Early growth and non-alcoholic fatty liver disease in adulthood—the NAFLD liver fat score and equation applied on the Helsinki Birth Cohort Study

Figures & data

Table I. Characteristics of the study participants.

Measurement	Males (n = 646)		Females (n = 941)
	Mean/%	SD/Quartiles	Mean/%	SD/Quartiles
Birth
Length (cm)	50.6	2.0	50.0	1.8
Weight (g)	3463	482	3358	463
Ponderal index (kg/m^3)	26.6	2.3	26.7	2.2
Gestational age (days)	280	11	281	11
Age 2 years
Height (cm)	86.7	3.0	85.6	3.0
Weight (kg)	12.4	1.1	11.9	1.1
Body mass index (kg/m^2)	16.7	1.2	16.4	1.2
Age 7 years
Height (cm)	121.0	4.7	120.1	4.7
Weight (kg)	22.5	2.6	22.2	2.9
Body mass index (kg/m^2)	15.5	1.1	15.5	1.3
Age 11 years
Height (cm)	141.6	5.9	141.7	6.6
Weight (kg)	33.8	4.5	34.3	5.7
Body mass index (kg/m^2)	16.8	1.5	17.0	1.9
Adult
Age (years)	61.6	2.8	61.6	3.0
Height (cm)	176.7	6.0	163.4	5.7
Weight (kg)	85.2	12.7	73.1	12.4
Body mass index (kg/m^2)	27.3	3.7	27.4	4.4
Waist circumference (cm)	99.9	10.8	90.3	11.8
Systolic blood pressure (mmHg)	146.4	19.7	144.1	21.0
Diastolic blood pressure (mmHg)	90.2	10.7	87.6	10.2
ALT (U/L)^a	16.0	12.0; 22.0	13.0	9.0; 17.0
AST (U/L)^a	27.0	22.0; 33.0	23.0	19.0; 28.0
Fasting insulin (pmol/L)^a	9.2	6.1; 14.5	7.7	5.3; 11.4
Fasting glucose (mmol/L)^a	5.7	5.4; 6.3	5.4	5.0; 5.8
HDL cholesterol (mmol/L)^a	1.4	1.2; 1.6	1.7	1.4; 2.0
Triglycerides (mmol/L)^a	1.3	1.0; 1.9	1.3	1.0; 1.7
Liver fat per cent^a	4.2	2.5; 6.9	3.0	1.9; 5.3
Diabetes (%)	17.6		11.1
Metabolic syndrome (%)	56.7		45.9
Positive NAFLD score (%)	43.0		22.5

^aMedian values and interquartile ranges presented due to skewed data distribution.

Figure 1. The NAFLD liver fat score.

Figure 2. The NAFLD liver fat equation.

Table II. Odds ratios and 95% confidence intervals for a positive NAFLD liver fat score per unit of birth and childhood anthropometric measurements.

		Birth weight	Birth length	PI	Weight at 2 y	Height at 2 y	BMI at 2 y
Model 1^a	OR	0.93	0.98	1.01	0.89	0.97	0.92
	95% CI	0.71; 1.23	0.91; 1.05	0.96; 1.06	0.79; 0.99	0.93; 1.01	0.84; 1.02
	P	0.62	0.53	0.82	0.03	0.10	0.12
Model 2, male^b	OR	0.73	0.92	1.00	0.76	0.99	0.72
	95% CI	0.47; 1.15	0.82; 1.03	0.92; 1.08	0.63; 0.92	0.93; 1.06	0.60; 0.86
	P	0.18	0.15	0.91	0.01	0.81	< 0.001
Model 2, female	OR	0.79	0.99	0.94	0.80	0.96	0.85
	95% CI	0.50; 1.24	0.88; 1.12	0.87; 1.03	0.68; 0.95	0.90; 1.02	0.73; 0.99
	P	0.31	0.91	0.17	0.01	0.2	0.04
		Weight at 7 y	Height at 7 y	BMI at 7 y	Weight at 11 y	Height at 11 y	BMI at 11 y
Model 1	OR	1.01	1.00	1.05	1.02	1.00	1.07
	95% CI	0.97; 1.06	0.97; 1.02	0.95; 1.15	1.00; 1.04	0.99; 1.02	1.00; 1.14
	P	0.61	0.75	0.35	0.12	0.69	0.06
Model 2, male	OR	0.89	0.99	0.69	0.94	1.00	0.76
	95% CI	0.82; 0.96	0.95; 1.03	0.57; 0.83	0.90; 0.99	0.97; 1.03	0.66; 0.88
	P	0.004	0.60	< 0.001	0.01	0.96	< 0.001
Model 2, female	OR	0.98	1.00	0.93	0.98	1.01	0.91
	95% CI	0.92; 1.04	0.96; 1.04	0.80; 1.08	0.95; 1.02	0.98; 1.03	0.82; 1.01
	P	0.5	0.85	0.31	0.36	0.76	0.08

Significant associations (at 0.05 level) italicized for clarity.

Birth weight in kilos, birth length in centimetres, BMI in kg/m², PI in kg/m³.

OR = odds ratio; CI = confidence interval; BMI = body mass index; PI = ponderal index.

^aModel 1 adjusted for age, sex, and gestational age.

^bModel 2 additionally adjusted for adult BMI.

Table III. Relative per cent change of liver fat per cent per unit of birth and childhood anthropometric measurements.

		Birth weight	Birth length	PI	Weight at 2 y	Height at 2 y	BMI at 2 y
Model 1^a	%	–5.9	–0.4	–1.3	–3.6	–1.2	–2.3
	95% CI	–13.2; 2.0	–2.4; 1.6	–2.8; 0.3	–6.6; –0.6	–2.3; 0.0	–5.1; 0.6
	P	0.14	0.70	0.11	0.02	0.05	0.12
Model 2, male^b	%	–9.3	–1.0	–1.8	–4.8	–0.5	–5.4
	95% CI	–18.2; 0.4	–3.4; 1.6	–3.6; 0.1	–8.6; –0.7	–2.0; 1.0	–9.0; –1.7
	P	0.06	0.46	0.07	0.02	0.53	0.004
Model 2, female	%	–11.5	–0.8	–2.8	–6.9	–1.0	–6.3
	95% CI	–18.9; –3.2	–3.0; 1.5	–4.4; –1.1	–10.0; –3.8	–2.2; 0.2	–9.2; –3.3
	P	0.01	0.52	0.001	< 0.001	0.11	< 0.001
		Weight at 7 y	Height at 7 y	BMI at 7 y	Weight at 11 y	Height at 11 y	BMI at 11 y
Model 1	%	–0.5	–0.5	0.6	0.2	–0.4	1.8
	95% CI	–1.7; 0.8	–1.3; 0.2	–2.2; 3.5	–0.5; 0.9	–0.9; 0.2	–0.2; 3.9
	P	0.48	0.15	0.68	0.55	0.07	0.08
Model 2, male	%	–3.4	–0.4	–9.7	–1.8	–0.4	–6.7
	95% CI	–5.2; –1.7	–1.4; 0.6	–13.2; –6.0	–2.9. –0.8	–1.2; 0.4	–9.5; –3.7
	P	< 0.001	0.43	< 0.001	0.001	0.33	< 0.001
Model 2, female	%	–2.4	–0.8	–5.0	–1.2	–0.5	–3.9
	95% CI	–3.6; –1.1	–1.6; 0.0	–7.8. –2.1	–1.9; –0.5	–1.1; 0.1	–5.9; –2.0
	P	< 0.001	0.05	0.001	0.001	0.08	< 0.001

Birth weight in kilos, birth length in centimetres, BMI in kg/m², PI in kg/m³.

Significant associations (at 0.05 level) italicized for clarity.

Liver fat per cent variable logarithmized due to skewness. Per cent change calculated by (exp(regression coefficient) – 1) × 100; percentages rounded to one decimal.

CI = confidence interval; BMI = body mass index; PI = ponderal index.

^aModel 1 adjusted for age, sex, and gestational age.

^bModel 2 additionally adjusted for adult BMI.

Table IV. Odds ratios and 95% confidence intervals for a positive NAFLD liver fat score per SD of conditional growth.

		Cond. weight growth 0–2	Cond. weight growth 2–7	Cond. weight growth 7–11	Cond. height growth 0–2	Cond. height growth 2–7	Cond. height growth 7–11
Model 1^a	OR	0.88	1.18	1.12	0.91	1.08	1.09
	95% CI	0.78; 0.99	1.05; 1.33	0.99; 1.25	0.81; 1.03	0.96; 1.22	0.97; 1.23
	P	0.03	0.01	0.07	0.14	0.19	0.15
Model 2, male^b	OR	0.77	0.89	1.00	1.02	0.95	1.09
	95% CI	0.63; 0.94	0.72; 1.09	0.82; 1.21	0.84; 1.25	0.78; 1.16	0.90; 1.32
	P	0.01	0.25	0.98	0.83	0.61	0.38
Model 2, female	OR	0.79	1.14	0.91	0.87	1.11	1.09
	95% CI	0.65; 0.96	0.94; 1.37	0.75; 1.10	0.72; 1.06	0.92; 1.33	0.90; 1.31
	P	0.02	0.18	0.31	0.16	0.27	0.38
		Cond. BMI growth 0–2	Cond. BMI growth 2–7	Cond. BMI growth 7–11		Cond. BMI growth 2–11
Model 1	OR	0.91	1.14	1.10		1.17
	95% CI	0.81; 1.03	1.01; 1.28	0.98; 1.24		1.04; 1.32
	P	0.12	0.04	0.10		0.01
Model 2, male	OR	0.69	0.81	0.92		0.80
	95% CI	0.56; 0.84	0.66; 0.99	0.75; 1.12		0.65; 0.98
	P	< 0.001	0.04	0.40		0.03
Model 2, female	OR	0.84	1.03	0.86		0.92
	95% CI	0.70; 1.02	0.85; 1.24	0.71; 1.04		0.75; 1.11
	P	0.08	0.77	0.12		0.37

Significant associations (at 0.05 level) italicized for clarity.

OR = odds ratio; CI = confidence interval; BMI = body mass index; PI = ponderal index.

^aModel 1 adjusted for age, sex, and gestational age.

^bModel 2 additionally adjusted for adult BMI.

Table V. Relative per cent change of liver fat per cent per SD of conditional growth.

		Cond. weight growth 0–2	Cond. weight growth 2–7	Cond. weight growth 7–11	Cond. height growth 0–2	Cond. height growth 2–7	Cond. height growth 7–11
Model 1^a	%	–3.3	2.1	3.7	–3.3	0	0.3
	95% CI	–6.7; 0.1	–1.4; 5.9	0.1; 7.3	–6.6; 0.1	–3.4; 3.6	–3.1; 3.9
	P	0.06	0.23	0.04	0.06	0.99	0.85
Model 2, male^b	%	–4.2	–6.6	–0.7	–1.0	–1.1	–1.5
	95% CI	–8.4; 0.2	–10.8; –2.1	–5.2; 3.9	–5.4; 3.7	–5.5; 3.6	–5.8; 2.9
	P	0.06	0.004	0.75	0.67	0.64	0.50
Model 2, female	%	–6.8	–1.6	–2.2	–2.8	–2.3	0.2
	95% CI	–10.1; –3.1	–5.4; 2.3	–5.8; 1.6	–6.4; 0.9	–5.9; 1.4	–3.5; 4.0
	P	< 0.001	0.33	0.25	0.14	0.22	0.93
		Cond. BMI growth 0–2	Cond. BMI growth 2–7	Cond. BMI growth 7–11		Cond. BMI growth 2–11
Model 1	%	–2.0	2.9	4.0		4.9
	95% CI	–5.4; 1.5	–0.6; 6.5	0.4; 7.6		1.4. 8.7
	P	0.25	0.11	0.03		0.006
Model 2, male	%	–5.5	–8.3	–1.5		–7.2
	95% CI	–9.7; –1.2	–12.4. –4.1	–5.9; 3.1		–11.4; –2.8
	P	0.01	< 0.001	0.53		0.002
Model 2, female	%	–6.3	–2.0	–3.6		–4.1
	95% CI	–9.8; –2.7	–5.7; 1.8	–7.2; 0.1		–7.7; –0.3
	P	0.001	0.30	0.06		0.04

Significant associations (at 0.05 level) italicized for clarity.

CI = confidence interval; BMI = body mass index; PI = ponderal index.

Liver fat per cent variable logarithmized due to skewness. Per cent change calculated by (exp(regression coefficient) – 1) × 100; Percentages rounded to one decimal.

^aModel 1 adjusted for age, sex and gestational age.

^bModel 2 additionally adjusted for adult BMI.

Table VI. Odds ratios^a and 95% confidence intervals for a positive NAFLD liver fat score per tertile of BMI at age 2 and conventional BMI groups in adulthood.

BMI at age 2 years (kg/m^2)	BMI at age 62 years (kg/m^2)
	≤ 25						25–30						> 30
	Cases	n	%	OR	95% CI	P	Cases	n	%	OR	95% CI	P	Cases	n	%	OR	95% CI	P
–16	25	207	12.1	1.0			73	225	32.4	3.7	2.2; 6.1	< 0.001	73	108	67.6	18.5	10.1; 33.6	< 0.001
–17	15	159	9.4	0.7	0.4; 1.4	0.31	65	227	28.6	2.6	1.6; 4.4	< 0.001	79	130	60.8	13.2	7.5; 23.2	< 0.001
> 17	4	113	3.5	0.26	0.1; 0.8	0.01	80	273	29.3	2.5	1.5; 4.2	0.002	73	141	51.8	8.8	5.0; 15.2	< 0.001

n = 1,583 (4 subjects excluded: 2 due to missing data on BMI at 2 years and 2 due to missing adult BMI).

OR = odds ratio; CI = confidence interval; BMI = body mass index.

^aAdjusted for sex and age.