The notion of twins and twinning involves a multiplicity of meanings and contexts that altogether encompass an unexpectedly wide and significant part of human experience, culture, and endeavor. This cultural polysemy is, to some extent, also an attribute of twin research, which has structured itself around a multiplicity of scientific areas of enquiry, and across time, throughout a multiplicity of births and rebirths, periodically declining and resurging as a phoenix from its ashes. What is proposed is a short voyage through this polysemy and phoenixity of twinning and twin research, and through the structuring process that has accompanied its developments, international scope, and organization. No claim to completeness, but an attempt to dig into personal memory and experience, and share some recollections of the main steps of the process, and particularly the evolution of the journal, the society, the international meetings, and their role in supporting the area's persistence and continuous revivals and adaptations until today.

The surgical separation of a pair of conjoined twins in the year 1689 by Johannes Fatio was the subject of a recent article in this journal. The reference used as publication of the case was Fatio's book, Der Arzney Doctor, Helvetisch-Vernüftige Wehe-Mutter, published in 1752, although the case was presented in literature by three earlier sources. Two articles were published in the Miscellanea Curiosa sive Ephemeridum MedicoPhysicarum Germanicarum Academiae Imperialis Leopoldinae Naturae Curiosorum in 1689 by Emanuel König and another in 1690 by Theodor Zwinger who described and illustrated the case in detail. Besides these articles, a Flug Blatt was published on the case between 1689 and 1695. Fatio copied the engraved plate in his book from König's engraving. These two sources should be cited as the first publications on the successful separation of Elisabet and Catherina, and not Fatio's book from 1752.

Thirteen sets of monozygotic (MZ) twins from an extended multi-generation family are reported. Zygosity was determined by interviewing families for overall physical similarity and by assessment of facial photographs. A hypothetical gene was traced back five generations to a common grandfather. Familial monozygotic twinning in this pedigree is compatible with autosomal dominant inheritance with reduced penetrance. Other plausible mechanisms of inheritance are discussed.

Aretrospective study involving 972 twin births was conducted to evaluate the maternal and fetal outcomes of twin pregnancies complicated by single fetal death. The incidence of single fetal death in twin pregnancies after 20 weeks was 3.3%. Preterm birth rates for 37 and 32 gestational weeks were 81.3% and 41.6% respectively. The median interval between the diagnosis of fetal death and the delivery was 11 days (range 1–27 days). Eighteen (56%) infants were delivered by cesarean and 14 (43%) vaginally. Twin–twin transfusion syndrome (TTTS) was the cause of single fetal death in 8 of 32 twin pregnancies (25%). Ten of the surviving co-twins were lost in the neonatal period (31.3%) and half of those neonatal deaths were due to TTTS. TTTS is the major contributor for perinatal mortality in same-sex twins complicated by single fetal death. The death of one twin in utero should not be the only indication for preterm delivery, and in case of severe prematurity with a stable intrauterine environment; expectant management may be advisable until fetal lung maturation ensues.

We analyze the association between the rates of multiple maternities. Correlation analysis is suitable if there are at least monotonic relationships between the variables. A decreasing tendency can be observed in the rates of multiple maternities in Sweden and in its 25 counties for the period 1751–1960 and the effect of external variables can be assumed to be monotonic. After 1960, the rates of multiple maternities show marked increases, mainly caused by ovulation stimulants and the introduction of other artificial reproduction techniques. We transformed the triplet and quadruplet rates according to Hellin's law in order to obtain rates on the same scale as the twinning rate. The time trends for the multiple maternities in Sweden as a whole were quite similar. The regional differences in the twinning rates could not be satisfactorily explained by maternal age. Alternative attempts to eliminate the effect of other time-dependent factors were to study partial correlation coefficients when the time was kept fixed and the correlation coefficients based on cross-sectional regional data. Both the ordinary and the partial correlation coefficients showed strong regional variation. Cross-sectional analyses gave correlation coefficients similar to the partial correlation coefficients for Sweden as a whole. The variations in the correlation coefficients between the twinning and the triplet rates seem to be caused by other time-dependent factors and the effects of these factors show strong regional variation. After elimination of such factors, the correlation between the twinning and the triplet rates is moderate.

We investigated the effects of classroom separation on twins' behavior, progress at school, and reading abilities. This investigation was part of a longitudinal study of a nationally-representative sample of twins (the E-risk Study) who were assessed at the start of school (age 5) and followed up (age 7). We examined three groups of twins: pairs who were in the same class at both ages; pairs who were in separate classes at both ages; and pairs who were in the same class at age 5, but separated by age 7. When compared to those not separated, those separated early had significantly more teacher-rated internalizing problems and those separated later showed more internalizing problems and lower reading scores. Monozygotic (MZ) twins showed more problems as a result of separation than dizygotic (DZ) twins. No group differences emerged for externalizing problems, ADHD or prosocial behaviors. The implications of the findings for parents and teachers of twins, and for school practices about separating twins, are discussed.

Reports on the first successful separation of conjoined twins in 1689 and especially the publication of this achievement, as late as 1752, in the Helvetisch-vernünftiche Wehe-Mutter by Johannes Fatio are discussed in this paper with the intention to correct several historical inaccuracies.

The Danish Twin Registry was established formally in 1954 and thus celebrates its 50th anniversary in 2004. Here we give an account of its founding and the early years, and a brief summary of more recent progress.

The present study deals with the determination of zygosity in twins of childhood age by simple questionnaire. The subjects were 224 twin pairs and their mothers, consisting of 159 monozygotic and 65 same-sex dizygotic pairs, identified by genetic markers including DNA samples. Mothers of twins responded to 19 questionnaire items dealing with twin similarity in 16 items about physical features and 3 items about the degree of similarity and frequency of being mistaken (confusion of identity) when twins were about 1 year of age. The twins themselves responded to three questionnaire items dealing with only confusion of identity items. The results of stepwise logistic regression analysis were as follows: the total accuracy of the mothers' questionnaire was 91.5% when using only the items dealing with confusion of identity. This accuracy was slightly lower than that obtained by twins' self-reports dealing with nearly the same question items of confusion of identity, answered by both twins separately with 93.3% accuracy. The total accuracy of mothers' questionnaire responses rose to 95.1% when we used all 19 items. In addition to ‘the frequency of being mistaken‘, two physical features, namely ‘shape of fingers’ and ‘shape of eyebrow’, were very informative. In conclusion, twin zygosity can be estimated by the use of the mothers' simple questionnaire with sufficient accuracy even in very young twins about 1 year of age.

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gameteintrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from ≤ 20 weeks of gestation and gave birth to infants after ≥ 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.

Every statistical model is based on explicitly or implicitly formulated assumptions. In this study we address new techniques of calculation of variances and confidence intervals, analyse some statistical methods applied to modelling twinning rates, and investigate whether the improvements give more reliable results. For an observed relative frequency, the commonly used variance formula holds exactly with the assumptions that the repetitions are independent and that the probability of success is constant. The probability of a twin maternity depends not only on genetic predisposition, but also on several demographic factors, particularly ethnicity, maternal age and parity. Therefore, the assumption of constancy is questionable. The effect of grouping on the analysis of regression models for twinning rates is also considered. Our results indicate that grouping influences the efficiency of the estimates but not the estimates themselves. Recently, confidence intervals for proportions of low-incidence events have been a target for revived interest and we present the new alternatives. These confidence intervals are slightly wider and their midpoints do not coincide with the maximum-likelihood estimate of the twinning rate, but their actual coverage is closer to the nominal one than the coverage of the traditional confidence interval. In general, our findings indicate that the traditional methods are mainly satisfactorily robust and give reliable results. However, we propose that new formulae for the confidence intervals should be used. Our results are applied to twin-maternity data from Finland and Denmark.

Mothers of multiples who choose to feed their infants breast milk are faced with a seemingly overwhelming set of circumstances. Since mothers of multiples could potentially feed their infants differing proportions of breast milk, current methods of obtaining breastfeeding data for mothers of singletons may not adequately describe the breastfeeding behaviors of mothers of twins and triplets. The goal of our study was to determine the proportion of breast milk each infant of a multiple set was fed over a six-month period and compare the feeding regimens of sibling infants. Results of this retrospective study based on maternal reports indicated that there was almost complete agreement in the proportion of breast milk fed to siblings born from the same pregnancy, regardless of stratification based on gestational age, plurality, or location of the infants (hospital vs. home). The Pearson correlation coefficient for duration of breast-milk feeding between sibling twins was 0.99 (p < .0001); among sibling triplets the values were .97, .98 and .99 (p < .0001). A better understanding of the process by which twins and triplets are fed breast milk sets the stage for future research and can ultimately lead to the development of strategies to increase breast-milk feeding rates for multiple birth children.

This paper examines why parents of twins or adult twins themselves request zygosity testing. Of 405 multiples including 8 sets of triplets, the majority (93%) were monozygotic. Age of testing ranged from 0 days to 73 years. About 50% of requests came from parents or twins who were curious about, or expressed a need to be certain of, their zygosity. Other reasons included health concerns (current or future), other twins in the family, and misinformation about zygosity, frequently because of the erroneous assumption that all dichorionic twins are dizygotic. Parents of monozygotic twins may expect their twins to be ‘identical’ and believe their twins to be dizygotic because of minor phenotypic differences between them. Dizygotic twins like other siblings may share a phenotypic resemblance. Health professionals should be aware that zygosity of multiples may not always be obvious to parents and that accurate knowledge of zygosity may be justified.

Though twinning rates have been rapidly increasing in Japan, the problem of zygosity misclassification at birth has been paid little attention. By analyzing four independent samples, the authors found that at a constant rate about 25–30% of monozygotic twins were misclassified as dizygotic twins at birth. This percentage is in very good accordance with that of monozygotic twins having dizygous placenta. Generally the obstetricians informed twins' parents about their children's zygosity. The number of placentas, as informed by obstetricians, was very strongly associated with zygosity. Concluding, even now many monozygotic twins in Japan may be misclassified as dizygotic at birth by obstetricians based solely on the number of placenta.

This study aimed to compare birthweight distribution of twins and singletons from three different socioeconomic level hospitals and evaluate the possible contribution of assisted reproduction technologies (ART). Data for twins and singletons were collected in the 1990s from hospitals A (370 twins, 370 singletons), B (306 twins, 306 singletons), and C (562 twins, 562 singletons). Only hospitals B and C have ART procedures. Gestational age was significantly lower in hospital C for singletons and twins. Birthweight for singletons was lower at hospital A (p < .005 for hospital B and p = .000 for hospital C); however, birthweight for twins was lower for hospitals A and C compared to hospital B (p = .000 for both comparisons). There were no differences between the mean birthweight for singletons and twins either to primigravidae or multigravidae in hospital A; nevertheless, for B and C the mean birthweight of twins was significantly lower in primigravidae than in multigravidae (p = .029 and p = .006, respectively). Considering twins up to 37-weeks of gestational age, hospital C showed the highest percentage of twin births (73.3%). These data suggest that the use of ART accounts for a disproportionate number of low birthweight and/or premature infants in primigravidae of higher socioeconomic level.

Aloss of function mutation in growth differentiation factor 9 (GDF9) in sheep causes increased ovulation rate and infertility in a dosage-sensitive manner. Spontaneous dizygotic (DZ) twinning in the human is under genetic control and women with a history of DZ twinning have an increased incidence of multiple follicle growth and multiple ovulation. We sequenced the GDF9 coding region in DNA samples from 20 women with DZ twins and identified a four-base pair deletion in GDF9 in two sisters with twins from one family. We screened a further 429 families and did not find the loss of function mutation in any other families. We genotyped eight single nucleotide polymorphisms across the GDF9 locus in 379 families with two sisters who have both given birth to spontaneous DZ twins (1527 individuals) and 226 triad families with mothers of twins and their parents (723 individuals). Using case control analysis and the transmission disequilibrium test we found no evidence for association between common variants in GDF9 and twinning in the families. We conclude that rare mutations in GDF9 may influence twinning, but twinning frequency is not associated with common variation in GDF9.

Following the Derom et al. paper recently published in Twin Research (2003, 6, 19–21), we investigated our French sample, studying the retrospective validity of information given by parents to determine the chorion type of their monozygotic twins. The sample included 44 MZ pairs of known chorion type. Chorion type was established by a pathologist specialising in the study of placenta and zygosity diagnosis using molecular genetic techniques. Results show that of the parents who had information, there was a high level of uncertainty of the chorion type. It therefore seems impossible to obtain valid retrospective determination from parents and the only solution is to have accurate information in the birth records.

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.

A sample of pairs of twins who were born in the United States in 1919 and survived to adulthood is identified through an innovative and large-scale application of the methodology of probabilistic linkage. The social security program began in the United States in November 1936, and the file of applicants for a social security number — which was used in this study — is the closest thing in the United States to a population register. The study results are very satisfactory, and demonstrate the superiority of probabilistic linkage to exact linkage. We estimate that about 33,000 twin pairs were born in the United States in 1919 and about 19,000 survived to age 17. Since the social security number was not then, at the inception of the program, the universal identifier that it is today, the number of enumerated twin pairs is somewhat less. Nonetheless, over 16,000 twin pairs can be identified by the method of probabilistic linkage. By comparison, only about half as many can be identified by straightforward exact linkage.