Twin seasonality in a rural Catalonian population

The seasonality of twinning in the Spanish populations has not been studied until now. Differences between seasonal distribution of the twin conceptions and those of the single births have been observed in other populations. The aim of this work is to explore the frequency of twinning in a rural population from Catalonia during the nineteenth century, as well as the seasonality patterns characterizing each of the twinning types. Data corresponding to all births recorded at Tortosa (South Catalonia) from 1801 to 1900 have been analyzed in order to study the twinning distribution. The distribution of the moving averages of the monthly rates of twins shows a peak in autumn. Twinning distribution differs from the total births' distribution in Tortosa. This fact is very clear in the case of unlike-sexed twins that have their greater incidence in the last quarter of the year, while the total maternities have their peak in the first one.     

The epidemiological characteristics of twinning in Northwest India

The data on twin births from four different places in Northwest India were analyzed to study epidemiological characteristics of twinning. Gujjars manifested the highest incidence of twinning (30.2 per 1000 births). The twinning rate at Amritsar for the year 1987 was 19.20. At Bathinda and Jammu, the average twinning rate over the period 1984–93 were 10.70 and 11.40 respectively. Stillbirth rate among twins was much higher in Gujjars as compared to other three samples. Regional trends of twinning rate showed the highest incidence in the state of Uttar Pradesh, while the lowest in Tamilnadu. There were no significant differences between states for MZ twinning rate, while differences in the DZ twinning rate were significant in some instances. Maternal age and parity specific twinning rate showed the highest incidence at parity 4 and in the maternal age group 30–34 years. There was evidence of both seasonality and secular trends in twin births. The highest incidence of twin births over the period 1984–93 was noted in the summer season followed by rainy season, while the lowest in autumn. The average incidence of twinning in the Jammu region decreased from 13.76 during the years 1984–89 to 9.07 during the year 1990–93.     

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.     

Twinning rates in a rural area of Bangladesh

In this study we investigate the incidence of twin births over a period of 16 years in a rural area of Bangladesh using data from the Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research. Over the study period twinning rates fluctuated between 7.8 and 11.2 per 1000 live births. The twinning rate was strongly correlated with maternal age; the rate for mothers over 35 years of age was about 3 times higher than for mothers younger than 20 years. The variation in twinning rate with maternal age is due to the variation in dizygotic twinning; the rate of monozygotic twinning is almost constant for all ages. Twinning rates were higher in the treatment area than in the comparison area after controlling for maternal age and parity. The rates were lower for monozygotic twinning and higher for dizygotic twinning in the treatment area than in the comparison area. Seasonality was observed for both twins and singletons, but the peak for twinning precedes that for singleton births by more than a month.     

A familial association between twinning and upper-neural tube defects.

An increased twinning rate has been observed in the near relatives (sibs, parents, and aunts and uncles) of probands with neural tube defects (NTDs) occurring at the level of the 11th thoracic vertebra and above (upper NTDs). The twin rate was more than double that of the near relatives of probands with lower NTDs and of those of probands with Mendelian disorders (the controls). The excess twinning was same sex and can therefore consist of either MZ or same-sex DZ twins. Furthermore, upper-NTD families with twins had a higher NTD-sibling occurrence rate than did families without twins. These findings, if corroborated, may imply an etiology common to twinning and NTDs and can perhaps be applied in counseling NTD families.     

A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

A loss 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.     

Twinning rate in spontaneous abortions.

An unselected series of spontaneous abortions and their mothers were karyotyped with Q-bands to obtain a frequency of twin conceptions lost during the first trimester. Among 661 spontaneous abortions, 15 twin pairs were identified including two sets of conjoined twins. Analysis of Q-band variants permitted the exclusion of cases with two cell lines that could be attributed to maternal contamination or mosaicism. The twinning rate among spontaneous abortions was 1/44 compared with 1/103 live births and stillbirths in the Ontario population. If Weinberg's differential method is applied to these data, the frequency would be as high as 1/30 under the assumption that the incidence of monozygotic twins among abortions is the same as that for live births.     

Seasonal variation of livebirths, stillbirths, extramarital births and twin maternities in Switzerland.

A study was made of the seasonal variation in all births, and births according to marital status, multiplicity and birth status (live and still) in Switzerland recorded between 1876 and 1990. To obtain seasonal variation in as pure as possible form, our analyses are based on rates. When comparing the seasonality in data sets showing markedly different levels, standardised indices were used. Assuming the length of pregnancies with twins to be about one month shorter than for pregnancies with singletons, lagged twinning rates were calculated but, in comparison with actual twinning rates, the general seasonal variation remained. Therefore, this study was based on actual twinning rates. A monotonic increase in the amplitude of the seasonal variation in general births was noted for the period 1876-1930, with strong seasonal variation holding for 1921-1980. After that, a marked decline in the amplitude can be observed. Seasonality of both all births and twin maternities showed very similar pattern for the periods 1876-1930 and 1969-1990, with maxima in the spring (March-May) and troughs in late autumn (October-December). Twin maternities showed a strong seasonality for the period 1876-1930, being about 20% higher in March than in October. The twinning rate in the period 1876-1930 was about 2.6 per thousand units higher than in the period 1969-90. For twin maternities there was also a stronger seasonal variation during the earlier period than during the later one. The pattern of the seasonal variation for extramarital births, showing a maximum in February (conceptions in May-June) and a minimum in August (conceptions in November-December) with a difference of no less than 24% was more marked than for the marital births. It seems likely that this seasonality of extra-marital maternities was due mainly to seasonal variation of coital rates and multiple ovulation in the early summer months coinciding with optima of light, temperature and food supply. A strong reduction in the rate of stillbirths (gestational age more than 29 weeks) was observed during the twentieth century. The stillbirth rate declined from about 40 per 1000 in the 1870s to fewer than 5 per 1000 in the 1980s. Irrespective of this strong decline in the stillbirth rate, the same seasonal rhythm was noticed throughout the period with high stillbirth rates among births around March and low rates during the summer and autumn.     

Monthly trend and seasonal variation in twinning rate in Japan, 1975–1994

We examined birth records from Japanese statistics, 1975–1994, to investigate the seasonality of twin births. We could identify 198 924 pairs of twins (97.9% of all the registered twin records) and estimated the numbers of mono- and dizygotic twin pairs. The seasonal index of the twinning rate for each month was calculated by dividing the crude rate by the estimated trend value for the month. There were significant variations in the seasonal index for overall, dizygotic and monozygotic twinning rates. Peak months with values more than 3% higher than expected were July and October–December for dizygotic twins, and April and June for monozygotic twins; these seasonalities were statistically significant by analysis of variance and the patterns were similar in recent years, with a sharp increase in the total twinning rate. When observed year-by-year, however, there were years that did not show these typical seasonalities. It is suggested that the mechanisms for probable seasonal variations in twinning rates are different for dizygotic and monozygotic twin pregnancies, and that factors involved in these variations are not effective every year. Received: 2 September 1998 / Revised: 6 May 1999 / Accepted: 26 May 1999     

Paternal familial twinning: hypothesis and genetic/medical implications.

The phenomenon of paternally dependent familial twinning has been known in human and animal genetics since the 1920s, but still remains without any theoretical explanation and is indeed a neglected field of inquiry. Over the last two decades investigations in reproduction biology have discovered the significant role of multiple paternally dependent errors in fertilization including androgenic triploidy and moles. We suggest the hypothesis that the fathers of twins in the relevant families carry gene variants that increase the probability of dispermy, diplospermy and male pronucleus heterochrony as well as involvement of two male pronuclei in the fertilization of two female meiotic products. Any resulting twins would be an exceptional intermediate between MZ and DZ twins - and might properly be described as "sesquizygotic" (SZ). Paternal familial twinning may also go together with infertility due to triploidy, moles and chimerism. The hypothesis: (i) places the curiosities of paternally derived twinning within the framework of current knowledge of reproductive genetics and verifiable phenomena; (ii) predicts the existence of families in which twinning is associated with reproductive abnormalities; (iii) predicts an occurrence in relevant families of the third and intermediate category of SZ twins. Families with paternal twinning may thus provide the natural selective system for the search of unusual cases of primary chimeras, the frequency of which is still unknown.     

Neural tube defects among twin births.

To obtain accurate, unbiased rates of neural tube defects (NTDs) in twins, we conducted a population-based study that included live births and fetal deaths in Los Angeles County, California, ascertaining cases by multiple methods. Twenty-eight twin cases yielded a prevalence-at-birth of 1.6/1,000 twin births, which is significantly higher than the singleton prevalence of 1.1/1,000 births. In twins compared with singletons, the prevalences of both encephalocele and anencephaly are increased, whereas spina bifida is decreased. The twin case male/female sex ratio (.55) is lower than the singleton case sex ratio (.77). Concordance is relatively low at 3.7%, but appears to be higher than recently reported recurrence risks in other low prevalence areas. Stillbirths were most common among female cases and like-sex twins. Our study tends to support proposed etiologic theories associating NTDs with females or monozygotic twins, or both. There is increasing evidence that the etiology of NTDs may differ in high and low prevalence areas. We suggest also that twins and singletons may differ in their response to etiologic factors. The variations among anencephaly, spina bifida, and encephalocele in their association with twinning suggest that there may be different factors that influence the development of each specific NTD. The noted differences among the malformations also indicate that some of the variation among results of other studies of NTDs and twinning may be due to case ascertainment. Including spina bifida cases would decrease the proportion of twins in a study population, while including anencephalics would increase the proportion. Importantly, ascertaining fetal deaths would increase the proportion of anencephalics and case females, so studies of NTDs that do not include fetal deaths will show fewer twins than expected. On the basis of our findings and those of Layde et al., excluding encephaloceles will also decrease the number of twins among NTD cases. When investigating etiologic hypotheses for NTDs, these potential biases must be recognized.     

On the twin risk in autism

Autism is considered by many to be the most strongly genetically influenced multifactorial childhood psychiatric disorder. In the absence of any known gene or genes, the main support for this is derived from family and twin studies. Two recent studies (Greenberg et al. 2001; Betancur et al. 2002) suggested that the twinning process itself is an important risk factor in the development of autism. If true, this would have major consequences for the interpretation of twin studies. Both studies compared the number of affected twin pairs among affected sib pairs to expected values in two separate samples of multiplex families and reported a substantial and significant excess of twin pairs. Using data from our epidemiological study in Western Australia, we investigated the possibility of an increased rate of autism in twins. All children born between 1980 and 1995 with autism, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) were ascertained. Of the 465 children with a diagnosis, 14 were twin births (rate 30.0/1,000) compared to 9,640 children of multiple births out of a total of 386,637 births in Western Australia between 1980 and 1995 (twin rate weighted to number of children with autism or PDD per year 26.3/1,000). These data clearly do not support twinning as a substantial risk factor in the etiology of autism. We demonstrate that the high proportion of twins found in affected-sib-pair studies can be adequately explained by the high ratio of concordance rates in monozygotic (MZ) twins versus siblings and the distribution of family size in the population studied. Our results are in agreement with those of two similar studies by Croen et al. (2002) in California and Hultman et al. (2002) in Sweden.     

Time trends in twin perinatal mortality in northern England, 1982-94. Northern Region Perinatal Mortality Survey Steering Group.

The dynamics of perinatal mortality rates (PNMR) and causes of death in twin pregnancies over 13 years in the Northern Region of the National Health Service in England is described. All twin perinatal deaths occurring between 1982-1994 were identified from the Northern Region Perinatal Mortality Survey. The twinning rate increased from 9.9 per 1000 maternities in 1982 to 12.0 in 1994. There was a total of 10,734 twin pregnancies and of these 421 resulted in 530 perinatal deaths. The perinatal mortality rate in twins significantly decreased over time (1982-87, 55.4 per 1000; 1988-94, 44.4 per 1000; P = 0.01). The PNMR was significantly higher for twins from like-sexed than from unlike-sexed pairs (53.5 and 34.4 per 1000 respectively, P < 0.001). Despite no improvement in birthweight distribution in the twin population, birthweight-specific perinatal mortality rates for both like and unlike-sexed twins decreased for each birthweight category in 1988-94 compared with 1982-87. Twins with very low birthweight (< 1500 g) comprised 69%, and preterm twins (< 37 completed weeks of gestation) 74.9% of all twin perinatal deaths. The major immediate cause of early neonatal death was pulmonary immaturity (63%); antepartum anoxia caused 76.9% of antenatal deaths. Unexplained preterm labour and intrauterine death were the leading obstetric factors underlying death in twins. Despite a decrease over the 13 years, the perinatal mortality rate in twins in the Northern Region remains high. Continued monitoring of trends in twinning and mortality rates is needed to inform health care planning.     

Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the “Twins'' Town” due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the “Nazi''s experiment” and of the “founder effect” hypotheses. We surveyed a total of 6,262 baptism records from 1959–2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the “Nazi''s experiment hypothesis”, there is no spurt in twinning between the years (1964–1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927–1958 and 1959–2008 (P = 0.638). On the other hand, the “founder effect hypothesis” is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the “Nazi''s experiment hypothesis” and strongly suggest that the “founder effect hypothesis” is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified.     

Reproductive failure,possible maternal infanticide,and cannibalism in wild moustached tamarins, <Emphasis Type="Italic">Saguinus mystax</Emphasis>

Maternal infanticide in wild non-human primates has only been reported twice. In this paper, we report a possible new case of infanticide and cannibalism within a series of four successive reproductive failures in wild moustached tamarins, Saguinus mystax. Necropsy and genetic analyses of the corpses enabled us to rule out any pathology, and to determine paternity. The mother was seen biting and then eating the head of its own infant during a period when another female was pregnant and gave birth just 1 month later. Before that, the perpetrator had given birth to twins three times successfully when four to five adult and subadult males were present in the group. Although we do not know for certain that the infant was alive when the mother started biting it, our field observations preceding the event suggest it probably was. The possible infanticide case and the two cases of births and early death of the infants occurred while only two to three adult males were present in the group. This could be the second case of maternal infanticide reported in the genus Saguinus and the similar circumstances suggest a common pattern. We discuss these events in the light of the different functional explanations of infanticide and conclude that parental manipulation was the most likely: the mother could have terminated the investment in offspring that had low chances of survival in a group with low availability of helpers.     

Possible cytogenetic mechanisms of direct paternal influence on the human twinning tendency and their consequences: a hypothesis

Certain cytogenetic mechanisms are suggested to explain the puzzling cases of the direct male influence on the repeated twin births in mammals including humans. The hypothesis is based on the peculiarities of female oogenesis and meiosis, the peculiarities of fertilization and on the established facts of the occurrence of true viable chimaeras produced by separate fertilization of two meiotic products of oogenesis. We postulate that definite genetic factors are transferred from the paternal side whose products become active in male gametes and promote penetration of two spermatozoa (polyspermy) or appearance of two male pronuclei in the egg cytoplasm. The results of such events may be twinning and occurrence of chimaeric or heteroploid individuals. The appearance of viable twins produced by male-dependent polyspermy may be considered as a fortunate outcome of various possible cytogenetic anomalies of fertilization, meiosis, and cleavage divisions. The existence of non-canonical cases of twins, except mono-and dizygotic ones is postulated, according to the hypothesis. Twins pairs produced by two paternal and one maternal genomes may be called "one and halfzygotic or sesquizygotic". The different types of twins may be classified in an order, according to the degree of genetic similarity; monozygotic, chimaeric, sesquizygotic chimaeric, sesquizygotic and dizygotic. This gives an opportunity to explain the appearance of 2 to 3% of "doubtful cases" in mass classification of twin pairs into mono- and dizygotic. The verification of the hypothesis involves the special thorough genetic and cytogenetic analysis of all twin sibs and their parents in families with the direct paternal influence on twin births.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low twinning rate and seasonal effects on twinning in a fertile population,the Hutterites

This paper analyzes from the mid 18th century to 1987 the birth records of the Dariusleut, one of the three subgroups of the Hutterite population. The aim of this study is to describe several aspects of the twinning rate in a fertile population. The overall rate of twinning was 0.90%:103 twins among all 11492 maternities. The rate peaked at the 7th birth order and at the maternal age of 40 years and over. Until the mid 19th century when the Hutterites lived in Russia, the twinning rate was higher (1.5%), and it decreased during the migration period in the second half of the 19th century (0.7%). After the group had settled in the USA and Canada, the population maintained a twinning rate of 1.0% until 1965. After 1965 the rate decreased to 0.7%, partly due to a decline in fertility among women aged 30 years and over. There was a significant seasonal variation: the twinning rate decreased to 0.5% in May–July compared to 1.2% for the other three seasons during the years up to 1965 (P<0.01), while more recent mothers did not show such a seasonal variation. The incidence of twin births in this population seems to have been influenced by environmental factors, which would change their effect seasonally and secularly.     

Multiple birth and Down's disease]

The frequency of twinning among newborns with Down's syndrome (2,11+/-0,6%)was significantly higher than in the general populaltion (0,73+/-0,3%). The increase in the rate of multiple births of children with trisomy-21 occurred due to almost three-fold excess in the frequency of dizygotic (discordant) twin pairs over the expected level. The increase in the frequency of dizygotic twins with Down's syndrome was explained by the combined effect of two independent factors: the increase in probability of dizgotic twins natality and the enhanced rate of children birth with trisomy-21, which depended on the increase in mother's age.     

Twinning and heteropaternity in chimpanzees (Pan troglodytes)

Unlike monozygotic (MZ) twins, dizygotic (DZ) twins develop from separate ova. The resulting twins can have different sires if the fertilizing sperm comes from different males. Routine paternity testing of a pair of same-sexed chimpanzee twins born to a female housed with two males indicated that the twins were sired by two different males. DNA typing of 22 short-tandem repeat (STR) loci demonstrated that these twins were not MZ twins but heteropaternal DZ twins. Reproductive data from 1926-2002 at five domestic chimpanzee colonies, including 52 twins and two triplets in 1,865 maternities, were used to estimate total twinning rates and the MZ and DZ components. The average chimpanzee MZ twinning rate (0.43%) equaled the average human MZ rate (0.48%). However, the chimpanzee DZ twinning rate (2.36%) was over twice the human average, and higher than all but the fertility-enhanced human populations of Nigeria. Similarly high twinning rates among African chimpanzees indicated that these estimates were not artifacts of captivity. Log-linear analyses of maternal and paternal effects on recurrent twinning indicated that females who twinned previously had recurrence risks five times greater than average, while evidence for a paternal twinning effect was weak. Chimpanzee twinning rates appear to be elevated relative to corresponding estimated human rates, making twinning and possibly heteropaternity more important features of chimpanzee reproductive biology than previously recognized.