Unlike-sex Twins Research Articles

Genetic and environmental influences on gambling disorder liability: a replication and combined analysis of two twin studies.

Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date. Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972-79) and 4764 (mean age 37.7, born 1964-71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women. In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45-76%) and unique environmental (40%; 95% CI 24-56%), but not shared environmental contributions (0%; 95% CI 0-0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD. Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.

Hypertensive disorders during monozygotic and dizygotic twin gestations: A population-based study

ABSTRACTObjective: To determine whether the incidence of hypertensive disorders is different in monozygotic compared to dizygotic twin pregnancies. Methods: A registry-based survey of twin pregnancies delivered during 2003 to 2012. We used the best clinical estimate of zygosity based on the concept that all monochorionic twins are monozygotic and all unlike-sex pairs are dizygotic, thus excluding same-sex dichorionic twin gestations for which zygosity cannot be ascertained on clinical grounds. Study cohorts were twin pregnancies with or without preeclampsia and gestational hypertension. Results: A total of 3419 twin gestations met the inclusion criteria, of which 442 (12.9%) were monochorionic and 1255 (36.7%) were unlike-sex twins, excluding 1722 same-sex dichorionic twin gestations (50.4%). There was no significant difference in the incidence of preeclampsia (OR: 0.9; 95% CI: 0.4–2.0 for monozygotic males and OR: 0.6; 95% CI: 0.3–1.4 for monozygotic females) and gestational hypertension (OR: 0.7; 95% CI: 0.2–2.5 for monozygotic males, and OR: 0.7; 95% CI: 0.2–2.3 for monozygotic females) between monochorionic and unlike-sex pairs. Maternal prepregnancy obesity and nulliparity were the only significant associated factors of preeclampsia (OR: 3.8; 95% CI: 2.0–7.0, and OR: 2.5; 95% CI: 1.4–4.4, respectively). Maternal prepregnancy obesity (OR: 5.5; 95% CI: 2.5–12.2), maternal age ≥36 years (OR: 2.5; 95% CI: 1.1–6.1), and family history of hypertension (OR: 2.6; 95% CI: 1.3–5.1) were significantly associated with gestational hypertension. Conclusion: Based on a large population-based dataset and on the best clinical estimate of twin zygosity, it appears that zygosity is not associated with hypertensive disorders in twin gestations.

Prevalence and Risk of Down Syndrome in Monozygotic and Dizygotic Multiple Pregnancies in Europe

During the past 20 years, the prevalence of Down syndrome (DS) has increased with the increase in mean maternal age. The prevalence of multiple births has also increased because of older maternal age and use of assisted reproductive technologies. This study was designed to determine the maternal age–specific prevalence of DS in monozygotic and dizygotic pregnancies, assess risk relative to singleton pregnancies, as well as compare prenatal diagnosis and pregnancy outcomes for DS fetuses in multiple and singleton pregnancies. The database of the European Surveillance of Congenital Anomalies includes live-born congenital anomaly cases, stillborn cases and fetal deaths after 20 weeks’ gestation, as well as prenatally diagnosed cases resulting in termination of pregnancy for fetal anomaly. The study population consisted of 14,827,105 pregnancies between 1990 and 2009, of which 2.89% were multiple gestations. Individual fetuses/babies with DS from multiple and singleton pregnancies were considered “cases.” Twin pairs with both twins having DS were “concordant” pairs. Relative risk (RR) with the 95% confidence interval (CI) was used to estimate the prevalence of cases with DS among multiple births relative to that among singleton births. From 1990 to 1999, the total corrected prevalence of DS cases from multiple pregnancies as opposed to singleton pregnancies per 10,000 births was 0.40 (95% CI, 0.36–0.45), rising to 0.47 (95% CI, 0.42–0.53) in 2000 to 2009 (P > 0.05). Overall (1990–2009), the prevalence of DS cases per 10,000 multiple births was 15.1 (95% CI, 14.6–15.9); and per 10,000 singleton births, 20.1 (95% CI, 19.9–20.3). The prevalence of DS cases per 10,000 multiple births rose with age of 44 years or younger, after which it was considerably lower. The adjusted RR of DS for babies from multiple births relative to singleton births was 0.58 (95% CI, 0.53–0.62). Of 19,397 babies born to mothers older than 44 years, 2043 (10.5%) were from multiple births. Only 1 fetus from a multiple pregnancy was a DS case, a prevalence of 4.48 (95% CI, 0.67–35.1) per 10,000 multiple births, compared with 562 singleton DS cases, a prevalence of 327 (95% CI, 301–356) per 10,000 singleton births (RR, 0.015; 95% CI, 0.002–0.107). In 8.7% (n = 54) of affected pairs, the twins were concordant for DS, 51 same-sex twin pairs and 3 unlike-sex twin pairs. The maternal age–adjusted RR of a monozygotic pregnancy being affected was 0.34 (95% CI, 0.25–0.44) compared with singleton pregnancies. No affected monozygotic twin pregnancies occurred in the group older than 44 years. For dizygotic pregnancies, the maternal age–adjusted RR of at least 1 twin being affected was 1.34 (95% CI, 1.23–1.46) compared with singleton pregnancies. For age older than 44 years, the RR was 0.04 (95% CI, 0.01–0.27). The proportion of DS cases prenatally diagnosed was lower for multiple than for singleton pregnancies at all maternal ages, for an overall maternal age–adjusted odds ratio (OR) of 0.62 (95% CI, 0.50–0.78). The overall proportion of termination of pregnancy for fetal anomaly cases from multiple pregnancies was lower than singletons at every maternal age, giving an overall maternal age–adjusted OR of 0.52 (95% CI, 0.41–0.65). Down syndrome cases from multiple births were not more likely to be stillbirths/fetal deaths than from singleton births; the maternal age–adjusted OR was 1.03 (95% CI, 0.59–1.78). Individual fetuses from twin pregnancies are at lower risk for DS than those from singleton pregnancies. The estimates of the lower maternal age–specific DS risk in twin pregnancies, combined with the clinician’s knowledge of zygosity/chorionicity and maternal age at ovulation for women having assisted reproductive technologies, should allow more accurate risk estimates for genetic counseling and prenatal screening.

Stillbirth Rates and Risk Factors for Stillbirths among Zygotic Twins in Japan, 1995-2008

We aimed to determine the Stillbirth Rates (SRs) for monozygotic (MZ) and dizygotic (DZ) twins, with the risk factors for stillbirth. SRs were estimated using Japanese vital statistics from 1995 to 2008. The SRs of zygotic twins significantly decreased during the period. The SR was the lowest at maternal age (MA) of 30-34 years for MZ (66) and DZ twins (18) and significantly higher at MA <20 years than the other MA groups for both zygosities. The SR was the lowest at Gestational Age (GA) of 37 weeks for MZ (5.7) and DZ twins (1.8). The SR was significantly higher for MZ than for DZ twins at each GA group except for those born at GA 39 and GA ≥ 40 weeks. The SR significantly decreased from 1995-1998 to 2004-2008 except GA ≥ 40 for both zygotic twins and 32-35 weeks for DZ twins. Incidences of preterm delivery increased from 1995 (43% for MZ and 38% for DZ twins) to 2008 (62% and 55%, respectively). The SRs were significantly higher in like-sexed twins than in unlike-sexed twins in every birth weight (BW) group. The SR was similar between BW 2000–2499 g and ≥ 2500 g in each twin group. The SR increased progressively when the percentage of BW discordance exceeds 10% for MZ twins and exceeds 20% for DZ twins. The SR due to twin–twin transfusion syndrome was 14% among spontaneous stillbirths in MZ twins. In conclusion, declining SR attributed to medical care during twin pregnancies less than 40 weeks for MZ and DZ twins. Excess BW discordance of 10% for MZ twins lead to higher SRs compared with those in DZ twins. The increased premature rate in twins might bring severe problems such as cardiovascular risk in their future life.

Impact of sex on perinatal mortality and morbidity in twins

Twin studies offer opportunities to investigate mechanisms underlying sex-associated differences in perinatal outcomes. The objective of the study was to investigate sex-related differences in perinatal complications. A cohort of 16,045 twin pregnancies - 32,090 twins - was explored for obstetric complications, perinatal and infant mortality, and neonatal morbidities. Twin pregnancies with a female fetus had an increased risk for preeclampsia, but otherwise there were no pregnancy complications associated with fetal sex. After birth, female-female twins had lower early neonatal and infant mortality, and lower risk for respiratory morbidities than male-male twins at all gestational ages. In unlike-sexed twin pairs, very preterm males had higher respiratory morbidity than females and, females were at higher risk for being growth restricted. Male-male twins have higher respiratory morbidity and neonatal mortality than female-female twins. In unliked-sexed twin pairs, the males seem to be protected by having a female co-twin.

A closer look at the evidence for sex differences in the genetic and environmental influences on gambling in the National Longitudinal Study of Adolescent health: from disordered to ordered gambling

To reconcile an inconsistency in the disordered gambling literature by revisiting a previous study that claimed to find evidence for large gender differences in the magnitude of genetic and environmental influences. Univariate structural equation twin models were fitted to decompose the variation in gambling behavior into additive genetic, shared environmental and unique environmental influences. United States. Participants were 1196 same-sex and unlike-sex twins (18-28 years of age, 49% male, 51% female) from the National Longitudinal Study of Adolescent Health (Add Health). Eight questions about normative and problematic gambling involvement were assessed by in-person interview. Although disordered gambling symptoms were assessed, the number of individuals who were administered these questions precluded twin analysis, including analysis of potential gender differences. Of the eight questions, only three were deemed usable for twin analysis-these were all questions about normative gambling involvement. Individual differences in (non-disordered) gambling involvement were explained completely by family [C = 38% (30-46%)] and unique environmental factors [E = 62% (54-70%)]. There was no evidence for genetic factors (A = 0), nor was there evidence for sex differences (Δχ(2) = 1.23, d.f. = 2, P = 0.54). There appears to be no evidence for gender differences in the genetic contributions to disordered gambling. Family environment appears to play a significant role in explaining individual differences in (non-disordered) gambling involvement among emerging adults.

Behavioral correlates of depressive symptoms in older unlike-sex twin pairs

This study examines gender-specific behavioral correlates of depressive symptoms using a secondary data analysis of a cross-sectional, population-based sample of older unlike-sex twins. Unlike-sex twins aged 69-88 were identified through a national Swedish registry and sent a survey about health, including depressive symptoms (CES-D) and the frequency of engaging in physical, social and mental activities. A total of 605 complete twin pairs responded. Depressive symptom scores were associated with frequency of engagement in physical and mental activities, but only in men. No statistically significant associations with depressive symptom scores for any of the three types of activities were found in women. The results suggest that engaging in physical and mental activities may protect older men from developing depressive symptoms, but longitudinal data are needed to offer more conclusive findings on the role that physical, mental, and social activities play in the maintenance of psychological health in older men and women.

Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple-Gestation Births

To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs. The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs. LOS occurred in 25.0% (3797 of 15,178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs. LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.

Similarly increased congenital anomaly rates after intrauterine insemination and IVF technologies: a retrospective cohort study

While intrauterine insemination (IUI), a simple, inexpensive and non-invasive technique, is the most used assisted reproduction technology (ART) worldwide, the risk of major birth defects following IUI is paradoxically not well documented. Retrospective cohort study performed in Burgundy, France, over a 9-year period which consisted of the cross analysis of two prospective databases, the Burgundy perinatal network database and the database of the assisted conception units in Burgundy. A total of 1348 ART singletons [in vitro fertilization technologies (IVFT): n= 903; IUI: n= 445] matched with 4044 infants conceived naturally, 552 ART twins (IVFT: n= 362; IUI: n= 190) matched with 1656 twins who were conceived naturally. The major birth defects were categorized according to the European Surveillance of Congenital Anomalies classification EUROCAT. Compared with naturally conceived singletons, singletons born after IUI and IVFT had a higher prevalence of major congenital malformations, with adjusted odd ratios (AOR) of 2.0 [95% confidence interval (CI) 1.0-3.8] and 2.0 (CI 1.3-3.1); 3.6 and 4.2% of infants born, respectively. All twins and unlike-sex twins born after IVFT but not IUI, have an increased prevalence of major birth defects compared with naturally conceived twins; AOR of 3.0 (CI 1.6-5.6) and 3.7 (CI 1.1-16.9), respectively. When comparing IUI with IVFT, no differences were observed for singletons (AOR 1.0; CI 0.4-2.2), all twins (AOR 0.4; CI 0.1-1.2) and unlike-sex twins (AOR 0.3; CI 0.1-4.5). The risk of major birth defects in singletons conceived through IUI was increased over naturally conceived singletons. This risk was no different from that observed after IVFT.

Estimated Number of Siblings in Japanese Families with Multiple Birth Children using Two Sets of Census Data: 1990 and 1995

The purpose of this study was to estimate the number of siblings in each Japanese family with multiple birth children using two sets of census data, from 1990 and 1995. The mean number of siblings for singletons was 2.3 in 1990 (2.4 in 1995), 2.9 (2.9) for one set of twins, 4.6 (4.5) for two sets of twins, and 3.5 (3.3) for one set of triplets. For birth order of multiples, the highest mean sibling number was 4.4 for one set of twins (the middle), 7.5 for two sets of twins (the middle-middle), and 4.3 for one set of triplets (the last). The mean sibling number was slightly higher for like-sexed twins and triplets than in unlike-sexed twins and triplets. The mean sibling number was highest in the Okinawa District, among nine districts (0.4 for singletons, 0.6 for one set of twins, 1.0 for two sets of twins and 0.6 for triplets). The current study of the number of siblings in each family with multiple birth children will help provide data for designing programs to help support multiple-birth families. The method of using census data on multiple births might result in a system to analyze nationwide data on multiple birth children if there is no national registry of multiple births after live births in any country.

Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?

Background Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. Aims To follow up children conceived by IVF with respect to risk for CP. Methods Infants born after IVF were identified from all IVF clinics in Sweden 1982–2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. Results The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52–2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004–2007) when the twinning rate after IVF was <10%, the odds ratio for CP was 0.97 (95% CI 0.57–1.66). Conclusions The moderately increased risk for CP was most likely a consequence of an increased risk of neonatal morbidity, notably associated with multiple births.

Twins born following assisted reproductive technology: perinatal outcome and admission to hospital

Compared with spontaneously conceived (SC) singletons, adverse perinatal outcome, neonatal intensive care unit (NICU) admission and hospital admission in infancy are more common in those born following Assisted Reproductive Technology (ART). Similar comparisons for twins have shown conflicting results. We investigated perinatal outcome and hospital admission during the first 3 years of life for all twin children born in Western Australia between 1994 and 2000 [700 ART, 4097 SC]. ART twins had a greater risk of adverse perinatal outcome including preterm birth, low birthweight and death compared with SC twins of unlike-sex. In their first year of life, ART twins had a longer birth admission; were 60% more likely to be admitted to a NICU; and had a higher risk of hospital admission. The increased risk of hospital admission continued in the second and third year but was not statistically significant in the third year. Couples undertaking ART should be aware that in addition to the known increased perinatal risks associated with a twin birth, ART twins are more likely than SC twins to be admitted to a NICU and hospitalized in the first 3 years of life.

Subfertility among parents of men diagnosed with testicular cancer

It is well known that men with testicular cancer also have reduced fertility before diagnosis. It is unclear, however, whether their parents also have reduced fertility. We performed a population-based record linkage study comparing parental fertility among 3711 testicular cancer cases and 371 100 control males. The cases were diagnosed from 1961 to 2001, and the data were analysed by logistic regression. Included indicators of parental fertility were number of children, rate of unlike-sex twins as a proxy for dizygotic twinning rate, and proportion of boys. The number of children was reduced across increasing sibship size among both mothers [odds ratio (OR) = 0.95, p(trend) = 0.003] and fathers [OR = 0.97, p(trend) = 0.057] of subjects with testicular cancer. The proportion of unlike-sex twins was also reduced among their mothers [(OR = 0.56, p = 0.049 (adjusted for year of birth)] and fathers [(OR = 0.56, p = 0.049 (adjusted for year of birth)]. The results were only marginally changed when also adjusting for respective parental age. Our study indicates that parents of testicular cancer cases have reduced fertility. This suggests that genetic factors are important in the association between testicular cancer and reduced fertility.

Gestation and Birthweight in Dizygotic Twins: Girls Call the Tune

AbstractUnlike-sex twins provide a unique natural experiment to investigate the influence of sex on gestation. Our data showed that length of gestation of unlike-sex pairs is similar to that of female same-sex pairs, and significantly (0.4 wks,p= .02) longer than that of male same-sex pairs. Birthweight of female unlike-sex twins was similar to female same-sex twins, but male unlike-sex twins weighed 78 g more than male same-sex twins (p= .001). These data show that in unlikesex pairs it is the girl that prolongs gestation for her brother, resulting in a higher birthweight than that of same-sex boys.

“Masculinizing” Effect on Respiratory Morbidity in Girls From Unlike-Sex Preterm Twins: A Possible Transchorionic Paracrine Effect

Preterm male infants are at a disadvantage when compared with female infants regarding the incidence of respiratory and neurologic morbidity and mortality. At term, female infants from unlike-sex twin pairs have birth weights that are closer to their male co-twins than to girls from like-sex twin pairs. We hypothesized that if the male disadvantage is mediated via factors that affect fetal lung development, there may be a potential effect on the incidence of respiratory distress syndrome and its complications in female infants from unlike-sex pairs. In this population-based study we used data from the Israel Neonatal Network, which included data from 8858 very low birth weight (500-1500 g) infants of 24 to 34 weeks' gestation. The incidence of morbidity and mortality was compared in male and female infants from singletons and like-sex and unlike-sex twin pairs. Multivariable analyses were used, accounting for relevant confounding variables. Male singletons and like-sex twins were at increased risk for mortality, respiratory distress syndrome, pneumothorax, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, and periventricular leukomalacia. However, in unlike-sex twin pairs, no difference was seen in the incidence of respiratory morbidity between male and female twins. The male disadvantage was maintained for mortality and periventricular-intraventricular hemorrhage. These findings suggest that the difference in morbidity and mortality between male and female premature infants represents a male disadvantage as opposed to a female advantage and that this disadvantage may be transferred from boys to girls in unlike-sex twin pairs, perhaps via an intrauterine paracrine effect.

The Frequency of Recurrent Multiple Maternities Using Two Sets of Census Data in Japan: 1990 and 1995

Frequencies of recurrent multiple maternities were estimated using two sets of census data in Japan in 1990 and 1995. The repeat frequency (RF) of the twinning rate is the frequency of 2 sets of twins among families or couples who have already had 1 set of twins and 2 more siblings. The overall RFs were 9.6 per 1000 couples in 1990 and 9.3 in 1995. The RFs of the monozygotic (MZ) twinning rates were 5.9 per 1000 couples in 1990 and 5.5 in 1995. The RFs of the dizygotic (DZ) twinning rates were 3.7 in 1990 and 3.8 in 1995. For unlike-sexed propositus twins, the RF of MZ twins were 5.0 per 1000 couples in 1990 and 5.5 in 1995. The RF of DZ twins were 5.3 in 1990 and 4.6 in 1995. As for like-sexed propositus twins, the corresponding RFs were 6.2 and 5.5 for MZ twins, and 3.4 and 3.6 for DZ twins, respectively. In mothers who have experienced a twin maternity, the overall RF of twinning was 1.5 to 2 times as high as the average mother's chance of having twins. There was no RF for triplets for both census years. As for geographic variations of the overall RF, the rates in Okinawa (16.2) and Hokkaido (15.3) were significantly higher than those in the Tohoku (8.7), Kanto (8.0) and Kyushu (7.4) districts.

O-159: Singleton and twin pregnancies after assisted reproduction (IVF And non-IVF): A risk pregnancy is born!

To investigate the perinatal morbidity and mortality of singleton and twin babies born after assisted reproduction (ART). Although non-IVF hormonal treatment is the most commonly performed infertility treatment worldwide, the majority of data reported on perinatal health of babies born after ART only include IVF and ICSI-pregnancies. In this cohort study we compared the perinatal outcome of babies born after IVF/ICSI, non-IVF (ovarian stimulation with or without artificial insemination) and natural conception (NC). The main outcome measures were gestational age, birth weight, admission to the neonatal intensive care unit (NICU), perinatal mortality and perinatal morbidity including convulsions, intracranial bleeding and assisted ventilation A retrospective cohort study of nearly all deliveries in Flanders (Belgium) from 1993 until 2004 to compare perinatal parameters of babies born after IVF/ICSI, non-IVF and natural conception. In Flanders, the Study Centre for Perinatal Epidemiology collects data on the obstetric history and perinatal events of each hospital delivery of > 21 weeks of gestational age and ≥ 500 grams at birth. Full cooperation of all 80 departments of Obstetrics in Flanders has been established since 1993. Quality of data is controlled on a full time basis through checking of the incoming records for internal inconsistencies, exactness and completeness. Correction and completion is assured by telephone calls, additional questionnaires and visits to the local departments. The data manager visits ad random the 80 maternity units to operate a double check. A total number of 691,228 births were investigated. We studied the perinatal outcome of 642,613 singletons (8,995 IVF/ICSI, 13,195 non-IVF, 642,613 NC) and 25,313 twins (6,118 IVF/ICSI, 3,349 non-IVF, 15,846 NC). Logistic regression analysis included mode of conception, female age, fetal sex, parity and year of delivery. For the statistical analysis comparing perinatal outcome differences between IVF/ICSI, non-IVF and naturally conceived births after adjustment for the different confounding factors, we used the odds-ratio, 95 % confidence interval and its corresponding p-values. IVF/ICSI singletons had a significantly worse outcome when compared to non-IVF and NC for almost all investigated perinatal parameters. Non-IVF singletons were also significantly disadvantaged for birthweight and prematurity when compared to NC. Non-IVF singletons had a better outcome for most perinatal parameters when compared to IVF/ICSI. The outcome of twin pregnancies was similar for the three groups unless only the unlike-sex twins were studied separately. Among this subgroup, IVF/ICSI carried a higher risk for low birth weight when compared to NC and non-IVF unlike-sex twins were also at increased risk for low birth weight and perinatal mortality if compared to NC. Not only multiple births are responsible for the poor perinatal outcome after assisted reproduction. Singletons born after assisted reproduction are also at increased risk when compared to natural conception babies. Singletons after IVF/ICSI have a worse prognosis compared to non-IVF. Our data also show that non-IVF infertility treatment is also responsible for a large part of the adverse outcome associated with ART-related pregnancies. Unlike-sex ART-twins were at increased risk for low birth weight and perinatal mortality if compared to NC.

Fertility Among Brothers of Patients with Testicular Cancer

Patients with testicular cancer have decreased fertility prior to the diagnosis of cancer, although it is not clear whether the subfertility is the result of an emerging tumor, or whether subfertility and testicular cancer share causes. To test if they share causes, we assessed fertility among brothers of patients with testicular cancer. We compared 5,613 siblings (2,878 brothers) of patients with germ-cell testicular cancer, diagnosed in Sweden from 1960 to 2002, with 6,151 population controls (3,202 men). Using the Swedish Multi-Generation Register, we obtained information on the number of children born (until December 2003) from cases (n = 9,480) and controls (n = 10,739). Fertility was measured using two indicators, (a) offspring twinning rates, as dizygotic twinning is reduced by male subfertility, and (b) number of children. We used unconditional logistic regression, and analyzed brothers and sisters separately. Analyses on the number of children were restricted to subjects (39%) born prior to 1954, for whom information on reproductive life until age 50 was available. Brothers, but not sisters, of patients with testicular cancer were less likely to have unlike-sex twins than controls (for unlike-sex twins, the odds ratio for the father being a sibling of testicular cancer patient was 0.53; 95% confidence interval, 0.26-1.09). The likelihood of being a brother of a patient with testicular cancer decreased monotonically with increasing number of children (P = 0.05), whereas no association was observed for the sisters. The decreased fertility found among brothers of patients with testicular cancer argues in favor of shared causes between cancer-associated subfertility and testicular cancer. Genetic links and shared environment could explain the association.

Correlates of regular cigarette smoking in a population‐based sample of Australian twins

To investigate the role of measured risk factors and the influence of genetic and environmental factors on regular cigarette smoking. Design Members of monozygotic and dizygotic, including unlike-sex twin pairs (n = 6257) from a young adult cohort from the Australian Twin Registry. Cox proportional hazards models were used to determine whether putative risk factors were significantly associated with regular cigarette smoking. Risk factors were classified into four tiers: tier 1 (parental history, including parental education, alcoholism and cigarette smoking), tier 2 (early home and family influences), tier 3 (early life events, e.g. trauma) and tier 4 (psychiatric symptoms/disorders with onset prior to 14 years), after controlling for gender, zygosity and their interactions. Genetic models were fitted to examine the heritability of smoking behavior before and after controlling for significant covariates from the four tiers. Parental history of cigarette smoking and alcoholism, parental closeness and home environment, as well as incidence of childhood sexual abuse or other trauma, a history of early onset panic attacks and conduct problems were associated with regular cigarette smoking. Important age interactions were found, particularly for family background risk factors. Regular cigarette smoking was moderately heritable, even after accounting for significant covariates. Several measured risk factors are associated with regular smoking. While some of the genetic influences on regular smoking may be shared with these risk factors, a significant proportion of the genetic vulnerability to regular smoking is phenotype-specific.

Use of folic acid supplementation and risk for dizygotic twinning

Background An increase in dizygotic twinning rate after folic acid supplementation has previously been described, but in a recent study from China, no such effect was seen. Aims To further investigate the association between use of folic acid supplement and dizygotic twinning. Study design Using the Swedish Medical Birth Registry, the rate of dizygotic twinning among infants of women who reported the use of folic acid was studied, taking a number of confounders into consideration. Comparisons were made with all women recorded in the register. Outcome measure Unlike-sexed twin pairs were used as representatives of dizygotic twinning. Results A number of confounders for the association between folic acid use and twinning were identified and taken into consideration. Women who were immigrants (who used less folic acid and had slightly lower twinning rates than women born in Sweden) and women who reported subfertility problems or treatment for subfertility (who had a high use of folic acid and a high twinning rate) were excluded, and adjustment was then made for year of birth, maternal age, parity, and smoking in early pregnancy. Folic acid use and twinning risk increased with maternal age and decreased with parity. Smokers used less folic acid than nonsmokers. Concomitant use of other drugs was no important confounder except for those used at subfertility. The odds ratio (OR) for dizygotic twinning after folic acid supplementation was then 1.71 (95%CI=1.21–2.42) and for the years 2000–2001 even 2.09 (95%CI=1.39–3.12). Conclusion There is an increase in twinning rate after folic acid supplementation in a Western population which should be taken into consideration when folic acid supplementation or food fortification is recommended.