▎ WuXi AppTec content team editor
Hypertensive diseases during pregnancy include hypertension during pregnancy and preeclampsia or eclampsia, which affect about 10% to 15% of pregnant women and are one of the leading causes of maternal and neonatal mortality and morbidity worldwide. Preeclampsia is a major risk factor for intrauterine growth retardation, placental abruption, and preterm birth.
For pregnant people, normal maternal thyroid function is essential to avoid complications during pregnancy. Although multiple observational studies have evaluated the relationship between thyroid dysfunction and hypertensive disorders in pregnancy, the methods and definitions of abnormal thyroid function tests are heterogeneous and the results are contradictory.
This question was further answered recently by a systematic review and meta-analysis study published in The Lancet Diabetes & Endocrinology. The results showed that subclinical hypothyroidism in pregnancy was associated with a higher risk of preeclampsia compared with normal thyroid function.
Screenshot source: The LancetDiabetes & Endocrinology
In this systematic review and meta-analysis, the researchers retrieved data from databases such as MEDLINE (Ovid), Embase, Scopus, and Cochrane from their inception date to December 27, 2019, including prospective cohort studies, including maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, and gestational hypertension, preeclampsia, or both.
The primary outcomes of the study were documented as hypertension and preeclampsia during pregnancy. Secondary outcomes were combined outcomes for hypertension or preeclampsia during pregnancy in cohorts with data on preeclampsia and hypertension in pregnancy, or in studies that did not separately report hypertension and preeclampsia during pregnancy. The researchers analyzed individual participant data using a logical mixed-effects regression model that was adjusted based on maternal age, BMI, smoking, fetal count, race, and gestational age at the time of blood sampling.
In the end, 19 cohorts were included in the analysis with the authors' consent, including 46,528 pregnant women with an average age of 29.1 years (SD 5.2 years), a median gestational age of 12.5 weeks (95% range 7.0 to 39.7) at blood collection, and an average BMI of 23.8 kg/m (SD 4.4) for pregnant women. Of these, data (TSH, FT4 concentration, and TPO antibody status) were sufficient for 39,826 (85.6 percent) women, which could be classified according to their thyroid function status.
Image credit: 123RF
Analysis showed that among these women,
1275 (3.2%) had subclinical hypothyroidism, 933 (2.3%) had simple hypothyroxinemia, 619 (1.6%) had subclinical hyperthyroidism, and 337 (0.8%) had significant hyperthyroidism. In addition, 3,005 of the 39,736 women with TPO (7.6%) were positive for TPO antibodies.
With subclinical hypothyroidism, the risk of preeclampsia is increased by 53% (2.1% vs 3.6%, OR 1.53 [95% CI 1.09–2.15]) compared with normal thyroid function, but is not significantly associated with gestational hypertension (5.7% vs 4.2%, OR1.18 [95% CI 0.91–1.53]).
Subclinical hypothyroidism also increased the risk of compound outcomes by 45% (8.9% vs 5.6%, OR 1.45 [95% CI 1.14–1.85]).
Significant hyperthyroidism was not associated with gestational hypertension or preeclampsia, however, it increased the risk of compound outcomes by 90% (9.3% vs 5.6%, OR 1.90 [95% CI 1.21–2.99].
Subclinical hyperthyroidism, simple hypothyroxinemia, or positive TPO antibodies were not associated with gestational hypertension or pre-eclampsia.
In the continuous analysis, both the increase and decrease in TSH concentration were associated with an increased risk of preeclampsia (p=0.0001) and were U-shaped. The FT4 concentration is independent of the measured results.
The results of this meta-analysis, which quantify the risk of hypertension or preeclampsia in pregnancy in women with thyroid dysfunction, add evidence to the risk of thyroid dysfunction in pregnancy to adverse outcomes for mothers and infants, and have potential implications for setting optimal treatment goals for levothyroxine in pregnancy, which could be evaluated in future interventional studies.