Sex ratio at birth is associated with first-trimester maternal thyrotropin in women receiving levothyroxine

The sex ratio at birth (male out of total alive newborns) is historically established at 0.515 and is influenced by numerous factors. It is not known, however, whether it is influenced by maternal thyroid conditions. Our aim was to analyze its association with maternal thyroid autoimmunity and first-trimester thyrotropin (TSH).

We performed a retrospective cohort study at a tertiary care center. We studied 167 women who had received pregestational treatment with levothyroxine for hypothyroidism or differentiated thyroid carcinoma and gave birth to live infants. Women with secondary/tertiary hypothyroidism, pregestational diabetes mellitus, or multiple pregnancies were excluded. Autoimmunity was defined as present/absent, and mean first-trimester TSH was tested both as a quantitative variable and using six predefined categories. The outcome measure was sex ratio at birth.

The sex ratio at birth was 0.485, not significantly different from expected. Maternal characteristics were similar in mothers of female and male newborns with the exception of mean first-trimester TSH, which was higher in pregnancies of female fetuses (3.27 vs. 2.52 mUI/L, p<0.025). Newborn sex differed across predefined TSH categories (p<0.021, with a sex ratio of 0.200 [95% confidence interval 0.00-0.402] for TSH ≥10 mUI/L). A multiple logistic regression analysis to predict newborn male sex confirmed maternal mean first-trimester TSH as the single predictor (odds ratio 0.900 [95% confidence interval 0.823-0.984], p<0.020).

In women under pregestational treatment with levothyroxine, mean maternal first-trimester TSH is negatively associated with sex ratio at birth. This association has not been previously described.