Hypothyroidism and the increased risk of preeclampsia – interpretative factors?

Figures & data

Figure 1. Flowchart demonstrating exclusions and group division of the study cohort

Table 1. Demographic and clinical characteristics of 149 women using levothyroxine, 88 women with preeclampsia and using levothyroxine, 1252 women with preeclampsia, and 1195 control women

	All women	Women using levothyroxine			Women with preeclampsia and levothyroxine			Women with preeclampsia			Controls, no preeclampsia or levothyroxine
Maternal or perinatal characteristics	N (%)	N (%)	Unadjusted OR (Cl 95%)^b	p value	N (%)	Unadjusted OR (Cl 95%)^b	p value	N (%)	Unadjusted OR (Cl 95%)^b	p value	N (%)
Maternal age, years ± SD	29.1 ± 5.7	31.0 ± 6.0	1.06 (1.03 ‒ 1.09)	<0.001	30.8 ± 6.0	1.06 (1.02 ‒ 1.10)	0.005	29.2 ± 6.0	1.01 (0.99 ‒ 1.02)	0.358	28.9 ± 6.0
<20	87 (3.5)	2 (1.3)	0.38 (0.09 ‒ 1.55)	0.175	2 (2.3)	0.65 (0.16 ‒ 2.70)	0.558	50 (4.0)	1.40 (0.91 ̶ 2.15)	0.130	37 (3.1)
20–40	2361 (94.1)	139 (93.3)	1.00		82 (93.2)	1.00		1161 (92.7)	1.00		1143 (95.6)
>40	60 (2.4)	8 (5.4)	2.46 (1.15 ‒ 5.28)	0.021	4 (4.5)	1.99 (0.70 ‒ 5.61)	0.195	41 (3.3)	2 .23 (1.29 ̶ 3.87)	0.004	15 (1.3)
BMI kg/m^2 ± SD	25.2 ± 5.63	28.0 ± 6.9	1.07 (1.05 ‒ 1.10)	<0.001	29.0 ± 7.3	1.09 (1.06 ‒ 1.11)	<0.001	26.4 ± 0.2	1.09 (1.07 ‒ 1.11)	<0.001	23.9 ± 4.7
<25	1572 (62.7)	64 (43.0)	1.00		29 (33.0)	1.00		661 (52.8)	1.00		876 (73.3)
25–30	526 (21.0)	46 (30.9)	1.89 (1.25 ‒2.85)	0.002	30 (34.1)	3.11 (1.84 ‒ 5.25)	<0.001	313 (25.0)	2.03 (1.66 ̶ 2.48)	<0.001	203 (17.0)
>30	410 (16.3)	39 (26.2)	2.98 (2.00 ‒ 4.42)	<0.001	29 (33.0)	4.20 (2.49 ‒ 7.08)	<0.001	278 (22.2)	2.90 (2.31 ̶ 3.65)	<0.001	116 (9.7)
Parity
Nulliparous	1284 (51.2)	69 (46.3)	1.00		35 (39.8)	1.00		818 (65.3)	1.00		756 (63.3)
Primi- or multiparous	1224 (48.8)	80 (53.7)	0.90 (0.65 ‒ 1.25)	0.530	53 (60.2)	0.68 (0.44 ‒ 1.06)	0.086	434 (34.7)	0.31 (0.26 ̶ 0.37)	<0.001	439 (36.7)
Comorbid medical information
Hypertension	224 (8.9)	22 (14.8)	1.85 (1.15 ‒ 2.98)	0.011	17 (19.3)	2.56 (1.48 ‒ 4.43)	<0.001	194 (15.5)	7.49 (5.06 − 11.10)	<0.001	25 (2.1)
Diabetes or GDM	370 (14.8)	54 (36.2)	3.68 (2.58 ‒ 5.24)	<0.001	37 (42.0)	4.55 (2.93 ‒ 7.05)	<0.001	254 (20.3)	2.50 (1.98–3.17)	<0.001	99 (8.3)
Smoking^a
Before pregnancy	145 (5.8)	8 (5.4)	0.94 (0.45 ‒ 1.96)	0.861	5 (5.7)	1.09 (0.43 ‒ 2.75)	0.859	75 (6.0)	1.10 (0.78 ̶ 1.54)	0.583	67 (5.6)
At some time during pregnancy	324 (12.9)	23 (15.4)	1.23 (0.77 ‒ 1.95)	0.394	20 (22.7)	2.00 (1.19 ‒ 3.38)	0.009	195 (15.6)	1.55 (1.22 ̶ 1.97)	<0.001	126 (10.5)
Throughout pregnancy	183 (7.3)	9 (6.0)	0.83 (0.41 ‒ 1.67)	0.598	4 (4.5)	0.68 (0.24 ‒ 1.90)	0.462	66 (5.3)	0.58 (0.42 ̶ 0.79)	0.001	112 (9.4)
All women	2508 (100)	149 (100)			88 (100)			1252 (100)			1195 (100)

BMI body mass index

^acompared to nonsmoking

^banalyzed by logistic regression, GDM gestational diabetes mellitus

Table 2. Type of hypothyroidism, results of thyrotropin stimulating hormone measurements and medication among 149 women using levothyroxine during pregnancy in relation to the development of preeclampsia

Thyroid disease	All N (%)	Preeclampsia N (%)	Controls N (%)	p-value
Hypothyreosis	103 (69.1)	58 (65.9)	45 (73.8)	0.221^a
Subclinical hypothyreosis	46 (30.9)	30 (34.1)	16 (26.2)	0.307^a
Hypothyroidism diagnosed before pregnancy	95 (63.8)	53 (60.2)	42 (68.9)	0.278^a
TSH 1. measurement GWs, mean ± SD	13.1 ± 7.9	13.3 ± 8.4	12.7 ± 7.2	0.707^b
1–15 GWs	97 (65.1)	58 (65.9)	39 (63.9)
>15 GWs	34 (22.8)	20 (22.7)	14 (23.0)
Not reported	18 (12.1)	10 (11.4)	8 (13.1)
TSH 1. measurement mU/L, mean ± SD	2.70 ± 2.00	2.74 ± 1.98	2.64 ± 2.04	0.789^b
< 2.5	64 (43.0)	36 (40.9)	28 (45.9)
> 2.5	67 (45.0)	42 (47.7)	25 (41.0)
Not reported	18 (12.1)	10 (11.4)	8 (13.1)
TSH
Highest value during first trimester (<15 GWs) mU/L, mean ± SD	3.17 ± 2.21	3.16 ± 2.22	3.17 ± 2.23	0.993^b
Highest value during pregnancy mU/L, mean ± SD	3.61 ± 3.03	3.60 ± 2.66	3.62 ± 3.54	0.973^b
Medication started
Before pregnancy	85 (57.0)	45 (51.1)	40 (65.6)	0.080^a
During pregnancy	54 (36.2)	37 (42.0)	17 (27.8)	0.077^a
Levothyroxine max dose µg/day^c	300	300	200
Total	149 (100)	88 (100)	61 (100)

TSH thyrotropin stimulating hormone, GW gestational week; Analyzed by ^aPearsons Chi-Square test or ^bIndependent samples t-test; ^c maximum dose in one or more women

Table 3. Comparison of 1 252 preeclamptic women with and without levothyroxine medication during pregnancy

	Women with preeclampsia and no levothyroxine N (%)	Women with preeclampsia and levothyroxine N (%)	p-value
Mild preeclampsia	680 (58.4)	51 (58.0)	0.932^a
Severe preeclampsia	484 (41.6)	37 (42.0)	0.932^a
Gestational week at delivery, GWs ± SD	37.0 ± 3.6	36.8 ± 3.0	0.673^b
Term ≥ 37	826 (71.0)	56 (63.6)
Moderately preterm, 32–36	216 (18.6)	26 (29.5)
Extremely preterm, ≤ 31	122 (10.5)	6 (6.8)
Birth weight, g	2922.6 ± 906.1	2993.6 ± 846.0	0.792^b
All women	1164 (100)	88 (100)

Cases were identified according to the International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) codes: Mild preeclampsia (O13 and O14.0), Severe preeclampsia (O14.1, O14.9, O15.0, O15.1, O15.2 and O15.9). GW gestational week; Analyzed by ^aPearsons Chi-Square test or ^bIndependent samples t-test