Abstract
ObjectiveTo investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes.MethodsIn total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed.ResultsPatients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05).ConclusionThe lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.
Highlights
Hypothyroidism in pregnancy refers to a systemic hypometabolic syndrome caused by hypothyroxinemia or thyroid hormone resistance and has a prevalence of 0.5%, and its etiology remains unclear [1]
The inclusion criteria were based on the diagnostic criteria according to the 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum [13] and the specific threshold reference range formulated by the laboratory of the Third Affiliated Hospital of Zhengzhou University [hypothyroidism during pregnancy: FT4 < 11.5 pmol/L and TSH > 4.0 mIU/L; normal pregnancy women: 11.5 < FT4 < 22.7 pmol/L, 0.4 < TSH< 4.0 mIU/L]
No significant difference was found in age, body mass index (BMI) and gestational week between the study case and control group (P > 0.05), which minimized the influence of confounding factors on the experimental results
Summary
Hypothyroidism in pregnancy refers to a systemic hypometabolic syndrome caused by hypothyroxinemia or thyroid hormone resistance and has a prevalence of 0.5%, and its etiology remains unclear [1]. The maternal and fetal needs for thyroid hormone increase during pregnancy. If the low level of thyroid hormone in pregnant women with hypothyroidism is not effectively improved, there is an increased risk of adverse pregnancy outcomes, such as premature birth, miscarriage, and low birth weight, and the neurointelligence development of the offspring can be seriously affected [2, 3]. Z. et al [6] showed that the abundance of the Paraprevotella was increased in patients with primary hypothyroidism, whereas the abundances of the genera Haemophilus and Clostridium were decreased, and the thyroid function of mice with fecal microbiota transplantation (FMT) using flora from patients with hypothyroidism was abnormal. The relationship between plasma lipid metabolites and intestinal microflora and their effects on the pathological mechanism of hypothyroidism during pregnancy remain unclear
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