LAURA TEIXEIRAParents have a unique opportunity to influence their children’s development and help them grow into healthy adults. However, this entails having to pay close attention and take swift action. This unique opportunity comes up early on and lasts for a short time. It starts at conception and lasts for a mere one thousand days – 270 days of pregnancy plus 730 days that correspond to the child’s first two years of life. In principle, the possibility of allowing a healthy baby to grow up this way and remain in the same state demands that apparently simple measures be adopted: namely, provide the baby with protection and comfort and feed him properly. Proper nutrition includes a balanced diet for the mother during pregnancy, breastfeeding the baby during the first six months without adding any other kind of food and, after the six-month period, breastfeeding together with water, fruit juices, teas, baby food and food rich in protein, vitamins and dietary minerals, as recommended by the World Health Organization (WHO).
This is nothing new, yet this recipe can avoid serious health problems later on in life. Experiments on rodents show that substituting breast milk with other foods – including other kinds of milk – during this stage of development alters the taste and creates hormonal imbalance that can last for a lifetime and lead to weight gain. Proper nutrition, on the other hand, reduces the risk of adult obesity and cardiovascular diseases, as seen by population studies conducted in five developing countries (Brazil, South Africa, Guatemala, the Philippines, and India). Also according to these research studies, breastfeeding enhances intellectual performance.
For several decades, teams from these countries, including the team led by Brazilian epidemiologist César Victora, evaluated, on a regular basis, the growth of 10,912 children. The children that were started on other foods prior to the age of six months – 69% of the Brazilian babies were started on other foods prior to the third month of age – accumulated more body fat throughout their lifetime. The earlier these babies were put on baby food, fruit juices and other kinds of milk, the more fat they accumulated, which increases the risk of cardiac diseases and strokes. These conditions account for 30% of the deaths around the world, according to the researchers’ report published in the September issue of the International Journal of Epidemiology. “The biggest cause for the accumulation of fat was not the length of the breastfeeding period, but the early introduction of other foods into the baby’s diet”, says Victora, a professor at the Federal University of Pelotas, in the State of Rio Grande do Sul, and Johns Hopkins University, in the United States.
For nearly 30 years, Victora, Fernando Barros, and a team of epidemiologists have periodically kept track of the health of all the children born in the years 1982, 1993 and 2004 in Pelotas, a town of 330 thousand inhabitants located in the southernmost part of Brazil. This long-term follow-up, referred to as cohort, led Victora and colleagues from other countries a few years ago to review the adequate development pattern up to the age of 5 years and propose a new growth curve, which was recognized by the WHO in 2006. This growth curve has been adopted by pediatricians from more than 100 countries.
The cohorts in Pelotas and other parts of the world showed that babies fed only on breast milk up to the age of six months grew at a different pace than babies who were fed powdered milk or other formulas. Breast-fed babies gained weight and grew more rapidly in the first four months of life, after which they developed at a slower pace. “These are healthy children, although they are thinner”, he says. Babies on powdered milk or other formulas that imitate human breast milk gained weight faster from the age of seven months onwards.
A possible explanation for this faster development at a later age is the consumption of more calories than the recommended amount. Marina Rea, of the Institute of Health (IS) of São Paulo, and Ana Maria Corrêa, of the State University of Campinas, verified years ago that children on bottles and other foods during the first few months after birth consumed 50% more calories (see Pesquisa FAPESP nº 123).
“It is never too much to repeat that human breast milk is the only food that a baby needs up to the age of six months”, says Victora. Human breast milk has more sugar and fat than cow’s milk. In addition, it has adequate levels of proteins and other nutrients for the baby, and a high amount of immunologically active compounds.
LAURA TEIXEIRANonetheless, it is not easy to follow the recommendation of the WHO. The fact that more women are entering the labor market, coupled with the lack of proper information on how and for how long babies should be breast-fed, results in a baby’s diet being changed before it should. “In addition”, says Victora, “many physicians do not respect the recommendation of the WHO and put babies on foods that are not necessary at this stage of the babies’ lives.”
The result is that in Brazil the proportion of mothers who breastfeed their babies for six months without adding any other foods is low in comparison to other countries. However, this proportion is higher in comparison to ten years ago. Nowadays, 51% of the mothers breastfeed their babies during the first four months – in comparison to 36% in 1999 – and 41% breastfeed their babies for up to six months, according to a survey conducted by the Ministry of Health under the coordination of pediatrician Sonia Venancio, of the IS. This percentage is still lower than the ideal percentage, but the figures have improved significantly. In 1974, 50% of the babies were breast-fed up to the age of two and a half months. In 2006, the period went up to 14 months.
Sonia evaluated data from 2008 on 34.4 thousand children from all state capitals and from the Distrito Federal. She noticed that evolution is slow, in spite of recent improvements. In the first month after delivery, 18% of the babies were already given other liquids and at the age of two months, half of the babies were fed other foods in addition to breast milk. “There is still a lot that has to be done”, says Sonia, who published the referred data in the Jornal de Pediatria pedriatics journal in the middle of the year.
The benefits deriving from proper nutrition during the baby’s early months are not only physical. In another paper published in the February issue of the Journal of Nutrition, Victora and collaborators analyzed the academic performance of 7,945 children from India, Guatemala, the Philippines, Brazil, and South Africa. Babies that grew healthily during pregnancy – an indication of adequate maternal diet – and were born weighing more than the average, had a better chance of achieving successful development. Each 500 additional grams at birth represented 2.5 additional months of schooling during adulthood and 8% less risk of failing a school grade. Even babies who were delivered weighing less than 2.5 kilos, which is lower than the desirable weight, achieved good intellectual development when, by being given the adequate diet, they reached a normal growth pace and reached the proper weight for that age until the age of two. In the course of this period, the babies gained 9 kilos on average, and every additional 700 grams above the average meant five additional months of schooling.
“During the first two years, the child still has the opportunity of growing more than the average and of becoming a healthy adult if, in addition to being breast-fed, the child is immunized and gets good health care”, says the epidemiologist. During this crucial development phase, which Victora refers to as “one thousand days of opportunity”, the organs are still developing: bones are still growing longer, the muscles are becoming stronger and the brain grows (the brain reaches 70% of its total growth when the child is two years old). “From the third year onwards, accelerated growth results in the accumulation of fat”, he explains.
The changes that the epidemiologists observe by using scales and metric tapes are beginning to be supported by a physiological explanation. Experiments with rodents have helped unveil the biochemical mechanisms through which the introduction of other foods during the breastfeeding period lead to the accumulation of fat.
One of these changes is related to taste. In a research study coordinated by Raul Manhães de Castro and Sandra Lopes de Souza, of the Federal University of Pernambuco, nutritionist Lisiane dos Santos Oliveira interrupted the breastfeeding of a group of rats, by separating them from the mother on the fifteenth day after birth, which is equivalent to the three months in a human baby, and allowed the rats to eat as much animal feed as they wanted. The rats were weighed periodically and food consumption was measured, but there was no difference in the weight nor in the intake between the rats that had been weaned earlier and the rats that were nursed until the age of 30 days.
The difference only showed up in a food preference test. As soon as the animals reached adulthood, the researchers simultaneously left two different diets at the disposal of the rats for a couple of days: the standard animal feed of the vivarium and another tastier diet (based on chocolate and hazelnuts), with more calories and fat. Both groups preferred the more palatable diet over the standard animal feed. However, the rats that had been weaned earlier ate much more, the researchers report in an article to be published in Behavioural Processes. “Although there were no weight-related changes or changes in the daily feeding pattern of the animals, the preference for a high-calorie diet was manifested as soon as this kind of food became available”, says Lisiane. “In the long-term, the preference for high-calorie food may lead to metabolic disturbances”, says the nutritionist.
Another test conducted by the group from Pernambuco showed that rats weaned at 15 days took twice as long to feel sated when reaching adulthood. After a brief fast, they ate continuously for 42 minutes, while the animals who had been nursed until the 30th day felt sated in 23 minutes. According to the study, which will be published in the same journal, the rodents weaned at an earlier age showed more changes in the daily food consumption pattern (circadian): they ate more at different periods of day and night than the periods during which the other rats ate, even though the amount of food was similar.
LAURA TEIXEIRAThese behavioral changes stem from hormone and metabolic changes. In papers published recently in the Journal of Endocrinology and in the Journal of Physiology, the team led by endocrinologist Egberto Gaspar de Moura, of the State University of Rio de Janeiro, showed that early weaning alters the body composition and reduces the sensitivity to the leptin hormone which leads to satiety and puberty.
By adopting a different experimental model from the previous one, the group from Rio de Janeiro provoked early weaning by applying a compound to the mother rat preventing the production of prolactin, the hormone that induces the secretion of the breast milk, instead of removing the baby rats from their mother. The animals that had been weaned earlier reached adulthood weighing 10% more, had 40% more total fat, and up to 300% more visceral fat (that is located inside the abdominal cavity and is more harmful). Confirming the deleterious effect of visceral obesity, the rats weaned earlier had higher levels of glucose, cholesterol and triglycerides in their blood and lower levels of HDL, the protein that removes the cholesterol from the blood and avoids the formation of fat plaques in the veins. These changes are referred to by physicians as metabolic syndrome, a condition that increases the risk of developing diabetes and cardiovascular diseases.
The team from Rio de Janeiro also observed that, when reaching adulthood, the leptin levels of the animals that had been nursed for a shorter period of time were three times higher than normal. In spite of such an enormous quantity of this hormone, which is produced by the fat cells and tells the body when to stop eating, the leptin did not produce this effect on the referred animals. After a 12-hour fast, the researchers gave leptin to two groups of rats: one group had been breastfed for the standard period of time, while the other group’s breastfeeding had been interrupted. As expected, the rodents from the first group ate less, while the rodents from the second group kept on eating – a sign that they were not responding to the hormone.
Moura also observed another kind of hormonal imbalance: the rats that had been weaned earlier developed hypothyroidism. Their thyrotropin levels were 50% lower than normal. Thyrotropin is a hormone that activates the thyroid gland, which produces the hormones that stimulate energy consumption. According to the endocrinologist, hypothyroidism could be a consequence of resistance to leptin. As leptin acts in a region of the brain called hypothalamus, which commands the production of other hormones (among them thyrotropin), the lack of a response can affect the functioning of the thyroid. “Apparently, this hormonal and metabolic alteration is an epigenetic programming (alteration in the functioning of the genes) phenomenon”, says Moura. However, this still has to be proved.
Given that researchers have not yet discovered what triggers these alterations and how to control them efficiently, the best thing to do is to prevent the problem by recommending that babies be raised exclusively on human breast milk during their first six months. In the city of Recife, the team led by pediatrician Sonia Coutinho showed that it is possible to encourage mothers to breastfeed their babies by adopting inexpensive measures, such as training health care professionals in this respect, especially the community agents that work under the Family Health Program (see Pesquisa FAPESP nº 119).
At the University of São Paulo, a team from the Center for Epidemiologic Research on Nutrition and Health (Nupens) has a bolder proposal, which does not prevent the metabolic alterations associated with early weaning, but can mitigate the health problems provoked by them. The team’s recommendation is that Brazilians change their dietary habits by eating more fruit, greens and vegetables; at present, Brazilians eat less than one-fourth of the recommended quantities. One of the reasons for such low consumption is the high price of these foods. Rafael Claro, of Nupens, calculated how much it would cost for people to eat the recommended quantities of these foods, such quantity corresponding to 12% of the total calorie intake. The diet would be 30% more expensive.
However, if the prices were to drop, even poor people would eat more vegetables. For a couple of months in 2007, the team from Nupens set up a facility in Grajaú, one of the poorest neighborhoods in the city of São Paulo, to sell fruit and vegetables at subsidized prices. As they had expected, the consumption of fruit and vegetables increased. “The cost of these foods is a significant barrier to consumption”, says Claro. His proposed solution is that the State reduces the taxes levied on these foods and raises the taxes levied on ultra-processed foods that contain preservatives, dyes and stabilizers, as well as excess sugar, fat and salt. “Lower tax proceeds”, he says, “would be offset by lower health care costs.”
Early onset of puberty
Action of the leptin hormone on the region of the hypothalamus triggers sexual maturity
Brazilian neuroscientist Carol Elias went a step forward to unveil a phenomenon that has alarmed North American physicians: the onset of female puberty at an early age. Carol and her team have identified the region of the brain where the leptin hormone acts and triggers sexual maturity. This region is referred to as the premammilary ventral nucleus.
The first signs that leptin, produced by fat cells and known to reduce hunger pangs, drove the development of the sexual organs and fertility, were observed years ago. Without leptin, mice and human beings did not go through the physiological transformations that prepare the body for procreation.
When she was at Harvard University, Carol – currently working as a researcher at the University of Texas – helped identify the regions of the brain that produce leptin receptors – the protein which binds with the hormone to stimulate the functioning of the neurons. Among the regions of the hypothalamus that express these receptors, the premammilary ventral nucleus (NPV) attracted the researcher’s attention. The premammilary ventral nucleus is a group of cells connected to a part of the brain that produce the sex hormones.
However, it took a while to prove that the action of leptin on the NPV triggered puberty. Invited to join the team led by Joel Elmquist in Texas, Carol and researchers José Donato Júnior, Roberta Cravo and Renata Frazão raised genetically modified mice to, under certain conditions, produce the leptin receptor only in the referred nucleus. According to the article published in the December issue of the Journal of Clinical Investigation, unfertile females went into puberty when the production of this receptor was stimulated in the NPV.
There is an explanation: the neurons in this nucleus activate cells that produce the hormone that releases gonadotropins, which, in turn, activate the release of sex hormones. This effect helps understand why there is an increasing number of girls aged seven and eight in the United States experiencing puberty. “It is possible that higher levels of leptin in obese children is stimulating regions of the brain that would normally be activated at a later age”, says Carol.
VICTORA, C.G.; et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. v. 371(9.609), p. 340-57. 26 Jan. 2008.
DE MOURA, E.G. et al. Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny. Journal of Physiology. v. 587(20), p. 4 919-29. 15 Oct. 2009.
OLIVEIRA, L. S. et al. Early weaning programs rats to have a dietary preference for fat and palatable foods in adulthood. Behavioural Processes. Forthcoming.