3.1 Participants’ characteristics
Among the 4045 participants, 2845 pregnant women had a normal pre-pregnancy BMI (70.33%).The study participants were primarily 26–30 years old (43.85%), pregnant with their firstborn (60.74%). In addition, approximately half of the participants had a Bachelor’s degree or higher (43.97%), and many had a medium annual household income (59.26%). Only three women reported cigarette smoking and about 1% of the women consumed alcohol during pregnancy. Subjects with a higher BMI before pregnancy turned to have a lower GWG and an infant with a higher birth weight. The GWG values were 8.36 ± 5.80kg, 7.06 ± 1.96 kg, and 4.22 ± 3.74 kg, and the neonatal birth weights were 3222.89 ± 397.04g, 3325.11 ± 442.04 g, and 3438.24 ± 449.77 g for women categorized as pre-pregnancy underweight, normal weight, and overweight/obesity, respectively (Table 1).
Table 1
Demographic, pregnancy and delivery characteristics of study participants, stratified by pre-pregnant body mass index (BMI)
Demorgraphic features
|
Pre-pregnant BMI
|
|
All
|
Underweight
|
Normal weight
|
Overweight
|
P
|
|
N
|
%/Mean(sd)
|
n
|
%/Mean(sd)
|
n
|
%/Mean(sd)
|
n
|
%/Mean(sd)
|
|
Age
|
4045
|
|
523
|
28.25(4.13)
|
2845
|
29.38(4.39)
|
677
|
30.30(4.43)
|
|
20 ~ 25,yrs
|
506
|
12.51%
|
91
|
17.40%
|
352
|
12.37%
|
63
|
9.31%
|
|
26 ~ 30
|
1774
|
43.85%
|
262
|
50.10%
|
1256
|
44.15%
|
256
|
37.81%
|
|
31 ~ 35
|
1225
|
30.28%
|
127
|
24.28%
|
850
|
29.88%
|
248
|
36.63%
|
|
36 ~ 40
|
540
|
13.35%
|
43
|
8.22%
|
387
|
13.60%
|
110
|
16.25%
|
|
Parity
|
|
|
523
|
|
2845
|
|
677
|
|
|
firstborn
|
2457
|
60.74%
|
358
|
68.45%
|
1727
|
60.70%
|
372
|
54.95%
|
|
secondborn
|
1588
|
39.26%
|
165
|
31.55%
|
1118
|
39.30%
|
305
|
45.05%
|
|
Educational level
|
|
|
521
|
|
2841
|
|
677
|
|
|
High school or less
|
997
|
24.68%
|
119
|
22.84%
|
695
|
24.46%
|
183
|
27.03%
|
|
College
|
1266
|
31.34%
|
150
|
28.79%
|
875
|
30.80%
|
241
|
35.60%
|
|
University or higher
|
1776
|
43.97%
|
252
|
48.37%
|
1271
|
44.74%
|
253
|
37.37%
|
|
Income
|
|
|
520
|
|
2837
|
|
676
|
|
|
Low
|
692
|
17.15%
|
78
|
15%
|
482
|
16.99%
|
132
|
19.53%
|
|
Middle
|
2391
|
59.26%
|
303
|
58.27%
|
1689
|
59.53%
|
399
|
59.02%
|
|
High
|
950
|
23.54%
|
139
|
26.73%
|
666
|
23.48%
|
145
|
21.45%
|
|
Smoking habits
|
|
|
521
|
|
2838
|
|
676
|
|
|
Never smoker
|
3934
|
97.50%
|
507
|
97.31%
|
2779
|
97.92%
|
648
|
95.86%
|
|
Stopped before pregnancy
|
98
|
2.43%
|
13
|
2.50%
|
57
|
2.01%
|
28
|
4.14%
|
|
Current smoker
|
3
|
0.07%
|
1
|
0.19%
|
2
|
0.07%
|
0
|
0%
|
|
Alcohol intake
|
|
|
520
|
|
2831
|
|
675
|
|
|
Never drinker
|
3611
|
89.70%
|
473
|
90.96%
|
2534
|
89.51%
|
604
|
89.48%
|
|
Stopped before pregnancy
|
373
|
9.26%
|
37
|
7.12%
|
270
|
9.54%
|
66
|
9.78%
|
|
Current drinker
|
42
|
1.04%
|
10
|
1.92%
|
27
|
0.95%
|
5
|
0.74%
|
|
pregnant features
|
|
|
|
|
|
|
|
|
|
Gestational weight gain(kg)
|
4041
|
6.75(4.86)
|
|
8.36(5.80)
|
|
7.06(4.96)
|
|
4.22(3.74)
|
|
Birth weight(g)
|
4040
|
3328.04(463.07)
|
|
3222.89(397.04)
|
|
3325.11(442.04)
|
|
3438.24(449.77)
|
|
a Demographic characteristics were presented as frequency [proportion (%)]. Gestational weight gain and birth weight were expressed as the mean [standard deviance (SD)]. |
b Subjects were categorized as underweight (BMI < 18.5kg/m2), normal weight (BMI = 18.5–24.9kg/m2), and overweight/obese (BMI≥25.0kg/m2) based on their pre-pregnancy BMI. |
3.2 Association between trimester-specific quartiles of thyroid hormone and GWG
Table 2 shows the association between trimester-specific quartiles of thyroid hormones and GWG. For the first and third trimester, there was a substantially inverse association between maternal FT4 and GWG. After adjustment for covariates, GWG was lower for participants with an FT4 level in the 4th quartile (ß=−1.45kg, 95% CI: −2.48,−0.42]) compared with that in the1st quartile at the first trimester (p = 0.01). At the third trimester, GWG was lower for participants with an FT4 level in the 2nd quartile (ß=−1.27kg, 95% CI: −2.03, −0.51]) and 3rd quartile (ß=−1.10 kg, 95%CI: −1.95, −0.24]) compared with that in the1st quartile (p < 0.001, p = 0.01). A significant inverse association for TT4 and GWG was observed at the third trimester (Q2 vs. Q1: ß=−0.92 kg, 95%CI: −1.77,−0.07, p = 0.03; Q3 vs. Q1: ß=−1.18 kg, 95%CI: −2.06,−0.30, p = 0.01; Q4 vs. Q1: ß =−1.67kg, 95%CI: −2.54, −0.81, p < 0.001). We detected a significant positive association for FT3 with GWG at the second trimester. Increased GWG was observed in the 2nd quartile (ß = 0.81 kg, 95% CI: 0.02, 1.61, p = 0.04) and the 4th quartile (ß =1.44 kg, 95% CI: 0.59, 2.28, p < 0.001) for FT3 compared with that in the 1st quartile. No other thyroid function parameters were associated with GWG.
Table 2
Multivariate associations between maternal thyroid hormone quartiles and gestational weight gain, stratified by trimesters
|
|
First trimester
|
Second trimester
|
Third trimester
|
|
|
Crude
β(95%CI)
|
Adjusted
β(95%CI)
|
p
|
Crude
β(95%CI)
|
Adjusted
β(95%CI)
|
p
|
Crude
β(95%CI)
|
Adjusted
β(95%CI)
|
p
|
TSH
|
Quartile 1
|
0.00
|
0.00
|
|
0.00
|
0.00
|
|
0.00
|
0.00
|
|
|
Quartile 2
|
0.48(-0.30,1.26)
|
0.43(-0.35,1.21)
|
0.28
|
0.30(-0.53,1.13)
|
0.08(-0.73,0.90)
|
0.84
|
-0.15(-1.10,0.80)
|
-0.10(-1.05,0.85)
|
0.83
|
|
Quartile 3
|
0.54(-0.23,1.32)
|
0.51(-0.28,1.30)
|
0.21
|
-0.01(-0.84,0.82)
|
-0.25(-1.07,0.58)
|
0.55
|
2.44(-0.69,1.19)
|
0.26(-0.68,1.20)
|
0.59
|
|
Quartile 4
|
0.44(-0.39,1.26)
|
0.46(-0.36,1.29)
|
0.27
|
0.06(-0.78,0.90)
|
-0.09(-0.92,0.74)
|
0.83
|
2.30(-0.61,1.20)
|
0.18(-0.73,1.09)
|
0.70
|
FT3
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
0.19(-0.89,1.27)
|
0.35(-0.71,1.42)
|
0.52
|
0.52(-0.28,1.33)
|
0.81(0.02,1.61)
|
0.04
|
0.13(-0.62,0.89)
|
0.41(-0.35,1.16)
|
0.29
|
|
Quartile 3
|
0.38(-0.63,1.39)
|
0.65(-0.36,1.66)
|
0.21
|
0.17(-0.65,0.99)
|
0.65(-0.16,1.47)
|
0.12
|
0.66(-0.17,1.51)
|
0.69(-0.15,1.54)
|
0.11
|
|
Quartile 4
|
-0.44(-1.41,0.51)
|
-0.06(-1.04,0.91)
|
0.90
|
0.53(-0.31,1.38)
|
1.44(0.59,2.28)
|
< 0.001
|
0.73(-0.33,1.79)
|
0.92(-0.16,1.99)
|
0.10
|
FT4
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
-0.18(-1.36,1.00)
|
-0.18(-1.34,0.98)
|
0.76
|
-0.02(-0.79,0.75)
|
-0.34(-1.10,0.42)
|
0.38
|
-1.14(-1.89,-0.38)
|
-1.27(-2.03,-0.51)
|
< 0.001
|
|
Quartile 3
|
-0.91(-1.99,0.16)
|
-0.93(-2.00,0.14)
|
0.09
|
-0.20(-1.00,0.59)
|
-0.55(-1.34,.0.23)
|
0.17
|
-1.04(-1.90,-0.19)
|
-1.10(-1.95,-0.24)
|
0.01
|
|
Quartile 4
|
-1.00(-2.01,0.03)
|
-1.45(-2.48,-0.42)
|
0.01
|
0.28(-0.60,1.17)
|
-0.14(-1.02,0.73)
|
0.74
|
-0.44(-1.49,0.60)
|
-0.58(-1.63,0.45)
|
0.27
|
TT3
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
-0.30(-1.05,0.43)
|
-0.10(-0.85,0.64)
|
0.78
|
-0.45(-1.37,0.45)
|
-0.16(-1.05,0.74)
|
0.73
|
-0.47(-1.39,0.43)
|
-0.46(-1.37,0.44)
|
0.31
|
|
Quartile 3
|
0.47(-0.30,1.26)
|
0.71(-0.08,1.51)
|
0.08
|
0.50(-0.37,1.37)
|
0.81(-0.04,1.67)
|
0.06
|
-0.71(-1.63,0.20)
|
-0.64(-1.56,0.27)
|
0.17
|
|
Quartile 4
|
-0.39(-1.26,0.48)
|
0.48(-0.40,1.37)
|
0.29
|
-0.21(-1.05,0.64)
|
0.82(-0.03,1.67)
|
0.06
|
-0.35(-1.25,0.54)
|
0.11(-0.80,1.02)
|
0.81
|
TT4
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
0.15(-0.67,0.96)
|
0.07(-0.74,0.88)
|
0.87
|
-0.30(-1.16,0.55)
|
-0.64(-1.48,0.20)
|
0.13
|
-0.64(-1.49,0.20)
|
-0.92(-1.77,-0.07)
|
0.03
|
|
Quartile 3
|
-0.44(-1.23, 0.36)
|
-0.48(-1.28,0.32)
|
0.24
|
0.12(-0.72,0.96)
|
-0.09(-0.92,0.74)
|
0.83
|
-1.00(-1.87,-0.13)
|
-1.18(-2.06,-0.30)
|
0.01
|
|
Quartile 4
|
-0.20(-1.02,0.61)
|
-0.15(-0.97,0.66)
|
0.71
|
-0.07(-0.91,0.76)
|
-0.41(-1.24,0.41)
|
0.32
|
-1.69(-2.55,-0.83)
|
-1.67(-2.54,-0.81)
|
< 0.001
|
a Abbreviations: TSH, thyroid stimulating hormone; TT4, total thyroxine; FT4: free thyroxine; TT3, total triiodothyronine; FT3, free triiodothyronine; TRAb, thyrotrophin receptor antibody; TPOAb, thyroid peroxidase antibody; TGAb, anti-thyroglobulin.
b Model was adjusted for age, parity, maternal education, pre-pregnancy BMI, urinary iodine, household income and gestational age.
c Bold red text indicates P < 0.05.
3.3 Association between birth weight Z-score and trimester-specific quartiles of thyroid hormones
As shown in Table 3, multivariate analysis revealed a clear negative association between FT4 and birth weight Z-score in the second and third trimesters. At the second trimester, mothers with the 2nd, 3rd, and 4th quartile of FT4 levels were associated with lower birth weight Z-score of -0.14 (95% CI: -0.01, -0.28, p = 0.04), -0.19 (95%CI:−0.33,−0.05, p = 0.01), and − 0.19 (95% CI: −0.35, −0.03, p = 0.05), respectively, compared with mothers with the 1st quartile of FT4 levels. The mothers with the 2nd quartile of FT4 levels were associated with lower birth weight Z-score of -0.12 (95% CI: −0.25, −0.01, p = 0.05) at the third trimester. Additionally, the birth weight Z-score of the newborns of mothers with the 4th quartile of total T4 levels was associated with a decrease in birth weight Z-score of -0.15 (95% CI: −0.30, −0.01, p = 0.04) compared with that of the 1st quartile of total T4 levels at the second trimester. Other maternal thyroid function parameters showed no statistically significant associations with neonatal birth weight.
Table 3
Multivariate associations between maternal thyroid hormone quartiles and birth weight, stratified by trimesters
|
|
First trimester
|
Second trimester
|
Third trimester
|
|
|
Crude
|
Adjusted
|
p
|
Crude
|
Adjusted
|
p
|
Crude
|
Adjusted
|
p
|
TSH
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
-0.01(-0.15,0.14)
|
0.03(-0.10,0.15)
|
0.68
|
-0.05(-0.22,0.10)
|
-0.08(-0.23,0.06)
|
0.25
|
0.08(-0.08,0.25)
|
0.07(-0.08,0.23)
|
0.35
|
|
Quartile 3
|
0.09(-0.05,0.24)
|
0.07(-0.05,0.20)
|
0.26
|
0.06(-0.09,0.22)
|
-0.01(-0.15,0.14)
|
0.99
|
0.02(-0.14,0.18)
|
0.00(-0.15,0.15)
|
0.97
|
|
Quartile 4
|
0.06(-0.10,0.21)
|
0.07(-0.06,0.20)
|
0.32
|
0.01(-0.14,0.18)
|
-0,04(-0.19,0.10)
|
0.54
|
0.04(-0.11,0.20)
|
0.03(-0.12,0.17)
|
0.72
|
FT3
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
-0.07(-0.28,0.13)
|
-0.03(-0.21,0.14)
|
0.67
|
0.01(-0.14,0.17)
|
0.01(-0.13,0.16)
|
0.87
|
0.09(-0.03,0.22)
|
0.07(-0.04,0.19)
|
0.24
|
|
Quartile 3
|
0.01(-0.17,0.21)
|
0.08(-0.08,0.24)
|
0.35
|
0.11(-0.04,0.27)
|
0.09(-0.05,0.24)
|
0.22
|
0.09(-0.05,0.23)
|
0.05(-0.08,0.19)
|
0.44
|
|
Quartile 4
|
0.12(-0.06,0.30)
|
0.14(-0.02,0.30)
|
0.09
|
0.12(-0.04,0.29)
|
0.06(-0.09,0.21)
|
0.45
|
0.14(-0.04,0.32)
|
0.02(-0.15,0.19)
|
0.85
|
FT4
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
0.12(-0.10,0.34)
|
0.17(-0.01,0.36)
|
0.08
|
-0.16(-0.31,-0.01)
|
-0.14(-0.28,-0.01)
|
0.04
|
-0.12(-0.25,0.01)
|
-0.12(-0.25,-0.01)
|
0.04
|
|
Quartile 3
|
0.03(-0.17,0.24)
|
0.12(-0.05,0.29)
|
0.19
|
-0.22(-0.37,-0.06)
|
-0.19(-0.33,-0.05)
|
0.01
|
-0.13(-0.27,0.02)
|
-0.12(-0.26,0.01)
|
0.07
|
|
Quartile 4
|
0.07(-0.13,0.26)
|
0.16(-0.01,0.33)
|
0.06
|
-0.28(-0.45,-0.10)
|
-0.19(-0.35,-0.03)
|
0.02
|
-0.13(-0.31,0.04)
|
-0.09(-0.26,0.07)
|
0.27
|
TT3
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
0.03(-0.11,0.17)
|
0.06(-0.06,0.18)
|
0.35
|
0.01(-0.17,0.18)
|
-0.05(-0.21,0.11)
|
0.51
|
-0.11(-0.26,0.04)
|
-0.07(-0.21,0.08)
|
0.35
|
|
Quartile 3
|
-0.01(-0.16,013)
|
-0.01(-0.13,0.12)
|
0.94
|
0.07(-0.10,0.24)
|
0.05(-0.10,0.21)
|
0.52
|
0.09(-0.06,0.250
|
0.07(-0.07,0.22)
|
0.33
|
|
Quartile 4
|
0.00(-0.16,0.16)
|
0.05(-0.09,0.20)
|
0.48
|
0.11(-0.05,0.28)
|
0.04(-0.11,0.20)
|
0.58
|
0.14(-0.01,0.30)
|
0.05(-0.09,0.20)
|
0.49
|
TT4
|
Quartile 1
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
1.00
|
1.00
|
|
|
Quartile 2
|
-0.03(-0.18,0.12)
|
0.05(-0.08,0.19)
|
0.44
|
-0.08(-0.25,0.08)
|
-0.04(-0.19,0.11)
|
0.59
|
-0.14(-0.29,-0.01)
|
-0.05(-0.19,0.09)
|
0.45
|
|
Quartile 3
|
-0.07(-0.22,0.08)
|
-0.00(-0.13,0.13)
|
0.10
|
-0.14(-0.31,0.02)
|
-0.12(-0.27,0.02)
|
0.10
|
-0.20(-0.35,-0.05)
|
-0.12(-0.26,0.02)
|
0.09
|
|
Quartile 4
|
-0.00(-0.15,0.15)
|
0.04(-0.09,0.17)
|
0.57
|
-0.20(-0.36,-0.04)
|
-0.15(-0.30,-0.01)
|
0.04
|
-0.09(-0.24,0.05)
|
-0.07(-0.21,0.07)
|
0.33
|
a Abbreviations: TSH, thyroid stimulating hormone; TT4, total thyroxine; FT4: free thyroxine; TT3, total triiodothyronine; FT3, free triiodothyronine; TRAb, thyrotrophin receptor antibody; TPOAb, thyroid peroxidase antibody; TGAb, anti-thyroglobulin.
b Model was adjusted for age, parity, maternal education, pre-pregnancy BMI, household income and gestational age.
c Bold red text indicates P < 0.05.