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Background: Dolutegravir, an integrase strand transfer inhibitor (InSTI), is a major antiretroviral agent for HIV infection. Its use is promising, especially in low- and middle-income countries, because of a high resistance barrier and a good safety profile. Very recently, a World Health Organization safety signal has been raised regarding neural tube defects after the first-trimester exposure. Furthermore, to date, the experience is limited regarding the use of the other InSTI drugs (raltegravir and elvitegravir) during pregnancy. Our objective is to analyze the safety of InSTI drugs in pregnant women., Setting: Nation-wide database cohort analysis., Methods: We evaluated the risk of major birth defects according to EUROCAT classification in pregnant women, which had had a first-trimester exposure to dolutegravir, raltegravir, or elvitegravir., Results: We found a major birth defect rate of 1.9% in the general population between 2012 and 2016. As InSTI drugs are not used as first-line therapy in pregnant women, we found a very low exposure in this population. Among 49, 240, and 70 pregnancy outcomes exposed to dolutegravir, raltegravir, and elvitegravir, respectively, during the first trimester, there were 2, 3, and 1 major birth defects, respectively. There was no case of neural tube defect., Conclusions: Drug exposure to InSTI is limited in our nation-wide database. Nevertheless, our data do not support a pharmacovigilance signal on neural tube defects in women exposed to dolutegravir, raltegravir or elvitegravir during pregnancy. Owing to a small number of pregnancy outcomes, these results need to be confirmed with further studies.

Objective: Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors. Method: Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case‐control design. Results: Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio [OR] 1.7, 95% confidence interval [95% CI] 1.3–2.2) and PTB (OR 1.8, 95% CI 1.4–2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB. Conclusion: About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability. [ABSTRACT FROM AUTHOR]

• About 40% of women with systemic vasculitis were treated by immunosuppressive drugs during pregnancy. • The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy. • Proportion of systemic vasculitis flare did not increase significantly during pregnancy. Systemic vasculitis (SV) rarely affects women of childbearing age and only small series have been reported to date in pregnant patients. The discovery of an unplanned pregnancy can be an urgent cause for modifying treatments. This study aimed to describe immunosuppressive drugs use before, during and after pregnancy in women with SV. We conducted a cohort study using the French nationwide claims database. We included all women with SV being pregnant between 2013 and 2018. Exposure of interest was defined as exposure to oral systemic or injectable immunosuppressive drug identified using out-hospital reimbursement data and in-hospital reimbursement for expensive drugs. Of 3,246,454 pregnancies, 649 pregnancies were observed in 606 women with SV. Immunosuppressant and glucocorticoids use decreased before pregnancy and then increased after pregnancy (48.4%, 40.7%, 50.4%, respectively before, during, after). Prevalence of glucocorticoids use was broadly stable during pregnancy from 27.9% to 27.6% and 23.7% in the 1st, 2nd and 3rd trimesters, respectively, with a daily dose of about 5 mg. The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy and then increased after delivery, whereas proportion of systemic vasculitis flare, estimated from the glucocorticoids daily dose, did not increase significantly during pregnancy. Immunosuppressants and glucocorticoids use decreased before pregnancy and remained stable throughout, suggesting a vasculitis control during this period. Our findings support the importance of pre-conceptional consultations to review medications, and switch not-recommended and teratogenic medications to drugs considered being safe during pregnancy. [ABSTRACT FROM AUTHOR]