una gran preocupación cuando se detecta una AUU prenatalmente, ya que no hay pautas de actuación tras su identificación. El objetivo de este trabajo es analizar comparativamente la AUU en dos series consecutivas de nacimientos, con y sin defectos congénitos. Pacientes y métodos Se utilizaron 19.909 casos y 19.148 controles del Registro del Estudio Colaborativo Español de Malformaciones Congénitas, y se analizaron: sexo, peso, talla, perímetro cefálico, edad gestacional, prematuridad, parto por cesárea, longitud del cordón umbilical, peso de la placenta, supervivencia a las 72 h, primiparidad, oligoamnios y polihidramnios. Se calculó la frecuencia relativa, el odds ratio (OR) e intervalos de confianza del 95 %, chi cuadrado, valor p de Fisher, y la t de Student. Resultados El 2,29 % de los casos y el 1,03 % de controles tenían AUU (p = 0,0000001), mostrando variación secular por la mejora del diagnóstico prenatal, e interrupciones del embarazo. Comparando casos con y sin AUU, los que tenían AUU presentaban menores valores de somatometría al nacimiento, longitud del cordón y edad gestacional, y mayor riesgo de oligohidramnios, polihidramnios, cesárea y muerte antes de las 72 h. Entre los controles, sólo diferían en que los que tenían AUU, presentaban cordón más corto y mayor frecuencia de oligoamnios. Conclusiones Los resultados sugieren que ciertas malformaciones asociadas a la AUU, podrían ser responsables de las diferencias entre los casos. El acortamiento del cordón y oligohidramnios podrían relacionarse con la AUU, porque se asocia tanto entre casos como entre controles. Comparando los casos con los controles se sugiere que la AUU podría tener diferente etiopatogenia en ambos grupos

Background and objective The implications of the presence of a single umbilical artery (SUA) are unknown. Although most articles are based on selected samples, they suggest a relationship between SUA and malformations. Consequently, prenatal detection of SUA causes concern, since there are no definitive guidelines that can be followed after identification of this abnormality. The objective of this study was to comparatively analyze SUA in two series of consecutive births, with and without congenital defects. Patients and methods A total of 19,909 cases and 19,148 controls from the Registry of the Spanish Collaborative Study on Congenital Malformations were studied. The variables analyzed were sex, birth weight, length, occipito-frontal circumference, gestational age, prematurity, delivery by caesarean section, umbilical cord length, placental weight, survival at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations included relative frequency, odds ratios (OR) and 95 % confidence intervals, the chi-square test, Fisher's p-value, and Student's t-test. Results SUA was found in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures showed secular variation due to improvements in prenatal diagnosis and interruption of some pregnancies. When cases with and without SUA were compared, those with SUA had lower values of somatometry at birth, umbilical cord length and gestational age and had a higher risk for oligohydramnios, polyhydramnios, caesarean section, and death in the first 72 hours. Among controls, the only differences were a shorter umbilical cord and a higher frequency of oligohydramnios among infants with SUA. Conclusions The results suggest that certain malformations associated with SUA could cause some of the differences among cases. Shortening of the umbilical cord and oligohydramnios could be related to SUA, as these abnormalities were found in both cases and controls. Comparison of cases and controls suggests that the etiopathogenesis of SUA could differ in the two groups

[Wiedemann-Beckwith syndrome: clinical and epidemiological analysis of a consecutive series of cases in Spain]. / Síndrome de Wiedemann-Beckwith: análisis clínico-epidemiológico de una serie consecutiva de casos en España.

OBJECTIVE: Wiedemann-Beckwith syndrome is a multisystemic pattern of congenital anomalies with overgrowth. The most characteristic clinical features are macroglossia, high birth weight, omphalocele, visceromegaly and hypoglycemia. PATIENTS AND METHODS: We show the clinical and epidemiological characteristics of the 18 cases with Wiedemann-Beckwith syndrome identified in the consecutive series of 25,967 malformed liveborn infants detected among 1,431,368 livebirths surveyed by the Spanish Collaborative Study of Congenital Malformations (ECEMC) between April 1976 and June 1997. RESULTS AND CONCLUSIONS: The minimal estimated frequency of Wiedemann-Beckwith syndrome in Spain is 0.13 per 10,000 liveborn infants. These infants have a high birth weight for their gestational age and are born of shorter pregnancies (prematurity 33.3%). The clinical manifestations of our cases are concordant with the variable expression of the syndrome; the most frequent features were macroglossia (100%), omphalocele or umbilical hernia (77.8%) and high birth weight (64.7%). Other findings were polyhydramnios and placentomegaly. All of the cases were sporadic.

[The Townes-Brocks syndrome in Spain: the epidemiological aspects in a consecutive series of cases]. / Síndrome de Townes-Brocks en España: aspectos epidemiológicos en una serie consecutiva de casos.

INTRODUCTION: Townes-Brocks syndrome is constituted by a multi-systemic pattern of congenital anomalies with autosomal dominant inheritance. The most characteristic defects are those affecting hearing and the auricle, anal atresia and thumb anomalies. PATIENTS AND METHODS: We present the epidemiological characteristics of six cases of Townes-Brocks syndrome identified in the consecutive series of 25,967 malformed live born infants detected among 1,431,368 live births surveyed by the ECEMC (Spanish Collaborative Study of Congenital Malformations) between April 1976 and June 1997. RESULTS AND CONCLUSIONS: The minimal estimated frequency of Townes-Brocks syndrome in our data is 0.42 cases per 100,000 liveborn infants. These infants have low birth weights. Similar to other published studies, we have observed in our cases a wide variation in the clinical expression of the syndrome, showing great inter-family, as well as intrafamily variability.

[Jarcho-Levin and Casamassima syndromes: differential diagnosis and frequency in Spain]. / Síndromes de Jarcho-Levin y Casamassima: diagnóstico diferencial y frecuencia en España.

OBJECTIVE: Jarcho-Levin syndrome is characterized by the presence of only costal-vertebral defects. However, this diagnosis has been used in any case presenting with costovertebral defects, whether associated to other congenital defects or not. Recently, it has been demonstrated that costovertebral defects constitute a developmental field defect and, because of this, they can be observed in different clinical and etiological patterns. On the other hand, Casamassima syndrome is characterized by the presence of costovertebral defects, genito-urinary anomalies and anal atresia, which make it easily distinguishable from Jarcho-Levin syndrome. PATIENTS AND METHODS: We present the cases with Jarcho-Levin and Casamassima syndromes identified among 1,405,374 liveborn (LB) infants registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC). RESULTS: Frequencies of these two syndromes in the ECEMC are 0.2 per 100,000 LB for Jarcho-Levin syndrome and 0.3 per 100,000 LB for Casamassima syndrome. We present the clinical manifestations and other characteristics of all the cases registered with these syndromes in the ECEMC. CONCLUSIONS: Jarcho-Levin syndrome is defined by the presence of costoveriebral defects without any other congenital defect. However, given that the alterations of the axial skeleton are a developmental field defect, they can be observed in different clinical-etiological patterns that should not be considered as Jarcho-Levin syndrome. Among these, Cassamassima syndrome can be clearly distinguished, being autosomal recessive as is Jarcho-Levin syndrome.

[Fraser syndrome: frequency in our environment and clinical-epidemiological aspects of a consecutive series of cases]. / Síndrome de Fraser: frecuencia en nuestro medio y aspectos clínico-epidemiológicos de una serie consecutiva de casos.

OBJECTIVE: Four major characteristics (cryptophthalmos, syndactyly, genital anomalies and affected siblings) and eight minor characteristics (alterations of the nose, ears, larynx, oral clefts, umbilical hernia, renal agenesis, skeletal anomalies and mental retardation) have been defined for the diagnosis of Fraser syndrome. The generally accepted criterion for the diagnosis is at least the presence of 2 major and one minor characteristic, or one major and four minor characteristics. The etiology of the syndrome is autosomal recessive and siblings are frequently affected. PATIENTS AND METHODS: We show the characteristics of the 7 cases of Fraser syndrome identified in the consecutive series of 1,405,374 liveborn infants and 9,042 stillborn children surveyed by the Spanish Collaborative Study of Congenital Malformations (ECEMC) between April 1976 and March 1997. RESULTS AND CONCLUSIONS: The minimal estimated frequency of Fraser syndrome is 0.43 per 100,000 liveborn infants and 11.06 per 100,000 stillbirths. As has been shown in other case studies, we have observed a wide clinical expression of this syndrome. At present it is possible to prenatally detect some of the characteristics of Fraser syndrome through ultrasound examination of eyes, digits and kidneys. Four out of the 7 cases we present here were gypsies and the frequency of the syndrome among liveborn gypsy infants is 129.3 times higher than among the non-gypsy population. Therefore, given that the frequency of the gene is higher in the gypsy population than in other ethic groups, it is recommended that a special search among gypsies for the identification of this and other autosomal recessive syndromes be performed.

[Epidemiological aspects of children of women with bicornuate uterus]. / Aspectos epidemiológicos de los hijos de mujeres con útero bicorne.

BACKGROUND: Most published papers on women with a bicornuate uterus analyze their fertility problems, as well as certain pregnancy complications. We have not found any epidemiological study on the infants of mothers with this uterine malformation. Only in some papers a reference is made about the relationship of maternal bicornuate uterus with congenital deformations and disruptions in their infants. PATIENTS AND METHODS: Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), which has a case-control methodology, some characteristics in a series of 26,945 malformed infants, such as birth weight, sex, gestational age, umbilical cord length, placental weight and maternal age, were analyzed by separating infants of mothers with normal uterus and those of mothers with a bicornuate uterus. RESULTS: Results showed that women with a bicornuate uterus have more daughters than sons and an increased risk for intrauterine growth retardation and prematurity with respect to infants of mothers with a normal uterus. On the other hand, the risk of having an infant with congenital defects is higher for women with a bicornuate uterus than for those with a normal uterus. CONCLUSIONS: Pregnancies of women with a bicornuate uterus have to be considered at risk since they have more risk for complications and for having an infant with congenital defects, premature birth and with intrauterine growth retardation.

[An epidemiological study of the thrombocytopenia with radial aplasia syndrome (TAR) in Spain]. / Estudio epidemiológico del síndrome de trombocitopenia con aplasia de radio (TAR) en España.

OBJECTIVE: There are numerous published papers on TAR syndrome. Nevertheless, most of them refer to cases or families with several affected members, but we could find no publication epidemiologically analyzing a consecutive series of cases. PATIENTS AND METHODS: We show the characteristics of the six cases with TAR syndrome identified in the consecutive series of 25,967 malformed live born infants detected among 1,431,368 live births surveyed by the ECEMC (Spanish Collaborative Study of Congenital Malformations) since April 1976 until June 1997. RESULTS: The minimal estimated frequency of TAR syndrome in our area is 0.42 per 100,000 live born infants, with a confidence interval of 0.15 to 0.91. There was no known consanguinity among the cases' parents, nor other affected family members. The sex ratio was 1:1. Although it is generally considered that the syndrome is autosomal recessive, genetic heterogeneity cannot be ruled out. CONCLUSIONS: Our cases concur with published data with respect to the low frequency of consanguineous parents. However we did not find a higher proportion of girls affected as has been described previously.

[Low birth weight as an additional indication for chromosomal analysis]. / Bajo peso al nacimiento como una indicación más para el estudio cromosómico.

INTRODUCTION: Even though there are few epidemiological studies evaluating the birth weights of different groups of malformed babies with chromosomal abnormalities, it is widely known that infants with trisomy 18, and to a lesser degree those with trisomy 13 and other chromosomal alterations, have low birth weights. PATIENTS AND METHODS: In this study we present the analysis of the birth weights and gestational ages of a large sample of babies (23,155 malformed and a similar number of nonmalformed babies), separating the different groups of chromosomal anomalies and comparing the weight in the clinical groups of malformed infants. RESULTS: Most of the groups with chromosomal abnormalities present lower birth weights in comparison to the other groups. CONCLUSIONS: The results of our study support the conclusion that the relationship between chromosomal alterations and low birth weight is sufficiently important that such a low birth weight in children with minor or major anomalies should be considered as one more indication to perform chromosomal analysis.

[Etiologic distribution of children with congenital defects]. / Distribución etiológica de los niños con defectos congénitos.

INTRODUCTION: Although it has been generally admitted that we know the cause of congenital malformations in about 40% of the cases, these data are based on very few studies. PATIENTS AND METHODS: Here we present the distribution of 22,784 malformed infants in our country by type of cause of their defects. RESULTS: Our results show a great impact of chromosomal alterations in causing congenital anomalies. On the other hand, performing the chromosomal study will enable the diagnosis of genetic entities, as well as environmental ones that are clinically similar to the clinical patterns produced by chromosomal abnormalities. CONCLUSIONS: We can recognize the cause of congenital defects in a proportion higher than the 40% which is generally accepted. Nowadays, there is no reason that justifies not performing a chromosomal study with high resolution band techniques in infants with congenital defects.

[Clinical diagnosis of Down's syndrome based on 11 signs. Epidemiological analysis of the specificity of the studied signs]. / Diagnóstico clínico del síndrome de Down basado en 11 rasgos. Análisis epidemiológico de la especificidad de los rasgos estudiados.

OBJECTIVE: Down's syndrome (trisomy 21) is the most frequent viable chromosomal abnormality, as well as the only one that can be postnatally diagnosed on the basis of a series of clinical signs. However, none is specific by itself. It is generally accepted that the diagnosis can be made on the basis of the concurrence of a large number of signs. Nevertheless, since most of the clinical signs can be observed in the general population, each one of them has a different level of specificity for the diagnosis of Down's syndrome, depending on its frequency in every population. PATIENTS AND METHODS: We have studied in our population the frequency and specificity of 11 signs for the diagnosis of Down's syndrome by using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC). RESULTS: The analysis of the 11 signs shows great specificity for some of them and for the concurrence of four or more. CONCLUSIONS: We consider that although the final diagnosis will come from chromosomal analysis, it can be very useful to have indicators available for the clinical diagnosis at birth. This is extremely important so that the corresponding chromosomal analysis is immediately performed, which will result in early and correct information to the parents.

[Anophthalmia/micro-ophthalmia in syndromes: epidemiology study of newborns in Spain]. / Anoftalmía/microftalmía en síndromes: estudio epidemiológico en recién nacidos en España.

OBJECTIVE: The objective of this study was to perform an epidemiological analysis of the frequency of anophthalmia/microphthalmia (A/M) in syndromes identified in newborn infants in Spain. PATIENTS AND METHODS: Data of the Spanish Collaborative Study of Congenital Malformations during the period of 1976-1994, corresponding to more than 1,200,000 births, was analyzed. Among these, 86 newborn infants with A/M presented some of the recognized syndromes. RESULTS: There is a wide etiological heterogeneity among the syndromes with this ocular defect, with chromosomal syndromes being the most frequent (67.9% of total syndromes with A/M), followed by monogenic syndromes (19.1%), environmental (9.5%) and those of unknown etiology (3.6%). CONCLUSIONS: Some guidelines when a baby is born with A/M are derived from this study. First, given the tendency of the defect to present together with other anomalies, it is advisable to perform a detailed study to rule out or to confirm the existence of other defects. Adequate samples should be taken (even in stillborn infants) for cytogenetic study. Examine carefully the prenatal history, looking for chronic diseases, infectious processes or exposure to teratogens. Depending on the baby's survival, follow-up of the psychomotor development should be made. All of these aspects are always important in malformed babies, but especially in infants with A/M given the tendency of the defect to present in syndromes as the etiologic diagnosis determines the counselling regarding the risk of recurrence, detection of carriers in some cases and possible prenatal diagnosis.

[Syndromes with neural tube defects: epidemiologic analysis in Spain]. / Síndromes con defectos del tubo neural: análisis epidemiológico en España.

OBJECTIVE: We present, from an epidemiological perspective, the analysis of syndromes which present neural tube defects (NTD). Although there are many epidemiological studies on NTD all over the world, most of them are on isolated NTD; that is, when the infant only has NTD as the only anomaly. PATIENTS AND METHODS: The methodology is based on the review of hospital records of infants with congenital anomalies. This permitted the analysis of the prevalence. RESULTS: The results show that the frequency of syndromes with NTD is 27.5 time higher among stillborn infants than among liveborn infants. Nevertheless, there are not many syndromes in which the NTD are present more or less frequently. In fact, only 1.93% of the total cases with syndromes presented NTD, with the majority (43.4%) with genetic etiology. We also analyze the specific types of syndromes with NTD.

[Birth weight of children born without congenital defects. I. Birthweight percentiles by gestational age]. / Estudio del peso al nacimiento sobre una población de niños sin defectos congénitos. I. Curvas de percentiles del peso por edad gestacional.

We studied the birthweight by gestational age and sex from a population of 14,097 liveborns without congenital defects who were monitored by the Spanish Collaborative Study of Congenital Malformations (ECEMC). We have calculated the curves of percentiles for gestational age in males and females. As our sample size is very large, and it includes births from almost the whole country, we think these curves are enoughly representative of the Spanish population, fitter than the Denver's (1) which are widely utilized. On the other hand, we stress our attention in making curves of birthweight for malformed and not malformed babies separately.

[Birth weight of infants born without congenital defects. II. Effect of tobacco and parity of the mother on the wight of the newborn infant]. / Estudio del peso al nacimiento sobre una población de niños sin defectos congénitos. II. Efecto del tabaco y número de gestaciones de la madre sobre el peso del recién nacido.

We analyzed the effect that number of gestations, smoking and number of cigarettes per day during pregnancy have on the birthweight using a sample of 14,097 liveborns without birth defects identifiable within the first three days of life. To our purposes, we controlled the effect of gestational age, sex and maternal age through multiple regression analysis. From the results we concluded that the birthweight is increased 39.80 g per each pregnancy of mothers, showing a progressive but smoothed increase by a negative quadratic effect. Smoking in mothers decreases the weight of newborns and has no effect on the gestational age. The decrease of birthweight was stronger when we looked at the number of cigarettes per day, showing a diminishing trend when the number of cigarettes per day, showing a diminishing trend when the number of cigarettes is increased, but again smoothed by a positive quadratic effect. From the multiple regression analysis controlling some factors we got a formula that permitted to us to estimate the average in decreasing weight depending on the number of cigarettes that mother smokes during pregnancy.