While half of all miscarriages are associated with chromosomal abnormalities, the remainder are euploid where miscarriage probably occurs as a result of implantation failure . Thus, a significant proportion of these euploid miscarriages are potentially salvageable .
The possibility levothyroxine may salvage some miscarriages caused by TPOAb is a potentially important finding given approximately 6% of women in early pregnancy may be TPOAb positive [6, 7]. It is perhaps now timely to consider how such a test could be meaningfully integrated into clinical care. This might inform both future clinical practice and the design of validation trials of levothyroxine treatment for miscarriage in women who are TPOAb positive.
We would propose women who have never previously had a liveborn but have suffered one or more miscarriages may be the appropriate cohort to screen for TPOAb. And we suggest it would be clinically pragmatic to screen women on the day women they present for management of their miscarriage. The TPOAb results can be reviewed at a six-week review where potentially, levothyroxine could be prescribed. The approach is analogous to current clinical management of unexplained stillbirths, where a number of tests are performed during the time women are admitted for induction of labour to empty the uterus.
In this study, we have independently confirmed that higher levels of TPOAb are associated with miscarriage [1–4]. Furthermore, we have confirmed TPOAb levels do not significantly vary with serum hCGs levels suggesting it is may be valid to screen for TPOAb at the time women present for management of their miscarriage. This contrasts with our results for TSH, fT3 and fT4, where we observed correlations with serum hCG levels that were either significant, or just failed to meet significance. This suggests while hCG is able to stimulate the TSH receptor, it does not appear to affect TPOAb levels.
Among the control group, the prevalence of TPOAb was 8.8% (when using the manufacturer’s cut off defined as > 2 standard deviations above the mean). This figure is relatively similar to the prevalence of TPOAb positivity reported in two very large cohort studies. Abbassi-Ghanavati et al. measured TPOAb in serum samples from 17,298 women within the first 20 weeks of gestation and found 6% were TPOAb positive . Similarly, Clearly-Goldman et al. also reported the prevalence of TPOAb positivity among 10,990 samples obtained in the first trimester was 6% . This suggests potentially, our findings may be generalisable to other populations.
Vitamin D deficiency was not associated with an increased risk of miscarriage in our study. In fact, we found vitamin D levels were increased among those who miscarried. This finding was contrary to our hypothesis, which was based on preliminary observations that vitamin D deficiency is associated with thyroid autoimmunity [10, 11], as well as other autoimmune diseases in which miscarriage rates may be increased . The biological significance of this finding, if any, is unclear. Given this ran contrary to our hypothesis and the P value just reached significance (P = 0.013), this finding may be a Type I error. Therefore, it firstly requires confirmation in future studies before it merits further consideration.
It is remarkable that even in a region with relatively high levels of sunlight such as southeast Australia, only 12% of pregnant women of predominantly Caucasian descent are vitamin D sufficient. The high prevalence of insufficient vitamin D levels in our cohort is potentially concerning, given that maternal vitamin D deficiency may be associated with a number of adverse pregnancy outcomes . However, the optimal vitamin D level to reduce the risk of pregnancy-associated complications remains unknown.
Our study has some strengths. All samples were collected prospectively and processed in a similar manner at a single centre. The laboratory analyses’ were done in one batch, and by an operator blinded to the sample identities. Finally, we used commercial assays that are used to process samples for clinical care.