Glycemic Control in Pregnancies Complicated by Pre-Existing Diabetes Mellitus and Congenital Malformations: A Danish Population-Based Study

Figures & data

Table 1 Maternal and Infant Characteristics According to Maternal Diabetes Mellitus Status Among All Singleton Liveborn Infants Born in the North Denmark and Central Denmark Regions, 2000–2015

			Maternal Pregestational Diabetes						Total Population
	No Diabetes		Type 1 Diabetes			Type 2 Diabetes
	n	% ^a	n	%^a	Prevalence^b	n	% ^a	Prevalence^c	n	% ^a
Overall	311,727	99.2	2020	0.64	6,43	498	0.16	1.58	314,245	100.0
Maternal characteristics
Maternal age (years)
13–24	39,407	12.6	183	9.1	4.62	20	4.0	0.50	39,610	12.6
25–29	110,890	35.6	614	30.4	5.50	115	23.1	1.03	111,619	35.5
30–34	110,168	35.3	713	35.3	6.42	170	34.1	1.53	111,051	35.3
≥35	51,262	16.4	510	25.2	9.81	193	38.8	3.71	51,965	16.5
Parity
0	98,583	31.6	630	31.2	6.34	139	27.9	1.40	99,352	31.6
1	82,602	26.5	567	28.1	6.80	153	30.7	1.84	83,332	26.5
≥2	42,956	13.8	332	16.4	7.64	146	29.3	3.36	43,434	13.8
Missing	87,586	28.1	491	24.3	5.57	60	12.0	0.68	88,127	28.0
Cigarette smoking
No	260,594	83.6	1655	81.9	6.30	397	797	1.51	262,646	83.6
Yes	46,442	14.9	308	15.2	6.58	87	17.5	1.86	46,837	14.9
Missing	4691	1.5	57	2.8	11.97	14	2.8	2.94	4762	1.5
Body mass index (kg/m^2)
<18.5	9272	3.0	21	1.0	2.26	6	1.2	0.65	9299	3.0
18.5–24.9	139,860	44.9	663	32.8	4.72	92	18.5	0.65	140,615	44.7
25.0–29.9	50,107	16.1	411	20.3	8.12	112	22.5	2.21	50,630	16.1
≥30	29,734	9.5	484	24.0	15.89	239	48.0	7.85	30,457	9.7
Missing	82,754	26.5	441	21.8	5.30	49	9.8	0.59	83,244	26.5
Preeclampsia
No	302,875	97.2	1,772	87.7	5.81	453	91.0	1,48	305,100	97.1
Yes	8852	2.8	248	12.3	27.12	45	9.0	4.92	9145	2.9
Hypertension
No	307,314	98.6	1,868	92.5	6.03	450	90.4	1.45	309,632	98.5
Yes	4413	1.4	152	7.5	32.95	48	9.6	10.41	4613	1.5
Diabetic complications
No	311,727	100	1,465	72.5	4.67	472	94.8	1.50	313,664	99.8
Yes	0	0	555	27.5	955.24	26	5.2	44.75	581	0.2
Infant characteristics
Gender
Female	151,921	48.7	972	48.1	6.35	246	49.4	1.61	153,139	48.7
Male	159,806	51.3	1,048	51.9	6.51	252	50.6	1.56	161,106	51.3
Birth year
2000–2002	59,200	19.0	286	14.2	4.81	29	5.8	0.49	59,515	18.9
2003–2005	58,036	18.6	320	15.8	5.48	45	9.0	0.77	58,401	18.6
2006–2008	57,015	18.3	334	16.5	5.81	105	21.1	1.83	57,454	18.3
2009–2011	53,999	17.3	371	18.4	6.81	132	26.5	2.42	54,502	17.3
2012–2014	48,786	15.7	422	20.9	8.56	108	21.7	2.19	49,316	15.7
2015	34,691	11.1	287	14.2	8.19	79	15.9	2.25	35,057	11.2

a Notes: ^aFor maternal and infant characteristics, the column shows the row percentage distribution. Due to rounding to one decimal, the percentages may not add to 100%. ^bPrevalence of type 1 diabetes per 1,000 women. ^cPrevalence of type 2 diabetes per 1,000 women

Abbreviation: n, number.

Figure 1 Flow chart of the study population.

Figure 2 Prevalence of maternal diabetes according to calendar years, among all singleton liveborn infants born in the North Denmark and Central Denmark regions, 2000–2016.

Table 2 Odds Ratios of Major Congenital Malformations According to Type of Pregestational Diabetes Among 314,245 Live Born Singleton Children, North Denmark and Central Denmark Regions, 2000–2015

	Type of Diabetes Mellitus	Total n	Cases n	Prevalence (95% CI)	Crude OR (95% CI)	Adjusted^a OR (95% CI)
Major Congenital Maformations, Overall	No Diabetes Mellitus	311,727	8,116	2.6 (2.5; 2.7)	Reference	Reference
	Type 1 diabetes	2,020	153	7.6 (6.4; 8.7)	3.1 (2.6–3.6)	2.9 (2.5–3.5)
	Type 2 diabetes	498	26	5.2 (3.3; 7.2)	2.1 (1.4–3.1)	1.9 (1.3–2.8)
Nervous System	No diabetes mellitus	311,727	416	0.1 (0.1–0.1)	Reference	Reference
	Type 1 diabetes	2.020	< 5	0.2 (0.0–0.4)	1.5 (0.6–4.0)	1.6 (0.6–4.2)
	Type 2 diabetes	498	< 5	0.4 (0.0–1.0)	3.0 (0.8–12.1)	3.3 (0.8–13.2)
Eye	No diabetes mellitus	311,727	373	0.1 (0.1–0.1)	Reference	Reference
	Type 1 diabetes	2.020	7	0.3 (0.1–0.6)	2.9 (1.4–6.1)	2.9 (1.4–6.1)
	Type 2 diabetes	498	< 5	0.2 (0.0–0.6)	1.7 (0.2–12.0)	1.6 (0.2–11.5)
Ear, face, neck	No diabetes mellitus	311,727	99	0.0 (0.0–0.0)	Reference	Reference
	Type 1 diabetes	2.020	< 5	0.1 (0.0–0.2)	3.1 (0.8–12.7)	3.1 (0.8–12.7)
	Type 2 diabetes	498	< 5	0.0 (0.0–0.0)	0.0 (0.0-I)	0.0 (0.0-I)
Orofacial Clefts	No diabetes mellitus	311,727	524	0.2 (0.2–0.2)	Reference	Reference
	Type 1 diabetes	2.020	5	0.2 (0.0–0.5)	1.5 (0.6–3.6)	1.2 (0.5–3.3)
	Type 2 diabetes	498	< 5	0.2 (0.0–0.6)	1.2 (0.2–8.5)	1.3 (0.2–9.0)
Congenital heart diseases	No diabetes mellitus	311,727	3048	1.0 (0.9–1.0)	Reference	Reference
	Type 1 diabetes	2.020	101	5.0 (4.0–6.0)	5.3 (4.4–6.5)	5.0 (4.1–6.2)
	Type 2 diabetes	498	15	3.0 (1.5–4.5)	3.1 (1.9–5.3)	3.0 (1.8–5.0)
Respiratory System	No diabetes mellitus	311,727	156	0.1 (0.0–0.1)	Reference	Reference
	Type 1 diabetes	2.020	< 5	0.2 (0.0–0.4)	4.0 (1.5–10.7)	2.7 (0.9–8.5)
	Type 2 diabetes	498	< 5	0.2 (0.0–0.6)	4.0 (0.6–28.8)	3.2 (0.4–23.2)
Digestive System	No diabetes mellitus	311,727	541	0.2 (0.2–0.2)	Reference	Reference
	Type 1 diabetes	2.020	7	0.3 (0.1–0.6)	2.0 (0.9–4.2)	2.0 (1.0–4.3)
	Type 2 diabetes	498	< 5	0.4 (0.0–1.0)	2.3 (0.6–9.3)	2.3 (0.6–9.3)
Abdominal wall defects	No diabetes mellitus	311,727	74	0.0 (0.0–0.0)	Reference	Reference
	Type 1 diabetes	2.020	< 5	0.0 (0.0–0.1)	2.1 (0.3–15.0)	2.5 (0.4–18.3)
	Type 2 diabetes	498	< 5	0.0 (0.0–0.0)	0.0 (0.0-I)	0.0 (0.0-I)
Genital Organs	No diabetes mellitus	311,727	878	0.3 (0.3–0.3)	Reference	Reference
	Type 1 diabetes	2.020	10	0.5 (0.2–0.8)	1.8 (0.9–3.3)	1.7 (0.9–3.2)
	Type 2 diabetes	498	< 5	0.2 (0.0–0.6)	0.7 (0.1–5.1)	0.7 (0.1–4.7)
Urinary System	No diabetes mellitus	311,727	948	0.3 (0.3–0.3)	Reference	Reference
	Type 1 diabetes	2.020	10	0.5 (0.2–0.8)	1.6 (0.9–3.0)	1.5 (0.8–2.8)
	Type 2 diabetes	498	< 5	0.4 (0.0–1.0)	1.3 (0.3–5.3)	1.3 (0.3–5.2)
Musculoskeletal System	No diabetes mellitus	311,727	1007	0.3 (0.3–0.3)	Reference	Reference
	Type 1 diabetes	2.020	9	0.4 (0.2–0.7)	1.4 (0.7–2.7)	1.2 (0.6–2.5)
	Type 2 diabetes	498	< 5	0.4 (0.0–1.0)	1.2 (0.3–5.0)	0.6 (0.1–4.3)
Other Malformations	No diabetes mellitus	311,727	587	0.2 (0.2–0.2)	Reference	Reference
	Type 1 diabetes	2.020	6	0.3 (0.1–0.5)	1.6 (0.7–3.5)	1.5 (0.7–3.4)
	Type 2 diabetes	498	< 5	0.6 (0.0–1.3)	3.2 (1.0–10.0)	2.9 (0.9–8.9)

Note: ^aAdjusted for maternal age, cigarette smoking, parity, and year of birth.

Abbreviations: CI, confidence interval; n, number; OR, odds ratio.

Figure 3 Prevalence (%) of major congenital malformations according to level of maternal HbA1c among all singleton liveborn infants of mothers with pre-existing diabetes, in the North Denmark and Central Denmark regions, 2000–2016.

Table 3 Odds Ratios of Major Congenital Malformations According to Level of HbA1c Among 314,245 Live Born Singleton Children, North Denmark and Central Denmark Regions, 2000–2016

Type of Diabetes	Level of HbA1c, %		Major Malformations		Model 1^a		Model 2^b
			n	Prevalence 95% CI	Crude OR	Adjusted^a OR (95% CI)	Crude OR	Adjusted^b OR (95% CI)
No diabetes	–	311,727	8,116	2.6 (2.5; 2.7)	–	–	1.0	1.0 (reference)
Type 1 diabetes	<5.5	253	11	4.3 (1.8; 6.9)	1.0	1.0 (reference)	1.7	1.4 (0.9; 2.6)
	5.5 – <6.5	374	14	3.7 (1.8; 5.7)	1.0	0.9 (0.4; 2.1)	1.5	1.3 (0.7; 2.3)
	6.5 – <7.5	509	39	7.7 (5.4; 10.0)	1.8	2.1 (1.0; 4.4)	3.1	3.0 (2.1; 4.3)
	7.5 – <8.5	334	31	9.3 (6.2; 12.4)	2.3	2.8 (1.3; 6.0)	3.8	3.9 (2.6; 6.0)
	8.5 – <9.5	185	21	11.4 (6.8; 15.9)	2.8	4.6 (2.0; 10.1)	4.8	6.2 (3.8; 10.2)
	≥9.5	131	26	19.8 (13.0; 26.7)	5.4	6.1 (2.7; 13.8)	9.3	8.7 (5.3; 14.5)
No diabetes	–	311,727	8,116	2.6 (2.5; 2.7)	–	–	1.0	1.0 (reference)
Type 2 diabetes	<5.5	116	<5	3.4 (0.1; 6.8)	1.0	1.0 (reference)	1.3	1.7 (0.9; 3.5)
	5.5 – <6.5	173	9	5.2 (0.5; 5.1)	1.5	1.3 (0.4; 4.5)	2.1	0.5 (0.1; 3.9)
	6.5 – <7.5	65	<5	4.6 (0.0; 9.7)	1.4	0.5 (0.0; 4.5)	1.8	2.9 (0.7; 12.2)
	7.5 – <8.5	27	<5	11.1 (0.0; 23.0)	3.5	2.1 (0.3; 13.5)	4.7	4.8 (1.1; 21.4)
	≥8.5	16	<5	12.5 (0.0; 28.7)	4.0	4.2 (0.7; 27.3)	5.3	1.7 (0.9; 3.5)

Notes: ^a1: women with diabetes mellitus and HbA1c<5.5% as the reference group, adjusted for maternal age, cigarette smoking, parity and year of birth. ^bModel 2: women without diabetes mellitus as the reference group, adjusted for maternal age, cigarette smoking, parity and year of birth.

Abbreviations: CI, confidence interval; n, number; OR, odds ratio.