Database of Families with Twins and Higher Order Multiples in Japanese Twins Mothers Clubs.

It is desirable for twin researchers to be aware of the needs and concerns of families of multiples and provide participants with appropriate and useful feedback and advice based on scientific evidence. Our most recent database on families with twins throughout Japan is based on a questionnaire survey conducted in 2016. Mailed questionnaires, consisting of over 500 items, were used to collect the basic data. The response rate was 38% (566/1478). This is part of a nationwide study designed to assess the long-term effect of perinatal conditions on mothers of multiples. Its aim was to study the growth and development of multiples in childhood, and for the creation of a multifetal mother and child health handbook, and to conduct a genetic epidemiologic study to test the developmental origin of health and disease hypothesis. One of the ultimate aims of this research was to provide evidence-based information on parenting of multiples for families with multiples.

Twin Database of the Secondary School Attached to the Faculty of Education of the University of Tokyo.

This article profiles the historical twin databases of the secondary education school attached to the Faculty of Education at the University of Tokyo. The school was established in 1948. Every year, about 50 pairs of twins of all sex and zygosity combinations, aged 11-12 years, take an examination, and about 10-20 pairs are admitted based on the results. Three datasets exist: one for applicants (11-12 years old), one for junior and senior high school students (12-18 years old) and one for graduates (18-85 years old). Linking the records from these three databases should facilitate several important research projects, for example, life course genetic epidemiologic studies and the verification of the so-called developmental origins of health and disease hypothesis.

Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts.

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.

Associations between birth size and later height from infancy through adulthood: An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project.

BACKGROUND: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. AIM: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. METHODS: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. RESULTS: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14-4.25 cm and 0.18-0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. CONCLUSION: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.

Association between birthweight and later body mass index: an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project.

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood.

Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study.

BACKGROUND: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. OBJECTIVES: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. DESIGN: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. RESULTS: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. CONCLUSIONS: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity.

Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts.

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Birth defects after assisted reproductive technology according to the method of treatment in Japan: nationwide data between 2004 and 2012.

OBJECTIVES: The purpose of the present study was to analyze birth defects (congenital anomalies) after assisted reproductive technology (ART) according to the method of treatment, namely in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and frozen-thawed embryo transfer (FET). METHODS: Individual lists of all ART pregnancies resulting in birth defects from birth year 2004 to 2012 presented in the annual reports by the Japan Society of Obstetrics and Gynecology were used as the initial sources of information. Relative risks (RRs) with the corresponding 95 % confidence intervals (CIs) were calculated with IVF as the reference group when calculating RR of ICSI for IVF, and with FET as the reference group when calculating the RR of fresh embryo transfer for FET. RESULTS: In total, 2725 stillbirths or live births with birth defects were analyzed. The prevalence of birth defects was slightly yet significantly higher in ICSI compared with IVF throughout the study period (RR = 1.15, 95 % CI 1.02-1.29) and in the 2004-2006 period (RR = 1.26, 95 % CI 1.00-1.58). The prevalence of birth defects was significantly higher for fresh embryo transfer compared with FET in the 2004-2006 period (RR = 1.39, 95 % CI 1.12-1.72). The prevalence of birth defects in multiple births was significantly lower in fresh embryo transfer compared with FET (RR = 0.70, 95 % CI 0.55-0.90, live births of 2007-2012). CONCLUSIONS: The present descriptive epidemiological study suggests that the impacts of different ART methods on birth defects might differ.

Tai chi improves cognitive and physical function in the elderly: a randomized controlled trial.

[Purpose] To investigate the effect of Tai Chi on cognitive and physical function in the elderly. [Subjects and Methods] A randomized trial design was used. A total 150 subjects were enrolled and were divided into Tai Chi and control groups. Subjects in the Tai Chi group participated Tai Chi for 6 months, and subjects in the control group participated in other non-athletic activities. [Results] There were no differences between the groups in the one leg standing time with eyes open, left grip strength, or the Frontal Assessment Battery at bedside after 3 and 6 months of intervention. The Mini-Mental State Examination scores after 3 and 6 months were higher in the Tai Chi group than in the control group. The right grip strength after 3 months increased more in the Tai Chi group than in the control group. Both the 5-m high walking speed and 10-m normal walking speed were significantly lower after 3 and 6 months of Tai Chi practice. [Conclusion] These results suggest that regular Tai Chi practice may improve cognitive and physical function in the elderly.

An overview of human handedness in twins.

There has been a long-standing debate on the complex correlation between the development of human hand preference and brain lateralization. Handedness, used as a proxy for cerebral lateralization, is a topic of considerable importance because of its potential to reveal the mechanisms of the underlying pathophysiology of problems related to brain development or cognitive systems. Twin studies, which represent an important method of research in human genetics, would provide valuable suggestions to the studies on the relationship between lateralization and cognitive systems. Many studies have been performed using twin subjects; however, the results are inconsistent, partly because of sample size, background assumptions, data limits or inaccuracies, incorrect zygosity classification, and/or lack of birth histories. In summary, within the long history and large number of twin studies performed on handedness, a surprisingly large number of controversial findings have been reported, suggesting the complicated nature of this phenotype. In this mini review, the wide variety of twin studies on human handedness performed to date are introduced.

Characteristics of fatal child maltreatment associated with multiple births in Japan.

The purpose of the present study was to clarify the characteristics of fatal child maltreatment in families with multiple births in Japan. An exhaustive information search was performed to find multiple-birth cases between July 2003 and March 2011. There were 437 cases of fatal maltreatment of children aged 0-17 years during this period, including 14 involving multiple-birth children. A keyword search was performed to create a full profile for each multiple-birth case. The 14 multiple-birth victims were twins from 13 families. No significant difference between twins and singletons with fatal maltreatment was observed for most characteristics. However, in the case of twins, 0-month victims were rare, and the number of children per family was larger. One twin died from shaken baby syndrome. The victim's siblings were also maltreated in six out of 12 relevant cases, including all six co-twins. Premature birth, having a disabled co-twin, delay of growth or development, and parental disfavor tended to be factors of maltreatment when only one twin was maltreated. Four families were given suspended sentences in total, including three mothers who acted as solitary murderers (43% = 3/7). In conclusion, recent Japanese nationwide data suggests that the non-specific overburden of child rearing might be one possible reason for higher frequency of child maltreatment for multiples compared with singletons, and parental comparisons between two twins might be another. The penal sentences for fatal child maltreatment might be more lenient for perpetrators of this crime against twins than against singletons.

Fatal child maltreatment associated with multiple births in Japan: nationwide data between July 2003 and March 2011.

OBJECTIVES: The purpose of the present study is to clarify the impact of multiple births in fatal child maltreatment (child death due to maltreatment). METHODS: The national annual reports on fatal child maltreatment, which contain all cases from July 2003 to March 2011, published by the Ministry of Health, Labor and Welfare of Japan, were used as the initial sources of information. Parent-child murder-suicide cases were excluded from the analyses. Multiple births, teenage pregnancy and low-birthweight were regarded as the exposed groups. The relative risks (RRs) and their 95 % confidence intervals (CIs) were estimated using the data from the above reports and vital statistics. These analyses were performed both including and excluding missing values. RESULTS: Among 437 fatal child maltreatment cases, 14 multiple births from 13 families were identified. The RRs of multiple births per individual were 1.8 (95 % CI 1.0-3.0) when including missing values and 2.7 (95 % CI 1.5-4.8) when excluding missing values. The RRs of multiple births per family were 3.6 (95 % CI 2.1-6.2) when including missing values and 4.9 (95 % CI 2.7-9.0) when excluding missing values. The RR tended to be much lower than the RR of teenage pregnancy (RR 12.9 or 22.2), but slightly higher than the RR of low-birthweight (RR 1.4 or 2.9). CONCLUSIONS: Families with multiple births had elevated risk for fatal child maltreatment both per individual and per family unit. Health providers should be aware that multiple pregnancies/births may place significant stress on families and should provide appropriate support and intervention.

Maternal age and birth defects after the use of assisted reproductive technology in Japan, 2004-2010.

BACKGROUND: Older mothers are becoming more common in Japan. One reason for this is the widespread use of assisted reproductive technology (ART). This study assesses the relationship between maternal age and the risk of birth defects after ART. METHODS: Nationwide data on ART between 2004 and 2010 in Japan were analyzed. Diseases that were classified as code Q00-Q99 (ie, congenital malformations, deformations, and chromosomal abnormalities) in the International Classification of Diseases, tenth edition, were selected. There were 219,185 pregnancies and 153,791 live births in total ART. Of these, 1943 abortions, stillbirths, or live births with birth defects were recorded. Percentage of multiple birth defects in total birth defects, the prevalence, crude relative risk and 95% confidence interval per 10,000 pregnancies and per 10,000 live births were analyzed according to the maternal age class (ie, 25-29, 30-34 (reference), 35-39, and 40+ years). RESULTS: Multiple birth defects were observed among 14% of the 25-29 year old class, and 8% among other classes when chromosomal abnormalities were excluded. The prevalence of chromosomal abnormalities per pregnancy and per live birth became significantly and rapidly higher in mothers in the age classes of 30-35 and 40+ years. Nonchromosomal birth defects per pregnancy decreased linearly with advanced maternal age, while the number of nonchromosomal birth defects per live birth formed a gradual U-shaped distribution. The prevalence per pregnancy of congenital malformations of the nervous system was significantly lower with advanced maternal age. The relative risk per live birth was significant regarding congenital malformations of the circulatory system for a maternal age of 40+ years. Some other significant associations between maternal age and birth defects were observed. CONCLUSION: Maternal age is associated with several birth defects; however, older maternal age in itself does not produce noticeable extra risk for nonchromosomal birth defects overall.

Two cohort and three independent anonymous twin projects at the Keio Twin Research Center (KoTReC).

The Keio Twin Research Center has conducted two longitudinal twin cohort projects and has collected three independent and anonymous twin data sets for studies of phenotypes related to psychological, socio-economic, and mental health factors. The Keio Twin Study has examined adolescent and adult cohorts, with a total of over 2,400 pairs of twins and their parents. DNA samples are available for approximately 600 of these twin pairs. The Tokyo Twin Cohort Project has followed a total of 1,600 twin pairs from infancy to early childhood. The large-scale cross-sectional twin study (CROSS) has collected data from over 4,000 twin pairs, from 3 to 26 years of age, and from two high school twin cohorts containing a total of 1,000 pairs of twins. These data sets of anonymous twin studies have mainly targeted academic performance, attitude, and social environment. The present article introduces the research designs and major findings of our center, such as genetic structures of cognitive abilities, personality traits, and academic performances, developmental effects of genes and environment on attitude, socio-cognitive ability and parenting, genes x environment interaction on attitude and conduct problem, and statistical methodological challenges and so on. We discuss the challenges in conducting twin research in Japan.

Congenital hypothyroidism after assisted reproductive technology in Japan: comparison between multiples and singletons, 2005-2009.

BACKGROUND: The relationship between congenital hypothyroidism (CH) and multiple pregnancy has not been fully studied in Japan. METHODS: Complete nationwide data of assisted reproductive technology (ART) in Japan from 2005 to 2009 presented by the Japan Society of Obstetrics and Gynecology, which include information on CH and birth defects were used for analyses. Diseases were reclassified according to the International Classification of Diseases, tenth edition (ICD-10, 2003 version). The relative risk (RR) and 95% confidence interval (CI) of the incidence rate for CH was calculated with singletons as the reference group. Additional birth defects with CH were examined. The probandwise concordance rate of multiples and recurrence risk ratio were calculated. RESULTS: There were 18 patients with CH, consisting of 12 singletons and 6 multiples. The incidence rates of CH per 1,000 live births in singletons and multiples are 0.14 (=12/87,145) and 0.31 (=6/19,533), respectively. The incidence rate was more than twofold higher in multiple births than in singleton births, but the difference was not statistically significant (RR=2.2, 95% CI 0.8-5.9). Additional birth defects were present in three patients with CH (17%=3/18). The multiples were affected by other birth defects more frequently (33%=2/6) than the singletons (8%=1/12). The six multiple-births patients were derived from one concordant twin pair, which consisted of two twin patients; three discordant twin pairs, which consisted of three twin patients; and one discordant triplets set, which consisted of one triplet patient. Thus, the probandwise concordance rate was 33.3% (=2/(2+4)). The estimated recurrence risk ratio was 1976 (for the total ART population) or 609 (for the Japanese general population). CONCLUSIONS: CH was more frequent in multiples compared to singletons. A higher percentage of additional birth defects was also observed in multiples compared to singletons. The familial aggregation of CH was suggested.

Twin database of the secondary school attached to the Faculty of Education of the University of Tokyo: lifecourse database of twins.

This article profiles the historical twin databases of the secondary education school attached to the Faculty of Education at the University of Tokyo. The school was established in 1948. Every year, about 50 pairs of twins of all sex and zygosity combinations and aged 11-12 years take an examination, and about 10-20 pairs are admitted based on the results. Three data sets exist: one for applicants (11-12 years), one for junior and senior high school students (12-18 years), and one for graduates (18-79 years). Record linkage of these three databases should facilitate several important research projects; for example, the lifecourse genetic epidemiologic studies and verification of so-called developmental origin of health and disease hypothesis.

Japanese database of families with twins and higher-order multiples.

To gain widespread participation, epidemiologic studies of twins from pregnancy through the childhood period are expected to reflect the needs and concerns of families and provide participants with appropriate and useful feedback based on scientific evidence. Our most recent database on families with twins throughout Japan is based on a questionnaire survey conducted from January 2010 to August 2011. Mailed or hand-delivered questionnaires, consisting of over 550 items were used to collect the basic data. The response rate was 40% (956/2,401). This is part of a nation-wide study designed to assess the long-term effect of perinatal conditions on mothers of multiples. Its aim was to study the growth and development of multiples in childhood, and to conduct a genetic epidemiologic study to test the developmental origin of health and disease hypothesis. One of the ultimate aims of this research was to provide evidence-based information on parenting multiples from pregnancy through childhood to families with multiples.

Concordance rates of birth defects after assisted reproductive technology among 17 258 Japanese twin pregnancies: a nationwide survey, 2004-2009.

BACKGROUND: Most twins after assisted reproductive technology (ART) are dizygotic. Analysis of dizygotic twin pairs is useful in assessing familial aggregation in the development of birth defects. METHODS: Using nationwide post-ART data from the Japan Society of Obstetrics and Gynecology, recurrence risk ratios (RRRs)-defined as probandwise concordance rates of birth defects in twins divided by the prevalence of birth defects in the general population-were calculated as indicators of familial aggregation. Birth defects were then reclassified according to the ICD-10 categories corresponding to codes Q00-Q99. From 2004 to 2009, there were 17 258 twin pregnancies. RESULTS: At least 1 birth defect was noted in 236 twin pairs: 11 concordant and 225 discordant pairs. Regarding major organ systems, high probandwise concordance rates were observed for congenital malformations of eye, ear, face, and neck (11.8%), cleft lip and cleft palate (10.5%), congenital malformations of the nervous system (9.8%), and other congenital malformations of the digestive system (9.5%). High RRRs were observed for congenital malformations of eye, ear, face, and neck (RRR = 233), specifically other congenital malformations of the ear (RRR = 449); congenital malformations of the great arteries (RRR = 235), specifically those of the patent ductus arteriosus (RRR = 530); and for cleft lip and cleft palate (RRR = 208), specifically cleft palate with cleft lip (RRR = 609). The probandwise concordance rate of any birth defect (8.9%) was nearly identical to the approximated recurrence risk of sib-pairs (8.8%), which assumed multifactorial inheritance. CONCLUSIONS: The present findings suggest that familial aggregation is a factor in some birth defects.

Theoretical model of the relationship between single embryo transfer rate and multiple pregnancy rate in Japan.

The purpose of the present study was to examine the effect of single embryo transfer (SET) in assisted reproductive technology (ART) on the reduction of the multiple pregnancy rate. We also estimated the monozygotic (MZ) twinning rates according to the SET diffusion indirectly. A reverse sigmoid curve was assumed and examined using nationwide data of SET from 2007 to 2009 in Japan. The multiple pregnancy rate decreased almost linearly where the SET pregnancy rate was between about 40% and 80% of regression approximation. The linear approximation overestimated multiple pregnancy rates in an early period and underestimated multiple pregnancy rates in the final period. The multiple pregnancy rate seemed to be influenced by the improvement of the total pregnancy rate of ART in the early period and by the MZ twinning after SET in the final period. The estimated MZ twinning rate after SET was around 2%.