Although Francis Galton was the first to use twins for comparative genetic studies in a scientific way, there had been considerable interest and speculation about twinning from very early times. This has been referred to in numerous publications in the past, and indeed, Professor Gedda, Founding President of our Society, has written extensively on this [9]. The earlier writings referred almost entirely to the twins themselves, and there seemed to have been little attention paid to the mothers, except that they were either considered to have had intercourse with two men, or indeed, with a deity. Galton also referred in his publication of 1876 [8] to the largeness of the families into which twins are born, but a graduate of Aberdeen University, James Matthews Duncan, had pointed out some of the characteristics of mothers having twins ten years earlier. In 1865 he published his paper “On the Comparative Frequency of Twin-Bearing in Different Pregnancies” [7] and in this he showed that mothers of twins tended to be of higher parity and older. This very accurate observation has since been confirmed, but is was not clear whether age and parity were separate factors until Anderson, again working in Aberdeen, showed in 1956 that the twinning incidence increased up to a peak at age 35 and thereafter fell [1].

Francis Galton was born on 16th February 1822 (the same year as Mendel). His mother Violetta (1783-1874) was the daughter of Dr. Erasmus Darwin (1731-1802), a medical practitioner in Derby who had scientific interests, particularly in plants, and produced various mechanical inventions. He was also grandfather to Charles Darwin. Galton's father, Samuel Tertius Galton (1783-1844), was a Birmingham banker but possessed a number of scientific instruments. His father (Francis Galton's grandfather), Samuel Galton (1735-1832), also had scientific interests, including colour vision, and was elected a Fellow of the Royal Society.

Francis Galton became a medical student in Birmingham in 1838, subsequently attending King's College London, Cambridge and St. George's Hospital. However, he gave up his medical studies in 1844 after the death of his father [5,17]. Later he travelled in Egypt and South Africa about which he wrote various articles and books, including “The Art of Travel” (1855) [6] of which a total of eight editions were published. His scientific work from these expeditions won him his first medal, the gold medal of the Royal Geographical Society awarded in 1853. Subsequently he wrote further on scientific matters, mainly concerning geography, travel and meteorology. He worked on stereoscopic maps and problems associated with wind currents and sailing ships and introduced the word “anticyclone”. He was elected a Fellow of the Royal Society in 1856 and later to the Council of the Royal Geographical Society, becoming Secretary of the British Association for the Advancement of Science in 1863 [4,19].

Physiological adaptation including expansion in plasma volume is exaggerated in women with twin pregnancies. In singleton pregnancy and multiparous twin pregnancies there is an association between plasma volume expansion and birth weight, but this is not so in primigravid twin pregnancies. Women with twin pregnancies have a similar dietary intake to singleton pregnancies, but it is not known whether there are differences with parity or zygosity. Absorption and utilisation of nutrients may be increased to meet demands for extra fetal growth. Nutrient supply and plasma volume expansion will be further discussed and their association with birth weight presented.

The relation between spontaneous abortions and twinning was studied in the years 1980-1981 in 22 towns of the South Moravian Region, Czechoslovakia. Each town has more than 10,000 inhabitants and less than 750 births per year. The number of spontaneous abortions and the number of twin births were evaluated separately for each town and for a time unit of three months. The comparison indicated that the group with a higher number of spontaneous abortions also had a lower number of twin births. The relation between spontaneous abortions and twinning is discussed.

A total of 204 cases of twin pregnancy occurred between 1970 and 1972 have been compared with 102 cases occurred between 1976 and 1978. During the interval of time, specialised care was instituted for the early diagnosis and management of twins. The incidence of twin pregnancy in Singapore decreased from 1:131 to 1:141 pregnancies. With a background of improved socioeconomic conditions and obstetric care, there has been a dramatic decline in perinatal mortality from 76.4 to 29 per 1000. In undiagnosed cases, the perinatal mortality of the first vs the second twin in the earlier group was 64.4 vs 93.6 per 1000. No such difference was observed in the later period, with the average birthweights of twins being significantly higher. The principles of our antenatal supervision, antenatal tocography, and management are presented and the value of early diagnosis, bedrest, and tocolytic therapy discussed. The reduced perinatal mortality and mobidity gives evidence of an improvement in prematurity and augmented intrauterine growth.

The authors have performed selective birth in two twin pregnancies in the same patient. The couple's first pregnancy resulted in the birth of a male with Tay Sachs disease: their Pergonal-induced second pregnancy was a twin gestation discordant for Tay Sachs disease. A fetal intracardiac puncture, exsanguination, and fetal intracardiac air embolization were then performed. The patient went into premature labor 9 days later and delivered a normal immature infant, who died, and the macerated cotwin. The third Pergonal-induced pregnancy was a singleton with Tay Sachs disease and the pregnancy was terminated. Their fourth Pergonal-induced pregnancy was a twin gestation discordant for Tay Sachs disease. At 20 weeks gestation, fetal intracardiac air embolization was performed with immediate demise of the affected fetus. The pregnancy was followed closely with ultrasonography and coagulation studies and proceeded to term without complication. A normal female and a fetus papyraceous were delivered by cesarean section.

The diagnosis of multiple gestation at the time of genetic amniocentesis is a routine occurrence. In a combined series of 2765 patients referred for antenatal genetic studies from the Medical College of Virginia and the University of Iowa, 34 twin pregnancies were encountered (1.2%). Twenty-six of the patients with twins were referred for advanced maternal age. The other indications were previous neural tube defects (1), previous trisomy 21 (2), known carriers of Tay Sachs disease (2), previous Turner's syndrome (1), family history of trisomy 21 (1), and one pregnancy was referred because of an abnormal ultrasound. Amniocentesis procedures, outcome of the twin pregnancies, and genetic counseling issues, are discussed.

Fifteen cases were reviewed over a five-year period at a perinatal centre with intrauterine demise of one member of a multiple gestation. Nine cases were monozygotic twin pairs, two were dizygotic, and two were triples. Gestational age ranged from 27 to 39 weeks. The management protocol consisted of delivery in all cases after confirmation of the diagnosis. In 4 cases delivery was immediate because of spontaneous labor. In the other cases elective delivery was performed if the gestational age was 37 weeks or greater or there was evidence of preeclampsia or if amniocentesis revealed a mature lecithinsphingomyelin (L/S) ratio. Steroids were given if the L/S was immature or the attempt at amniocentesis was unsuccessful and delivery was performed 48 hours after initiation of steroid therapy. Cesarean section was the mode of delivery in 14 of the 15 cases. All of the cotwins and cotriplets survived. One survivor of a monozygous twin pair has multicystic encephalomalacia possibly implicating perinatal arterial occlusion or in utero disseminated intravascular coagulation (DIC). The intrauterine deaths are categorized into possibly avoidable deaths (2/15), unavoidable due to congenital anomalies (3/15), and unknown or unavoidable deaths (8/15).

An increased incidence of twinning has been reported among patients with Klinefelter's syndrome (XXY) and their relatives, but no data have been reported about the incidence of XXY among twins. Results from our institution's antenatal testing clinic provide data about twins and XXY. In 1842 pregnancies tested, 21 were noted to be twin gestations. Five fetuses with XXY were detected in all pregnancies, of which there was a pair of MZ twins concordant for XXY and a pair of DZ twins discordant for XXY. The incidence of XXY in twins was thus 7,1%. The fetal phenotype of XXY was examined in aborted MZ twins and found to be mild. Notably, the testicular histology was normal. These cases confirm the previously reported association of twinning and XXY. The association of twinning and XXY implies a commonality of causation; however, a maternal age effect cannot be excluded. Our data suggest that there is an increased risk of XXY among twins.

Selective feticide by fetoscopic air embolism was carried out in six twin pregnancies complicated by discordance for a severe abnormality. In three, a previous diagnostic fetoscopy had been performed. The procedure was effective and uncomplicated in all cases. One patient is undelivered and five have delivered healthy babies, three at term and two preterm. One of the latter, delivered at 28 weeks, died of complications in the neonatal period.

A preliminary analysis of twins or triplets with heart defects, ascertained in five centres, confirms earlier suggestions that monozygotic (MZ) twins are over represented among twins with heart defects, even after excluding persistent ductus arteriosus and conjoined twins. An MZ twin individual has a risk of cardiovascular malformation approximately twice that of DZ twins and singletons. It is suggested that the twinning process itself affects one of the pair. Disturbance of laterality (‘mirror imaging’) is probably a more important mechanism than twin-twin transfusion. Inappropriate use of the twin method in the past has caused the importance of genetic factors in the etiology of congenital heart defects to be underestimated. Neverthless, twins do provide a useful illustration of the likely importance of epigenetic factors in heart development.

A 38-year-old woman, gravida 5, para 3, with a triplet prgnancy discordant for anencephaly, is reported. The diagnosis was made prenatally by ultrasound. Autopsy of the anencephalic member revealed small adrenal glands with absent fetal cortex, and a coincidental tetralogy of Fallot. Studies of the histocompatible lymphocyte antigens of both parents were performed and they failed to demonstrate HLA B-27. The literature on anencephaly in triplets is summarized. The association of congenital heart disease and HLA B-27 with anencephaly is discussed.

During a 10-year period (1971-1980) 16 sets of conjoined twins were delivered in the author's hospital. The incidence of those twins was 1 in 4242 deliveries, 1 in 69 multiple births, and 1 in 139 congenitally malformed babies. All diagnoses were made during labour or at operation and all babies were lost. There were no maternal deaths.

A case is reported of a 14-year old male MZ twin pair, with only one partner affected by situs viscerum inversus, whereby the condition is termed situs viscerum specularis. The high degree of mirror imaging is seen as an abnormal variation of the biological time of the cleavage giving rise to MZ twinning. Electrocardiographic findings are presented and the biological implications of the condition are discussed.

During 1967-79 the population-based Medical Birth Registry of Norway registered 7,660 twin pairs (1% of births) born to 7,596 mothers, who gave birth to 6,608 additional infants (twin siblings). The total rate of malformations among twins (278.1/10,000) was not significantly different than among singletons (302.1/10,000), nor among twin siblings (314.8/10,000). By specific type of defect, twins had significantly higher rates than singletons of central nervous system (CNS) defects (Rate Ratio = 1.8) and cardiovascular defects (RR = 1.5). The twins also had a significantly low rate of congenital hip dislocation (RR = 0.4), which may explain the relatively low incidence of malformations in twins. Like-sex (LS) twins had a slightly higher rate of malformations than unlike-sex (US) twins (RR = 1.1), as well as a higher rate of CNS defects (RR = 3.0). The siblings also had a significantly increased rate of CNS defects compared to singletons (RR = 1.9), but not of cardiovascular defects (RR = 0.9). The results indicate that twins have elevated rates of at least some congenital malformations. The observations about CNS defects suggest common factors that can lead to either like-sex twinning, CNS defects, or both. The increased frequency of cardiovascular defects in twins appears to be associated with the biologic conditions of twinning.

Problems of ascertainment bedevil the investigation of the etiology of congenital anomalies in singletons and in multiple births by epidemiological methods. It is shown that the definition of the population of affected births is ambiguous and that the problem of tracing etiology is complicated by the systematic way in which anomalies may be missed at birth. The available methods of dealing with problems of ascertainment are reviewed. Methods of adjusting for possible bias of ascertainment of affected births, by fitting statistical models to data from several sources, have been employed in some previous studies. In these methods, it is assumed that there are no errors of diagnosis or of recording. However, it is shown that there may be discrepancies in recorded diagnoses between sources, rendering this assumption untenable. In these methods, it is also assumed that the model which is the best fit to the data on the ascertained cases in also the best model for the cases which were not ascertained. This assumption is tested indirectly in a retrospective analysis of data from Aberdeen and Belfast collected concurrently through routine recording systems. It is demonstrated that there was a social process in ascertainment which renders the methods of adjusting for bias of ascertainment at best very complicated and at worst inapplicable.

The rates of MZ and DZ twin births and of triplet births slightly decreased in Japan in 1955-1967 and 1974, whereas that of trizygotic triplets tripled. The rates of triplet and quadruplet births were comparable to those of Caucasians. Although the sample size is small, Japan seems to be characterized by higher rates of triplets and quadruplets of polyembryonal origin and lower rates of those of polyovulational origin as compared to Caucasian populations. Stillbirth rates in both MZ and DZ twins gradually decreased in 1960-1967 and 1974. The rate was higher in MZ than DZ twins, and higher in males than females. The secular trends of stillbirth rates in like-sexed triplets was similar to that in twins, whereas the rate in unlike-sexed triplets remained almost constant for the entire period. The rate was higher in like-sexed than unlike-sexed triplets.

A total of 178 placentas of twins born in Tokyo in 1961-1982 were examined. Only just over one third were dichorionic, 110 being monochorionic and DZ twins were estimated to account for 24.7% of the pairs. The lower frequency of DZ twinning in Japan is attributed to lower gonadotropin values in Japanese women as compared to European, American, or African women. High fetal morbidity was found in monochorionic twins and this is attributed to a frequent occurrence of vascular anastomoses.

Old-age twinning rates were evaluated over a period of 250 years (1611-1860), from 80,256 parish records of baptism in a church office in Görlitz, East Germany. Two periods with high and two periods with low twinning rates were observed. Twinning rates were relatively stable in spring and fall, but varied greatly in winter and summer.