Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

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 Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] 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 After the addition of 5 unpublished data sets, a total of 19 cohorts were included.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 FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 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 insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Changes in objectively measured smoking in pregnancy by time and legislative changes in Finland: a retrospective cohort study.

OBJECTIVES: To study the changes in prevalence, characteristics and outcomes of pregnant smokers over time and legislative changes. DESIGN AND SETTING: Retrospective nationwide cohort. PARTICIPANTS: Our study consisted of 9627 randomly selected pregnancies from the Finnish Maternity Cohort (1987-2011), with demographic characteristics and pregnancy and perinatal data obtained from the Medical Birth Registry and early pregnancy serum samples analysed for cotinine levels. Women were categorised based on their self-reported smoking status and measured cotinine levels (with ≥4.73 ng/mL deemed high). Data were stratified to three time periods based on legislative changes in the Tobacco Act. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of pregnant smokers and demographics, and perinatal and pregnancy outcomes of pregnant smokers over time. RESULTS: Overall, 71.6% of women were non-smokers, 16.2% were active cigarette smokers, 7.7% undisclosed smoking but had high cotinine levels and 4.5% were inactive cigarette smokers. The prevalence of active cigarette smokers decreased from mid-1990s onwards among women aged ≥30 years, probably due to the ban of cigarette smoking in most workplaces. We observed no changes in the prevalence of inactive smokers or women who undisclosed smoking by time or legislative changes.Women who undisclosed smoking had similar characteristics and perinatal outcomes as inactive and active smokers. Compared with non-smokers, women who undisclosed smoking were more likely to be young, unmarried, have a socioeconomic status lower than white-collar worker and have a preterm birth. CONCLUSIONS: Women who undisclosed smoking were very similar to pregnant cigarette smokers. We observed a reduction in the prevalence of active pregnant cigarette smokers after the ban of indoor smoking in workplaces and restaurants, mostly among women aged ≥30 years.

Inhibitory effect of the angiotensin converting enzyme inhibitors captopril and enalapril on the conversion of procollagen to collagen.

OBJECTIVE AND DESIGN: Angiotensin converting enzyme inhibitors are reported to inhibit the collagen accumulation involved in left ventricular hypertrophy. We tested the effect of captopril and enalapril on the conversion of procollagen to collagen in short-term tissue cultures in order to study the possible mechanisms by which the antifibrotic effect of this group of inhibitors takes place. METHODS: We employed short-term cartilage and tendon tissue cultures to monitor the conversion of procollagen to collagen. After pulse-labelling with [14C]-proline, the cultures were incubated further with the test compounds in different concentrations for a 180 min chase period. The reaction was stopped and radioactive collagenous peptides were analysed by gel electrophoresis. The amounts of collagenous proalpha and alpha chains were estimated, and the inhibition of procollagen to collagen conversion was calculated relative to 0 min control (100% inhibition) and 180 min control (0% inhibition) samples. RESULTS: Inhibition (50%) was obtained with 7 mmol/l captopril and 22 mmol/l enalapril in the cartilage cultures. Both compounds seemed to inhibit the conversion in clearly lower concentrations in tendon cultures, 4 mmol/l and 7 mmol/l, respectively, were sufficient for 50% inhibition. Angiotensin I, II, saralasin and bradykinin did not have any effect on conversion at 3.5, 9, 2 and 4 mmol/l concentrations, respectively. CONCLUSION: The peptidase inhibitors captopril and enalapril are able to inhibit the conversion of procollagen to collagen, which is a proteolytic process, possibly by inhibiting the specific procollagen proteases. Whether this phenomenon is involved in the antifibrotic property of angiotensin converting enzyme inhibitors warrants further study, as does the question of whether new antifibrotic agents could be developed on this basis.