The importance of nutrition in pregnancy and lactation: lifelong consequences Nicole E. Marshall, MD, Barbara Abrams, DrPH, RD, Linda A. Barbour, MD, MSPH, Patrick Catalano, MD, Parul Christian, DrPH, Jacob E. Friedman, PhD, William W. Hay Jr, MD, Teri L. Hernandez, PhD, RN, Nancy F. Krebs, MD, MS, Emily Oken, MD, MPH, Jonathan Q. Purnell, MD, James M. Roberts, MD, Hora Soltani, PhD, MMedSci, RM, PGDip, PGCert, Jacqueline Wallace, PhD, DSc, Kent L. Thornburg, PhD Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR (Dr Marshall); School of Public Health, University of California, Berkeley, CA (Dr Abrams); Departments of Medicine (Dr Barbour) and Obstetrics and Gynecology (Dr Barbour), University of Colorado School of Medicine, Aurora, CO; Department of Obstetrics and Gynecology, Mother Infant Research Institute, Tufts University School of Medicine, Boston, MA (Dr Catalano); Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (Dr Catalano); Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD (Dr Christian); Departments of Physiology (Dr Friedman), Medicine (Dr Friedman), Biochemistry (Dr Friedman), and Microbiology and Immunology (Dr Friedman), Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK; University of Colorado, Denver, CO (Dr Hay); Department of Medicine, College of Nursing, University of Colorado Anschutz Medical Campus, Aurora, CO (Dr Hernandez); Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO (Dr Krebs); Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA (Dr Oken); Department of Medicine, Knight Cardiovascular Institute, Bob and Charlee Moore Institute of Nutrition and Wellness, Oregon Health & Science University, Portland, OR (Dr Purnell); Departments of Obstetrics and Gynecology and Reproductive Sciences (Dr Roberts), Epidemiology (Dr Roberts), and Clinical and Translational Research (Dr Roberts), Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Maternal and Infant Health, Sheffield Hallam University, Sheffield, England (Dr Soltani); Rowett Institute, University of Aberdeen, Aberdeen, Scotland (Dr Wallace); and Department of Medicine, Center for Developmental Health, Knight Cardiovascular Institute, Bob and Charlee Moore Institute of Nutrition and Wellness, Oregon Health & Science University, Portland, OR (Dr Thornburg).
can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report “prudent” or “health-conscious” eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.
Engineering, and Medicine workshop.3 The need for additional well-designed research on this topic became apparent in a recent series of systematic reviews from the US Department of Agriculture (USDA): Nutrition Evidence Systematic Review, Pregnancy and Birth to 24 Months Project.4 Of note, 29 of the most important questions related to pregnancy and infant milk-feeding practices were systematically reviewed, with the highlights related to nutrition during pregnancy presented in Figure 1. Each topic was summarized by a conclusion statement and was assigned a grade based on the quality of evidence. For 5 conclusion statements, a grade was not assignable, and the remaining 3 pregnancy questions received a grade that reflected only limited available evidence.5,6 For the infant milk topics, 4 received a grade indicating moderate evidence, 10 had limited evidence, and a grade was not assignable for 21 questions.7 The uncertain conclusions of the aforementioned systematic reviews underscored the need for more well-conceived studies to address specific questions regarding the role of nutrition in pregnancy. However, the inadequate numbers of studies capable of meeting the strict criteria of the reviews, do not negate the large number of robust studies on related topics, from which the scientific community may benefit. In this review, we have included such studies that give important insight into the many aspects of nutrition for women during their reproductive years. In the past, public policy guidelines did not include pregnant or lactating women or infants under the age of 2. Fortunately, the 2020 to 2025 Dietary Guidelines for the first time include recommendations for infants, toddlers, and pregnant women that will provide added benefits for healthcare professionals and the public. The USDA released its final guideline document (USDA 2020–2025 Dietary Guidelines) in December 2020.8 Although this report was not available at the time of the Nutrition in Pregnancy: Lifelong Impact conference in 2019, which was the motivation for this review, the findings and recommendations of this document were nevertheless consistent with the new USDA guidelines.9 Other reviews on this topic bring additional clarity to the issue.10 The conclusions offered herein come from recommendations from assembled experts on (1) the health benefits of consuming nutritious food before, during, and after pregnancy, (2) the value of promoting improved nutrition among pregnant women, and (3) the gaps in knowledge regarding nutrition during reproductive years that require urgent attention. Although the meeting was largely focused on women in the United States, there were also important insights from global partners
birthweight for gestational age), each of which is associated with increased risks of developing childhood and adult chronic diseases. 3. The dietary patterns of pregnant adolescents are generally less healthy than those of pregnant adult women and are critically important during a time of continued maternal growth and development, indicating the need for enhancing diet quality among young pregnant mothers. Many adolescent mothers face multifaceted socioeconomic and lifestyle difficulties that require professional and social support to aid in optimizing their diets and other aspects of their health and social care before, during, and after their pregnancies. 4. The consumption of a beneficial dietary pattern before and during pregnancy is associated with a reduced risk of disorders of pregnancy, including gestational diabetes mellitus (GDM), preterm birth, obesity-related complications, and, in some populations, preeclampsia and gestational hypertension. Nutrition therapy provides the foundation for the treatment of GDM and is especially important for pregnant women with obesity who have undergone bariatric surgery or who have preexisting diabetes mellitus (DM). 5. A diet with balanced macronutrient intake provides the best chance for a healthy pregnancy and optimal perinatal outcomes. Nutritious diets are those that 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 as promoted by the popular press are widespread and may be especially harmful during pregnancy because of the resulting nutrient imbalance and consequent nutrient deficiencies or ketosis. 7. Growing evidence indicates that maternal prepregnancy body mass index (BMI) impacts the influence of gestational weight gain (GWG) on complications of pregnancy. Although the optimal time to improve maternal body weight and nutrition-related lifestyle is well before conception occurs, GWG goals, including a diet that limits nonnutritive, calorie-dense foods, maybe more achievable intervention targets for some women than weight modification before pregnancy. 8. Human 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. Human milk composition is influenced by maternal dietary intake during lactation and maternal adipose nutrient stores, which together influence maternal milk and nutrient production and composition. Among women with GDM, there is evidence that exclusive breastfeeding for at least 6 months decreases the risk of type 2 DM (T2DM) for the mother and is protective for the risk of childhood obesity in her offspring.
- The regular consumption of 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 the cessation of lactation 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. A review of the scientific bases for points of agreement is explained below. Comprehensive Improvements in Nutrition and Health Status of Women Before Conception and During Pregnancy will Contribute to Optimal Fetal Growth, Favorable Obstetrical Outcomes, Improved Perinatal Survival, and the Potential for Better Long-Term Health in Both the Mother and Offspring Background and current status Recent national data suggested that many women in the United States do not meet the recommendations for healthful weight and nutrition before and during pregnancy. As of 2019, 29% of women met the criteria for obesity before pregnancy, which increased by 11% from 2016. Overall, only 32% of US women gain weight within the recommended range during gestation, and the distributions of low or excessive weight gain varied accordingly by prepregnancy BMI.11 In 2015, only half of US women surveyed met the guidelines for physical activity, and 29.7% of women reported taking a vitamin or folate supplement regularly before pregnancy.12 National data on food intake in US women before and during pregnancy women are limited; however, several reports have suggested that substandard quality diets are common.13–16 For example, between 2010 and 2013, a cohort of 7500 nulliparous women from 8 large US medical centers recalled their usual diet within 3 months of conception, and researchers assessed their diet quality using the Healthy Eating Index (HEI)-2010.14 More than half of the women reported an inadequate number of servings of the component food groups. The authors estimated that 39% of calories came from foods containing added sugars, solid fats, and alcohol, and the mean HEI score was only 63 of 100 points.14 When the same index was estimated for 795 pregnant participants in the National Health and Nutrition Examination Survey (NHANES; 2003–2012), the score was lower (poorer diet quality) at 50.7.13 In another recent analysis of pregnant women in NHANES, more than a third of the women reported diets below the estimated average requirement for key nutrients, such as vitamins D and E, iron, and magnesium, even with the use of dietary supplements, whereas 99.9% of the women reported diets too high in sodium.16 Social disadvantage plays a role in food behavior, and researchers have identified characteristics of US women, such as education level below a college degree and women of color who may be at the highest risk of less healthy intakes13–15 or low levels of nutritional biomarkers.13,17 Marshall et al. Page 5 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Impact on pregnancy outcomes In the 20th century, researchers and clinicians considered the fetus to be “a perfect parasite”18 who could meet its nutritional requirements in all but extreme famine.19 This perspective encouraged pregnant women to restrict their diet and minimize GWG in the middle 20th century.20 Infants with LBW were assumed to be “skinny” but “relatively untroubled.”19 However, current evidence found that maternal body size, dietary practices, and nutritional status before and during pregnancy are important factors for fetal health. Both inadequate nutrition and excessive nutrition and weight before and during pregnancy contribute to complications related to fertility (maternal and paternal); conception; development of the placenta, embryo, and fetus; fetal size; and perinatal complications, resulting in suboptimal pregnancy consequences for the mother and infant (Table 1).14,21–29,30,31 Animal models and human studies have suggested that maternal nutrition and maternal pre-pregnancy metabolic condition regulate fetal-placental gene expression, organ structures, metabolism, and growth during critical periods of development, affecting offspring risk of cardiovascular, metabolic, respiratory, immunologic, neuropsychiatric, and other chronic conditions starting during childhood development and into adulthood, with and without LBW.28,32–34 The intrauterine environment can establish poor trajectories of health that may be increased when nutrient restriction in utero is followed by postnatal nutrient excess.35,36 To illustrate, in Holland during World War II, where the population recovered from the Dutch Hunger Winter famine relatively quickly, exposure to famine early in pregnancy was associated with a higher risk of offspring obesity and cardiovascular disease (CVD) in adulthood, whereas exposure to famine in the second half of pregnancy led more commonly to T2DM.35 Opportunities for positive impact Unfortunately, recognition of the importance of preconception nutrition, except for micronutrients, such as folate for the prevention of neural tube defects, is limited among healthcare workers, policymakers, and the public. The WHO Report of the Commission on Ending Childhood Obesity37 recognized preconception and pregnancy care as 1 of 6 key areas of action and called for clear guidance and support for the promotion of good nutrition and dietary counseling in antenatal care. Although healthy eating and physical activity counseling for adequate weight gain is recommended, the availability of effective support during pregnancy is limited. Weight gain in pregnancy in low-to-middle–income countries (LMICs) is not monitored routinely in some countries, and prepregnancy BMI is generally unknown. In addition, culturally acceptable, affordable, nutritious food supplements are urgently needed in areas where the prevalence of maternal undernutrition and poor food quality is high. Comprehensive improvements in nutrition and health status of women before conception and during pregnancy may have immediate effects on fetal growth, obstetrical outcomes, and perinatal survival. In a recently completed multicountry trial in which the effects of a comprehensive nutrition intervention initiated before conception was compared with the same intervention initiated late in the first trimester of pregnancy (vs no intervention), birth outcomes, including birth length and birthweight, LBW, SGA, and stunting, were strongly impacted by the nutritional intervention, with the largest effects in the preconception arm.38 Nulliparity and preconception anemia were strong effect modifiers of the response to intervention with more modest effects by baseline BMI.38,39 Marshall et al. Page 6 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript The WHO global guidance for antenatal care recommends several central nutritional and health interventions for a healthy pregnancy, including multiple micronutrient supplements containing iron and folic acid, calcium supplementation for the prevention of preeclampsia in low intake contexts, and balanced energy and protein supplementation for undernourished populations to reduce LBW.2 For women with easy access to low-quality food and who are overweight or have obesity, evidence to support preconception nutrition is insufficient and mostly observational. Limited evidence suggested that a specific benefit of a diet higher in vegetables, fruits, whole grains, nuts, legumes, and fish and lower in red and processed meats before and during pregnancy is associated with a reduced risk of hypertensive disorders of pregnancy (HDP) and GDM.5 Overweight and obesity are a major public health problem affecting more than two-thirds of women of reproductive age.40,41 Limited studies have shown improvement in maternal diet after preconception lifestyle interventions,42,43 but the field of published preconception prospective interventional trials has remained severely lacking.44 Poor and Inappropriate Maternal Nutritional Status is Causally Associated with Abnormal Fetal Growth Patterns Including Low Birthweight (4–4.5 kg), and Large for Gestational Age (>90% Birthweight for Gestational Age), Each of Which is Associated with Increased Risks of Developing Childhood and Adult Chronic Diseases Background and status Examples of the powerful influence of maternal nutrition on fetal development are demonstrated by the pregnancy outcomes associated with neonates at the extremes of birthweight: (1) neonates below the 10th percentile in weight for gestational age at birth are defined as SGA, and (2) neonates born exceeding the 90th percentile in weight for age are defined as LGA. These birthweights represent, in part, the nutritional status of the mother before and during pregnancy but do not necessarily reflect infant body composition (lean and fat mass).45 One of the WHO’s global nutrition targets calls for a 30% reduction in LBW.46 A recent Lancet paper estimated that 20.5 million infants will be born with LBW globally; thus, progress toward achieving the target has been slow.47 Maternal nutritional status, including low and high prepregnancy BMI scores, inadequate weight gain, short stature, anemia, and micronutrient deficiency, were causally associated with LBW, which may be a result of preterm birth, impaired fetal growth, or both. Impact of maternal nutrition on pregnancy outcomes During extremes of maternal undernutrition, the fetus develops chronic FGR,48,49 a prime example of “survival at the expense of growth.” This phenotype includes decreased pancreatic growth, development, and insulin secretion; increased capacity for glucose uptake in peripheral tissues (such as skeletal muscle)50; reduced utilization of amino acids for protein synthesis and cell growth; and development of hepatic insulin resistance with Marshall et al. Page 7 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript increased glucose production in an ovine model that produced hypoxia and reduced nutrient supply in the fetus.51 We now know that the FGR phenotype, especially when followed by later life excess caloric intake, is a risk of the development of obesity, insulin resistance, and DM later in life.52,53 Unfortunately, no strategy has emerged that improves growth and development of the FGR fetus once diagnosed in pregnancy. Previous attempts (maternal oxygen supplementation, bed rest, augmented nutrition, and medications) have either not worked or caused harm.54 Therefore, current management of pregnancies with FGR involves fetal surveillance and delivery of the fetus when adverse physiology becomes apparent, in hopes that the neonate with FGR can be treated more effectively outside the uterus.55 Although there is no direct nutritional strategy for treating FGR, recent studies in sheep have revealed that uteroplacental gene therapy involving vascular endothelial growth factors safely increased fetal growth velocity and reduced the incidence of FGR.56 In addition, recent data indicated that nutritional support and exercise before pregnancy may be more efficacious in promoting healthy placentation and fetal growth than during pregnancy.57 Moreover, the current postnatal strategy in which infant weight is a primary criterion for neonatal intensive care unit or hospital discharge may contribute to excessively rapid catchup growth, especially for body fat mass, as parents and providers are motivated to align newborn intake and nutrition to meet weight gain targets rather than to maintain normal fetal in utero growth trajectories.58,59 At the other extreme, fetal overnutrition from maternal obesity, DM, and high fat and sugar intake may result in macrosomia or LGA.60 These conditions that present excess glucose and lipid supply to the fetus are increasingly common and associated with several complications. Fasting and pulsatile postprandial hyperglycemia promote fetal insulin secretion, contributing to excess glycogen storage and fat accretion in the fetus, especially in pregnancies complicated by T2DM, GDM, and type 1 DM (T1DM), particularly when complicated by obesity.61 Although pregnancies complicated by DM are commonly associated with macrosomia and/or LGA, most cases of these infants are born to mothers with obesity alone, which now affects up to 1 of 3 women.40 Even greater fetal fat mass accumulation occurs with the combination of high maternal plasma glucose and lipid concentrations.61–63 Recent evidence suggested that maternal triglycerides, made available to the fetus by placental lipases that hydrolyze the triglycerides to free fatty acids (FFAs), are primary drivers of fetal fat mass growth in pregnancies with obesity and contribute to accelerated fat mass accumulation in the fetus.61,64,65 Fetuses have limited capacity for fatty acid (FA) oxidation66,67 but can store fat. Excess fat mass accreted in utero might contribute to later obesity, but postnatal fat mass accretion especially during the first 1 to 2 years of life can persist into later life leading to obesity in childhood. In a nonhuman primate model, a maternal Western-style diet resulting in intermittently higher postprandial glucose and lipid exposure to the fetus resulted in the 3-year-old offspring demonstrating higher glucose excursions. Furthermore, the child’s pancreatic islets secreted more insulin, suggesting that these islets were primed before birth to hypersecrete insulin.68 In contrast, extremely high and relatively constant glucose concentrations in the fetus actually can suppress insulin production and response to glucose stimulation.69 This, along with abnormal placentation and decreases in placental perfusion, may explain why some women with long-standing T1DM complicated by vascular diseases will have neonates who are not only SGA but Marshall et al. Page 8 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript also at increased risk of later metabolic disease, especially when exposed to an obesogenic environment.19,69 There is increasing evidence that persistent, very high fetal glucose concentrations can inhibit fetal neuronal development, leading to reduced neuronal number, dendritic proliferation, and synapse formation, ultimately leading to reduced cognitive function in such offspring later in their lives.70 In humans, a recent study in adolescent offspring from women with T1DM showed that cognitive function was significantly diminished, with lower intelligence scores and greater learning difficulties in the offspring whose mothers had more severe hyperglycemia associated with DM.71 Moreover, the rates of congenital heart defects and major malformations of the central nervous system derived from the neural tube, such as caudal regression syndrome, were higher in offspring of mothers with both T1DM and T2DM, and the risk period during organogenesis (30 kg/m2 , regardless of obesity class. Epidemiologic data published since then suggest that the ideal GWG varies by obesity class. For obesity grades I (BMI, 30–34.9 kg/m2 ) and II (BMI, 35.0–39.9 kg/m2 ), studies suggested that maternal gains less than the lower limit of the IOM recommendation may not increase adverse outcomes and may decrease LGA and GDM,161,163,167 although other studies indicated an increased risk of SGA and infant mortality with weight loss and very low weight gain.168–170 However, for women with obesity grade III (BMI, ≥40.0 kg/m2 ), lower levels of gain, or even weight loss, may be optimal, but the current evidence is observational and based on weight alone, not maternal diet or lifestyle behaviors.168,170,171 Because of insufficient evidence at the time, the 2009 guidelines did not provide evidencebased recommendations regarding diet or physical activity changes that would best help women to achieve recommended gains. The recent evidence report and systematic review for the US Preventive Services Task Force (USPSTF) found that counseling and active behavioral interventions to limit GWG were associated with lower risk of GDM, macrosomia, LGA and emergency cesarean delivery and reduced GWG of −1.02 kg172 The led the USPSTF to issue a new recommendation statement that clinicians offer pregnant persons effective behavioral counseling interventions aimed at promoting healthy weight gain and preventing excessive GWG in pregnancy (B recommendation).173 Marshall et al. Page 16 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript As the IOM guidelines focused on high-resource settings, low-resource settings may need different standards to support women who are underweight and have low GWG. In LMICs, improved GWG (100 g/wk) was associated with significantly improved birthweight and length, as was baseline prepregnancy BMI, early weight gain, and GWG from 12 to 32 weeks of gestation.174 Human 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 Lite. Human Milk Composition is Influenced By Maternal Dietary Intake During Lactation And Maternal Adipose Nutrient Stores, Which Together Determine Maternal Milk and Nutrient Production and Composition. Among Women With Gestational Diabetes Mellitus, There is Evidence That Exclusive Breastfeeding For At Least 6 Months Decreases The Risk of Type 2 Diabetes Mellitus For The Mother And is Protective For The Risk of Childhood Obesity in Her Offspring Human milk provides personalized nutrition and is associated with long-term health benefits for infants and mothers.175,176 According to the 2012 American Academy of Pediatrics policy statement, “Given the documented short- and long-term medical and neurodevelopmental advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice.”176 Milk composition is influenced by maternal dietary intake during lactation and maternal adipose nutrient stores, which together are responsible for the nutrients available for milk biosynthesis and ultimately maternal milk and nutrient production.177 To meet all infant nutritional needs, human milk is constantly changing, composition varies by infant age, between breasts, within a feed, throughout the day, during lactation, among women, and among populations. In light of these significant variations, accurate assessment of milk composition remains a challenge for researchers. The evaluation of donor milk pools assumed to come from women not only with adequate milk production to meet their infants’ nutritional needs but also with sufficient quantity to nourish other infants showed significant variations in composition. Among donor pools from the first and third quartiles, milk demonstrated up to a 33% difference in fat content, 22% difference in protein, and 16% difference in energy content.178 Importantly, individual women showed a greater difference in milk composition compared with variation by age of infant or length of time breastfeeding.178,179 Regarding individual macronutrients, maternal diet does not have a major impact on milk protein content or the total amount of fat in human milk, but it affects the types of FAs present in breast milk.180,181 Maternal adipose stores remain an important source of nutrients for human milk, although women with greater fat mass do not produce more or higher fat milk.182 Different lipids are the most variable component of human milk. Lipid composition variability is inversely related to the degree of breast fullness and milk volume. Marshall et al. Page 17 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript In addition to macronutrients and essential micronutrients, there is moderate evidence that flavors from the maternal diet during lactation are transferred into breast milk and that infants can detect diet-transmitted flavors,183 which may impact future taste preferences. The ratio of omega-6 vs omega-3 FAs in human breast milk seemed to promote postnatal fat development; however, this relationship requires further study.184 Interestingly, human milk from women with obesity or T2DM does not seem to expose the infant to a different macronutrient composition; however, it has been shown to have higher insulin levels and to influence the early infant microbiome population; moreover, any effects on infant appetite or growth remain unclear.185,186 Women with GDM who breastfeed have decreased risk of developing T2DM, with a longer duration and increased intensity of breastfeeding associated with a lower 2-year incidence of T2DM.187,188 Furthermore, breastfeeding is associated with a decreased maternal risk of metabolic syndrome,189 CVD,190 and cancer.191 Unfortunately, women who are overweight or women with obesity commonly experience difficulties in lactation and are less likely to meet exclusive breastfeeding goals,192 which suggests additional physiological barriers. The Regular Consumption of Multiple Micronutrient 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 The Cessation of Lactation Or At Least 4 To 6 Weeks After Delivery Evidence supports the benefit of comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) associated with improved birth outcomes of major public health interest (eg, stunting, LBW, and SGA).193 This is supported by the 2020 WHO recommendation stating “antenatal multiple micronutrient supplements that include iron and folic acid are recommended in the context of rigorous research”2 for pregnant women and adolescent girls. Preconception folic acid is recommended for the prevention of neural tube defects.30 Routine supplementation is adequate regardless of the methylenetetrahydrofolate reductase geneotype.194 A recent Cochrane systematic review provided evidence that a daily, multiple micronutrient supplement containing iron-folic acid vs iron-folic acid alone significantly reduces the risk of LBW and SGA in LMIC.31 Wellnourished women who consume an adequate diet may not require additional multivitamin supplementation, but in the absence of comprehensive evaluation by a dietitian, routine supplementation is encouraged in the United States.195 Subgroups that particularly warrant targeted interventions for improving nutrition include nulliparous women and those who are anemic. Anemia in nonpregnant women has recently increased in the United States196 and is estimated to impact 38% of women on a global basis; the prevalence is much higher (> 50%) in certain regions, including South Asia and Central and West Africa.197 Anemia before pregnancy and in the first trimester of pregnancy has been associated with preterm delivery and LBW.198,199 Recently, a growing number of randomized controlled studies suggested Marshall et al. Page 18 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript that the supplementation of choline, especially in women with a history of alcohol use, may improve neurodevelopmental outcomes.200–203 These findings underscored the need for revising the current policy and recommendations for supplement use in pregnancy as an adjunct to the nutritious diet described previously, as supplements alone cannot substitute for a healthy diet. It is Imperative That Healthcare Providers Have The Time And Means to Provide Educational Support And to Discuss Optimal Nutrition With Women of Reproductive Age to Improve Their Health Transformative change is needed for addressing women and girls’ nutrition as they hold roles in their communities that make them drivers of development as individuals and influencers of the health and well-being of their families. Optimal reproductive health can be achieved when maternal nutritional well-being exists. This occurs only when known nutrition interventions are integrally linked to health programs and delivered at scale. Global commitment and political will are needed for driving this agenda forward. Conference experts emphasized the need for preventive health services for women, including nutrition advice during the reproductive cycle. They cited a linkage of individual health behavior change and supportive policy and healthcare environment.204 Thus, greater efforts supporting interventions that provide wholesome nutrition and total micronutrient support are needed. This support will ensure that more women who will become pregnant will experience robust placentation and embryogenesis, resulting in lower risks of diseases in their offspring because of optimal epigenetic regulation of organs.205 Key Questions Question 1: What are the unique nutritional requirements of a normal pregnant woman and what unique features of diets produce optimal health and growth of her fetus and infant? The WHO defines good nutrition as “intake of food necessary for optimal growth, function, and health. Good nutrition is defined as a well-balanced diet that provides all essential nutrients in optimal amounts and proportions, whereas poor nutrition is defined as a diet that lacks nutrients (either from imbalance or [from] overall insufficient food intake) or one in which some components are present in excess.”26 Additional features of a healthy diet include foods that are accessible, acceptable, affordable, safe, culturally appropriate, and composed primarily of whole foods consumed in moderation. There is growing evidence that diet and nutritional status at preconception, starting as early as childhood and adolescence, seems to be equally or even more important26 than during pregnancy, because of growing evidence that nutrition affects fertility and the early development of the placenta and fetus, which occur well before a woman recognizes that she is pregnant21 About half of US women of childbearing age consume unhealthy diets that are too high in processed ingredients, fat, sugar, and other refined carbohydrates and do not meet current nutritional recommendations.13,14,16 Marshall et al. Page 19 Am J Obstet Gynecol. Author manuscript; available in PMC 2022 June 09. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Although it is commonly said that pregnant women are “eating for two,” for most women, average energy requirements increase only modestly.206 In contrast, assuming that the preconception diet was adequate, prenatal needs for some micronutrients, for example, folate and iron, increase by one-third to one-half, respectively.207 The WHO has declared iodine deficiency as the single most common cause of brain damage, after starvation, and mild iodine deficiency is still a public health concern in both developing countries and Western industrialized nations, especially Europe.208 Iodine requirements are increased during pregnancy and in nursing mothers from 250 to 300 μg per day (compared with 150 μg outside of pregnancy). These requirements begin very early because of the fetal need to synthesize thyroid hormone, critical for early neurogenesis, proliferation migration, differentiation, neurite outgrowth and guidance, synaptogenesis, and myelination. The fetal thyroid begins to concentrate iodine at 10 to 12 weeks of gestation and begins making thyroid hormone with complete independence from maternal thyroid hormone production by 18 weeks of gestation.209,210 It has been demonstrated that mild-moderate iodine deficiency, which is common in pregnancy, is associated with a 10-point decrease in total intelligence quotient score and an increase in attention-deficit and hyperactivity disorder in the offspring.211 Women and providers commonly ask what a healthy diet for a pregnant woman should look like and the message to US women should be “eat better, not more.” This can be achieved by basing the diet on a variety of nutrient-dense, whole foods, including fish, fruits, vegetables, omega-3 FAs, and whole grains, in place of poorer quality processed foods and beverages to enhance nutritional quality without excessive energy intake (USDA Dietary Guidelines) (Figure 3; Table 2). Maternal requirements vary by individual characteristics, and in addition to considering dietary quality before pregnancy, factors, such as maternal body size, age, gestational age, multiple gestation, 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 (https://www.choosemyplate.gov/browse-by-audience/view-all-audiences/adults/ moms-pregnancy-breastfeeding). Table 3 shows the primary features of a healthy diet for discussing a healthy diet with patients, and Tables 4 and 5 shows questions as conversation starters for healthcare providers when talking to patients. Question 2: What is the optimal balance of macronutrients during pregnancy and lactation to support and maintain appropriate nutrient supply to the infant through lactation? Diet planning is especially important for women planning to conceive, during pregnancy, and during lactation. Dietary patterns are an evolving area of research involving the entirety of the diet rather than focusing on individual nutrients or foods. There is limited but consistent evidence primarily in healthy White women with access to healthcare that dietary patterns before and during pregnancy higher in vegetables, fruits, whole grains, nuts, legumes, fish, and vegetable oils and lower in meat and refined grains are associated with a reduced risk of disorders of pregnancy, including preeclampsia, gestational hypertension, GDM, and preterm birth.4–6 Conclusions about the association between dietary patterns during pregnancy and birthweight outcomes is less consistent and restricted by inadequate