Study Highlights

• The retrospective cohort for this study using the Taiwan National Health Insurance Research Database included 1,443,657 pregnant women aged at least 18 years with their first infant born between January 1, 2004, and December 31, 2014.
• The statin-exposed group comprised 469 women diagnosed with hyperlipidemia before pregnancy and receiving prescription statins during pregnancy (mean age, 32.6±5.4 years; mean gestational age, 38.4±1.6 weeks).
• These were matched by age to 4690 controls (mean age, 32.0±4.9 years; mean gestational age, 37.3±2.4 weeks) with no statin exposure during pregnancy.
• Women who used statins had a higher prevalence of comorbid conditions.
• RRs were calculated in multivariable analyses, using Poisson regression models to adjust for potential confounders, including maternal comorbidities and age.
• The statin-exposed group had greater risk for low birth weight (LBW) among offspring (RR, 1.51; 95% CI, 1.05-2.16), of preterm birth (RR, 1.99; 1.46-2.71), and of lower 1-minute Apgar score (<7; RR, 1.83; 95% CI, 1.04-3.20), but not of 5-minute Apgar score.
• Congenital anomalies were not associated with statin exposure during pregnancy.
• Despite the association with LBW, statin exposure was not associated with small-for-gestational age status, after adjustment for maternal age and comorbid hypertension and diabetes.
• Multivariable analysis showed no association between statin use for periconceptual hyperlipidemia and adverse perinatal outcomes among women who had used statins before pregnancy.
• There were no increases in adverse perinatal outcomes, including congenital anomalies, LBW, preterm birth (PTB), very LBW, low Apgar scores, and fetal distress, among offspring of women who received statins before conception for more than 3 months and with continuous use of statins after conception compared with women who stopped statin use after conception.
• The investigators concluded that statins may be safe when used during pregnancy because there was no association with congenital anomalies, but caution is needed because of increased risk for LBW and preterm labor.
• The findings also suggest that women with long-term use of statins before pregnancy could safely use statins during pregnancy.
• Further research is needed to confirm or disprove these findings.
• Statins have been contraindicated during pregnancy because of possible teratogenicity, which may result from interruption of cholesterol synthesis.
• Cholesterol and its derivatives are essential components for fetal development and are involved in synthesis of steroids and cell membranes.
• Cholesterol synthesis is essential for central and peripheral nervous system development.
• Few studies have examined the link between maternal cholesterol reduction and neonatal outcomes, despite concerns regarding teratogenicity arising from animal models.
• The present finding that statin exposure during pregnancy is not associated with congenital anomalies is inconsistent with previous animal studies and human reports that showed central nervous system and limb anomalies in offspring of mothers with statin exposure during pregnancy, but the finding is similar to those of other recent studies.
• The lower 1-minute Apgar score may suggest that infants of mothers exposed to statins during pregnancy may more frequently require resuscitation after birth.
• Lipophilic statins were associated with more adverse outcomes including LBW, which may reflect the lower likelihood that hydrophilic statins enter the embryo during pregnancy, affect cholesterol biosynthesis, and adversely affect the developing infant.
• Although no studies have examined long-term cardiovascular outcomes of treatment cessation among women taking statins who discontinue use before or during pregnancy, strong evidence indicates that discontinuing statins increases incidences of cardiovascular and cerebrovascular events.
• As studies have also shown that children born to mothers with a higher blood cholesterol level during pregnancy are more likely to have advanced aortic atherosclerotic plaques, the necessity of statins for treatment of dyslipidemia during pregnancy should be evaluated.
• The researchers suggest that statins may be used during pregnancy with no increase in rate of congenital anomalies.
• For pregnant women at low risk, statins should be used carefully after assessing risks for LBW and PTB.
• For women with dyslipidemia or high-risk cardiovascular disease, and for those using statins before conception, statins may be continuously used without increased risks of neonatal adverse effects.
• Study limitations include cohort study design rather than randomized clinical trial; lack of data on maternal conditions including smoking status, body mass index, and previous birth histories; relatively small subgroup with preconception statin exposure; and lack of data on miscarriage or intrauterine fetal death.