Birth weight, sex, and celiac disease: a nationwide twin study

Figures & data

Table 1 Descriptive information, number (percentage of non-missing values within each variable) if not else stated

Characteristics	CD, n (%)(yes)	No record of CD, n (%) (no)
Total	669 (0.5)	146,161 (99.5)
Sex
Female	446 (66.7)	74,057 (50.7)
Male	223 (33.3)	72,104 (49.3)
p-valuea	<0.001
Birth weight
Mean (SD), g	2662 (552)	2638 (543)
p-valuea	0.349
≤1499 g	12 (2.5)	2519 (2.5)
1500–2499 g	151 (32.0)	35,651 (35.0)
2500–3499 g	281 (59.5)	58,628 (57.5)
≥3500 g	28 (5.9)	5112 (5.0)
p-valuea	0.508
Missing	197 (29.4)	44,249 (30.3)
p-valuea	0.673
z-score meanb	0.07 (0.99)	0.00 (1.00)
p-valuea	0.252
Missing	378 (56.5)	99,104 (67.8)
p-valuea	<0.001
Birth length
Mean (SD), cm	47.28 (2.82)	47.22 (2.92)
p-valuea	0.689
≤39 cm	5 (1.1)	1440 (1.4)
40–44 cm	61 (13.6)	13,591 (13.7)
45–49 cm	290 (64.6)	63,427 (63.8)
≥50 cm	93 (20.7)	20,931 (21.1)
p-valuea	0.937
Missing	220 (32.9)	46,772 (32.0)
p-valuea	0.654
Gestational age
Mean (SD), days	259.22 (17.42)	259.08 (18.45)
p-valuea	0.892
≤27 weeks	2 (0.7)	401 (0.8)
28–31 weeks	15 (5.1)	1958 (4.1)
32–36 weeks	91 (31.1)	16,236 (34.3)
37–40 weeks	179 (61.1)	27,738 (58.6)
≥41 weeks	6 (2.0)	978 (2.1)
p-valuea	0.741
Missing	376 (56.2)	98,823 (67.6)
p-valuea	<0.001
Birth years
≤1944	88 (13.2)	19,860 (13.6)
1945–1954	61 (9.1)	17,930 (12.3)
1955–1964	43 (6.4)	16,277 (11.1)
1965–1974	49 (7.3)	15,930 (10.9)
1975–1984	57 (8.5)	14,729 (10.1)
1985–1994	206 (30.8)	23,832 (16.3)
1995–2004	148 (22.1)	26,908 (18.4)
2005–2008	17 (2.5)	10,695 (7.3)
p-valuea	<0.001
Zygosity
MZ	152 (27.3)	32,285 (27.2)
Same-sexed DZ	200 (35.9)	36,812 (31.1)
Opposite-sexed DZ	205 (36.8)	49,420 (41.7)
p-valuea	0.025
Missing	112 (16.7)	27,644 (18.9)
p-valuea	0.167
Complete twin pairs
Yes	615 (91.9)	132,453 (90.6)
No	54 (8.1)	13,708 (9.4)
p-valuea	0.275

Notes:

a p-values from either a Student’s t-test (continuous) or a Pearson chi-square test (categorical) for difference between the group with CD and the group without CD. The p-values refer to variables presented above each p-value row.

b z-score refers to sex and gestational age-standardized birth weight.

Abbreviations: CD, celiac disease; DZ, dizygotic; MZ, monozygotic.

Figure 1 Observed proportion with CD by birth weight.

Notes: Percentiles refer to the percentage of individuals with a birth weight lower than indicated. Linear refers to a modeled proportion in a logistic regression with an effect that is linear on the log-odds scale. 95% CI refers to 95% bootstrap CIs of modeled proportion with CD based on 10,000 repeats.
Abbreviations: CD, celiac disease; CI, confidence interval.

Figure 2 Observed proportion with CD by gestational age-standardized birth weight (z-scores).

Notes: Percentiles refer to the percentage of individuals with a birth weight lower than indicated. Linear refers to a modeled proportion in a logistic regression with an effect that is linear on the log-odds scale. 95% CI refers to 95% bootstrap CIs of modeled proportion with CD based on 10,000 repeats.
Abbreviations: CD, celiac disease; CI, confidence interval.

Table 2 Analyses of the association between birth weight and CD, estimate (95% CI)

ORs per 1000 g increase in birth weight	Crude	Adjusted for sex and birth year	Adjusted for sex, birth year, and gestational age	Within DZa	Within MZ
Both sexes	1.08 (0.91–1.30) N=102,384	1.16 (0.97–1.38) N=102,384	1.15 (0.85–1.54) N=47,348	1.26 (0.69–2.29) N=66,871; from CD-discordant pairs=670	0.95 (0.26–3.41) N=28,318; from CD-discordant pairs=144
Malesb	1.51 (1.12–2.04) N=49,655	1.50 (1.11–2.02) N=49,655	2.09 (1.39–3.15) N=23,006	0.85 (0.20–3.71) N=15,713; from CD-discordant pairs=104	0.17 (0.01–2.10) N=12,987; from CD-discordant pairs=48
Femalesb	0.98 (0.79–1.23) N=52,729	1.00 (0.81–1.24) N=52,729	0.86 (0.59–1.24) N=24,342	1.22 (0.47–3.16) N=34,294; from CD-discordant pairs=208	2.22 (0.32–15.46) N=15,331; from CD-discordant pairs=96

Notes: Birth year and gestational days are treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for.

a Adjusted for sex where applicable.

b Twins from same-sexed and opposite-sexed pairs. Bold figures indicate statistically significant (p<0.05).

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; OR, odds ratio.

Table 3 Analyses of the association between z-score (birth weight standardized per gestational age) and CD, estimate (95% CI)

ORs per 1 SD increase in z-score	Crude	Adjusted for sex and birth year	Within DZa	Within MZ
Both sexes	1.07 (0.95–1.21) N=47,348	1.06 (0.93–1.19) N=47,348	1.03 (0.75–1.41) N=29,081; from CD-discordant pairs=276	1.44 (0.70–2.96) N=15,196; from CD-discordant pairs=58
Malesb	1.40 (1.17–1.67) N=23,006	1.38 (1.15–1.65) N=23,006	0.82 (0.36–1.90) N=7179; from CD-discordant pairs=44	1.47 (0.47–4.56) N=7011; from CD-discordant pairs=20
Femalesb	0.95 (0.82–1.10) N=24,342	0.94 (0.81–1.09) N=24,342	0.86 (0.53–1.39) N=6994; from CD-discordant pairs=98	1.42 (0.59–3.45) N=8185; from CD-discordant pairs=38

Notes: Birth year is treated as categorical variable.

a Adjusted for sex where applicable.

b Twins from same-sexed and opposite-sexed pairs. Bold figures indicate statistically significant (p<0.05).

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; OR, odds ratio.

Table 4 Analyses of the association between low birth weight (≤2499 g) and CD, estimate (95% CI)

ORs if low birth weight compared with no low birth weight	Crude	Adjusted for sex and birth year	Adjusted for sex, birth year, and gestational age	Within DZa	Within MZ
Both sexes	0.88 (0.72–1.07)	0.84 (0.69–1.03)	0.85 (0.63–1.15)	1.02 (0.59–1.75)	1.17 (0.39–3.47)
Malesb	0.73 (0.51–1.03)	0.74 (0.52–1.05)	0.53 (0.28–1.03)	1.40 (0.44–4.41)	2.00 (0.37–10.92)
Femalesb	0.91 (0.71–1.15)	0.90 (0.71–1.14)	0.99 (0.70–1.38)	1.00 (0.43–2.31)	0.75 (0.17–3.35)

Notes: Birth year and gestational days treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for (sample sizes equal to Table 2).

a Adjusted for sex where applicable.

b Twins from same-sexed and opposite-sexed pairs.

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; OR, odds ratio.

Figure S1 Observed proportion with CD by birth weight in subsample born in 1980–2004.

Notes: Percentiles refer to the percentage of individuals with a birth weight lower than indicated. Linear refers to a modeled proportion in a logistic regression with an effect that is linear on the log-odds scale. 95% CI refers to 95% bootstrap CIs of modeled proportion with CD based on 10,000 repeats.

Abbreviations: CD, celiac disease; CI, confidence interval.

Table S1 Analyses of the association between birth weight and CD, estimate (95% CI)

ORs per 1000 g increase in birth weight	Crude	Adjusted for sex and birth year	Adjusted for sex, birth year, and gestational age
Both sexes
DZ cohort	1.01 (0.80–1.28)	1.08 (0.86–1.35)	1.16 (0.80–1.68)
MZ cohort	1.21 (0.88–1.66)	1.28 (0.93–1.74)	1.05 (0.61–1.80)
Malesa
DZ cohort	1.39 (0.80–2.42)	1.40 (0.81–2.42)	1.75 (0.80–3.81)
MZ cohort	1.55 (0.94–2.56)	1.56 (0.94–2.58)	1.54 (0.83–2.86)
Femalesa
DZ cohort	0.87 (0.65–1.16)	0.90 (0.68–1.18)	0.83 (0.44–1.55)
MZ cohort	1.21 (0.81–1.79)	1.18 (0.81–1.73)	0.93 (0.47–1.82)

Notes: Length, birth year, and gestational days are treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for.

a Twins from same-sexed and opposite-sexed pairs.

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; OR, odds ratio.

Table S2 Analyses of the association between birth weight and CD in subsample born in 1980–2004 (N=58,771), estimate (95% CI)

ORs per 1000 g increase in birth weight	Crude	Adjusted for sex and birth year	Adjusted for sex, birth year, and gestational age
Both sexes	1.08 (0.86–1.36)	1.15 (0.91–1.45)	1.20 (0.88–1.63)
Malesa	1.80 (1.18–2.74)	1.79 (1.18–2.72)	2.28 (1.52–3.41)
Femalesa	0.94 (0.72–1.23)	0.94 (0.72–1.23)	0.87 (0.59–1.29)

Notes: Birth year and gestational days are treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for.

a Twins from same-sexed and opposite-sexed pairs.

Abbreviations: CD, celiac disease; CI, confidence interval; OR, odds ratio.

Table S3 Analyses of the association between birth weight and CD among same-sexed twin pairs, estimate (95% CI)

ORs per 1000 g increase in birth weight	Crude	Adjusted for birth year	Adjusted for birth year and gestational age	Within DZ	Within MZ
Males	1.51 (1.01–2.27)	1.51 (1.01–2.26)	1.71 (0.98–2.97)	0.85 (0.20–3.71)	0.17 (0.01–2.10)
Females	1.12 (0.85–1.47)	1.13 (0.86–1.47)	0.89 (0.56–1.41)	1.22 (0.47–3.16)	2.22 (0.32–15.46)

Notes: Birth year and gestational days are treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for.

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; OR, odds ratio.

Table S4 Analyses of the association between birth weight and CD stratified by whether twin pair was complete, estimate (95% CI)

ORs per 1000 g increase in birth weight	Crude	Adjusted for sex and birth year	Adjusted for sex, birth year, and gestational age	Within DZa	Within MZ
Complete twin pairs
Both sexes	1.08 (0.90–1.31) N=93,764	1.16 (0.96–1.39) N=93,764	1.51 (0.85–1.55) N=43,528	1.26 (0.69–2.29) N=60,665; from CD-discordant pairs=670	0.95 (0.26–3.41) N=26,721; from CD-discordant pairs=144
Malesb	1.43 (1.04–1.97) N=45,547	1.42 (1.04–1.95) N=45,547	2.04 (1.34–3.10) N=22,568	0.85 (0.20–3.71) N=14,314; from CD-discordant pairs=104	0.17 (0.01–2.10) N=12,210; from CD-discordant pairs=48
Femalesb	1.02 (0.81–1.29) N=48,217	1.04 (0.83–1.30) N=48,217	0.87 (0.60–1.26) N=23,916	1.22 (0.47–3.16) N=30,912; from CD-discordant pairs=208	2.22 (0.32–15.46) N=14,511; from CD-discordant pairs=96
Incomplete twin pairs
Both sexes	1.11 (0.60–2.04) N=8620	1.16 (0.64–2.10) N=8620	1.08 (0.19–6.12) N=864	NA N=6206	NA N=1597
Malesb	2.44 (1.09–5.48) N=4108	2.43 (1.06–5.60) N=4108	8.44 (2.36–30.23) N=438	NA N=1399	NA N=777
Femalesb	0.55 (0.27–1.12) N=4512	0.61 (0.30–1.25) N=4512	0.55 (0.08–3.97) N=426	NA N=3382	NA N=820

Notes: The within estimates cannot be calculated in incomplete pairs. Birth year and gestational days treated as categorical variables. The number of observations differs between columns because of missing data in variables adjusted for.

a Adjusted for sex where applicable.

b Twins from same-sexed and opposite-sexed pairs.

Abbreviations: CD, celiac disease; CI, confidence interval; DZ, dizygotic; MZ, monozygotic; NA, not applicable; OR, odds ratio.