The occurrence of chronic disease and other conditions in a large population-based cohort of native Californian twins.

We describe the prevalence of chronic diseases and conditions in a large cohort of twins, which has been developed to facilitate studies of the role of genetics and environment in the development of disease. The California Twin Program (CTP) comprises twins born in California between 1908 and 1982. Birth records from all multiple births (256,616 in total) were linked (multiple times between 1990 and 2001) with the California Department of Motor Vehicles (DMV) roster of licensees to obtain address information. The linkages have revealed 161,109 matches and, because of less complete DMV records in some years, were less successful in older females than in all others. To date over 51,000 of these twins have completed a detailed 16-page mailed risk factor questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, our crude response rates are as high as 63.6% (among females currently in their 50s), with an overall crude response rate of 37.9%. Similar to our previous report regarding the first 42,000 twins, the current group who have completed the questionnaire are representative of the population from which they were drawn (in terms of age, sex, race and residential distribution). Self-reported disease frequencies are provided, along with current estimates of future cancer incidence and mortality rates likely to be observed in the group. We outline our plans for cohort expansion, additional studies using the cohort, and future plans for inviting collaboration.     

Challenges in recruiting older twins for the Sri Lankan twin registry.

The National Twin Registry of Sri Lanka was established in 1997 as a volunteer register. To extend it to a population-based register, we examined the effectiveness of tracing older twins by inspecting birth records and recruiting them by postal invitation and in-person contact. Birth records at a divisional secretariat reported from 2 maternity hospitals between the years of 1954-1970 were scrutinised to identify a random sample of twins. These hospitals had the highest twin delivery rates for the whole country. We identified 620 twins and a questionnaire was mailed to them. Research assistants visited a cohort of non-respondents (71) in the postal survey. These 620 twins were identified after perusing 20700 birth records. The twinning rate was estimated at 29.95 ([620/20700] x 1000) twins per 1000 registered births (CI 27.63-32.27). In the postal survey, 37 (12%) responded and 62 letters were returned (20%). Both twins were still alive in 20 pairs, one was still alive in 15 pairs, and both twins were dead in 2 pairs. During field visits, 42 (59.2%) addresses were located. Information was available on 16 twin pairs. Both twins were alive in 8 pairs, one each in 4 pairs, and both were dead in 4 pairs and at least one twin was traced in 10 pairs (14%). Both the postal and the field survey gave a low yield. This finding is different from tracing younger twins born between 1985-1997 by using the same methods. Migration, urbanization and development in the country might have affected tracing older twins from the birth record addresses, which were decades old.     

Feasibility of using different approaches for recruiting younger twins to establish a population based twin register in Sri Lanka.

Identifying twins for a population-based register can be achieved through birth records or community surveys. We studied the feasibility and effectiveness of different methods of identifying and recruiting twins to establish a population based register. To trace twins a population survey was carried out using an interviewer administered questionnaire. We also inspected the birth registration certificates at a divisional secretariat reported from a specified hospital between the years of 1985-1997 and compared it to the birth register of this same hospital. To recruit twins a random sample of 75 twin pairs (150 twins) identified at the Divisional Secretariat were contacted through the post and 25 twin pairs (50 twins) were personally visited. The prevalence of twins was 6.5 twins per 1000 people in the area surveyed. The twinning rate at the hospital was 18.92 twins per 1000 births. A discrepancy of 38 multiples births between the hospital labour room records and those registered at the DS was noted. The response from the postal invitation for recruitment was 59% and the response from the personal invitation was 68%. (Difference 9.4% 95% CI; 7.06-11.73). Community survey and systematic inspection of birth records either at the hospital or the birth registration office was an effective method to trace twins. Once traced, personal contact was more effective than the postal invitation for recruitment of younger twins. A cost-effective approach would be to use a postal coverage followed by personal contact for non-responders. The alternative method, community coverage, would have financial implications.     

A longitudinal genetic study of vocabulary knowledge in adults.

Vocabulary test scores were obtained from a total of 997 adults, all twins or a sibling of twins in this study. Some (N = 217) individuals were tested twice, around 6 years apart. Heritability varied from 50% at the first test occasion to 63% at the second test occasion. The correlation of scores across time was.74. Structural equation modelling showed that stability in vocabulary knowledge over time can largely (around 76%) be explained by genetic factors. Part of the non-shared environmental variance was stable over time also. Any influence from shared environmental factors could not be detected. Results were similar for the two sexes, except that males generally outperformed females. Results were also similar for two age cohorts, except that the older cohort generally outperformed the younger cohort.     

First occurrence of twins in provisioned free-ranging Tibetan macaques (Macaca thibetana) at Huangshan, China

A first case of newborn Tibetan macaque (Macaca thibetana) twins was observed in a free-ranging group at Huangshan, China. The female that gave birth to the twins was studied during their first 5 months post-partum, and her activity budget was compared to those of adult females with single or no offspring in order to assess her behavioral changes. Our report shows that female Tibetan macaques can produce twins, and that twins can successfully survive. The adult female with twins spent more time foraging and resting, but less time moving and engaged in other social behaviors than adult females with a single infant or no infant. Our report provides a case of successfully surviving twins in a wild environment and suggests that the mother modified her behavior patterns to adapt to the heavy burden. We conclude that both food provisioning and the mother’s behavioral strategies facilitated the survivorship of twins. This expands our understanding of the reproductive biology of Tibetan macaques.     

Potential bias regarding birth weight in historical and contemporary twin data bases.

In this study we examine the hypothesis that monozygotic (MZ) twins in historical databases are less discordant for birth weight due to negative selection of severely discordant MZ twins. Furthermore, we test the hypothesis that MZ twins are less discordant for birth weight when comparing a volunteer based twin registry with a population based twin registry, due to selective registration. Data were available on 3927 twin pairs from the volunteer Australian Twin Registry born before 1964, 3059 volunteer twin pairs from the Netherlands Twin Register born 1987-1989 and 454 Belgian twin pairs from The East Flanders Prospective Twin Survey born 1987-1989. Intrapair relative birth weight differences (RBWD) were computed for MZ and dizygotic (DZ) twins from each twin registry. Comparing birth weight differences between MZ and DZ twins provides support for the hypothesis that MZ twins are subject to a negative selection in historical databases. Furthermore, Australian MZ twins have a lower RBWD compared to Dutch MZ twins when corrected for the RBWD of Australian and Dutch DZ twins, indicating circumstances which only affect MZ twins. Our hypothesis that MZ twins are less discordant for birth weight in a volunteer based twin registry compared to a population based twin registry had to be rejected. We suggest that investigators using historical databases to test the fetal origins hypothesis should be aware of this increased likelihood of selective exclusion of individuals with extreme morphometric parameters at time of birth.     

On fitness and partial migration in a large herbivore – migratory moose have higher reproductive performance than residents

Partially migratory populations comprise both resident and migratory individuals. These tactics may coexist if their demographic contribution to future generations (i.e. fitness) are equal or vary temporally with environmental conditions, or if individuals switch between being migrant and resident. Alternatively, the choice of movement tactic can be based on individual attributes such as age, competitive ability or personality. In the latter cases, the two tactics are not expected to have similar average fitness. In this study, we examined the effect of movement tactic on reproductive performance and survival of 82 GPS‐marked female moose and their offspring in a partial migratory population in central Norway. The results indicated higher growth in the migrating part of the population because migrating females produced more twins than resident females. We found no differences in pregnancy rates or survival of adults or their offspring, indicating a net fitness benefit of being migrant. We found the average shoulder height of residents to be slightly lower than of migrants, but doubt that this affected their migration ability. A more likely explanation is that migratory females are both more fecund and grow bigger because of better conditions in their summer ranges. This may be a temporal phenomenon if the fitness differences between migratory and resident moose vary according to environmental fluctuations.     

Maternal age and birth weight characteristics of twins born to nulliparous mothers: a population study.

In order to examine birth weight characteristics of twins delivered to nulliparous mothers in relation to maternal age, we used a population-based cohort of Israeli twins delivered between 1993-98 to select all 4793 (37.6%) nulliparas who delivered twins. Maternal age was subdivided as less than 20 years, 20-24, 25-29, 30-34, 35-39, and 40 years or more. We counted the frequencies of each total twin birth weight (twin A + twin B) in each of three categories (less than 3000, 3000-4999, and more than 5000 g) and the frequency of very low birth weight (VLBW, less than 1500 g) neonates in each of the six maternal age categories. There were significantly more nulliparas in the twin population at age groups less 30 years and significantly less at ages 30 years or more. We found a highly significant inverse correlation between the proportion of nulliparas and maternal age group, decreasing from 71.8% at less than 20 years to 18.6% at age 35-39 years (% nulliparas = 85 - 13.7 x age group, Pearson R2 = 0.98). However, this trend changed abruptly to the observed figure of 25.9% nulliparas aged 40 years or more instead of the expected 2.8%. We failed to reveal any significant difference in birth weight characteristics between the maternal age groups (all p > 0.05, all confidence intervals included 1.0). The more than tenfold deviation of the observed from the predicted frequency of nulliparas aged 40 years or more suggests that a different relationship between parity and age occurs at this age group. Maternal age of nulliparas is not associated with different birth weight characteristics of their twins.     

Age at menarche as a fitness trait: nonadditive genetic variance detected in a large twin sample.

The etiological role of genotype and environment in recalled age at menarche was examined using an unselected sample of 1,177 MZ and 711 DZ twin pairs aged 18 years and older. The correlation for onset of menarche between MZ twins was .65 +/- .03, and that for DZ pairs was .18 +/- .04, although these differed somewhat between four birth cohorts. Environmental factors were more important in the older cohorts (perhaps because of less reliable recall). Total genotypic variance (additive plus nonadditive) ranged from 61% in the oldest cohort to 68% in the youngest cohort. In the oldest birth cohort (born before 1939), there was evidence of greater influence of environmental factors on age at menarche in the second-born twin, although there was no other evidence in the data that birth trauma affected timing. The greater part of the genetic variance was nonadditive (dominance or epistasis), and this is typical of a fitness trait. It appears that genetic nonadditivity is in the decreasing direction, and this is consistent with selection for early menarche during human evolution. Breakdown of inbreeding depression as a possible explanation for the secular decline in age at menarche is discussed.     

Age-specific birth rates of California sea lions (Zalophus californianus) in the Gulf of California, Mexico

Estimates of demographic parameters are essential for assessing the status of populations and assigning conservation priority. In light of the difficulties associated with obtaining such estimates, vital rates are rarely available even for well-studied species. We present the first estimates of age-specific birth rates for female California sea lions ( Zalophus californianus ) >10 yr of age. These rates were estimated from the reproductive histories of five cohorts of animals branded as pups between 1980 and 1984 at Los Islotes colony in the Gulf of California, Mexico. Age-specific birth rates varied among age classes and ranged between 0.06 and 0.80. The highest birth rates were observed for females between 10 and 15 yr of age, with decreased birth rates among older females. The effect of age, year, and resighting effort were explored using logistic regression analysis. Based on Akaike Information Criteria, birth rates were best explained by female age, while year and resighting effort did not have a significant effect. The odds ratio of producing a pup decreased with age but did not change significantly for middle-aged females. Our estimates of age-specific birth rates are consistent with general patterns observed for other large vertebrates.     

Suckling behavior in goitered gazelle: do females invest more in twins or singletons?

The mother–offspring social unit is a universal feature in the social life of all mammals and nursing is the most direct and vital component of maternal investment in young. Living in diverse environments, various ungulate species have different strategies for rearing offspring, from bearing a single, relatively large newborn and supplying only limited amounts of milk, to bearing several relatively small newborns with intensive post-partum lactation. In this paper, we consider the rearing strategy of goitered gazelle with a focus on suckling behavior, which, until now, has never been a subject of special investigation. Adult females of this species in their reproductive prime typically bear twins when environmental conditions are favorable, but the proportion of singletons increases when conditions are unfavorable. We expected that in goitered gazelles suckling intensity would be maximal during the first weeks after birth, and then decrease with the growth of the young; we also expected that twins would demand more energy, but receive significantly less maternal investment per young than singletons. We found that, indeed, suckling behavior had similar dynamics as typical of all bovid species, but our expectation for less maternal investment in twins vs. singletons was wrong. In reality, female goitered gazelles suckled twins significantly more intensively and terminated suckling less often compared to singletons. We concluded that in favorable situations females of high quality have the ability to show significantly more maternal investment in each twin, while singletons are typically born to weaker females. This ability of females to produce mostly twins allows goitered gazelles to take advantage of any favorable opportunity to quickly increase their population in an environment with unpredictable and abrupt yearly changes typical of the arid regions of Central Asia.     

Reproductive efficiency of captive Chinese- and Indian-origin rhesus macaque (Macaca mulatta) females

Reproductive and survival records (n=2,913) from 313 Chinese-origin and 365 Indian-derived rhesus macaques at the Tulane National Primate Research Center (TNPRC) spanning three generations were studied. Least-squares analysis of variance procedures were used to compare reproductive and infant survival traits while proportional hazards regression procedures were used to study female age at death, number of infants born per female, and time from last birth to death. Chinese females were older at first parturition than Indian females because they were older when placed with males, but the two subspecies had similar first postpartum birth interval (1st PPBI) and lifetime postpartum birth interval (LPPBI). Females that gave birth to stillborn infants had shorter first postpartum birth intervals (1st PPBI) than females giving birth to live infants. Postpartum birth intervals decreased in females from age 3 to 12 but then increased again with advancing age. Chinese infants had a greater survival rate than Indian infants at 30 days, 6 months, and 1 year of age. Five hundred and forty-three females (80.01%) had uncensored, or true records for age at death, number of infants born per female, and time from the birth until death whereas 135 females (19.91%) had censored records for these traits. Low- and high-uncensored observations for age at death were 3 and 26 years for Chinese, and 3 and 23 years for Indian females. Uncensored number of infants born per female ranged from 1 to 15 for Chinese females and 1 to 18 for Indian females. Each of these traits was significantly influenced by the origin×generation interaction in the proportional hazards regression analyses, indicating that probabilities associated with age at death, number of infants born per female, and time from last birth to death for Chinese and Indian females did not rank the same across generations.     

Mortality rate of Japanese twins: Infant deaths of twins after birth to one year of age

Abstract

In twin individuals born in Japan in the first half of 1974, rates of infant mortality up to one year of age were computed according to sex and order of birth. The rates were 5.50 per cent for males and 3.81 per cent for females. A lower mortality rate for first‐born twins indicates a reduced viability for second‐born twins, even in MZ twins. The effect of maternal age, gestational age, and birth weight on the rates of infant mortality were also analyzed.     

Harnessing the Medicaid Analytic eXtract (MAX) to Evaluate Medications in Pregnancy: Design Considerations

Background

In the absence of clinical trial data, large post-marketing observational studies are essential to evaluate the safety and effectiveness of medications during pregnancy. We identified a cohort of pregnancies ending in live birth within the 2000–2007 Medicaid Analytic eXtract (MAX). Herein, we provide a blueprint to guide investigators who wish to create similar cohorts from healthcare utilization data and we describe the limitations in detail.

Methods

Among females ages 12–55, we identified pregnancies using delivery-related codes from healthcare utilization claims. We linked women with pregnancies to their offspring by state, Medicaid Case Number (family identifier) and delivery/birth dates. Then we removed inaccurate linkages and duplicate records and implemented cohort eligibility criteria (i.e., continuous and appropriate enrollment type, no private insurance, no restricted benefits) for claim information completeness.

Results

From 13,460,273 deliveries and 22,408,810 child observations, 6,107,572 pregnancies ending in live birth were available after linkage, cleaning, and removal of duplicate records. The percentage of linked deliveries varied greatly by state, from 0 to 96%. The cohort size was reduced to 1,248,875 pregnancies after requiring maternal eligibility criteria throughout pregnancy and to 1,173,280 pregnancies after further applying infant eligibility criteria. Ninety-one percent of women were dispensed at least one medication during pregnancy.

Conclusions

Mother-infant linkage is feasible and yields a large pregnancy cohort, although the size decreases with increasing eligibility requirements. MAX is a useful resource for studying medications in pregnancy and a spectrum of maternal and infant outcomes within the indigent population of women and their infants enrolled in Medicaid. It may also be used to study maternal characteristics, the impact of Medicaid policy, and healthcare utilization during pregnancy. However, careful attention to the limitations of these data is necessary to reduce biases.     

Philopatry and reproductive success in Bornean orang-utans (Pongo pygmaeus)

Behavioural observations suggest that orang-utans are semi-solitary animals with females being philopatric and males roaming more widely in search of receptive partners, leading to the prediction that females are more closely related than males at any given site. In contrast, our study presents evidence for male and female philopatry in the orang-utan. We examined patterns of relatedness and parentage in a wild orang-utan population in Borneo using noninvasively collected DNA samples from animals observed to defecate, and microsatellite markers to assess dispersal and mating strategies. Surprisingly, resident females were equally as related to other resident females (mean r(xy) = 0.303) as resident males were to other resident males (mean r(xy) = 0.305). Moreover, resident females were more related to each other and to the resident males than they were to nonresident females, and resident males were more related to each other (and resident females) than they were to nonresident males. We assigned genetic mothers to 12 individuals in the population, while sires could be identified for eight. Both flanged males and unflanged males achieved paternity, similar to findings reported for Sumatran orang-utans.     

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology.

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], gamete-intrafallopian 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 < or = 20 weeks of gestation and gave birth to infants after > or = 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.     

Competition between larvae in a butterfly Pieris napi and maintenance of different life-history strategies

1. In scramble competition all individuals suffer equally from competition, whereas in contest competition some individuals outperform the others. Generally, larger individuals gain asymmetric advantage in competition over smaller ones. Given the positive correlation between age and size, asynchronous birth may result in asymmetric competition among juveniles. 2. In Pieris napi (Lepidoptera: Pieridae), reproductive rate is determined by the females' intrinsic mating tactic. The early reproductive rate is high in females with a low mating frequency and low in females with a high mating frequency, whereas lifetime fecundity shows the opposite pattern. Thus, offspring of monandrous females start to develop in relatively low densities and they are relatively large when the offspring of highly polyandrous females start to hatch. 3. The purpose of this study was to explore if asymmetry in larval competition could outweigh the late-life benefits of polyandry. In a laboratory experiment, P. napi larvae of different ages were reared together in different densities. 4. Increasing density decreased both larval survival and reachable pupal mass, but had no effect on duration of larval period. Younger larvae suffered from high mortality and reduced size compared with the older larvae. Mortality decreased in the older cohort with increasing age difference between the cohorts, and the reverse occurred in the younger cohort. Increasing age difference between the cohorts was associated with increase in pupal mass in both cohorts. All the variables showed a lot of variation between broods of different females. 5. The results suggest that polyandrous females, or more generally females with a low early reproductive rate, may lose a great proportion of their late-life benefits, which may partly explain the maintenance of polymorphism in reproductive strategies within species.     

Twins are more different than commonly believed,but made less different by compensating behaviors

Twin studies are popular, because twins are believed to be the same/similar in genes and environmental exposures. It is well documented, however, that the firstborns are healthier at birth. We use the entire U.S. record of twin births during 1995–2000 to show that the survival duration parameters differ between twins depending on the birth order. We also find that wiser (i.e., older or educated) or married (i.e., resource-richer) mothers take more care of the weaker, which is a “compensating” behavior reducing the twin difference, as opposed to “reinforcing (the twin difference)” behavior. The systematic survival pattern difference and the mother's intervention against nature send cautions to twin studies that regard twins homogeneous to interpret their findings accordingly. Since the survival duration in our data is 97% right-censored in one year, we devise a quantile-based ‘fixed-effect’ semiparametric estimator that can handle heavy censoring, which is our methodological contribution.     

Sri Lankan Twin Registry.

Sri Lanka is an island with genetic diversity between the five main population groups. Our twin registry is the first in the developing world. Initially, we established a volunteer cohort of 4600 twin pairs through a competition advertised in the media. In addition, we have volunteer cohorts, birth registration-based cohorts through hospitals, and community-based cohorts. There is also a nationwide population-based younger twin cohort (1992-1997) traced through the Department of Birth and Death Registration. Additionally, we have adapted a Zygosity determination questionnaire and validated it. Establishing ethical guidelines for twin research was a priority because the field of bio-ethics is at an early stage of development in Sri Lanka. These guidelines were from a developing world perspective. A sister organization, the Multiple Birth Foundation, was formed to cater to twins and their special needs and to represent their interests, and several branches have been formed. We intend to build capacity by establishing a genetic lab and through crosscultural collaboration. Our vision is to establish a multidisciplinary research foundation. Based on our research findings, we plan to build services to cater to needs of twins by working with professionals, statutory services and government policy makers.     

Population based ascertainment of twins and their siblings, born in Western Australia 1980 to 1992, through the construction and validation of a maternally linked database of siblings.

This paper describes the creation of a unique maternal identifier for use in the investigation of perinatal, postneonatal and child outcomes in relation to maternal characteristics. All Midwives' records of Western Australian (WA) births were routinely linked to registrations of births and deaths for infants born from 1980 to 1992 inclusive, then linked to WA hospital discharge data and to registries of birth defects and cerebral palsy to create a longitudinal health record for each infant. However, since each birth to a woman was recorded as a separate event, there was no way to identify siblings. Probabilistic record linkage, based on information about the mother, was used for this task. Logical inconsistencies within the data were used to test the validity of the linkages between birth records attributed to each mother. Information about the mother from other epidemiological studies and data abstracted from hospital case notes was also used to validate sibships. Linkage of the records of 310,255 births in WA during that period resulted in the formation of 181,133 sibships of one or more children. Pooling the results of all of the validation methods gave an error of 0.9%. Linkage identified 3678 sibships containing multiple births, and 305 sets of maternal twins. Ascertainment of twins and their siblings for an ongoing twin register, the WA Twin Child Health (WATCH) study, was a natural consequence of this process.