The baby girl weighed 5.1 pounds when she was born in a Philadelphia hospital in July 1967. A month later, she had dropped to 4 pounds, and doctors realized she was dying of starvation.
The newborn had a severe birth defect, small bowel atresia, that resulted in intestinal blockage. But even after surgery, she could not digest what the medical team was feeding her.
They decided to try a novel treatment. In research just the year before, six beagle puppies had received all their nutrients intravenously, completely bypassing the gastrointestinal tract. And they were healthy and thriving.
Doctors inserted a catheter into one of the baby girl’s major veins and cautiously infused a basic formula, adding a new nutrient every day. After 45 days, she had gained 3.5 pounds and grew 5.5 centimeters in length. Almost two years later, she was up to 18.5 pounds.
She was the first baby in the world to be fed intravenously. Nearly six decades later, total parenteral nutrition is a common and lifesaving method for premature or sick newborns. More commonly known as IV nutrition, it provides a mixture of electrolytes, fluid, minerals, protein, sugars and vitamins. Also included are intravenous lipids, which contain fatty acids.
“Traditionally and historically, in the United States and across the world, the type of IV fat is 100% soybean oil,” said Kara L. Calkins, MD. “So it’s like eating a Big Mac every day.”
Dr. Calkins is a neonatologist and professor of pediatrics at the David Geffen School of Medicine at UCLA. She researches nutritional interventions – specifically in the IV formula – to solve the problems she sees bedside in the neonatal intensive care unit. She believes nutritional science is neglected in medicine, compared with drugs and surgeries.
“Nutrition is a very cheap, easy and powerful tool that can alter someone's life course,” said Dr. Calkins. “Nutrition during pregnancy and early in life can set the stage for either potential disease or disorders, or perhaps prevent some of those diseases or disorders.”
Fatty acid levels
Most recently, she focused on retinopathy of prematurity (ROP), a mostly treatable disease that develops when blood vessels of the retina, in the back of the eye, grow abnormally. It is especially critical for the 1 in 10 babies in the U.S. who are prematurely born. ROP is the No. 1 cause of preventable blindness in children.
A premature baby misses out on the placental transfer of two fatty acids in the third trimester. Docosahexaenoic acid and Arachidonic acid are crucial building blocks for brain and eye development. The IV nutrition given in the NICU lacks both fatty acids. Though breast milk has some, it does not reach the levels in utero.
“We studied the fatty acid levels in preterm babies to show that when they're really low, they're more likely to get ROP,” said Dr. Calkins. “And the next question we have to ask is if we normalize those levels, will their eyes be better?”
Her collaborator, Alison Chu, MD, showed in animal models that introducing more omega-3 fatty acids protected against ROP. Dr. Calkins is now studying an IV fat emulsion that mimics the Mediterranean diet, with soybean oil, olive oil, coconut oil and fish oil.
“I think it may help,” she said. “But I don't think it's going to solve the problem entirely. I think we need to give babies an oral supplement in addition to IV fat with Docosahexaenoic acid and Arachidonic acid.”
Earlier in her career, Dr. Calkins examined aspects of fetal origins of adult disease (FOAD), which is especially applicable to the origins of obesity.
For example, people who are overweight or obese are prone to nonalcoholic fatty liver disease (NAFLD). An advanced form of NAFLD is one of the leading causes of liver failure.
Dr. Calkins studied the body compositions of cohorts of fetuses, infants, preteens and adolescents, and found that babies born to mothers with gestational diabetes have an increased risk for NAFLD.
“We think that early on during pregnancy there's metabolic programming that leads to increased fat in the fetal liver,” said Dr. Calkins. “Once you're born, depending upon the environment or your diet, it continues to progress and could lead to early-onset obesity, insulin resistance, high blood pressure and fatty liver disease.”
This led to her long-standing interest in researching lipid metabolism in the liver. In the NICU, she treated infants with intestinal failure-associated liver disease. Infants who have a diseased or non-functional gut – like the baby girl in Philadelphia – rely on prolonged IV nutrition. It can result in liver dysfunction and failure. Though rare, the disease has a high mortality and may require a liver transplant.
Replacing soybean oil with fish oil
Through different studies, Dr. Calkins dug into the constituents of the IV soybean oil. It contains omega-6 fatty acids, known to be inflammatory. She also found that the IV nutrition contained phytosterols which are hepatotoxic and can damage the liver.
Dr. Calkins hypothesized that omega-3 fatty acids – which are found in fish oil and are anti-inflammatory – would be a better fat in the IV nutrition.
With special permission from the U.S. Food and Drug Administration, Dr. Calkins replaced the soybean oil with fish oil for a few high-risk patients.
“It's like switching a big Mac with salmon,” she explained.
Over weeks and months, their liver disease reversed. When the study was expanded to 100 patients, about three-quarters were prevented from developing liver failure. In 2018, the FDA approved a fish oil lipid emulsion for pediatric patients to prevent liver disease associated with parenteral nutrition.
“Babies and children are very resilient,” said Dr. Calkins. “It’s remarkable. It's very rewarding to see children who've been ill become healthy and live to their fullest potential.”
