Demographer Anjani Chandra never asked anyone to send her infant formula after she became pregnant. But 10 to 15 packages filled with formula and bottles were sent to her Baltimore home anyway.
There's no escaping it. When an American woman is having a baby, she gets a fast introduction to formula.
More than 70 percent of American babies are fed with infant formula by the time they are 3 months old, federal surveys show, even though a vast array of health officials recommend breast-feeding during the first year of a baby's life if the mother is healthy. With just under 4 million newborns each year, the demand creates a $3 billion formula market in this country.
But what is this infant formula? How good is it? And how are scientists seeking to improve the quality of formula, to make it more like breast milk?
These questions have taken on a new urgency as the U.S. Food and Drug Administration (FDA) prepares revised regulations for infant formula -- the first official re-examination of formula since 1985.
The new regulations will determine which specific nutrients will be required in formula, and at what levels they will be allowed. An expert panel that studied the issue for the FDA has proposed adding three nutrients to the 29 currently required, and also has recommended that new maximum levels be set for 12 of them.
"So far as we know, the baby getting formula today will either get all the essential nutrients he needs or will be able to make them out of what he gets," said Samuel J. Fomon, professor emeritus at the University of Iowa Hospitals and Clinics, and a member of the expert panel convened by the Life Sciences Research Office (LSRO) under contract with the FDA. "It's not as good as breast milk, and can never be breast milk. But it can be a healthy alternative and is always being improved."
The regulations will also address the controversial question of whether companies should be allowed to supplement formula with docosahexaenoic acid (DHA) and related long-chained fatty acids, which a large number of scientists believe may somewhat improve the vision and brain functions of children. Proponents of these fatty acids say their introduction to formula would make it more like breast milk. But the expert panel recommended against including them in formula, setting off a loud and contentious dispute.
While decades of formula use have shown it to be safe and nourishing, there has long been heated debate over its component parts. Last fall, when the panel members recommended that maximum levels be set for most nutrients, they were largely concerned that formula makers might otherwise increase levels too high as they try to distinguish their products. But the International Formula Council, which represents some U.S. formula makers, has attacked the proposed maximum levels as unnecessary.
The expert panel has also called for an increase in fat content to be closer to mother's milk and a decrease in iron. It also recommended additions of the mineral selenium and the vitamin carnitine (both of which are found in breast milk), as well as alpha-linolenic acid, a fatty acid that was found in very low levels in most formula until the early 1990s when it was increased voluntarily.
While the panel often used human milk as its standard, it also made clear that it couldn't be the reference point for all its components. For example, some infants are allergic to milk. For them formula is based on carbohydrates from soybeans, even though it is absent from mother's milk.
The LSRO's Daniel J. Raiten, who oversaw the expert panel for the FDA, said the group struggled to find the proper relationship between breast milk and formula.
"There's a real difficulty in taking the existence of something in breast milk and assuming that if you make it synthetically, you can just put it back in," he said. "Because once you take that nutrient out of its natural milieu, serious questions are raised about putting it back in. You need a reasoned and very judicious approach."
The Standard of Breast Milk
Formula has come a long way since the first commercial batches were produced in 1867 in Germany. The ingredients then were cow's milk and wheat and malt flour, cooked with a little potassium bicarbonate to make it less acidic. By 1915, artificial milk was produced with fat content designed to simulate mother's milk. Later came vegetable oils for added fat and the division of milk into whey (its watery part) and and casein (the more solid, protein part) to be, again, more similiar to mother's milk.
Today, most formulas share a base of nonfat milk, vegetable oils and lactose, plus 29 required nutrients, including vitamins, iron, zinc, potassium and folic acid. In most instances, these additions have made formula more like breast milk. Increasingly, formula makers' efforts to mimic mother's milk is becoming an important marketing tool as well.
The makers of Similac, for instance, advertise their "improved" formula as "closer than ever to mother's milk" because they have added nucleotides to their mix. Nucleotides are compounds that are made by the body into nucleic acids, which are believed to help develop the infant's immune system. Taurine is another substance recently added to some formula, an amino acid found in high concentrations in the brains of newborns. These nutrients were proposed after being found to be plentiful in breast milk.
But there are important ways in which formula cannot imitate breast milk. Antibodies produced by the mother and present in breast milk give an enormous boost to an infant's immune system--helping to protect against infections, allergies and asthma--and researchers say formula can never provide the kind of specific immune response that breast milk does. And while researchers and formula makers feud over the merits of adding the fatty acid DHA, breast milk still has 160 other fatty acids not found in formula.
According to Fomon of the expert panel, there are also ways in which formula should not try to emulate breast milk. Mother's milk is low in iron, he said, and infants through the centuries made up for that deficit when they put iron-rich dirt in their mouths while they played. In today's more hygienic world, children can become iron-deficient unless they consume some iron-fortified foods. However, the new recommendations cut the amount of iron because children don't need as much as manufacturers have been adding.
Fomon described a similar dynamic with protein levels in breast milk. Because evolution has led new mothers to preserve protein for themselves, he said, most breast-fed babies get less protein after their first few weeks than nutritionists now consider optimal. Formula is considerably higher in protein, he said. And then there is the fat cholesterol, which is found in high concentrations in breast milk. But proposals to give formula more cholesterol, which has been associated with later heart disease, have not gone far.
While scientists are fast gaining insight into the composition of breast milk, regulators have been traditionally slow to make significant changes in formula. Some of that hesitancy stems from the results of a controversy in the late 1970s about how much salt should be in formula. During a period of vocal concern that salt levels were too high, a manufacturer produced some formula that was too low in salt. Scores of infants were harmed by the lack of chloride and initially suffered from a failure to thrive. This put them at risk of long-term developmental and cognitive problems that, so far, have not occurred.
That incident helped pass the Infant Formula Act of 1980, which gave the FDA greater authority in regulating formula. The current FDA review of nutrients flows from that legislation. Now that the FDA has recommendations from the panel, it will write and propose formal regulations.
In addition, with a rising number of American infants born premature, the FDA decided that it needed a second expert panel to examine their formula independently. The panel for pre-term formula is expected to report back by the end of the year.
The new FDA proposals are being written as the formula market gets its first generic infant formula, a product that distributors say will cut a third or more from the cost of formula. The company's sales pitch relies on those FDA requirements, saying that all infant formulas have to provide the same essential nutrients and so are basically the same. Spokesmen from other formula makers dispute this, arguing that the fats, carbohydrates and proteins they use come from higher-quality sources.
Paul Manning, chief executive officer of PBM products, which markets house brands for stores such as Wal-Mart and Target, as well as other no-name formula, said, "Just as the public grew comfortable with generic drugs, we think parents will grow comfortable with generic formula."
The formula is produced by Wyeth Labs Nutritionals, which has a long history of making formula for the American and foreign markets. "Nutritionally, there are pretty tight ranges for each ingredient set by the FDA, so parents can be confident all formulas have the nutrients their babies need," Manning said.
Behind the Research on DHA
Recent efforts to improve formula have focused most intensely on DHA, a fatty acid that has spawned scores of research projects around the world. The World Health Organization has recommended that infant formula be supplemented with DHA and more than 60 countries now allow its use.
While the panel that advised the FDA felt it was too soon to recommend the addition of DHA, other scientists point to what they feel is compelling research showing its benefit.
One of the places where DHA research is taking place is at the National Institutes of Health primate laboratory in Poolesville. When a stranger approaches them, the monkeys may jump forward with a screech or they may cower together and chatter. Among the scores of monkeys at the lab are 28 involved in a long-term study into the effects of infant formula.
Starting two years ago, the baby monkeys were fed different types of primate formula--one group got a mix of Similac and a special primate blend, and the other got the same formula supplemented with the fatty acids DHA and arachidonic acid (AA).
Researchers from around the world have been studying the molecule for a decade, since it was discovered that high concentrations of DHA are found in the retinas and brains of breast-fed infants. That gave rise to their hypothesis that DHA is essential for the optimal development of babies. Infant formula does not contain pre-formed DHA, although it does contain some of its fatty acid building blocks. But the researchers found that babies fed standard formula show considerably lower levels of the molecule in their bloodstreams and their brains than found in breast-fed babies.
Efforts to supplement formula with DHA have proved controversial, and the FDA has withheld approval. The American Academy of Pediatrics has also declined to recommend it. DHA is a potentially powerful substance and members of the panel were concerned that its addition could create a biochemical imbalance in formula. But advocates believe that without DHA, infant formula is out of balance.
As part of a study with Joseph Hibbeln of the National Institute on Alcohol Abuse and Alcoholism, the Poolesville monkeys will be studied over their natural life spans, usually about 25 years in captivity. But researchers believe they already have intriguing results.
According to Maribeth Champoux, a researcher with the National Institute of Child Health and Human Development, the monkeys were first tested at 7 and 14 days old. They were run through a battery of vision and behavior tests, including one based on the work of pediatrician T. Berry Brazelton that involved following and reaching for a Mickey Mouse toy. The testers did not know which monkeys had been fed supplemented formula.
"Especially following the Mickey Mouse, some of the monkeys did surprisingly better than others," Champoux said. Some monkeys also did better in motor maturity. In both cases, it was monkeys in the DHA-supplemented group that tended to do best. A control group of breast-fed monkeys performed at the same higher level as the DHA-supplemented group.
The effects, however, did not last beyond 21 days, and it is not known yet whether the enhancement has long-term implications.
Numerous human tests of DHA have also been conducted with mixed results. Studies using higher levels of DHA have generally found effects; those with lower levels have not. But none of the studies have been sufficiently long-term to be definitive.
A study of 44 infants in England, for instance, found that babies fed DHA-supplemented formula performed significantly better than those drinking regular formula on a series of problem-solving tests. The study, published last fall in the Lancet, tested the ability of 10-month-olds to find, uncover and retrieve a toy.
Research by Eileen Birch of the Retina Foundation of the Southwest has tested the effects of supplementation of DHA and AA on the eyesight and brain development of 108 infants. In a study published last year in the journal Pediatric Research, she reported that electrical measures of the infant's visual acuity were significantly enhanced in those babies fed supplemented formula.
In a workshop this spring at the NIH, Birch reported that this improvement in visual-brain function was repeated when she tested the same infants at 18 months for early motor development abilities. The group that drank DHA-supplemented formula, she found, performed the tasks better. Birch is now performing IQ tests on older children in the study.
"That's the big issue on everyone's mind--do the subtle effects we are seeing translate later in life to improvements in IQ?" she said. "We don't have enough data yet to be conclusive, but the early indications are positive."
But other large studies with supplemented formula, often with significantly lower levels of added fatty acids, have not shown much effect.
Studies by the Ross Products Division of Abbott Laboratories, makers of Similac and now skeptics regarding DHA addition, have consistently shown little or no effect in supplemented infants. In addition, some tests of infants whose breast-feeding mothers had DHA-supplemented diets did not show predicted improvements. One Ross study of 197 infants, published in Pediatric Research, found no significant differences in brain-related visual acuity.
"We started looking into the long-chain fatty acids [like DHA] 10 years ago, and I thought then we would probably find them to be important," said William McLean, vice president for pediatric nutrition research at Ross. "But we are letting the science lead us, and it is showing us no impact from DHA supplementation. We followed kids for 39 months, and we found no differences between the regular and supplemented formula."
Formula makers acknowledge that infants have a need for DHA in their brains. But officials at Ross and other scientists say their research shows that infants can make enough of the DHA from the precursor fatty acid, alpha-linolenic acid, which has been added to formula for more than a decade. (The expert panel has recommended requiring it now in all formula.) Other researchers disagree strongly that alpha-linolenic can ever suffice, and the scientific debate on that issue, like so many others regarding DHA, is fierce.
Sheila Innis, a University of British Columbia researcher who was the formula panel's main expert on fatty acids, has caused controversy over her often-voiced caution regarding DHA. Yet even she said that while DHA should not be added now because its safety and usefulness has not been proven beyond a doubt, she thinks it probably will be added in the future.
"Because of the complexity of the role of these long-chained fatty acids in the brain, there will always be doubts about their essentiality. But that doesn't mean they shouldn't be added," she said. "It takes strong proponents to move a scientific idea forward. And it takes regulations like the FDA's to make sure we make decisions in the right way."
Free Formula Raises Concerns
While industry surveys show that overall formula sales are steady in the United States, there is concern about one large group of babies that has experienced a significant rise in formula use over the past decade, despite the benefits of breast-feeding. They are the babies from poor and near-poor families covered by the federal Women, Infant and Children (WIC) supplemental food program, and they now make up almost half of all American infants.
Industry sources estimate that as much as 60 percent of all formula is purchased today through WIC, double the level of a decade ago. The program has expanded quickly in recent years as federally mandated competitive bidding for infant formula has pushed prices down to a small fraction of wholesale price. The result: Free formula has been made available to millions of mothers and their babies.
Yet official federal policy, including WIC policy, is to promote breast-feeding as the best way to feed an infant. In an effort to address the apparent contradiction in its policies, WIC has been hiring breast-feeding specialists to encourage and help WIC mothers, and now provides an upgraded package of foods for breast-feeding women. Officials believe breast-feeding rates in WIC have increased recently as a result, but acknowledge they remain low.
"People tend to think of us as a place that dispenses formula," said Pat Garrett, a WIC breast-feeding specialist in the Falls Church office. "It's a misunderstanding, but it's widespread."
Garrett says that not enough WIC mothers receive good information about the mechanics and benefits of breast-feeding in the hospital. As a result, they are easily attracted to formula, which most are given as going-home gifts. She said many WIC mothers come from homes where breast-feeding is not supported and where formula is seen as the surest way to keep the baby healthy and sleeping through the night.
Statistics about breast-feeding by WIC mothers are sketchy. A 1997 study by the Department of Agriculture found that 31 percent of WIC mothers initiated breast-feeding, but that only 16 percent were still nursing at five months. Another study sponsored by the Department of Health and Human Services and published this year found that 40 percent of mothers at a WIC clinic in Baltimore started breast-feeding, but that only 20 percent were still nursing after 10 days. In the general population, 58 percent of women start breast-feeding, but only about 30 percent are still nursing at three months.
"The whole bottle-feeding culture is so pervasive," said Kiran Saluja, head of the Breastfeeding Promotion committee of the National Association of WIC Directors. "It's easy and it's available--you can see how much your baby has gotten and it seems like you don't have as many worries."
"The benefits of breast-feeding take a longer time to see," she said. "So I think we have to talk more about the health problems that can come along with formula for mother and the baby. And we need to make workplaces and neighborhoods friendlier for breast-feeding women."
While WIC officials do want more mothers to breast-feed, they believe much of the WIC formula is serving a worthy purpose. "Many poor women using formula now might otherwise be using cow's milk, which is much worse," Saluja said. Cow's milk, she said, lacks many of the nutrients that infants need to thrive.
Experts Say Breast Is Best for Babies
Breast-fed babies are less likely to suffer from diarrhea and allergies than their bottle-fed peers. They are less inclined to develop asthma or urinary tract infections, and are less likely to become overweight.
For these reasons and more, experts on infant nutrition are unanimous in recommending breast-feeding as the best possible way to feed a baby unless there are medical complications. In a controversial position paper released in 1997, the American Academy of Pediatrics (AAP) advised women to breast-feed "for at least 12 months, and thereafter for as long as mutually desired."
"If you look at the anthropological information, you would see that through most of evolution humans have breast-fed for three years or so," said Lawrence M. Gartner, chairman of the AAP working group on breast-feeding. "The data seems clear that the longer you breast-feed, the greater the benefit to the infant."
Researchers are also trying to learn what effect breast-feeding might have on cognitive development, but the science is still evolving. According to the AAP, "Breast-feeding has . . . been related to possible enhancement of cognitive development." But even less clear is how long-term any improvements might be.
The recommendation to breast-feed, however, has come into conflict with the realities of American life, where a majority of women work and where the culture remains less than friendly toward women nursing outside their homes.
Statistics reflect this ambivalence: A federal survey in 1995 found that 58 percent of women began breast-feeding their babies, the same percentage as in the early 1980s. But almost 20 percent fewer mothers were still nursing after three months in 1995 than in the mid-1980s. A study by Ross Products, makers of Similac, found that only 14.5 percent of infants in 1997 were still being breast-fed after one year.
However, the Ross study did find a general increase in the percentage of women breast-feeding throughout the 1990s. Wealthier and better-educated women have breast-fed the most in recent decades, but Ross found the greatest increase in breast-feeding among women with a grade school or high school education. White mothers are the most likely to nurse their babies, the study found, and black mothers are the least likely.
What's in Formula
Nutrients required by FDA in formula (1985): protein, linoleic acid, fat, choline, carbohydrate, inositol, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, sodium, potassium, chloride, vitamin A, vitamin D, vitamin E, vitamin K, thiamin, niacin, pyridoxine, cobalamin, folic acid, biotin, panthothenic acid, ascorbic acid.
1998 requirements by life Sciences research office (lsro): selenium, carnitine, linolenic acid.
Allowed but not required by lsro: fluoride, nucleotides, taurine.
CAPTION: Maribeth Champoux, an NIH researcher, holds one of the monkeys being tested for visual and motor abilities as part of an experiment on supplements to infant formula.
CAPTION: Pat Garrett, right, a counselor who works with women receiving food through the federal WIC program, talks with Martha Rivera about breast-feeding her month-old daughter Marissa. A translator, Miriam Montecinos, is in the center.