Association of Normal-Range Hemoglobin A1c Value During Midpregnancy with Adverse Birth Outcomes

Figures & data

Figure 1 Flowchart of study population.

Figure 2 Associations between HbA1c level and adverse birth outcomes, stratified by maternal prepregnancy BMI (kg/m²).

Abbreviations: OR, odds ratio; LGA, large for gestational age.

Table 1 Characteristics of the Study Population Based on HbA1c (%) (n=8389)

HbA1c(%) Category	Q1≤4.7 (n=1881)	Q2(4.8–4.9) (n=2132)	Q3(5.0–5.1) (n=2123)	Q4(5.2–6.3) (n=2253)	P
Maternal age(yr)	28.20 ± 4.54	29.06 ± 4.53	29.61 ± 4.64	30.33 ± 4.68	<0.001
Gestational age at delivery (wk)	39.22 ± 1.26	39.17 ± 1.30	39.07 ± 1.38	38.89 ± 1.49	<0.001
Birth weight(g)	3334.34 ± 411.13	3357.37 ± 425.18	3364.96 ± 466.86	3402.62 ± 496.32	<0.001
Prepregnancy BMI (kg/m^2)					<0.001
<18.5	293 (15.58%)	218 (10.23%)	178 (8.38%)	90 (3.99%)
18.5–24.9	1291 (68.63%)	1524 (71.48%)	1480 (69.71%)	1408 (62.49%)
25–29.9	142 (7.55%)	246 (11.54%)	327 (15.40%)	530 (23.52%)
≥30	26 (1.38%)	51 (2.39%)	54 (2.54%)	133 (5.90%)
Not recorded	129 (6.86%)	93 (4.36%)	84 (3.96%)	92 (4.08%)
HbA1c of Gestational week	25.06 ± 1.04	25.23 ± 1.09	25.39 ± 1.07	25.52 ± 1.25	<0.001
Caesarean section					<0.001
No	878 (46.68%)	925 (43.39%)	915 (43.10%)	868 (38.54%)
Yes	1003 (53.32%)	1207 (56.61%)	1208 (56.90%)	1384 (61.46%)
Sex					0.479
Female	896 (47.63%)	985 (46.20%)	970 (45.69%)	1021 (45.32%)
Male	985 (52.37%)	1147 (53.80%)	1153 (54.31%)	1232 (54.68%)
LGA					<0.001
0	1644 (87.40%)	1830 (85.83%)	1752 (82.52%)	1778 (78.92%)
1	237 (12.60%)	302 (14.17%)	371 (17.48%)	475 (21.08%)
Macrosomia					<0.001
0	1799 (95.64%)	2029 (95.17%)	1971 (92.84%)	2060 (91.43%)
1	82 (4.36%)	103 (4.83%)	152 (7.16%)	193 (8.57%)
Preterm birth					<0.001
0	1816 (96.54%)	2046 (95.97%)	2007 (94.54%)	2117 (93.96%)
1	65 (3.46%)	86 (4.03%)	116 (5.46%)	136 (6.04%)

Note: Data are presented as mean ± standard deviation or n (%).

Abbreviations: OR, odds ratio; Ref, reference; LGA, large for gestational age; 0, no; “1”, yes.

Table 2 Univariate Analysis of Adverse Birth Outcomes

Variables	Preterm Birth			Macrosomia			LGA
	Value	OR(95% CI)	P	Value	OR(95% CI)	P	Value	OR(95% CI)	P
HbA1c(%)	4.96 ± 0.29	2.52 (1.78, 3.58)	<0.0001	4.96 ± 0.29	2.81 (2.06, 3.82)	<0.0001	4.96 ± 0.2	2.29 (1.87, 2.80)	<0.0001
Maternal age(yr)	29.35 ± 4.66	1.03 (1.01, 1.05)	0.0034	29.35 ± 4.66	1.03 (1.01, 1.05)	0.0007	29.35 ± 4.66	1.04 (1.03, 1.05)	<0.0001
Pre-pregnancy BMI (kg/m^2)
<18.5	779 (9.29%)	Ref		779 (9.29%)	Ref		779 (9.29%)	Ref
18.5–24.9	5703 (67.98%)	1.08 (0.75, 1.57)	0.6686	5703 (67.98%)	2.27 (1.42, 3.63)	0.0006	5703 (67.98%)	2.57 (1.92, 3.45)	<0.0001
25–29.9	1245 (14.84%)	1.43 (0.94, 2.18)	0.0964	1245 (14.84%)	5.31 (3.27, 8.65)	<0.0001	1245 (14.84%)	4.90 (3.59, 6.68)	<0.0001
≥30	264 (3.15%)	0.80 (0.38, 1.69)	0.5554	264 (3.15%)	6.93 (3.93, 12.24)	<0.0001	264 (3.15%)	6.32 (4.29, 9.29)	<0.0001
Not recorded	398 (4.74%)	1.58 (0.93, 2.68)	0.0900	398 (4.74%)	2.12 (1.12, 4.01)	0.0217	398 (4.74%)	2.74 (1.85, 4.04)	<0.0001
Gestational age at delivery (wk)	39.08 ± 1.37	0.00 (0.00, 0.01)	<0.0001	39.08 ± 1.37	1.67 (1.53, 1.82)	<0.0001	39.08 ± 1.37	1.27 (1.21, 1.33)	<0.0001
Birth weight(g)	3366.28 ± 453.53	1.00 (0.99, 1.00)	<0.0001	3366.28 ± 453.53	—^§	0.9414	3366.28 ± 453.53	1.02 (1.02, 1.02)	<0.0001
Caesarean section
No	3586 (42.75%)	Ref		3586 (42.75%)	Ref		3586 (42.75%)	Ref
Yes	4802 (57.25%)	1.64 (1.32, 2.03)	<0.0001	4802 (57.25%)	1.30 (1.08, 1.56)	0.0048	4802 (57.25%)	1.47 (1.31, 1.66)	<0.0001
Sex
Female	3872 (46.16%)	Ref		3872 (46.16%)	Ref		3872 (46.16%)	Ref
Male	4517 (53.84%)	1.26 (1.03, 1.55)	0.0245	4517 (53.84%)	1.98 (1.63, 2.39)	<0.0001	4517 (53.84%)	1.14 (1.01, 1.28)	0.0280
HbA1c(%) category
Q1	1881 (22.42%)	Ref		1881 (22.42%)	Ref		1881 (22.42%)	Ref
Q2	2132 (25.41%)	1.17 (0.85, 1.63)	0.3373	2132 (25.41%)	1.11 (0.83, 1.50)	0.4771	2132 (25.41%)	1.14 (0.95, 1.37)	0.1469
Q3	2123 (25.31%)	1.61 (1.18, 2.20)	0.0025	2123 (25.31%)	1.69 (1.28, 2.23)	0.0002	2123 (25.31%)	1.47 (1.23, 1.75)	<0.0001
Q4	2253 (26.86%)	1.79 (1.33, 2.43)	0.0001	2253 (26.86%)	2.06 (1.58, 2.68)	<0.0001	2253 (26.86%)	1.85 (1.56, 2.20)	<0.0001

Notes: Data are mean ± standard deviation or n (%). ^§The model failed because of the small sample size.

Abbreviations: OR, odds ratio; Ref, reference; LGA, large for gestational age.

Table 3 Relationship Between HbA1c and Adverse Birth Outcomes in Different Models

Outcomes	HbA1c(%)		HbA1c(%) Category							P for trend
	OR(95% CI)	P	Q1	Q2		Q3		Q4
				OR(95% CI)	P	OR(95% CI)	P	OR(95% CI)	P
Preterm birth
Non-adjusted	2.52 (1.78, 3.58)	<0.0001	Ref	1.17 (0.85, 1.63)	0.3373	1.61 (1.18, 2.20)	0.0025	1.79 (1.33, 2.43)	0.0001	<0.0001
Adjust I	2.39 (1.67, 3.44)	<0.0001	Ref	1.16 (0.84, 1.62)	0.3689	1.57 (1.15, 2.16)	0.0045	1.72 (1.26, 2.35)	0.0007	<0.0001
Adjust II	2.37 (1.65, 3.41)	<0.0001	Ref	1.16 (0.83, 1.61)	0.3852	1.57 (1.15, 2.16)	0.0046	1.71 (1.25, 2.34)	0.0007	0.0001
Macrosomia
Non-adjusted	2.81 (2.06, 3.82)	<0.0001	Ref	1.11 (0.83, 1.50)	0.4771	1.69 (1.28, 2.23)	0.0002	2.06 (1.58, 2.68)	<0.0001	<0.0001
Adjust I	1.91 (1.39, 2.63)	<0.0001	Ref	1.01 (0.75, 1.36)	0.9448	1.46 (1.10, 1.93)	0.0085	1.53 (1.16, 2.02)	0.0024	0.0001
Adjust II	2.25 (1.61, 3.13)	<0.0001	Ref	1.00 (0.74, 1.36)	0.9841	1.50 (1.13, 2.00)	0.0052	1.68 (1.26, 2.22)	0.0003	<0.0001
LGA
Non-adjusted	2.29 (1.87, 2.80)	<0.0001	Ref	1.14 (0.95, 1.37)	0.1469	1.47 (1.23, 1.75)	<0.0001	1.85 (1.56, 2.20)	<0.0001	<0.0001
Adjust I	1.64 (1.33, 2.02)	<0.0001	Ref	1.05 (0.87, 1.26)	0.6170	1.28 (1.07, 1.54)	0.0064	1.44 (1.20, 1.71)	<0.0001	<0.0001
Adjust II	1.82 (1.47, 2.25)	<0.0001	Ref	1.05 (0.87, 1.26)	0.6177	1.32 (1.10, 1.58)	0.0027	1.53 (1.28, 1.83)	<0.0001	<0.0001

Notes: Model I adjusted for maternal age and prepregnancy BMI. Model II adjusted for maternal age, prepregnancy BMI, gestational age at delivery, caesarean section, and sex. (Preterm birth does not adjust the gestational age at delivery.

Abbreviations: OR, odds ratio; Ref, reference; LGA, large for gestational age.