Statins in Pregnancy Don’t Lead to Congenital Anomalies: Cohort Study

Statin use during pregnancy does not appear to lead to congenital anomalies, but it is linked to higher risks of low birth weight and preterm labor, according to a cohort study. Importantly, however, long-term statin use prior to pregnancy does not seem to cause fetal abnormalities.

After years of being contraindicated in pregnant women due to their potential teratogenicity, statins are not frequently used to control hyperlipidemia in these patients. Last year, however, the US Food and Drug Administration relaxed its warning on statin use during pregnancy based on new data, notably in those with familial hypercholesterolemia (FH) and with or at risk for preeclampsia.

“Our findings suggested that statins may be used during pregnancy with no increase in the rate of congenital anomalies,” write Jui-Chun Chang, MD (Taichung Veterans General Hospital, Taiwan), and colleagues. “For pregnant women at low risk, statins should be used carefully after assessing the risks of low birth weight and preterm birth. For women with dyslipidemia or high-risk cardiovascular disease, as well as those who use statins before conception, statins may be continuously used with no increased risks of neonatal adverse effects.”

Considering an overall increased awareness of cardiovascular disease as the leading cause of maternal morbidity and mortality in the US, Indu Poornima, MD (Allegheny Health Network, Pittsburgh, PA), told TCTMD this latest analysis is welcome. “This adds to the body of literature that is already out there in terms of confirming that congenital malformations are typically not caused by continuation of statins in early pregnancy,” she said. “Women should feel reassured as a result of this that if they do get pregnant while they are taking statins, especially women with homozygous FH, the option of continuing the statins should be discussed with their provider.”

The findings, moreover, should be reassuring to clinicians who may have previously thought they needed to discuss termination should a patient on statins become pregnant, Poornima continued, adding that “around the world, there is recognition that this is an issue that requires more guidance.”

Statins and Pregnancy

For the cohort study, published last week in JAMA Network Open, Chang and colleagues included more than 1.4 million pregnant women in Taiwan who gave birth to their first child between 2004 and 2014. They compared 469 women (mean age 32.6; mean gestational age 38.4 weeks) who used statins during their pregnancy with 4,690 age-matched controls who had no statin exposure during pregnancy.

After adjustment for maternal comorbidities and age, patients in the statin-exposed group more commonly reported low birth weight (RR 1.51; 95% CI 1.05-2.16), preterm birth (RR 1.99; 95% CI 1.46-2.71), and lower 1-minute Apgar score (RR 1.83; 95% CI 1.04-3.20). There was no increase in risk for congenital anomalies in the group who received statins.

In subgroup analyses, there was no link with adverse perinatal outcomes among women who used statins for periconceptual hyperlipidemia or for those who were on statins for long periods prior to pregnancy. Also, while both hydrophilic and lipophilic statins were associated with an increased risk of preterm birth, only the latter upped the risk for low birth weight.

At this point, there is not yet enough data to suggest that statins could be used routinely for women with or at risk for preeclampsia, Poornima said, although she would like to see more work in this space as the condition affects one in 10 pregnancies in the US. “It can have long-term cardiovascular implications in terms of higher risk of heart attack, strokes, etcetera,” she said. “So if we can figure out a way of preventing it, that obviously would be extremely impactful.”

But for women with FH, especially homozygous FH, as well as those who need to be on statins because of a prior MI, Poornima said there is enough evidence to support at least having a conversation with the medical team about staying on statins through the pregnancy. “I think it's reasonable to have a discussion with the patient, giving them the option to continue with the treatment with the recognition that the fetal abnormalities are not there,” she said, adding that these women are typically already at higher risk based on their medical histories alone, never mind the drugs they may be taking.

“The question is whether it's the underlying diabetes and [other comorbidities] that is causing the preterm labor versus being on the statins,” Poornima continued, adding that only a randomized trial could shed light on this question. While ethical issues may forestall the conduction of such studies, she would like to see more cohort studies replicate these results. “The good news is we don't see increased fetal losses and we do not see increased congenital anomalies, which are the two big concerns when it comes continuation of any medication during pregnancy,” Poornima said.