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Try out PMC Labs and tell us what you think. Learn More. To investigate the twin testosterone transfer TTT hypothesis by comparing early-life mortality risks of opposite-sex OS and same-sex SS twins during the first 15 years of life. We performed a population-based cohort study to compare mortality in OS and SS twins. We included 68, live-born Danish twins from to identified through the Danish Twin Registry and performed piecewise stratified Cox regression and log-binomial regression.
Among deaths, we found ificantly higher mortality for twin boys than for twin girls. For both sexes, OS twins had lower mortality than SS twins; the difference persisted for the first year of life for boys and for the first week of life for girls. Although the mortality risk for OS boys was in the expected direction according to the TTT hypothesis, the for OS girls pointed in the opposite direction, providing no clear evidence for the TTT hypothesis.
It is well known that boys have higher risk of infant mortality and morbidity than girls [ 1 , 2 ]. Sex differences in mortality have been explained by a combination of biological, social, and environmental factors, but lifestyle and behavioral factors are less likely to explain sex difference in infant mortality [ 3 ]. Studies of animal models find that males exhibit reduced immune responses and increased intensity and prevalence of infections compared with females [ 4 ]. These sex differences may reflect the immunosuppressive effects of testosterone, as well as the positive effects of progesterone and estradiol on immune responses [ 4 , 5 ].
Whether these findings apply to humans is unknown [ 1 ], but there is evidence that girl infants have lower mortality from infections [ 6 ] and respiratory conditions [ 7 ] compared with boys. It is hypothesized that the male disadvantage begins in utero [ 8 ], where the gonadal steroid production differs between the sexes [ 3 ].
Twin studies offer unique opportunities to investigate mechanisms underlying sex differences. There is evidence suggesting that male sex hormones could influence the female fetus in opposite-sex OS twins. For instance, studies in mammals have found that female fetuses positioned between two males are likely to express masculinization of anatomical, physiological, and behavioral traits in adult life [ 9 ]. Sex hormones are lipid soluble steroids capable of crossing fetal membranes [ 10 ].
The twin testosterone transfer TTT hypothesis states that human fetuses gestated with a male co-twin are masculinized in development, which may be due to the exposure of prenatal androgens [ 11 ]; however, the evidence remains inconclusive for reviews, see [ 11 , 12 ]. Hence, early-life mortality risks in OS and same-sex SS twins may also differ due to zygosity differences. MC twins are at increased risk for perinatal mortality and morbidity compared with DC twins [ 14 ]. The literature comparing OS and SS twins with regard to early-life mortality risks is limited and inconsistent, but higher infant mortality for SS boys than for OS boys [ 15 — 17 ] and adverse outcomes including increased respiratory morbidity and higher mortality for OS twin girls in agreement with the TTT hypothesis have been reported [ 18 — 20 ].
Our study using data on a sample of 68, Danish twins aims to compare mortality in twin boys and girls and in OS and SS twins by age and over time within the first 15 years of life. This study consists of all twins born in Denmark during the period — The twins were identified through the Danish Twin Registry [ 21 , 22 ]. The Danish Twin Registry has collected data on twins including zygosity of SS twin pairs born up to , which is based on questions about the degree of co-twin similarity [ 23 ]. However, both twins have to be alive beyond infancy to have their zygosity assessed by questionnaire and therefore zygosity is generally available only for twin pairs surviving infancy [ 21 ].
All twins both live-born and stillborn have been identified through the Danish Medical Birth Registry since [ 24 ]. For these twins, information about the personal identification s for the infant and the mother, information on deaths among live-born twins, as well as information on emigrations came from the Danish Civil Registration System [ 25 ].
Information on causes of death was obtained from the Danish Registry of Causes of Death [ 26 ]. Information on maternal education came from the Danish Education Registers [ 27 ], and information about birth weight was obtained from the Medical Birth Registry [ 28 ]. In total, 68, live-born twins were eligible for analyses Table 1. For the birth cohorts —, information about stillborn twins was available for 34, twins.
Possible confounders in this study were year of birth, maternal education, and maternal age. Year of birth ranged from to and was stratified into decades birth cohorts: —, —, —, — Maternal education refers to the highest completed education until year The categorization of education was based on the International Standard Classification of Education [ 29 ]. Maternal age at delivery was categorized as younger than 20 years, 20—34 years, and 35 years and older.
However, all analyses were repeated including birth weight, and the were similar not shown. Based on age-at-death, we generated four separate risk periods according to the definitions of the of infant deaths: early neonatal deaths 0—7 days , late neonatal deaths 8—28 days , postneonatal deaths 29— days , and child mortality 1—15 years [ 30 ].
Differences in continuous background variables maternal age and birth weight were investigated using t tests. Relative risks RRs for child mortality 0—15 years for each of the possible confounders were calculated stratified by sex applying log-binomial regression both crude and adjusted for the other covariate.
All estimates were adjusted for decades. To analyze the associations of mortality between girls and boys and between OS and SS twins, we used piecewise stratified Cox regression, adjusting for the nonindependence of twins in a pair [ 31 ]. The twins were followed up for 15 years or until July 1, , whichever came first. The Cox proportional hazards assumption was fulfilled in all risk periods. Mortality HRs, taking into emigrations as censoring, were reported including adjustment for decades, crude, and adjusted for maternal age and education.
Analyses of sex differences were done within all twins as well as within intact OS twin pairs. All analyses were repeated within each decade, and analyses of OS and SS twins were conducted separately for each sex. Cause-specific mortality was classified according to the main groups in the International Classification of Disease 8 and 10 9 was never used in Denmark. We performed two sensitivity analyses regarding zygosity: First, we included all twins with unknown zygosity UZ in the MZ and same-sex dizygotic ssDZ twin groups, respectively, and compared these twin groups with the OS twins.
These groups were then compared with the OS twins and this analysis was repeated 10 times with this random distribution of the UZ twins. Moreover, differences in the risk of stillbirth and perinatal mortality between girls and boys and between OS and SS twins born between and were investigated. A stillbirth was defined as a delivery of a dead fetus at 28 or more completed weeks of gestation.
Perinatal mortality was defined as stillbirths and deaths of live-born infants within the first seven days of life. A total of deaths of all causes were observed in 68, twins Table 1. Differences in neonatal deaths early and late , postneonatal deaths and child mortality for live-born boys and girls, and OS and SS twins are shown in Table 2. We found that boys had ificantly higher mortality than girls at all ages. For stillbirth and perinatal mortality, the ificant sex differences were verified Table 3.
When we compared the mortality for boys and girls within OS twin pairs, the ificant differences vanished in all age groups. Among live births, OS twins had ificantly lower mortality than SS twins for both sexes. For girls, the difference was only found for early neonatal deaths HR: 0. Adjustments for maternal age and education did not change the effect estimates to any substantial degree Table 2. Of the six groups of death causes Supplementary Table 1 , we did not find ificant differences between OS and SS twins except from higher risk of external causes injuries for OS compared with SS girls 3.
However, when comparing OS and SS twins regarding infectious and respiratory diseases separately, we found that OS boys had lower mortality from infectious diseases compared with SS boys 0. Both sensitivity analyses confirmed a lower mortality for OS compared with ssDZ twins. All HRs were below 1 for both sexes. For boys, all associations were ificant in the neonatal period and the HRs ranged between 0.
For girls, the HRs ranged between 0. The same pattern was found when analyzing perinatal mortality Table 3. Overall mortality within the first 15 years of life has decreased during the last 4 decades in Denmark for OS and SS twins of both sexes. For live-born boys, the mortality decreased from 5.
For girls, the mortality decreased from 4. From the s to the s, the decrease in mortality was only ificant for SS boys, and for OS boys, a tendency was found in the opposite direction toward higher mortality with time HR: 1. The raw associations between the potential confounding variables and mortality showed an inverse association between maternal education and child mortality for both sexes, however, only ificant for twin girls whose mothers had the lowest education. Maternal age was not ificantly associated with mortality for twins; however, a tendency was indicated toward higher mortality among twins with mothers below age 20 and a lower mortality for twins with mothers above age 35 Supplementary Table 3.
A large population-based cohort study was used to compare mortality in OS and SS twins within the first 15 years of life. We confirmed the known sex differences in mortality. For live-born boys, the demonstrated a ificantly lower mortality for OS than for SS twins in the neonatal early and late and postneonatal periods. There are at least two possible explanations for this: first, the inclusion of the MZ twins in the SS twin group; second, lower exposure to testosterone in utero for OS than for SS boys.
For girls, we found similar mortality between live-born OS and SS twins, except that OS girls had the lowest mortality within the early neonatal period. The risk of stillbirth was ificantly lower for OS than for SS twins for both sexes. An overall decrease in mortality was observed for both OS and SS twins during the last 4 decades in Denmark. The present study agreed with twin studies reporting higher mortality for male-male than for female-female twins [ 15 — 17 ].
However, we found that within OS twin pairs, sex-related differences in mortality were much less pronounced with no ificant mortality differences between girls and boys, also consistent with earlier reports [ 17 , 32 ]. One of the major findings from the East Flanders Prospective Twin Survey, where perinatal data such as chorion type and zygosity are established at birth, is that MZ twin pairs have a ificantly higher risk of perinatal mortality than DZ twin pairs; however, the difference was limited to the MC subgroup and was especially the case before birth [ 14 ].
A large Danish study comprising twin pregnancies with ultrasound chorionicity determination before 15 weeks of gestation confirmed a higher mortality rate for MC compared with DC twins, but this difference leveled off after 24 weeks of gestation and neonatal mortality was not correlated with chorionicity [ 33 ]. In accordance with these , we found the largest difference in mortality between OS and SS twins for stillbirths.Fuck girls in twin United States
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