Elizabeth M. Miller

Development of the preterm infant gut microbiome: a research priority

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

Field and laboratory methods in human milk research

Human milk is a complex and variable fluid of increasing interest to human biologists who study nutrition and health. The collection and analysis of human milk poses many practical and ethical challenges to field workers, who must balance both appropriate methodology with the needs of participating mothers and infants and logistical challenges to collection and analysis. In this review, we address various collection methods, volume measurements, and ethical considerations and make recommendations for field researchers. We also review frequently used methods for the analysis of fat, protein, sugars/lactose, and specific biomarkers in human milk. Finally, we address new technologies in human milk research, the MIRIS Human Milk Analyzer and dried milk spots, which will improve the ability of human biologists and anthropologists to study human milk in field settings. Am. J. Hum. Biol., 2013.

Iron status and reproduction in US women: National Health and Nutrition Examination Survey, 1999-2006.

Women experience significant changes in iron status throughout their reproductive lifespans. While this is evident in regions with high rates of malnutrition and infectious disease, the extent of reproductive-related changes is less well known in countries with low rates of iron deficiency anemia, such as the United States. The goal of this study is determine the relationship between womens reproductive variables (pregnancy, parity, currently breastfeeding, regular menstruation, hormonal contraceptive use, and age at menarche) and iron status (hemoglobin, ferritin, transferrin receptor, and % transferrin saturation) using an anthropological framework for interpreting the results. Data from women aged 18–49 were taken from the 1999–2006 US NHANES, a nationally representative cross-sectional sample of US women. Using multiple imputation and complex survey statistics, womens reproductive variables were regressed against indicators of iron status. Pregnant women had significantly poorer iron status, by most indicators, than non-pregnant women. All biomarkers demonstrated significantly lower iron levels with increasing parity. Women who were having regular periods had iron indicators that suggested decreased iron levels, while women who used hormonal contraceptives had iron indicators that suggested increased iron levels. Despite relatively good iron status and widespread availability of iron-rich foods in the US, women still exhibit patterns of iron depletion across several reproductive variables of interest. These results contribute to an ecological approach to iron status that seeks to understand variation in iron status, with the hopes that appropriate, population-specific recommendations can be developed to improve womens health.

The reproductive ecology of iron in women

Reproductive ecology focuses on the sensitivity of human reproduction to environmental variation. While reproductive ecology has historically focused on the relationship between energy status and reproductive outcomes, iron status is equally critical to womens reproductive health, given the wide-ranging detrimental effects of iron-deficiency anemia on maternal and infant well-being. This review interprets the vast literature on iron status and womens reproduction through an evolutionary framework. First, it will critique the evidence for iron deficiency caused by blood loss during menstruation, reinterpreting the available data as ecological variation in menses within and between populations of women. Second, it will highlight the scant but growing evidence that iron status is implicated in fertility, a relationship that has deep evolutionary roots. Third, this review proposes a new hypothesis for the transfer of iron from mother to infant via pregnancy and breastfeeding: reproductive iron withholding. In this hypothesis, mothers transfer iron to infants in a manner that helps infants avoid iron-mediated infection and oxidative stress, but trades off with potential risk of maternal and infant iron deficiency. Finally, this review explores two main factors that can modify the relationship between iron status and the gestation-lactation cycle: (1) the relationship between long-term reproductive effort (parity) and iron status and (2) supplementation schemes before and during pregnancy. The review concludes by suggesting continued research into iron homeostasis in women using evolutionary, ecological, and biocultural frameworks.

Milk immunity and reproductive status among Ariaal women of northern Kenya

Abstract Background: The immune factors in human milk protect infants from infection and promote immune development. Evidence suggests that the production of milk-specific immunoproteins is energetically costly, making them a form of maternal investment in offspring health that is subject to life history trade-offs. Aim: This research tests the relationship between measures of reproductive effort and the production of milk immunoglobulin A (IgA) among Ariaal women, a settled northern Kenyan pastoralist population that experiences nutritional and disease stress. Subjects and methods: Two hundred and forty-three lactating Ariaal women participated in a questionnaire, anthropometric measurement and milk collection. Milk IgA was analysed using ELISA. Results: There was a significant U-shaped relationship between post-partum months and milk IgA, reflecting decreasing investment in the current offspring over the early post-partum period and subsequent recovery of maternal energy status near the end. There was also a significant inverse U-shaped relationship between milk IgA and parity, with high parity women showing a drop in milk IgA. In contrast, anthropometric measures of energy status were not associated with the production of milk IgA. Conclusion: This research shows that patterns of reproductive investment can be demonstrated in milk IgA in the absence of measured energy changes.

A comparison of three infant skinfold reference standards: Tanner–Whitehouse, Cambridge Infant Growth Study, and WHO Child Growth Standards

As researchers increasingly focus on early infancy as a critical period of development, there is a greater need for methodological tools that can address all aspects of infant growth. Infant skinfold measures, in particular, are measurements in need of reliable reference standards that encompass all ages of infants and provide an accurate assessment of the relative fatness of a population. This report evaluates three published reference standards for infant skinfold measurements: Tanner-Whitehouse, Cambridge Infant Growth Study, and the World Health Organization (WHO) Child Growth Standards. To assess these standards, triceps skinfolds from a population of rural Kenyan infants (n = 250) and triceps skinfolds and subscapular skinfolds from infants in the National Health and Nutrition Examination Survey 1999-2002 (NHANES; n = 1197) were calculated as z-scores from the lambda-mu-sigma curves provided by each reference population. The Tanner-Whitehouse standards represented both the Kenyan and US populations as lean, while the Cambridge standards represented both populations as overfat. The distribution of z-scores based on the WHO standards fell in the middle, but excluded infants from both populations who were below the age of 3 months. Based on these results, the WHO reference standard is the best skinfold reference standard for infants over the age of 3 months. For populations with infants of all ages, the Tanner-Whitehouse standards are recommended, despite representing both study populations as underfat. Ideally, the WHO will extend their reference standard to include infants between the ages of 0 and 3 months.

What is significant about a single nursing session? An exploratory study

Researchers and clinicians specializing in breastfeeding often rely on measuring one nursing session to characterize the breastfeeding relationship. However, less is known about the descriptive or statistically predictive characteristics of one nursing session. The purposes of this study are twofold: (1) to explore the relationships between variables in a single nursing session; and (2) to study the association between variables in a single nursing session and infant length‐for‐age (LAZ) and weight‐for‐age (WAZ).

Hormone replacement therapy affects iron status more than endometrial bleeding in older US women: A role for estrogen in iron homeostasis?

High iron levels in women of post-reproductive age may be related to their increased risk of chronic disease as they become older, but the causes of this rise in iron in late life is unclear. Recently estrogen has been implicated in non-human models of iron homeostasis. Studying iron in women who take hormone replacement therapy (HRT) may provide insight into the relationship between iron status and hormonal status in older women. This study examines the association between HRT and iron status in women aged 50+ who took part in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). Data were analyzed using multiple imputation, which corrects for missing data, and complex survey regression, which adjusts for NHANES sampling. Current HRT use was associated with lower ferritin (β=-34.13, p=0.0002), controlling for potential breakthrough bleeding with a hysterectomy variable. HRT was associated with lower iron stores in women of post-reproductive in the absence of uterine blood loss, indicating potential homeostatic hormonal control of iron status. This research demonstrates the utility of studying clinical hormonal therapy to advance new understandings about the basic biology of iron homeostasis in women.

One Step for a Hospital, Ten Steps for Women: African American Women’s Experiences in a Newly Accredited Baby-Friendly Hospital:

Background: Despite strides made by the Baby-Friendly Hospital Initiative to improve and normalize breastfeeding, considerable racial inequality persists in breastfeeding rates. Few studies have explored African American women’s experience in a Baby-Friendly Hospital Initiative system to understand sources of this inequality. Research aim: This study aimed to explore African American women’s experiences of the Ten Steps to Successful Breastfeeding at a women’s center associated with a university-affiliated hospital that recently achieved Baby-Friendly status. Methods: Twenty African American women who had received perinatal care at the women’s center and the hospital participated in qualitative interviews about their experiences. Data were organized using the framework method, a type of qualitative thematic analysis, and interpreted to find how African American women related to policies laid out by the Ten Steps to Successful Breastfeeding. Results: Three key themes emerged from the women’s interviews: (a) An appreciation of long-term relationships with medical professionals is evident at the women’s center; (b) considerable lactation problems exist postpartum, including lack of help from Baby-Friendly Hospital Initiative sources; and (c) mothers’ beliefs about infant autonomy may be at odds with the Ten Steps to Successful Breastfeeding. Conclusion: Hospitals with Baby-Friendly status should consider models of breastfeeding support that favor long-term healthcare relationships across the perinatal period and develop culturally sensitive approaches that support breastfeeding beliefs and behaviors found in the African American community.

Ecological immunity of human milk: Life history perspectives from the United States and Kenya

OBJECTIVES Previous research has established population variation in anti-inflammatory immunological biomarkers in human milk. This immunity is potentially ecology-dependent and may alter the life history trade-off between growth and maintenance in infants. The current study has two aims: (1) to assess the ecological differences in milk immunity in two populations, one from the urban U.S. and one from rural Kenya; and (2) to test the hypothesis that milk immunity can affect infant growth indicators. MATERIALS AND METHODS Kenyan Ariaal (n = 233) and U.S. (n = 75) breastfeeding mother-infant pairs participated in a cross-sectional study at two separate field sites. Laboratory analysis was performed on milk for the anti-inflammatory biomarkers TGF-β2, sTNF-αRI, sTNF-αRII, and IL-1ra using ELISA. Multiple imputation was used to extrapolate data below the limit of detection before multivariate analysis. RESULTS There were significant differences between U.S. and Kenyan mothers on all four milk biomarkers, with Kenyan mothers having significantly higher sTNF-αRI and sTNF-αRII and lower TGF-β2 and IL-1ra than U.S. mothers. U.S. mothers with higher milk TGF-β2 and IL-1ra have infants that are significantly longer and heavier for their age, while Kenyan mothers with higher sTNF-αRI have significantly longer and heavier infants for their age, and those with higher TGF-β2 have marginally significantly longer infants. DISCUSSION There were significant differences in ecological milk immunity between U.S. and Kenyan mothers. These differences potentially play a role in the growth of their infants. Further research in milk immunity should consider the possibility of shared maternal-infant life histories.