Maternal Cholesterol Tied to Both Small and Large for Gestational Age Term Births

(Reuters Health) – Maternal total cholesterol levels at mid-pregnancy may be associated with offspring born at term that are small for gestational age (SGA) and large for gestational age (LGA), a Japanese cohort study suggests.

Researchers examined data on 37,449 women without diabetes or hypertension who had full-term singleton births. Overall, 2,638 (7.0%) infants were small for gestational age, defined as less than the 10th percentile, and 3,709 (9.9%) were large for gestational age, defined as at least the 90th percentile.

Each one standard deviation decrement in maternal total cholesterol was linearly associated with SGA offspring (odds ratio 1.20).

By contrast, each one standard deviation increment in maternal total cholesterol was linearly associated with LGA offspring (OR 1.13).

“Monitoring maternal total cholesterol levels in mid-pregnancy would be worthy to find a high-risk pregnancy for SGA and LGA,” said lead study authors Kayo Kaneko and Yuki Ito of the Department of Occupational and Environmental Health at the Nagoya City University Graduate School of Medical Sciences in Japan.

In the study, the mean gestational age when women had total-cholesterol blood tests was 22.7 weeks.

Maternal total cholesterol levels influenced the risk of SGA and LGA offspring independent of several potential confounders assessed in the study, including pre-pregnancy BMI and weight gain during pregnancy, the study team reports in the Journal of Clinical Endocrinology & Metabolism.

“Generally, we consider major risk factors of SGA are lower pre-pregnancy BMI and/or gestational weight gain, and risk of LGA is increased by gestational diabetes and higher blood glucose levels,” Kaneko and Ito said by email.

“But our study had shown if maternal total cholesterol levels are decreased or increased, such status could be an early sign of the risk of SGA or LGA, even with normal pre-pregnancy BMI, gestational weight gain, and blood glucose levels,” Kaneko and Ito said.

Low cholesterol during pregnancy might indicate deficiencies of micronutrients that are needed for normal fetal development, the study authors note. By contrast, consumption of a high-fat diet during pregnancy has been associated with negative health outcomes including abnormal adipose tissue development, the authors write.

One limitation of the study, the authors point out, is that they lacked data on sex hormone levels that might influence infants’ size at birth.

The researchers also didn’t have data on triglyceride and lipid profiles, including levels of low- and high-density lipoprotein cholesterol and fatty acids.

However, previous research has established that maternal hypercholesterolemia and other dysmetabolic conditions can contribute to an elevated risk of cardiovascular diseases, hypertension, and type 2 diabetes, and other conditions programmed during fetal development, said Dr. Wulf Palinski of the University of California, San Diego.

“In general, attempts to correct for pathogenic consequences of SGA or LGA after birth have failed to yield benefits,” Dr. Palinski, who wasn’t involved in the study, said by email.

“The more promising clinical approach is certainly that of treating the underlying dysmetabolic condition in mothers,” Dr. Palinski said. “We have been calling for routine measurements of maternal cholesterol during pregnancy for a long time, but it is still not accepted as a risk factor and not paid for by U.S. insurance companies.”

SOURCE: Journal of Clinical Endocrinology & Metabolism, online August 20, 2021.

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