A retrospective review of triplets delivered at a Boston perinatal center from 1977 to 1986 was performed. Comparison was made between this group (study group) and previously published data on triplets in our institution (control group). Since 1977 there was a more liberal use of abdominal delivery. Cesarean sections (CS) of all triplets with malpresentation was our protocol. Of the 15 sets of triplet pregnancies in the study group, 11 were delivered by CS and 4 by vaginal delivery, vs only 1 CS in the control group wich consisted also of 15 triplets. The corrected mortality rate in the study group was lower than in the control group (2.6% vs 7.1%) but did not reach statistical significance. Apgar scores at 1 and 5 minutes were significantly higher in the study group (P < 0.002). Apgar scores for the third triplet were also higher in the study group (P < 0.05). In comparing the combined mortality and morbidity between the study group and the control group, no difference was found in the first triplet, but those of the second and third triplets were significantly lower in the study group. Of interest is the finding that the combined mortality and morbidity was not different statistically among the first, second, and third triplets in the study group, while in the control group an increase from the first to the third triplet was noted (21%, 31%, and 43%, respectively). A more liberal approach toward abdominal delivery of pregnancies of higher fetal number is advocated.

Certain congenital malformations occur in excess among twins and also among first-degree relatives of twins. In the general population, these anomalies are familially associated with each other, and, like twinning, familially associated with unusual brain function asymmetry. They affect structures built by fusion of bilateral embryonic halves and remodeled under major influence of neural crest mesenchyme. This conjunction of associations suggests that twinning, symmetry development, and this group of malformations might share causai elements at least some of which are heritable. The problem here is the absence of zygosity differences in these relationships, because of which they cannot be explained within the biology of twinning as it has been understood. A potential resolution is offered by way of a mechanism common to MZ and DZ twinning, involving a relationship between oocyte organization and the determination of body symmetries.

The condition of low birth weight is compared in twins and in singletons in terms of birth weight distributions and with respect to factors such as the incidence of sillbirths, length of gestation, maternal age, parity, and legitimacy. In the light of demographic, biological, and developmental considerations, it is concluded that low birth weight in twins is a different condition from low birth weight in singletons and should be dealt with independently, especially in view of the different implications for child growth and survival.

Among 93 cases of thalidomide embryopathy ascertained in Brazil, one pair of female dizygotic twins was found. One of them presented complete paraxial hemimelia in the right arm while the other showed a triphalangeal thumb at the left hand and had duodenal stenosis. Of the eight dizygotic twin pairs exposed to thalidomide in utero described thus far, only four were concordant for the type of malformation.

To search for an association of twin zygosity with tooth size, 56 dental variables measured from 65 pairs of twins (43 MZ, 22 DZ) were studied. Results of the t′ test for equality of the means showed no association of zygosity with any of the variables in males or in females. Results of the F′ test for homogeneity of total variances between zygosities showed evidence for unequal total variances in 15 variables in males and 13 in females. Sex influence was further noted on the association of zygosity with the variance of tooth size. Where total variances were unequal, genetic variance estimates differed when only the within-pair mean squares were used and when combined estimates designed to be unbiased by differences in environmental variances were used.

A review of the case histories of 471 diabetic children admitted to a children's hospital during the decade 1960 to 1970 showed that the proportion of diabetics among hospitalized Negro children was significantly lower than that among white children (3.8 Negro vs. 10.7 white per 1000 admissions same ethnic group, P < 0.005). However, the proportion of mild diabetes, characterized by absence of ketosis and no insulin requirement, was higher among Negro (18%) than among white diabetic children (0.5%). These differences could not be explained by differences in environmental factors considered. It is suggested that genetic factors may account for a substantial part of this Negro-white difference.

A twin study was undertaken with the twofold aim (a) of studying the hereditary behaviour of digital dermatoglyphic traits both at the qualitative and quantitative level, and (b) of working out a method for discriminating MZ and DZ twins by means of fingerprints.

Fingerprints of 50 MZ (25 ♂ and 25 ♀) and 50 DZ (25 ♂ and 25 ♀) twin pairs were thus examined and analyzed by means of a special methodology and of a 7044/K32 IBM computer.

The qualitative analysis has shown a significantly higher concordance in MZ than in DZ twin pairs, with a certain variability of single finger concordance values. The quantitative analysis has shown significantly higher correlation values in MZ than in DZ twin pairs, with very limited confidence intervals in the former. Single ridge counts apparently behave as cumulative counts on the five or ten fingers, although with an obviously higher random variability.

Digital dermatoglyphics thus appear to show practically complete genetic conditioning, which, rather than at a cumulative level for the ten fingers, as is largely believed, appears to act on single finger quali-quantitative traits. The total finger ridge count, rather than a trait, only appears to be a useful, but artificial cumulative value. Actually, applied to the diagnosis of zygosity, it provides, by itself, a fairly high, general probability (0.86) of a correct diagnosis.

Behavioral development during childhood is examined in relation to recent concepts and data from evolutionary theory and developmental genetics. The epigenetic framework of Waddington is proposed as a powerful tool for analyzing the progressions in behavior, particularly for recognizing that development involves coordinated pathways of change over time. Many of these pathways appear to depend upon the activity of timed gene-action systems that switch off and on according to a predetermined plan. Behavioral development thus gives expression to the dynamics of preprogrammed change; and in this perspective, behavioral discontinuities may be as strongly rooted in the epigenetic ground plan as the continuities are. The present paper aims to pull together some common themes from different areas that bear on the central issues of behavioral development—the neural foundations, the time course followed, the interplay of maturation and experience, the extent of preorganization furnished by the genetic program, and the adaptive significance of such behaviors in an evolutionary perspective. The final section touches on some hypotheses drawn from developmental neurobiology and developmental genetics that may enrich the analyses of human behavioral development.

The retardation of fetal growth in twin as compared to singleton gestations may be due to maternal and/or placental factors. The separate birthweights and related placental weights of 487 dichorial twin pairs were recorded, and the heavier placental weights of firstborns in comparison with second-borns were found to be related to the heavier birthweights of firstborns compared to second-borns. The lighter placental weights of firstborns compared to second-borns were found to be related to the lighter birthweights of firstborns compared to second-borns. Obviously, the placenta itself may may very well be the cause of the retardation of fetal growth in twin gestations.

A case of monozygotic male twins discordant for skeletal and cardiac defect is reported. One twin had the hemifacial microsomia type of the oculo-auriculo-vertebral dysplasia. The cotwin had no asymmetry of the face and normal ears, but preaxial polydactyly and ventricular and auricular septal defects. The cotwins were concordant for craniostenosis with a ridge metopic suture. Karyotypes were normal.

A survey of triplet pregnancies in Linköping, Sweden, 1973-1981, showed a low perinatal mortality (4%) and low morbidity possibly due to prophylactic bed rest and tocolytic treatment. All children were followed at child health clinics. In one child, a persistent growth retardation was recorded at 4 years of age. No psychomotor deviations were found in the group. An interview concerning social and economic factors after delivery was carried out. The answers revealed considerable strain in daily life for all families.

During the 10-year period, 1975-1984, 105 triplet pregnancies were delivered at Harare Maternity Hospital, Zimbabwe, among 286,338 pregnancies in the Greater Harare Unit, giving an incidence of triplets of 1:2,727. The mean gestational age at delivery was 32.5 wk with 81 women (77.1%) delivering before 37 wk. Primigravidas delivered at a significantly earlier mean gestational age (P < 0.05) and had a higher perinatal mortality (P < 0.001) compared with grand multigravidas. Of the 315 babies, 277 (87.9%) weighed < 2500 g. The overall perinatal mortality rate was 327‰, with a pernital mortality rate of 146‰ for infants weighing ≥ 1000 g. Women hospitalised for bed rest during the antenatal period had fewer perinatal deaths compared with those diagnosed during the antenatal period, but not hospitalised for bed rest (P < 0.02). No difference was found in the mean gestational age at delivery or the mean birth weights between these two groups. Among infants ≥ 28 wk gestation there were fewer perinatal deaths in triplets delivered by cesarean section compared with triplets delivered vaginally (P < 0.0004). This suggests that cesarean section may offer the optimal mode of delivery in triplet pregnancy.

Other than a specific case of concordant Vitiligo in MZ twins, the development of which has been followed for more than 11 years up to now, MZ twins suffering from Vitiligo have been described only three times. In all the four cases, three were concordant, one discordant; this last was accompanied by a discordant disorder of basal metabolism, by hyperhydrosis and exophtalmus. The greater degree of concordance found up to the present day, notably contrasts with the relative extreme rarity of familiar Vitiligo.

The probability of a twin birth depends strongly and almost equally on the age of the mother and on the number of children she has had. Even when these variables are held constant, the frequency of twinning varies between countries or geographic regions and between years or decades. This variation has been thought perhaps to result from economic and environmental factors, but another explanation can be suggested.

Bulmer (1959) found that twins are frequent among the earliest conceptions after marriage. Eriksson and Fellman (1967) found twins to be frequent among illegitimate births and suggested that the mothers of twins conceive more easily than other women; in other words, that they are more fecundable. We can present some new evidence for this hypothesis, and we believe that high fecundability in the mothers of twins can account for variations in the twinning rate.

Fig. 1 shows the wide range of twinning rates in the US white population, in different parts of the country and for three periods, centering on 1937, 1954 and 1964. The nine geographic divisions are shown in descending order according to the twinning rates in 1937. The two regions at the right, with the lowest rates in 1937, had nearly stable twinning rates over the three time periods. They are the oldest and most urban parts of the country.

The rate of twinning, both MZ and DZ, as determined by the Weinberg formula, remained fairly static in Scotland up to 1958, when it fell (Fig. 1), due to a fall in the DZ twinning rate. These figures are based on the returns from the Registrar General for Scotland.

As age has a marked influence on the incidence of twinning, it was thought that the difference might be due to a reduced number of older women having babies. However, this does not seem to be the whole answer (Fig. 2). The most marked change would be expected in the women over 35, but this did not occur. It was not possible to look at other factors such as parity, social class and height in the figures for Scotland. The details of all births in the City of Aberdeen are known because of the very high hospital delivery rate, and more detailed studies have been made on the twinning rates for Aberdeen.

These figures, again, showed that from 1959 onwards there was a fall in the twinning rate in Aberdeen and this was due to the fall in the number of DZ twins. The fall in incidence occurred both in Primigravidae and in multigravidae (Tab. I), and more in older than in younger Primigravidae (Tab. II), but there was little difference by age in the fall in multigravidae (Tab. III).

Another factor which is related to the incidence of twinning is the height of the mother. This, in turn, reflects the social class, as tall women are more commonly from the upper, and small women from the lower social classes. The rate of twinning in Aberdeen was highest in the tall women before 1954 (Tab. IV). The rates in all women fell from 1954 onwards, but most dramatically in the tall women. The rates from 1959 onwards show very little difference according to height.

The NHLBI Twin Study is a longitudinal study of cardiovascular disease risk factors in 514 pairs of white, middle aged, male, veteran twins. The initial examination took place between 1969-1973. Ten years later, 81% of the living cohort returned for a second examination. Data collected up to 30 years prior to recruitment for the initial examination were used to characterize participants and nonparticipants; data from the initial examination were used to characterize returnees and nonreturnees to the second examination. Participants had significantly lower diastolic blood pressure and higher socioeconomic status than nonparticipants as measured thirty years earlier. Between the first and second examinations, the mortality of participants was less than 50% of the mortality of nonparticipants. Returnees to the second examination had a better health profile at the initial examination than nonreturnees, with significantly lower levels of cigarette smoking, glucose intolerance, hypertension, and diabetes and higher levels of pulmonary function. However, returnees were more obese than nonreturnees. Thus, this study of cardiovascular disease risk factors in twins appears to be affected by response bias in a way similar to studies of individuals. Additional analyses of biases that may affect the genetic component of the study indicated that factors related to classical twin analyses were relatively unaffected by selection.

Sixteen pairs of term discordant twins (weight discrepancy of more than 20% when the, lighter twin was compared to the heavier) were evaluated at birth. Weight, length, head circumference, anterior fontanel area, and combined ossification of the knee epiphyses were measured, and ponderal index (weight/length ratio) calculated. The most severely growth retarded infants had markedly decreased ossification and larger anterior fontanels.

Eleven pairs had physical measurements at one year of age. With individual exceptions, the lighter twins at birth remained smaller in all dimensions. Despite these persistent differences between twin pairs, the values for length at one year of age were within normal limits for both the heavier and lighter twins. Infants without ossification at birth had a greater incremental linear growth by one year than those infants with ossification.

A study of 111 mothers of twins in Nottinghamshire, England, in 1981-82 showed that at least 12 had used ovulation stimulants, compared to 2 of 102 mothers of singletons. Thus, the use of ovulation stimulants increased the twinning rate of this population by about 10 percent; this may explain the recently noted levelling off in the secular decline in twinning rates. In contrast to a recent study in France, no association between twinning and prior use of oral contraceptives was seen.

A high frequency of twin births has been observed in Linha São Pedro, a small settlement which belongs to the city of Cândido Godói, located 524 km Northwest from Porto Alegre, Rio Grande do Sul, Brazil, in an ethnically homogeneous population of German descent restricted to a small geographic region. From 1990 to 1994, the proportion of twin births in Linha São Pedro was 10%, significantly higher than the 1.8% rate for the state of Rio Grande do Sul as a whole. Genealogical analysis showed a high recurrence of multiple births within families, as well as a high level of inbreeding in the community. Zygosity data indicated that 9 of the 17 pairs of twins studied (53%) were dizygotic. No external environmental factors were detected that could be influencing the appearance of this characteristic. This preliminary investigation confirmed the presumed existence of a high twinning rate in the community. The high familial recurrence and the high inbreeding rate suggests the presence of genetic twinning factors. Complementary studies of twins that have yet to be evaluated and the search for additional risk factors, as well as linkage studies, should contribute to a further understanding of the biological factors related to twin births in the human species.

1. Investigations carried out on twins and the families have revealed that within the major group of brain gliomatosis and glioblastomatosis there is a minor group (up to day) of accumulated familiar clinical cases.

Topographically, they are tumours localized in the region of the ventricular germinative centres, that is to say, in the background of the brain (they are not cortical gliomas!). They depend on the disturbances and inhibition of the matricial cellules on the ventricular wall towards the cerebral cortex. Histologically they are considered as dysplasias with a blastomatosis character, that is to say, neoplastological productions on an heredogenetic basis the cause of which lies in histological disorders, disontoge-netic, and therefore, congenital.

2. A work hypothesis is settled and established according to wich 2 factors at least are necessary for the formation of a tumour: a local one, hereditary: the neuroglial dyplasia in the region of the ventricular germinal centres with a tendency to tumours degeneration; and another or several general factors dependent on endogenous and exogenous influences, which on account of a disturbance of the general constitution (for example, hormone mechanisms of puberty, of the premenopause and of the beginning of the involution) which would allow the tumour to develop starting with the tumours genetic disposition.

3. At the present time it is not known whether the genesis causing this neuroglial dyplasia and the concomitant malformations of other organs, sonsists in the mutation of a gen, since so far the gen is ignored as well the pleotropic effet of the action developed by the gen.

4. The fact, that within the major group, in the majority of cases evidently not hereditary of gliomatosis and glioblastomatosis, there should appear a minor group, hereditary, must be considered, within the general investigation of the neoplasias, as a further proof that the essential thing of the hereditary predisposition to the development of tumours, must be considered as a specific local factor.

5. The attention is called to the possible existence, within the astrocytomes of a small hereditary group of familial cases.

6. The casuistry so far known has been enlarged with 20 cases (discordant) of twins and 6 observation in families which were compiled at the Neurological Clinic of Miinster Westfalen University.