Groundbreaking study to assess safety of drugs passed through breastmilk

The Pediatric Trials Network (PTN) is undertaking a groundbreaking study to assess the safety of commonly used off-patent medications when they are given to breastfeeding mothers. The study will track how different drugs are passed through breastmilk to determine dosing levels that are safe for both mom and baby.

Although the U.S. Food and Drug Administration (FDA) has implemented a guidance document on conducting lactation studies, off-patent drugs are not included in that rule. The PTN seeks to fill this knowledge gap.

Dr. Kevin Watt

“Although the benefits of breastfeeding are well-documented, we still don’t know enough about the effects of many prescription and over-the-counter off-patent drugs when they are passed to infants through their mother’s breastmilk,” said Dr. Kevin Watt, an assistant professor of pediatrics at Duke University who is leading the study. “As a rule, we discourage unnecessary drug use during lactation, but it’s quite common for new mothers to have symptoms or medical conditions that must be treated with drugs.”

“Many breastfeeding moms struggle with the decision to take medications because of the fear that these drugs will harm their children,” Watt said. “In the end, it often comes down to either stopping breastfeeding or discontinuing needed medications. We want to take the guesswork out of this decision and allow moms to breastfeed without worry.”

The study is expected to begin in April of 2018 and will enroll approximately 50 lactating women, along with their breastfed infants, for each drug studied. Initially 10 off-patent drugs will be studied, including medications used to treat bacterial infections, depression and anxiety, high blood pressure, diabetes, and chronic pain. Mothers will be enrolled in the study only if they are already taking one of the study drugs as part of their routine care.

Mothers who participate in the study will provide samples of breastmilk, their blood, their infants’ blood, or a combination to help researchers measure drug levels and determine the safest dose. Mothers and infants are expected to remain in the study until the infants reach 180 days of age.

The study, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), will also explore the effects of maternal obesity on drug exposure and long-term outcomes of breastfed infants exposed to drugs in breastmilk.

See the NIH LactMed database for more information on the levels of various substances in breastmilk and infant blood, and possible adverse effects.

Dr. Shakhnovich offers guidelines for prescribing GERD medications to obese kids


Dr. Valentina Shakhnovich, Children’s Mercy

When treating gastroesophageal reflux disease (GERD) in obese kids, the common practice of dosing stomach acid blockers based on children’s weight could actually cause more harm than good, said Dr. Valentina Shakhnovich, investigator for the Pediatric Trials Network (PTN) and Associate Program Director for the Gastroenterology Fellowship Research Program at Children’s Mercy Hospitals in Kansas City, Missouri. Shakhnovich shared her research on The Children’s Mercy’s Transformational Pediatrics podcast.

Listen to the podcast here.

GERD, commonly called acid reflux, is a long-term condition in which stomach acid comes back up into the esophagus, causing heartburn, indigestion, and tissue damage. Because the occurrence of GERD is associated with excess weight gain, pediatricians are seeing more cases, as the number of overweight and obese children increases.

Pantoprazole belongs to a class of drugs known as proton-pump inhibitors (PPIs), which have long been used to treat GERD and other conditions related to excess stomach acid. Pediatricians typically dose pantoprazole based on a child’s weight. However, this common practice can actually put bigger kids at risk for unwanted long-term side effects, associated with higher doses of PPIs, such as low bone density and vitamin deficiencies.

“A lot of us have the knee-jerk reaction that if we see a 10-year-old who’s twice the size of an average 10-year-old, maybe we should double the dose,” Dr. Shakhnovich said. “What our research has shown is that’s actually not the best thing to do for obese kids, and it appears that they actually require a lower dose of proton-pump inhibitors than their non-obese counterparts.”

Dr. Shakhnovich suggested including a statement on the pantoprazole label, warning pediatricians not to give more of the drug to overweight and obese children. “Until clear dosing guidelines come from the FDA, think twice before dose escalating just because a child is obese,” she said.

She commended PTN for its awareness of the problem and for leading the way in finding the safest and most effective dose of commonly used medications for overweight and obese children.

“One in 6 children is obese. One in 3 is overweight,” Dr. Shakhnovich said. “It’s essential to start including obese patients in clinical trials so we’re not trying to guess at the correct dose and we’re not trying to play catch-up.”

PTN study contributes to successful treatment of MRSA abscess in preterm infant

Early this summer, Lucas,* a one-month-old infant born 9 weeks prematurely, was receiving routine respiratory support in the neonatal intensive care unit at the University of North Carolina Children’s Hospital when he suddenly developed a dangerous neck abscess. Upon testing, the infection was found to be caused by methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Staphylococcus infections in general can be life-threatening in the NICU, but because MRSA is resistant to many commonly used antibiotic therapies, Lucas’ treatment options were limited from the outset.

Dr. Jackie Patterson
Dr. Jackie Patterson, UNC Children’s Hospital

Neonatologist Jackie Patterson, who was caring for Lucas in the NICU, immediately turned to the medical literature to determine the best course of treatment. During her search, she found an article published in the May 2016 issue of Antimicrobial Agents and Chemotherapy that was directly relevant to Lucas’ case. The article reported results from a trial sponsored by the Pediatric Trials Network (PTN) that explored dosing for antibiotics including clindamycin in infants being treated for staph infections.

Clindamycin was originally approved by the FDA in 1997 and is used to treat bacterial infections when other antibiotics, including penicillin and methicillin, are ineffective. The PTN “Anti-Staph Trio” study, a multicenter trial that evaluated 3 different antibiotic therapies for staph infections, was designed to identify drug dosages appropriate for use in term and pre-term infants—information that was not available in existing product labeling.

By combining their findings with pharmacokinetic and safety data from two other studies, the authors were able to describe a dosing regimen for clindamycin in premature infants based on postmenstrual age and total body weight that would allow physicians to effectively treat the infection while avoiding unwanted side effects.

Dr. Patterson knew, based on lab results, that Lucas’ particular strain of MRSA was sensitive to clindamycin. Thanks to the data published in the PTN study, she was able to choose a dosing strategy that would be most effective for Lucas.

“After only a couple of days, we saw a dramatic improvement with no adverse effects,” she said. Lucas recovered completely by the end of the week-long treatment, and was discharged healthy later in the summer.

Although Lucas’s parents had initial concerns about the treatment, they were reassured when Dr. Patterson referenced the study.

“We were confident about our treatment because of the literature,” she said. “This made the family confident in us.”

However, Dr. Patterson noted that this is not always the case, pointing out that information to guide dosing for infants and premature neonates is often sorely lacking.

“In pediatrics, we’re often extrapolating from adult data,” Dr. Patterson said. “In part because families are reluctant to enroll their children in clinical trials, it’s hard to find data specifically related to infants and children.”

Bridging this gap is a key goal for the PTN, an alliance of more than 100 clinical research sites cooperating in the design and conduct of pediatric clinical trials. Sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the PTN works to improve healthcare for the youngest patients by providing much-needed information on optimal dosing of commonly used drugs.

“The work that PTN is doing is critical,” Dr. Patterson said. “Especially when working with life-threatening conditions in the newborn population, the more science behind our medical practices, the more confident we can be that we will deliver the best outcomes for our patients and their families.”

*Name has been changed to protect confidentiality.