Previous studies have shown that pregnancy can be risky for women with LAM, leading to faster worsening of lung function and a higher chance of lung collapse (pneumothorax). Sirolimus (rapamycin) is the main medication used to treat LAM. However, its safety during pregnancy has not been clearly established, and animal studies have raised concerns about possible adverse effects on the baby.

In this retrospective study, we analyzed data from 12 pregnancies in 9 women with LAM who used sirolimus during pregnancy. These data were collected from multiple clinics across the LAM clinic network and included patients from the United States, Brazil, France, and England. In general, the patients had moderately impaired lung function prior to pregnancy (average lung function (FEV1): 56% predicted). None of the women had a diagnosis of tuberous sclerosis.

Most patients (10 out of 12) stayed on sirolimus throughout pregnancy. Two patients withheld sirolimus prior to pregnancy but restarted in the second trimester after experiencing a lung collapse (pneumothorax) in the first trimester. The average dose of sirolimus during pregnancy was 1mg daily with an average blood trough level of 3ng/ml.

The main findings from our study are:

• Lung function remained stable during pregnancy.
• There were no lung collapses (pneumothoraces) when patients were on sirolimus.
• 10 out of the 12 pregnancies resulted in live births. One pregnancy ended in miscarriage, and another was ended because of molar pregnancy (a rare complication).
• After about 3.5 years of average follow-up, all 10 babies appear to be healthy and growing normally.
• 70% of the babies were breastfed while the mothers were on sirolimus, with no apparent ill effect on the child’s growth.

These results suggest that low-dose sirolimus may be relatively safe during pregnancy, has the potential to help stabilize lung function, and prevent LAM-related complications such as pneumothoraces. The study presents cautiously optimistic preliminary findings. However, the study had a small number of participants and no control group, so the findings should be interpreted with caution. We emphasize the need for larger studies and propose creating an international registry to collect more data to help doctors and patients make better decisions about using sirolimus during pregnancy.

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