Recruitment of Twins and Higher Order Multiple Births

The Registry was previously known as the Kinki University Twins and Higher Order Multiple Births Registry (Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995a, Reference Yokoyama, Shimizu and Hayakawa1995b). Since the 1990s, twins, triplets, quadruplets, quintuplets, and their families have been recruited for the registry from several sources, including mothers who responded to magazine articles on nursing guidance for families of multiples, the various Japanese Mothers’ Organizations for Twins and Higher Order Multiple Births, and referrals from public health centers in west Japan (Yokoyama, Reference Yokoyama2002b; Yokoyama et al., Reference Yokoyama, Sugimoto and Ooki2005, Reference Silventoinen, Karvonen, Sugimoto, Kaprio, Dunkel and Yokoyama2011b).

Nishinomiya city, a residential area with a population of approximately 460,000 is included within the catchment area. The number of births per year in this area is about 4,700, with an increase in multiple births being observed from 2000 onwards. The current number of multiple births per year is between 110 and 170. The public health centers in Nishinomiya city collaborate with the author to provide appropriate childcare information for families with multiples, based on evidence obtained since 2002 (Sugimoto et al., Reference Sugimoto, Yokoyama, Wada, Matsubara, Saito and Sono2008; Yokoyama et al., Reference Yokoyama and Ooki2004, Reference Yokoyama, Wada, Sugimoto, Katayama, Saito and Sono2006, Reference Yokoyama, Wada, Sugimoto, Saito and Sono2007, Reference Yokoyama, Sugimoto, Sono, Kaprio and Silventoinen2011a). Expectant mothers and fathers of multiples living in the city participate in childbirth classes for multiple births and are now offered childcare information based on the findings, including optimal maternal weight gain and gestational periods in twin and triplet pregnancies, physical growth and development features of twins and triplets in childhood, child-rearing problems, and measures in mothers with multiple children and so on (Yokoyama, Reference Yokoyama2002a, Reference Yokoyama, Sugimoto, Pitkäniemi, Kaprio and Silventoinen2002b; Yokoyama & Ooki, Reference Yokoyama and Ooki2004; Yokoyama & Shimizu, Reference Yokoyama and Shimizu1999, Reference Yokoyama and Shimizu2001; Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995a, Reference Yokoyama, Shimizu and Hayakawa1995e, Reference Yokoyama, Shimizu, Yura and Hayakawa1997, Reference Yokoyama, Nakahara, Matsubara, Sugimoto, Koyama and Mitsutsuji2004, Reference Yokoyama, Wada, Sugimoto, Katayama, Saito and Sono2006, Reference Yokoyama, Wada, Sugimoto, Saito and Sono2007, Reference Yokoyama, Sugimoto, Sono, Kaprio and Silventoinen2011a). In addition, the public health centers in Osaka city have also started to collaborate with the author. Osaka city is an urban area with a population of approximately 2,665,000, and the number of births per year is about 23,000. Table 1 provides a summary of the number of families with twins and higher order multiples included in the registry and those who participated in at least one survey, namely 3,536 pairs of twins, 1,385 sets of triplets, 39 sets of quadruplets, 6 sets of quintuplets, and their families.

TABLE 1 The West Japan Twins and Higher Order Multiple Births Registry

Determining Zygosity

Zygosity of the same-sex twin pairs was initially diagnosed using a three-item questionnaire (Ooki & Asaka, Reference Ooki and Asaka2004) based on physical resemblance rated by mothers of twins when twins are around 1 year of age. The three items used were: ‘Are they like two peas in a pod?’, ‘Are they often confused for each other?’, and ‘If so, by whom?’ According to the degree of similarity, the first question was scored from 1 (like two peas in a pod) to 3 (quite different), the second question from 1 (very often) to 3 (never), and the third from 1 (parent) to 4 (no-one). In accordance with the cut-off point established, those with a total score of 6 to 10 were determined to be monozygotic (MZ) and those with a score of 13 to 19 as dizygotic (DZ). Those with a total score of 11 or 12 were judged as unidentified.

Health Check-Ups and Measurements

In Japan, the postnatal health monitoring system changes according to the child's age. Birth weight, body length, head circumference, and chest circumference are measured at hospitals and recorded along with information on gestational age. Until 6 years of age, routine health check-ups are administered by the Ministry of Health, Labor and Welfare under the Maternal and Child Health Law. Information on physical and motor development is recorded in the Maternal and Child Health Handbooks provided to expectant mothers by local authorities upon notification of the pregnancy. This handbook was established under the Maternal and Child Health Law. The purpose of the handbook is to maintain a record of maternal and child health. It includes information on health check-ups during pregnancy, the condition of the newborn, progression of infant growth, and periodic medical infant check-ups and vaccination recorded by obstetricians or pediatricians. After 6 years of age, Japanese children receive health check-ups administered by the Ministry of Education, Culture, Sports, Science and Technology under the School Health Law. The physical measures performed during these school-based health check-ups are routinely recorded in the school records and made available to each family.

Mothers participating in this study were offered childcare information specific to families of multiples based on several articles written by authors who also cooperated with this study (Yokoyama, Reference Yokoyama2002a, Reference Yokoyama2002b; Yokoyama & Ooki, Reference Yokoyama and Ooki2004; Yokoyama & Shimizu, Reference Yokoyama and Shimizu1999; Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995e, Reference Yokoyama, Sugimoto, Silventoinen and Kaprio2008, Reference Yokoyama, Sugimoto, Silventoinen, Pitkäniemi and Kaprio2009). Mothers were advised to refer to these records when completing the questionnaire. Table 2 shows the information obtained in the questionnaires and physical measures study. Follow-up questionnaires are being mailed every 2 to 3 years as part of longitudinal survey studies.

TABLE 2 Information in the Questionnaire and Physical Measures for Multiples

¹Yokoyama et al. (Reference Yokoyama, Shimizu and Hayakawa1995a); ²Yokoyama et al. (Reference Yokoyama, Shimizu and Hayakawa1995b); ³Yokoyama et al. (Reference Yokoyama, Shimizu and Hayakawa1995c); ⁴Yokoyama et al. (Reference Yokoyama, Shimizu and Hayakawa1995d); ⁵Yokoyama & Shimizu (1999); ⁶Yokoyama (Reference Yokoyama2002b); ⁷Yokoyama (Reference Yokoyama2003); ⁸Yokoyama et al. (Reference Yokoyama2003); ⁹Yokoyama & Ooki (Reference Yokoyama and Ooki2004); ¹⁰Yokoyama et al. (Reference Yokoyama, Sugimoto and Ooki2005); ¹¹Yokoyama et al. (Reference Yokoyama, Wada, Sugimoto, Katayama, Saito and Sono2006); ¹²Yokoyama et al. (Reference Yokoyama, Wada, Sugimoto, Saito and Sono2007); ¹³Yokoyama et al. (Reference Yokoyama, Sugimoto, Silventoinen and Kaprio2008); ¹⁴Yokoyama et al. (Reference Yokoyama, Sugimoto, Silventoinen, Pitkäniemi and Kaprio2009); ¹⁵Yokoyama et al. (Reference Yokoyama, Sugimoto, Sono, Kaprio and Silventoinen2011a); ¹⁶Yokoyama et al. (Reference Yokoyama, Sugimoto, Pitkäniemi, Kaprio and Silventoinen2011b); ¹⁷Yokoyama et al. (Reference Yokoyama, Pitkäniemi, Kaprio and Silventoinen2012); ¹⁸Silventoinen et al. (Reference Silventoinen, Kaprio and Yokoyama2010); ¹⁹Silventoinen et al. (Reference Silventoinen, Karvonen, Sugimoto, Kaprio, Dunkel and Yokoyama2011a); ²⁰Silventoinen et al. (Reference Silventoinen, Kaprio and Yokoyama2011b).

Focus of the Study

One of the major focuses of this study has been to investigate the degree of risk of disabilities in twins, triplets, and quadruplets, and to identify factors associated with the increased risk. Figure 1 shows the prevalence rates of cerebral palsy in twins, triplets, and quadruplets by gestational age at birth (Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995a). Children with cerebral palsy tend to have a lower gestational age compared to those without cerebral palsy among twins, triplets, and quadruplets. Moreover, the risk of at least one child being disabled was found to be approximately 1 in 13 pairs of twins (7.4%), one in four to five sets of triplets (21.6%), and one in two sets of quadruplets and quintuplets (50.0%). There was also a significantly higher clustering tendency of disabilities in twins and triplets compared with the expected frequency calculated from the incidence rate of disabilities (Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995b, Reference Yokoyama, Shimizu and Hayakawa1995c).

FIGURE 1 Cerebral palsy and gestational age of twins, triplets, and quadruplets.

Physical growth and development features of twins and triplets in childhood were also extensively analyzed as part of the study (Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995d, Reference Yokoyama, Sugimoto and Ooki2005, Reference Yokoyama, Sugimoto, Silventoinen and Kaprio2008, Reference Yokoyama, Sugimoto, Silventoinen, Pitkäniemi and Kaprio2009, Reference Yokoyama, Sugimoto, Sono, Kaprio and Silventoinen2011a, Reference Yokoyama, Sugimoto, Pitkäniemi, Kaprio and Silventoinen2011b, Reference Yokoyama, Pitkäniemi, Kaprio and Silventoinen2012). The present dataset represents the largest triplet sample in the world for which accurate data on age after birth are available. The weight and height deficits of triplets compared to the general population of Japan were found to be between 10% and 17% for weight and between 2% and 5% for height until 12 years of age. We also analyzed the genetic architecture of the growth process (Silventoinen et al., Reference Silventoinen, Kaprio and Yokoyama2010, Reference Silventoinen, Kaprio and Yokoyama2011a, Reference Silventoinen, Karvonen, Sugimoto, Kaprio, Dunkel and Yokoyama2011b). Our results suggested that the genetic architecture of BMI development in the Japanese population is generally similar to that found in previous twin studies in Caucasian populations. Moreover, head circumference (HC) was found to be strongly genetically regulated. Several other studies have examined maternal and child health of families with multiples (Yokoyama, Reference Yokoyama2002a, Reference Yokoyama2002b; Yokoyama & Shimizu, Reference Yokoyama and Shimizu1999, Reference Yokoyama and Shimizu2001; Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995e; Reference Yokoyama, Shimizu, Yura and Hayakawa1997; Yokoyama, Reference Yokoyama2003; Yokoyama et al., Reference Yokoyama2003, Reference Yokoyama, Nakahara, Matsubara, Sugimoto, Koyama and Mitsutsuji2004).

Future Directions

Raising multiples entails a higher physical, mental, and economic burden than raising singletons (Yokoyama, Reference Yokoyama, Yamashiro and Ooki2003; Yokoyama & Shimizu, Reference Yokoyama and Shimizu2001; Yokoyama et al., Reference Yokoyama, Shimizu and Hayakawa1995e, Reference Yokoyama, Shimizu, Yura and Hayakawa1997, Reference Yokoyama2002a, Reference Yokoyama, Sugimoto and Ooki2005). This registry therefore aims not only to provide data for research on human genetics and maternal and child health, but also to provide appropriate information for families with multiples. Expectant mothers and fathers of multiples living in Nishinomiya city and Osaka city that collaborate with the author are offered childcare information based on the findings through childbirth classes for multiple births and so on.

Collaboration is welcomed, especially with investigators currently employing similar measuring tools and who are interested in pooling resources.