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Objective: The aims of this study were to investigate and compare the prevalence of dental caries and the frequency of oral habits, molar relationships and occlusal traits between children of multiple births, and singletons, and to determine the relative contributions of genetics and environmental factors to these parameters by using twin study design. Methods: The study group consisted of 345 multiple births (34 monozygotic and 122 dizygotic twin pairs, 11 sets of triplets) and 345 singletons between the ages of 2 and 17. The prevalence of dental caries, and the frequency of tooth brushing, the children's oral habits, molar relationships, and occlusal traits were recorded. Results: The percentage of children who brushed their teeth more than twice daily was statistically significantly higher in multiple births than in singletons. Higher correlation coefficients were found in dental caries index, except for decayed, filled (df) (2–5 age group) and filled (f) (6–11 age group), in the monozygotic twin pairs compared to those in the dizygotic twin pairs. In children between the ages of 6 and 11 years, mouth breathing, bruxism, lip biting, and pencil biting were higher in singletons than in children of multiple births. There were statistically significant differences between children of multiple births and singletons, with increased overjet in the 2–5 year age group being observed. Conclusion: When analyzing these parameters, environmental factors must also be investigated. Due to the low incidence of twin births, longitudinal follow-up studies with more twin pairs are necessary to determine whether these results are generalizable. [ABSTRACT FROM AUTHOR]

Background: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications. [ABSTRACT FROM AUTHOR]

Background: The rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11-14 weeks for prevention of preterm birth.Methods: This is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome.Results: A total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks.Conclusions: Rectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth.Trial Registration: The trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120. [ABSTRACT FROM AUTHOR]

Background: The analysis of twin data presents a unique challenge. Second-born twins on average weigh less than first-born twins and have an elevated risk of perinatal mortality. It is not clear whether the risk difference depends on birth order or their relative birth weight. This study evaluates the association between birth order and perinatal mortality by birth order-specific weight difference in twin pregnancies.Methods: We adopt generalized additive mixed models (GAMMs) which are a flexible version of generalized linear mixed models (GLMMs), to model the association. Estimation of such models for correlated binary data is challenging. We compare both Bayesian and likelihood-based approaches for estimating GAMMs via simulation. We apply the methods to the US matched multiple birth data to evaluate the association between twins' birth order and perinatal mortality.Results: Perinatal mortality depends on both birth order and relative birthweight. Simulation results suggest that the Bayesian method with half-Cauchy priors for variance components performs well in estimating all components of the GAMM. The Bayesian results were sensitive to prior specifications.Conclusion: We adopted a flexible statistical model, GAMM, to precisely estimate the perinatal mortality risk differences between first- and second-born twins whereby birthweight and gestational age are nonparametrically modelled to explicitly adjust for their effects. The risk of perinatal mortality in twins was found to depend on both birth order and relative birthweight. We demonstrated that the Bayesian method estimated the GAMM model components more reliably than the frequentist approaches. [ABSTRACT FROM AUTHOR]

Background: Telomere attrition is extremely rapid during the first years of life, while lifestyle during adulthood exerts a minor impact. This suggests that early life is an important period in the determination of telomere length. We investigated the importance of the early-life environment on both telomere tracking and adult telomere length.Methods: Among 184 twins of the East Flanders Prospective Twin Survey, telomere length in placental tissue and in buccal cells in young adulthood was measured. Residential addresses at birth and in young adulthood were geocoded and residential traffic and greenness exposure was determined.Results: We investigated individual telomere tracking from birth over a 20 year period (mean age (SD), 22.6 (3.1) years) in association with residential exposure to traffic and greenness. Telomere length in placental tissue and in buccal cells in young adulthood correlated positively (r = 0.31, P < 0.0001). Persons with higher placental telomere length at birth were more likely to have a stronger downward shift in telomere ranking over life (P < 0.0001). Maternal residential traffic exposure correlated inversely with telomere length at birth. Independent of birth placental telomere length, telomere ranking between birth and young adulthood was negatively and significantly associated with residential traffic exposure at the birth address, while traffic exposure at the residential address at adult age was not associated with telomere length.Conclusions: Longitudinal evidence of telomere length tracking from birth to adulthood shows inverse associations of residential traffic exposure in association with telomere length at birth as well as accelerated telomere shortening in the first two decades of life. [ABSTRACT FROM AUTHOR]

Background: Weight gain during pregnancy has an important impact on maternal and neonatal health. Unlike the Institute of Medicine (IOM) recommendations for weight gain in singleton pregnancies, those for twin gestations are termed "provisional", as they are based on limited data. The objectives of this study were to determine the neonatal and maternal outcomes associated with gaining weight below, within and above the IOM provisional guidelines on gestational weight gain in twin pregnancies, and additionally, to explore ranges of gestational weight gain among women who delivered twins at the recommended gestational age and birth weight, and those who did not.Methods: A retrospective cohort study of women who gave birth to twins at ≥20 weeks gestation, with a birth weight ≥ 500 g was conducted in Nova Scotia, Canada (2003-2014). Our primary outcome of interest was small for gestational age (<10th percentile). In order to account for gestational age at delivery, weekly rates of 2nd and 3rd trimester weight gain were used to categorize women as gaining below, within, or above guidelines. We performed traditional regression analyses for maternal outcomes, and to account for the correlated nature of the neonatal outcomes in twins, we used generalized estimating equations (GEE).Results: A total of 1482 twins and 741 mothers were included, of whom 27%, 43%, and 30% gained below, within, and above guidelines, respectively. The incidence of small for gestational age in these three groups was 30%, 21%, and 20%, respectively, and relative to gaining within guidelines, the adjusted odds ratios were 1.44 (95% CI 1.01-2.06) for gaining below and 0.92 (95% CI 0.62-1.36) for gaining above. The gestational weight gain in women who delivered twins at 37-42 weeks with average birth weight ≥ 2500 g and those who delivered twins outside of the recommend ranges were comparable to each other and the IOM recommendations.Conclusions: While gestational weight gain below guidelines for twins was associated with some adverse neonatal outcomes, additional research exploring alternate ranges of gestational weight gain in twin pregnancies is warranted, in order to optimize neonatal and maternal outcomes. [ABSTRACT FROM AUTHOR]

Background: X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression.Case Presentation: We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G > A (p. Trp96Ter) mutation was detected in both patients.Conclusions: Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy. [ABSTRACT FROM AUTHOR]

Background: Results from observational studies suggest that people who drink little or no alcohol are less healthy than medium drinkers. This has been demonstrated for many different measures of health, including sick leave. However, whether these associations are causal or due to confounding remains to be clarified. The aim of this study was to use a discordant twin design to determine whether the increased level of sick leave associated with a low level of alcohol consumption, as compared to those with a medium level of consumption, reflects a causal mechanism or is due to genetic or environmental confounding.Methods: Six thousand seven hundred thirty-four young adult twins from the Norwegian Institute of Public Health's twin panel were in 1998 assessed for frequency of alcohol use and binge drinking. Data were linked to the Norwegian National Insurance Administration's recordings of sick leave over a 10 year period. The associations between alcohol consumption and sick leave were first estimated in the total study population, and then within di- and monozygotic twin pairs discordant for alcohol use.Results: Compared to medium consumption, both low and high alcohol consumption was associated with increased risk of sick leave. When low level drinkers were compared to medium level drinkers in a discordant twin design, the results were consistent with the association being due to genetic confounding rather than a causal effect.Conclusions: The increased level of sick leave observed with low level drinkers seems to be mainly explained by confounding from genetic factors. In all observational studies of the relationship between alcohol consumption and health, one should be aware that important genetic confounders are likely to influence the results. [ABSTRACT FROM AUTHOR]

Background: Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding.Methods: This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day) was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models.Results: Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations.Conclusions: Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow-up. The association was found after adjusting for several confounders, including familial factors. Hence, the results point to the conclusion that education has an independent role in the development of long-term physical inactivity and tailored efforts to promote physical activity among lower educated people would be needed throughout adulthood. [ABSTRACT FROM AUTHOR]

Background: Obesity is a multifactorial abnormality which has an underlying genetic control but requires environmental influences to trigger. Numerous epidemiological studies have examined the roles of physical inactivity and dietary factors in obesity development. Interactions between obesity-related genes and these lifestyles have also been confirmed. However, less attention has been paid to these complex relationship between cigarette smoking, alcohol drinking and obesity. The purpose of this study was to assess whether cigarette smoking and alcohol drinking were associated with body mass index (BMI), and whether these lifestyle factors modified the genetic variance of BMI.Methods: Subjects were twins recruited through the Chinese National Twin Registry, aged 18 to 79 years, and the sample comprised 6121 complete male twin pairs. Information on height, weight, cigarette smoking and alcohol drinking status were assessed with self-report questionnaires. The associations of cigarette smoking and alcohol drinking with BMI were evaluated by linear regression models. Further, structure equation models were conducted to estimate whether cigarette smoking and alcohol drinking status modified the degree of genetic variance of BMI.Results: After adjustment for a variety of socio-demographic and lifestyle factors, former smokers had higher BMI (β = 0.475; 95 % CI, 0.196 to 0.754) whereas moderate to heavy smokers had lower BMI (β = -0.115; 95 % CI, -0.223 to -0.007) when compared with nonsmokers. BMI decreased with increased cigarette pack-years (β = -0.008; 95 % CI, -0.013 to -0.003). These effects still existed substantially in within-MZ twin pair analyses. By contrast, current alcohol drinking had no significant influence on BMI when additionally controlled for shared factors in within-pair analyses. Genetic modification by alcohol drinking was statistically significant for BMI (β = -0.137; 95 % CI, -0.215 to -0.058), with the intake of alcohol decreasing the additive genetic component of BMI.Conclusions: Cigarette smoking was negatively associated with BMI independent of genetic influences. The influence of genes on BMI was moderated by alcohol drinking, such that for individuals who were regular drinkers, genetic factors became less influential. Our findings highlight gene-alcohol interaction in finding candidate genes of BMI and elucidating the etiological factors of obesity. [ABSTRACT FROM AUTHOR]

Compared to singletons, multiple births are associated with a substantially-higher risk of maternal and perinatal mortality worldwide. However, little evidence exists on the perinatal profile and risk of neurodevelopmental disabilities among the survivors, especially in developing countries. This cross-sectional study, therefore, set out to determine the adverse perinatal outcomes that are potential markers for neurodevelopmental disabilities in infants with multiple gestations in a developing country. In total, 4,573 mothers, and their 4,718 surviving offspring in an inner-city maternity hospital in Lagos, Nigeria, from May 2005 to December 2007, were recruited. Comparisons of maternal and infant outcomes between single and multiple births were performed using multivariable logistic regression and generalized estimation equation analyses. Odds ratio (OR) and the corresponding 95% confidence interval (CI) for each marker were estimated. Of the 4,573 deliveries, there were 4,416 (96.6%) singletons and 157 (3.4%) multiples, comprising 296 twins and six triplets together (6.4% of all live 4,718 infants). After adjusting for maternal age, ethnicity, occupation, parity, and antenatal care, multiple gestations were associated with increased risks of hypertensive disorders and caesarean delivery. Similarly, after adjusting for potential maternal confounders, multiple births were associated with low five-minute Apgar score (OR: 1.47, 95% CI 1.13-1.93), neonatal sepsis (OR: 2.16, 95% CI 1.28-3.65), severe hyperbilirubinaemia (OR: 1.60, 95% CI 1.00-2.56), and admission to a special-care baby unit (OR: 1.56, 95% CI 1.12-2.17) underpinned by preterm delivery before 34 weeks (OR: 1.91, 95% CI 1.14-3.19), birthweight of less than 2,500 g (OR: 6.45, 95% CI 4.80-8.66), and intrauterine growth restriction (OR: 9.04, 95% CI 6.62-12.34). Overall, the results suggest that, in resourcepoor settings, infants of multiple gestations are associated with a significantly-elevated risk of adverse perinatal outcomes. Since these perinatal outcomes are related to the increased risk of later neurodevelopmental disabilities, multiple-birth infants merit close developmental surveillance for timely intervention. [ABSTRACT FROM AUTHOR]

Background: Most studies have revealed that the incidence of morbidity and mortality of preterm male infants is greater than that of preterm female infants. Recently, conflicting outcomes have been reported regarding mixed-gender twins. The aim of this study was to estimate the association between gender and outcome in newborn twins of different gender.Methods: We conducted a retrospective review of mixed-gender twins weighing < 1500 g that were born at Shamir Medical Center (Assaf Harofeh) between the years 1995 and 2016 (158 newborns). The incidence of morbidity and mortality until discharge from the hospital were evaluated while looking at gender differences.Results: No significant differences were found in neonatal mortality or morbidity between females and males from different-gender twins. Even after considering confounding variables (gestational age, birth weight & birth order) in linear and logistic regression models, no significant differences were found between the genders.Conclusions: Our study suggests that there are no significant differences in neonatal mortality or morbidity among different-gender twins. Our results support the need for further studies. [ABSTRACT FROM AUTHOR]

Background: Late Language Emergence (LLE) in the first two years of life is one of the most common parental concerns about child development and reasons for seeking advice from health professionals. LLE is much more prevalent in twins (38%) than singletons (20%). In studies of language development in twins without overt disability, adverse prenatal and perinatal environments have been reported to play a lesser role in the etiology of LLE than adverse postnatal environments. However, there is a lack of population-level evidence about prenatal and perinatal risk factors for LLE in twins. This study investigated the extent to which prenatal and perinatal risk factors were associated with LLE in a population-level sample of twins at age 2 without overt disability.Methods: The sample comprised 473 twin pairs drawn from a population sample frame comprising statutory notifications of all births in Western Australia (WA), 2000-2003. Twin pairs in which either twin had a known developmental disorder or exposure to language(s) other than English were excluded. Of the 946 twins, 47.9% were male. There were 313 dizygotic and 160 monozygotic twin pairs. LLE was defined as a score at or below the gender-specific 10th percentile on the MacArthur Communicative Development Inventories: Words and Sentences (CDI-WS) (Words Produced). Bivariate and multivariable logistic regression was used to investigate risk factors associated with LLE.Results: In the multivariable model, risk factors for LLE in order of decreasing magnitude were: Gestational diabetes had an adjusted odds ratio (aOR) of 19.5 (95% confidence interval (CI) 1.2, 313.1); prolonged TSR (aOR: 13.6 [2.0, 91.1]); multiparity (aOR: 7.6 [1.6, 37.5]), monozygosity (aOR: 6.9 [1.7, 27.9]) and fetal growth restriction (aOR: 4.6 [1.7, 12.7]). Sociodemographic risk factors (e.g., low maternal education, socioeconomic area disadvantage) were not associated with increased odds of LLE.Conclusions: The results suggest that adverse prenatal and perinatal environments are important in the etiology of LLE in twins at age 2. It is important that health professionals discuss twin pregnancy and birth risks for delayed speech and language milestones with parents and provide ongoing developmental monitoring for all twins, not just twins with overt disability. [ABSTRACT FROM AUTHOR]