Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.

OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.

Effects of genetic vs. environmental factors on cardiovascular autonomic function: a twin study.

AIMS: Cardiovascular autonomic function is often assessed in patients with diabetes by measuring heart rate variability and baroreflex sensitivity, the heritability of which is not fully understood. The present study was aimed to determine the effects of genetic and environmental factors on heart rate variability and baroreflex sensitivity in monozygotic and dizygotic adult healthy twin pairs. METHODS: A total of 101 (63 monozygotic, 38 dizygotic) adult twin pairs (n = 202; mean age 44.3 years) were investigated. Anthropometric variables and serum metabolic markers were measured, while environmental characteristics were evaluated by questionnaires. Linear and spectral indices of heart rate variability and baroreflex sensitivity were determined by non-invasive methods. All measurements were adjusted for age and gender (model 1) and for all significantly relevant covariates (model 2). Heritability A-C-E structural equation models were used for characterizing the proportion of additive genetic, shared and unshared environmental influences. RESULTS: Genetic influence of different cardiovascular autonomic indices was estimated between 10.3 and 39.4%, common environmental influence was found between 0.0 and 33.2%, while unshared environmental influence was observed between 60.6 and 81.4% in model 1 analysis. In multivariable-adjusted heritability estimates (model 2), the magnitude of the genetic effects decreased to 0.0%, common environmental influence was nearly unchanged (values between 4.4 and 14.5%), while unshared environmental influence slightly increased (values between 85.5 and 96.5%). CONCLUSIONS: Unshared environmental but not genetic factors have substantial influence on cardiovascular autonomic function, suggesting that appropriate treatment of all modifiable environmental factors is of importance in order to prevent or ameliorate cardiovascular autonomic neuropathy.

Maternal employment status and isolated orofacial clefts in Hungary.

AIMS: To study the role of maternal employment status as indicator of socioeconomic status in the origin of isolated orofacial clefts (OFC) and in the use of periconceptional folic acid/multivitamin supplementation. METHODS: 1,975 cases with OFC (1,374 cases with cleft lip +/- palate and 601 cases with posterior cleft palate), 38,151 population controls without any defects and 20,868 patient controls with other isolated defects were compared in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996. RESULTS: The proportion of professionals and managerials was lower, while the proportion of unskilled workers, housewives and others was higher in the mothers of cases with OFC compared with the population control group. However, the comparison of OFC and patient control groups did not show any difference in the employment status of mothers. A lower level of folic acid supplementation occurred in the professional and skilled worker mothers of cases with OFC compared with the population control group. This difference was confirmed by the comparison of folic acid used by mothers of cases with OFC compared with patient controls. An infrequent multivitamin use was displayed in the studied groups. CONCLUSIONS: The prevalence of OFC at birth shows a slightly lower maternal employment status as indicator of socioeconomic status than in the population control group. The higher level of maternal education does not imply a higher rate of folic acid supplementation in the group of OFC.

Congenital malformations in twins: an international study.

Data provided by nine registries based in European and Latin America countries were analyzed to assess whether there is an excess of malformations in twins compared to singletons. Specific congenital malformations were coded according to the ninth revision of the International Classification of Diseases (ICD). Malformation rates and rate ratios (RR) for twins compared to singletons were calculated for each registry, and the homogeneity of the RRs was tested using the test of Breslow and Day. If departure from homogeneity in the different registries was not significant, registry-adjusted RRs with 95% confidence intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were reported. A total of 101 different types of malformations or groups of defects was identified, and a homogeneous estimate of the RRs among registries was found for 91.1% of the malformations. Thirty-nine of the 92 malformations with homogeneous estimates of RRs were more common in twins than in singletons. For the remaining nine malformations, heterogeneous estimates of RRs were obtained. This study confirms the majority of already known associations and further identifies previously unreported malformations associated with twins. In conclusion, there is an excess of malformations in twins compared with singletons, and all anatomical sites are involved. The number of specific malformations associated with twins is higher than that previously reported in smaller studies.

[Peri-conceptional multivitamin administration may result in higher frequency of twin pregnancies]. / Multivitamin periconceptionalis adását követóen észlelt nagyobb ikergyakoriság.

A randomized controlled trial of periconceptional multivitamin supplementation including 0.8 mg folic acid was carried out for at least 28 days before conception. The trial was continued until at least until the second missed menstrual period to test the effectiveness of this new primary preventive method in the reduction of neural tube defects. However, other pregnancy outcomes were also evaluated. Of total of 5,502 pregnant women, 4,846 births were analysed in the final data base. The rate of multiple births was significantly higher in the multivitamin group (3.8%) than in the placebo-like trace-element control group (2.7%), and in both groups exceeded the multiple birth rate of 2.2% of women in the Hungarian population at large. 7.3% of women in the multivitamin and 7.9% of women in the trace-element groups received ovarian stimulation treatment (mainly clomiphen) for hormonal dysfunctions, e.g. anovulation. Nonetheless, our study showed that periconceptional multivitamin supplementation, with or without stimulation, increases the rate of multiple births.

Congenital limb reduction defects in twins.

UNLABELLED: The study relates to congenital limb reduction defects (CLRDs) in twins from a 10-year-period (1975-1984) and is based on cases from the Hungarian Congenital Abnormality Registry. In order to clarify the respective contributions of genetic and environmental factors to CLRDs and the role of causal factors in common with twinning, the occurrence of CLRDs in twins was studied. In eight multiple CLRD twin cases (i.e. those with additional non-limb malformations), one monozygous concordant and one semi-concordant twin pair was found, indicating that genetic factors play a limited role in pathogenesis. There is no correlation between twinning and isolated CLRDs. Frequency of CLRDs in general was no higher in twins than in all births, although there was a non-significantly higher twinning rate in multiple CLRD cases. Twins with CLRDs were more often male, especially in multiple cases. CONCLUSION: There may be a relationship between twinning and congenital abnormalities, but twinning is not a major factor contributing to CLRD cases.

The effect of preconceptional multivitamin supplementation on fertility.

A significantly higher rate of conceptions occurred after preconceptional multivitamin supplementation in comparison with a placebo-like trace element supplementation in the Hungarian randomised, double-blind, controlled trial. This difference was explained by 5% shorter time in the achievement of conception.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part I: Csángós from Egyházaskozár Region.

This paper reports the results of a study on alcohol drinking habits, alcohol-related acute symptoms, and alcohol abuse among Csángós, an ethnic minority in Hungary. The demographic data revealed their social characteristics: growing old, low education, endogamous marriages, early maternal age at birth of the first baby, and a high child number per family. Alcohol use survey revealed that alcohol consumption of the Csángós is considerably high; more than half of Csángó males and more than one-quarter of Csángó females are heavy drinkers. While all kinds of alcohol are consumed by males, wine drinking is more common among females. Acute reactions to a moderate dose of alcohol evoked a series of physical and physiological symptoms including facial flushing, higher pulse rate, tachycardia and euphoria among at least one third of the probands. There was a distinct gender difference in response to alcohol drinking. While a higher percentage of females reported intense skin flush (34%), a greater percentage of males reported symptoms such as sleepiness, euphoria and aggressiveness. The distribution of clinical chemical markers of alcohol abuse in the sera of the individuals under study confirmed heavier alcohol consumption among males than among females. Alcohol-related mortality data indicate liver cirrhosis and liver cancer as the leading cause of deaths among Csángó males. A high alcohol consumption among Csángó ethnic group reflects the acceptance of alcohol use in the community as an integral part of their lifestyle.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part II: Palócs from Mátraderecske.

An epidemiological study on alcohol drinking habits, alcohol metabolism rate, alcohol-related acute physiological symptoms, and alcohol misuse among Palócs, an ethnic minority in Hungary, was conducted. The demographic and sociocultural correlates revealed their ethnic identity: low to moderate education, relatively low number of children per family and higher percentage of skilled workers among males. Alcohol use survey revealed that frequency of alcohol consumption among Palóc male population is considerably high. While about 41% of the Palóc males reported to drink daily between 30 ml and 90 ml pure alcohol, only 5% of the females reported to consume this amount regularly. 53% of males and less than 1% of females were classified as heavy drinkers (consuming more than 60 ml absolute alcohol per day). While all kinds of alcoholic beverage was reported to be consumed by the males, Pálinka (a kind of brandy) drinking was more common among females. About 45% of the Palócs reported to experience acute reactions after drinking a moderate dose of alcohol. The physical and physiological reactions include facial flushing, higher pulse rate, tachycardia and euphoria. While there was no distinct gender difference in facial flushing response to alcohol drinking, a higher percentage of males (70%) reported symptoms such as sleepiness, euphoria and aggressiveness as compared to about only 36% females reporting such reactions. Distribution of clinical chemical markers, in particular GGT values confirmed a heavier alcohol consumption among males than among females. High GGT value also correlated with a positive alcohol-related facial flushing reaction in males.

Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report.

The effect of periconceptional multivitamin/trace element supplementation on pregnancy outcomes was evaluated in a randomised controlled trial. The final data-base included 5,502 females with confirmed pregnancy. A multivitamin including 0.8 mg folic acid or a trace element were supplemented for at least 28 days before conception and continuing for at least until the second missed menstrual period. Number of pregnancies, terminations of pregnancies, four types of fetal deaths, livebirths including low birth weight, preterm birth and sex ratio were analysed. Periconceptional multivitamin supplementation increased fertility (higher rates of cumulative conceptions and multiple births), had no significant effect on the rate of different groups of fetal deaths, low birth weight and preterm birth in singletons. This primary preventive method can reduce the occurrence and recurrence of neural-tube defects and had no other significant effect on pregnancy outcomes except multiple births.

The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes.

A randomized controlled trial of periconceptional multivitamin supplementation (including 0.8 mg folic acid--see the Materials and Methods section for the precise composition of the multivitamin and trace-element supplementation) was carried out for at least 28 days before conception. The trial was continued until at least until the second missed menstrual period to test the effectiveness of this new primary preventive method in the reduction of neural tube defects. However, other pregnancy outcomes were also evaluated. Of a total of 5,502 pregnant women, 4,846 births were analysed in the final data base. The rate of multiple births was significantly higher in the multivitamin group (3.8%) than in the placebo-like trace-element control group (2.7%), and in both groups exceeded the multiple birth rate of 2.2% in the Hungarian population at large. 7.3% of women in the multivitamin and 7.9% of women in the trace-element groups had received ovarian stimulation treatment (mainly clomiphene) for hormonal dysfunctions, eg. anovulation. Nonetheless, our study showed that periconceptional multivitamin supplementation, with or without ovarian stimulation, increases the rate of multiple births.

Environmental trichlorfon and cluster of congenital abnormalities.

Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and 6 were twins. Of the 11, 4 had Down syndrome. Likely causes of such clusters (known teratogenic factors, familial inheritance, consanguinity) were excluded. A case-control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms. The content of this chemical was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed.

Characterization of hypervariable locus-specific probes derived from a (CAC)5/(GTG)5 multilocus fingerprint in various Eurasian populations.

Population genetic studies were performed using oligonucleotide probes (Hz1103, Hz4103, and Hz4201) that recognize three hypervariable loci (D11S859, D9S128 and D22S265) in the human genome. DNA from 17 Eurasian population samples including 37 monozygotic twin pairs were digested with HinfI and hybridized with Hz4103. Allele frequency distribution profiles and high degrees of heterozygosity were similar in each ethnic group. Among 804 unrelated individuals tested, we detected one case of mosaicism caused by a somatic recombination event in a monozygotic twin. In addition, samples of DNA from three ethnic groups (Germans, Assamese Hindus and Thais) and from German and Thai families were restricted with MboI and probed with Hz1103, Hz4103, and Hz4201. The results showed considerable degrees of heterozygosity and locus-specific allele distribution profiles, rather than interpopulation differences. Among 262 meioses (12 three-generation families with a total of 131 children) analyzed, a single recombination event was observed following hybridization with the DNA probe Hz4201.

Unidentified multiple congenital abnormalities in twins. A population-based Hungarian study.

Of 1038 index patients with multiple congenital abnormalities, 34 were twins. This 3.3 per cent is higher than the Hungarian birth rate of about 2.1 per cent. However, after the exclusion of cases with congenital abnormality association of low birth weight newborn infants and with genital anomalies of the male, the twin birth rate was 1.8 per cent. Thus, the unidentified multiple congenital abnormalities have no common cause with twinning.

[Prevalence of severe visual impairement in school-age children in Hungary]. / Az iskoláskorú súlyos látási fogyatékos gyermekek gyakorisága Magyarországon.

The recorded prevalence of 6 to 14 year-old children with severe visual handicap was 0.43 per 1000 in Hungary, 1983/84. The territorial distribution showed significant difference in prevalences, the highest figures were found in two entities with three special institutions for severely visually handicapped children. Thus, the recorded figures are underascertained and the estimated rates are 0.52-0.60 and 0.21 per 1000 for children with severe visual handicap and, within it, blindness, respectively.

Effects of mental load on the spectral components of heart period variability in twins.

The contribution of genetic and environmental control to stress-related cardiovascular reactions was investigated in 10 monozygotic and 10 dizygotic twin pairs during mental arithmetics. Non-invasive indices reflecting vagal and sympathetic activity were used, namely: indices of myocardial contractility based on impedance cardiogram, and spectral components of heart period variance. Autoregressive algorithms were developed for heart period power spectral density estimation providing automatic decomposition of heart period spectra into individual spectral components. During the mental task spectral energy of the mid-frequency (central frequency approximately 0.1 Hz) and high frequency (around respiratory frequency) components of heart period variance significantly decreased indicating vagal withdrawal. A task-related increase of the mid-frequency component relative to the high-frequency component was obtained. This change in the ratio of the two components as well as the considerable shortening of the contractility indices are pointing to sympathetic activation. When comparing intraclass correlations computed separately for monozygotic and dizygotic twins highly significant correlations were found for the mid-frequency component in monozygotic but not in dizygotic twin pairs in resting condition indicating a substantial genetic contribution to the control mechanisms involved in the baroreflex. Contribution of genetic factors to the control of stress-related interplay of autonomic outflows has been shown.

[Comparative study of the consumption of cariogenic food in monozygotic and same-sex dizygotic twins]. / Monozygota és azonos nemü dizygota ikrek cariogen élelmiszer fogyasztási frekvenciáinak összehasonlító vizsgálata.

The eating habits of the 111 monozygotic and 67 like-sexed dizygotic twins were compared with respect to cariogenic foods. The food habits were recorded using a seven-day dietary history with the weekly frequency of the cariogenic foods examined. The biometrical analysis showed that the eating habits of the monozygotic pairs were more similar than that of the dizygotic twin pairs. The differences were statistically significant. Based on these findings, it seems that genetic factors play a role in the development of the food habits.

Conjoined twins in Hungary, 1970-1986.

The total prevalence of conjoined twins (birth + prenatally diagnosed) was 1:68,000 in the study of 1970-1986. Symmetrical cases (the so-called siamese twins) have an obvious predominance (92.3%). Associated major malformations occurred in 80% of conjoined twins and more than 1/5 were discordant. The surviving time of liveborn conjoined twin sets was not more than two days except in two surgically successfully separated pairs. The family study did not indicate a higher recurrence risk. The case group was compared to two control groups and it appeared that the periconceptional use of oral contraception and ovulation induction were mentioned more frequently in pregnancies resulting in conjoined twins.