Low Maternal Total Cholesterol Linked to Preterm Delivery

Laurie Barclay, MD

October 01, 2007

October 1, 2007 — Mothers with low cholesterol (<10th population percentile) are more likely to deliver preterm and to have low-birth-weight babies, according to the results of a study reported in the October issue of Pediatrics.

"Based on our initial findings, it appears that too little cholesterol may be as bad as too much cholesterol during pregnancy, but it is too early to extrapolate these results to the general population," senior author Max Muenke, MD, from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health in Bethesda, Maryland, and colleagues. "More research is needed to replicate this outcome and to extend it to other groups. For now, the best advice for pregnant women is to follow the guidance of their health care providers when it comes to diet and exercise."

The investigators retrospectively evaluated mother–infant pairs from a cohort of 9938 women referred to South Carolina prenatal clinics for routine second-trimester serum screening. Low total cholesterol was defined as lower than the 10th percentile of assayed values in banked sera (159 mg/dL at mean gestational age of 17.6 weeks).

"The right amount of cholesterol is fundamental for good health, both before and after birth," Dr. Muenke said. "During pregnancy, cholesterol is critical for both the placenta and the developing baby, including the brain."

Inclusion criteria were age 21 to 34 years, nonsmoking, and without diabetes in the women, with a liveborn neonate after a singleton gestation. Before risk group assignment, total cholesterol (TC) values of eligible mothers were adjusted for gestational age at screening.

Of 1058 women studied, 118 women had low total cholesterol and 940 women had higher total cholesterol. Multivariate regression models compared rates of preterm delivery, fetal growth parameters, and congenital anomalies between women with low total cholesterol and those with mid–total cholesterol values (<10th percentile but >90th percentile).

In mothers with low total cholesterol, prevalence of preterm delivery was 12.7% vs 5.0% in mothers with mid–total cholesterol. Low maternal serum cholesterol was associated with preterm birth only among white mothers. On average, term infants of mothers with low total cholesterol weighed 150 g less than did those born to control mothers. Although low maternal serum cholesterol was not associated with risk for congenital anomalies, there was a statistically insignificant trend of increased risk for microcephaly among neonates of mothers with low total cholesterol.

As in earlier studies, very high cholesterol levels (>261 mg/dL) were a major risk factor for premature delivery, with prevalence about 12% in both white and black women.

"This study sheds important light on the intricate biological mechanisms at work during human gestation," said NHGRI Scientific Director Eric Green, MD, PhD. "In light of these findings, researchers have a renewed impetus to establish the genetic and environmental causes of low cholesterol levels because of its relevance to pregnancy."

Study limitations include an inability to generalize specific numeric thresholds for low and high TC to other populations with different profiles of gestational risk; incomplete ascertainment of potential study subjects; that the group with low maternal serum cholesterol differed from the control group in baseline characteristics, including lack of access to some sociodemographic variables known to correlate with birth outcome; and lack of generalizability to the general population.

The Division of Intramural Research, NHGRI, supported this study. The authors report no relevant financial relationships.

In an accompanying commentary, Mario Merialdi, MD, from the World Health Organization in Geneva, Switzerland, and Jeffrey C. Murray, MD, from the University of Iowa Carver College of Medicine in Iowa City, note that these findings will need to be replicated, but they may apply to a range of socioeconomic strata and have wide application.

"It is likely that the effect of low cholesterol on preterm birth could be even larger among populations with inadequate nutritional status," Dr. Merialdi and Dr. Murray write. "From this perspective, the results of the study suggest that relatively simple, affordable and culturally acceptable nutritional interventions could contribute substantially to reduce the risk of preterm birth among those populations most in need of effective preventive strategies. The results also provide insights into the pathophysiology of parturition and suggests pathways to investigate for genetic contributors to preterm labor, as well."

Dr. Murray is supported by grants from the National Institute of Child Health and Human Development and the March of Dimes.

Pediatrics. 2007;120:723–733 .

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