Children who start out skinny and small, but gain weight relatively rapidly after the age of two are at increased risk for Coronary heart disease later in life, researchers here reported.

Conversely, rapid weight gain between birth and two years is good, said David Barker, M.D., Ph.D., of the Oregon Health and Science University’s heart research center here.

The increased risk for those who gain weight rapidly after age two is present even if the child is not obviously fatter than his or her peers, Dr. Barker and colleagues reported in the Oct. 27 issue of the New England Journal of Medicine.

What’s important for low-birth-weight children, he said in an interview, is the “trajectory” of weight gain in childhood, not whether they appear overweight in the schoolyard.

Dr. Barker is known for his research showing that poor prenatal nutrition - resulting in low birth weight - predisposes people to Coronary heart disease as adults. But, he said, it was never likely that the biological process would stop at birth, he said. “The obvious next question was how does growth after birth add to or subtract from the risks acquired before birth.”

The answer to the question, he and colleagues reported, came from a data set in Helsinki, Finland - highly detailed records of weight and height from birth to age 11 for 8,760 people born between 1934 and 1944, coupled with medical histories that included deaths and hospitalizations for Coronary heart disease.

“The Helsinki data are just fantastic, because each person was measured on average 11 times between birth and two years,” Dr. Barker said. From ages two to 11, they were measured six times on average.

The data contained a “very, very clear answer” to the question, Dr. Barker said. Rapid weight gain between birth and age two is good, but the same sort of gain after two years is bad.

Specifically, the study found:

 
• Of the total cohort, 357 men and 87 women had either been admitted to hospital for or had died from Coronary heart disease.  
• The mean birth weight of boys who would later have a coronary event was 0.2 standard deviations below the average for the cohort and weight and body mass index (BMI) and remained low until age two, when the boys began to gain weight rapidly, approaching average BMI by age 11.  
• The same pattern was seen for the girls who would later have a coronary event, although they would slightly exceed the average BMI.  
• A pattern of low BMI at age two and a relatively high BMI at age 11 was associated with increased coronary risk.

The researchers stratified the subjects into thirds, according to BMI at age two, and then analyzed their risk of a coronary event according to BMI at age 11. Those with a BMI greater than 17 at two and less than 16 at 11 were used as a reference group.

In comparison with the reference group, those who were at the other extreme - with a BMI less than 16 at age two and greater than 17.5 at 11 - had a three-fold increase in risk. The 95% confidence interval ranged from 1.4 to 6.3.

Strikingly, none of the children had an extremely high BMI, Dr. Barker said. “We’re talking about children who grew up in Finland during the war, and there were no fat children in those years at all.”

That means, he said, “the people who will end up in intensive care are invisible when you go to the school on one visit.”

While the biology underlying the finding remains unclear, Dr. Barker said, one possible explanation is that babies who are born small and remain so for the first two years of their lives don’t develop the right amount of muscle.

If they later put on weight, it will be disproportionately fat tissue, rather than muscle, he said.

The research has some lessons for clinicians, he said:

 
• Good prenatal nutrition remains the key to healthy babies.  
• It’s important to ensure that a child gains weight during the “critical period” of the first two years.  
• It’s “no longer appropriate” to judge the health of children by comparing them with their peers using standardized charts and tables. Instead, “you have to measure a child in relation to where it has come from” in terms of previous measurements, Dr. Barker said.

Nevertheless, the conventional wisdom that a child should gain weight rapidly during the first two years of life has been challenged by recent observational studies, said Matthew Gillman, M.D., of Harvard Medical School, in an accompanying editorial.

Those studies suggest that accelerated weight gain in infancy can lead to overweight, insulin resistance, high leptin levels, and high blood-pressure, he said, adding that Dr. Barker’s study complicates the issue.

Dr. Gillman added, “If rapid weight gain in infancy is indeed harmful to adult health, then clinicians and public health professionals are faced with many challenges, including those of overcoming cultural stereotypes suggesting that ‘a big baby is a healthy baby.’ “

Responded Dr. Barker, Dr. Gillman is “quite right to articulate this issue,” especially in light of growing concern over obesity in the Western world. But, he added, the concern is unwarranted: “What we’re able to add is the long-term consequences of being a big baby - and they’re all positive,” he said.

Source: New England Journal of Medicine