Retrospective evaluation of the relationship of maternal subclinical hypothyroidism and adverse obstetric outcomes

Introduction and Objective: Subclinical hypothyroidism (SCH) is a biochemical diagnosis, often asymptomatic, common among women of reproductive age (7.5 – 8.5%). It is well-known that sufficient maternal thyroid hormone during pregnancy is important for both maternal and fetal health. In contrast to overt hypothyroidism, the effects of SCH and its treatment on pregnancy and fetomaternal outcomes are not yet clearly known. On another note, the previously recommended first trimester upper limit of thyroid stimulating hormone (TSH) for hypothyroidism diagnosis of 2.5 mU/L is revised to 4.0 mU/L by clinical guidelines in the light of recent studies. This has led to a dispute over the clinical approaches to pregnancies with first trimester thyroid stimulating hormone (TSH) levels within 2.5 – 4.0 mU/L. In this work, the healthy pregnancies are compared to pregnancies with SCH and overt hypothyroidism in their risk of developing intrauterine growth restriction (IUGR), premature birth, hypertensive diseases and fetal macrosomia. The pregnancies with SCH are further subdivided depending on whether thyroid hormone treatment is given and the effect of the treatment on fetomaternal outcomes are investigated. Additionally, in this study, the relation between smoking and SCH as well as the effects of first trimester free thyroxine hormone (fT4) and TSH levels on pregnancy outcomes are explored, since the relevant data in literature is scarce to the best of our knowledge. Material and Method: The entries of pregnancies with thyroid function tests within the first 14 weeks available are inspected and the ones which pass the criteria to be included in this study are grouped into three, according to the TSH and fT4 levels: healthy (TSH<2.5 mU/L, fT4: 0.93–1.71 pg/dl) , with SCH (TSH: 2.5–4.0 mU/L, fT4: 0.93–1.71 pg/dl) , and with overt hypothyroidism (TSH> 4.0 mU/L, fT4< 0.93 pg/dl). The pregnancy entries, medical examinations, lab results, and birth reports are studied retrospectively, in terms of adverse pregnancy outcomes such as pregnancy loss, IUGR, premature birth, pregnancy related hypertensive diseases and fetal macrosomia. We note that the patients included in this study are communicated and their informed consents are taken over the phone while their personal data in the entries are verified. Results: Although the IUGR (7.1% and 7.0% with p of 0.06) and pregnancy loss (12.4% and 11.0% with p of 0.13) rates in the groups of SCH and overt hypothyroidism are statistically similar, the pregnancy related hypertensive diseases (4.4% and 10.0% with p of 0.023) and fetal macrosomia (5.1% and 9.5% with p of 0.047) rates in the overt hypothyroidism group are found to be statistically higher. While pregnancy loss (1% and 2.38% with p of 0.3108), IUGR (6.5% and 7.5% with p of 0.12), premature birth (13.5% and 11.9% with p of 0.66), and fetal macrosomia (5.0% and 5.2% with p of 1) rates are statistically insignificant in the group of SCH with thyroid hormone treatment, a statistically significant increase in the pregnancy related hypertensive diseases (7.0% and 2.4% with p of 0.006) is found. It is observed that the effect of first trimester free thyroxine hormone (fT4) and TSH levels on pregnancy outcomes is insignificant. In the groups of SCH and overt hypothyroidism, smoking is found to increase the risk of IUGR (2.1% and 9.8% with p of 0.003 and 4.9% and 16.2% with p of 0.02, respectively) and premature birth (6.1% and 13.4% with p of 0.034 and %8.0 and 24.3% with p of 0.008, respectively). Conclusion: While rates of pregnancy loss, pregnancy related hypertensive diseases, and fetal macrosomia are found to be similar between the control group and the SCH group; there are statistically significant differences between the control group and the overt hypothyroidism group. These findings show that for healthier pregnancy outcomes the first trimester upper limit of TSH must be at 4.0 mU/L. Medication for pregnancies with SCH is found to be ineffective on the pregnancy outcomes considered in this study and even counterproductive for pregnancy related hypertensive diseases. The results show no meaningful connection between the first trimester fT4 and TSH levels and the pregnancy outcomes. In addition, smoking is found to increase the risk of IUGR and premature birth for the control and overt hypothyroidism groups while the relation is insignificant for the SCH group. Keywords: Fetal macrosomia, intrauterine fetal growth restriction, pregnancy loss, pregnancy related hypertensive diseases, premature birth, subclinical hypothyroidism