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Development and representativeness of a large population-based cohort of native Californian twins.

We have established a large cohort of twins to facilitate studies of the role of genetics and environment in the development of disease. The cohort has been derived from all multiple births occurring in California between 1908-82 (256,616 in total). We report here on our efforts to contact these twins and their completion of a detailed 16 page risk factor questionnaire. Addresses of the individuals were obtained by linking the birth records with the California Department of Motor Vehicles (DMV) roster of licensees. To date this has been completed for twins born between 1908 and 1972 (200,589 individuals). The linkage has revealed 112,468 matches and, because of less complete DMV records in some years, was less successful in older females than in younger females and all males. Over 41,000 twins have participated by completing the questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, we estimate our crude response rate to be between 42.2% and 49.6%, highest among females in their 40s (62.8%). We describe the representativeness of the twins in the original birth cohort, those identified by the linkage, and those completing the questionnaire. Compared to the 1990 resident population of California-born resident singletons, the respondents were of similar age, sex, race and residential distribution (for although we were able to locate fewer older females, they had a higher response rate), but were less likely to have been educated for more than 12 years. We provide a brief synopsis of studies nested within this cohort. We also elucidate our plans for expanding the cohort in the near future.

Adolescent↗

Twins born following fertility treatment: implications for quantitative genetic studies.

The rate of multiple births is substantially elevated in women who have had assisted reproduction treatment (ART; approximately 26%) compared to the general population ( approximately 1%), and these offspring are usually included in twin studies. Several studies have attempted to identify possible consequences of undergoing ART on the subsequent offspring. However, most studies have only included singleton births. We first examined whether twins born by ART differed from other twins on measures of childhood psychopathology, putative risk factors and correlates, and secondly tested for differences in the degree of twin similarity for available outcome measures. From a population-based twin sample, 101 families with dizygotic (DZ) twins conceived via ART were identified and compared with 1073 naturally conceived (NC) control DZ twin pairs. Analyses performed were (1) univariate and multivariate comparisons of between-group mean differences; and (2) comparison of twin 1-twin 2 correlations between the groups. The groups differed significantly on demographic factors (parental age, family size and social class) and pregnancy variables (smoking during pregnancy and birthweight) but did not differ on family conflict scores or in the frequency of obstetric complications. Family cohesion was higher in the ART group but this was accounted for by demographic factors. For child psychopathology there was a difference between the groups only for teacher-rated ADHD (Attention Deficit Hyperactivity Disorder). Differences were also found between groups for twin correlations. The differences found between ART and NC twins on group means and twin correlations suggest that researchers should be aware that including ART twins may influence results from twin studies.

Antisocial Personality Disorder↗

Having a co-twin with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder which occurs more often in twins than singletons. This article focuses on the psychosocial consequences of having a co-twin with ADHD. Specifically, the level of anxiety (generalized and separation) in non-ADHD children who have a co-twin with ADHD is examined using data from the Australian Twin ADHD Project (ATAP). Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their siblings were used to examine (i) anxiety symptoms in twin pairs discordant for ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are related to the type of ADHD, and (iii) whether the effects are greater for the nonaffected twin than nontwin siblings. Results show that anxiety was high in co-twins of children with the combined subtype of ADHD, with increased symptoms of both generalized and separation anxiety. Inattentive ADHD had smaller effects, which were confined to generalized anxiety and were specific to the co-twin rather than other siblings. These results have clinical implications in managing the entire multiple birth family where one twin has ADHD, and also has implications for genetic analysis in modeling the relationship of ADHD to internalizing disorders.

Adolescent↗

Clinical evaluation of the overweight patient.

Evaluation of an overweight patient is the first step in any therapeutic program. The syndromes of obesity can be classified in several ways. The first is an anatomic classification based on the size, number, and distribution of fat cells and fat tissue. The second is an etiologic classification based on identification of specific diseases and settings that produce obesity. Hypothalamic injury and endocrine disease such as Cushing's disease and the polycystic ovary syndrome are three identifiable causes of obesity. In this medicated society drugs are always candidates to produce weight gain. The most common causes, however, are stopping smoking, overconsumption of high-fat foods, a decrease in the level of activity, and aging. The natural history of obesity provides a useful framework in which to view both preventive and therapeutic strategies. Some individuals will never become overweight, but of those who do, about one-third will do so during the first two decades, and the remaining two-thirds will become overweight after age 20. A number of epidemiological and metabolic factors can serve as a guide to those individuals who are at high risk. Having overweight parents tops the list, but multiple births, cessation of smoking, and a sedentary lifestyle are additional factors. Therapeutic decisions should be based on risk-benefit decisions. The risk can be assessed from the body mass index, the distribution of fat in upper or lower body obesity, the rate of weight gain, and the degree of physical inactivity. After assessing risk, the therapeutic choices can be selected from the age category of the patient. With any therapeutic activity, involvement of the patient in a realistic approach to the treatment process is essential.

Adipose Tissue↗

Pulmonary hemorrhage in neonates of early and late gestation.

Our objectives in this study of pulmonary hemorrhage (PH) were to define common characteristics of infants who develop PH, identify factors associated with PH and report the outcome. Neonates (42/2980 admissions) with PH and matched controls were identified. Early gestation (< or = 35 weeks) infants with PH [EGPH] (n = 34; 12 survived) had occurrence of PH at 3.6 +/- 1.1 (mean +/- sem) days and were significantly associated with multiple births (p = 0.03), RDS (p < 0.01) and use of Survanta (p < 0.02). Among EGPH, small for gestational age (SGA) infants (n = 7) had a 100% mortality rate. Late gestation (> or = 36 weeks) infants with PH [LGPH] (n = 8; 6 survived) had occurrence of PH at 0.7 +/- 0.3 days and were significantly associated with low 1 minute (p = 0.04) and 5 minutes (p = 0.01) Apgar scores. All infants were managed with increases in mean airway pressure (MAP) and/or use of cocaine/epinephrine through the endotracheal tube. We have identified 2 groups of neonates with distinct factors associated with PH; use of 1:10,000 epinephrine (0.1 ml/kg) and/or 4% cocaine (4 mg/kg) may be useful adjuncts to increases in MAP for management of PH.

Biological Products↗

Infant mortality among singletons and twins in the United States during 2 decades: effects of maternal age.

OBJECTIVE: Whereas it is well-established that maternal age has a U-shaped relationship with infant mortality among singletons, effects on the risk of mortality among multiple births remains unexplored. If there is a relationship, then assessment of maternal age may identify pregnancies and births that should be targeted by both clinical and public health interventions. The objective of this study was to characterize the relationship between maternal age and infant mortality in singleton and twin births in the United States. METHODS: A retrospective cohort study was conducted of all live births (singleton: n = 22 546 718; twin: n = 535 544) in the United States in 1985-1986, 1990-1991, and 1995-1996. Risks and relative risks for infant deaths by maternal age before and after adjustments for birth cohort, gravidity, birth weight, and gestational age were measured. RESULTS: Maternal age had a U-shaped association with mortality among singletons, with highest rates seen at extremes of age. Among twins, however, there was a steep and inverse relationship between age and mortality, with those born to young mothers experiencing the highest mortality rates. Seven percent of twin births resulted in an infant death for women who were younger than 20 years, 2.7% for those 30 to 34 years, and 2.0% for women 40 to 49 years. Even after adjustments for gravidity, birth weight, and gestational age, these trends persisted. Additional examination by timing of death indicated that this relationship was primarily a function of postneonatal rather than neonatal mortality. CONCLUSIONS: The highest mortality among twins occurred to women who delivered in their teens and early 20s. The implications of these findings, both from a clinical and a public health perspective, deserve attention.

Adolescent↗

Complications in cesarean and non-cesarean deliveries: United States, 1980.

Using 1980 National Hospital Discharge Survey data, complications reported for cesarean and non-cesarean deliveries coded by the Ninth Revision ICD-CM are compared. While over 16 per cent of all deliveries in 1980 were by C-section, 94 per cent of the deliveries where maternal-infant disproportion was noted were by C-section, and this complication was noted in one-fourth of all C-section deliveries. Similarly, where malposition or malpresentation of the fetus was evident, 59 per cent of the mothers were delivered by C-section, and this complication was noted in one-sixth of all C-section deliveries. C-sections were also associated with placenta praevia, pre-eclampsia, infections of the genito-urinary tract, anemia, multiple births, and were almost universal for mothers who had had a previous C-section delivery. Competing explanations for the rise in C-sections from 5.5 per cent of deliveries in 1970 to 16.5 per cent in 1980 are discussed in the context of these findings.

Cesarean Section↗

Breed effects of foster lamb and foster dam on lamb viability and growth.

The objective of this study was to compare maternal ability under natural and fostered rearing conditions in four breeds of sheep for lamb survival and growth to weaning age. Data included records from 1981 through 1991 of 24,696 lambs of four breeds, Rambouillet, Columbia, Targhee, and Polypay, reared by their natural dam, and 720 records of lambs fostered within their breed or across breeds. The majority (94%) of the foster lambs were from multiple-birth litters and were approximately .5 kg lighter than lambs reared by their natural dams (P < .05). Viability up to 3 wk of age was influenced by breed of foster dam; lambs reared by Polypay dams had the highest viability (96%) and lambs reared by Targhee dams the lowest (81%). Targhee dams were less successful in rearing foster lambs (75%) to weaning than the other breeds studied (average 84%). The lower viability of Targhee-reared foster lambs could not be explained by lower birth weights of foster lambs, increased starvation, or lower milk scores for Targhee dams. Although there were breed differences in weaning weights at 120 d of age, the foster lambs were lighter but the ranking by breed did not change. These results suggest that there are small breed differences in maternal ability for a ewe to raise her own lamb or foster lamb(s), except for the Targhee ewe, which has a lower success in rearing a foster lamb. Management practices to reduce the mortality rate of foster lambs should be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Twinning rate in Norwegian cattle: frequency, (co)variance components, and genetic trends.

The overall twinning rate was shown to increase from .6% in the first parity to 4.0% in the sixth parity, and a positive phenotypic trend for twinning rate was observed during the time period considered (1978 to 1995). The distribution of bulls according to the average percentage of multiple births of daughters in first and second parity showed that some bulls had an extremely low twinning frequency and others exceeded the population mean by approximately six times. (Co)variance components were estimated for twinning in first and second parities using a linear sire model. The analysis included either first- and second-crop daughters (1.4 and .9 million records for first- and second-parity cows, respectively) or first-crop daughters only (.6 and .4 million records for first- and second-parity cows, respectively) from 2,043 sires. Heritability estimates were .7 to .8% in the first parity and 2.8% in the second parity. The genetic correlation between twinning in the first and second parities was approximately 1. Part of the phenotypic trend observed can be explained by a genetic trend for twinning rate.

Animals↗

Analysis of litter size and days to lambing in the Ripollesa ewe. II. Estimation of variance components and response to phenotypic selection on litter size.

A performance data set from 376 Ripollesa purebred ewes of the experimental flock of the Universitat Autònoma of Barcelona was analyzed using a bivariate Bayesian threshold-linear model. The data set contained 1,598 litter size records and 1,699 days-to-lambing records. The model included the additive genetic effect of each animal and 3 nongenetic sources of variation: ewe age, year of lambing, and the permanent environmental effect characterized by the ewe. The flock was phenotypically selected for litter size since 1986, and replacement ewes and rams were selected from the progeny of the more prolific ewes, which had at least 3 deliveries recorded. The phenotypic trend for litter size was positive, whereas days to lambing followed an unclear pattern. Both traits had low heritabilities; 0.13 for litter size and 0.11 for days to lambing. Response to selection was evaluated through (a) the average breeding value of the ewe lambs chosen annually, and (b) the average breeding value of the overall flock. The first measurement suggested a positive trend for litter size, although it showed important oscillations. On the other hand, the average breeding value for the overall flock showed a stable positive tendency after yr 4 of selection, with estimates clearly different from zero after yr 11 of selection. A significant increase in the incidence of multiple births was observed, with a mode of approximately 10%. The correlated response in days to lambing did not show a significant trend. The effect of year of lambing also positively influenced both litter size and days to lambing, although important oscillations were observed between years. Results indicated that litter size in sheep can be effectively improved through phenotypic selection, even in small flocks; moreover, days to lambing could also be genetically improved, given the estimate obtained for its heritability.

Animals↗

Ovulation rate in sheep selected for weaning weight or litter size.

Ovulation rate was measured by laparoscopy at two consecutive cycles on 366 ewes 2 yr old and over and 85 yearling ewes of five lines of Targhees from the base base population; 53 yearling linecross ewes were also included. The lines were two unselected controls (HCl and DC), two selected for 21 yr for increased 120-d weight (HW and DH) and one selected for 19 yr for multiple births (T). Ewes were synchronized in late July or early August at the start of the normal breeding season with intravaginal pessaries impregnated with 60 mg methylacetoxyprogesterone and examined at first and second estrus. Ovulation had occurred in both cycles in 327 (89%) and 177 (85%) of the mature and yearling ewes, respectively. Overall mean numbers of corpora lutea at first and second estrus were 1.42 and 1.63, respectively for ewes 2 yr and over and 1.20 and 1.44 for yearlings, indicating an effect of synchronizing treatment, season, flushing, or a combination of these. Among mature ewes, ovulation rate was higher (P less than .05) in DH (+.20), HW (+.19) and T (+.16) than in controls at first estrus, and in HW (+.29) and T (+.21) but not DH (-.04) at second estrus. Among yearlings, differences were significant only at second estrus (HW, +.40; T, +.35) and again not for DH (+.08). The failure of line DH to increase in ovulation rate from first to second estrus as did other lines was transmitted to linecross progeny. Body weight within line affected ovulation rate significantly, with a greater effect at second estrus, in both age groups. Adjustment for body weight removed the difference between HW and controls but not between T and controls. Repeatability of corpora lutea count was .27 and .25 for mature and yearling ewes, respectively.

Animals↗

Genetic and environmental factors affecting immunoglobulin G1 concentrations in ewe colostrum and lamb serum.

Presuckle colostral samples and lamb serum samples taken 36 h postpartum were assayed for immunoglobulin G1 (IgG1) concentration (mg/ml) using single radial immunodiffusion. Breeds sampled included Polypay (P), Rambouillet (R), Targhee (T), Columbia (C), Finnish Landrace (F) and Finn crosses (Fx). Sources of variation examined in IgG1 concentration in colostrum (dam trait) included dam's sire breed, dam's sire, age of ewe and number of lambs born. All sources of variation were statistically significant. Least-squares means of IgG1 levels for sire breed were 80, 64, 67, 64, 72 and 69 mg/ml for P, R, T, C, F and Fx breed groups, respectively. A fetal stimulus may exist to increase the mass of IgG1 in colostrum available for multiple births (61, 69 and 77 mg/ml for single, twin and triplet, respectively). Ewe age was a significant source of variation because of a high mean concentration of IgG1 in the yearling's colostrum (100 mg/ml), whereas only slight differences occurred between the other age groups (65 to 67 mg/ml), except for the 7-yr older group (53 mg/ml). Sources of variation examined in IgG1 concentration of lamb serum at 36 h postpartum (lamb trait) included lamb's sire breed, lamb's sire, age of dam, birth type and sex, with dam's colostral IgG1 concentration and day born as covariates. Sire within breed, birth type and the two covariates were significant. Least squares means for sire breed were 36, 32, 33, 32, 31 and 32 mg/ml of serum for P, R, T, C, F and Fx groups, respectively. Lamb serum IgG1 decreased as birth type increased. The heritability of IgG1, estimated by paternal half-sib analyses, was .19 +/- .12 for colostrum and .18 +/- .06 for lamb serum.

Animals↗

Pregnancy following treatment with human gonadotropins in primary unexplained infertility.

Six patients with primary unexplained infertility of 2 to 9 years duration, and who failed to conceive after repeated trials of clomiphene treatment, were treated with human gonadotropins; 3 of them became pregnant following one or two courses of treatment. Three patients failed to conceive in spite of 3 courses of human gonadotropins, 2 of them had high titers of sperm-agglutinating antibodies found in their sera, which may explain their infertility. None of the 13 treatments resulted in hyperstimulation syndrome or multiple births. This preliminary result seems encouraging but awaits further study.

Adult↗

A comparison of the expressive communication skills of triplet, twin and singleton children.

Few studies have focused on the language acquisition of higher multiple birth sets. In this study, the communication skills of 51 triplet children are described. The measures used were: mean length of utterance; type-token ratio; conversational acts; phoneme repertoire; and number of different types of phonological processes used. The data gained were used to compare the communication skills of triplets with those of twins, singletons and normative data available in the literature. Siblings within triplet sets were also compared using language samples obtained from adult-child interactions and when the three children were playing together. The results indicated that the triplets' early communication skills were different from those of both singletons and twins. The triplets' difficulties included delayed syntactic development, limited use of different language functions and delayed phonological development. In contrast, twins' communication profile is characterised by disordered phonological development.

Child, Preschool↗

Comparison of two timed artificial insemination (TAI) protocols for management of first insemination postpartum.

Two estrus-synchronization programs were compared and factors influencing their success over a year were evaluated. All cows received a setup injection of PGF2alpha at 39 +/- 3 d postpartum. Fourteen days later they received GnRH, followed in 7 d by a second injection of PGF2alpha. Cows (n = 523) assigned to treatment 1 (modified targeted breeding) were inseminated based on visual signs of estrus at 24, 48, or 72 h after the second PGF2alpha injection. Any cow not observed in estrus was inseminated at 72 h. Cows (n = 440) assigned to treatment 2 received a second GnRH injection 48 h after the second PGF2alpha, and all were inseminated 24 h later. Treatment, season of calving, multiple birth, estrual status at insemination, number of occurrences of estrus before second PGF2alpha, prophylactic use of PGF2alpha, retained fetal membranes, and occurrence of estrus following the setup PGF2alpha influenced success. Conception rate was 31.2% (treatment 1) and 29.1% (treatment 2). A significant interaction occurred between protocol and estrual status at insemination. Cows in estrus at insemination had a 45.8% (treatment 1) or 35.4% (treatment 2) conception rate. The conception rate for cows not expressing estrus at insemination was 19.2% (treatment 1) and 27.7% (treatment 2). Provided good estrous detection exists, modified targeted breeding can be as successful as other timed artificial insemination programs. Nutritional, environmental, and management strategies to reduce postpartum disorders and to minimize the duration of postpartum anestrus are critical if synchronization schemes are used to program first insemination after the voluntary waiting period.

Animal Husbandry↗

Pre-conception energy balance and secondary sex ratio--partial support for the Trivers-Willard hypothesis in dairy cows.

According to the Trivers-Willard hypothesis, maternal condition at or around conception affects the secondary sex ratio in mammals. However, there are little or no data available on indicators of maternal condition in dairy cows on the sex of the resultant offspring. A total of 76,607 body condition score (BCS; scale of 1 to 5) records and 76,611 body weight (BW) records from 3,209 lactations across 1,172 cows were extracted from a research database collated from one research herd between 1986 and 2004, inclusive. Exclusion of multiple births and cows with no information before calving (e.g., nulliparous animals) resulted in 2,029 records with BCS and BW observations from the previous calving, and 2,002 and 1,872 lactations with BCS and BW observations at conception and midgestation, respectively. Change in BCS and BW between calving and conception and between conception and midgestation was calculated per lactation. Generalized estimating equations were used to model the logit of the probability of a male calf, in which cow was included as a repeated effect with a first-order autoregressive correlation structure assumed among records within cow. Of the BCS variables investigated, there was a linear relationship between the logit of the probability of a male calf and BCS change between calving and conception, the rate of BCS change over this period (BCS divided by days in milk), and BCS at the calving event immediately before conception. The birth of a bull calf was 1.85 times more likely in cows that lost no BCS from calving to conception compared with cows that lost one BCS unit from calving to conception. This increase in odds was equivalent to a 14% unit increase in the probability of a male calf (from 54 to 68%). The amount of BW lost between calving and conception and the rate of loss affected the sex of the resultant offspring. Less BW loss or greater BW gain between calving and conception was associated with greater likelihood of a male calf. Results suggested a positive effect of pre-conception BCS and BW change on secondary sex ratio, agreeing with the Trivers-Willard hypothesis that females in good physiological condition are more likely to produce male offspring.

Animal Feed↗

Inheritance of calf mortality for Brown Swiss cattle.

Worksheets with reports of calf mortality were voluntarily submitted by dairy producers to the Brown Swiss Cattle Breeders Association. Objective was to assess genetic and nongenetic factors influencing calf mortality of Brown Swiss. Multiple births were removed prior to analysis. Three traits recorded and analyzed were dead at birth, death through 2nd d after birth including dead at birth, and death from 1st to 7th d of life. Male calves were more likely to be dead at birth, to die through 2nd d, and to die from 1st to 7th d of life than female calves. Dead birth was greater for calves from primiparous than multiparous dams; however, death from 1st to 7th d did not differ by parity status of dam. Death from 1st to 7th d was greater from December to May than from June to November. Heritabilities for Brown Swiss were .05, .07, and .04 for dead at birth, dead through 2nd d, and death from 1st to 7th d, respectively. Mortality rates and heritabilities were similar to estimates for Holsteins from the literature. Rank correlations of sires for transmitting abilities of calf mortality and production were near zero.

Animals↗

[Cerebral palsy in twins in Okinawa].

Twin pregnancy is an important risk factor associated with cerebral palsy (CP). We investigated the prevalence and clinical features of CP in twins born from 1988 to 1994 in Okinawa prefecture. The prevalence of CP in twins was 10.1 per 1000 multiple births, and it was 6 times that in singletons (1.6 per 1000 live births). Twins weighing more than 2500 g had a higher prevalence of CP than singletons, but those weighing less than 2500 g had no significant difference. Our results indicate that the higher rate of CP in twins reflect their tendency to be low-birth weight. There may be specific events affecting twins weighing 2500 g or more.

Birth Weight↗