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Cesar Victora

Cesar Victora: Health behind the statistics

026-031_Entrevista_208Liane Neves

When he landed in England in 1980 to begin his doctoral studies, Cesar Gomes Victora, a physician from the Brazilian state of Rio Grande do Sul, was carrying precious material that he had obtained from the Brazilian Institute of Geography and Statistics (IBGE). It consisted of social, economic and health data on about 1% of the Brazilian population. The data were stored on an enormous roll of magnetic tape, a then-sophisticated data storage medium. Upon presenting it to his thesis advisor, epidemiologist John Patrick Vaughan, he was immediately told, “I don’t trust armchair epidemiology.”

That first lesson caused Victora to return to Brazil earlier than planned. He had to take to the road and travel around Rio Grande do Sul looking for information on living conditions and child health in the inland parts of the state. His work there revealed important socioeconomic determinants of health—the levels of malnutrition and mortality were lower in areas that had a more balanced income distribution and family farms—and convinced him of the principle introduced by his thesis advisor. Victora shares it with his students to this day: an epidemiologist has to go into the field to gather his data.

After completing his doctorate, Victora, feeling averse to urban hustle and bustle, returned in 1984 to distant, easy-going Pelotas, where he was already a professor at the then-recently-created Federal University of Pelotas. In that friendly, welcoming city—a major economic hub for the state in the late 19th century that produced leather and charque, the beef jerky that served to sustain cattlemen and slaves alike—he helped friend and pediatrician Fernando Barros to create one of Brazil’s first birth cohorts. These are long-term studies that monitor the health of people born in a specific place during a given year. Initiated in 1982 and still ongoing, this cohort generated repercussions that brought the pair national and international recognition and transformed the Center for Epidemiological Research, which they founded, into an international model in that field.

Age: 61-years-old
Federal University of Rio Grande do Sul (undergraduate degree)
London School of Hygiene and Tropical Medicine (doctorate)
Federal University of Pelotas

Regarded as one of the world’s most highly respected epidemiologists in child health, Victora, 61, has been retired from the university since 2009 but remains highly productive. He has published more than 500 papers, nearly 70 of them in the past four years. When not traveling—he spends 40 days a year flying from one country to another—he is usually working at home looking out over Lagoa dos Patos, the major lagoon where he windsurfs whenever wind conditions permit. Between commitments in March, he welcomed Pesquisa FAPESP in Pelotas for this interview.

One particular fact in your career stands out. You graduated in 1977, and the next year you were already a professor at Pelotas. How did that come about?
It was a coincidence. I was doing a community health residency in Porto Alegre and, in the middle of the program, the University of Pelotas was federalized. Before that, the school of medicine had been independent and was called the Lay School of Medicine of Pelotas, because there was another, Catholic medical school. And the lay school was looking for professors because it needed to have a department of social medicine. They went to my program looking for people, and I decided to come. I’m from São Gabriel, which is inland, and I always wanted to live in a city smaller than Porto Alegre, which I considered huge.

Did you begin your research in public health when you went to England for your doctoral studies?
Shortly before that. As soon as I came here, I started doing research under Kurt Kloetzel, the founder of the department, and he was the one who brought me here.

What was the subject of your research?
I began by studying child mortality and malnutrition. I had always worked with the very poor, slumdwellers in Pelotas and Porto Alegre, and I had noticed that the children always came back [to the health clinic] with the same problems: diarrhea, malnutrition, pneumonia. I would treat a child and he would return two weeks later with the same thing. They were living in a very impoverished environment, with no running water; they were not breastfed and they were exposed to environmental pollution. It was at that point that I decided to go into epidemiology and try to do something oriented towards disease prevention.

How did you decide to go to London?
I had my doubts about it. I was accepted into one program in San Francisco, California, and another in London. I began reading papers, and I found myself more attracted to English epidemiology. The studies weren’t overly ambitious. American epidemiology was doing enormous studies with multiple objectives and using sophisticated technology. I thought that kind of approach wouldn’t be useful in Brazil, which was a poor country at the time. My doctoral work focused on profiling malnutrition in Rio Grande do Sul. I compared the frequency of malnutrition in the state and showed that the South, which was home to large landholdings, had a high child mortality rate. In the North, which had predominantly small farmers who had their own land and grew their own food, malnutrition and mortality rates were low.

At the time, your colleague Fernando Barros was returning to Brazil. Were the two of you already planning to initiate the studies monitoring the health of people born in Pelotas—the birth cohorts?
We had planned a few studies, but we were amateurs. We had no specific training. A few years earlier, David Morley, a British professor who was Fernando’s advisor for his Masters program, introduced us to John Patrick Vaughan, the epidemiologist who became our doctoral thesis advisor. The one who created the first cohort was Fernando. He planned the 1982 survey during his doctoral studies. When I came back from England in 1983, I had obtained financing for another study and there was some money left over. We did the 1983 survey there. The 1982 study was a survey to measure child mortality, prematurity and other characteristics of newborns, and it included the 6,000 births in the city that year. Brazil is full of studies done at a single hospital, which doesn’t allow for that population characteristic. After that, Fernando, Patrick and I obtained financing from England to continue.

What was the scope of the survey?
In 1982 we got 99% of the registered births at hospitals and maternity clinics in Pelotas, because 1% were born at home. The following year we went looking for the addresses given by the parents and we found 83%. We lost 17%. It’s a reasonable percentage, but if I lose that much in a year, how am I going to monitor a reasonable number in the long term? At that time people were not leaving Pelotas. They moved between neighborhoods. So I had an idea: what if we went from house to house to find them? It even gave rise to a sick joke. They dubbed it Operation Herod, because we were looking for children in the city, just like Herod went from house to house looking for Jesus. Using that strategy in 1984, we found 87.5%. The higher percentage is paradoxical, because over time it tends to drop. In fact, one of the distinguishing features of the Pelotas cohorts is the fantastic monitoring rate, higher than ones done in other regions of Brazil and even in other countries. There is a famous English cohort from 1970 that, 30 years in, did not find as many people as we found last year, when our first cohort reached 30 and we located 68% of those born in 1982.

Were you expecting to do that long a follow-up?
We did a visit to all the children when they reached the age of two, and then again at four, and we thought we were done. We didn’t come back to the cohort until they were 15. We lost information at a critical phase of development. We could have done a visit at seven and another at 10 or 11 years, like we’re doing with the more recent cohorts.

Was it hard to get financing to continue?
That’s a constant challenge. The financing agencies love the project, but after a certain amount of time they tire of it and their priorities change. From 2004 to 2014 we had financing from Wellcome Trust for the 1982, 1993 and 2004 cohorts. [In May, the Ministry of Health’s Department of Science and Technology (DECIT) approved financing for the principal Brazilian birth cohorts—Pelotas, Ribeirão Preto in Minas Gerais State, and São Luís in Maranhão State.]

What projects came about after the first cohort?
Fernando and I started working in northeastern Brazil with UNICEF [United Nations Chidren’s Fund] to map malnutrition and child mortality. Between 1987 and 2001, we did surveys in nine states and found very high rates of child mortality [more than 100 deaths per 1,000 births]. We interfaced with Health Ministry departments and were able to target the lines of activity for the states on the basis of the research results. But our group was a small one. Fernando and I trained interested colleagues on an amateur basis. In 1990 we saw that we needed people who knew how to do epidemiology. So we created the master’s program in 1991. It was our biggest coup. We are now training over 100 master’s candidates and 50 doctoral candidates. Most of them leave, but we have a critical mass. It’s a strong group, with recognition in Brazil and a Qualis score of 7 from the Coordinating Agency for the Improvement of Higher Education Personnel (CAPES).

What led you to seek out the 1982 children again?
In 1997 we obtained money from UNICEF, which was interested in adolescent health. Since the funds were limited, we were only able to evaluate 25% of the cohort. In 2000, when they were 18, the boys went into the army. We set up a clinic at the barracks to examine them. We were able to see over 80% of the original sample. We also sought out 25% of the girls. At that time we asked Wellcome for money and, in 2004 when the subjects were 23 or 24, we found 75%. At 30 years now, we’ve found 68%.

How are they doing?
The striking thing is that they are fat. More than half are overweight or obese. Earlier they were undernourished.

Have they started manifesting problems because of the excess weight?
Yes. In exams they’re already presenting with high cholesterol, hypoglycemia, high blood pressure, and high C-reactive protein levels [a marker for chronic inflammation]. I want to educate young people because I’m hoping this cohort will last for another 30 or 40 years, like the classic cohorts. This kind of research gives an idea of what we call life cycle epidemiology, which begins at conception and covers an entire life span.

Over the 30 years, what have you learned from the cohorts?
The main thing is the importance of the early risk factors and the first thousand days of life, when irreversible damage can occur. We were able to prove that rapid weight gain is good during the period from conception to the age of two. After that, it starts becoming harmful.

How should you care for a child during those first thousand days?
The first thing to do is ensure that the woman starts with a healthy gestation. Make sure she’s not undernourished, or obese, or diabetic. During gestation, you need to offer good-quality prenatal care. In Brazil there is a lot of prenatal care, but the quality is low. High-tech care is not necessary. You have to do basic exams and give nutritional guidance. After childbirth, you need to advise the mother to breastfeed during the first six months with no supplementation, and to try to continue breastfeeding for up to two years. Only after six months should she start with high-protein foods and nutrients. It’s during that period that we see further development of the brain, liver, pancreas and internal organs that can cause problems during adulthood. Starting at the age of two, the challenge is to prevent the child from getting fat. Our results show that rapid weight gain at the beginning of life turns into bones, muscles and internal organs such as the liver and the brain. After two years, it turns into fat.

And the fat leads to problems…
The worst combination is to be undernourished at the beginning of life and obese later on. A child who is undernourished in utero is born with low weight and has a height deficit during the first two years of life. His body is programmed to be small, and later in life he won’t be able to tolerate a diet like ours, with fatty, high-calorie foods. Brazil is at a critical stage. Adults at 30 are the children who grew up when malnutrition and undernutrition were common. Now we are faced with an obesogenic environment, with little physical activity and an abundant food supply. I thought the Zero Hunger program was a mistake. If there’s hunger in Brazil, it’s of the pocketbook. Everyone has food to eat, but they’re eating the wrong things because those foods are cheap.

Are the results from Pelotas, a city of 300,000, valid for Brazil?
Cohorts are generally done at just one location. The study that was most helpful in understanding the risk factors for cardiovascular disease is the Framingham Study, which was conducted in a small, wealthy community in the U.S. state of Massachusetts. Any study of this type starts with a microcosm. Now, there are two things to consider. One is to measure the prevalence of a disease. If I want to know how many people in Brazil have hypertension, the Pelotas study won’t give me the answer. I’d need a national study. But if want to know if a person who is fat has more hypertension, I don’t need to look at all of Brazil. I take a city where there is some variability, not all rich or all poor, not all fat or all thin, and I do a study that has internal validity and that can show an association of factors. Pelotas is interesting because it looks at the Southern poor, the poor mixed in with the rich, more similar to the rest of Brazil than to Rio Grande do Sul. In the Pelotas studies I can find associations between risk factors and disease that are applicable to the entire country.

So the focus is on finding factors that determine a person’s health later on.
Exactly. And what we’re seeing here, I’m sure, is true for the rest of Brazil. When they invited me to coordinate a series of papers that came out in The Lancet in 2008, I went looking for the largest cohorts outside of the wealthy countries. I identified ones in Guatemala, Pelotas, Soweto [South Africa], New Delhi [India] and the Cebu islands [Philippines]. We created the Consortium of Health Orientated Research Studies on Health in Transitioning Societies—COHORTS. The results are very similar. We’re publishing papers in The Lancet on the subject of the thousand days. These papers show, for the first time in a systematic study in several countries, that gaining weight is different from gaining height. A child with rapid height gain will be a healthier, more intelligent, more productive and better-educated adult.

Is there some biological reason?
Yes. Height is lean body mass: bone, muscle and internal organs. It makes a taller, stronger adult with a larger brain, larger liver and larger pancreas. That person has more capacity for insulin production, his liver has more processing capacity, and his kidneys do a better job of filtering. Not so for weight gain. In the beginning stage of life, what we want is weight gain. During that time it influences height. A pediatrician is going to have to think about how to make the child grow in height without gaining too much weight.

Do we know how to make this happen?
No. We know that some things help to promote height gain, like breastfeeding and a diet rich in high-quality protein—especially from animals—and in some micronutrients.

If the child is still small after that period, is it better to leave it at that?
Everyone who’s a pediatrician, myself included, when he gets a three- or four-year-old child who is skinny, what does he do? He fattens him up. But he can’t gain lost height. The thousand-day window has already passed. We’re going to have to change how we think about growth and about health and nutrition programs.

How do we convince pediatricians?
It’s a paradox. When a pediatrician in Pelotas discovers something like that, he can’t convince other pediatricians in Pelotas. In the 1980s we did a study showing that up to six months, a child should have only mother’s milk. Nobody believed it. We were able to convince the World Health Organization [WHO] and UNICEF, and they convinced the Ministry of Health, which convinced Brazilian pediatricians. Now all good pediatricians recommend it. There is a cycle [of knowledge dissemination] that is not always direct. We were invited to present the data on the thousand days in March at a meeting of WHO. We’re beginning the process of translation—transforming the results of a scientific study into clinical practice, a health policy. It’s a slow process.

Would you describe the study that established the ideal pattern of child growth?
Cohorts provide descriptive information. That other study was looking for prescriptive information on what ideal growth is for humans up to the age of five. It’s a simple curve: weight, age, height. To establish this type of curve, I have to study people who exhibit good growth, and the cohorts include people with good, poor, and moderate growth. Everyone was saying that Brazilians are different from Jamaicans, Norwegians or Indians. Then we did an ambitious study. We got a sample of over 7,000 children in Brazil, the United States, Norway, Oman, Ghana and India. We chose mothers and children from a good socioeconomic level—the mothers had had prenatal care, were non-smokers with no major illnesses, and the children had been breastfed—and we looked at how well the children grew. To even our surprise, their growth patterns were very similar. People think that Brazilians are short and Norwegians are tall. But at two years, the Brazilians were 0.2 centimeter taller than the Norwegians.

What part of the study was done in Pelotas?
We helped develop the methodology. Our center was the first to do this study. Health personnel from other countries came here for training. Today this growth curve is used in 140 countries.

It must be a source of pride for you.
For me, yes, it is. To do research and write a paper is nice, but I’m nearing the end of my career, and I want to see practical results.

Does the curve indicate whether environmental factors affect healthy growth?
The most striking thing is that a child in New Delhi, Oman or Pelotas can grow as much as one in California or Norway, if conditions are appropriate. The notion that there is a genetic difference falls apart. A person might be short or tall due to matters of genetics. But every population has short and tall people. Generally speaking, however, healthy populations are very much alike.

You’re beginning another predictive study, fetal growth curve. What is it like?
It’s the same idea. There are no worldwide standards for doing ultrasound during gestation to tell if the child is growing well. There are curves done with data from a single location. We’re doing a study with eight centers, gathering data from the ninth week of pregnancy to the 38th, 39th or 40th week for a group of mothers whose health conditions allow for ideal growth. The work, under the coordination of Fernando Barros, is moving along. We have data from 360 mothers out of 500.

How did you decide to begin other cohorts?
We started noticing that the situation was changing and we thought it would be interesting to do another cohort 10 years after the first one. We asked the European Community for financing, but the project got behind and came out in 1993. As a result, we decided to do the third cohort in 2004 in order to keep the 11-year interval. We already have money to start another one in 2015. We have data from when the children from all three cohorts were four years old. Between the first and the third, obesity at four years doubled. The situation changed quite a bit during those 30 years. For example, the percentage of adolescents who had been assaulted is much higher now than in 1982.

Are you assessing any other issues besides physical health?
We have anthropologists, sociologists and criminologists in the group. These cohorts no longer include just public health. They assess work, social life and behavior.

What was the biggest change?
They have more education. In the first cohort, many of the children did not finish the first years of school. Today everybody goes. The number of smokers appears to be falling. They are more obese and there are more premature births, which has me concerned. We’re also seeing less physical activity. Children used to walk or bicycle to school. Today they go by car or take a bus.

In the rest of the country, what has changed from when you were a student here?
Four things come to mind. Reduced child mortality and undernutrition; more obesity; and the increase in premature births. This last change is related in part to the increase in the number of Cesarian sections. Today, 54% of births in Pelotas are by C-section. In Brazil it’s about 50%. It’s 90% in the private sector, and in the public sector it’s 35%, which is still high. The ideal is 15% or lower. There’s an epidemic. At the same time, breastfeeding has improved. When we started, it was two to three months. Now it’s up to 14 months.

Are the improvements in public health also a consequence of the creation of the National Healthcare System, the SUS?
I think so. I’m in favor of the SUS and the PSF, the Family Health Program. They made an enormous difference. The SUS is currently underfinanced. The Brazilian government doesn’t put much money into the SUS, in relation to the size of the machinery. So the problems just continue to mount. Those who can are jumping over to the private plans because of the poor quality of the SUS. The situation is better than before, but the SUS is being jeopardized by underfinancing. Brazil spends proportionately less on public health than the United States [which does not have a universal public health system].

You’ve raised the level of sophistication for the type of measurement you’re doing in the cohorts. What information do you hope to obtain?
Until just a short time ago we had only the BMI, the body mass index, which can be high because the person has either high lean mass or high fat mass. We know that lean body mass is beneficial and fat mass is detrimental. The first improvement was to adopt methods to separate lean mass from fat mass, and to separate harmful fat mass such as intra-abdominal mass, from less-harmful fat mass such as fat on the thighs, the buttocks, and surface belly fat. The data have just been gathered. We want to know why some people accumulate the more harmful fat from the beginning.

Are there other new tools?
We have the blood tests and DNA from 4,000 people in the 1982 cohort. We’re doing genome scanning to try and see the genes associated with accumulation of intraperitoneal fat. I think it’s the biggest sample in Brazil to use this technique. It took three or four years to begin because of Brazil’s bureaucratic hurdles. By now we could have published the results.

What were the hurdles?
When we asked the National Commission for Ethics in Research [CONEP] for authorization to collect genetic material and study the DNA, we asked what the terms of authorization would be and we did what was indicated. At no time did they say it was necessary to report that the genetic material would be studied outside Brazil. Later on, CONEP said we didn’t have that clause in the contract and we had to redo the whole procedure. What difference does it make where the examination is done if the person authorized the collection and the data are confidential? We also had trouble paying for the exams. The Brazilian Audit Court requires international competitive bidding. That doesn’t exist in other countries. These kinds of unwarranted problems hamper research in Brazil. For a federal university doing observational research—I won’t be prescribing drugs, I won’t be doing surgery or anything that might endanger a life—that is in the public interest, there needed to be a speedy approval system. These bureaucratic hurdles that affect our international competitiveness are the cost of doing research in Brazil.