The Birth-Weight Factor

Small babies may face lifelong problems metabolizing meds

Among the questions you may be asked someday by doctors who prescribe your medications is one that few people can probably answer: What was your birth weight?

To help doctors and pharmacists optimize dosages and personalize dosing regimens for their patients, researcher Ganesh Cherala is investigating the impact of birth weight on drug metabolism. (Photo: Dennis Wolverton)

To help doctors and pharmacists optimize dosages and personalize dosing regimens for their patients, researcher Ganesh Cherala is investigating the impact of birth weight on drug metabolism. (Photo: Dennis Wolverton)

Research by Ganesh Cherala of the Oregon State University College of Pharmacy suggests that when physicians prescribe drugs ranging from Tylenol to cancer chemotherapies, they may need to factor birth weight along with body weight into dosing decisions for their patients.

In tests with laboratory rats, Cherala found that the kidneys of underweight animals born to mothers that were fed low-protein diets during pregnancy and nursing had significantly less ability to process and transport drugs than animals whose mothers had adequate protein. His results suggest that low birth weight may hinder the body’s ability to process therapeutic drugs, thereby jeopardizing their effectiveness.

The culprit appears to be a protein called a “drug transporter,” says Cherala, an assistant professor who has a joint appointment with Oregon Health & Science University.

“These transporters, which sit on the cell membrane, grab the drug molecules from the blood and put them into the cell,” Cherala explains from his laboratory overlooking Portland’s waterfront. “Then a second set of transporters grab the drug from the cell and dump it into the urine.”

In the low birth-weight animals, the transporters Cherala looked at — OAT 1 (Organic Anion Transporter) and Pgp (P Glycoprotein) — were anywhere from two to 50 times less prevalent than in the normal birth-weight animals, depending on age and transporter type. The gap showed up across genders, although females showed a greater deficit over time.

Fewer kidney transporters mean that less medication can be excreted out of the body, according to Cherala. The harmful results can range from toxic buildup of drugs in the blood to inadequate therapeutic benefits from the medication prescribed.

Compounding the Challenge

There are several ironies in this finding. First, scientists know that low birth weight increases risks for diabetes in humans, as well as for cardiovascular disease and metabolic syndrome (high levels of cholesterol, blood sugar and blood pressure). Thus, low birth-weight patients are more likely than normal birth-weight people to need medication during their lifetime. Yet these same subjects may be less able to process the drugs they need.

Second, researchers have found a link between low birth weight and adult obesity in humans. Because current weight is a major determiner of drug dosages (along with height, age and gender), obese patients typically get higher doses from their doctors than non-obese patients. But if a patient’s obesity stems from low birth weight, the higher dose may be more than his or her body can process.

“Let’s say I’m low birth weight, and because of that I become obese,” says Cherala. “If you dose me because of that higher body weight, you’re actually compounding the problem. You’re making the assumption that if you’re higher body weight, you have more transporters. Actually, it’s exactly the opposite.”

Health-care professionals have long known that underweight babies can face a lifetime of health problems. By factoring birth weight — and its impact on drug metabolism and transport — into health-care decisions, pharmacists and physicians may help mitigate some of these risks down the road.

“The main goal of our lab is to discover how we can use birth weight to optimize the dose and personalize the dosing regimen,” Cherala says.

 

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