Maternal weight gains and thyroid function; a narrative study

Weight gain during pregnancy can affect maternal mortality, pregnancy complications, and delivery, as well as healthy fetal growth and birth weight. Studies have shown that in addition to maternal obesity, which is associated with an increased risk of gestational hypertension, gestational diabetes, stillbirth, and large for gestational age, higher gestational weight gain has also adverse effects on maternal and fetal pregnancy outcomes. Besides, being overweight during pregnancy is associated with problems with breastfeeding in the postpartum period and causes postpartum weight gain, which can persist for up to three years after delivery. This, in turn, can leads to the unfavorable outcome of labor during subsequent pregnancies.Most weight gain during pregnancy is related to the uterus and its contents, breasts, and increased blood volume and extravascular fluid. Besides, the weight gain is due to metabolic changes that lead to an increase in cellular water. Between 20 and 30 weeks of gestation, weight gain is largely due to increased maternal fat stores, and between 30 and 40 weeks of gestation, most of the weight gain is due to fetal growth and increased extravascular fluid.Several factors such as pre-pregnancy weight, height, ethnicity, age, parity, smoking, socioeconomic status, and daily energy consumption affect the rate of weight gain during pregnancy. Also, metabolic factors such as fat biomarkers (adipocytokines) and less rest are associated with more weight gain.  Maternal thyroid function also appears to influence maternal weight gain and may have an adverse effect on maternal and neonatal outcomes. Maternal free thyroxine (FT4) has an important relationship with maternal fat stores so that in euthyroid individuals, maternal fat stores are associated with lower FT4. While this hormone is much less related to fetal growth and increased extravascular fluid, it is associated with weight gain between 30 and 40 weeks of pregnancy. Studies on the relationship between maternal thyroid function and weight gain during pregnancy are limited in this review study, we summarized the studies that assessed the effect of maternal thyroid function on maternal weight gain.

In this systematic review, the PubMed, Web of Science, and Scopus, as well as SID, Irandoc, and Magiran (Persian databases) were searched with appropriate keywords for the English and Persian related articles up to March 2020. The comprehensive electronic literature searching was conducted independently by two authors, who were familiar with search methods and information sources, without any restrictions. Furthermore, to maximize the identification of eligible studies, review articles and the reference lists of studies included were manually evaluated as well. We also excluded non-original studies including guidelines, review articles, case reports, animal studies, commentaries, editorials, letters to the editor, meeting abstracts, as well as studies that did not provide accurate and clear data. The quality of the studies was critically appraised for their methodology and results. Two authors, blinded to study author, journal name, and institution, evaluated the quality of the studies independently. The Newcastle-Ottawa scale was used to evaluate the quality of articles for cohort studies. This scale evaluates the quality of published nonrandomized studies in terms of selection, comparability, and outcomes. In the current review, out of 121 articles (115 English articles and 6 Persian articles) in the initial search, finally, 5 eligible studies were reviewed. The results of the quality assessment of the studies showed that all 5 studies had the desired (high) quality.

The results of some studies showed a strong association between maternal thyroid function and weight gain during pregnancy. Higher TSH levels and lower maternal FT4 levels in early pregnancy and lower FT4 levels in mid-pregnancy have been associated with an increased risk of overweight gain during pregnancy. The basic mechanisms associated with maternal thyroid function and maternal weight gain during pregnancy are still unclear. However, there seems to be a two-pronged effect in this regard.Maternal weight gain in early pregnancy largely reflects maternal fat deposition, and in mid-and late pregnancy reflects increased maternal fluid and amniotic fluid and fetal, placental, and uterine growth. Studies have shown that maternal thyroxin (FT4) levels have a significant relationship with maternal fat reserves. Adipocytes increase the level of the hormone leptin, which in turn affects neurons in the hypothalamus and thus the thyrotropic axis and TSH secretion. Both cross-sectional and longitudinal studies have shown that increased leptin levels lead to higher TSH levels above the upper limit of reference. Changes in leptin levels are associated with weight gain and may affect thyroid function via hypothalamic-pituitary-thyroid stimulation.Increased hCG levels stimulate the thyroid gland through stimulation of the TSH receptor, leading to increased FT4 and decreased TSH levels during pregnancy. Because hCG levels are highest at the end of the first trimester, TSH levels are lower early in pregnancy. However, maternal hCG levels may also affect maternal weight during pregnancy, and it has been suggested that the effect of hCG may somewhat explain the weaker association between maternal TSH levels and maternal weight during pregnancy. Studies of the association of high body mass index (BMI) with maternal FT4 may also be explained by the effect of human chorionic gonadotropin (hCG).

Maternal weight during pregnancy should be considered as one of the important variables in studies focusing on the effect of maternal thyroid function during pregnancy on pregnancy and child outcomes. There is insufficient data on the relationship between maternal thyroid function during pregnancy and maternal weight gain, and the underlying mechanisms are unclear. The effect of thyroid hormones on maternal weight gain seems to be implemented through several biological pathways and seems to be a two-way effect. While thyroid function has a clear effect on basal metabolism and can affect fat stores, on the other hand, maternal weight gain may lead to altered thyroid function. What is certain is that more studies are needed to gain more insight into the observed relationships and their underlying complex mechanisms, especially among pregnant women. Future research is also needed to review thyroid hormone intervention strategies in women with high pre-pregnancy BMI and low FT4, as well as their impact on lower weight gain during pregnancy and better outcome outcomes.