Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia

Karianne Svendsen; Jacob Juel Christensen; Jannicke Igland; Henriette Walaas Krogh; Liv J Mundal; David R Jacobs Jr; Martin P Bogsrud; Kirsten B Holven; Kjetil Retterstøl

doi:10.1016/j.atherosclerosis.2025.120442

Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia

Atherosclerosis. 2025 Sep:408:120442. doi: 10.1016/j.atherosclerosis.2025.120442. Epub 2025 Jul 10.

Authors

Karianne Svendsen¹, Jacob Juel Christensen², Jannicke Igland³, Henriette Walaas Krogh⁴, Liv J Mundal⁵, David R Jacobs Jr⁶, Martin P Bogsrud⁷, Kirsten B Holven⁸, Kjetil Retterstøl⁹

Affiliations

¹ Lipid Clinic, Oslo University Hospital, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: karianne.svendsen@fhi.no.
² Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: j.j.christensen@medisin.uio.no.
³ Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Health and Caring Sciences, Centre for Evidence-Based Practice, Western Norway University of Applied Sciences, Bergen, Norway. Electronic address: Jannicke.Igland@uib.no.
⁴ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Non-Communicable Diseases, Division of Prevention and Public Health, Norwegian Directorate of Health, Oslo, Norway. Electronic address: henriette.walaas.krogh@helsedir.no.
⁵ Lipid Clinic, Oslo University Hospital, Oslo, Norway. Electronic address: liven2026@gmail.com.
⁶ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: jacob004@umn.edu.
⁷ Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway. Electronic address: martin.proven.bogsrud@helsedir.no.
⁸ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Norwegian National Network on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway. Electronic address: k.b.holven@medisin.uio.no.
⁹ Lipid Clinic, Oslo University Hospital, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: kjetil.retterstol@medisin.uio.no.

PMID: 40669098
DOI: 10.1016/j.atherosclerosis.2025.120442

Abstract

Background and aims: Sparse data exist on the risk of adverse pregnancy outcomes in women with familial hypercholesterolemia (FH). We investigated associations between FH and adverse pregnancy outcomes, and between statin exposure in pregnancy and adverse pregnancy outcomes among women with FH.

Methods: We studied 3869 pregnancies among 1869 women with genetically-proven FH and 68225 pregnancies among 33661 women from the general population. Data on adverse pregnancy outcomes were obtained during 1967-2018 from the Medical Birth Registry of Norway. Data on pharmacy-dispensed statins were obtained from the Norwegian prescription database (2004-2018) in 1051 women with FH. Associations were presented as odds ratio (OR) with 95 % CI from logistic regression adjusted for mother's age, parity, and offspring's birth year.

Results: Women with FH had a higher risk of preeclampsia (OR 1.21 [1.00-1.46]), but lower risk for gestational diabetes (OR 0.58 [0.36-0.92]) and intrapartum hemorrhage during delivery (OR 0.81 [0.71-0.92]) compared to controls. No excess risk of adverse pregnancy outcomes in offspring was observed for FH. Among women with FH, statin exposure (mainly in the first trimester) may be associated with higher risk of low birth weight in offspring born at term (OR 2.42 [0.51, 11.45]).

Conclusions: Women with FH had lower risk of gestational diabetes and intrapartum hemorrhage, but a higher risk of preeclampsia compared to controls. No adverse birth outcomes were observed for offspring of mothers with FH, but the association between statin exposure in pregnant women with FH and low birth weight in offspring warrants further study.

Keywords: Adverse pregnancy outcomes; Diabetes; Familial hypercholesterolemia; Gestation; Hemorrhage; Low birthweight; Malformations; Preeclampsia; Premature births; Statins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Diabetes, Gestational / epidemiology
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Hyperlipoproteinemia Type II* / diagnosis
Hyperlipoproteinemia Type II* / drug therapy
Hyperlipoproteinemia Type II* / epidemiology
Infant, Newborn
Norway / epidemiology
Pre-Eclampsia / epidemiology
Pregnancy
Pregnancy Complications* / epidemiology
Pregnancy Outcome*
Registries
Risk Assessment
Risk Factors
Young Adult

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors