Perinatal characteristics and risk of polio among Swedish twins

Perng W, Cnattingius S, Iliadou A, Villamor E. Perinatal characteristics and risk of polio among Swedish twins. Paediatric and Perinatal Epidemiology 2012; 26: 218–225. Prenatal exposure to adverse environmental conditions is related to increased adult mortality in regions where infections are highly prevalent, yet there is little evidence of the impact of perinatal conditions on the risk of severe infections throughout life. Using prospectively collected data from 21 604 like‐sexed Swedish twins of known zygosity born in 1926–1958, we examined the risk of polio in relation to perinatal characteristics using cohort and nested co‐twin case–control analyses. Polio incidence was determined through an interview in 1998, and linkage with the Swedish national inpatient and death registries. There were 133 cases of polio. In the cohort analysis, birth length, birthweight and head circumference were positively associated with polio risk. After adjustment for sex, birth year, gestational age at birth and within‐twin pair correlations, twins of shortest length (<44 cm) had a 67% ([95% CI: 6%, 88%]; P = 0.04) lower risk of polio compared with the reference group (47–49 cm). After additional adjustment for birth length, every 100‐g increase in birthweight was related to a 34% increased risk of polio ([95% CI: ?1%, 82%]; P = 0.06), and every 10‐mm increase in head circumference was related to a 17% greater risk of polio ([95% CI: 5%, 31%]; P = 0.004). In co‐twin control analyses among 226 disease‐discordant twins, birth length, birthweight and head circumference were 0.3 cm (P = 0.19), 84 g (P = 0.07) and 3 mm (P = 0.08) higher in cases than controls, respectively. Similar associations were observed among monozygotic (n = 84) and dizygotic (n = 142) twins. These findings suggest that early intrauterine growth restriction may be inversely related to the incidence of polio.     

活产双胎低出生体重儿影响因素分析

目的探讨活产双胎低出生体重与相关因素关系。方法将657对活产双胎按出生体重分为体重均低组、单低体重组和体重正常组,配对分析双胎性别、出生次序与低出生体重的关系;分析母亲因素（孕龄、孕周、孕次、产次、血压、血红蛋白等）与出生体重的关系。结果双胎中第2个出生胎儿为低体重者明显多于第1个出生胎儿,女婴显著多于男婴。各体重组母亲孕周、产次比较差异有统计学意义;低体重组母亲孕初舒张压显著低于正常组,血红蛋白值始终高于体重正常组。结论双胎低出生体重与胎儿性别、出生顺序、母亲孕周、产次有关。双胎母亲孕期血压、血红蛋白与胎儿低出生体重间的关系是否属于对双胎妊娠的一种适应,有待进一步探讨。     

双生子A型人格与高血压及血生化指标研究

目的 了解双生子A型人格与高血压及血液生化指标的关系。方法 利用遗传流行病学方法对青岛市89对24岁以上双生子(同卵55对，异卵34对)进行调查。并进行A型人格测试，以比较同卵与异卵双生于A型人格得分的相关程度、A型人格及血压的一致性。推测遗传与环境因素对A型人格的影响，A型人格与高血压的关系，并探讨血液生化指标与A型人格的关系。结果 经KAPPA一致性检验，同卵(MZ)双生子之间A型人格存在着显的一致性(P＜0．001)，而异卵(DZ)双生子之间的一致性无显性差异(P＝0．802)。同时，MZ双生子之间A型人格和血压也存在显的一致性(P＜0．001)，而DZ双生子之间A型人格和血压无明显一致性(P＝0．102)。有A型人格的双生子血压的收缩压明显高于非A型人格的双生子(P＜0．05)。许多生化指标与A型人格因素相关，但是所计算出的相关系数大都小于0．30，属于弱相关。结论 MZ双生子A型人格及高血压之间存在着显的一致性，而这种一致性在DZ双生子表现不明显。A型人格是高血压的危险因素之一。A型人格与所研究血液基本生化指标之间相关较弱。     

Birth weight and risk of angina pectoris: analysis in Swedish twins

Objective: Intrauterine nutrition approximated by birth weight has been shown to be inversely associated with risk of coronary heart disease (CHD). By investigating the association within twin pairs discordant for disease, the influence of genetic and early environmental factors is substantially reduced. Methods: We have investigated the association between birth weight and angina pectoris in same-sexed twins with known zygosity included in the population-based Swedish Twin Registry. Self-reports of birth weight and angina pectoris were collected in a telephone interview between 1998 and 2000. The cohort analyses were based on 4594 same-sexed twins, and the within-pair analyses included 55 dizygotic and 37 monozygotic twin pairs discordant for angina pectoris. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Results: Compared with birth weight between 2.0 and 2.9 kg, low birth weight (<2.0 kg) was associated with increased risk of angina pectoris in the twin cohort, (OR: 1.46; 95% CI: 1.14–1.87), but after adjustment for potential confounders the risk decreased, and did not reach significance. Within twin pairs discordant for angina pectoris, low birth weight was significantly associated with increased risk of angina pectoris within dizygotic twins (adjusted OR: 5.73; 95% CI: 1.59–20.67), but not within monozygotic twins (adjusted OR: 1.20; 95% CI: 0.40–3.58). Conclusions: The results suggest that genetic differences associated with foetal growth and adult risk of CHD may have affected previously reported associations between birth weight and CHD.     

The influence of birth weight and genetic factors on lipid levels: a study in adult twins

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19-50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (-0.53 mmol/l per kg (95 % CI -0.97, -0.09), P = 0.02 and -0.39 mmol/l per kg (95 % CI -0.76, -0.02), P = 0.04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.     

Maternal birthweight and outcome of twin pregnancy

There is evidence from singletons that maternal birthweight is positively related to offspring gestational length and birthweight, and some evidence of an inverse relationship with preterm birth. Among twins very preterm birth is the major cause of neonatal mortality and of immediate and later morbidity, including neurodevelopmental impairment. We hypothesised that the relationship between maternal birthweight and gestational length would be more evident in twin than in singleton pregnancies, as there is more variation in gestation in the former. Among 131 singleton mothers carrying twins, there was weak evidence of a positive relationship between maternal birthweight and twin gestational length (+0.6 weeks [95% CI -0.05, +1.3] per kg increase in maternal birthweight, but stronger evidence among 56 of these who went into labour spontaneously (+1.9 weeks [+0.7, +3.1], P = 0.003 for interaction). In the latter group we estimated that the odds of very preterm birth (at <32 weeks) were reduced by 50% [95% CI 10%, 82%] per 250 g increase in maternal birthweight. In the whole cohort, and in this subgroup, maternal birthweight was strongly positively related to both twin offspring total birthweight and total placental weight. Our data, consistent with intergenerational programming of early development, suggest the possibility of a stronger and more clinically relevant association among twins than among singletons. Nevertheless, our sample size was modest and this finding needs to be confirmed in a larger cohort.     

The relationship between maternal birthweight and gestational age in twins and singletons and those of their offspring in Norway

In order to elucidate whether maternal plurality affects offspring intrauterine growth, the relationship between birthweight and gestational age of twins and singletons and those of their first singleton liveborn children in Norway was studied using data from the Medical Birth Registry. The population-based sample consisted of 49 698 mother–offspring pairs (48 842 with singleton and 856 with twin-mothers). In bivariate analyses, no significant differences in mean birthweight and gestational age of offspring of twin and singleton mothers were found, although the mean birthweight and gestational age of the twin-mothers themselves were significantly lower than those of singletons (819 g and 14 days respectively). In multiple regression analysis, the expected birthweight of offspring was 230.3 g (95% CI: 193.2–267.4 g) higher when the mother was a twin than when the mother was a singleton, when controlling for non-standardised maternal birthweight. When adjusting for relative maternal birthweight ( z -score), the association between maternal plurality and offspring birthweight was not statistically significant. The results suggest that being born as a twin has no substantial consequences on offspring growth in utero and show that mean differences in birthweight between twins and singletons should be standardised when both groups are included in multivariate studies.     

Lifestyle factors in monozygotic and dizygotic twins

In examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like-sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4-day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within-pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely "genetic"--as implicit in conventional measures of heritability--is likely to overestimate the influence of genetic factors.     

Physical activity and mortality: is the association explained by genetic selection?

Public health recommendations promote physical activity to improve health and longevity. Recent data suggest that the association between physical activity and mortality may be due to genetic selection. Using data on twins, the authors investigated whether genetic selection explains the association between physical activity and mortality. Data were based on a postal questionnaire answered by 13,109 Swedish twin pairs in 1972. The national Cause of Death Register was used for information about all-cause mortality (n=1,800) and cardiovascular disease mortality (n=638) during 1975-2004. The risk of death was reduced by 34% for men (relative risk=0.64, 95% confidence interval: 0.50, 0.83) and by 25% for women (relative risk=0.75, 95% confidence interval: 0.50, 1.14) reporting high physical activity levels. Within-pair comparisons of monozygotic twins showed that, compared with their less active co-twin, the more active twin had a 20% (odds ratio=0.80, 95% confidence interval: 0.65, 0.99) reduced risk of all-cause mortality and a 32% (odds ratio=0.68, 95% confidence interval: 0.49, 0.95) reduced risk of cardiovascular disease mortality. Results indicate that physical activity is associated with a reduced risk of mortality not due to genetic selection. This finding supports a causal link between physical activity and mortality.     

双胎发育不均衡早产儿早期并发症及纠正年龄12月内神经系统预后分析

目的 分析双胎发育不均衡早产儿生后早期并发症及纠正年龄12月时神经发育的差异,为双胎发育不均衡早产儿预防并发症提供依据。方法 采用前瞻性队列研究,选择2016年1月1日-2017年12月31日郑州大学第三附属医院新生儿科收治的活产、双胎且出生体重差异≥25%,除外双胎输血综合征的早产儿67对,分为轻胎组67例,重胎组67例,观察其生后早期并发症和纠正年龄12月以内的神经发育发育情况。结果 1)轻胎组发生新生儿呼吸窘迫综合征(NRDS)、喂养不耐受和感染性疾病的比例,住院期间放弃或死亡例数及住院天数均高于重胎组,差异有统计学意义(t=4.418、4.251、3.983、5.858、4.733,P＜0.05)。2)双胎均痊愈出院者共55对,随访至纠正年龄12月者43对。在不同出生胎龄中(＜32周,32~33⁺⁶周,34~36⁺⁶周),轻胎组新生儿行为神经测定(NBNA)得分均显著低于重胎组(6月龄:t=3.735、2.494、2.129;12龄:t=4.850、3.269、3.381,P＜0.001);纠正年龄6月和12月龄时,不同胎龄中,轻胎组与重胎组智力发育指数(MDI)差异均无统计学意义(P>0.05),而轻胎组运动发育指数(PDI)均显著低于重胎组(t=4.269、3.233、2.578,P＜0.01)。结论 双胎发育不均衡的早产儿中,低出生体重小者生后早期并发症多,预后不良的发生率较高,要严密随访,尤其注意运动能力的发育状况。     

Maternal smoking and adverse birth outcomes among singletons and twins

OBJECTIVES: This study assessed the effects of maternal smoking on birth outcomes among singletons and twins. METHODS: An algorithm was developed to link twins with their siblings in the 1995 Perinatal Mortality Data Set. A random-effects logistic regression model was then used to estimate the association between maternal smoking and several adverse outcomes for a random sample of singletons and for all twins with available maternal smoking information. RESULTS: The algorithm successfully linked sibling pairs for 91% of the twin sample. Maternal smoking was associated with a significantly increased risk of low birthweight, very low birthweight, and gestation of less than 33 weeks for both singletons and twins and with an increased risk of gestation of less than 38 weeks, infant mortality, and placental abruption for singletons. Among smokers, negative impacts on the risk of low birthweight, very low birthweight, and extreme premature delivery were significantly higher for women carrying twins. CONCLUSIONS: Some of the negative effects of smoking on low birthweight and preterm delivery are greater for twins than for singletons. Women carrying twins should be warned that smoking increases their already high risk of serious infant health problems.     

The association between body height and coronary heart disease among Finnish twins and singletons

OBJECTIVE: An inverse association between body height and the incidence of coronary heart disease (CHD) has been observed. However, the mechanisms behind this association are still largely unknown. We will examine the role of genetic and familial factors behind the association in a large twin data set. DESIGN AND SETTING: The data were derived from the Finnish Twin cohort including 2438 singletons, 4073 monozygotic (MZ) twins, and 9202 dizygotic (DZ) twins aged 25-69 years at baseline in 1976. Incident CHD cases were derived from hospital discharge data and cause of death data between 1977 and 1995. Cox regression analysis and conditional logistic regression analysis were used. RESULTS: In population-level analyses no differences in the general risk of CHD between zygosity groups were found. The association between body height and CHD was similar between sexes and zygosity groups. When men and women in all zygosity groups were studied together an increased risk of CHD was found only among the shortest quartile (hazard ratio [HR] = 1.34, 95% CI: 1.14-1.57). Among the twin pairs discordant for CHD a suggestive increased risk for the shorter twin was seen among DZ twins (odds ratio [OR] = 1.19, 95% CI: 0.95-1.48) when men and women were studied together. CONCLUSION: An inverse association between body height and CHD was broadly similar between sexes and twin zygosity groups and was associated with short stature. Among discordant twin pairs we found a weak association among DZ twins but not MZ twins. This may suggest the role of genetic liability behind the association between body height and CHD.     

Childhood neurological disorders in twins

Summary. In order to examine neurological outcome in twins, a multicentre prospective cohort study of infants was used. Women entered at the first prenatal visit, with follow-up of offspring to the age of 7 years. Outcome measures were death, cerebral palsy, seizure disorders including neonatal, febrile or nonfebrile, and intelligence quotient. Among a total of 52364 livebirths, there were 1079 twins. Overall, rates of fetal or neonatal death and cerebral palsy were higher in twins. Neonatal and febrile seizures occurred with similar frequency in twins as in singletons. Although twins were much more likely than singletons to be low in birthweight, twins < 2500 g were not at higher risk for cerebral palsy than low birthweight singletons. The risk of cerebral palsy and of nonfebrile seizure disorders was similar in monozygous and dizygous pairs, and in like-sex and unlike-sex pairs. Death of one twin was associated with higher rates of cerebral palsy and of nonfebrile seizure disorders in survivors, but not with lowered intelligence. Data from this cohort suggest that low birthweight and survival status of the co-twin are dominant predictors of childhood neurological morbidity in twins.     

The role of genetic and environmental factors in the association between birthweight and blood pressure: evidence from meta-analysis of twin studies

BACKGROUND: An inverse association between birthweight and later blood pressure has been found in many studies in singletons. Twin studies have been used to examine whether genetic factors or family environment could account for this association. METHODS: A systematic review identified 10 studies covering 3901 twin pairs. Meta-analysis of regression coefficients for the association between birthweight and systolic blood pressure was carried out for unpaired versus paired associations and for paired associations in dizygotic versus monozygotic pairs. RESULTS: After adjustment for current weight or body mass index (BMI), the difference in systolic blood pressure per kg birthweight was -2.0 (95% CI: -3.2, -0.8) mmHg in the unpaired analysis and -0.4 (95% CI: -1.5, 0.7) mmHg in the paired analysis in the same subjects. In the paired analysis by zygosity, in all twins the coefficients were -0.7 (95% CI: -2.3, 0.8) mmHg in dizygotic pairs and -0.8 (95% CI: -2.1, 0.4) mmHg in monozygotic pairs, but in studies which included zygosity tests the coefficients were -1.0 (95% CI: -3.3, 1.6) mmHg in dizygotic pairs and -0.4 (95% CI: -1.9, 1.3) mmHg in monozygotic pairs. CONCLUSIONS: The attenuation of the regression coefficient in the paired analysis provides support for the possibility that factors shared by twins contribute to the association between birthweight and blood pressure in singletons. Comparison of paired analysis in monozygotic and dizygotic pairs could not provide conclusive evidence for a role for genetic as opposed to shared environmental factors.     

Shared transmission of eating disorders and anxiety disorders

OBJECTIVE: Eating disorders have high comorbidity with mood, anxiety, and substance use disorders. Using twins from the population-based Minnesota Twin Family Study (MTFS), we examined comorbidity and shared transmission between eating pathology and these disorders. METHOD: Female twins (N = 672), ages 16-18 years, completed structured clinical interviews assessing anorexia nervosa and bulimia nervosa (as described in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV; American Psychiatric Association, 1994]), as well as mood, anxiety, and substance use disorders (as described in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders [DSM-III-R]). Shared transmission was examined using a discordant monozygotic (MZ) twin design. RESULTS: Significant comorbidity was found between eating disorders and major depression, anxiety disorders, and nicotine dependence. Within MZ twin pairs discordant for eating disorders (n = 14), non-eating-disordered cotwins demonstrated increased risk for anxiety disorders compared with controls. Similarly, within MZ twin pairs discordant for anxiety disorders (n = 52), non-anxiety-disordered cotwins demonstrated increased risk for eating disorders compared with controls. DISCUSSION: Findings support shared transmission between eating disorders and anxiety disorders. However, the nature of this shared diathesis remains unknown.     

Regression models for clustered binary responses: implications of ignoring the intracluster correlation in an analysis of perinatal mortality in twin gestations

PURPOSE: Dependent binary responses, such as health outcomes in twin pairs or siblings, frequently arise in perinatal epidemiologic research. This gives rise to correlated data, which must be taken into account during analysis to avoid erroneous statistical and biological inferences. METHODS: An analysis of perinatal mortality (fetal deaths plus deaths within the first 28 days) in twins in relation to cluster-varying (those that are unique to each fetus within a twin pregnancy such as birthweight) and cluster-constant (those that are identical for both twins within a sibship such as maternal smoking status) risk factors is presented. Marginal (ordinary logistic regression [OLR] and logistic regression using generalized estimating equations [GEE]) and cluster-specific (conditional and random-intercept logistic regression models) regression models are fit and their results contrasted. The United States "matched multiple data" file of twin births (1995-1997), which includes 285,226 twins from 142,613 pregnancies, was used to examine the implications of ignoring of clustering on regression inferences. RESULTS: The OLR models provide variance estimates for cluster constant covariates that ranged from 7% to 71% smaller than those from GEE-based models. This underestimation is even more pronounced for some cluster-varying covariates, ranging from 21% to 198%. CONCLUSIONS: Ignoring the cluster dependency is likely to affect the precision of covariate effects and consequently interpretation of results. With widespread availability of appropriate software, statistical methods for taking the intracluster dependency into account are easily implemented and necessary.     

Atopic diseases in twins born after assisted reproduction

We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations.     

Genetic susceptibility to burnout in a Swedish twin cohort

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout.     

Fetal growth and neonatal mortality in Korea

The fetal growth curve and neonatal mortality rate, based on gestational age and birthweight, are important for identifying groups of high-risk neonates and developing appropriate medical services and health-care programmes. The purpose of this study was to develop a national fetal growth curve for neonates in Korea, and examine the Korean national references for fetal growth and death according to their characteristics. Data of Korean vital statistics linked National Infant Mortality Survey conducted on births in 1999 were used in this study. The total livebirths were 621,764 in 1999, which were grouped into singletons (n = 609,643) and twins (n = 9805) for analysis. Birthweight/gestational age-specific fetal growth curves and neonatal mortality rates were based on 250 g of birthweight and weekly gestational age intervals for each characteristic of the birth. The features of high-risk neonates such as small-for-gestational-age and the limit of viability in Korea were different from those of Western countries. Difference in fetal growth and death was also detected in other characteristics of the fetus (gender and plurality of birth) besides race. The fetal growth curve of males was higher than that of females, and was higher in singleton than in twins. The neonatal mortality rate was higher in males (singleton, 2.6; twin, 23.5) than females (singleton, 2.1; twin, 15.9), and higher in twins (19.8/1000) than in singletons (2.4/1000). However, in neonates with gestational age >29 weeks and birthweight >1000 g, the neonatal mortality rate was lower in twins than in singletons. The limit of viability was gestational age 27 weeks and birthweight 1000 g, which was similar in singletons and twins regardless of gender. To improve the health of neonates in a country, it is imperative to investigate the characteristics of fetal growth and death under the particular circumstances of the country. When risk is defined for neonates account must be taken of differences in race, gender and plurality of birth, as the neonatal mortality rate varies depending on those factors.