Weight Gain in Pregnancy Linked to Overweight in Kids

Pregnant women who gain excessive or even appropriate weight, according to current guidelines, are about four times more likely than women who gain inadequate weight to have a baby who becomes overweight in early childhood. The findings, from the Department of Ambulatory Care and Prevention at HMS and Harvard Pilgrim Health Care, appear in the April issue of the American Journal of Obstetrics and Gynecology.

Courtesy Emily Oken

For women who gained adequate or excessive weight during pregnancy according to Institute of Medicine (IOM) recommendations, the odds of having a child who was overweight at age 3 years were, respectively, 3.77 times and 4.35 times greater than for women who gained inadequate weight according to the IOM.

“Maternal weight gain during pregnancy is an important determinant of birth outcomes,” said lead author Emily Oken, an HMS instructor in the department. “These findings suggest that pregnancy weight gain can influence child health even after birth and may cause the obstetric community to rethink current guidelines.”

Oken and colleagues examined data from 1,044 mother–child pairs in Project Viva, a prospective study of pregnant women and their children based at the department’s Obesity Prevention Program. The authors studied whether pregnancy weight gain within or above the recommended range increased the risk of a child being overweight at age 3.

In 1990, the Institute of Medicine (IOM) published guidelines for gestational weight gain (Nutrition During Pregnancy) that were motivated by evidence that low weight gain in pregnant women may cause low birth weight. The guidelines call for smaller gains in mothers with a higher body mass index (BMI) and generally permit greater gains than previous recommendations.
The IOM report remains the standard for clinical recommendations regarding gestational weight gain. Yet some have questioned whether evidence is sufficient that greater gains promote better birth outcomes in modern developed nations.

In this study, 51 percent of women gained excessive weight; 35 percent gained adequate weight; and 14 percent gained inadequate weight, according to the IOM framework. Women with adequate or excessive gain were approximately four times more likely than those with inadequate gain to have an overweight 3-year-old. The authors defined overweight as a BMI greater than the 95th percentile for the child’s age and sex.

Gestational weight gain may be linked to child overweight through several pathways. Mothers who gain weight readily because of genetic or dietary and other behavioral factors may have children who are more likely to gain weight. In addition, the amount of weight gained during pregnancy might alter the intrauterine environment, not only influencing fetal growth, but possibly resulting in persistent programming of child weight.

“It has been 17 years since the IOM came out with its last set of recommendations, before the obesity epidemic hit with full force,” said Matthew Gillman, HMS associate professor of ambulatory care and prevention and senior author of the study. “Now, women are coming into pregnancy at higher weights and likely gaining excessively more than they used to. We need to find out how to counter this trend—but not go too far back in the other direction when women were gaining too little weight.”

—Leah Gourley

Broad Patterns Found in MicroRNA Control of Gene Expression

A meta-analysis of microarray datasets has identified a new characteristic of genome regulation. The analysis revealed that microRNAs—derived from genes that do not code for proteins—regulate their chromosomal neighbors. The finding, reported in the March 20 Proceedings of the National Academy of Sciences, adds to the growing evidence that genes located close to each other on the chromosome can be turned on and off together.

Until recently, there was no particular reason to believe that genes in proximity along a chromosome interact with each other. But in the last five years, Isaac Kohane, the Lawrence J. Henderson associate professor of pediatrics and health sciences and technology, and others have discovered that genes near each other often get turned on together. This relationship has been noticed in yeast, worms, and humans.

Kohane and his research team wondered how these genes could be interacting to alter each other’s expression. The researchers turned to microRNAs, which have been shown to increase or degrade a protein without actually coding for protein. MicroRNAs are important during development, and their dysregulation is related to disease phenotypes like cancer. “We wondered whether microRNA could be the cause of a concerted action of genes near each other,” said Kohane, who is also director of the Countway Library of Medicine.

The researchers examined dozens of microarray datasets from mouse tissues looking for patterns of expression near genetic regions encoding microRNA. “On average, we found a massive dip of expression around microRNA,” Kohane said. The suppression of gene expression around microRNA was found in a variety of tissues—including kidney, brain, liver, lung, and heart—suggesting that microRNA’s control is genomewide. Transcription factors were the most commonly suppressed genes, implying that the inhibitory effect of
microRNA is indirect.

The analysis also revealed that the amount of microRNA suppression differed according to age. In immature tissue, the dip surrounding microRNA was about 100,000 bases long. The dip extended to 1 million bases in mature tissue.

Genes related to chromatin remodeling, a process that goes awry in disease states such as cancer, were particularly well targeted for silencing by microRNA. “The control of inactivation near microRNAs may cause a predisposition to cancer if disturbed,” Kohane said.

—Molly McElroy

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