Any breastfeeding, regardless of duration or exclusivity, is associated with lower blood pressure at 3 years of age

Article Title: Breastfeeding in the First Days of Life is Associated with Lower Blood Pressure at 3 Years of Age
Journal: Journal of the American Heart Association
Date: August 3, 2021

Summary:
The results of this large prospective cohort study shows that any amount of breastfeeding ever, including early and limited breastfeeding in the first days of life, is associated with lower blood pressure at 3 years of age - independent of many potential maternal and infant confounding variables. The size of the observed effect in this study is substantial (3.5 mm Hg higher blood pressure in never breastfed children). Given that blood pressure tracks from childhood into adulthood, this finding suggests that supporting the initiation of breastfeeding could have substantial impacts on cardiovascular disease prevention later in life, and that regardless of duration or exclusivity, being breastfed – even if only in the first days postnatal - confers important health benefits.

A novel aspect of this study is that researchers assessed infant feeding in the first days of life, something not typically captured in other birth cohort studies. Using feeding data from hospital records, they included infants who were “ever breastfed”, meaning those who received even a relatively small amount of their mother’s early breast milk (colostrum). Researchers also included infants who were “never breastfed”, meaning there was no attempt to breastfeed while in the hospital or at home, as a comparison group.

Previous studies that have looked at the association between breastfeeding and blood pressure either

• excluded mothers who did not initiate breastfeeding in the hospital (“never breastfed”), or
• excluded those mother/baby dyads that breastfed only during their hospital stay (“ever breastfed”). 

The exclusion of hospital feeding data from previous studies might explain prior conflicting results regarding the association of breastfeeding and blood pressure. The authors speculate this may be due to the potential misclassification of “ever breastfed” infants. For example, researchers in this current study found 98 mothers who reported “never breastfeeding” but had actually provided early, limited breastfeeding during the neonatal period at the hospital. Such a misclassification would not affect results if sustained breastfeeding was required to affect the outcome of interest. But if early and limited breastfeeding is enough to affect the outcome, such as the association with lowered blood pressure at age 3, it’s critical to capture and consider very early feeding.  

Key takeaways/Why this is important:
Evidence suggests that risk factors for poor cardiovascular health (including high blood pressure), trace back to childhood and are influenced by early life exposures. There are many biological reasons why consuming early breast milk (colostrum) during the first days of life could influence cardiovascular health:

• Early breastfeeding strongly affects the colonization and composition of the intestinal microbiome.
  • Early research indicates an altered microbiota may be involved in promoting the formation of plaque in the arteries.
• Nutrients and bioactive components that are enriched in colostrum, such as stem cells and vascular endothelial growth factor, may have long-lasting developmental benefits.
• Colostrum is rich in high concentrations of n-3 long-chain polyunsaturated fatty acids, which are important structural components of the vascular endothelium (inner lining of arteries, veins and capillaries).
• Even relatively small elevations in blood pressure could predispose young children to hypertension later in adulthood.

Implications:
The findings from this study have important implications for individual and public health. The researchers emphasize the importance of prenatal education and immediate postpartum lactation support to help women initiate breastfeeding, so more infants receive colostrum.

This study’s findings are also relevant to health care practice and policy. Hospitals that implement cost-cutting strategies like discharging a new mother within 24 hours of having a vaginal delivery, and eliminating lactation support services on post-partum units, may see short-term savings. However, those savings could be greatly outweighed by the delayed cost burden of future cardiovascular disease. 

Note: many other studies have shown sustained and exclusive breastfeeding confers many more health benefits for both mother and baby. For babies, this includes increased protection against obesity, asthma, Type 1 diabetes, SIDS, ear infections, gastrointestinal distress and more. For mothers, it lowers her risk for high blood pressure, Type 2 diabetes, ovarian cancer and breast cancer. There are also well-documented psychological, neurological and emotional benefits to exclusive and sustained breastfeeding. Current American Academy of Pediatrics recommendations call for exclusive breastfeeding for the first six months, and then continued breastfeeding while introducing complementary foods until 12 months or older.

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The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults.

Miliku, K., Moraes, T.J., Becker, A., Mandhane, P.J., Sears, M.R., Turvey, S.E., Subbarao, P., Azad, M.B., (2021). Breastfeeding in the first days of life is associated with lower blood pressure at 3 years of age. Journal of the American Heart Association, 10(15), e019067 https://doi.org/10.1161/JAHA.120.019067

Title: The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences
Journal: American Journal of Obstetrics and Gynecology
Date: May 2022

Most women in the United States do not meet the recommendations for healthy nutrition and weight before and during pregnancy. Women and health care providers often ask what a healthy diet for a pregnant woman should look like. The topic has been the subject of much debate and has produced inconsistent and sometimes confusing advice for pregnant women who are trying to do the right thing.

In a new paper, three OHSU researchers, along with 12 other national and international researchers, came to consensus about nutrition in pregnancy and during breastfeeding. The paper was birthed, so to speak, out of a 2019 Nutrition in Pregnancy conference, hosted by the OHSU Bob and Charlee Moore Institute of Nutrition & Wellness. The paper, The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences, was published May 6, 2022 in the American Journal of Obstetrics and Gynecology.

Incredibly, before 2020, dietary guidelines did not include pregnant or breastfeeding women – or infants under the age of two. That changed in 2020, when both the USDA and National Institutes of Health (NIH) included guidelines and recommendations for infants, toddlers and pregnant women. This paper was authored just prior to those changes being announced, and the findings and recommendations are consistent with the new guidelines. 

Consensus points
The authors arrived at ten points of consensus about nutrition in pregnancy and lactation:

1. Comprehensive improvements in the nutritional and health status of women before and during pregnancy, will contribute to optimal fetal growth, better outcomes in childbirth, improved perinatal survival, and the potential for better long-term health in both the mother and child.
    
2. Low birth weight, small and large for gestational age, fetal growth restriction and other abnormal growth patterns are associated with poor maternal nutritional status.
    
3. Dietary patterns of pregnant adolescents are generally less healthy than adult pregnant women. This, during a critical time for their own nutritional status, indicates the need for enhancing diet quality among young pregnant mothers.
    
4. There is an association between healthy dietary patterns before and during pregnancy, and a reduced risk for disorders such as gestational diabetes, preterm birth, obesity-related complications, and in some populations, preeclampsia and high blood pressure. Nutrition therapy is used to treat gestational diabetes and is especially important for pregnant women with obesity who have undergone bariatric surgery or who have preexisting diabetes.
    
5. Nutritious diets include ample quantities of vegetables, fruits, whole grains, nuts, legumes, fish, oils enriched in monounsaturated fat, and fiber — and are lower in fatty red meat and refined grains. Furthermore, healthy diets avoid simple sugars, processed foods, and trans and saturated fats.
    
6. A diet that consistently and substantially restricts any macronutrient should be avoided during pregnancy. Fad diets may be especially harmful during pregnancy because of the resulting nutrient imbalance, nutrient deficiencies or ketosis.
    
7. The best time to improve nutrition and BMI is before becoming pregnant. However, having weight gain goals during pregnancy may be more feasible for some women. That would mean limits on foods with empty calories and calorie dense foods may be more achievable. Growing evidence indicates that BMI before pregnancy does affect the degree of influence that gestational weight gain has on pregnancy complications.
    
8. Breast milk is uniquely suited to meet the nutritional needs of normal infants born at term for the first 4 to 6 months of life, and its consumption during infancy is associated with lower risks of chronic disease in later life. Breast milk composition is influenced by what the mother eats, and her adipose nutrient stores. Among women with gestational diabetes, there is evidence that exclusive breastfeeding for at least 6 months decreases the risk of Type 2 diabetes for the mother and is protective against the risk of childhood obesity in her offspring.
    
9. Regularly consuming multivitamin and mineral supplements that contain optimal amounts of folic acid, among other micronutrients, is recommended for all reproductive-age women to augment a balanced diet, starting at least 2 to 3 months before conception and continuing throughout pregnancy until she stops nursing, or at least 4 to 6 weeks after delivery. Women who become pregnant after bariatric surgery need additional supplements and close monitoring before and during pregnancy.
    
10. It is imperative that healthcare providers have the time, knowledge and means to discuss optimal nutrition — and provide educational support to women of reproductive age to improve their health before, during and after pregnancy.

Eat better, not more
The author’s core message, “eat better, not more,” can be achieved by eating a diet based on a variety of nutrient-dense, whole foods that include fish, fruits, vegetables, omega-3 fatty acids and whole grains — in place of poorer quality, processed foods and beverages — to enhance nutritional quality without excessive energy intake.

Nutritional requirements vary by each mothers’ individual characteristics, and in addition to considering dietary quality before pregnancy — factors such as maternal body size, age, gestational age, number of pregnancies, activity level and medical conditions — should be considered. The USDA provides interactive online tools for health professionals to tailor dietary recommendations for women before and during pregnancy — and the MyPlate interactive tool that women can use to plan their diets.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults.

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N.E. Marshall, et al (2019). The importance of nutrition in pregnancy and lactation: lifelong consequences. Am J Obstet Gynecol, 226(5), pp. 607-632
https://doi.org/10.1016/j.ajog.2021.12.035

Lessons learned from 25 years of research into long-term consequences of prenatal exposure to the 1944-1945 Dutch famine

Journal: International Journal of Environmental Health Research     
Date: May 2021

The Dutch famine, also known as the Dutch Hunger Winter, occurred in The Netherlands at the end of World War II. The Nazis had cut off food supplies to the western part of The Netherlands in retaliation for the exiled Dutch government supporting the Allies. Some twenty thousand people died and 4.5 million were affected by the direct and indirect consequences of the famine, which took place from November 1944 through May 1945. In addition to an exceptionally harsh winter, bad crops, and four years of brutal war, the population was forced to live on rations of 400-800 calories per day. People had to eat grass and tulip bulbs to survive.

This article reports on the lessons learned from 25 years of research into the long-term health effects the famine has had on those who were in utero during the time it occurred. This group is called the Dutch Famine Birth Cohort. Studies have also focused on the children of this cohort, and their grandchildren.

 Several factors allowed researchers to study the effects of this tragic event in great detail:

• There was a sudden onset and rapid relief from the famine (well defined time period).
• It was imposed on a previously well-nourished population.
• Food availability was registered accurately throughout the famine.
• Midwives and doctors continued to provide obstetric care and kept detailed medical records throughout the famine, some of which have been kept for decades – allowing long-term, follow-up studies.

Summary
Prenatal exposure to the famine had permanent effects on health outcomes that emerged later in life among the offspring.  People who were in utero during the famine suffered a variety of physical and mental health issues as adults. The two main lessons reported out in this journal article were:

1) There were effects of prenatal famine exposure in the absence of effects on body size at birth. In other words, in spite of adaptations that enable the fetus to grow to a normal size during famine, undernutrition still had adverse, long-term health consequences.

2) The effects of undernutrition in the womb depended on the timing of when organs and systems were developing.

• The effects on health later in life were most pronounced among those exposed to famine in early gestation. This may not be surprising considering the fact that all organs are laid down in early pregnancy. An insufficient food supply in early gestation interferes with basic organ development.  
• Exposure to famine in mid gestation was linked to an increase in micro-albuminuria in adulthood (an early sign of vascular disease) and a decrease in creatinine clearance (waste filtered from the blood by the kidneys and excreted in urine). These are both factors that signify an elevated risk for heart and kidney disease. Mid gestation is when the number of filtering units (nephrons) in the kidney rapidly increase, and exposure to famine in mid-gestation prevented robust kidney development. Mid gestation is also the time when lungs are developing and the bronchial tree grows most rapidly. Those exposed to famine in mid gestation had an increased prevalence of obstructive airways disease. Studies of the Dutch hunger winter provide another layer of evidence that undernutrition in the womb permanently affects the structure and physiology of the lungs and kidneys.

Other findings (not exhaustive)

• Males and females exposed at any stage in utero put them at higher risk for type 2 diabetes and heart disease.
• Exposed females grew up to have more children, give birth to twins more often, be less likely to remain childless and start having children at a younger age than unexposed females.
• Females exposed in early gestation had an increased prevalence of breast cancer, higher cardiovascular mortality, cancer mortality and breast cancer mortality.
• At age 63, women (but not men) exposed to the famine in early gestation had an overall higher mortality rate compared to unexposed 63-year-old women.
• Children whose mothers were in utero during the famine were heavier at birth, while those whose fathers were exposed in utero were heavier in adult life – suggesting different epigenetic influences according to the sex of the parent. 
• At age 58, both men and women exposed to famine in early gestation had poorer cognitive function.
• Males exposed to famine in early gestation had a higher risk for neurodegenerative diseases.
• Males exposed to famine in early gestation reported more symptoms of anxiety and depression.

Key takeaways/Why this is important:
This paper provides a long-term view of the consequences of undernutrition during pregnancy by studying the effects of the Dutch famine for decades. The findings can be used to provide guidance on preventive strategies and remedial actions today. The authors argue we should prioritize a more equal distribution of food across the world so that the consequences of poor diets due to both undernutrition and overnutrition will be prevented, and that priority should be given to women of reproductive age. Based on the findings presented in this review, the authors expect that adequately feeding women before and during pregnancy will allow future generations to reach their potential and lead healthier and more productive lives - ultimately leading to a healthier and more equitable future.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults.

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De Rooij, SR, Bleker, LS, Painter, RC, Ravelli, AC, & Roseboom, TJ (2021). Lessons learned from 25 Years of Research into Long term Consequences of Prenatal Exposure to the Dutch famine 1944–45: The Dutch famine Birth Cohort. International Journal of Environmental Health Research, Retrieved online DOI: 10.1080/09603123.2021.1888894

Study shows when moms with asthma breastfeed longer, their babies are less likely to wheeze

Article Title: Breastfeeding, Maternal Asthma and Wheezing in the First Year of Life: A Longitudinal Birth Cohort Study
Journal: European Respiratory Journal  
Date: May 1, 2017

Summary:
Researchers sought to understand the impact breastfeeding has on respiratory health, particularly when the mother has asthma. The study involved 2,773 mother-infant pairs, grouped into one of three groups: exclusive breastfeeding, no breastfeeding and partial breastfeeding. The partial breastfeeding group was broken down into two sub groups: those who supplemented with formula and those who supplemented with complementary foods. Caregivers then reported on infant feeding and wheezing episodes at three, six and 12 months of age.

For the mothers who had asthma (21%), infant wheezing was reduced by breastfeeding. These results were independent of maternal smoking status, education level and other risk factors.

The group that exclusively breastfed for six months saw wheezing reduced by 62%, when compared to the no breastfeeding group. Babies in the partial breastfeeding group that supplemented with complementary foods showed infant wheezing was reduced by 37%, when compared with no breastfeeding. However, when infant breastfeeding was supplemented with formula, there was no significant protection against wheezing – in spite of having been partially breastfed.

Key takeaways/Why this is important:
Wheezing is one of the most common reasons infants see a healthcare provider or are hospitalized. Early wheezing is a risk factor for asthma and chronic obstructive pulmonary disease later in life. Even transient wheezing is associated with reduced lung function and increased asthma risk in adolescence. Finding ways to prevent or reduce early wheezing is an important public health priority.

This study strengthens the evidence that breastfeeding provides protection against wheezing in early life and identifies new information:

• The longer and more exclusive the mothers breastfed, the stronger the protection from wheezing. This was especially true if the mother had asthma herself.
• An unexpected finding was that breastfeeding is more protective against wheezing in male infants. Being born male is a well-known risk factor for infant wheezing, which highlights the importance of considering sex differences in breastfeeding research.
• If babies were fed complementary foods before six months of age, partial breastfeeding was a little more than half as protective against wheezing as exclusive breastfeeding.
• If babies were fed supplemental formula before six months of age, the benefits of partial breastfeeding did not confer significant protection against wheezing.

Breastfeeding is an effective way to prevent infant wheezing and promote lifelong respiratory health. This study contributes to the growing base of knowledge about the multiple, substantial health benefits it confers.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults.

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Azad MB, Vehling L, Lu Z, et al. Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study. Eur Respir J 2017; 49: 1602019 [https://doi.org/10.1183/13993003.02019-2016].

Study Shows Housing and Hunger are Linked

Journal: Journal of the Academy of Nutrition and Dietetics
Date: August, 2020 

Summary: The study used longitudinal data from the Fragile Families and Child Wellbeing Study. This study monitored 4,898 children born between 1998 and 2000 in 20 U.S. cities. Interviews with mothers and fathers were conducted at birth, and when the child was one, three, five, nine, and 15 years old, as well as in-home assessments at ages three and five. The study used data from birth interviews, and the in-home assessments at ages three (referred to as Wave 3) and five (referred to as Wave 4) to examine the relationship between food insecurity and housing instability. Both food insecurity and housing instability are associated with negative health outcomes in children and adults. The authors found that families who experience food insecurity are at increased risk of experiencing housing instability, and vice versa, which they refer to as a bidirectional relationship. They also found that families who experienced both food insecurity and housing instability were more likely to be racial/ethnic minorities and more socioeconomically disadvantaged.

Key takeaways / Why this is important: 
Intervention programs are generally designed to focus on one issue. For example, the Supplemental Nutrition Assistance Program (SNAP) aims to reduce food insecurity and provide access to healthy foods. Given the bidirectional relationship between food insecurity and housing stability identified in this study, would a holistic approach be more effective? For example, families who qualify for SNAP could automatically qualify for a Low Income Home Energy Assistance Program, or something similar. Such comprehensive approaches could allow more space for addressing the stress and mental health impacts associated with both food insecurity and housing instability, which are known to impact long-term health. 

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

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Lee CY, Zhao X, Reesor-Oyer L, Cepni AB, Hernandez DC. (2021) Bidirectional Relationship Between Food Insecurity and Housing Instability. J Acad Nutr Diet. Jan; 121(1): 84-91. https://doi.org/10.1016/j.jand.2020.08.081. Epub 2020 Oct 12. PMID: 33060025. 

Neighborhood provides the environment for pregnant mothers

Journal: Environmental Health Perspectives
Date: March 2012

Summary
Where a woman lives during her pregnancy can have consequences for her baby. At the OHSU Moore Institute, we often say, “while the mother is the environment for the baby, society is the environment for the mother.” In essence, the mother’s surroundings have a profound effect on her stress levels and her ability to access healthy opportunities , as she carries and grows the next generation. This research brief is about a study showing a direct link between the built environment where women lived while pregnant, and the birthweight of their babies.

Birthweight is important, because DOHaD science has shown the link between low birthweight and an increased risk for chronic disease later in the baby’s life. In other words, the quality of a woman’s surroundings during pregnancy can predict health risks in her baby - the next generation.                                   

In 2008, a group of researchers set out to investigate the relationship between the quality of a residential area and negative birth outcomes. The study combined data from direct observations, tax assessment information, public safety reports, vital records, and U.S. Census data, and overlaid that onto 17,000 tax parcels within 873 blocks of an area in Durham, North Carolina. The researchers identified seven categories of important residential features, with variables in each category, to describe residential quality.

Features of residential quality:

housing damage: roof damage, broken windows, peeling paint, fire damage, boarded window or door, etc.

property disorder: discarded furniture, no grass, high weeds, standing water, discarded tires, cars on lawn, etc.

security measures: security bars, beware of dog signs, barbed wire, no trespassing signs, etc.

tenure: proportion of renter or owner-occupied housing

nuisances in public spaces: shopping carts, litter, discarded appliances, diapers, cigarette butts, fallen wire, condoms, batteries, alcohol containers, etc.

vacancy: proportion of vacant housing

crime rate: theft, property crime, vice, violent crime, etc.

A score was generated for each of the residential categories, using statistical analysis to rank the many variables within each category. The more instances of a variable, the higher the score. For tenure, the more rentals meant a higher score.

Birth outcomes of interest
Researchers were interested in five adverse birth outcomes. Three of these are well known: preterm birth (less than 37 weeks), small for gestational age (less than 10^th percentile of birthweight for gestational age), and low birthweight (less than 5.5 pounds). The other two outcomes were for a continual scale of fetal weight, which is a more precise way to determine weight for gestational age. For brevity, this research brief will only summarize the first three outcomes listed here.

All the information was gathered through anonymous public records. Researchers used National Center for Health Statistics for to gather information on singleton births during 2000-2004. They then sorted the births that occurred between 20-44 weeks’ gestational age by sex (males and females grow differently). They also collected data on the mothers’ ages, which birth this was for them, their level of education and marital status, as well as their race and ethnicity. Ultimately, they analyzed 4,279 birth records for this study.

What they found
All categories of residential quality were associated with preterm birth, small for gestational age and low birthweight babies. However, there were some maternal characteristics that confounded the results – meaning researchers couldn’t be confident other life factors such as educational level or age were partly responsible for the results. So, they adjusted the results for maternal factors and found the following:

• Preterm birth (PTB):
  Living in an area with high amounts of housing damage, property disorder, nuisances, tenure (rental units) and vacant housing remained associated with PTB. However, only tenure (high number of rentals) remained statistically significant. No associations between crime or security measures and PTB were observed.
• Small for gestational age (SGA):
  As with PTB, living in an area with high amounts of housing damage, property disorder, nuisances, rentals and vacant housing were associated with SGA. After adjusting for maternal factors, housing damage remained statistically significant. No associations between crime or security measures and SGA were observed.
• Low birthweight (LBW):
  Living in an area with more property disorder, rentals, vacancies and nuisances was associated with lower birthweight babies. Living in residential areas with more housing damage showed an enduring statistically significant link to LBW in both the unadjusted and adjusted analysis. Again, no associations between crime or security measures and LBW were observed.

Tying it all together
This study suggests a very real and meaningful relationship between the location where a woman experiences her pregnancy, and the outcomes of that pregnancy. The built environment surrounding pregnancy contributes to health disparities by way of birth outcomes. This relationship may seem obvious enough, and now it’s backed by research studies. This is by far not the only study to analyze the way in which the built environment impacts health. The physical environment is a leading determinant of individual and community-wide health and can predict health disparities and inter-generational health.                                                                                   

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

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Miranda, M.L., Messer, L.C., Kroeger, G.L., (2012). Associations between the Quality of the Residential Built Environment and Pregnancy Outcomes among Women in North Carolina. Environmental Health Perspectives, March; 120(3): CID: https://doi.org/10.1289/ehp.1103578 

Low birthweight babies carry unique risks

Journal: Clinical Journal of the American Society of Nephrology
Date: January 2009

Summary
Kidneys are truly amazing. Within each one there is a world with millions of tiny filtering units called nephrons. These complex and delicate workhorses filter our blood and help remove waste and excess fluid from our bodies. Every day about 200 quarts of blood pass through our nephrons. The blood is filtered, cleaned and returned to our bloodstream. All except about two quarts, that is, which gets excreted as urine. Babies who are born small, whether premature or full-term with a low birthweight, have fewer of these filtering units. This puts them at risk for kidney disease later in life. However, there are ways to protect every precious nephron at birth and into childhood.

Nurturing our nephrons
Groups of nephrons develop much like onions do, in layers. This means that newly formed nephrons are on the outer layer, while the more developed nephrons become embedded deeper inside. Once the layering stops, at about 35 weeks gestational age, no new nephrons can be formed in our lifetime. Postnatal kidneys continue to grow larger to match our body size, as do nephrons, but the total number stays the same. In the editorial, Developmental Origins of Renal Disease: Should Nephron Protection Begin at Birth?, author and nephrology specialist Susan Bagby, M.D. applies a DOHaD framework to make the case that it should. Since nephron number is proportional to birthweight, the first clinical clue to a reduced nephron endowment is whether the baby is premature or small at birth. And if care is taken to nurture those newborn nephrons through the first minutes, days, weeks and months, it can make a difference. 

Low birthweight implications
Premature and low birthweight babies are born with fewer layers of nephrons. This has implications for kidney disease later in life, as it sets the stage for a mismatch between body size and the kidney’s functional capacity. Over time, this causes a progressive loss of nephrons because of that mismatch. If a person’s body size increases to an extent that stresses the kidneys’ ability to handle the increased filtering load, it creates heightened pressure inside the nephron’s complex structure. This slowly damages and scars the nephrons over time. Low birthweight babies tend to grow rapidly in early childhood, and have an increased risk for being overweight and obese. Overweight and obesity increases their risk for kidney disease even more, because of the increased mismatch between kidney function and body size. It’s important to remember that this represents increased vulnerability to disease, and not actual disease per se. There are always opportunities in life to improve a person’s health.

Post-natal opportunities for protecting at-risk kidneys
Bagby points out there are postnatal opportunities to protect and help the kidneys of premature and low birthweight babies:

• In premature babies (< 35 weeks), nephrons may (but do not always) continue developing for up to 40 days after birth, even if they never reach what would be considered normal levels. This potential for postnatal growth should be nurtured as much as possible by identifying what might harm or help the developing nephrons in the earliest days of life. The Neonatal Intensive Care Unit (NICU) experience, while critical for survival, is fraught with frequent exposures that are toxic for the kidneys. Many standard interventions were developed before there was an awareness of the potential for their effects on newborn kidneys. This topic needs to become a part of the training for neonatologists. In addition,  determining the optimum levels of macro- and micro-nutrients that would support postnatal nephron growth while in the NICU should be a high priority for the research community.
• Another potentially critical period of kidney growth occurs during the first 18 months of life. Normally, kidneys continue to grow in size in relation to a person’s body size, even while nephron numbers remain set. However, kidney growth during this time period may remain poor in low birthweight and premature babies. So not only are they born with smaller kidneys, the kidneys may not grow as well as they should in the first 18 months of life. Understanding why this happens could reveal opportunities for early therapeutic interventions.
• A third period warranting attention is when low birthweight babies rapidly gain weight in later childhood and adolescence. This accelerated growth often leads to obesity. Slowing and normalizing growth in childhood may not only prevent obesity, but it may prevent or delay the onset of kidney disease in those who are at risk. 

Bagby suggests a combination of early intervention strategies for at-risk newborns would be reasonable, including:

• Adding birthweight and gestational age to the standard clinical history
• Monitoring for signs of kidney dysfunction from birth (high blood pressure, urine protein, serum creatinine)
• Educating parents and adult patients about their unique risks and the benefits of favorable lifestyle practices

While there are other known and unknown factors that affect kidney development, it’s clear that premature and low birthweight babies carry a unique risk for kidney disease later in life because they are born with fewer nephrons. This is a powerful case for addressing nephron protection at birth and throughout childhood, before kidney disease develops. Favorable lifestyle practices, combined with identifying and monitoring clinical symptoms, can help protect nephrons and optimize kidney health throughout life.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

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Bagby S.P., (2009). Developmental origins of renal disease: should nephron protection begin at birth? Clin J Am Soc Nephrol, Jan;4(1):10-3. PMID: 19129313. Retrieved from DOI: 10.2215/CJN.06101108

Lessons from the Dutch Hunger Winter

Journal: Placenta
Date: May 2011

Summary
During World War II, food supplies became increasingly scarce in The Netherlands as the nation plunged into an unusually harsh winter. Then, in November 1944, the Germans retaliated against the Dutch for a failed attempt to stop the transport of Nazi troops by rail. The Nazis blocked food and fuel supplies to western Holland, resulting in severe hunger and starvation for 4.5 million people. This is known as the Dutch Hunger Winter, or the Dutch Famine. Somewhere between 18,000 and 22,000 people died of starvation by the time food supplies were restored in May of 1945, when allies liberated The Netherlands. Many more were severely malnourished - including women who were pregnant, or about to become pregnant.   

Dutch medical professionals documented the course of women’s pregnancies with great detail, including mothers’ weight and blood pressure, the weight and size of babies and placentas at birth, the length of umbilical cords and written descriptions of labors and deliveries. The babies born from these mothers are known as the Dutch Hunger Winter cohort. Many studies have followed the famine’s effects on the health of the cohort throughout their lives. The subject of this research brief is how placentas responded to the famine during different stages of pregnancy.  

In a study entitled Effects of famine on placental size and efficiency, the authors collected data from the cohort birth records to gain a better understanding of how the placenta responds and adapts to famine.  
 
Key findings: 

1. Overall, babies that were either conceived during the famine or who were already in utero, had smaller placentas, were shorter, thinner and had smaller head circumferences at birth than those born before the famine. The reduced placental size changed the ratio of baby weight per gram of placenta, which is considered the measure for placental efficiency – or how well it’s doing its job. Depending on the stage of pregnancy during the famine, the placenta became either more or less efficient as a result.

2. In early pregnancy, the famine affected the way the placenta implanted into the womb, impairing the placenta’s ability to establish adequate blood vessels for nutrient and oxygen supplies to the fetus. In response, the placenta stayed small relative to the size of the fetus. This suggests the placenta adapted by becoming more efficient as a result of exposure to famine during the early stage of pregnancy.

3. Babies that were in mid or late pregnancy during the famine were smaller at birth in relation to the size of the placenta, than babies born before the famine. This suggests that the placenta became less efficient as a result of exposure to famine during mid or late pregnancy.

4. There were sex differences in placental response to the famine. Among boys, famine during early pregnancy resulted in smaller placental size and thickness, suggesting the implantation process was impaired. In girls, thickness increased during late pregnancy. The authors speculate that the increased thickness is an attempt to compensate for reduced growth, by burrowing deeper into the utero-placental arteries for more nutrients. 

5. Women who lived through the famine and conceived a child afterward, also had reduced placental size and thickness, for up to 18 months post-famine (the end of the study period). Their placentas were also more oval shaped than those of babies born before the famine, suggesting implantation was impaired for some time after having been exposed to famine. The authors note this oval shape is similar to placentas from preeclamptic pregnancies – a disorder initiated by impaired implantation.   

Making sense of it
The placenta is one of the most important organs in the body. During pregnancy, it carries oxygen and nutrients to the fetus, provides immune system protections, secretes hormones and discards waste. It grows and functions in response to available nutrition, and changes size and shape depending on the mother’s nutritional status.  

We know that boys and girls differ in the way they grow in the womb. The findings from this study are consistent with the hypothesis that the growth of boys in the womb depends more on the immediate maternal diet than does the growth of girls. This is because boys grow as fast as possible over the course of pregnancy with as little placental tissue as possible, making them more vulnerable if their nutrition is compromised.  Girls are more influenced by maternal metabolism and make a larger investment in placental growth.  

Putting all of this into context with other information gathered from the Dutch Hunger Winter cohort, researchers are now able to better predict health outcomes of babies born from pregnancies with altered placental function as a result of nutritional deprivation. The findings of this study contribute to our understanding of placental health, maternal-newborn health and the long-term effects of nutrition. It demonstrates that the placenta is a key organ in the life of every individual and clearly shows the need for a nutrient-rich diet for women during pregnancy.    

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

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Roseboom TJ, Painter RC, de Rooij SR, van Abeelen AF, Veenendaal MV, Osmond C, Barker DJ. (2011). Effects of famine on placental size and efficiency. Placenta, 32(5):395-9. PMID: 21435715. Retrieved from https://doi.org/10.1016/j.placenta.2011.03.001

Analyzing policies through a DOHaD lens

Journal: International Journal of Environmental Research and Public Health
Date: December 2018

Summary
Public health policies are designed to improve community health and safety in ways that benefit every person. These policies have the potential to address structural inequities in society, which are some of the most important determinants of human health.  What if we were to analyze the impact policies have on human health, using a Developmental Origins of Health and Disease (DOHaD) lens? This is what researchers did, in a 2018 commentary in the International Journal of Environmental Research and Public Health.

The authors chose three areas of policy that have the potential to affect early life experiences so significantly that they could improve the lifespan trajectory of future generations: family leave, sugar sweetened beverage taxes and housing policies. They synthesized evidence related to these policies and examined the health implications for multiple generations.

Findings
Paid family leave (PFL): These policies have the most direct implications for intergenerational health. PFL is associated with lower levels of job turnover, long-lasting mental health benefits for mothers and decreased stress levels during pregnancy. Decreased stress can result in augmented growth of babies and newborns and a decrease in preterm births. Birthweight is an indicator of fetal development, and low birthweight leads to intergenerational, chronic health consequences.

The evidence showed that children of adults who had access to PFL were more likely to be breastfed and immunized, had higher quality mother-infant interactions and attachment security, better short-term developmental outcomes and lower infant and child mortality. The authors noted that these effects could be amplified due to the benefits of breastfeeding, which are numerous and long lasting. Breastfeeding reduces the likelihood of many chronic diseases as well as attention-deficit disorder, hearing problems, frequent ear infections and of being overweight.

Sugar sweetened beverage (SSB) taxes: These are implemented to change dietary behavior in order to improve both individual and public health, by making the drinks more expensive to buy. SSBs offer no nutritive benefit and add a large number of empty calories to the diet. The authors note that SSB consumption is highest among adolescents, a critical time in a person’s development, and that drinking SSBs is associated with higher obesity and diabetes risk in children and adults. SSB consumption in pregnancy is associated with adverse birth outcomes that alter lifelong disease risk in offspring.

The authors noted that in order to apply the DOHaD lens to the effects of SSB tax policies in pregnancy, we would need to know more about the intergenerational effects of consuming SSBs before, during and after pregnancy – as well as the consumption by fathers.  This information is not currently available.  However, there are several models around the world that simulate the effects the tax would have at a population level. For example, a simulation built on observed reductions in consumption following Mexico’s SSB tax, predicted a 2.5 percent reduction in obesity after ten years, and prevention of at least 86,000 cases of diabetes by 2030.

Housing policies: These have direct and indirect effects on health, and housing is recognized as a main social determinant of health. Where you live determines your education and your economic opportunities. It determines your stress levels, your transportation options and whether you have access to nutritious food. It determines your access to healthcare, your safety and your early life exposures. Housing policies that offer assistance, like rental vouchers and housing subsidies improve lives, fight poverty and create upward mobility. Other policies that impact housing, such as economic development policies, show mixed results depending on your race and ethnicity.

Even the risk of foreclosure or the threat of eviction can cause mental and physical health problems. Applying the DOHaD lens to housing policies like subsidies or vouchers, the authors found a link between women who had to move out of public housing or who had housing instability, and an increased risk for preterm low birthweight. They note the literature rarely extends to the potential effects on pregnancy and fails to take into account the long-term health implications that birth outcomes set in motion.

Recent work exploring the effects of neighborhood gentrification found that among non-Hispanic Black women, very high levels of gentrification were linked to increased preterm birth, compared to those experiencing low levels of gentrification. However, for non-Hispanic white women, living in a very highly gentrified neighborhood had a protective effect against preterm birth. From a DOHaD perspective, urban renewal that results in the displacement of pregnant women will likely affect the children by increasing the likelihood their babies will be born too soon or too small, both of which sets the trajectory for poor health over the life course.

DOHaD researchers are gaining clear insight to the expected 100-year health effects caused by poor nutrition, unaffordable or unsuitable housing, gender-based violence, racism, poverty, lack of education or work opportunities and other adverse events in peoples’ lives. The authors make a case for using a Health Impact Assessment-type approach to policy-making, using the DOHaD lens to clarify potential effects that policies might have on women of reproductive age. Using this approach, public health would have a more precise tool to evaluate the multi-generational effects of policies, and provide recommendations to decision-makers as they consider which policies to adopt and implement to improve public health.  The OHSU Bob and Charlee Moore Institute of Nutrition & Wellness supports this approach to policy making in the interest of improved health for all Oregonians.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

_________________________________________________________________________________________________________________________

Goodman, J., Boone-Heinonen, J., Richardson, D., Andrea, S., & Messer, L. (2018). Analyzing Policies Through a DOHaD Lens: What Can We Learn? International Journal of Environmental Research and Public Health, 15(12), 2906. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijerph15122906

Why our social environment matters

Journal: Obstetrics and Gynecology Clinics of North America
Date: March 2020

Summary
At the moment of fertilization, an embryo immediately begins sensing for nutrients in the surrounding environment. As it makes its way to the womb, big structural changes are already occurring in order to create the only organ to last just nine months: the placenta. Once the fertilized egg embeds itself into the uterine wall, the placenta begins to immediately send out roots that find and reshape blood vessels in the womb, seeking to connect itself to the mother and invade her arteries for nutrients that will help it grow, mature and nurture the new fetus.  

Within those nine months, the placenta provides all of the nutrient building blocks to create a new human being. Yet we actually know very little about it. It’s usually an afterthought – the afterbirth – something discarded and forgotten about. It turns out that growing an entire organ during pregnancy   reveals a lot more than we previously knew. Most importantly, it determines how well the baby grows and is nourished. But more than that, there are numerous factors that help or hinder its ability to do its job – and many of these are related to the social environment of the mother. 

A 2020 journal article titled Social Determinants of Placental Health and Future Disease Risks for Babies, the authors propose that the social conditions a mother experiences before and during pregnancy affect the developing baby by way of the placenta. Their whole premise is that the placenta is far more affected by a woman’s social environment than we thought, and therefore the health of her baby - and future generations - are too. We’re learning that the placenta is exquisitely sensitive to everything happening in a woman’s life - from her nutritional status, to her relationships, economic status, chemical exposures and psychological state of mind. In short, her stress levels. 

Mom’s environment is society. Where she lives, plays, gets her food, and where she goes to work and school. How a mother thrives determines how her baby thrives – and we all want the best for our babies. All human beings should have nutrient-rich diets, low stress levels, economic stability, clean air to breathe and clean water to drink. This is especially important for pregnant women, because their health and well-being determines the health and well-being of future generations.  

 But that’s not the reality for an untold number of women. The social stresses many women face during pregnancy include poverty, lack of social support, domestic violence, racism, misogyny, housing insecurity, crime, environmental pollution and hunger. What happens when mothers lack the social and physical support they need? They suffer. This means their babies suffer too, and their growth, development and long-term health are compromised because of it.   

When a mother is stressed, she releases the well-known hormone cortisol. Cortisol stimulates the placenta to increase production of its own stress hormone, which rises in step with mom’s cortisol production. Nature does have a built-in protection, however. The placenta has the ability to chemically neutralize cortisol to its inactive form, called cortisone. However, this protective mechanism can get overwhelmed under extremely stressful conditions. When this happens, cortisol makes its way through the placenta to the baby. Cortisol inhibits fetal growth, so even babies born at full term to highly stressed mothers can be small. We know that babies who are born at the low end of the birthweight scale have a higher risk for developing heart disease, type 2 diabetes, obesity and other diseases later in life.  

In addition to cortisol, environmental contaminants can cross the placenta and cause problems. These exposures are responsible in part for preterm births because the placenta’s protective mechanisms get overwhelmed and compromised by inflammatory processes. Chemicals in cigarette smoke, heavy metals, fine particulates in the air, plasticizers, pesticides and other contaminants do more damage when they are combined with high stress levels – something called a synergistic effect. 

Toxic stress also contributes to several medical conditions that can lead to placental abnormalities. Conditions like maternal obesity, gestational diabetes, preeclampsia and a disturbed maternal microbiome. The microbiome, an ecosystem of some 100 trillion microorganisms living in our intestines, plays a large role in physical and mental health. A mother’s microbiome can be diminished by a number of stressors, which in turn affects her digestion and the transfer of beneficial bacteria to her baby.  

Over the last three generations, the health of the US population has worsened. We’ve become more vulnerable to diseases like heart disease, type 2 diabetes and obesity. What is behind this trend? Social factors known as the social determinants of health. They include things like social and community context, economic stability, the built environment, educational attainment, and health and health care. All of these are largely determined by where you live – in other words, your zip code. Not having access to these basic needs creates a chronic stress response with direct biological implications. Social stressors contribute to the diseases we mentioned above, in very pervasive ways. Think of all the pregnant women in our society who are experiencing toxic levels of stress, and how this epidemic of stress is harming not only this generation, but the future health of our society.   

Many social determinants of health overlap and intersect. Let’s look at five of them, through the lens of a pregnant woman:

• Social Context: This is critical for a pregnant woman’s well-being. It can include the support network she has, whether she has child care for her other children, if she’s in a healthy relationship with the father and others, and if she’s experiencing injustices like violence, racism, misogyny and crime. Feeling unsafe and unprotected while pregnant is extremely stressful. This can be an exceptionally vulnerable time in a woman’s life.  

• Economic stability: This translates directly into things like where you can afford to live, what food you have access to, whether you have transportation options or if you can take sick days. When a pregnant woman has limited income and financial support, she may have a limited food budget, and be more likely to eat low-cost, processed foods. Fresh, whole foods may be unavailable or too expensive. We know that poverty and obesity are linked - and maternal obesity is associated with gestational diabetes, preeclampsia and cesarean sections. Maternal obesity also affects placental growth and function, and puts the developing baby at higher risk of childhood obesity and carries other metabolic and behavioral consequences. 

• The built environment: Where she lives can determine whether a mother is exposed to toxic pollutants, and the quality of air and water she has. It determines where and how she gets her food, the quality of her food and whether it’s safe to exercise outdoors and maintain healthy social connections with people in the community. It also determines her exposure to the stressors of crime, violence, excess noise, trash and having to be on guard for fear of being violated.  

• Education: A mother’s level and quality of education intersects with her economic stability, health, social context and built environment. Lacking basic knowledge or the ability to reason and be self-aware are tied in with educational attainment and the kinds of social skills that improve health. Studies show that higher academic achievement is associated with increased health behaviors and lowered risk behaviors. We also know the more educated a woman is, the healthier her children are likely to be.  

• Health and healthcare: Health is more than just the absence of disease. Outside of the health care system, policies that promote health and health equity make the biggest improvements in community-wide health. Within the health care system, it means having access to culturally appropriate, affordable and timely pre- and post-natal care, as well as to a pediatrician or family care.  

There is a clear link between the social environment, a woman’s health, her placental function, her baby’s health and the health of future generations. The authors of this journal article make the case that evaluating a baby’s risk for future disease should also include an assessment of the social context of a woman’s pregnancy. Although most of the effects of toxic stress on a baby’s health haven’t been investigated, there is enough evidence to suggest that these exposures and interactions warrant further study and that more investment is needed into policies that improve the social determinants of health for women. 

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

____________________________________________________________________________________________________________________________________
Thornburg K., Boone-Heinonen J., Valent A., (2020). Social Determinants of Placental Health and Future Disease Risks for Babies, Obstetrics and Gynecology Clinics of North America. 47(1), 1-15. https://doi.org/10.1016/j.ogc.2019.11.002 

Mother's milk provides health benefits that last a lifetime

Journal: Cell Host & Microbe
Date: July 2020

Summary
Within our intestines is an ecosystem of some 100 trillion living microorganisms, including bacteria, viruses and fungi that play important roles like breaking down food, synthesizing vitamins and defending against pathogens - among other things. We call this ecosystem our intestinal ‘microbiome.’ It turns out that breastfeeding plays an important role in establishing a healthy microbiome in babies, which in turn has long-term implications for our overall health.

Breastmilk contains a rich and varied array of nutrients that are unique to each mom and baby. It also contains beneficial bacteria and prebiotics – “food” for the beneficial bacteria. In an article titled “Breastmilk Feeding Practices Are Associated with the Co-Occurrence of Bacteria in Mothers’ Milk and the Infant Gut: The Child Cohort Study”* researchers found that beneficial bacteria are shared through breastmilk and that feeding directly from the breast is the best way to support this process. The milk itself is amazing enough, but feeding directly at the breast increases the transfer of beneficial organisms. This is because approximately ten percent of the bacteria introduced to the infant is from the skin around a mother’s areola. There is also a beneficial alchemy that occurs with the bacteria and enzymes inside the infant’s mouth, facilitating a healthy oral microbiota in the baby. 

Long-term health implications of a healthy microbiome
A healthy microbiome is developed within the first three years of life and plays a number of critical roles throughout the lifespan, including how well people are able to fight disease and prevent infections. Breastmilk seeds and nurtures the microbiome with beneficial bacteria, until it is fully mature. Beneficial gut bacteria play a role in lowering risk for chronic diseases like asthma, obesity, allergies, dermatitis, inflammatory bowel disease and neurodevelopmental disorders. They also play a role in regulating anxiety, mood, cognition and pain via the brain/gut axis.

It has been well established that breastfeeding is a powerful, modifiable factor in establishing a baby’s microbiome, but the study in the above mentioned journal article was the first to evaluate breastfeeding practices (mode, exclusivity and duration), along with milk bacteria and milk components - and the composition of infant gut microbiota - at multiple points in a baby’s first year. This research involved 1,249 mother/baby pairs who are part of the ongoing Canadian CHILD Cohort Study.

There are many factors involved in establishing a healthy microbiome, including whether the baby was born vaginally or via C-section, the status of the mother’s microbiome and BMI during pregnancy and lactation, whether the baby is born pre- or full-term, the mother’s stress levels, antibiotic use, the duration of breastfeeding, which solid foods are first introduced, whether the baby has siblings, the mother’s diet while breastfeeding, milk composition at various stages of lactation and even if there is a pet in the home. Researchers are just beginning to tease apart these factors in an effort to understand how best to support mothers and babies during the first years of life, for the best health outcomes.

Regardless of all these factors, evidence shows that any amount of breastmilk is beneficial - even if only for a short period of time. And even though the process of pumping, storing and bottle-feeding breastmilk may reduce the transfer of viable milk bacteria from mom to baby, pumped milk still provides many health benefits. This study provides important new knowledge that can help improve recommendations on how to handle and store breastmilk for when moms need to pump.

Highlights

• Breastfed babies have higher levels of beneficial gut bacteria and healthier growth patterns than babies who are not breastfed.
• Breastfed babies have a lower rate of wheezing – one of the most common reasons infants are hospitalized or receive medical care.
• Breastfed babies have a lower risk of developing asthma as they get older.
• How a baby is breastfed matters too – meaning, there is a difference between feeding directly from the breast and feeding pumped breastmilk from a bottle.
• Breastmilk is unique to each mom and baby.

What about formula fed babies?
While there is rock solid evidence that breastfeeding provides health advantages for babies and mothers, the fact that there are millions of adults who were formula fed indicates that women who are unable to breastfeed can still raise normal, healthy children. Women often feel guilty for not nursing, or being able to nurse, their babies. However, there are many circumstances where they are simply unable to. There are a variety of physiological reasons why a woman might not produce an adequate supply of milk. They may have latching problems, pain, medical complications, or need to return to work early and choose not to breastfeed. Some babies are adopted and the parents don’t have access to breastmilk. This study on the microbiome provides important insight into how microbes could be manipulated and used to optimize health for all infants.

Supporting women’s personal goals
The World Health Organization (WHO) and the American Academy of Pediatrics (AAP) recommend that babies are exclusively breastfed until six months of age, and that mothers continue breastfeeding while introducing complimentary foods for at least one year (at least two years or more according to WHO). Oregon has a strong track record in the number of women who breastfeed but due to an overall lack of support, many aren’t able to meet their original breastfeeding goals. According to the Oregon Public Health Division, over 90 percent of Oregon mothers breastfeed their new babies, but only six in ten women are able to continue for as long as they had planned. Families, employers, child care and health care providers, hospitals and communities all play a role in reducing barriers to breastfeeding and ensuring that mothers get the support they deserve. 

Learn more about why breastfeeding matters.

Additional resources:
La Leche League of Oregon
OHSU Center for Women’s Health lactation services
U.S. Breastfeeding Committee
USDA WIC Breastfeeding Support

*The senior author on the study, Dr. Megan Azad, is a widely recognized expert on human pregnancy and nutrition in childhood. She is a valued friend of the Moore Institute. Dr. Azad is Associate Professor of Pediatrics at the University of Manitoba, and co-Directs the new Manitoba Interdisciplinary Lactation Centre (MILC). Her research program is focused on the role of infant nutrition and the microbiome in child growth, development and resilience. Dr. Azad also co-leads the Manitoba site of the CHILD Cohort Study, the largest multidisciplinary, longitudinal, population-based birth cohort study in Canada. It’s designed to be one of the most informative studies of its kind in the world.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

________________________________________________________________________________________________________________________

Kelsey Fehr, Shirin Moossavi, Hind Sbihi, Rozlyn C.T. Boutin, Lars Bode, Bianca Robertson, Chloe Yonemitsu, Catherine J. Field, Allan B. Becker, Piushkumar J. Mandhane, Malcolm R. Sears, Ehsan Khafipour, Theo J. Moraes, Padmaja Subbarao, B. Brett Finlay, Stuart E. Turvey, Meghan B. Azad. (2020). Breastmilk Feeding Practices Are Associated with the Co-Occurrence of Bacteria in Mothers’ Milk and the Infant Gut: the CHILD Cohort Study. Cell Host & Microbe 28(2):285-97.e4, ISSN 1931-3128. https://doi.org/10.1016/j.chom.2020.06.009.

Risky growth strategy can lead to hypertension later in life

Journal: American Journal of Human Biology
Date: April 2010

Summary
In the womb, boys have a more dangerous growth strategy than girls. Boys grow more rapidly and invest less in placental growth, putting them at risk of becoming undernourished if maternal nutrients becomes scarce during pregnancy. Since the placenta both nourishes the baby and sustains itself, banking on adequate nutrition from the mother in lieu of a larger placenta is a risky strategy.

In a study involving 2,003 Finnish men and women aged 62 years, scientists set out to understand the role the placenta plays in the long-term risk for developing hypertension. Amazingly, the birth records in Finland contained information about their birthweight, mother’s height, and data on the father’s occupation, grouped into middle and lower class. They also included the weight and width of the placenta. Since the placenta is oval shaped, two measurements were noted: the length and the width. In men, hypertension was associated with a placenta that was wider - in relation to birthweight. The authors set out to discover why.

The study suggests this placental enlargement happens in response to inadequate nutrition during pregnancy. Pregnancies with boys compensate for a lack of immediate nutrition by enlarging the placenta, in an effort to extract more nutrients. It’s the width of the placenta that grows in response to this effort, and it occurs toward the end of pregnancy when a smaller placenta’s ability to transport nutrients would begin to limit fetal growth. In other words, the boys rely on immediate and ongoing nutrition as a growth strategy. Thus, boys have a rapid growth strategy in the womb. They stimulate their mother’s appetite so that she eats more and gains more weight than if she were carrying a girl. When nutritional sources become scarce, the adaptive course of boys is to enlarge the placenta in an effort to extract more nutrients from mother. Girls do not follow the same developmental strategy, and rely more on a mother’s long-term nutritional stores – making it a far less risky approach if there were nutritional shortfalls. The high risk strategy can be fatal for boys. During the Chinese Great Leap Forward famine of 1960-63 more boys died in the womb than did girls.

Compensating for nutritional shortfalls
Compensatory expansion of the placenta has also been studied in sheep. Sheep farmers know that if ewes are put on poor pasture during mid-pregnancy, the placenta will enlarge - presumably to extract more nutrients from the mother. If the ewes are then returned to good pasture in late pregnancy, the enlarged placenta leads to larger lambs. This type of compensatory growth of the placenta also happens in human babies and most often in boys. However, we know from detailed records kept during food shortages in Helsinki before and during the Second World War, as well as the Dutch Famine of 1944-45, that compensatory placental growth usually only occurs if the mother was well nourished at conception and then experiences a subsequent food shortage.

If the food shortage is ongoing, this compensatory placental growth results in a smaller baby with a higher risk for hypertension later in life. This is because the baby had to make developmental “trade-offs” in the womb, with lower priority organs such as the kidneys. During gestation the placenta performs most of the functions that the kidneys would normally perform – thus making the kidneys less of a priority during times of poor nutrition compared to the brain or heart. If this happens, the kidneys take a hit and develop fewer nephrons, becoming permanently shortchanged. The number of nephrons kidneys have is set in the womb, and we now know that this trade-off increases the risk of both hypertension and progressive renal disease.

Conclusion
This study suggests that during development in the womb, boys are more responsive to the mother’s immediate diet than are girls. If the nutritional needs are adequate, boys grow big and weigh more at birth on average than girls. If there are shortfalls, however, their growth strategy puts them at risk for hits to their kidneys and therefore puts them at a high risk for hypertension later in life.

The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

________________________________________________________________________________________________________________________

Eriksson, J. G., Kajantie, E., Osmond, C., Thornburg, K., & Barker, D. J. (2010). Boys live dangerously in the womb. American journal of human biology : the official journal of the Human Biology Council, 22(3), 330–335. https://doi.org/10.1002/ajhb.20995&nbsp;

Pregnancy-Induced Hypertension has Long-Term Health Implications for Both Mother and Child

Journal: Journal of the American Heart Association
Date: April 2020

Summary
Preeclampsia is a condition of persistent hypertension that some women develop during pregnancy or in the postpartum period. Preeclampsia is a more severe form of pregnancy-induced hypertension (high blood pressure). Five to eight percent of all births in the United States are impacted by preeclampsia, which used to be called “toxemia”.  Most women with preeclampsia will deliver healthy babies and fully recover. However, some women experience complications - several of which may be life-threatening to mother and/or baby. If not properly recognized and managed, preeclampsia can progress to eclampsia, a very severe complication that includes the sudden onset of grand mal seizures and sometimes death. The rate of preeclampsia in the United States has increased by 25 percent in the last two decades, and is a leading cause of maternal and infant illness and death. It occurs more commonly among women of color. 

Women who’ve had preeclampsia are three to four times more at risk for high blood pressure later in life, and have double the risk for heart disease and stroke. They also have an increased risk of developing diabetes. It’s unknown whether these risks are caused by preeclampsia itself, or if the women were already predisposed, but they first emerge in the years following a complicated pregnancy such as one with preeclampsia. Moore Institute Director Kent Thornburg, Ph.D., was invited to write a commentary on a recent study published in the April edition of the Journal of the American Heart Association. The study suggests maternal hypertension and preeclampsia are not only potential warnings for heart disease risk in the mother – but also in the offspring. This research brief provides an overview of the journal study and Dr. Thornburg’s analysis.  

New information
What hadn’t been known before is the degree to which maternal hypertension affects the development of her baby’s heart before birth.  In order to understand this, researchers at Oxford University used echocardiography to measure the hearts of 134 infants born at term, and then again at three months of age. Fifty-four of the infants’ mothers did not develop hypertension in pregnancy and 80 either developed pregnancy-induced hypertension, or the more severe form, preeclampsia. They discovered that the heart's right ventricle was 20 percent smaller than normal at birth in infants born to hypertensive mothers. This deficit persisted at three months. It also showed evidence of changes in the thickness of the hearts’ ventricle walls at three months of age: the left ventricle walls were eight percent thicker, and the right ventricle walls were 23 percent thicker in babies born to hypertensive mothers, than those whose mothers didn’t have hypertension.    

But what’s the biological connection between pregnancy-induced hypertension and altered cardiac growth in the baby? The short answer is, we don’t know. However, this is where studies on the developmental origins of health and disease- comes in.  

The placenta 
The role the placenta plays in preeclampsia is unclear, but evidence has shown that poor blood flow to the placenta can lead to chemical stress within the placenta and to fetal tissues. In addition, a poorly constructed arrangement of blood vessels in the placenta increases the resistance that the developing baby’s heart must face in pushing blood through the placenta to obtain nutrients and oxygen. This high placental resistance is common among babies whose intrauterine growth is slow. This leads to high blood pressure in the baby and changes in the anatomy of the developing heart.  High blood pressure in the baby also results in fewer heart muscle cells at birth.   

But why did the hearts of babies born to mothers with hypertension grow abnormally over the first three months after birth when they are no longer attached to the mother? Thornburg speculates the total resistance that was needed to maintain normal flow was higher in the babies born to mothers with higher blood pressure and led to changes in the growth of the fetal ventricles that worsened during the first three months of life.  

Conclusion 
On the basis of this recent study, in combination with extensive animal studies, Thornburg speculates that babies born to mothers who have pregnancy-induced hypertension will have elevated risk for coronary heart disease and/or heart failure later in life. This finding is one more important clue toward solving the mystery of why a medical condition in a mother during pregnancy can lead to disease risk in her offspring. 
 
The OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

____________________________________________________________________________________________________________________________________________________

Thornburg, K.L., Drake, R., Valent, A.M. (2020). Maternal Hypertension Affects Heart Growth in Offspring. Journal of the American Heart Association, 9(9), e016538, https://doi.org/10.1161/JAHA.120.016538

Study Suggests Our Weight at Age Two Sets Our Ability to Regulate Metabolic Hormones as Adults

Journal: Journal of Endocrinology
Date: February 2020

Summary
Researchers designed a study to determine whether indicators of cardiovascular disease risk were associated with weight at different ages in childhood.  As part of the study, the investigators tested the hypothesis that the levels of three hormones in healthy French university 20-year-olds was related to their growth patterns in childhood.  They found that elevated risks for heart disease, insulin resistance and metabolic syndrome later in life is associated with weight at age two. Metabolic syndrome is characterized by insulin resistance and elevated levels of cholesterol and blood pressure.

The most well-known hormone studied, insulin, is made in the pancreas. It helps regulate blood sugar levels by stimulating muscles to take up the sugar for fuel. The second hormone studied was leptin, which is made primarily by fat cells and is a powerful regulator of appetite. However if leptin levels in the blood get too high, it causes inflammation in the heart and blood vessels and is associated with cardiovascular disease. The third metabolic hormone studied was adiponectin. Adiponectin is also made by fat cells, and protects blood vessels from inflammation.

Findings

• The smaller the participants (young, healthy 18-25-year olds) were at age two, the higher their levels of leptin and insulin.
• High leptin levels in young adults are associated with insulin resistance, which allows blood sugar to remain elevated after a meal.
• ‘Set points’ for leptin and insulin are determined in early childhood-- by the age of two.
• Low weight at age two, due to low muscle mass, predicted lower levels of adiponectin in later life. Adiponectin protects against vascular inflammation and thus, low levels are a risk factor for metabolic syndrome. Further study into this relationship is warranted.

The primary finding of this study is that blood concentrations of the three hormones studied in healthy young adults, are determined by the growth patterns of a person during their first 1000 days after conception. Thus, it explains, in part, why people born at the low end of the birth-weight scale are at a higher risk for cardiovascular disease as they become adults. This finding, along with studies on brain wiring, also suggests that a person’s appetite is highly influenced by growth patterns up to the age of two years. 

he OHSU Bob and Charlee Moore Institute for Nutrition & Wellness supports human research that seeks to find the links between maternal stresses, including poor nutrition, and elevated disease risks for babies as they become adolescents and adults. 

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Simeoni, U., Osmond, C., Garay, R., Buffat, C., Boubred, F., Chagnaud, C., Jouve, E., Audebert, C., Antoine, J., & Thornburg, K. (2020). Leptin and insulin in young adulthood are associated with weight in infancy, Journal of Endocrinology, 244(2), 249-259. https://doi.org/10.1530/JOE-18-0538