Lundgaard Maja Hjelm, Sinding Marianne Munk, Sørensen Anne Nødgaard, Handberg Aase, Andersen Stig, Andersen Stine Linding
Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, 9000, Aalborg, Denmark.
Matern Health Neonatol Perinatol. 2024 Aug 2;10(1):16. doi: 10.1186/s40748-024-00186-4.
Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se.
We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999-2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011-2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity.
In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2-1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3-2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1-5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6-1.2)).
In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.
孕期母体甲状腺功能减退被认为会增加先兆子痫的风险，但潜在的因果机制仍存在不确定性。因此，甲状腺功能减退的孕妇发生先兆子痫风险增加是由于甲状腺激素缺乏还是自身免疫本身所致仍不清楚。
我们对丹麦人群中的两个妊娠队列进行了一项回顾性研究。全国性队列（n = 1,014,775）基于登记数据，包括1999年至2015年丹麦所有单胎妊娠。区域性队列（n = 14,573）包括2011年至2015年丹麦北部地区孕妇甲状腺刺激激素（TSH）、甲状腺过氧化物酶抗体（TPO-Ab）和甲状腺球蛋白抗体（Tg-Ab）（西门子医疗的ADVIA Centaur XPT）的生化检测结果，这些孕妇在孕早期采集血样作为染色体异常常规产前筛查的一部分。使用逻辑回归（调整比值比（aOR）及95%置信区间（CI））评估已诊断和生化评估的甲状腺功能减退与先兆子痫诊断之间的关联，并对潜在混杂因素进行调整，如产妇年龄、糖尿病和产次。
在全国性队列中，无甲状腺功能减退病史的孕妇（参照组（ref.））中有2.2%被诊断为先兆子痫，而甲状腺功能减退的孕妇中这一患病率为3.0%（aOR 1.3（95%CI：1.2 - 1.4）），孕期新诊断甲状腺功能减退的女性中为4.2%（aOR 1.6（95%CI：1.3 - 2.0））。在区域性队列中，孕早期TSH < 2.5 mIU/L的女性（参照组）中有2.3%被诊断为先兆子痫。TSH≥6 mIU/L的女性中，患病率为6.2%（aOR 2.4（95%CI：1.1 - 5.3））。考虑甲状腺自身免疫情况，孕早期TPO-Ab（> 60 U/mL）或Tg-Ab（> 33 U/mL）阳性的女性中有2.2%被诊断为先兆子痫（aOR 0.86（95%CI：0.6 - 1.2））。
在两个丹麦孕妇大型队列中，母体甲状腺功能减退始终与先兆子痫的较高风险相关。母体甲状腺功能的生化评估显示甲状腺功能减退的严重程度很重要。此外，结果不支持甲状腺自身免疫本身与先兆子痫之间存在关联。
