Isolated Maternal Hypothyroxinemia in the First Trimester Increases the Risks of Macrosomia and Large for Gestational Age During Pregnancy: a Retrospective Cohort Study

Background Thyroid hormones are very important for normal growth and development of fetus. Hypothyroidism during pregnancy and Graves' hyperthyroidism in pregnancy are well-known risk factors for small for gestational age (SGA). However, the influence of isolated maternal hypothyroxinemia (IMH) in the first trimester during pregnancy on birthweight is less analyzed and controversial. Objective To examine the correlation of IMH in the first trimester during pregnancy with birthweight. Methods This was a retrospective cohort study involving singleton pregnant women with medical files and receiving prenatal examination, delivery or termination of pregnancy in the Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2016 to October 2020. According to the 2.5th and 97.5th percentiles of free thyroxine (FT4) and thyroid stimulating hormone (TSH), participants were assigned into IMH group (n=344) and control group (n=19 426). Binary Logistic regression was used to analyze the correlation of IMH in the first trimester during pregnancy with birthweight. Then according to the pre-pregnancy body mass index (PPBMI), participants were assigned into the overweight/obesity group (PPBMI≥24.0 kg/m2, 69 cases in IMH group and 3 376 cases in control group) and non-overweight/obesity group (PPBMI<24.0 kg/m2, 275 cases in IMH group and 16 050 cases in control group). The pregnancy outcomes of different groups were compared and the relationship between IMH and pregnancy outcomes was compared. Results The results of multivariate Logistic regression analysis showed that, the incidence of macrosomia and large for gestational age (LGA) in the IMH group was 1.627 times (OR=1.627, 95%CI=1.103-2.399, P=0.014) and 1.681 times higher than the control group (OR= 1.681, 95%CI=1.288-2.196, P<0.001), respectively. However, there were no significant differences in the incidences of low birth weight (LBW) and SGA between the two groups (P>0.05). Among participants with PPBMI<24.0 kg/m2 (non-overweight/obesity group), the incidence of macrosomia and LGA in the IMH group was 2.021 times (OR=2.021, 95%CI=1.320-3.093, P=0.001) and 1.788 times (OR=1.788, 95%CI=1.322-2.418, P<0.001) higher than the control group, respectively. Among participants with PPBMI≥24.0 kg/m2 (overweight/obesity group), there were no significant differences in the incidences of macrosomia, LBW, LGA and SGA between the two groups (P>0.05) . Conclusion IMH in the first trimester increases the risks of macrosomia and LGA during pregnancy, especially in pre-pregnancy non-overweight/obese women. Among pre-pregnancy overweight /obese women, IMH in the first trimester does not increase the risks of macrosomia and LGA. However, the incidences of LBW and SGA are comparable in the total cohort, women with pre-pregnancy overweight/obese or those without pre-pregnancy overweight/obese.