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Nutrition During Pregnancy and Lactation: Exploring New

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Nutrition During Pregnancy and Lactation: Exploring New Evidence: Proceedings of a Workshop
Maternal Intakes and Nutritional Status

During Lactation and the Implications
for Maternal and Infant Health
Evidence on the complex interplay between maternal nutrition,

health, exposures, and lactation and the implications for maternal and
infant health has grown in recent years. There have been improvements
in the techniques for assessing the nutrient content of breast milk, which
could inform updates of estimates of infant nutrient needs. With the
growing prevalence of obesity and diabetes in the population, studies
have explored the relationship between these conditions and lactogenesis
and breast milk composition. A growing body of evidence also suggests
that breastfeeding has long-term metabolic consequences for the mother,
lowering her risk of cardiometabolic disease. Session 6 of the workshop,
moderated by Deborah O’Connor of the University of Toronto, provided
an overview of these topics. Highlights from the session presentations are
presented in Box 7-1.
MATERNAL MICRONUTRIENT STATUS AND INTAKE:

EFFECTS ON HUMAN MILK COMPOSITION
Lindsay H. Allen, director of the U.S. Department of Agriculture’s
(USDA’s) Agricultural Research Service Western Human Nutrition Research
Center acknowledged that human milk is an infant’s best source of nutri-
tion. “I think the fear of upsetting this concept has in a way [inhibited]
research on what is in milk as far as micronutrient composition,” she said.
In her review of current evidence on the relationship between maternal
nutrient status, maternal intake, and human milk composition, Allen dis-
cussed the analysis of human milk micronutrient composition, updated
87
PREPUBLICATION COPY—Uncorrected Proofs
Copyright National Academy of Sciences. All rights reserved.

88 NUTRITION DURING PREGNANCY AND LACTATION
BOX 7-1
Highlights from the Session 6 Presentations
• Data on micronutrient content of breast milk in the United States is lacking

(Allen).
• Some previous estimates of breast milk nutrient composition may have over-
estimated content, leading to Adequate Intake values for infants and lactating
women that potentially exceed their needs, but milk nutrient content is lower
where maternal dietary quality is poor (Allen).
• There is evidence of bidirectional relationships between lactation and both
maternal obesity and diabetes, but there may be confounding by metabolic
status prior to and during pregnancy (Demerath).
• A number of research gaps remain regarding relationships between maternal
metabolic status and breast milk composition and merit further exploration
(Demerath).
• Lactation can reset maternal metabolism, including lowering triglycerides,
low-density lipoprotein-cholesterol, blood glucose concentrations, and fast-
ing insulin levels, and preserving higher high-density lipoprotein-cholesterol
concentrations (Gunderson).
• Longer lactation duration and greater lactation intensity are associated with up
to 50 percent lower risk of incident type 2 diabetes in women independent of
metabolic status before conception or during pregnancy, obesity, and lifestyle
factors, and this lowering of risk has also been shown in women with gesta-
tional diabetes (Gunderson).
• Lactation is a lifestyle behavior with important implications for women’s cardio
metabolic health that requires investigation of the biochemical mechanisms
underlying the epidemiologic evidence (Gunderson).
NOTE: These points were made by the individual workshop speakers identified
above. They are not intended to reflect a consensus among workshop par-
ticipants. The statements have not been endorsed or verified by the National
Academies of Sciences, Engineering, and Medicine.
estimates for selected nutrients, and the Mothers, Infants and Lactation
Quality (MILQ) study.
Analysis of Human Milk Micronutrient Composition

Describing the state of the evidence on human milk micronutrient
composition in the United States as poor, Allen reviewed several challenges
that exist. A primary challenge is determining the appropriate approach
to measure each of the 40 or more nutrients of interest. The human milk
matrix is different from plasma, requiring different analytical techniques.
Human milk collection is also an issue, as the best approach is not yet

MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 89
known. Additionally, there are various maternal factors (e.g., supplement

use) that need to be considered in analyzing and interpreting data.
Some, but not all, nutrients in human milk are dependent on maternal
status and to a lesser extent on maternal intake. For instance, human milk
concentrations of folate, calcium, iron, copper, and zinc do not change with
maternal supplementation. By contrast, human milk concentrations of the
fat-soluble vitamins, thiamin, riboflavin, vitamin B6, vitamin B12, choline,
iodine, and selenium are affected by maternal status and are the nutrients
that have the most implications for public health interventions, noted Allen.
The Dietary Reference Intakes (DRIs) include estimates of nutrient
needs. For infants, Adequate Intakes (AIs) are established using breast milk
composition data available at the time of review. Reiterating that the evi-
dence on breast milk nutrient composition is poor, Allen showed the basis
of select infant AIs and noted that estimates have been derived from single
studies with few participants (see Table 7-1). She characterized the state of
TABLE 7-1 Summary of Data Available for Setting Adequate Intakes for
Infants and Lactation for Select Nutrients
Nutrient Value Used by IOM Data Range/Other Studies
Vitamin B1 0.21 ± 0.4 mg/L Only study,
source unknown
Vitamin B2 0.35 (0.31–0.51) mg/L n = 5, USA Only 1 study with valid
methods
Niacin 1.8 (1.2–2.8) mg/L n = 23 Only 1 study
(UK 16–244 d)
Pantothenic 1.7 mg/d 2 studies Range: 2.2–2.5 mg/L, but
acid (UK, USA) higher values include women
consuming supplements
Vitamin B6 0.13 (0.07–0.18) mg/L n = 6 (USA, Intakes were < RDA
3 wk to 30 mo) mean = 0.24 versus 0.31 if
intake > RDA
Biotin 5 μg/d 3 studies Range: 3.8–7ug/L but different
methods across studies
Vitamin B12 0.42 (0.01–1.47) μg/L n = 9 (Brazil, 0.31 (vegan), 0.34, 0.91
4 d to 3 mo) (supplemented)
Choline 125 mg/d 2 studies 160–200 mg/L
Vitamin C 50 mg/L 8 studies, Range 34–83 mg/L if no
n = 12–200/study supplement
NOTE: d = day; IOM = Institute of Medicine; mg/L = milligrams per liter; μg/d = micrograms
per day; μg/L = micrograms per liter; mo = months; RDA = Recommended Dietary Allowance.
SOURCES: Presented by Lindsey Allen. Adapted from Allen et al., 2018.

the evidence as “an appalling sparsity of data on which to set the recom-
mendations for infants and for lactation.”
Allen’s lab focuses on developing efficient analytical methods for
analyzing breast milk composition, using techniques such as inductively
coupled plasma mass spectrometry and high-performance liquid chroma-
tography. She indicated that mass spectrometry has been transformative
and can be used to measure most of the B vitamins. Allen’s team is also
starting to investigate metabolomics. Recent breast milk estimates globally
show median concentrations below the values that were used for the exist-
ing infant AIs for several micronutrients.
Updated Estimates for Select Nutrients

Allen showed examples of where new evidence has emerged on breast
milk micronutrient concentrations. Her remarks included comments on
thiamin, vitamin B6, iodine, vitamin B12, and vitamin D.
Thiamin
The breast milk concentration used to establish the infant AI for
thiamin was 210 μg/L and was derived from a single study. New evidence
from a collection of high-income countries revealed a median thiamin
concentration in breast milk of 125 μg/L. A supplementation trial con-
ducted in Cambodia was able to increase breast milk concentrations from
approximately this level to the concentrations used to establish the infant
AI for thiamin. However, the new estimate of median concentrations is
likely closer to normal and suggests the infant AI for thiamin is higher than
infant needs, said Allen.
Vitamin B6
The prevalence of vitamin B6 deficiency is not well characterized
nationally or internationally. Based on 2014 National Health and Nutri-
tion Examination Survey (NHANES) data, 24 percent of U.S. women who
do not use supplements have low serum pyridoxal phosphate; serum and
breast milk concentrations are correlated, added Allen. In several countries,
particularly low-income countries, breast milk vitamin B6 concentrations
are below 0.13 mg/L, the value used to establish the infant AIs. One small
study, conducted in lactating women from Davis, California, who were
not taking supplements during lactaction, found an average vitamin B6
concentrations of 0.3 mg/L. Allen suggested that this higher concentration
could possibly be attributable to high vitamin B6 content of some prenatal
vitamins.

Iodine
“I would say of all the nutrients, iodine is the most sensitive to maternal
intake,” stated Allen. She noted that despite salt fortification programs, low
concentrations of iodine in breast milk are common. Across longitudinal
studies iodine concentrations in breast milk are variable, but generally there
is a marked decrease in iodine content during the first month of lactation.
The only longitudinal study assessing the iodine content of breast milk in the
United States was conducted in 31 Mexican American women and found
concentrations below the values used to establish the iodine AIs for infants.
Breast milk iodine concentrations mirror maternal urinary iodine excretion.
In a systematic review of 57 studies, the concentration of iodine in breast
milk was 13–18 μg/L among women with goiter, whereas women in areas
with effective salt iodization had breast milk iodine concentrations exceeding
90 μg/L.
Different groups have considered improving the iodine status of lactat-
ing women. For instance, the American Pediatric Association and American
Thyroid Association recommend that lactating women supplement with
150 μg/day, and the World Health Organization (WHO) recommends that
lactating women in areas with moderate or severe iodine deficiency supple-
ment their diets with 250 μg/day. Iodine is preferentially lost in breast milk
over urine when status is low during lactation. To that end, it has been
suggested that the iodine content of breast milk may be a better indicator
of iodine status among lactating women (Dold et al., 2017).
Allen noted that older analytical techniques for measuring iodine
concentrations in breast milk are no longer considered valid. The breast
milk iodine concentration, used in the derivation of the iodine AIs for
infants and lactating women, came from a single study from 1984. New
evidence suggests infant needs are lower than previously estimated, mean-
ing the iodine AI for lactating women is likely too high, said Allen. She
continued with the caveat that infants have limited opportunity for iodine
exposure. Weaning infants are at risk of iodine deficiency, particularly
when breast milk iodine content is low, as complementary foods tend to
be low in iodine.
Vitamin B12
A recent systematic review has assessed the state of the evidence on the
vitamin B12 content of breast milk (Dror and Allen, 2018). Allen reported
that 7 of the 26 identified studies used invalid analytical techniques. Vita-
min B12 concentrations vary widely, but they appear to decrease during
early lactation. The vitamin B12 content of breast milk correlated with
maternal intake, along with maternal and infant status.

There is no consensus on whether lactating women in high-income

countries should be supplementing with vitamin B12. Danish investigators
who support supplementation have reported that breast milk vitamin B12
concentrations dramatically decrease during the middle of lactation, which
is accompanied by increases in infant methylmalonic acid concentrations.
Allen’s recent data do not support a drop in vitamin B12 concentrations
during the middle of lactation
Allen’s lab found that the vitamin B12 concentrations of breast milk
in Canada, Denmark, Ghana, and the United States are close to the value
used to establish the infant AIs for vitamin B12. Concentrations were
markedly lower in countries with lower intakes of animal sources of food.
This evidence indicates vitamin B12 concentrations in breast milk are heav-
ily influenced by maternal intake. Despite this, there is virtually no data
available on vegetarian and vegan lactating women in the United States,
indicated Allen.
Allen explained that three studies conducted in Guatemala have char-
acterized the continuum of maternal–child vitamin B12 depletion. Deple-
tion during pregnancy can lead to low vitamin B12 stores in infants at
birth and in breast milk. Infant stores will be depleted by 3 months of age
and will remain so for 7 to 12 months, despite supplementation or more
frequent breastfeeding. Cow milk intake can improve infant status, as its
vitamin B12 concentration is higher than breast milk. Vitamin B12 deple-
tion of infants after about 3 months of age can lead to growth and motor
development deficits.
Evidence from intervention studies underscore the importance of
improving maternal vitamin B12 status during pregnancy, noted Allen.
Maternal serum vitamin B12 concentrations in early pregnancy are asso-
ciated with infant status at 4–6 months of age. Allen suggested the dose
matters, and smaller repeated exposures during lactation, rather than a
single one-a-day supplement appear to be more effective. Despite the link
with maternal dietary patterns, Allen stated that current intake is not the
main influence on breast milk vitamin B12 concentrations.
Vitamin D
Breast milk is a poor source of vitamin D. As such, the American
Academy of Pediatrics recommends 400 IU/day of vitamin D be given to
breastfed infants. A recent study has demonstrated that lactating women
who take a 6,400 IU/day vitamin D supplement can supply infants with
sufficient vitamin D through breast milk (Hollis et al., 2015). Pointing out
that the supplement dose exceeds the vitamin D Tolerable Upper Intake
Level of 4,000 IU/d, Allen indicated that such an intervention may not be

practical, but demonstrates the level of supplementation needed to increase

vitamin D concentrations in breast milk.
Other Micronutrients
Allen stated that there is no breast milk composition data for several
micronutrients. As an example, she explained that survey data from C anada,
Europe, Ireland, and the United Kingdom found riboflavin depletion in
20–60 percent of adults and commented that there are no estimates for the
United States. Severe riboflavin deficiency has been associated with poor
infant growth and development. Evidence from low-income countries indicate
that breast milk concentrations respond to maternal intake to a greater degree
than many of the other nutrients. Maternal supplementation during lacta-
tion, however, may not be an effective strategy for some nutrients. A study of
exclusively breastfed infants in Malawi found that 2–5 percent of nutrients in
a supplement given to lactating women appears in their breast milk.
MILQ Study
Allen closed her presentation by providing a brief overview of the
MILQ study. The goal of the project is to create human milk reference
values for nutrients during the first 9 months of lactation. The study aims
to recruit 1,000 well-nourished, nonsupplemented women and their infants
from four countries.
THE IMPLICATIONS OF MATERNAL WEIGHT AND METABOLIC

STATUS FOR LACTATION AND BREAST MILK COMPOSITION
Ellen Demerath, professor of epidemiology and community health at
the University of Minnesota School of Public Health, opened her remarks
by emphasizing that the weight and metabolic status of the population has
significantly changed over the past 30 years. When Nutrition During Lacta-
tion report was published in early 1990s, the prevalence of obesity among
adults was 11.4 percent and the prevalence of gestational diabetes was
2 percent (IOM, 1991). Current estimates are markedly higher: 37 percent
of U.S. women 20–39 years of age are estimated to have obesity (Flegal
et al., 2016); 19.3 percent of U.S. adults have prediabetes (Menke et al.,
2018); and anywhere from 5–6 percent to 15–20 percent of women have
gestational diabetes (NIH Consensus Development Panel, 2013). Given this
context, Demerath went on to discuss the implications of these conditions
for maternal health and infant programming, breastfeeding outcomes, and
breast milk composition.

Implications for Maternal Health and Infant Programming

Maternal obesity has been linked to a host of negative pregnancy,
maternal, and childhood outcomes. Odds of gestational diabetes, pre-
eclampsia, stillbirth, Cesarean section, and being large for gestational age
increase with maternal obesity. Excessive gestational weight gain has been
associated with postpartum weight retention, and maternal obesity has been
associated with maternal risk for type 2 diabetes. The offspring of mothers
who have obesity are at increased odds of having obesity during childhood
and developing type 2 diabetes (Catalano and Shankar, 2017; Kulie et al.,
2011; Lahti-Pulkkinen et al. 2019).
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study
and HAPO Follow-Up Study provided critical insight into the influence of
gestational diabetes. Compared to women who did not develop gestational
diabetes, those who did had higher rates of Cesarean section, offspring
who were large for gestational age, preterm infants, preeclampsia, maternal
prediabetes, maternal type 2 diabetes, and offspring diabetes (Hod et al.,
2019).
Demerath noted that, in the past 30 years, the fields of epidemiology
and public health have embraced the concept that chronic disease risk is
set in early life. “We talk about two-generational policies and programs
now,” she said. Breastfeeding helps to set the infant’s metabolic expecta-
tions for future growth and may help to reset maternal insulin resistance
that occurred during pregnancy. The concept of lactational programming
suggests that maternal nutrition, health, and exposures can affect the com-
position of her breast milk, having implications for programmed offspring
outcomes (see Figure 7-1).
Using a rodent model, Vogt et al. (2014) demonstrated that lactation
serves as a critical period for programming offspring appetite. A high-fat
diet, provided exclusively during lactation, led to increases in milk glucose
and insulin concentrations, reductions in neuronal fiber density in regions
of the brain associated with appetite regulation, and increases in offspring
bodyweight, adiposity, and glucose tolerance. The exposure to milk from
a maternal high-fat diet during lactation led to life-long effects in the off-
spring’s metabolic function and weight status, even when the offspring
consumed a low-fat diet after weaning.
Breastfeeding appears to modify metabolic risk transmission, indicated
Demerath. The Study of Women, Infant Feeding and Type 2 Diabetes after
GDM1 Pregnancy (SWIFT) found that infants of mothers with gestational
diabetes had lower weight status in the first year if they were intensively
breastfed (Gunderson et al., 2018). Other studies have reported that breast-
1 GDM is gestational diabetes mellitus.

FIGURE 7-1 Schematic of lactational programming concepts.

SOURCES: Presented by Ellen Demerath. Copyright Gregg Lab, reprinted with
permission.
feeding exclusivity and duration mitigate the effects of maternal gestational

diabetes and obesity on childhood outcomes, including adiposity and child-
hood obesity (Crume et al., 2011; Li et al., 2005; Mayer-Davis et al., 2006).
Demerath emphasized that breastfeeding has important maternal and child
health benefits, as compared to formula feeding, and that changes to mater-
nal metabolic status as a result of lactation have biological underpinnings.
She also underscored that the composition of breast milk is superior to
infant formula, but it can be affected by maternal obesity and diabetes.
Implications for Breastfeeding Outcomes

The Infant Feeding Practices Study (IFPS) found that one in eight
women did not achieve their breastfeeding goals (Steube et al., 2014). One
of the identified barriers to success was depression. “What is psychological
for the mother can become physiological and nutritional for the offspring,”
commented Demerath. The study also found obesity to be among the key
barriers.
Other studies have provided evidence that obesity affects breastfeeding
outcomes. For instance, an analysis of 2004–2011 data from the Preg-

nancy Risk Assessment Monitoring System (PRAMS) reported lower rates

of breastfeeding continuation among mothers with higher levels of pre-
pregnancy obesity (Kachoria et al., 2015). Maternal obesity has also been
associated with delayed prolactin release and a lower prolactin response to
suckling, and it appears to lower milk transfer, noted Demerath. She added
that women who have obesity have higher rates of Cesarean section, a
stressor that could have an effect on lactation. Issues of positioning, latch-
ing, body confidence, and comfort breastfeeding in public are other factors
that shorten breastfeeding duration among women with obesity. Demerath
explained there are disparities across different race and ethnicity groups,
which are confounded by socioeconomic status. Among 81,669 participants
in the Special Supplemental Nutrition Program for Women, Infants, and
Children (WIC) in Minnesota, for example, there was a graded increase in
the risk of breastfeeding cessation by 6 months among non-Hispanic white
and Hispanic mothers with increasing prepregnancy body mass index (BMI)
status, but the relationship was not see among African American mothers.
Evidence on the relationship between gestational diabetes and breast-
feeding outcomes are less clear. In the SWIFT study, approximately one-
third of women with gestational diabetes had delayed lactation, which
was exacerbated by insulin treatment, noted Demerath. In contrast, IFPS
II did not find shortened breastfeeding durations among women who self-
reported they had gestational diabetes (Wallenborn et al., 2017).
A more recent line of investigation has explored hormonal determi-
nants of lactation. The hormone leptin is elevated in individuals with obe-
sity. In vitro studies suggest leptin may inhibit oxytocin from promoting a
muscle-contracting effect, which could possibly affect breast milk ejection
(Moynihan et al., 2006). Elevated leptin may also promote prolactin resis-
tance (Buonfiglio et al., 2016). Insulin appears to promote expression of
genes related to milk protein synthesis, whereas insulin resistance may have
an opposing effect, reducing expression of a key milk production protein
(Lemay et al., 2013). Less is known about cortisol, but elevated levels may
counter the effects of insulin and prolactin, said Demerath.
Relationships between lactation and both maternal obesity and diabe-
tes appear to be bidirectional, but there may be confounding by metabolic
status prior to and during pregnancy, Demerath said. To improve breast-
feeding rates, she suggested that trials are needed to better understand
causal relationships with breastfeeding outcomes among women with obe-
sity and diabetes.
Implications for Breast Milk Composition

Breast milk is composed of more than 1,000 compounds, including
macronutrients, fatty acids, hormones, immune factors, antimicrobials,

oligosaccharides, microbiomes, and environmental pollutants. A host of

maternal, physiological, behavioral, and infant factors contributes to breast
milk composition (Fields et al., 2016). Breast milk often mirrors maternal
serum concentrations but not for all factors. Some compounds are actively
transported or synthesized in the lactocytes, leading to differences in con-
centrations. For instance, concentrations of adiponectin are higher, and
leptin, insulin, and fatty acid are lower in breast milk than in maternal
serum. Breast milk composition also changes as a women progresses from
producing colostrum to late mature milk. Demerath identified some limita-
tions in the literature, including a lack of evidence on breast milk compo-
sition after 6 months and studies being primarily observational in design
with small sample sizes.
Relationships between maternal metabolic status and breast milk
macronutrient composition have been explored. The Davis Area Research
on Lactation, Infant Nutrition and Growth (DARLING) study reported
that mothers with higher relative weight had higher lipid concentrations in
their breast milk (Nommsen et al., 1991). Women with obesity have also
been found to have higher omega-6 and lower omega-3 long-chain poly
unsaturated fatty acid composition in their breast milk, as compared to lean
women (García-Ravelo et al., 2018; Panagos et al., 2016). Other studies
of total breast milk lipid, protein, and lactose concentrations, however,
reported only small or no differences in composition across prepregnancy
BMI or gestational weight gain groups (Chang et al., 2015; Michaelsen et
al., 1994; Quinn et al., 2012). Demerath suggested that additional research
is needed to disaggregate the roles of maternal diet and obesity on breast
milk composition.
Evidence is less robust linking maternal metabolic status to breast
milk micronutrient composition. Carotenoid and vitamin D concentrations
have been reported to be lower in the breast milk of women with obesity
(Panagos et al., 2016). Characterizing the evidence as sparse, Demerath
thought that more evidence on the role of maternal metabolic status on
the vitamin, mineral, and polyphenol content of breast milk is warranted.
Demerath next discussed bioactive compounds in breast milk. Leptin,
insulin, and ghrelin are three hormones that play a role in appetite, satiety,
and metabolism, and concentrations are altered in the serum of adults with
obesity. Because they can survive digestion, these compounds have been
found to enter infant circulation intact and retain their bioactive proper-
ties. Maternal prepregnancy BMI is positively associated with breast milk
leptin and insulin content (Fields and Demerath, 2012; Sadr Dadres et al.,
2019; Whitaker et al., 2017; Young et al. 2017). Gestational weight gain,
particularly among women with a normal prepregnancy BMI, also appears
to influence bioactive concentrations in breast milk, indicated Demerath.
Emerging data suggest that insulin may have a stronger effect on gene

expression and phenotype in female infants as compared to male infants

(Fields et al., 2017). Other factors may not have relationships with mater-
nal weight status. Concentrations of interleukin-6 in breast milk at 1 and
3 months postpartum were not associated with maternal BMI or gestational
weight gain (Whitaker et al., 2017), although Collado et al. (2012) reported
higher concentrations among women with obesity. With the studies varying
in design and timing of sample collection, evidence of relationships between
concentrations of adiponectin in breast milk and prepregnancy BMI is
mixed (Chan et al., 2018; Ley et al., 2012; Sadr Dadres et al., 2019). Few
studies have explored breast milk immunological function by maternal
weight status (Erliana and Fly, 2019).
Diabetes may also alter breast milk composition. Higher breast milk
concentrations of insulin and glucose have been found in women with
type 1 and type 2 diabetes (Jovanovic-Peterson et al., 1989; Schaefer-Graf
et al., 2006; Whitmore et al., 2012). Concentrations of insulin and some
cytokines appear to be higher in the breast milk of women with gestational
diabetes, noted Demerath. Concentrations of ghrelin in breast milk appear
to be lower among women with gestational diabetes or preexisting diabetes,
but this relationship is not seen in mature breast milk (Aydin et al., 2007).
Preliminary data have explored breast milk metabolomic differences
by maternal BMI (Isganaitis et al., 2019). At 1 month postpartum, con-
centrations of nine breast milk metabolites were significantly different
between women who had overweight or obesity compared to women with
normal BMIs. Three of the differing metabolites were oligosaccharides,
including 2′-fucosyllactose, said Demerath. Maternal BMI and infant body
fatness were both positively associated with breast milk concentrations
of adenine and 5-methylioadenoisine. Evidence on maternal metabolism,
human milk oligosaccharides (HMOs), and the human milk microbiome is
rapidly emerging and evolving, Demerath said. In the largest study to date,
prepregnancy BMI and HMO concentrations in breast milk were not found
to be associated (Azad et al., 2018).
Demerath pointed out that little is known about the breast milk compo-
nents that influence infant growth, although evidence is emerging. Whereas
maternal obesity has been associated with higher circulating leptin concen-
tration, infant weight status and adiposity appears to be negatively associ-
ated with leptin concentrations in breast milk. Demerath thought that the
elevated concentrations of leptin may be serving their functional role in
infants and downregulating appetite.
To close her presentation, Demerath highlighted a few implications
from the evidence she presented. She suggested that the issues leading
women to not achieve their breastfeeding goals underscores the importance
of lactation support. Estimates of breast milk composition and its relation-
ship with maternal nutrition need to be updated, Demerath said. She also

noted that the comparative analysis of the existing body of evidence is dif-
ficult because of differences in study design and confounding. She said that
women of lower socioeconomic status are less likely to be reflected in the
data. Finally, she explained that while donor milk banks standardize for
macronutrients, they do not standardize for other breast milk factors, and
she thought further work was needed to preserve the content donor milk.
LACTATION AND THE FUTURE RISK OF

CARDIOMETABOLIC DISEASES IN WOMEN
Erica P. Gunderson, epidemiologist and senior research scientist at the
Division of Research, Kaiser Permanente Northern California, focused
her remarks on evidence of the lasting effects of lactation on metabolic
and cardiovascular health outcomes in women. Gunderson provided an
overview of the continuum of maternal health from preconception through
postdelivery; she also reviewed the limitations of the evidence base on lac-
tation and the development of type 2 diabetes and cardiovascular diseases
in women. In addition, Gunderson discussed the study designs and key
findings from the Coronary Artery Risk Development in Young Adults
(CARDIA) Study and SWIFT, and offered her reflections on the importance
of this emerging evidence base.
The Continuum of Maternal Health

The relationships between pregnancy, lactation, and long-term mater-
nal health outcomes has only recently become an active area of research. In
2010, an Agency for Healthcare Research and Quality review found that
women who did not breastfeed had higher risk of breast cancer and ovarian
cancer, but it reported that there were insufficient data to assess the risk of
type 2 diabetes and cardiovascular disease.
“Pregnancy and lactation form a single continuum within the repro-
ductive cycle where alterations of physiologic demands may have lasting
consequence for future disease outcomes in women,” said Gunderson.
Although this continuum extends before, during, and after pregnancy, most
studies have only focused on pregnancy rather than the preconceptual or
postpartum periods. During pregnancy, there are metabolic changes, such
as increased insulin resistance, altered glycemic control, fat mass deposi-
tion, and inflammation. Blood volume also expands 40–50 percent dur-
ing pregnancy, increasing cardiac output and decreasing blood pressure.
“Each of these different adaptations, if they happened in any other physi-
ological state, would be considered pathologic,” suggested Gunderson. She
further noted that prepregnancy obesity may exacerbate these metabolic
aberrations.

Women who had an uncomplicated pregnancy experience an increase

in chronic disease risk with age, typically occurring after age 60. Pregnancy
complications, however, increase the risk of women experiencing chronic
disease earlier in life. Women who had gestational diabetes are at increased
risk for type 2 diabetes, with a substantial portion of conversion occurring
in the first few years postpartum (Bellamy et al., 2009). As a risk factor for
cardiovascular disease, type 2 diabetes serves as an early predictor. Even if
a woman does not go on to develop type 2 diabetes, she is still at a 30 per-
cent higher risk for cardiovascular disease (Retnakaran et al., 2017; Tobias
et al., 2017). Lactation can “reset maternal metabolism,” Gunderson said,
including lowering triglycerides, low-density lipoprotein-cholesterol, blood
glucose concentrations, and fasting insulin levels, and preserving higher
high-density lipoprotein-cholesterol concentrations.
Limitations of Previous Studies

Studies assessing the relationships between lactation and lasting
effects on chronic disease risk have suffered from issues of study design,
asserted Gunderson. Most studies have not been designed to address the
potential for reverse causality. Randomized trials to investigate this topic
are not feasible, as randomization of individual women to breastfeed or
not is not ethical and randomizing clusters to breastfeeding support is
expensive and has low statistical power. Observational studies often rely
on self-reported data. Retrospective studies are limited by the lack ante-
cedent biochemical data (i.e., metabolic status prior to lactation). Some
prospective observational studies of older women can also suffer from
issues of retrospective reproductive exposure data and lack of antecedent
biochemical measures.
Pooled data from observational studies, many of which were cross sec-
tional or case–control design, found an approximate 7 percent reduction in
hypertension among women who breastfed, but there was no graded asso-
ciation based on reported duration of breastfeeding (Qu et al., 2018). These
studies did not assess pregnancy complications or antecedent risk factors,
and some included older women. A recently published 6-year prospective
study reported slightly stronger protective effect of lactation on cardio
vascular disease hospitalization, but it did not find a dose–response rela-
tionship with breastfeeding duration (Nguyen et al., 2019). The protective
effect was stronger for cardiovascular disease mortality, particularly among
older women. Gunderson showed that several prospective epidemiological
studies have found relatively weak relationships between breastfeeding and
cardiovascular disease, and noted that many of the studies were conducted
in older women. The European Prospective Investigation into Cancer and
Nutrition (EPIC) Study, which included young women, found breastfeed-

ing to be slightly more protective against cardiovascular disease and type 2

diabetes than other studies did (Jäger et al., 2014; Peters et al., 2016).
These previous epidemiological studies have suffered from issues of
internal validity, said Gunderson. None of the studies had metabolic or
cardiovascular disease risk factors measured prior to women initiating
breastfeeding, nor did they include assessments of pregnancy complications.
Measures of disease outcomes are also limited, as they are typically self-
reported. As women younger than 45 years of age are not routinely tested
for cardiometabolic risk factors or type 2 diabetes, Gunderson suggested
that this could lead to the selection bias of study participants. Additionally,
despite an overall relationship, the studies failed to find a dose–response
relationship.
CARDIA and SWIFT Studies: Longitudinal Biochemical Evidence

CARDIA and SWIFT are two robust longitudinal studies that were
designed to overcome the limitations of previous assessments of the rela-
tionships between lactation and long-term metabolic disease risk based
on longitudinal biochemical data. Whereas previous studies have enrolled
postmenopausal women and asked women to recall their lactation history
(retrospective design), CARDIA and SWIFT enrolled participants before
and during pregnancy, respectively, and followed them prospectively. Both
studies also obtained biochemical measurements both prior to and after
lactation, across time. The prospective and longitudinal measures of the
antecedent metabolic risk factors are crucial for any causal inferences,
because it is important to establish that women who breastfed or did not
breastfeed, or who differed in lactation duration, had equivalency of mater-
nal metabolism or obesity before lactation to address potential confound-
ing, explained Gunderson.
CARDIA
Gunderson highlighted some of the key study design elements that
sets CARDIA apart from other epidemiological studies that have explored
the relationship between lactation and long-term chronic disease risk. The
study enrolled 2,787 women 18–30 years of age (mean age: 24 years) who
were followed for 30 years. Half of the cohort was black and half was
white. Biochemical data were collected longitudinally beginning from the
preconception period, and assessments were performed years later to col-
lect measures of diabetes and metabolic disease. The study’s data collection
schedule allowed for a greater understanding of the cardiometabolic risk
factors present prior to pregnancy, the changes in the metabolic risk factors,
and other factors that may affect the lactation–disease relationship, includ-

ing adverse pregnancy outcomes. The prospective cohort naturally included

a group of women who never breastfed.
A 2010 analysis of CARDIA data found positive relationships between
increasing lactation duration and favorable changes in cardiometabolic
outcomes (Gunderson et al., 2010). There was a strong inverse associa-
tion between lactation duration and the incidence of metabolic syndrome
in both women with and without gestational diabetes. Although women
with gestational diabetes were at increased risk of developing metabolic
syndrome, longer breastfeeding duration conferred to them a similar lower
risk of metabolic syndrome, for whom the risk of the metabolic syndrome
was similar among women with and without gestational diabetes with
breastfeeding duration of 9 months or longer.
Overall, the CARDIA women were a relatively healthy cohort at base-
line. Those who never breastfed had slightly higher BMIs and modestly
higher insulin resistance than those with longer breastfeeding duration,
although Gunderson questioned the clinical significance of the differences
within normal levels. History of gestational diabetes and fasting glucose
results, however, did not differ across the lactation duration groups. Given
this context, Gunderson et al. (2018) found a strong, graded protective
association among lactation duration groups and the risk of developing
type 2 diabetes. Women who had gestational diabetes were at higher risk of
developing diabetes during the 30 years, but they showed a similar decrease
in relative risk with longer breastfeeding duration. Based on multivariate
models that accounted for numerous covariates, including preconception
metabolic risk factors,2 there remained strong inverse, graded associations
between lactation duration and diabetes risk. Compared to women who
never breastfed, those who breastfed for longer than 6 months had approxi-
mately a 50 percent relative reduction in the risk of developing diabetes.
Weight change did not explain the association, indicating that lactation may
exert other cardiometabolic effects.
SWIFT
SWIFT, also a prospective cohort study design, enrolled 1,035 women
who had gestational diabetes diagnosed by Carpenter and Coustan cri-
teria (Gunderson et al., 2012). All women underwent a research 2-hour,
75 g oral glucose tolerance test (OGTT) at each of three research visits
from study baseline (6 to 9 weeks postpartum) and annually for up to
2 years later. A fourth in-person research visit will be conducted in 2021
2 Gunderson reported the models controlled for fasting glucose, insulin resistance, family
history of diabetes, physical activity, diet quality, perinatal outcomes, and follow-up changes
in weight.

to 2023 to reclassify glucose tolerance in the cohort approximately 10 years

postbaseline. Each research visit also gathered research measurements of
anthropometry, and surveys of lactation, infant diet, lifestyle behaviors,
sleep, and sociodemographic factors. Electronic health records continued
to follow up after 2 years postbaseline for new diagnoses of diabetes.
Gunderson described the systematic biochemical testing for diabetes as
objective outcomes collected under research protocols. This study design
allowed for the assessment of changes in metabolic risk factors, factors that
may affect the lactation–disease relationships, and perinatal outcomes. The
cohort also included a group of women who did not breastfeed. Gunderson
noted there was high participant retention and the cohort was racially and
ethnically diverse (75 percent minority).
SWIFT observed that a substantial portion of progression to d iabetes
occurred during the first years after a gestational diabetes pregnancy.
Approximately 12 percent of SWIFT participants progressed to diabetes
within the 2 years postbaseline, which increased to 20 percent by 8 to
9 years postbaseline. Higher breastfeeding intensity at 6–9 weeks post
partum was associated with a 50 percent lower relative risk of incident
diabetes (Gunderson et al., 2015). The lactation intensity groups did not
differ with respect to the sum of the z-scores for the prenatal 3-hour, 100 g
oral glucose tolerance test, a measure of the severity of gestational diabetes,
or gestational diabetes treatment (e.g., medication, insulin), indicating simi-
lar antecedent metabolic risk status. Multivariate models, accounting for
potential confounders, showed a 50 percent lower relative risk of incident
diabetes among women who breastfeed for 5 or more months, as compared
to those who breastfed for 0–2 months. The lactation–incident diabetes risk
was not mediated through weight loss, reported Gunderson.
Importance of Findings from CARDIA and SWIFT

Both CARDIA and SWIFT provide robust evidence for breastfeeding
reducing the risk of developing diabetes in women across the childbearing
years. There were strong, graded inverse relationships for lactation mea-
sures and the 2-year and 30-year incidence of diabetes in women who did
and did not have gestational diabetes. This inverse relationship was seen
after controlling for antecedent biochemical and clinical risk factors prior to
lactation, psychosocial factors, sociodemographic risk factors, and lifestyle
behaviors.
Gunderson acknowledged that the biological mechanisms by which
lactation may protect against cardiometabolic disease have not been elu-
cidated and would be necessary for causal inferences. She suggested that
prolactin could exert an effect on pancreatic beta cells or that there could
be underlying differences in mobilization of fat depots (e.g., visceral fat)

(Gunderson et al., 2014), but she surmised that other mechanisms could be
driving the observed differences.
To contextualize the importance of the findings from CARDIA and
SWIFT, Gunderson explained that the Diabetes Prevention Program had
found that a 5 kilogram weight loss through a diet and physical activity
intervention reduced the risk of incident diabetes in adults with prediabetes
by 58 percent. Given the similar strength of associations for lactation inten-
sity and duration, she conjectured, “This is a specific lifestyle behavior in a
critical period, the postpartum period, that may actually have very strong
metabolic consequences.” Gunderson cited research evidence attributing an
annual excess of deaths for women later in life to suboptimal breastfeed-
ing. As heart disease is the leading cause of death among U.S. women, and
type 2 diabetes is a risk factor, she concluded that the impact of lactation
on women’s health has been underappreciated.
DISCUSSION
Allen, Demerath, and Gunderson responded to audience questions. In
the discussion, moderated by O’Connor, questions were raised related to
lactational programming, studying breast milk composition, and factors
affecting lactation success.
Lactational Programming
Prefacing that her question related to the application of the concepts of
lactational programming, Leanne Redman from the Pennington Biomedical
Research Center asked if there were existing recommendations related
to nutrition before, during, and after pregnancy to optimize breast milk
composition. Allen explained that there are no WHO recommendations
on supplementation during lactation. She thought that, until functional
deficits in infants are identified, there will remain inadequate interest and
investment in the topic.
A webcast audience member, who referenced a possible U-shaped
relationship between maternal leptin concentrations and offspring obe-
sity, wanted to know if there was an effect modification by BMI status.
Demerath responded that more data are needed to better characterize the
relationships. She noted that most studies do adjust for BMI, but effect
modification could still be a factor.
Studying Breast Milk Composition

Redman asked the panelists for their ideas on how to advance the evi-
dence on the relationships between maternal diet, maternal health, breast

milk composition, and infant outcomes, given that some randomized con-
trolled trials may not be ethical to conduct. Demerath acknowledged that
only certain types of trials would be considered unethical, such as remov-
ing an essential nutrient from the diet. She suggested that trials promoting
healthy dietary patterns coupled with pregnancy weight management would
be useful. Allen added that she has been involved in several micronutrient
trials in developing countries and said the challenge is identifying and mea-
suring functional outcomes in infants. When asked by a webcast audience
member if it is known whether breast milk that is pumped, as opposed to
consumed directly from the breast, confers the same health benefits for
mother and child, Gunderson responded that SWIFT collected such data,
but it has yet to be analyzed.
Referring to Allen’s presentation on the content of vitamin B12 in
breast milk among vegetarian and vegans, Johanna Dwyer of the National
Institutes of Health’s Office of Dietary Supplements pointed out that there
were observational studies conducted in the 1970s on mothers in Boston
following macrobiotic diets. Allen, who was involved in the study Dwyer
referenced, noted that detrimental effects were found in the infants, but she
said the analytical technique to measure vitamin B12 concentrations used
in those studies is no longer considered valid.
Factors Affecting Lactation Success

Amelia Foley of Community of Hope asked Demerath and Gunderson
whether their research had accounted for weight stigma and psychological
stress. From a clinical perspective, Demerath agreed that there is too much
focus on weight during pregnancy and postpartum, but she noted that
weight gain outside of the current guidelines could have deleterious effects
on birth outcomes and child health. She suggested that each individual’s
context should be considered. Although stress is not a topic her group
has investigated, Demerath thought it would be important to explore.
Gunderson added that, despite associations between weight status and
diabetes risk, lactation appears to have a physiological effect independent
of weight change. Agreeing that weight should not be the primary focus
during the postpartum period, she suggested that attention should be given
to preventing stress, preventing and addressing depression, helping women
get sufficient sleep, and helping women eat a healthy diet. Gunderson also
emphasized the importance of paid family leave to help women recover
from the physiological demands of pregnancy and lactation.
An unidentified audience member wanted to know if social factors that
affect a woman’s ability to initiate and continue breastfeeding could be
confounding results, and if there were evidence from countries with more
generous parental leave policies. Gunderson responded that it is difficult

to compare studies from Scandinavian countries and China to results from

the United States, as their leave policies can last up to a year. She explained
that the SWIFT study did not find relationships between perinatal outcomes
and breastfeeding intensity. Agreeing that social factors like employment
and social support systems play a role, Gunderson mentioned that both
CARDIA and SWIFT showed that black women were 50 percent less likely
to breastfeed, compared to their white, Asian, and Hispanic counterparts.
She suggested that more research into the factors that lead to suboptimal
breastfeeding is needed. Demerath added that a Canadian study reported
differences with respect to the microbiome, but echoed Gunderson’s senti-
ment that this is an area that is understudied.

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Maternal Intakes and Nutritional Status

Evidence on the complex interplay between maternal nutrition,

MATERNAL MICRONUTRIENT STATUS AND INTAKE:

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88 NUTRITION DURING PREGNANCY AND LACTATION

• Data on micronutrient content of breast milk in the United States is lacking

Analysis of Human Milk Micronutrient Composition

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 89

known. Additionally, there are various maternal factors (e.g., supplement

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90 NUTRITION DURING PREGNANCY AND LACTATION

Updated Estimates for Select Nutrients

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 91

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92 NUTRITION DURING PREGNANCY AND LACTATION

There is no consensus on whether lactating women in high-income

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 93

practical, but demonstrates the level of supplementation needed to increase

THE IMPLICATIONS OF MATERNAL WEIGHT AND METABOLIC

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94 NUTRITION DURING PREGNANCY AND LACTATION

Implications for Maternal Health and Infant Programming

1 GDM is gestational diabetes mellitus.

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 95

FIGURE 7-1 Schematic of lactational programming concepts.

feeding exclusivity and duration mitigate the effects of maternal gestational

Implications for Breastfeeding Outcomes

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96 NUTRITION DURING PREGNANCY AND LACTATION

nancy Risk Assessment Monitoring System (PRAMS) reported lower rates

Implications for Breast Milk Composition

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 97

oligosaccharides, microbiomes, and environmental pollutants. A host of

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98 NUTRITION DURING PREGNANCY AND LACTATION

expression and phenotype in female infants as compared to male infants

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MATERNAL INTAKES AND NUTRITIONAL STATUS DURING LACTATION 99

LACTATION AND THE FUTURE RISK OF