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Published in final edited form as: Twin Res Hum Genet. 2016 Apr;19(2):112–124. doi: 10.1017/thg.2016.11

Twin’s birth-order differences in height and body mass index from birth to old age: a pooled study of 26 twin cohorts participated in the CODATwins project

Yoshie Yokoyama 1, Aline Jelenkovic 2,3, Reijo Sund 2, Joohon Sung 4,5, John L Hopper 6,4, Syuichi Ooki 7, Kauko Heikkilä 8, Sari Aaltonen 2,8, Adam D Tarnoki 9,10, David L Tarnoki 9,10, Gonneke Willemsen 11, Meike Bartels 11, Toos CEM van Beijsterveldt 11, Kimberly J Saudino 12, Tessa L Cutler 6, Tracy L Nelson 13, Keith E Whitfield 14, Jane Wardle 15,, Clare H Llewellyn 15, Abigail Fisher 15, Mingguang He 16,17, Xiaohu Ding 16, Morten Bjerregaard-Andersen 18,19,20, Henning Beck-Nielsen 20, Morten Sodemann 21, Yun-Mi Song 22, Sarah Yang 4,5, Kayoung Lee 23, Hoe-Uk Jeong 24, Ariel Knafo-Noam 25, David Mankuta 26, Lior Abramson 25, S Alexandra Burt 27, Kelly L Klump 27, Juan R Ordoñana 28,29, Juan F Sánchez-Romera 30,29, Lucia Colodro-Conde 28,31, Jennifer R Harris 32, Ingunn Brandt 32, Thomas Sevenius Nilsen 32, Jeffrey M Craig 33,34, Richard Saffery 33,34, Fuling Ji 35, Feng Ning 35, Zengchang Pang 35, Lise Dubois 36, Michel Boivin 37,38, Mara Brendgen 39, Ginette Dionne 37, Frank Vitaro 40, Nicholas G Martin 41, Sarah E Medland 41, Grant W Montgomery 42, Patrik KE Magnusson 43, Nancy L Pedersen 43, Anna K Dahl Aslan 43,44, Per Tynelius 45, Claire MA Haworth 46, Robert Plomin 47, Esther Rebato 3, Richard J Rose 48, Jack H Goldberg 49, Finn Rasmussen 45, Yoon-Mi Hur 50, Thorkild IA Sørensen 51,46,52, Dorret I Boomsma 11, Jaakko Kaprio 8,53,54, Karri Silventoinen 2,55
PMCID: PMC5100672  NIHMSID: NIHMS826775  PMID: 26996222

Abstract

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were not statistically significant anymore. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first and second born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Keywords: birth order, BMI, height, zygosity


It is well known that growth patterns of twins during the third trimester of pregnancy differ from those of singletons. In addition to having two fetuses in utero, there are twin-specific factors, such as birth order (Glinianaia et al., 2000; Gielen, et al., 2007), zygosity (Loos,et al., 2005; Daw, et al., 1975; Buckler & Green, 2008) and chorionicity (Gruenwald, 1970; Ananth, et al., 1998; Naeye, et al., 1966; Bleker, et al., 1979; Gielen M, et al., 2009; van Beijsterveldt et al. 2015), which are associated with intrauterine twin growth. Previous studies of twins have reported that the second-born twin is, on average, lighter than the first-born twin at birth (Glinianaia et al., 2000; Gielen, et al., 2007; van Baal and Boomsma, 1998). The factors determining birth order have a greater influence on birth weight than zygosity or chorionicity (Gielen, et al., 2007; Sheay, et al., 2004).

The lower birth weight for second-born twins could be due to the fact that first-born twins have higher placental weights and have more often a central insertion of the umbilical cord, which are both positively correlated with birth weight. Possibly, first-born twins are also more optimally positioned with respect to nutrients intake (Gielen et al., 2006; Heinonen, et al, 1996). In addition, previous studies have shown that first-born twins are, on average, taller and heavier than second-born twins until adolescence (Silventoinen et al., 2007; Pietiläinen et al., 2002). Second-born twins have also higher morbidity and mortality (Armson, et al., 2006; Smith, et al., 2007; Shinwell et al., 2004; Luo, et al., 2014).

The persistence of the birth-order association suggests that prenatal factors can have long-lasting effects on body size. However, it is not known how these associations may change over the life course. Studies on age-dependent birth order differences in height and body mass index (BMI) are scarce, and small sample sizes make comparisons of the existing results difficult. Further, it is not known whether the factors behind birth order differences in height and BMI also induce variance differences. In this study, we aim to analyze birth-order differences in means and variances of height and BMI among MZ and DZ twins from infancy to old age and to test whether they can be explained by differences in birth weight. The data were derived from the large international CODATwins database, which was intended to collect together height and weight measurements from all twin cohorts in the world.

Data and methods

In the CODATwins database (Silventoinen, et al., 2015), there are 960,859 height and weight measures from twins at ages ranging from 0.5 to 103 years. Information on birth order, height and weight measures were self-reported (67%), parentally reported (19%), or based on measures by nurses and clinicians (14%). In this study, we included the following cohorts with information on birth order: Australian Twin Registry, Boston University Twin Project, Carolina African American Twin Study of Aging, FinnTwin12, FinnTwin16, Gemini Study, Guangzhou Twin Eye Study, Guinea-Bissau Twin Study, Hungarian Twin Registry, Japanese Twin Cohort, Korean Twin-Family Register, Longitudinal Israeli Study of Twins, Michigan Twins Study, Murcia Twin Registry, Norwegian Twin Registry, Peri/Postnatal Epigenetic Twins Study, Qingdao Twin Registry of Children, Quebec Newborn Twin Study, Queensland Twin Register, Swedish Young Male Twins Study of Adults, Swedish Young Male Twins Study of Children, South Korea Twin Registry, Swedish Twin Cohorts, Twins Early Developmental Study, West Japan Twins and Higher Order Multiple Births Registry and Young Netherlands Twin Registry. Height and weight measurement protocols, sample frames and other basic information of these cohorts have been described elsewhere (Silventoinen, et al., 2015). Age was classified to 1-year age groups from age 1 to 19 years (e.g., age 1 refers to 0.5–1.5 years range), and 10-year age groups from age 20 to 79 years (e.g., 20–29, . . . , and age 70–79 years). Since the number of twin participants at 80 years of age or older was small, this group was excluded from the analyses.

In total, we had 429,587 height and BMI measurements at ages 0.5–79.5 years with information on birth order. Additionally we had information on birth weight from 107,782 and birth length from 54,941 twin individuals. BMI was calculated as weight (kg)/square of height (m2). Outliers were checked by visual inspection of histograms for each age and sex group. They were removed to obtain an approximately normal distribution of height, whereas the distribution of BMI was allowed to be positively skewed. The number of observations removed (n=1134) represented less than 0.3% of the whole database. We also excluded extreme birth length (<25cm or >65 cm) or birth weight (<500g or >6000g) values. For the purpose of this study, we restricted the analyses to one observation per individual in each age group. The total number of height and BMI measures in this study was 397,466; in 307,606 of these cases we had information also on birth weight.

Equality of mean values between first- and second- born twins by zygosity, age group and sex was tested using fixed effects regression analysis corrected for clustering of twin pairs. Equality of variances was tested using the Levene’s clustered test based on the 10% trimmed mean (Iachine et al. 2010). This clustered version of the Levene’s test is robust under the non-normality of outcomes. The interaction effects between zygosity and birth order were tested using Bonferroni correction of multiple testing with alpha level 0.0005 (0.05/100 tests). Percentage difference (%) between first- and second-born twins in mean values [(first born mean-second born mean) / second born mean] * 100 and standard deviations (SD) [(first born SD-second born SD) / second born SD] * 100 of height and BMI were calculated by sex. We also tested how the adjustment for birth weight affected the birth order difference on height and BMI in the cohorts having this information available using the fixed effects multiple regression model in each age groups. Statistical analyses were conducted using the Stata statistical software package (version 12.0; StataCorp, College Station, Texas, USA).

The pooled analysis was approved by the ethical board of the Department of Public Health, University of Helsinki. The data collections procedures of participating twin cohorts were approved by local ethical boards following the regulation in each country. Only anonymized data were delivered to the data management center at University of Helsinki.

Results

Table 1 provides the mean birth length and birth weight according to birth order, sex and zygosity. In MZ twins, the first-born male twins had greater length than the second-born male twins. However, in DZ twins, average birth length was not significantly different between the first-born and the second-born twins. In MZ and DZ twins, the first-born twins had greater birth weight than the second-born twins. The SDs of birth weight in the first-born and the second-born twins in MZ and DZ twins were significantly different except in MZ boys.

Table 1.

Number of twin individuals, mean and standard deviation of birth length (cm) and birth weight (kg) by birth order, sex and zygosity

Birth order Boys
Girls
N Mean p valuea SD p valueb N Mean p valuea SD p valueb
Monozygotic twins Birth length 1 5304 47.0 0.002 3.58 0.001 5101 46.3 0.132 3.58 0.085
2 5293 46.8 3.69 5070 46.2 3.64
Birth weight (kg) 1 9617 2.54 <0.001 0.56 0.067 10383 2.43 <0.001 0.54 <0.001
2 9524 2.51 0.57 10330 2.39 0.55
Dizygotic twins Birth length 1 9160 47.4 0.207 3.55 0.009 7967 46.8 0.191 3.60 0.018
2 8914 47.4 3.65 8132 46.7 3.64
Birth weight (kg) 1 17468 2.63 <0.001 0.57 0.005 16562 2.53 <0.001 0.55 0.001
2 17098 2.58 0.58 16800 2.47 0.56

p valuea: p value for equality of means, p valueb: p value for equality of variances, SD: standard deviation.

Descriptive statistics by birth order, age, and sex in MZ and DZ twins are presented in Table 2 and 3 for height, respectively. Sample size for each birth order, age, and sex group ranged between 421 and 5,407 individuals from age 1 through 19 years, and between 117 and 4,398 individuals in adulthood (≥20 years). The 6 and ≥70-year age groups in MZ twins had the smallest sample sizes. In MZ twins, significantly taller height in the first-born than in the second-born twins were observed at the age of one, three, five, eight and 10 years in men and from the age of one to three, seven and 12 years in women (Table 2). However, in DZ twins, average height was not significantly different between the first-born and the second-born twins (Table 3). The SDs of height in the first-born and the second-born twins in MZ and DZ twin were not significantly different in the majority of age groups. Results were similar in men and women.

Table 2.

Number of twin individuals, mean and standard deviation of height (cm) by birth order, age and sex in monozygotic twins

Men
Women
Birth order N Mean p valuea SD p valueb N Mean p valuea SD p valueb
Age 1 1 2843 73.6 0.029 4.54 0.176 2994 72.4 0.014 4.55 0.267
2 2838 73.5 4.59 2991 72.3 4.55
Age 2 1 2310 86.5 0.121 4.41 0.047 2339 85.4 0.020 4.42 0.307
2 2293 86.4 4.46 2323 85.3 4.44
Age 3 1 2830 95.8 0.044 4.45 0.264 3140 94.9 0.002 4.39 0.775
2 2834 95.7 4.47 3125 94.8 4.38
Age 4 1 1600 102.1 0.181 5.17 0.045 1594 101.0 0.116 5.13 0.118
2 1588 101.9 5.33 1595 100.9 5.29
Age 5 1 1272 110.8 0.018 5.91 0.770 1341 110.2 0.299 6.16 0.496
2 1266 110.7 5.93 1328 110.1 6.06
Age 6 1 528 114.1 0.279 6.45 0.856 427 112.9 0.834 5.66 0.180
2 512 113.7 6.40 421 112.9 5.88
Age 7 1 2345 123.6 0.216 6.62 0.134 2540 122.9 0.020 6.49 0.973
2 2330 123.5 6.72 2536 122.8 6.53
Age 8 1 1057 127.6 0.016 6.35 0.322 1020 127.0 0.077 6.42 0.209
2 1042 127.4 6.23 1021 126.8 6.56
Age 9 1 1042 133.0 0.143 6.97 0.509 1005 132.0 0.232 6.93 0.590
2 997 132.8 7.04 986 131.8 6.92
Age 10 1 1988 140.0 0.044 7.18 0.737 2088 139.8 0.115 7.41 0.199
2 1924 139.9 7.19 2048 139.7 7.47
Age 11 1 1530 143.4 0.470 7.15 0.959 1588 144.2 0.180 7.30 0.003
2 1470 143.3 7.12 1530 144.0 7.48
Age 12 1 2032 151.4 0.434 8.30 0.884 2127 152.3 0.036 8.01 0.030
2 1955 151.3 8.24 2053 152.1 8.18
Age 13 1 692 157.9 0.693 9.30 0.301 642 157.3 0.269 7.40 0.494
2 620 157.6 9.39 591 157.2 7.54
Age 14 1 1328 165.4 0.815 8.95 0.808 1497 161.8 0.441 6.68 0.066
2 1280 165.4 9.09 1468 161.8 6.85
Age 15 1 658 171.5 0.433 8.68 0.968 639 164.5 0.615 7.32 0.029
2 639 171.7 8.70 606 165.1 7.00
Age 16 1 1074 175.5 0.731 7.61 0.546 1311 164.4 0.398 6.56 0.067
2 1028 175.5 7.56 1257 164.5 6.34
Age 17 1 1100 177.7 0.315 7.29 0.608 1411 165.6 0.710 6.62 0.601
2 1074 177.8 7.47 1388 165.8 6.59
Age 18 1 1253 178.9 0.207 7.05 0.085 826 166.1 0.450 6.48 0.495
2 1253 178.9 6.89 812 166.1 6.64
Age 19 1 639 179.2 0.345 7.04 0.250 717 166.1 0.255 6.98 0.279
2 607 179.3 6.85 702 165.9 6.83
Age 20–29 1 2890 179.2 0.117 6.90 0.412 3488 164.5 0.881 6.50 0.839
2 2878 179.0 6.98 3478 164.6 6.47
Age 30–39 1 2305 178.1 0.360 7.04 0.494 3378 164.0 0.233 6.67 0.554
2 2290 177.9 6.92 3349 164.0 6.62
Age 40–49 1 1420 177.2 0.295 7.04 0.370 1886 163.2 0.924 6.65 0.436
2 1355 177.1 7.03 1844 163.1 6.58
Age 50–59 1 1038 176.4 0.805 7.02 0.181 1601 162.5 0.613 6.50 0.047
2 1029 176.3 7.22 1609 162.4 6.70
Age 60–69 1 506 174.9 0.386 6.40 0.006 880 161.7 0.660 6.30 0.297
2 494 174.4 6.99 878 161.9 6.47
Age 70–79 1 126 173.7 0.412 7.09 0.199 273 161.3 0.378 6.91 0.162
2 117 173.1 7.48 268 160.8 6.61

p valuea: p value for equality of means, p valueb: p value for equality of variances, SD: standard deviation.

Table 3.

Number of twin individuals, mean and standard deviation of height (cm) by birth order, age and sex in dizygotic twins

Men
Women
Birth order N Mean p valuea SD p valueb N Mean p valuea SD p valueb
Age 1 1 5088 74.8 0.051 4.11 0.531 4759 73.4 0.113 4.06 0.359
2 4962 74.6 4.11 4821 73.2 4.14
Age 2 1 4184 87.4 0.340 4.22 0.265 3815 86.3 0.141 4.34 0.189
2 4102 87.2 4.28 3871 86.1 4.27
Age 3 1 5407 96.6 0.074 4.43 0.822 5085 95.6 0.159 4.55 0.257
2 5266 96.4 4.42 5208 95.4 4.62
Age 4 1 2993 102.4 0.873 5.27 0.872 2818 101.3 0.745 5.21 0.119
2 2954 102.5 5.31 2848 101.1 5.25
Age 5 1 2349 112.0 0.126 6.07 0.478 2099 111.1 0.143 6.37 0.602
2 2259 111.5 6.13 2189 110.7 6.41
Age 6 1 583 114.5 0.819 6.88 0.311 455 114.2 0.261 7.55 0.180
2 552 114.8 7.15 469 113.6 7.39
Age 7 1 3986 124.8 0.232 6.59 0.266 3877 123.8 0.359 6.71 0.239
2 3981 124.5 6.72 3864 123.8 6.65
Age 8 1 1478 129.2 0.533 6.42 0.154 1279 128.3 0.192 6.82 0.721
2 1433 128.9 6.65 1318 127.9 6.87
Age 9 1 1445 134.5 0.664 7.30 0.271 1354 133.9 0.994 7.25 0.830
2 1449 134.2 7.14 1316 133.9 7.38
Age 10 1 3171 141.8 0.097 7.02 0.226 2994 141.2 0.578 7.35 0.539
2 3148 141.4 7.21 2973 141.0 7.39
Age 11 1 2385 145.2 0.130 7.23 0.505 2146 145.1 0.691 7.77 0.279
2 2288 144.6 7.41 2153 145.4 7.92
Age 12 1 3152 152.5 0.945 7.82 0.617 3031 153.3 0.813 8.36 0.444
2 3021 152.3 7.92 3048 153.3 8.24
Age 13 1 1035 158.8 0.887 8.77 0.051 898 158.4 0.938 7.80 0.964
2 965 158.7 9.36 896 158.7 7.98
Age 14 1 2353 165.6 0.888 8.94 0.031 2332 162.8 0.358 6.74 0.529
2 2266 165.8 8.62 2370 162.5 6.87
Age 15 1 1143 172.2 0.878 8.84 0.729 1042 165.4 0.547 7.18 0.358
2 1078 172.3 8.87 1013 165.7 7.03
Age 16 1 1990 176.0 0.855 7.52 0.827 2086 165.4 0.952 6.61 0.174
2 1940 175.8 7.46 2090 165.5 6.43
Age 17 1 2159 178.5 0.317 7.30 0.415 2230 166.4 0.758 6.32 0.035
2 2092 178.0 7.16 2224 166.4 6.70
Age 18 1 1680 179.4 0.444 6.95 0.573 1281 166.8 0.434 6.77 0.267
2 1614 179.2 6.91 1320 166.3 6.49
Age 19 1 1044 180.4 0.973 6.72 0.362 1099 167.2 0.662 6.60 0.187
2 1049 179.8 6.86 1047 167.3 6.47
Age 20–29 1 4036 179.9 0.191 6.69 0.624 4398 165.8 0.255 6.56 0.167
2 4121 179.4 6.74 4270 165.5 6.50
Age 30–39 1 3221 179.2 0.674 6.82 0.209 4120 165.2 0.594 6.58 0.069
2 3351 178.9 6.64 3887 165.0 6.43
Age 40–49 1 2403 178.9 0.791 6.69 0.775 2877 164.6 0.836 6.36 0.961
2 2411 178.9 6.70 2775 164.9 6.33
Age 50–59 1 2678 178.0 0.532 6.73 0.281 3261 164.1 0.898 6.20 0.081
2 2634 177.7 6.56 3086 164.3 6.05
Age 60–69 1 1265 175.9 0.927 6.73 0.657 1560 162.9 0.813 6.13 0.280
2 1276 175.8 6.85 1532 162.9 6.27
Age 70–79 1 310 175.3 0.586 6.53 0.287 435 162.1 0.543 6.78 0.064
2 329 175.0 6.82 390 161.4 6.05

p valuea: p value for equality of means, p valueb: p value for equality of variances, SD: standard deviation.

Table 4 and 5 shows the respective results for BMI. The sample sizes are same as for height. In MZ twins, the first-born twins had greater BMI than the second-born twins except the 18 and ≥50-year age groups in men, and the 40–49 year age group in women. Statistical significance was attained in the majority of age groups until 12 years age groups (Table 4). In DZ twins, first-borns had greater BMI than the second-born twins except the 14 and 60–69 years old men. The differences were also statistically significant particularly until 5 years of age. The SDs of BMI in the first-born and the second-born twins in MZ twins were not significantly different. However, the SDs of BMI in the first-born and the second-born twins in DZ twins were significantly different at the age of one, three, 10, 15, 17, and 18 years in men, and the age of 16, 18, and 20–29 years in women (Table 5).

Table 4.

Number of twin individuals, mean and standard deviation of birth weight (kg) and BMI (kg/m2) by birth order, age and sex in monozygotic twins

Men
Women
Birth order N Mean p valuea SD p valueb N Mean p valuea SD p valueb
Age 1 1 2843 17.21 <0.001 1.41 0.798 2994 16.84 <0.001 1.42 0.755
2 2838 17.11 1.42 2991 16.74 1.42
Age 2 1 2310 16.62 <0.001 1.40 0.921 2339 16.17 <0.001 1.38 0.915
2 2293 16.51 1.39 2323 16.04 1.38
Age 3 1 2830 16.02 <0.001 1.41 0.276 3140 15.68 <0.001 1.50 0.217
2 2834 15.88 1.39 3125 15.58 1.47
Age 4 1 1600 15.90 0.023 1.78 0.506 1594 15.71 0.001 2.01 0.355
2 1588 15.84 1.81 1595 15.59 1.98
Age 5 1 1272 15.34 <0.001 1.54 0.671 1341 15.13 <0.001 1.64 0.360
2 1266 15.20 1.51 1328 15.01 1.64
Age 6 1 528 15.54 0.265 1.77 0.735 427 15.25 0.084 1.76 0.735
2 512 15.48 1.77 421 15.14 1.74
Age 7 1 2345 15.40 0.002 1.69 0.419 2540 15.44 <0.001 1.93 0.314
2 2330 15.31 1.71 2536 15.31 1.93
Age 8 1 1057 15.64 0.026 1.72 0.331 1020 15.65 <0.001 1.97 0.240
2 1042 15.54 1.67 1021 15.50 1.93
Age 9 1 1042 16.29 0.057 2.10 0.318 1005 16.33 0.152 2.38 0.556
2 997 16.23 2.17 986 16.22 2.39
Age 10 1 1988 16.64 0.005 2.30 0.042 2088 16.67 <0.001 2.45 0.502
2 1924 16.54 2.17 2048 16.56 2.40
Age 11 1 1530 17.32 <0.001 2.56 0.004 1588 17.37 0.035 2.72 0.374
2 1470 17.10 2.44 1530 17.30 2.80
Age 12 1 2032 17.87 <0.001 2.72 0.197 2127 17.92 <0.001 2.74 0.999
2 1955 17.72 2.67 2053 17.77 2.71
Age 13 1 692 18.45 0.092 2.89 0.051 642 18.94 0.094 3.19 0.383
2 620 18.30 2.79 591 18.82 3.27
Age 14 1 1328 19.28 0.132 2.86 0.422 1497 19.67 0.007 3.02 0.956
2 1280 19.23 2.82 1468 19.59 3.01
Age 15 1 658 19.64 0.194 2.92 0.416 639 19.95 0.168 3.20 0.503
2 639 19.59 2.93 606 19.80 3.15
Age 16 1 1074 20.68 0.138 2.99 0.106 1311 20.64 0.098 2.98 0.172
2 1028 20.55 2.87 1257 20.57 2.95
Age 17 1 1100 20.94 0.387 2.72 0.850 1411 20.73 0.112 2.87 0.982
2 1074 20.88 2.68 1388 20.60 2.85
Age 18 1 1253 21.32 0.479 2.57 0.098 826 21.00 0.286 2.82 0.170
2 1253 21.33 2.49 812 20.81 2.74
Age 19 1 639 21.66 0.513 2.51 0.900 717 21.00 0.892 2.76 0.300
2 607 21.59 2.59 702 20.95 2.83
Age 20–29 1 2890 23.09 0.010 2.96 0.554 3488 21.85 0.010 3.69 0.340
2 2878 22.94 2.97 3478 21.73 3.57
Age 30–39 1 2305 24.65 0.461 3.39 0.215 3378 22.86 0.712 4.03 0.309
2 2290 24.52 3.30 3349 22.85 4.07
Age 40–49 1 1420 25.44 0.137 3.59 0.042 1886 23.75 0.676 4.20 0.428
2 1355 25.25 3.33 1844 23.77 4.33
Age 50–59 1 1038 25.43 0.668 3.21 0.523 1601 24.65 0.384 4.30 0.368
2 1029 25.56 3.18 1609 24.55 4.13
Age 60–69 1 506 25.59 0.852 3.20 0.264 880 25.24 0.168 4.26 0.312
2 494 25.73 3.28 878 25.02 4.17
Age 70–79 1 126 24.74 0.925 3.20 0.532 273 24.95 0.675 4.30 0.213
2 117 24.90 3.27 268 24.58 3.71

p valuea: p value for equality of means, p valueb: p value for equality of variances, SD: standard deviation.

Table 5.

Number of twin individuals, mean and standard deviation of birth weight (kg) and BMI (kg/m2) by birth order, age and sex in dizygotic twins

Birth order Men
Women
N Mean p valuea SD p valueb N Mean p valuea SD p valueb
Age 1 1 5088 17.20 <0.001 1.39 0.037 4759 16.81 0.004 1.35 0.728
2 4962 17.04 1.34 4821 16.67 1.35
Age 2 1 4184 16.57 <0.001 1.41 0.930 3815 16.20 0.006 1.38 0.423
2 4102 16.40 1.40 3871 16.04 1.39
Age 3 1 5407 16.03 0.003 1.54 0.003 5085 15.74 0.010 1.53 0.314
2 5266 15.84 1.47 5208 15.63 1.57
Age 4 1 2993 16.01 0.047 1.87 0.808 2818 15.81 0.044 1.89 0.656
2 2954 15.82 1.89 2848 15.68 1.93
Age 5 1 2349 15.33 0.020 1.59 0.806 2099 15.24 0.049 1.68 0.195
2 2259 15.17 1.60 2189 15.09 1.71
Age 6 1 583 15.65 0.867 2.02 0.153 455 15.65 0.164 2.29 0.574
2 552 15.59 2.21 469 15.40 2.22
Age 7 1 3986 15.50 0.018 1.85 0.077 3877 15.59 0.178 2.09 0.144
2 3981 15.35 1.92 3864 15.41 2.03
Age 8 1 1478 15.75 0.296 2.09 0.625 1279 15.96 0.194 2.26 0.953
2 1433 15.63 2.04 1318 15.76 2.26
Age 9 1 1445 16.61 0.660 2.61 0.161 1354 16.77 0.181 2.80 0.765
2 1449 16.41 2.49 1316 16.58 2.82
Age 10 1 3171 16.70 0.060 2.43 0.002 2994 16.98 0.107 2.58 0.422
2 3148 16.48 2.32 2973 16.77 2.68
Age 11 1 2385 17.56 0.326 2.77 0.992 2146 17.77 0.710 3.01 0.465
2 2288 17.40 2.80 2153 17.65 3.04
Age 12 1 3152 18.06 0.237 2.99 0.853 3031 18.26 0.294 3.05 0.391
2 3021 17.89 2.99 3048 18.02 3.02
Age 13 1 1035 18.59 0.875 3.25 0.572 898 18.95 0.853 3.35 0.876
2 965 18.52 3.20 896 18.85 3.35
Age 14 1 2353 19.58 0.315 3.24 0.741 2332 19.92 0.339 3.16 0.539
2 2266 19.58 3.16 2370 19.70 3.11
Age 15 1 1143 20.03 0.106 3.28 0.007 1042 20.23 0.898 3.26 0.911
2 1078 19.62 2.90 1013 20.24 3.37
Age 16 1 1990 20.87 0.290 3.03 0.800 2086 21.05 0.109 3.34 0.046
2 1940 20.77 3.01 2090 20.75 3.11
Age 17 1 2159 21.39 0.644 2.85 0.038 2230 21.09 0.158 2.98 0.500
2 2092 21.30 3.04 2224 20.79 2.93
Age 18 1 1680 21.79 0.597 2.86 0.012 1281 21.29 0.148 3.02 0.024
2 1614 21.83 3.01 1320 20.93 2.76
Age 19 1 1044 21.91 0.785 2.61 0.969 1099 21.38 0.212 3.05 0.082
2 1049 21.83 2.67 1047 21.12 2.84
Age 20–29 1 4036 23.39 0.398 3.04 0.507 4398 22.07 0.171 3.58 0.040
2 4121 23.37 3.11 4270 21.82 3.42
Age 30–39 1 3221 24.81 0.813 3.42 0.987 4120 23.19 0.619 4.30 0.125
2 3351 24.75 3.41 3887 23.02 4.17
Age 40–49 1 2403 25.48 0.932 3.35 0.553 2877 24.07 0.929 4.23 0.975
2 2411 25.39 3.40 2775 23.99 4.25
Age 50–59 1 2678 25.69 0.970 3.35 0.673 3261 24.75 0.525 4.00 0.065
2 2634 25.63 3.28 3086 24.53 3.89
Age 60–69 1 1265 25.49 0.897 3.19 0.595 1560 25.15 0.769 4.19 0.373
2 1276 25.64 3.29 1532 25.07 4.09
Age 70–79 1 310 25.34 0.909 3.35 0.279 435 24.99 0.905 3.86 0.610
2 329 25.31 3.20 390 24.87 4.03

p valuea: p value for equality of means, p valueb: p value for equality of variances, SD: standard deviation.

Because the interaction effects between birth order and zygosity were not statistically significant after Bonferroni correction for height or BMI (nominal p-values 0.047–0.008), data from MZ and DZ twins were combined in the further analyses. Figure 1 illustrates the percentage difference (%) in the mean and SD of height between the first-born and the second-born twins in men and women in the pooled data of MZ and DZ twins. Figure 2 presents the same results for BMI. Both for height and BMI, the first-born twins showed almost always higher mean values than the second-born twins. The mean differences in height between the first-born and the second-born twins ranged from −0.1% to 0.3% in men (at the age of 15 years and 5 years) and from −0.3% to 0.4% in women (at the 15 and ≥70-year age groups). The first-born male twins presented up to 1.4% greater BMI than the second-born male twins until 17 years of age and decreased with age in adulthood. The mean differences between the first-born and the second-born twins ranged from 0.2% to 1.4% in women (at the age of 15 years and 18 years). For SD the differences were small and did not show any systematic pattern varying from negative to positive.

Figure 1.

Figure 1

Mean and standard deviation differences (%) in height between first- and second- born twins across ages.

Figure 2.

Figure 2

Mean and standard deviation differences (%) in BMI between first- and second- born twins across ages.

Table 6 shows the results of fixed effects regression analysis of height and BMI at each age in the sub-cohort with information on birth weight. Adjustment for birth weight decreased the birth order differences in height and BMI. After adjusting for birth weight, birth order was associated with height at the age of one, three, five, seven and 10 years in men, whereas birth order was not associated with height in women. Moreover, as adjusting for birth weight, birth order was associated with BMI from the age of one to five, seven, 10, 11 and 12 years in men, and from the age of one to five, seven, 10 and 12 years in women.

Table 6.

Fixed effects regression coefficients for the association of birth order with height and BMI

Height
BMI
Model 1 Model 2 Model 1 Model 2
B p value B p value B p value B p value
Men Age 1 −0.14 0.004 −0.02 0.565 −0.15 <0.001 −0.10 <0.001
Age 2 −0.10 0.120 0.00 0.980 −0.16 <0.001 −0.11 <0.001
Age 3 −0.18 0.008 −0.09 0.162 −0.15 <0.001 −0.12 <0.001
Age 4 −0.07 0.510 0.00 0.978 −0.11 0.005 −0.08 0.025
Age 5 −0.30 0.017 −0.17 0.167 −0.16 <0.001 −0.11 0.005
Age 6 −0.01 0.952 0.13 0.510 −0.03 0.635 0.00 0.981
Age 7 −0.20 0.045 −0.12 0.238 −0.13 0.001 −0.10 0.004
Age 8 −0.21 0.169 −0.11 0.455 −0.10 0.062 −0.06 0.250
Age 9 −0.10 0.572 −0.03 0.852 −0.07 0.376 −0.04 0.584
Age 10 −0.36 0.008 −0.24 0.064 −0.16 0.003 −0.13 0.015
Age 11 −0.29 0.089 −0.19 0.251 −0.17 0.015 −0.14 0.044
Age 12 −0.07 0.678 0.03 0.839 −0.18 0.004 −0.15 0.020
Age 13 −0.16 0.658 −0.08 0.813 −0.08 0.498 −0.04 0.708
Age 14 0.04 0.895 0.11 0.699 −0.08 0.415 −0.05 0.608
Age 15 0.03 0.932 0.09 0.825 −0.29 0.042 −0.28 0.058
Age 16 −0.03 0.900 0.05 0.845 −0.16 0.172 −0.13 0.249
Age 17 −0.28 0.239 −0.19 0.411 −0.05 0.663 −0.04 0.735
Age 18 −0.29 0.135 −0.10 0.607 −0.07 0.475 −0.04 0.638
Age 19 −0.21 0.536 −0.02 0.962 −0.11 0.477 −0.09 0.563
Age 20–29 −0.30 0.068 −0.12 0.447 −0.08 0.341 −0.07 0.445
Age 30–39 −0.59 0.095 −0.39 0.257 0.06 0.771 0.10 0.616
Age 40–49 0.17 0.770 0.22 0.697 −0.18 0.646 −0.17 0.660
Age 50–59 0.10 0.917 0.13 0.886 −0.01 0.990 −0.01 0.990
Age 60–69 −0.35 0.795 −0.33 0.784 −0.56 0.571 −0.56 0.577
Age 70–79 −4.00 0.753 −3.88 0.807 1.58 0.691 1.88 0.698
Women Age 1 −0.13 0.005 0.00 0.970 −0.13 <0.001 −0.07 0.002
Age 2 −0.15 0.015 0.00 0.959 −0.14 <0.001 −0.08 0.002
Age 3 −0.18 0.007 −0.08 0.185 −0.12 <0.001 −0.09 <0.001
Age 4 −0.11 0.288 −0.05 0.618 −0.15 <0.001 −0.13 0.002
Age 5 −0.24 0.056 −0.12 0.330 −0.15 <0.001 −0.11 0.008
Age 6 −0.35 0.188 −0.13 0.628 −0.18 0.033 −0.11 0.204
Age 7 −0.19 0.048 −0.12 0.223 −0.13 0.001 −0.10 0.006
Age 8 −0.35 0.031 −0.18 0.273 −0.18 0.003 −0.11 0.059
Age 9 −0.06 0.742 0.07 0.668 −0.16 0.046 −0.11 0.190
Age 10 −0.15 0.235 −0.04 0.729 −0.18 0.001 −0.13 0.016
Age 11 −0.04 0.820 0.01 0.972 −0.09 0.208 −0.07 0.306
Age 12 −0.18 0.269 −0.12 0.450 −0.17 0.007 −0.14 0.030
Age 13 −0.03 0.925 0.07 0.833 −0.12 0.344 −0.09 0.504
Age 14 −0.25 0.191 −0.17 0.369 −0.20 0.033 −0.18 0.053
Age 15 0.17 0.588 0.32 0.293 −0.11 0.506 −0.08 0.630
Age 16 −0.08 0.697 0.02 0.924 −0.24 0.036 −0.21 0.066
Age 17 −0.12 0.538 −0.01 0.951 −0.19 0.045 −0.17 0.071
Age 18 −0.32 0.226 −0.15 0.571 −0.28 0.047 −0.24 0.081
Age 19 −0.01 0.980 0.10 0.728 −0.21 0.180 −0.18 0.245
Age 20–29 −0.20 0.214 −0.07 0.647 −0.18 0.097 −0.16 0.159
Age 30–39 −0.16 0.457 −0.01 0.953 −0.11 0.475 −0.09 0.565
Age 40–49 0.04 0.914 0.10 0.790 0.08 0.778 0.08 0.788
Age 50–59 −0.25 0.564 −0.17 0.700 0.05 0.889 0.04 0.921
Age 60–69 0.22 0.675 0.40 0.438 0.09 0.833 0.12 0.802
Age 70–79 −0.73 0.554 −0.41 0.736 0.00 0.999 0.08 0.940

B: Unstandardized regression coefficient

Model 1: Unadjusted, Model 2: Adjusted for birth weight

Discussion

The CODATwins study established database with data on body size from twin cohorts in different countries from infancy to old age. Previous studies in twins have reported that the second-born twin was lighter than the first-born twin at birth (Glinianaia et al., 2000; Gielen M, et al., 2007) and our results from this very large international database are consistent with these studies. First-born twins were slightly taller than second-born twins in MZ pairs at some ages until 12 years of age. After adjustment for birth weight, birth order was associated with height in males only at some ages until 10 years of age. We did not find any strong evidence that birth order differences varied according to zygosity since the interaction effects between zygosity and birth order were not statistically significant after Bonferroni correction. These results suggest that birth order has a slight influence on height in twins during childhood mainly explained by birth weight.

Meanwhile, the current study revealed birth order differences in mean BMI until 12 years of age in MZ pairs, and in mean values of BMI until 5 years of age in DZ twin pairs. These birth order differences in mean values of BMI were generally modest but still statistically significant. Adjustment for birth weight reduced these differences, but a significant association of birth order with BMI remained until 12 years of age. Jelenkovic et al. (2015) reported that DZ twins are consistently taller than MZ twins, but mean BMI is not significantly different between MZ and DZ twins at young ages. Based on our study, birth order difference seems to associate more strongly with BMI than zygosity difference. For SDs of height and BMI the results were not statistically significant and did not show any systematic pattern either. Thus, it seems that the factors behind the mean differences between first-born and second-born twins were not associated with variances.

According to the Developmental Origins of Health and Disease hypothesis, birth weight is associated with disease risk later in life and is a determinant of adult health (Barker, 1998; Brodsky and Christou, 2004). This appears more salient for twins, who are born earlier and weigh less as compared to singletons (Loos, et al., 2005). However, it is indicated that growth of twins is not equal to growth of singletons after 29 weeks of gestation (Loos, et al., 2005), and the optimal intrauterine growth and lowest morbidity is achieved earlier in gestation for twins than for singletons (Luke, et al., 1993; Soucie, et al., 2006). In addition, previous studies in twins have reported that the second-born twin was lighter than the first-born twin at birth (Glinianaia et al., 2000; Gielen M, et al., 2007). Moreover, low birth weight predicts lower adult BMI in twins (Johansson & Rasmussen, 2001; Pietiläinen et al., 2001). Whitfield et al. (2001) reported that the correlation between birth weight and BMI in adulthood was positive, and the correlation is due to genetic factors and non-shared environmental factors. Gielen et al. (2007) indicated that the factors determining birth order, which is one of twin-specific factors, have a greater influence on birth weight than zygosity, chorionicity and fusion of the placentas. However it was not known how the birth order differences change over the life course. We found residual differences in BMI between the first-born and the second-born twins until 12 years of age in boys and girls after adjusting for birth weight. Our findings are in accordance with a previous Dutch study showing that the first-born twins were slightly heavier form three to 12 years of age (Silventoinen et al., 2007).

The reasons for the birth order difference in BMI in twins are not clear. It is possible that vascular and placental circumstances are important. Twins offer an opportunity to distinguish between maternal factors (smoking, alcohol, and total placental weight) affecting both twins and factors unique to each twin, such as individual placental weight and site of the insertion of the umbilical cord. Gielen et al. (2007) reported that the individual placental weight has a stronger association with birth weight than the total placental weight. This suggests that the unique factors are more important than the maternal factors. While placental factors appear to be important, consideration of chorionicity is also necessary.

There are three types of MZ twins based on chorionicity. MZ twins can either share one chorion and one amnion, each twin can have own amnion, or MZ twins can, like all DZ twins, each have their own chorion and amnion. Sharing the same chorion could create either a more similar or a more dissimilar prenatal environment (van Beijsterveldt et al. 2015). Kent et al. (2011) reported that monochorionic twins had higher rates of marginal and velamentous placental cord insertion, and noncentral cord insertion contributed to birth weight discordance in monochorionic twin pregnancies. Antoniou et al. (2011), who examine the genetic and environmental etiology of the umbilical cord in a large population of twins, indicated that partly genetic and unique environmental factors influence a number of the morphological characteristics of the overall umbilical cord development. Thus, even in the very early stages of life, twins can experience unique environmental influences (Antoniou et al., 2011). Unfortunately, our database does not have information on chorionicity, which is gathered reliably in few cohorts.

The birth order of twins is determined in early pregnancy, and the first twin at the beginning of pregnancy intrinsically remains in this position (Bronshtein et al., 1998). However, the relationship between the amniotic sac and the cervix, which remains relatively constant throughout gestation, may change near term or during labor in about 10% of twin pairs discordant for sex leading to a change in the anticipated twin order (Bronshtein et al., 1998). Since we did not find the interaction effects between birth order and zygosity, potential prenatal environmental differences between MZ and DZ twins do not seem to modify the birth order differences in BMI or height. However, we observed that birth order effects on BMI appear to last longer in MZ twins than in DZ twins, which may reflect the differences in chorionicity. The differences of intrauterine environment between the first-born and the second-born twins need more detailed research.

Birth order differences have been analyzed previously for perinatal and neonatal outcomes. Previous studies (Smith, et al., 2002; Sheay, et al., 2004; Smith, et al., 2005; Armson, et al., 2006; Smith, et al., 2007) have reported an increased risk of perinatal death of second-born compared with first-born twins. It has been proposed that this may be mainly a problem of more stillbirths in the second twins (Smith, et al., 2002). Luo et al. (2014) reported that perinatal mortality risk differences in second vs first twins depended on their relative birth size, and vaginal delivery at term was associated with a substantially greater risk of perinatal mortality in second twins. These early deaths would have resulted in such pairs not being included in our database.

With regard to neonatal morbidity, the studies of Hacking et al. (2001) and Donovan et al. (1998) both found that second-born twins have increased risk for respiratory distress syndrome. Shinwell et al. (2004) reported that very low birthweight (< 1500g) second twins were at increased risk for acute and chronic lung disease and neonatal mortality, irrespective of mode of delivery. Moreover, Marttila et al. (2004), who analyzed respiratory distress syndrome by gestational age in singletons, first-born and second-born twins, indicated that first-born twins had a significantly lower incidence of respiratory distress syndrome compared with second-born twins and singletons, except at less than 28 weeks of gestation. By being delivered by the same mother at the same time and gestational age, these factors cannot influence postnatal difference in growth, perinatal mortality, and neonatal morbidity risk between the second-born and the first-born twins. So, any such differences are likely to be attributable to birthweight, fetal growth, and intrauterine environment. Our study suggests that the impact of early morbidity, to the degree that it is indexed by birth order, is limited in time to early childhood, and more so on BMI than height.

The major strength of the present study is the large sample size of our international database of twin cohorts with height and weight measures covering almost the whole lifespan. However, a limitation is that countries or geographical regions are not equally represented, and the database is heavily weighted toward Caucasian populations. Accordingly, we could not study in detail possible ethnic differences in birth order differences. In addition, the number of twin participants in the oldest age groups is small. Multiple testing may have resulted in false-positive differences between the first-born and the second-born twins. However, mean values showed a consistent pattern across age and sex groups in both MZ and DZ twins, which provides considerable robustness to the results. Finally a large majority of height, weight and birth order measures are self- or maternally reported. This probably increases random error which lead to decreasing effect sizes. Our results may thus be underestimations of the real birth order differences.

In conclusion, the first-born twins had greater BMI and are slightly taller than the second-born twins. Birth order showed a significant association with BMI before 12 year of age. However, in generally, the differences in BMI and height between first-born and second- born twins were very modest even in early childhood. Adjustment for birth weight reduced the birth order differences but did not fully remove them for BMI. Evidence that birth order affects variances of height and BMI was limited.

Acknowledgments

The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE – European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government’s Operational Infrastructure Support Program. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Québécois de la Recherche sur la Société et la Culture, the Fonds de la Recherche en Santé du Québec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital’s Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science. The Murcia Twin Registry is supported by Fundación Séneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R).

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