Familial aggregation for disease is important; strong familial risk factors must exist even if the increased risk to a relative of an affected individual is modest. It is in practice difficult, however, to conduct studies in genetic epidemiology which conform to strict epidemiological principles. For twin studies there are two major questions: Are twins ‘no different’ from the population on which inference is to be made? Are study twins ‘no different’ to twins in the population? The importance of each question of bias depends on the scientific question, the trait(s) studied, and sampling issues. The strength of the twin design is its ability to refute the null hypothesis that genetic factors do not explain variation in a trait. Following the Popperian paradigm, alternate hypotheses should be considered in depth (both theoretically and empirically), with a design and sample size sufficient to exclude not just naive explanations. More sophisticated statistical techniques are now being applied, so the philosophy, assumptions, and limitations of statistical modelling must be appreciated. The concept of ‘heritability’ has, in the past, been misunderstood and misused. New advances in DNA technology promise to revolutionise epidemiological thinking, and so case-control-pedigree designs may well become standard tools. The strengths and limitations of studies based on related individuals as the sampling unit are discussed.

A comparison of physical capacity, (measured by vital capacity, muscular strength and physical work capacity) in twin boys and controls failed to indicate significant differences. Intrapair correlations showed the MZ twins to be much more similar than the DZ twins in all the capacity measures. The correlations were lower, however, for both MZ and DZ twins for physical work capacity than for the other two capacity variables. When amount of physical exercise during leisure time is kept under control, the DZ twins tend to be more similar for physical work capacity or muscular strength, and the correlations tend to be of the same magnitude for MZ twins. Physical work capacity therefore appears, in this study, to be a more environmentally influenced variable than either vital capacity or muscular strength.

In order to establish a protocol considering the definition, diagnosis, and management of growth-discordant twin gestations, a questionnaire was sent to 96 authors of twin-related obstetric articles. The views of the 61 responders comprise this international census survey. The data suggest that a clear cut-off value for discordancy is still needed; however, the data indirectly supported a two-grade definition, namely, mild (> 15% and < 25% birth-weight disparity) and severe (> 25%) growth discordants. Expectant management was advocated by the majority of participants with out-patient follow-up for mild discordants, while severe discordants may preferably be hospitalized. Follow-up should be done by non-stress testing (daily - 2/wk), biophysical profile (1-2/wk), Doppler velocimetry (1/wk - bi-weekly) and sonographic biometry (bi-weekly). The opinions considering termination of pregnancy because of intertwin growth discordancy were divided; however, discordancy per se, was not considered an indication for cesarean delivery. An adapted management flowchart that summarizes the survey's data is presented and may be used as a standard for future investigations.

In estimating twin frequencies from birth and mortality data, it is necessary to make some statistical corrections, the extent of which is demonstrated for the general population of the United States. In this population, twins constitute 2.19 per cent of all babies born since 1928. This rate is reduced to about 1.9 per cent by excess twin mortality within the first year of life, while the 2:1 ratio of same-sex to opposite-sex pairs observed at birth remains virtually unchanged. Later mortality reduces the proportion of males, but not to such an extent — even at age 75 — as to necessitate modification of the 1:1 sex ratio in estimating the proportion of monozygotic pairs by Weinberg's differential method.

After the first year of life, there is no evidence for a significant difference between the mortality rates of twins and nontwins, so that the proportion of twin individuals in the population may be assumed to remain nearly the same at all ages. However, as pairs are broken by mortality and migration, the number of intact pairs is reduced at successive ages. Among people who survive to an advanced age, the relative frequency of pairs represented by at least one twin may be nearly twice as great as at birth. For comparative purposes, therefore, the most useful way to express twin data is in terms of individuals rather than in terms of twin pairs.

In recent years, it has been realized that some infants of frankly alcoholic mothers escape the stigmata of fetal alcohol syndrome (FAS) and others have only a few of the characteristics. These infants are thought to display fetal alcohol effects (FAE). The controversy regarding the amount of alcohol a woman can safely drink during pregnancy and the effects of timing and individual physiology on producing FAS vs FAE in the infant are important questions which can perhaps be partially answered through examining twin pregnancies and offspring. Data are presented regarding the long-term growth and development of a set of dizygotic twins, one with FAS and one with FAE, delivered to a mother who drank moderate amounts of alcohol during pregnancy. The variation in the degree of abnormality found in dizygotic twins exposed to similar amounts of alcohol at the same time during gestation indicates that differences in fetal susceptibility to ethanol dysmorphogenesis are of prime importance to the expression of the fetal alcohol syndrome.

Recent changes in the estimated incidence of monozygotic twinning in 15 European populations are described. The overall trend was an increase in the monozygotic twinning rate (MZTR) since the 1960s, particularly in those countries in which the use of oral contraceptives (OC) was widespread. A slower increase or even a decrease in the MZTR was observed in countries with low use of OC. Some countries, eg, Sweden, demonstrated an unexpectedly sharp increase since the 1960s. In Poland and the Federal Republic of Germany the MZTR was already strongly increasing as early as in the 1950s, clearly before the introduction of the pill. The influence of several other factors on the MZTR is discussed, such as toxic and teratogenic agents, pelvic infection diseases caused by the use of intrauterine devices, the increased use of ovulation inducers and neuroleptics as well as changes in the registration of perinatal deaths.

To evaluate the relationship between genetic factors and back pain, 5029 MZ and 7876 DZ twin pairs were investigated by a questionnaire. The data were analyzed with regard to physical symptoms, eg, back pain, and certain work conditions. Pain was reported by about 17% of the male and 13% of the female twins in the material. The occurrence of back pain was strongly associated with work load, especially among the male twins. Twin concordance regarding back pain was considerably higher in MZ than in DZ twins. Of four groups who were studied, statistically significant differences between the two twin categories were observed in three cases. This result supports the assumption that a relationship exists between genetic factors and the occurrence of back pain. Official registrations for sick-leave pay in a sample of 247 twins confirmed the interview information on back pain. Just a few cases were wrongly classified, ie, they were sick-listed because of back pain but had stated no back pain in the questionnaire.

A formal model is presented for the analysis of longitudinal twin data, based on the underlying analysis-of-variance model for repeated measures. The model is developed in terms of the expected values for the variance components representing twin concordance, and the derivation is provided for computing within-pair (intraclass) correlations, and for estimating the percent of variance explained by each component. The procedures are illustrated with physical growth data extending from birth to six years, and concordance estimates are obtained for average size and for the pattern of spurts and lags in growth. A test of significance is also described for comparing monozygotic twins with dizygotic twins. The procedures are particularly useful for assessing chronogenetic influences on development, especially whether the episodes of acceleration and lag occur in parallel for genetically matched twins. The model may be employed with psychological data also.

In order to more adequately characterize patterns of intrauterine growth retardation in twins, the mean birthweights of all nonanomalous white or black twins born between 24 and 41 weeks of gestation and surviving until discharge over an 11-year period (547 infants) and all similar singletons (19,072 infants) were compared by completed weeks of gestation. Between 24 and 35 weeks of gestation, the mean birthweights for the 547 twins and the 19,072 singletons were comparable and did not consistently differ statistically. From 36 to 41 weeks gestation, however, the difference became large, consistent, and statistically significant for each week at P < 0.0001. This difference was present among all subgroups of twins, ie, in all males, females, blacks, and whites; it was still evident when the sample was further stratified by both race and sex (black males, white males, black females, white females). These data suggest a pattern of growth retardation in twins compared to singletons which is large, consistent, and statistically significant beginning at 36 weeks gestation. Clinically, these data also suggest the need for ultrasonic examination early in gestation (24-32 weeks) to document normal growth and to provide baseline data, and show the importance of such monitoring later in gestation, specifically after 36 weeks.

Twinning rates in all of Japan for 1951-1968 and 1974-1990 were analyzed using data from vital statistics of Japan. The twinning rate per 1,000 births was 6.43 in 1951 and remained nearly constant until 1968, then decreased to 5.79 in 1974 and gradually increased to 7.00 in 1990. The MZ twinning rate increased slightly up to 1966, but decreased thereafter, whereas the DZ rate declined over the entire period. As for maternal age, the DZ rate increased up to the age group 35-39 and decreased thereafter. The same tendency is seen in the MZ rate, but the maternal age effect is less marked than in DZ twins. The same tendency is also seen in the overall rate for 1975-1985. As for geographical variations, the MZ and DZ rates were computed in each prefecture for 1955-1959 and in 1974. The DZ rate increased from a low level in the southwest of Japan to a high level in the northeast for both periods, whereas the MZ rate was rather constant in 1974 throughout Japan. As for seasonal variation, the highest rates per 1,000 births for MZ(4.56) and DZ(2.20) twins were seen in April, with the lowest rate in September (3.69) for MZ twins and in July (1.71) for DZ twins.

Twin to twin transfusion, complicated by acute polyhydramnios in a monozygous twin pregnancy, is a difficult clinical problem. A precipitous course usually results in termination of the pregnancy within a few days and often is associated with a high perinatal mortality rate. Two cases are presented that were treated with repeated amniocenteses for the relief of extreme abdominal discomfort and to prevent imminent premature labor. The amount of amniotic fluid removed each time varied from 300 cc to 1200 cc, which was enough to relieve symptoms but not enough to induce uncontrolled uterine activity. A total of 3500 cc and 4750 cc of amniotic fluid were removed from the first and the second patient, respectively. The procedure was found to be safe and resulted in prolonging the pregnancies by 14 and 11 days, respectively. This management, with the addition of tocolysis and close fetal surveillance can offer some hope in an otherwise hopeless situation.

The birthweights and placental weights of 3000 singletons, 1500 twin pairs and 67 triplets are studied in relation to the gestational age. From 30-32 weeks onwards, newborns of twin- and triplet gestation show lower birthweight as compared to singleton newborns. Placental indices (placental weights related to birthweights) are about alike in singletons, twins and triplets. From about 24 weeks onwards placental weights of twin and triplet newborns are smaller as compared to those of singletons. Obviously, children in multiple gestations become growth retarded, preceded by and very likely due to poor early placental development (placental crowding of the uterus).

Over the past 50 years a large number of methods have been proposed for estimating heritability from twin studies. The present paper describes the most commonly cited of these estimates as a first step in evaluating their usefulness. A critical review will then follow.

It is estimated that at least one dizygotic (DZ) twin maternity in twelve is preceded by superfecundation (the fertilization of two ova by sperm from different coitions). Presumably this parameter varies from population to population eg. with coital rates and rates of double ovulation. Sometimes superfecundation occurs by two different men. The frequency with which this occurs must depend on rates of infidelity (promiscuity). It is suggested that among DZ twins born to married white women in the U.S., about one pair in 400 is bipaternal. The incidence may be substantially higher in small selected groups of dizygotic twin maternities, eg. those of women engaged in prostitution.

Accurate, unbiased malformation rates in twins must be obtained unselectively from population-based studies that include livebirths and stillbirths after a thorough ascertainment of cases. This type of study was conducted in Los Angeles County, California, where 28 twins with a neural tube defect (NTD) were identified. The prevalence in twins (1.6/1,000) was significantly higher than in singletons (1.1/1,000). The study then was expanded to include population-based data from the Medical Birth Registry of Norway which has a comparable overall NTD prevalence (1.0/1,000) and twinning rate (2%). The combined material shows a higher prevalence of anencephaly and encephalocele but not of spina bifida in twins compared to singletons. The male/female ratios in total twin and singleton cases were comparable (0.8), but varied by specific defect. Like-sex twin females appeared at highest risk for NTD as well as for fetal death.

This study supports theories which associate NTDs with monozygotic twins, either through developmental disruptions that cause susceptibility to environmental agents or through a common etiology. Furthermore, it suggests that twins and singletons differ in their response to etiologic factors for the development of NTDs and that the development of each type of NTD may be related to different factors.

Male, monozygotic twins (six pairs) were repeatedly tested before and after d-amphetamine, l-amphetamine, or placebo administration. Drug effects on cognitive, psychomotor, personality, mood, and pain variables were assessed. Members of a twin pair tended to respond similarly on several tests under placebo conditions, indicating genetic determination of the behavioral variables. In addition, cotwins tended to show similar responses to amphetamine as measured by one test of cognitive function, by several mood and personality variables (hostility, autonomic arousal, friendliness, feelings of tension and loss of control), and tended to have similar plasma levels of both amphetamine isomers. Although shared environmental effects cannot be ruled out, the results are consistent with genetic mediation of a variety of behavioral effects of amphetamines.

Data on alcohol use and smoking habits was available from the 1975 questionnaire of the entire cohort. Prior to pairwise analyses, the data of individuals was compared to that of age-sex matched groups of pairs reared together. The early separated twins had a higer alcohol consumption, while for smoking only slight differences were observed compared to twins reared together. Probandwise concordance rates were computed from smoking status (ever smoker/never smoker), alcohol use (user/nonuser) and “heavy” drinking (half-bottle of spirits on one occasion at least once a month). The following results were obtained in those pairs with the environmental dissimilarity score > 15:

Reference intervals for human placental lactogen (hPL) and dU-estrogens (dU-E) in uncomplicated twin pregnancies are found to be higher than singleton pregnancies and considerably wider. Significantly more monozygotic than dizygotic pregnancies, and significantly more monoplacental than diplacental pregnancies showed hPL values below the median on the normal range curve. The same was not found for dU-E. Significantly more growth-retarded fetuses were found in monoplacental than diplacental pregnancies. The benefit of measuring the two parameters in order to identify the intrauterine growth retarded fetuses were evaluated in terms of sensitivity and specificity. Both parameters were found less suitable for the purpose.

The dizygotic twinning rate in Western Nigeria is the highest on record (45—50 per mil maternities). It is suggested that, rather than to peculiarities in the population structure or to genetic factors, such a high incidence might be due to the presence in the diet of estrogen-like substances.

The risk for specific defects among twins compared to singletons was studied using data collected by the Spanish Collaborative Study of Congenital Malformations (ECEMC). A total of 136 twins had a major and/or minor congenital defect. The overall rate of congenital defects in twins (2.37%) did not deviate significantly from the rate in singletons (2.21%). Like-sex (LS) and male-male (MM) twin pairs had a slightly higher rate of birth defects than unlike-sex (US) and female-female (FF) pairs, respectively. Defects of the central nervous system, cardiovascular system and genitourinary system were significantly more frequent in LS twins than in singletons, with relative risks of 2.8, 2.5 and 1.6, respectively. No significantly increased risk was found among US twins. Among defects of the central nervous system, the rates of anencephaly, encephalocele and hydrocephaly were significantly higher in total and LS twins; however, no significantly increased risk for spina bifida was observed when compared to singletons. MM twins were also 1.9 times more likely to have hypospadias, but the risk among males of male-female (FM) pairs was decreased.