TABLE 2.

Integrating themes and related research needs identified by 2016 NIH workshop on iron screening and supplementation of pregnant women and young children (6–24 mo)¹

	Research needs
Integrating themes	Major focal area	Examples of specific topics
Elucidating adaptations of iron homeostasis to pregnancy and early infancy: uncertainties and implications	Mechanism(s) of “reset” of hepcidin to lower regulatory level	Molecular regulation in pregnancy and early infancy Relative roles of systemic and local regulatory factors Relative maternal and fetal regulation of placental iron transport Responsiveness to iron status of mother and fetus (baseline, supplementation, maternal dietary forms and bioavailability, non–transferrin bound iron, etc.)
	Responsiveness to other drivers of hepcidin-regulated homeostasis	Role of inflammation (physiologic, obesity, infection, etc.), erythropoiesis, and hypoxia
	Interaction with genetic and ethnic factors	Role of alleles of HFE and ferroportin in this adaptation
	Differential prioritization of iron to maternal, fetal and infant tissues during pregnancy, development and growth	Mechanism of this differential prioritization and its relation to adapted iron homeostasis
Improving assessment of iron status: challenges and opportunities in pregnancy and young children	Measurement	Standardization and accuracy
	Appropriateness of indicators across the full spectrum of iron status (ID, IDA, iron repletion, and iron excess) during pregnancy and young childhood	Cutoffs and interpretation relative to health outcomes beyond ID and IDA
	Limited assessment of infants aged 0–12 mo in the United States	Development of noninvasive measures or blood spot methods for use in large surveys
	Inflammation	Validation for correction during pregnancy and in young infants Identification and validation of indicators not subject to confounding by inflammation
	Innovative and nonhematological measures	Identification and validation of nonhematologic indicators that enable the assessment of ID of tissues with lower priority for iron before IDA Use of system biology approaches (proteomics, metabolomics, and genomics) to identify relevant indicators of early ID
Linking iron status to maternal and infant health outcomes: beyond hematology and IDA	Prioritization and relevance of health outcomes	Determine which outcomes are most informative of iron status across the full spectrum from IDA to ID to iron replete to iron excess
	Indicators of differential tissue prioritization	Evaluate indicators relative to health outcomes relevant to specific tissues, such as neurodevelopmental delay, cognitive development, and psychomotor development
Supplementing iron-replete pregnant women and young children: issues and uncertainties	Prioritization and relevance of possible short- and long-term health outcomes	Maternal GDM and postpartum T2D Fetal and young child growth Maternal and young child morbidity (diarrhea, constipation, etc.) Early iron excess and neurodegenerative disease, cognitive development, psychomotor development to understand the role of excess iron, and DOHaD Maternal and neonatal mortality
	Determination of mechanisms of heterogeneity of response	Interaction of high dietary iron with alleles of HFE Environmental and personal factors of responders and nonresponders
	Determination of short- and long-term intermediate outcomes	Microbiome profiles, GI inflammation, stem cell alterations, damage to β cells, and epigenome alterations

¹DOHaD, developmental origins of health and disease; GDM, gestational diabetes mellitus; GI, gastrointestinal; HFE, hemochromatosis protein; ID, iron deficiency; IDA, iron deficiency anemia; T2D, type 2 diabetes.