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Using maternal triglyceride levels as a marker for pregnancy risk

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It is widely known and taught that maternal blood lipid levels increase slightly during pregnancy. Lipid values throughout pregnancy, however, have not been well described, making it difficult to ascertain which changes are normal and which changes may be potentially troubling for the mother and/or the baby.

Similarly, the association between pregnancy outcomes and lipid levels prior to conception and during pregnancy has been studied only minimally. In both areas, more research is needed.

Dr. Arnon Wiznitzer

Yet despite the need for more research, it now appears that the mother’s lipid profile – particularly her triglyceride levels before and during pregnancy – warrants our attention. Results from several clinical studies suggest that elevated maternal triglyceride (TG) levels may be associated with gestational diabetes mellitus (GDM) and preeclampsia. Since these conditions can contribute to the development of peri- and postpartum complications and increase the mother’s risk of developing subsequent type 2 diabetes and systemic hypertension, a mother’s lipid profile – just like her glucose levels – may help us define who is at high risk of pregnancy complications and later adverse effects.

Research findings

In addition to assessing fetal health during pregnancy, ob.gyns. routinely measure and monitor maternal blood pressure, weight gain, and blood sugar, which fluctuate during normal pregnancies.

We have found that lipid levels, notably maternal TG, total cholesterol, and the major particles of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) also vary during pregnancy, with a nadir during the first trimester, followed by a gradual increase and a peaking before delivery.

It is well known that severely elevated blood pressure, gestational weight, or glucose can signify a pregnancy at risk for adverse outcomes. However, our research has shown that high levels of TGs, but not the levels of HDLs, LDLs, or total cholesterol, during pregnancy also are associated with an increased risk for preeclampsia and gestational diabetes mellitus (Am. J. Obstet. Gynecol. 2009;201:482.e1-8).

In our study, the rate of preeclampsia or GDM increased with maternal TG level, from 7.2% in women who had the lowest levels (<25^th percentile) to 19.8% in women who had the highest levels (>75^th percentile).

We found that TG levels in the upper quartile also were associated with a significantly higher risk of preeclampsia, compared with the lower quartile (relative risk, 1.87).

Similarly, among women without diagnosed GDM, those with TG levels in the upper quartile were more likely to have a fasting glucose level of 100 mg/dL or more, compared with the intermediate group (TG level between the 25^th and 75^th percentiles) and the lower quartile. Women with the highest TG levels also were more likely to have infants classified as large for gestational age.

Our findings are consistent with a review that showed a positive association between elevated maternal TG and the risk of preeclampsia (BJOG 2006;113:379-86), as well as a cohort study that found plasma TG levels in the first trimester were independently and linearly associated with pregnancy-induced hypertension, preeclampsia, and large-for-gestational age (J. Clin. Endocrinol. Metab. 2012;97:3917-25).

Interestingly, the cohort study did not show an association between elevated maternal TG levels, adverse pregnancy outcomes, and body mass index. This suggests that weight gain and TG may be independent risk factors.

In practice

At this point in time, without defined cut-off values and well-tested interventions, there is no recommendation regarding maternal lipid measurement during pregnancy. We have shown, however, that maternal TG levels above 140 mg/dL at 3 months’ gestation and TG levels of 200 mg/dL or more at 6 months’ gestation are very high and may indicate a high-risk pregnancy.

Like all ob.gyns., we advise women before pregnancy to lose weight and to normalize blood glucose levels before attempting to conceive to reduce pregnancy complications, but we also encourage our patients to lower their TG levels. Given the observed associations between higher TG levels and adverse pregnancy outcomes, we now routinely measure maternal lipids as well as blood glucose in our pregnant patients. We also test lipid levels in pregnant women who have other risk factors such as GDM in a prior pregnancy or chronic high blood pressure.

It is possible that lifestyle programs (such as those involving diet, weight reduction, and physical activity) prior to and during pregnancy, with a focus not only on maintaining a healthy weight but also on lowering TG levels, may help to further prevent complications during pregnancy and adverse birth outcomes. Although more research is needed, lowering TGs with cholesterol-reducing drugs also may help improve pregnancy outcomes. Indeed, there is currently a study investigating the pharmacologic treatment of high lipids during pregnancy.

For now, we should advise our patients who have higher TG levels in pregnancy to improve their diets and levels of physical activity. We also should monitor these patients for the increased likelihood of developing GDM and preeclampsia because higher lipid profiles appear to equate to a higher risk of adverse outcomes.

Finally, our attention to lipid profiles should extend beyond birth, since the long-term risk of cardiovascular disease may be influenced by preeclampsia and potentially by the lipid changes that escalate with the condition.

Dr. Wiznitzer reported having no financial disclosures related to this Master Class.

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Obstetrics

Lipid Disorders

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pregnancy, lipid levels, cholesterol

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Master Class

Author(s)

Arnon Wiznitzer, MD