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Mother and infant

Maternal diet during pregnancy is thought to be one of the most influential factors on child health and development. However, dietary interventions during this period may miss a critical window to improve health during childhood, as well as adult life.

In a recent series of articles in The Lancet, researchers address the significance of nutrition in the preconception period, or the time before a woman becomes pregnant. The series of three articles challenges the current perspective of the preconception period. Currently defined as 3 months before conception, the authors suggest preconception should also include any time a woman is at child bearing age. This revision is based on an understanding of the biological events occurring during the periconceptional period, or the time immediately surrounding conception. In addition, it addresses a lack of nutritional preparedness for pregnancy in women of reproductive age and the failure of dietary interventions during pregnancy in preventing adverse health outcomes.

How does pre-pregnancy nutrition affect child health?

The periconceptional period begins before fertilization occurs, with maturation of sperm and oocytes, and extends until implantation of the fertilized egg. From the time of fertilization, this process occurs relatively quickly (up to 9 days in humans) but is characterized by drastic changes developmentally, genetically, and metabolically. The embryonic genome undergoes epigenetic modifications, or alterations to the DNA that do not change the genetic code but rather affect how a gene is expressed by turning expression on or off. These modifications are responsive to environmental conditions and nutrient availability, and likely adapt to promote optimal survival under existing conditions. However, the established gene expression pattern may be detrimental in environmental conditions outside of the uterus, promoting disease development later in life.

Although epigenetic changes can occur throughout one’s lifetime, the periconceptional period is unique in that a small number of cells are present. Full exposure to the environment allows this founder population of cells to establish the genetic program that persists throughout development.

How does this change current practice?

The influence of maternal nutrition during the periconceptional period on disease and development in offspring is not a new concept. Both maternal overnutrition and obesity, as well as undernutrition have been known to adversely affect metabolic regulation in offspring and increase the risk for metabolic disease development.

More recently, analysis from the UK National Diet and Nutrition Survey suggest that less than 10% of women of reproductive age meet the recommended daily intakes during pregnancy for several key micronutrients including zinc, vitamin A, folate, and calcium. Only 30% of women meet the daily intake recommendations for iron. A lack of success of multiple micronutrient supplementation during pregnancy in improving child health outcomes, including survival, growth, body composition, and blood pressure, indicate the importance of correcting such nutritional deficiencies well before pregnancy.

These findings suggest that preconception intervention strategies should include population targeted interventions for women of reproductive age, in addition to those targeting the 3 months before conception. This will allow adequate time to correct for nutritional deficiencies before pregnancy.

By: Sheela Sinharoy, MPH

Sunday began with a symposium titled, Delivering Nutrition Interventions to Women during Pregnancy: Beyond Individual Interventions to Comprehensive Antenatal Guidelines and Care. A series of speakers made clear that as antenatal care (ANC) models continue to evolve, there is plenty of room for improvement to provide a positive pregnancy experience for women and their families.

ANC is not meeting its potential. This was the conclusion of the first speaker, Erica Phillips. She discussed the model of focused ANC (FANC) recommended by the World Health Organization (WHO), which involves 75-80 tasks for an intake visit and 60-65 tasks for each follow-up. She explained that following these recommendations would require an estimated 30-40 minutes for a first visit and 20 minutes for a follow-up. Even when recommended tasks are completed, quality of care may still be low. Ms. Phillips stated that “where FANC has been adopted, success has been limited.”

Still, ANC can be an effective platform for breastfeeding promotion, according to the next speaker, Mduduzi Mbuya. He presented a case study from the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in Zimbabwe. The country faces a critical shortage of health workers, with only 9.8 skilled health workers per 10,000 people (as compared to a ratio of 117:10,000 in the USA). SHINE therefore engaged community-based village health workers and found that the prevalence of exclusive breastfeeding at six months of age increased from 23% to 68%. Dr. Mbuya attributed this result primarily to strong fidelity of implementation by village health workers.

Micronutrient supplementation is another important component of ANC, and Kate Dickin spoke about a trial of calcium supplementation in Kenya and Ethiopia. There, researchers found that women were motivated and willing to take calcium supplements as recommended and that most women sustained their adherence to the supplements through the six-week study period and said they would continue through the end of their pregnancies. Dr. Dickin attributed this largely to the intervention’s behavior change communication strategy, which was based on extensive formative research and addressed context-specific motivators and barriers.

Next, Catharine Taylor spoke about the way forward and the need for integrated, women-centered models of care. She said that ANC models should take the local context into account; have all goods and personnel in same physical space; provide clear and consistent guidelines, training and supervision to health workers; provide demonstrations and encourage active engagement and discussion; provide incentives and support; and implement women-held records and integrated health registers. As examples, she described the Centering Pregnancy model and women’s support groups, which have shown promise in a number of developing country settings.

Finally, Rebecca Stoltzfus closed the session, emphasizing the need for more community-based evidence, especially looking at “packages of ANC that are contextually adapted to be delivered in the most effective ways.” Thus, symposium attendees walked away with a substantial research agenda for the strengthening of antenatal guidelines and care.

 

By Teresa Johnson, MSPH, RD

Robert Waterland, PhD, an associate professor at Baylor College of Medicine, described nutritional influences on human developmental epigenetics. Waterland defined epigenetics as “mitotically heritable stable alterations in gene expression potential that are not caused by changes in DNA sequence.” Multiple factors likely contribute to epigenetic changes, including cytosine methylation, histone modification, auto-regulatory transcription factors, and non-coding RNAs, Waterland pointed out, and they tend to work in a synergistic fashion to influence gene transcription. Waterland said he is particularly interested in DNA methylation because methylation requires dietary donors and cofactors, which is influenced by nutritional factors. He presented data demonstrating that periconceptual maternal nutrition status predicts hypomethylation in a mother’s infant. These changes are stable and maintained over a lifetime, Waterland said, and may point to evidence of metabolic imprinting as an adaptive response to early nutrition.

“We live in a microbial world,” said Dingding An, PhD, a researcher at Boston Children’s Hospital. An elaborated on the role of early life gut microflora in immune system development, and explained that microbial exposure begins at birth and influences our risk for chronic diseases such as inflammatory bowel disease, asthma, arthritis, and autism later in life. Many early-life factors impact the makeup of the gut microbial population in particular, such as nutrition, hygiene, and antibiotic use. An presented data indicating that some gut microbes enhance immune cell maturation and immune response. But the timing of microbial exposure is critical, An added, because later exposure diminishes the response, indicating that key windows of regulation have been missed.

Deborah Sloboda, PhD, an associate professor at McMaster University, provided insights into the impacts of fructose consumption during pregnancy. Fructose is a monosaccharide present in honey, maple syrup, and fruit sugar, and is widely available in processed foods. Fructose consumption differs by sex and age, Sloboda said, with highest consumption reported among lower socioeconomic status females during their reproductive years. This is important, Sloboda said, because “the early-life environment plays a very big role in determining health and disease risk later in life.” Her data from animal models indicate that high fructose intake during pregnancy induces changes in the offspring’s metabolic response. Taurine supplementation reversed fructose-induced adverse metabolic programming, Sloboda said, but not in the presence of a high fat diet, emphasizing the importance of correctly identifying the population in need of intervention.

Growing up in the now well-studied Swedish village Överkalix strongly influenced the research of Lars Bygren, MD, PhD, a professor at University of Umea. Bygren, who addressed the topic of transgenerational outcomes associated with paternal nutrition, explained that human responses to early-life exposures, especially in males, have the potential to impact development for multiple generations. In particular, exposure to high food availability during slow-growth periods negatively affects the health of subsequent generations, and could explain the present day prevalence of many chronic diseases. Byrgen said data from other studies, including the Taiwan betel nut study and the ALSCAP study, lend support to these conclusions.

By Corrie Whisner, PhD

I recently ran across an interesting article in the PLOS ONE journal entitled, “Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex” by Katie Hinde and colleagues at Harvard and Kansas State Universities. After the passing of International Women’s Day on March 8 and recently finishing the book Lean In by Sheryl Sandberg, I felt inspired to share Hinde’s findings and highlight the scientific side of “girl power!”

In this large retrospective analysis of dairy cow lactation records, researchers found that Holsteins produced 1.6% more milk for female versus male offspring. More interesting, is the finding that fetal sex of first-time mothers influenced milk production in subsequent pregnancies.  The advantage of having a female fetus during the first pregnancy carried over to the second pregnancy, resulting in greater milk production across both lactations regardless of whether the second fetus was male or female. The benefit of having a heifer during the first pregnancy was further documented when cows giving birth to a male in their first pregnancy showed significant increases in milk production if their second pregnancy was a female. This increase was evident when comparing data to milk production in dairy cows that gave birth to two consecutive male offspring; however, the milk production of male-female sequence mothers, did not increase to the level of female-first mothers.

According to Hinde, biologists have been interested in studying how mothers differentially allocate resources to male versus female fetuses during pregnancy. To date, little work has been done to investigate sex-biases in milk production which make this article very exciting! Reading this article definitely reminded me of the Barker Hypothesis and the earlier publication Boys Live Dangerously in the Womb, which both provide evidence for fetal programming in humans and suggest that male and female fetuses respond differently in utero to maternal cues.

Maternal milk is an ever-evolving elixir which fuels important changes throughout early development, so it isn’t hard to believe that milk production might differ between species. After reading this article I amazed to learn that mothers may allocate resources, such as milk, to the offspring sex that will receive maximal benefit. A current belief is that males from species with male-male competitive mating rituals will receive a greater investment across gestation and lactation from their mothers. Additionally, Rhesus monkeys have been found to produce energetically-dense milk, higher in fat, for their male offspring; however, female offspring received a greater milk volume which made up for the lack in energetic-density.

As research continues in this area, I wonder if we will start seeing different types of baby formula for boys and girls. Only time will tell…and to that, I say, “Let’s get MOO-ving, so we have more to talk about soon!”

References
1.    Katie Hinde, Abigail J. Carpenter, John S. Clay, Barry J. Bradford. Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex. PLoS ONE, 2014; 9 (2): e86169 DOI:10.1371/journal.pone.0086169
2.    Trivers RL, Willard DE (1973) Natural selection of parental ability to vary the sex ratio of offspring. Science 179(4068): 90–92. doi: 10.1126/science.179.4068.90
3.    Hinde K (2007) First-time macaque mothers bias milk composition in favor of sons. Curr Biol 17(22): R958–R959. doi: 10.1016/j.cub.2007.09.029
4.    Hinde K (2009) Richer milk for sons but more milk for daughters: Sex-biased investment during lactation varies with maternal life history in rhesus macaques. Am J Hum Biol 21(4): 512–519. doi: 10.1002/ajhb.20917

By: Jovana K.

Over the past decade the use of low fat milk has become more prominent than the use of whole milk because there is substantial scientific evidence that consumption of foods high in fat causes weight gain and increases the risk of heart disease and cancer. However, there is some controversy over whether processed low-fat pasteurized milk can meet the needs of developing offspring and whether it should be consumed during pregnancy and development.

Milk Consumption During Pregnancy

Human brain development involves increased incorporation of long-chain polyunsaturated fatty acids (LCPUFA) in brain phospholipids. From the third trimester through to second year of postnatal life LCPUFA (i.e. docosahexaenoic acid (DHA) and arachidonic acid (AA)) are actively incorporated into the developing brain. The proportion of DHA and AA that the infant has reflects the presence of these fatty acids in the maternal diet. Dietary sources of LCPUFA include fish, fish oil and DHA fortified dairy including milk.

Naturally, cow’s milk does not provide a rich source of DHA however in North America whole milk and partially skimmed milk (2%) are fortified with DHA by adding DHA rich feed additive to cattle’s diet. Skim milk or low fat milk (1%) cannot be fortified with DHA because DHA is contained in the milk fat. The DHA-fortified milk products may allow mothers who do not eat large quantities of fish to obtain the levels of DHA that their baby needs for brain and central nervous system development.

Milk Consumption During Postnatal Development

The American Academy of Paediatrics recommends that toddlers drink whole milk because fatty acids are helpful for brain and bone development. However, some doctors recommend low fat or skim milk to overweight or obese children. Whether low fat or skim milk protects children from weight gain is under debate.

According to a cohort study of 12,829 US children aged 9 to 14 years, weight gain is associated with excess calorie intake and consumption of low fat or skim milk, but is not associated with drinking whole milk products. This finding although surprising is consistent with some animal findings. Pigs fed reduced-fat milk gain weight easily while pigs fed whole milk stay lean. Male rats fed whole milk had significantly lower concentrations of plasma triglycerides, very low-density lipoproteins and apolipoprotein B than rats fed low fat milk. The effects of whole milk on lipid profile and body composition are not well understood, but the process of removing fat from milk may in part be responsible for some of the observed effects.

Milk is an emulsion of butterfat globules and water-based fluid. Butterfat contains unique nutrients that support thyroid function and help the body develop muscle rather than fat. The butterfat properties of whole milk are different from that of low fat or skim milk, which may help to explain the effects of whole milk on body composition. Future studies should explore the mechanism by which whole milk may protect infants from gaining weight.