Background: Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy.

Case: A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging.

Conclusions: A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Exposure to alirocumab during the first trimester of pregnancy: A case report	Birth defects research			2021	277	179

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Vuignier, Yann