IMPORTANCE Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. OBJECTIVE To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. DATA SOURCES AND STUDY SELECTION Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT 4 ] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. DATA EXTRACTION AND SYNTHESIS The primary authors provided individual participant data that were analyzed using mixed-effects models. MAIN OUTCOMES AND MEASURES The primary outcome was preterm birth (<37 weeks' gestational age). RESULTS From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT 4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT 4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). CONCLUSIONS AND RELEVANCE Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide i...

Studies on hypothyroidism and hyperthyroidism implicate that adequate maternal thyroid hormone availability is required for optimal fetal growth and development. Studies on the association of mild thyroid function test abnormalities with birth weight report heterogeneous results. Some studies indicate that high FT4 concentrations are associated with lower birth weight which could have implications for the treatment target in women already on levothyroxine therapy. We searched Medline (Ovid), Embase.com, Web-of-Science, Cochrane CENTRAL and Google Scholar up to March 18 th , 2018 and collected data on serum thyroid function tests and antibody status during pregnancy and birth weight from prospective cohort studies including treatment-naïve pregnant women.

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The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) is an important negative regulator of signal transduction through the T-cell receptors (TCR). Recently a single-nucleotide polymorphism (SNP) 1858 C/T within this gene was shown to be a risk factor for several autoimmune diseases, such as rheumatoid arthritis (RA), Graves' Disease (GD), systemic lupus erythematosus (SLE), Wegener's granulomatosis (WG) and type 1 diabetes mellitus (T1D). The aim of this study was to analyze a possible association between 1858 C/T SNP and a number of autoimmune diseases, including RA, GD and T1D in Russian population. Patients with T1D, GD, RA and healthy controls were genotyped for the 1858 C/T SNP in PTPN22 gene. We found a significant association between PTPN22 1858 C/T SNP and T1D and GD. 1858T/T genotype was observed more frequently in T1D and GD patients compared to control subjects. No such association was observed for RA. In concordance with a previous data establishing PTPN22 1858 C/T SNP association with several autoimmune diseases, our findings provide further evidence that the PTPN22 gene may play an important role in the susceptibility to some autoimmune diseases.

IMPORTANCE Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. OBJECTIVE To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. DATA SOURCES AND STUDY SELECTION Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT 4 ] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. DATA EXTRACTION AND SYNTHESISThe primary authors provided individual participant data that were analyzed using mixed-effects models. MAIN OUTCOMES AND MEASURESThe primary outcome was preterm birth (<37 weeks' gestational age).RESULTS From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT 4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT 4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).CONCLUSIONS AND RELEVANCE Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insig...