Early Life Nutrition: Susan Finn, Eamonn P. Culligan, William J. Snelling and Roy D. Sleator

Science Progress (2018), 101(4), 332 – 359
Paper 1800265 https://doi.org/10.3184/003685018X15360040523721
Early life nutrition

SUSAN FINN, EAMONN P. CULLIGAN, WILLIAM J. SNELLING and
ROY D. SLEATOR
Ms Susan Finn holds a BSc in Nutrition and Health Science

from Cork Institute of Technology. Susan’s research interests are
focussed on the impact of early life nutrition; specifically, how
different feeding methods affect health outcomes. E-mail: susan.
finn@mycit.ie
Dr Eamonn Culligan holds a PhD in Microbiology from

University College Cork. He is currently a Postdoctoral Industry
Fellow, based at nSilico and the Department of Biological
Sciences at Cork Institute of Technology. Dr Culligan is funded
by Science Foundation Ireland under grant number 16/IFA/4354.
Follow Culligan on Twitter @eamonnc83. E-mail: eamonn.
culligan@cit.ie
Dr William Snelling holds a PhD from the University of Ulster.

He is currently a Research Associate at NICHE (the Nutrition
Innovation Centre for Food and Health) at the University of
Ulster. E-mail: b.snelling@ulster.ac.uk
Prof. Roy Sleator holds a PhD from University College Cork and
a DSc from the National University of Ireland. He is currently a
Senior Lecturer at the Department of Biological Sciences at Cork
Institute of Technology. Follow Sleator on Twitter @roysleator.
E-mail: roy.sleator@cit.ie
ABSTRACT
Nutritionally, the first 1,000 days of an infant’s life – from conception to two years –
has been identified as a highly influential period, during which lasting health can be
achieved. Significant evidence links patterns of infant feeding to both short and long-
term health outcomes, many of which can be prevented through nutritional modifications.
332 Susan Finn, Eamonn P. Culligan, William J. Snelling and Roy D. Sleator
Recommended globally, breastfeeding is recognised as the gold standard of infant
nutrition; providing key nutrients to achieve optimal health, growth and development,
and conferring immunologic protective effects against disease. Nevertheless, infant
formulas are often the sole source of nutrition for many infants during the first stage of
life. Producers of infant formula strive to supply high quality, healthy, safe alternatives to
breast milk with a comparable balance of nutrients to human milk imitating its composition
and functional performance measures. The concept of ‘nutritional programming’, and
the theory that exposure to specific conditions, can predispose an individual’s health
status in later life has become an accepted dictum, and has sparked important nutritional
research prospects. This review explores the impact of early life nutrition, specifically,
how different feeding methods affect health outcomes.
Keywords: infant, breastfeeding, formula, nutrition
1. Introduction
An extensive body of evidence exists, and continues to grow, which addresses the
significant relationship between nutrition in early life, and health status throughout
the life cycle of the human being1,2. The environment encountered from foetal
life through infancy has a profound influence on physiological function and
developmental programming of disease including hypertension, diabetes and
obesity through adulthood3. The concept of ‘nutritional programming’ summarises
the relationship between early life nutrition and adult disease4. Early nutritional
programming is the theory that differences in nutritional experience at critical periods
in early life can programme a person’s development, metabolism and health for the
future5.
As the leading cause of death globally, non-communicable diseases (NCDs)
were responsible for 38 million (68%) of the world’s 56 million deaths in 2012, of
which 40% were premature, and preventable6. The main NCDs are cardiovascular
disease, cancers, diabetes and respiratory diseases. Conditions tend to be chronic,
long-term, and result from genetic, environmental, physiological and environmental
factors. Although associated with adult life, many NCDs originate in early life from
prenatal maternal undernutrition, low birth weight, or similarly, maternal obesity
and gestational diabetes7. Such early life exposures can lead to functional changes
in gene expression, resulting in a higher risk of chronic NCD development such as
obesity, diabetes, heart disease, and certain cancers, along with dysfunction of the
reproductive, immune and neurocognitive systems8. Thus, it is increasingly accepted
that nutritional programming has an ‘epigenetic component’ as maternal nutrition
and environmental exposure early in development can elicit lifelong effects on health
and well-being9–11. Epigenetic effects involve changes in gene expression due to
DNA methylation/acetylation and histone modifications rather than alterations in
DNA sequence12.
An extensive systematic review carried out by Gonzalez13 on behalf of the
United Nations Children’s Fund (UNICEF) details effective interventions in the
life-course of maternal, child and adolescence to prevent NCDs and related risk
www.scienceprogress.co.uk Early life nutrition 333

factors. Such interventions include the promotion of optimal growth in infancy to
prevent ischemic heart disease and type 2 diabetes, promoting behavioural changes
against tobacco, alcohol and poor nutrition in women of child-bearing age, and using
breastfeeding as a preventative strategy against obesity, metabolic diseases, high
blood cholesterol and type-2 diabetes. Furthermore, not only can such interventions
prevent the risk of NCDs, but the reduction in early-life stressors could potentially
maximise adult well-being by improving overall mental health14, optimising neuro-
cognitive development15 and increasing adult IQ, years of schooling and likely
income16.
The Early Nutrition Project (EARNEST) is the largest worldwide developmental
programming project funded by the European Union which aims to provide evidence-
based, scientific foundations for optimal early nutrition that incorporate long-term
health outcomes17. EARNEST is a 60-month project that includes four target groups:
women of child-bearing age, pregnant women, infants (breastfed and formula-fed
alike) and young children5. The results to date indicate that considerable preventative
opportunities exist through modifying risk trajectories such as optimising diet very
early in life to decrease later risk of disease.
Similarly, ‘The First 1,000 Days’ concept (from conception to 24 months) has
been identified throughout the most recent literature as a highly influential critical
window within which lasting health and prosperity can be achieved18. Evidence
suggests that poor early nutrition during this time predisposes the individual to an
array of medical problems and pathologic implications later in life19. The initiation
of the ‘First 1,000 Days’ campaign began in 2008 with the publication of a landmark
series of scientific papers by the British Medical Journal and The Lancet 20. The series
led to a shift in how the world addresses infant malnutrition and identified a need to
focus on the period from conception to the end of the child’s second year which
would bring health benefits throughout the life cycle of the human being. Following
on from this 2008 series, The Lancet launched a new series reassessing maternal and
infant nutrition, along with worldwide growing health problems21. Global prevailing
issues such as obesity, growth stunting and deficiencies of essential nutrients
emerged as key areas needing attention, along with their consequences. A novel
conceptual framework was developed, outlining dietary, behavioural and health
determinants of optimum health and nutrition, which can be changed to enhance
health. These include nutrition specific interventions that address the immediate
causes of suboptimal development and growth. Following the publication of the
series, the ‘1000 days concept’ has been adopted by agencies22 and international
non-governmental organisations22 as a public health strategy to attain healthy infant
development.
2. Evolution of infant nutrition

The historical evolution of infant formula includes wet nursing, the feeding
bottle and formula use, with wet nursing originally being the safest and most
common alternative used to mother’s breast milk until the late 19th century23.
Despite the recommendations of the French obstetrician Jacques Guillemeau
that the natural mother should nurse her child, wet nursing remained a well-paid,
highly organised, popular and respectable occupation (Figure 1). As artificial
feeding methods became safer, wet-nursing became less common24 and shifted
from an alternative of need to an alternative of choice23. The late 18th century saw
high mortality rates in Irish infants not breastfed by their mothers24. Physicians
recognised the effects of harmful substitutes to human milk, such as raw cow’s
milk, and the practice of wet nursing became associated with infant mortality
and economic exploitation. At the turn of the 19th century, artificial feeding
became an alternative substitute23, due to advances in artificial food production.
The employment of a wet-nurse was soon considered immoral, thus leading the
profession to become extinct by the 1900s. The first steps towards dehydrated
infant formula were in the mid 1800s, when milk was concentrated, evaporated
and finally dehydrated. The first large-scale method for drying milk was the roller
method, followed by spray-drying. Parallel with the evolution of dried milks, the
first infant food formulas were being devised23.
Although formula was available, more than two thirds of infants were breastfed
in the early 1900s25 many of them up until the first year of life26. General sanitation,
knowledge of hygiene and dairy processing methods were underdeveloped26, and
cow’s milk was known to be highly contaminated27. Furthermore, the role of vitamin
supplementation was not recognised, leading to a rise in scurvy and rickets28. Initially,
negative views on formula feeding arose from the observation that scurvy occurred
primarily in infants fed sterilised, condensed and pasteurised milk26. By the 1920s,
it became customary to supplement the diet of an infant with orange juice and cod
liver oil to decrease the prevalence of scurvy and rickets, leading to a modest rise in
successful formula feeding26.
Figure 1 Louis XIV as an infant with his

nurse Longuet de la Giraudière. Found in the
collection of Musée de l’Histoire de France,
Château de Versailles.

Improved home-prepared infant formulas were developed with an appreciation
of food safety, microbiology and nutrient requirements27. Formulas were composed
of evaporated milk, or pasteurised and homogenised fresh cow’s milk, fortified with
vitamin D. However, scurvy remained prevalent, as did iron deficiency, renal issues
and a lack of dietary essential fatty acids26. The complex biochemical differences
between cow’s milk and human milk were recognised, and further modifications
to the structure of infant formula were made, including corrected protein dilution,
the removal of animal fat and the balancing of micronutrient levels to better
simulate the composition of human milk29. Scientifically supported fortification
methods contributed to the evolution of infant formula, and a steady decline in both
breastfeeding initiation and incidence in the preceding decades saw rates fall to 22%
by 197225. Development of nutrient deficiencies and unwanted health outcomes in
formula fed infants initiated federal regulatory actions regarding the composition of
infant formula26. Based on recommendations by the Committee on Nutrition of the
American Academy of Paediatrics (AAP), in 1971, the Food and Drug Act (FDA)
declared minimum requirement levels for protein, fat, linoleic acid and 17 vitamins
and minerals30.
Initially, the aim of infant formula manufacturers was to match breastfeeding
performance by mirroring its composition. However, the unique nutritional
significance of breastfeeding was soon recognised, and multiple health organisations
began to endorse breastfeeding as the optimal form of infant nutrition29.
National and international public health strategies began to focus on the benefits
of breastfeeding towards the end of the 1970s, with a global effort to minimise
the marketing of infant formula in less-developed countries25. The superiority of
breastfeeding was recognised based on the unique characteristics of human milk,
and specific factors incriminating artificial feeding, including sound evidence
of increased infection, obesity and allergy31. This global movement sparked
a resurgence in breastfeeding, and an increase in initiation rates, attributed to
maternal education, changes in birthing practices and increased knowledge of the
benefits of breastfeeding by healthcare professionals25. Respected health bodies
and paediatricians began advocating the ‘breast is best’ slogan, advising exclusive
breastfeeding at least in the initial two weeks, with four months being preferential31.
‘The International Code of Marketing of Breastmilk Substitutes’ was introduced
by the World Health Organisation (WHO) in 1981, and provides guidelines for the
marketing and distribution of infant formula, with the aim of contributing to optimal
infant nutrition by the protection and promotion of breastfeeding32. EU and national
legislation are in conformance with the main principles and aims of the code33.
3. Breastfeeding
In 2001, the WHO and the United Nations Children’s Fund (UNICEF) provided a
global health recommendation, which stated ‘infants should be exclusively breastfed
for the first six months of life to achieve optimal growth, development and health’34.
The rationale stemmed from a thorough review of the effects of breastfeeding for six
months versus shorter durations and the subsequent improvements in infant, child and
maternal health. In the Republic of Ireland, the Department of Health and Children
updated their advice in 2003 to advocate adherence to this recommendation35. The
Food Safety Authority of Ireland (FSAI) also corresponded that breastfeeding was
the gold standard in infant feeding36.
Human breast milk is a complex matrix with a general composition of 87%
water, 3.8% fat, 1.0% protein and 7% lactose which provides the optimal blend of
macronutrients, vitamins, minerals, digestive enzymes and hormones to support
an infant’s development37. The complex range of bioactive antimicrobial and
antibacterial components, along with enzymes, hormones and growth factors
positively affect the infant’s immune status with short term protective effects in
relation to infection, as well as facilitating immune development38. Reviewing short-
term benefits, clear evidence exists regarding the protective effects against common
childhood infections such as diarrhoea incidence, prevalence, hospitalisations,
diarrhoea mortality, and all-cause mortality39. Studies show that soluble glycans
found in breast milk inhibit pathogens from binding to host cell-surface glycans
and thus account for the significant protection of breast-fed infants against enteric
diseases40. Consistent with these findings, significant protection by human milk has
been demonstrated in relation to respiratory tract infections41, ear infections42, and
neonatal enterocolitis incidence43. The protection against infection occurs through a
variety of complementary acquired and innate defence factors found in breast milk
such as oligosaccharides and their glycoconjugates40 that function as immunologic or
anti-infective agents44.
Additionally, several studies suggest that breastfeeding may have a protective role
against Sudden Infant Death Syndrome (SIDS). The most widely accepted definition
of SIDS, according to the American Academy of Paediatrics45 is: ‘The sudden death
of an infant under one year of age, which remains unexplained after a thorough
case investigation, including performance of a complete autopsy, examination of
the death scene, and review of the clinical history.’ While there is some dispute as
to the actual protective effect against SIDS offered by breastfeeding, a majority of
studies are in favour of this hypotheses46,47. Indeed, one of the largest of this kind
found that exclusive breastfeeding at one month of age almost halved the risk of
SIDS48. Furthermore, a recent meta-analysis, which extensively evaluated 18 studies,
found that breastfeeding had a protective effect against SIDS, and this was stronger
when breastfeeding was exclusive49. The authors suggested that breastfeeding
interventions should target high-risk groups that have higher incidence of SIDS, such
as socially disadvantaged mothers and racial/ethnic minorities as a strategy to reduce
occurrence. The apparent positive relationship between breastfeeding and a reduced
risk of SIDS has sparked the promotion of breastfeeding to be included in specific
SIDS prevention advice and campaigns45. The New Zealand Government initiated
‘The National Cot Death Prevention Programme’ in 1991 with the aim to reduce
the high rate of SIDS50. Based on existing scientific data, the Department of Health
in Ireland co-ordinated the development of a health education SIDS prevention

programme with the objective of increasing exclusive breastfeeding rates at three
months from 60% in 1995 to 70% by 1997 and 75% by 2000. SIDS cases were
halved within two years, with a continual decline thereafter, suggesting that the
health education programme had a significant beneficial influence improving infant
survival.
Growing evidence also suggests that breastfeeding has a long-term protective role
against prevailing NCDs including obesity, type-2 diabetes, cardiovascular disease
and factors linked to such disease states such as hypercholesterolemia, dyslipidaemia
and hypertension51. Furthermore, evidence exists that there is a positive relationship
between breastfeeding, and breastfeeding duration and enhanced cognitive
development. A meta-analysis of 20 controlled studies undertaken by Anderson
et al.52 confirmed that breastfeeding is accompanied by a more rapid and better
development of neurologic function. A homogenous and significantly enhanced
cognitive development score of 3.2 or higher in breast-fed compared to formula-fed
infants was observed. Not only did this enhanced cognitive function, manifest early
in development, but was also sustained through childhood and adulthood. In addition
to improved cognitive functioning, breastfeeding is also related to fewer internalising
behaviour problems later in life and emotional regulation such as anxiety, depression
and somatic symptoms53.
There are also significant beneficial effects of breastfeeding on maternal health
including reduced risk of osteoporosis and certain cancers, improved maternal
bonding and an accelerated return to pre-pregnancy bodyweight19. A recent
systematic review and meta-analysis conducted by Li et al.54 observed a significant
risk reduction of ovarian and epithelial ovarian cancers in women who had breastfed
compared to those who did not, a protective effect that increased with breastfeeding
duration, particularly for women who breastfed for > 12 months. Results from a
more recent meta-analysis showed that women who breastfed at any stage had a
30% reduced risk of ovarian cancer when compared to those who never breastfed,
with the highest risk reduction observed in women who had breastfed for more than
12 months55. The risk of developing breast cancer has also proven to be significantly
decreased in women who breastfed compared to those who did not, the protective
effects of which have been linked to a duration of > 12 months.
Breastfeeding also promotes postpartum weight loss due to the increased
caloric expenditures and energy demands required for lactation, along with possible
metabolic changes that are favourable to weight loss56. Jarlenski et al.57 reported
that exclusive breastfeeding provided a small but important weight loss relative to
not breastfeeding at all, or non-exclusively. The findings also indicated a higher
probability of returning to pre-pregnancy weight and body mass index (BMI)57, which
are important contributors to a reduced risk of long-term obesity and serious chronic
diseases among women58. The achievement of this relatively modest reduction in
weight at a population level has the potential to make a significant impact on the
burden of chronic disease, namely reduced prevalence of conditions such as lower
back pain, osteoarthritis, diabetes, hypertension and raised cholesterol58.
Finally, the release of the oxytocin hormone during breastfeeding exerts
important psychological effects, inducing a state of calm, and reducing maternal and
infant stress. Disruption in oxytocin homeostasis may affect both maternal mood
and breastfeeding success, resulting in two common conditions that frequently
occur together: failed lactation and perinatal depression59. Additionally, it was
found that consistently higher anxiety, depression symptoms and antidepressant
treatment correlate with lower levels of oxytocin60. Thus, the release of oxytocin
during breastfeeding represents a potential therapeutic pathway in post-partum
pathologies such as depression, and associates strongly with maternal bonding
behaviours, attachment indicators and higher levels of affectionate touch interactions
with the infant61. In addition to the potential mental health benefits, breastfeeding
has a significant food safety impact: reducing childhood exposure to unsafe potable
water, used to reconstitute baby formula. This is particularly significant given that
diarrheal diseases, resulting from contaminated water, is one of the leading causes
of childhood mortality, particularly among children in resource-limited countries62.
The economic value for breastfeeding is also potentially high. A study from the
National Health Service (NHS) of the UK estimated a substantial annual saving of
£11 million to be associated with increases in breastfeeding rates. This was attributed
to the reduction in the incidence of breast cancer in women, and four acute childhood
diseases, namely gastrointestinal infections, lower respiratory infections, acute otitis
media and preterm necrotising enterocolitis63. The 2012 UNICEF report on diseases
and developmental deficits estimates that an increase in breastfeeding rates could
potentially lead to fewer hospital admissions and GP consultations, saving the
NHS millions of pounds per annum64. Additionally, potential reduction in maternal
diseases such as breast and ovarian cancers could be achieved through the associated
protective factors of breastfeeding due to their associated costs63. As discussed
previously, growing evidence links breastfeeding to reduced incidence of NCDs later
in life51, the impact of which imposes large household, economic and social costs,
putting additional pressure on already stretched health and social care systems65.
Promotion of breastfeeding may act as a cost-effective, preventative measure to
reduce the prevalence of various NCDs in public health policy, which in turn results
in lower health care costs, benefiting the economy.
An often-overlooked benefit of breast milk is the reduced environmental
impact it has compared to formula. Human milk is a natural, renewable food
source, supporting complete nutritional requirements for the first six months of
life. Furthermore, there are no packages required, which ultimately reduces the
amount of unnecessary materials brought to landfill. Infant formula must also be
manufactured, packaged, stored and transported to retail stores, which incurs a
substantial environmental impact66.
4. Why women may not breastfeed?

It is well established that exclusive breastfeeding is considered the ‘gold standard’
in infant nutrition, from medical, maternal and moral perspectives. Yet findings

in a European Perinatal Health Report on the health and care of pregnant women
and babies in Europe in 2010 showed that the Republic of Ireland continues to
have one of the lowest rates of breastfeeding in the world67. Globally, only 40%
of infants less than six months are exclusively breastfed, and only 23 countries
have breastfeeding rates above 60% (ref. 68). Furthermore, rates of continued
breastfeeding drop off dramatically, particularly in the Americas, up to two years of
age (Figure 2). A review carried out by Renfrew et al.64 suggests factors associated
with the decision to breastfeed are multifaceted, and include the personal attributes
of the woman, the formal support provided by health professionals, or informal
support from peer groups along with social, medical, or economic reasons. The
authors also identified characteristics such as maternal age, educational status,
income levels and ethnicity as influencing the choice to breastfeed. In the USA,
results derived from national survey data regarding the prevalence of exclusive
breastfeeding for six months showed disparities according to family income,
race, the mother’s age, educational level, marital status and state of health69. The
cultural context of breastfeeding support and resources is also extremely variable
among women in different countries, resulting in broad disparities amongst global
breastfeeding initiation rates70. Although several ‘common categories’ required to
assist breastfeeding women exist, the ranking of these categories varies and greatly
influences breastfeeding outcomes. Common supportive factors include antenatal
breastfeeding education, practical support from family members71, continuous
support from healthcare professionals72, and maternal self-determination and
persistence70, with wide differences existing worldwide.
Castro et al.73 reported on some key differences in breastfeeding behaviour
between Irish and non-Irish mothers residing in the Republic of Ireland through the
national longitudinal study ‘Growing up in Ireland’. Stark variations in breastfeeding
rates by ethnic background were observed with Irish representatives having the
lowest rate of breastfeeding initiation compared to all other ethnic groups in the
study. Another interesting finding was the role of acculturation in feeding practices,
with the amount of non-national mothers initiating breastfeeding decreasing the
longer they had been living in Ireland. The authors suggested factors such as societal
pressures, language barriers and the perception of behaviour in the adopted Irish
culture as modern, as some of the mechanisms behind mothers adapting themselves
to formula feeding in Ireland.
Data from the National Immunization Survey (NIS) analysing breastfeeding
among US children born between 2002 and 2014 showed that a significant relationship
exists between the woman’s marital status and the duration of breastfeeding, where
married women breastfed for longer than others who were single or lived with a
partner74. The association between maternal age and breastfeeding duration showed
that the oldest category surveyed (31–40 years) breastfed for significantly longer than
the youngest category (< 20 years). Furthermore, women with a higher education
level were more likely to breastfeed and continued until the recommended time. In
2014, 32.2% of mothers with a university education breastfed exclusively through
www.scienceprogress.co.uk
Early life nutrition
341
Figure 2 Percent of countries by prevalence of breastfeeding outcome indicators, by region. Reproduced with permission from the WHO177.
to six months, compared to 18% of women with an education status less than high
school.
In Ireland, disparities in breastfeeding initiation and duration rates based on
sociodemographic factors have also been reported. Tarrant et al.75 found that 46%
of mothers with a third level degree/postgraduate education initiated breastfeeding,
compared to 23.3% of women with primary or secondary level education. Other
emerging themes from the study relate to the role of positive maternal attitudes and
perception of the acceptability of breastfeeding in public, with a startling 59.9% of
participants deeming the practice of breastfeeding as embarrassing, and a further
61.1% considering it as ‘not natural’. The study also underscored the importance of
positive support from the partner and involvement of the maternal grandmother to
encourage and entice women to breastfeed.
A religious factor has also been highlighted as influencing breastfeeding initiation
across Western countries76. Consistent negative correlations between the rate of
breast feeding initiation and Catholicism was observed within countries, including
Ireland. Conversely, Western countries that were closer to meeting the WHO’s
recommendations had a higher proportion of Protestants. The authors attributed this
to the 16th century’s traditions, where Catholic mothers were less likely to breastfeed
than their Protestant counterparts.
Regulations on maternity leave and workplace environment also affect
breastfeeding rates. Currently in Ireland under the Maternity Protection
(Amendment) Act 2004, 26 weeks maternity leave are entitled together with 16
weeks additional unpaid maternity leave, which begins immediately after the end
of maternity leave77. In comparison, Sweden has one of the most generous parental
leave systems in the world, offering 480 days (approx. 69 weeks) of paid leave under
The Parental Leave Act 1995:58478. Breastfeeding initiation rates are reflectively
promising in Sweden, at 98%, but not so favourable in Ireland at just 46% (ref. 70).
According to Johnston and Esposito79, the mother’s external workplace environment
acts as a major contributing factor, the elements of which can significantly influence
the feeding choice of the working woman. The researchers found a 9% lower
rate of breastfeeding at six months postpartum in employed women compared to
unemployed women. Low-flexibility of working hours, lack of on-site childcare,
the negative attitudes of co-workers, distribution of work duration and timing of
maternity-leave present as some of the main obstacles faced when attempting to
combine breastfeeding with the workplace.
Under certain circumstances, health conditions of the mother or infant may
justify a recommendation of ‘not to breastfeed’ temporarily or permanently80,81.
Case-by-case assessments need to be made by a healthcare professional to decide
whether the health of the mother or infant warrants an alternative feeding choice
based on potential contradictions to breastfeeding. The Centres for Disease Control
and Prevention outlines certain medical states that affect human milk, or disease
diagnosed in the infant that requires the adoption of replacement formulas82. Certain
medications or drugs such as cancer chemotherapy agents, antiretroviral medications
for HIV/AIDS treatment83, common migraine medications84, mood stabilisers such
as lithium or lamotrigine85 and even sedentary medications used to aid sleep86 can
enter the milk via passive diffusion, harming the infant.
For the infant, certain metabolic disorders such as galactosemia warrants
alternative feeding to breast milk to avoid the risks of cirrhosis of the liver, mental
retardation, cataracts and hypoglycaemia81. Although less extreme, breastfeeding
infants with phenylketonuria (PKU) can also prove a challenging practice. PKU is
an autosomal inborn error of phenylalanine (Phe) metabolism, which often requires
strict nutritional therapy with complementary amino acid supplementation to avoid
the risk of severe intellectual disability, epilepsy and behavioural problems87. The
infants may only be partially breastfed and supplemented with an appropriate amount
of phenylalanine-free formula due to the need to restrict phenylalanine intake88.
Successful breastfeeding in this unique population can be achieved through careful,
extensive monitoring by mothers and supporting healthcare advisors89.
5. Infant formulas
It is evident from the above studies that despite the recommendations by numerous
health and professional medical organisations regarding breastfeeding, its overall
prevalence remains low, globally70 (Figure 2). As discussed, there are several reasons
for new or expectant mothers needing or choosing to take different paths to feeding
their infants. For some, it is not a choice due to medical conditions, time constraints,
and work–life commitments. Economic, family, and environmental benefits of
breastfeeding have also been described. The decision to formula feed may also be
based on individual comfort, anxieties and honest personal choice. Consequently, the
use of infant formula and follow-on-milk is commonplace among parents and a large
percentage of children are exposed to infant formula at an early age90.
Worldwide, a variety of nutritious infant formulas are available for preterm
infants, full-term infants, and toddlers, in addition to other specialised formulas
to meet the needs of those with selected inborn errors of metabolism91. It is
fundamental that the infant formula industry works with healthcare professionals to
apply the findings of research studies to supply high quality options as a healthy,
safe alternative to breast milk with a comparable balance of nutrients. An identical
substitute to breast milk is complicated due to its varying nutritional composition,
but every effort must be taken to mimic the profile of human breast milk while
conforming to national and international criteria, when a substitute form of nutrition
is required37 (see Table 1 for a nutritional comparison of mature human milk with
reconstructed first infant formula).
The WHO and The Codex Alimentarius Commission of the Food and
Agriculture Organization of the United Nations (FAO) are responsible for the
development of standards and guidelines for protecting consumer health and
ensuring Fairtrade practices globally. Codex Standard 72-1981 on infant formula
was adopted in 1981, and was revised in 200792. The Standard is composed of
Section A, which focusses on infant formula in liquid or powdered form and Section

Table 1 Estimated nutritional comparison of 100 mL mature human milk versus 100 mL
reconstructed first infant formula
Mature human milk
Nutritional information: 0–6 months first
(National Health and Medical
typical values per 100 mL infant formula175
Research Council, 1995)
Energy 60–68 kcal* 65 kcal
2.2–3.7 g*
Fat 3.4 g
4.2 g
-Saturated NA 1.5 g
-Unsaturated NA 1.9 g
Carbohydrates 7.4 g 7.3 g
-Of which sugars NA 7.2 g
-Of which lactose NA 7.0 g
Fibre 0.6 g
0.9–2.2 g*
Protein 1.3 g
1.3 g
Vitamins
Vitamin A 60 µg 54 µg
Vitamin D 0.01 µg 1.2 µg
Vitamin E 0.35 mg 1.1 mg
Vitamin K 0.21 µg 4.4 µg
Vitamin C 3.8 mg 9.2 mg
Thiamine (B1) 0.016 µg 0.05 mg
Riboflavin (B2) 0.032 µg 0.12 mg
Niacin (B3) 0.23 µg 0.43 mg
Pantothenic Acid 0.26 µg 0.34 mg
Vitamin B6 0.006 mg 0.037 mg
Folic Acid 0.0052 µg (folate) 13 µg
Vitamin B12 0.01 µg 0.19 µg
Biotin 0.76 µg 1.4 µg
Minerals
Sodium 15 mg 17 mg
Potassium 60 mg 72 mg
Chloride 43 mg 46 mg
26–29 mg*
Calcium 55 mg
35 mg
11–17 mg*
Phosphorus 31 mg
15 mg
Magnesium 2.8 µg 5.1 mg
Iron 0.76 µg 0.53 mg
Zinc 0.295 µg 0.51 mg
Copper 0.039 µg 0.04 mg
Manganese 0.0012 µg 0.008 mg
Fluoride 0.007 µg (fluorine) ≤ 0.003 mg
Selenium 1.4 µg 1.7 µg
Iodine 7.0 µg 12 µg
*See ref. 176.
B, which focusses on Formulas for Special Medical Purposes Intended for Infants. It
defines infant formula as ‘a breast-milk substitute specially manufactured to satisfy,
by itself, the nutritional requirements of infants during the first months of life up
to the introduction of appropriate complementary feeding’. The Codex outlines all
requirements for production and distribution of infant formula. This ensures the
substitution formula meets the normal nutritional requirements of infants, whilst
also meeting compositional, quality and safety conditions. Similarly, the Food
and Drug Administration (FDA) rules on current Good Manufacturing Practices
for infant formula, Regulation 21 CFR 106.96, revised as of April 2007, requiring
that formulas adequately satisfy the quality factors of normal physical growth and
provide a sufficient biological quality of bioavailable protein component93. The Baby
Friendly Health Initiative (BFHI) is a global programme supported by the WHO
and UNICEF. For infants who are not breastfed, the BFHI recommends the use of
standard whey-based infant formula for the initial 12 months of life, unless medically
advised otherwise by a healthcare professional94.
6. Composition of infant formula

For full-term infants, typical formulas contain 64–70 kcal, and approximately
1.3–1.4 g of protein per 100 mL, with most common breast milk substitutes being
derived from a standard cow’s milk-base that is skimmed and diluted to more closely
resemble human breast milk95. In the USA, the composition of infant formula is
regulated solely by the FDA, based on recommendations by the American Academy
of Paediatrics Committee on Nutrition. In accordance with the FDA’s food additive
regulations (FFDCA 201(s) and 409), any substances added to infant formula
‘must be safe, lawful and only contain ingredients that have GRAS status’, i.e. are
generally recognised as safe96. This also applies to functional ingredients added to
formula including long-chain polyunsaturated fatty acids, nucleotides, prebiotics,
and probiotics. In the EU, Commission Directive 2006/141/EC lays down the
requirements for the composition and labelling of infant formula97. The Directive
gives criteria for the nutritional composition, i.e. energy, carbohydrate, protein, fat,
minerals, vitamins and additional ingredients, along with minimum and maximum
levels where required. An early goal for the composition of infant formula was to
mimic the nutritional composition of human breast milk including its breakdown
of macronutrients, vitamins, minerals and other bioactive components37. Infant
formulas are the predominant source of nutrition for many infants during a highly
sensitive developmental stage, and therefore can impact short and long-term health
consequences29. The essential composition of infant formula, including minimum
and maximum requirements to avoid toxic/deficient effects are outlined in The
Codex Standard for Infant Formula 72-198198. This ensures that the product will be
nutritionally adequate to promote normal growth and development.
Quantitatively, the core macronutrient composition of infant formulas has been
minimally altered over the past 25 years, and has sufficiently fulfilled the early goal
of the industry to resemble breast milk99. However, significant progress has been

made in recent years in the field of nutrition due to other remarkable developments
that improved our understanding of how the gut microbiome is influenced by
diet100. Exclusive and partial formula feeding have been shown to directly alter the
gut microbiome as well as the gene expression system of the host101. This results
in fewer pathways activating the production of bioactive compounds and a higher
level of pro-inflammatory bacteria in the intestinal microbiome101, attributed to the
lack of unique oligosaccharides naturally found in breast milk, but not in formulas102.
The gut microbiome of formula-fed infants is usually characterised by higher
microbial diversity than exclusively breastfed infants, with abundant occurrence of
the Verrucomicrobiaceae and Peptostreptococcaceae families102. Furthermore, an
overrepresentation of Clostridium difficile is more commonly detected in formula-
fed infants. This is a pathogen associated with a higher risk of enteric and atopic
disease such as dermatitis, wheezing, eczema and allergic sensitisation that has been
recently classified to the Peptoclostridium family103,104. Intestinal microbial diversity
is influenced by a variety of early life exposures, with ‘diet’ being a key modifiable
factor.
Infant formula based on cow’s milk must be skimmed and diluted to better
represent the protein, fat and mineral content of human milk. The document ‘Guiding
principles for feeding non-breastfed children 6–24 months of age’, published by
the WHO, states that unmodified cow’s milk should not be fed to infants under
12 months of age due to its relatively low iron content and the risk of adverse
gastrointestinal response that may cause blood loss, particularly in early infancy105. A
further issue outlined in the document lies in the renal solute load of pure cow’s milk,
due to its high protein and mineral content. This can exacerbate increased kidney
excretion, causing dehydration under conditions of water stress e.g. diarrhoea.
Furthermore, unmodified cow’s milk does not provide the adequate dose of vitamin
E or essential fatty acids for an infant. Although cow’s milk is one of the first foods
introduced into an infant’s diet, it is also one of the first and most common causes of
food allergy, with recent literature indicating an increase in its prevalence106. Cow’s
milk allergy is an immune mediated reaction, which causes affected infants to form
antibodies against large protein molecules contained in the milk107. Consequently, a
wide range of effective substitutes are needed for infants who are unable to tolerate
cow-based formulas, or who are showing signs and symptoms of other intolerances.
Such products include modifications made to lactose content, hydrolysed protein,
probiotic supplementation or formula made with added rice starch95.
Formula-fed infants with existing cow’s milk allergenic symptoms, confirmed
through elevated markers of cord blood immunoglobulin E (IgE) and serum IgE in
infancy, or through a family history of allergy may benefit from hyper allergenic
formula108. Furthermore, a review comparing results across the literature, managed
by Cabana109, highlighted the use of certain partially hydrolysed or extensively
hydrolysed formulas in reducing a broader spectrum of allergies such as eczema,
and other closely associated paediatric conditions, including asthma and allergenic
rhinitis. Using various techniques, the intact proteins could be hydrolysed into
smaller peptides which are associated with decreased allergenicity of the protein and
a lower risk of allergenic disease, compared to the non-hydrolysed form109.
Another alternative may be offered through soy-based formula which are
produced from corn-based carbohydrate and soy-protein, making them free from
lactose and cow’s milk protein. However, its widespread promotion is limited due
to ongoing research into the potential for adverse estrogenic effects of isoflavones110.
A review by Dinsdale and Ward111 suggested that early life exposure to soy-based
products may affect hormonally driven developmental outcomes, and could
negatively impact reproduction, particularly in females later in life. Although the
biological effects of soy are non-conclusive, the review outlines current scientific
data which warrants the need for further research into long-term effects of early
exposure of soy products on reproductive health. Furthermore, preterm infants
have significantly reduced weight-gain, and an increased risk of osteopenia when
exclusively fed soy-based formula instead of standard formula with equal caloric
density112. Thus, soy-based formulas should not be given to premature infants.
This leads to another concern for the infant formula industry, which is the
development of preterm and enriched formulas, to meet more specialised nutritional
requirements. A review prepared by Schneider and Garcia-Rodenas113 outlines
the need for optimal nutritional support and possible dietary interventions, aiming
to understand the complexity of the impact of nutrients on brain and cognitive
development in the preterm population. The outcome of the study indicated the
insufficient quantities of nutrients and energy contained in breast milk to meet the
greater nutritional needs of preterm infants, who are generally born with impaired
nutrient reserves.
Furthermore, another study114 has addressed the increased susceptibility of
preterm infants to a variety of physiological and metabolic stressors due to low
starting energy stores, immature skin, lack of essential amino acids, restricted
fluid intake and reduced absorptive capacity for some vitamins. This can result
in higher incidences of infection, inflammation and respiratory distress, which
not only increases nutritional requirements, but also delays hospital discharge,
preventing the initiation of breastfeeding. Additionally, mothers of preterm infants
requiring prolonged hospitalisation are often unable to produce sufficient milk115.
Therefore, mother’s own milk is nutritionally insufficient to meet the needs of the
preterm infant, and preterm formula may be selected for feeding. A review by Su116
evaluated effective nutritional interventions to optimise the health of the susceptible
preterm. In best practice, prior to hospital discharge the infant will commence
feeding on a protein enriched formula (2.0 g per 100 mL), matching the nutritional
content of breast milk (approx. 67 kcal per 100 mL). Higher energy formulas may
also be used yielding 81–101 kcal per 100 mL which contain a higher fat and lower
carbohydrate proportion with the aim of increasing nutritional density of a feeding
regime and promoting weight gain whilst maintaining a low fluid volume in the
event of fluid restriction. All preterm formula must be sufficiently enriched with
minerals, vitamins, and trace elements as a strategy to support intrauterine rates of

accretion. Drastic improvements to infant formula over the past ten years have been
made through modifications in fortification levels117. The addition of long-chain
polyunsaturated fatty acids, nucleotides and the enrichment of preterm formula with
selenium gives a nutrient composition closer to human milk with several studies
reporting greater catch-up growth117 and enhanced development of the immune
response rate118, increased functioning of the gastrointestinal system119 as well as
preventing further disease and their complications120.
7. Microbiological safety of infant formulas

The manufacturing process of infant formula is globally very similar and produced
in one of three ways: a dry-mix process, a wet-mix process or a combined
process121. Each process has associated risks and benefits with respect to microbial
contaminants, which may establish in the environment, and contaminate the final
product122.
Infants have distinct vulnerabilities and are highly susceptible to nutritional
inputs, illnesses and external environmental factors. Early infancy in particular
represents a period of rapid growth and development, the success of which relies
on the timely emergence of critical structures and developmental processes29. Thus,
optimisation of nutrition and minimisation of exposure to potentially harmful
substances in the food supply are heightened during infancy and should be of prime
importance to the industry.
Current standards need to allow for the presence of acceptable levels of
potential pathogens in infant formulas due to the inability of current technologies
to produce a commercially sterile product, free from potential contamination123.
The powdered product can become contaminated intrinsically during production124,
or extrinsically from utensils during the reconstitution of infant formula125. High
standards of hygiene must be maintained throughout the production process to limit
the possibility of contamination121. The primary microorganisms associated with
powdered infant formulas have been identified as Cronobacter spp., Salmonella
spp., Enterobacter spp. (agglomerans and cloacae), Hafnia alvei, Klebsiella spp.
(pneumoniae and oxytoca), Citrobacter spp. (koseri and freundii), Escherichia
coli, Serratia spp., Acinetobacter spp., Bacillus cereus, Clostridium spp. (difficile,
perfringens and botulinum), Listeria monocytogenes and Staphylococcus spp.
(FAO/WHO, 2007). Cronobacter, in particular, is a frequent contaminant of
infant formula; causing meningitis, septicaemia, necrotizing enterocolitis, and
brain abscesses126,127, with mortality rates of 40–80% (ref. 2). For this reason,
researchers are currently investigating novel approaches to reduce bacterial
contaminations of infant formulas, particularly by Cronobacter. As outlined by
Kent et al.121, promising approaches involve the inclusion of intrinsic protectants
such as: bioactive peptides, organic acids, probiotics and prebiotics, as well as
modifying its environment128. It is suggested that specific probiotic combinations
may significantly influence Cronobacter adhesion to intestinal mucous and provide
protection against infection129.
8. Control of nutritional adequacy of infant formulas
As discussed, infant formulas are the sole source of nutrition for many infants
during the first stage of life, and must provide adequate dietary support for optimal
growth and development during a critical period when inadequate nutrition imposes
serious consequences29. Infant formulas have been developed to successfully meet
the distinct nutritional needs of the infant by attempting to imitate human milk in
composition and functional performance measures130. Concentrations and types of
nutrients in infant formulas cannot always exactly match those in human milk91, but
it is the responsibility of the infant formula industry to attempt this task, by following
established nutrient standards131.
Infants are an extremely vulnerable population, and carry particularly high
risks for untoward effects of unbalanced diets132. Based on the opinions of the
Scientific Committee on Food, Directive 2009/39/EC sets essential requirements
for the composition of infant formula, using the composition of breast milk as the
model133. The Codex Alimentarius Commission also sets out global standards for
essential nutrients, permitted food additives and quality control measures concerning
labelling, contaminants, hygiene and packaging98. Infant formula requires the
strictest food safety and quality standards, exceeding most standards for food
products91. Occurrence of nutritional deficiencies due to compositional errors,
or equally, adverse health effects due to excessive supply of nutrients calls for the
application of extremely stringent quality control within the infant formula industry.
The industry is expected to use pure, safe and suitable ingredients which have been
thoroughly tested using high-quality control measures132. As commercial formula is
often the only source of nutrition for infants, formula efficacy can be determined
by a single factor; the ability to support normal infant growth, through adequate
levels of macronutrients and micronutrients131. Compliance of infant formula with
recommended daily allowances (RDA) for energy, proteins, lipids and micronutrients
such as calcium, iron, fat soluble vitamins and water-soluble vitamins, needs to be
monitored by the food manufacturer93,133.
9. Quality control of vitamin C content of infant formulas

Serious consequences of vitamin and mineral deficiencies are well recognised and
documented. The incidence of scurvy was a significant worry for preliminary infant
formula producers, with the disease occurring primarily in infants fed sterilised,
condensed or pasteurised milk26. Early on, it was viewed that prevention and
cure of scurvy were the predominant physiological functions of the ascorbic acid
– the reduced form of vitamin C134. Scurvy is a potentially fatal disease resulting
from severe vitamin C deficiency, characterised by the weakening of collagenous
structures, reduced wound healing ability and impaired immunity135.
The optimal dose of vitamin C for infants is 40 mg per day, which far exceeds the
risk of deficiency diseases136, while sufficiently promoting and maintaining general
health135. Vitamin C is an essential nutrient which cannot be synthesised by humans,

and must thus be adequately consumed through diet137. The body requires vitamin
C for normal physiological functions, aiding with collagen synthesis, collagen
maintenance, hormone activity, tissue healing and immune health138. The antioxidant
capacity of vitamin C plays an important role in the prevention of certain diseases
including cancers, cardiovascular diseases, cataracts, and age-related muscular
degeneration139.
Vitamin C is also required for enhancing iron absorption, and is in fact the most
efficient promotor of non-heme iron absorption in the body140. Anaemia in early
childhood caused by iron deficiency has significant health consequences including
impaired mental and motor development and is estimated to be the current leading
cause of years lived with disability among children141. Adequate dietary iron is
essential during the first two years of life and in non-breast-fed infants, is required
through supplementation, fortification, or complementary foods140.
Vitamin C is extremely labile and can be easily and rapidly oxidised138, a
process simulated during processing or storage by temperature, light, moisture, pH,
enzymes and certain trace elements142. Thus, the final vitamin C content in foodstuffs
represents a relevant indicator of overall product quality143, leading to the need for
its careful monitoring during the processing and storage of infant formula using
validated detection methods. To support various maximum and minimum nutrient
limits, infant formula manufacturers use various quality control measures to assure
the presence of appropriate measures of ingredients, such as vitamin C, within the
final product133. The classic method for vitamin C analysis and quantification is a
simplistic redox titration143.
10. Exploring the future of early life nutrition

It is now appreciated that the early life experience influences health determinants
through adulthood, and exerts permanent programmed effects on long-term
physiology and function38. The idea of early life programming, and the theory that
exposure to specific conditions can predispose an individual’s health status in later
life has become an accepted scientific concept5. Potential mechanisms of early life
programming have been identified as involving genetic and environmental factors,
and can be modifiable or static, with ‘nutrition’ being identified as a predominant
influencer144.
Strong associations have been shown with exclusive breastfeeding and enhanced
development of infantile immune status38, decreased prevalence of childhood disease
and infections39,40, protection against SIDS47, improved cognitive development52,
and decreased risk of NCDs in later life51. Maternal health benefits19,55,57,59
substantial economic benefits65, and advantageous environmental factors66 have
also been established. Conversely, risks of adverse health outcomes by choosing
infant formula over breastfeeding have been identified, including increased risk of
obesity145, increased risk of NCDs51, decreased neurological function of the infant52
and increased maternal cancer risk, retained gestational weight gain and metabolic
syndrome146. Formula fed infants are seemingly not protected to the same level as
breastfed infants, and consequently, their health, growth and development have been
shown to suffer. Evidently, continuous research within the infant formula industry is
required to understand the composition of human milk, and narrow the gaps between
breastfeeding and infant formula147.
Appreciation of the beneficial effects of human milk has led to the promotion,
protection and support of breastfeeding, and its recognition as ‘the gold standard’
of infant nutrition globally – a concept maintained by paediatricians, scientific and
health bodies, and infant formula manufacturers32,34. Despite recommendations,
overall prevalence of breastfeeding remains low globally68, meaning the use of infant
formula and follow-on-milk is commonplace among many parents, and a large
percentage of children are exposed to infant formula at an early age90. Therefore,
potential opportunities exist for the infant formula industry to further understand
the role of nutritional exposures to guide health outcomes throughout the life cycle
based on the presence of optimal, appropriate nutrition during infancy147. Knowledge
of the complex composition of human milk is increasing, with new components still
being identified148. Thus, infant formula manufacturers are continuously challenged,
to find novel technologies and ingredients to minimise differences between human
milk and infant formula.
11. Advances in infant nutrition research

Exact compositional analysis of breast milk is difficult as it changes over the course
of lactation and within each individual feed, reflecting maternal characteristics, along
with the unique needs of the infant149. It can be influenced by many factors, such
as genetics, maternal diet, geographical variation, environment and alimentation,
further complicating its precise composition150. Recently, metabolic profiling has
been applied to characterise the multicomponent variants of human milk present
at different stages, to understand the precise nutrients and metabolites required to
promote optimal development of the infant149. Such studies may assist in the design
and production of the best nutrient supply possible for infants, perhaps through
‘tailored formula’. Spalinger et al.130 demonstrated how an advanced-staged formula
system with evolving compositions tailored to closely mirror the dynamics of
human milk could more accurately support optimal growth standards and manifest a
healthy early weight gain pattern. Healthy infantile growth rates, reflecting optimal
WHO growth standards were demonstrated in the study130, reducing the infant’s
susceptibility to obesity in childhood, adolescence and adulthood151. Improved
knowledge of the features of human milk could be applied in the infant formula
industry, to formulate the most suitable nutritional substitution for each category of
new born, at each stage of growth150. Human milk varies in composition amongst
individuals, and at different stages of lactation, thus perhaps infant formula should
too reflect these alterations.
Disruption of the human microbiome directly influences the health of the
host, and is now accepted as a potential mechanism in the development of obesity
in infants and children152, along with an increased risk of health conditions153.

Established in infancy, the gut microbiota is also known to directly influence host
metabolism and immune homeostasis154. The third most prevalent components of
mother’s milk are human milk oligosaccharides (HMOs). The absence of HMOs
from cow’s milk ensures a major, notable difference between human milk and
infant formula155. HMOs are considered a natural prebiotic156, facilitating healthy
gut microbiota establishment, while aiding maturation of the immune system and
intestinal development153. An infant’s diet lacking in HMO’s results in interference
in the development of microbiome in the gastrointestinal tract of formula fed infants
compared with those who are breastfed157. This leaves the infant more susceptible
to developing common infections including diarrhoea, respiratory tract infections
and necrotising enterocolitis, along with diseases associated with impairment of the
immune system, such as asthma, celiac disease, diabetes and allergies153. To date,
more than one hundred HMOs have been identified, the amount and composition of
which vary between individuals, and can be affected by blood type and nutritional
and environmental factors158.
Manipulation of the gut microbiome through commercially available synbiotic,
prebiotic and probiotic formulations added to infant formula to simulate the HMOs
of breast milk holds promise for providing an immune-modulating, protective
effect against allergic manifestations and infections159. In recent years, the main
prebiotics added to infant formula are galacto-oligosaccharide (GOS) and fructo-
oligosaccharide (FOS), with the aim of mimicking HMOs, providing bifidogenic
effects on the host through metabolic activity, stool patterns, improved gut
microbiota and some immune markers157. Although the benefits of fortification of
infant formula with prebiotics have been documented156, the essential components
of HMOs are still lacking from infant formula, due to insufficient production
methods158. The synthesised ingredients currently lack the complexity and diversity
of HMOs, and thus lack the ability to transmit health benefits compared to human
milk. Despite structural differences, FOS and GOS do positively influence the gut
microbiota, but long-term effects of supplementing formula with these non-human
glycans warrants investigation158, and the industry currently lacks a completely
replicable preparation, and a clear, recommended formation process160. To deliver on
the ambition of bringing infant formula on par with human milk, additional studies
are required to define specific HMO composition. The true underlying mechanisms
of HMOs also need to be established. However, limited availability of expensive
HMO resources renders it difficult for current researchers to uncover the impacts of
HMO and related health benefits158. To date, the study of human milk components
has presented invaluable applications to infant formula manufacturers, and based on
current studies, further opportunities regarding its complexity are forthcoming.
Lipids are the dominant energy provider for infants during the first crucial
months of life. In addition to a nutritive role, the various lipid components of
human milk are known to aid gastrointestinal function, lipoprotein metabolism,
membrane composition and functioning and signalling pathways, thus influencing
the growth and development of the infant161. Human milk lipids, provided through
breastfeeding, contributes an average of 44% of the infant’s total energy supply,
providing energy, essential vitamins, polyunsaturated fatty acids, and bioactive
compounds162. Lipid content of human milk is extremely variable, fluctuating
with maternal dietary habits, over the course of lactation, and differing amongst
individual infants. Most of the lipid content of infant formula is far less complex,
based on fat derived predominantly from vegetable oil161. Currently, the lipids
in infant formula contain small fat droplets coated in protein, whereas the
lipids present in human milk are large, dispersed fat globules surrounded by
phospholipid membrane. This enables a reproducible product with a long shelf-
life, but a different lipid structure to that of human milk163. The outer layer of
the human milk fat globule membrane (MFGM) consists of high density
bioactive components, with important biological roles, including antimicrobial,
antibacterial and antiviral activities, essential for the development of nervous
and immune functions in the infant162. The phospholipid of the MFGFM has a
high sphingomyelin content, which acts as an emulsifier and stabilising agent,
and directly affects gut bacteria154. Several controlled trials have been conducted
using novel infant formulas, with lipid structures mimicking those found in
human milk by using MFGMs. Promising results have indicated cholesterol
homeostasis, improved fat digestion163, possible protection against obesity later
in life164, improved oral cavity microbiota165 and positive effects on structural and
functional neurodevelopment166. Nejrup et al.154 explored how differences in fatty
acid composition and emulsification applied in infant formula production affect
the gut microbiome of the host. The study showed how fat emulsifiers used in
infant formula reflected differences in infant gut microbiota and may influence
metabolic activity of the establishing microbial community.
Additional studies have focussed on the importance of dietary long-chain
polyunsaturated fatty acids (L-C PUFAs) for the development of infants. Straub
et al.167 suggested L-C PUFA enriched infant formula could potentially act as a
public health prevention strategy with substantial economic benefits, justified
by decreased hypertension-linked diseases in later life, lower blood pressure and
increased life expectancy. L-C PUFA supplemented formula has also indicated
positive associations with the development of intellectual functioning, and improved
information processing speed in later childhood, leading to improved long-term
cognitive functioning168. A trial conducted by Field et al.169 showed formula
containing L-C PUFAs positively supported immune changes in the infants, which
may be of physiological importance for future disease development. In accordance
with these results, a study undertaken by Robinson38, found reduced allergenic
illnesses in the first year of life, achieved through the protective effects L-C PUFA
supplemented formula.
Despite advances made through recent studies, the effects of lipid composition
on host health are scarce154. Careful exploration and evaluation of the methods used
is needed to obtain a clearer understanding of the complexities of lipids in early life
nutrition, and possible nutritional applications162.

Many additional constituents have been added to formula to shift the biology
of formula-fed infants closer to breastfed infants, yet no single ingredient has
successfully encapsulated the beneficial effects of breastfeeding170. Bovine
osteopontin, a multifunctional protein responsible for bone formation, mediating anti-
inflammatory responses and apoptosis has been added to formula to alter the gene
expression of the infant171. Alteration of protein concentration and composition has
been considered, with the enrichment of formula with bioactives of α-lactalbumin172,
and lactoferrin, hoping to impact infant growth, immune function, gut microbiota
and micronutrient uptake171. Varying supplemented doses of arachidonic acid (AHA)
and docosahexaenoic acid (DHA) added to formula have been experimented with, in
an attempt to match the functional benefits achieved with human milk173. However,
further studies are required to assess the safety, benefits, and implications of such
approaches.
Regardless of efforts to produce infant formulas with a composition equal
to breast milk, there are still differences between breastfed and formula fed
infants147. As discussed, breastfeeding remains the most favourable infant feeding
choice, delivering protective outcomes for mother and baby. Given the recognised
benefits, perhaps attention should focus on the promotion, support and protection
of breastfeeding as a global strategy, potentially resulting in the reduced prevalence
of NCDs. Imdad et al.174 have discussed how targeted breastfeeding interventions
focussed on education, support and counselling can positively impact rates of
duration and initiation and can be successful in both developed and underdeveloped
countries. Undoubtedly, persistent national efforts are required offering structured
programmes to entice the practice of breastfeeding, as the ‘normal way of providing
infants with the nutrients they need for healthy growth and development’34.
12. Conclusion
Early life is a critical period, when exposure to certain risk factors are not only
associated with adverse childhood outcomes, but also the development of metabolic
and non-communicable diseases later in life1. The link between nutrition in early
life and health status in adulthood is conceptualised as nutritional programming4.
The nutritional history of an individual begins at conception, and health status is
influenced from this point onwards. The first 1000 days – from conception to 24
months – is considered the most important period for growth and development,
greatly impacted by adequate feeding practices18. Early life nutritional research is
extremely complex, requiring a collaborative effort from the various scientific
disciplines. The development, and implementation of evidence based nutritional
guidance is required to understand the true connection between food choice and
long-term effects, that will lead to improved health for the global population.
Regarding early life nutritional research, the overall goal must be to determine
the best approaches to positively influence and protect overall health, growth and
development, ensuring infants are sufficiently nourished in a manner which can be
sustained through the complete course of life.
13. Acknowledgements
This publication has emanated from research supported in part by a research grant
from Science Foundation Ireland (SFI) under grant number 16/IFA/4354.
Published online: 8 October 2018
14. References
1. Duque-Guimaraes, D. and Ozanne, S. (2017) Biogeront., 18, 893–900.
2. Tall, B.D., Chen, Y., Yan, Q., et al. (2014) Sci. Prog., 97, 154–172.
3. Langley-Evans, S.C. (2015) J. Hum. Nutr. Diet., 28 (Suppl. 1), 1–14.
4. Langley-Evans, S.C. (2009) J. Anat., 215, 36–51.
5. Koletzko, B., Brands, B., Grote, V., et al. (2017) Ann. Nutr. Metab., 70,161–169.
6. World Health Organization (WHO) (2014) Global status report on noncommunicable diseases. WHO
Press, Geneva, Switzerland. http://apps.who.int/iris/bitstream/handle/10665/148114/9789241564854_
eng.pdf;jsessionid=F30925AA09F78507A1835CE7CA460133?sequence=1 [accessed 30 August
2018].
7. Hanson, M.A. and Gluckman, P.D. (2014) Phys. Rev., 94, 1027–1076.
8. Barouki, R., Gluckman, P.D., Grandjean, P., et al. (2012) Environ. Health, 11, 42.
9. Vickers, M.H. (2014) Nutrients, 6, 2165–2178.
10. Jang, H. and Serra, C. (2014) Clin. Nutr. Res., 3, 1–8.
11. Moody, L., Chen, H. and Pan, Y.X. (2017) Adv. Nutr., 8, 337–850.
12. Lee, H.S. (2015) Nutrients, 7, 9492–9507.
13. Gonzales, M., Brumana, L. and Arroyo, A. (2016) Systematic review of reviews of effective
interventions in the life course of maternal-child and adolescence to prevent NCDs and its risk
factors. UNICEF Latin America and the Caribbean Regional, Panama City Office, Panama.
14. Rincel, M., Lepinay, A.L., Delage, P., et al. (2016) Transl. Psych., 6, e966.
15. Wachs, T.D., Georgieff, M., Cusick, S., et al. (2014) Ann. NY Acad. Sci., 1308, 89–106.
16. Horta, B.L., Victora, C.G., de Mola, C.L., et al. (2017) J. Pediatr., 182, 85–91.e3.
17. Koletzko, B., Brands, B., Poston, L., et al. (2012) Proc. Nutr. Soc., 71, 371–378.
18. Koletzko, B., Brands, B., Chourdakis, M., et al. (2014) Ann. Nutr. Metab., 64, 187–196.
19. Ip, S., Chung, M., Raman, G., et al. (2009) Breastfeed. Med., 4 (Suppl. 1), S17–S30.
20. Black, R.E., Allen, L.H., Bhutta, Z.A., et al. (2008) Lancet, 371, 243–260.
21. Black, R.E., Alderman, H., Bhutta, Z.A., et al. (2013) Lancet, 382, 372–375.
22. WHO (2013) Essential nutrition actions: improving maternal, newborn, infant and young child
health and, nutrition. WHO press, Geneva, Switzerland.
23. Stevens, E.E., Patrick, T.E. and Pickler, R. (2009) J. Perin. Ed., 18, 32–39.
24. Weaver, L.T. (2006) Arch. Dis. Child., 91, 386–387.
25. Wright, A. and Schanler, R. (2001) J. Nutr., 131, 421s–425s.
26. Fomon, S. (2001) J. Nutr., 131, 409s–420s.
27. Obladen, M. (2014) Ann. Nutr. Metab., 64, 80–87.
28. Wickes, J.G. (1953) Arch. Dis. Child., 28, 416–422.
29. Institute of Medicine (IoM) (2004) Infant formula. National Acadamies Press, Washington DC, USA.
30. FDA (1971) Fed. Regist., 36, 23553.
31. Addy, D.P. (1976) Brit. Med. J., 1, 1268–1271.
32. WHO (1981) International code of marketing of breast-milk substitutes. WHO Press, Geneva,
Switzerland.
33. FSAI (2009) Guidance on the implementation of European communities (infant formulae and
follow-on formulae) regulations 2007 and 2009 (revision 1). Food Safety Authority of Ireland,
Dublin, Ireland.

34. WHO (2001) The optimal duration of exclusive breastfeeding, report of the expert consultation.
WHO Press, Geneva, Switzerland.
35. Department of Health (2003) Policy change in breastfeeding guidelines. Children Department
of Health, Dublin, Ireland.
36. FSAI (2011) Best practice for infant feeding in Ireland – guide for health professionals based
on 2011 recommendations on infant feeding in Ireland. Food Safety Authority of Ireland,
Dublin, Ireland.
37. Martin, C.R., Ling, P.R. and Blackburn, G.L. (2016) Nutrients, 8, 279.
38. Robinson, S.M. (2015) J. Dev. Orig. Health Dis., 6, 384–389.
39. Lamberti, L.M., Fischer, Walker, C.L., Noiman, A., et al. (2011) BMC Public Health, 11 (Suppl.
3), S15.
40. Morrow, A.L., Ruiz-Palacios, G.M., Jiang, X., et al. (2005) J. Nutr., 135, 1304–1307.
41. Lopez-Alarcon, M., Villalpando, S. and Fajardo, A. (1997) J. Nutr., 127, 436–443.
42. Scariati, P.D., Grummer-Strawn, L.M. and Fein, S.B. (1997) Pediatrics, 99, E5.
43. Verduci, E., Banderali, G., Barberi, S., et al. (2014) Nutrients, 6, 1711–1724.
44. Yang, Y., Xia, M., Tan, M., et al. (2010) J. Virol., 84, 9595–9607.
45. Mitchell, E.A. (2007) Arch. Dis. Child., 92, 155–159.
46. Gordon, A.E., Saadi, A.T., MacKenzie, D.A., et al. (1999) FEMS Immunol. Med. Microbiol.,
25, 175–182.
47. Alm, B., Wennergren, G., Mollborg, P., et al. (2016) Acta Paediatr., 105, 31–38.
48. Moon, R.Y. (2016) Pediatrics, 138, e10.
49. Hauck, F.R., Thompson, J.M., Tanabe, K.O., et al. (2011) Pediatrics, 128, 103–110.
50. Mitchell, E.A., Aley, P. and Eastwood, J. (1992) Aust. J. Public Health, 16, 158–161.
51. Kelishadi, R. and Farajian, S. (2014) Adv. Biomed. Res., 3, 3.
52. Anderson, J.W., Johnstone, B.M. and Remley, D.T. (1999) Am. J. Clin. Nutr., 70, 525–535.
53. Zou, X., Huang, J., Jin, Q., et al. (2013) J. Agric. Food Chem., 61, 7070–7080.
54. Li, D.P., Du, C., Zhang, Z.M., et al. (2014) APJPC, 15, 4829–4837.
55. Chowdhury, R., Sinha, B., Sankar, M.J., et al. (2015) Acta Paediatr., 104, 96–113.
56. Stuebe, A. (2009) Rev. Obstet. Gynecol., 2, 222–231.
57. Jarlenski, M.P., Bennett, W.L., Bleich, S.N., et al. (2014) Prevent. Med., 69, 146–150.
58. Kearns, K., Dee, A. and Fitzgerald, A.P. (2014) BMC Public Health, 14, 143.
59. Stuebe, A.M., Grewen, K., Pedersen, C.A., et al. (2012) J. Womens Health, 21, 264–272.
60. Stuebe, A.M., Grewen, K. and Meltzer-Brody, S. (2013) J. Womens Health, 22, 352–361.
61. Skrundz, M., Bolten, M., Nast, I., et al. (2011) Neuropsychopharmacology, 36, 1886–1893.
62. Mokomane, M., Kasvosve, I., de Melo, E., et al. (2018) Ther. Adv. Infect. Dis., 5, 29–43.
63. Pokhrel, S., Quigley, M.A., Fox-Rushby, J., et al. (2015) Arch. Dis. Child., 100, 334–340.
64. Renfrew, M.J., McCormick, F.M., Wade, A., et al. (2012) Cochrane Database Syst. Rev., 16,
Cd001141.
65. Divajeva, D., Marsh, T., Logstrup, S., et al. (2014) BMC Public Health, 14, 456.
66. Office of the Surgeon General, Center for Disease Conrol and Prevention, Office on Women’s
Health (2011) The Surgeon General’s call to action to support breastfeeding. Office of the
Surgeon General, Rockville, MD, USA.
67. Euro-Persistat Project with SCPE and EUROCAT (2010) European perinatal health report.
The health and care of pregnant women and babies in Europe in 2010. http://www.europeristat.
com/images/doc/Peristat%202013%20V2.pdf [accessed 30 August 2018].
68. WHO (2017) Babies and mothers worldwide failed by lack of investment in breastfeeding.
WHO Press, Geneva, Switzerland.
69. Li, R., Ogden, C., Ballew, C., et al. (2002) Am. J. Public Health, 92, 1107–1110.
70. Hauck, Y.L., Blixt, I., Hildingsson, I., et al. (2016). BMC Public Health., 16, 1067.
71. Emmott, E.H. and Mace, R. (2015) PloS One, https://doi.org/10.1371/journal.pone.0133547.
72. Odom, E.C., Li, R., Scanlon, K.S., et al. (2013) Pediatrics, 131, e726–732.
73. Castro, P.D., Layte, R. and Kearney, J. (2014) J. Nutr., 6, 1832–1849.
74. CDC (2014) Breastfeeding among U.S. children born 2002–2014, CDC National Immunization
Survey. US Department of Health and Human Services, Atlanta, USA.
75. Tarrant, R.C., Younger, K.M., Sheridan-Pereira, M., et al. (2010) Public Health Nutr., 13, 760–
770.
76. Bernard, J.Y., Cohen, E. and Kramer, M.S. (2016) BMJ Glob. Health, 1, e000151.
77. Irish Statute Book (ISB) (1994) Maternity Protection Act. Dublin, Ireland.
78. Government of Sweden (2015) Parental Leave Act (1995:584). Stockholm, Sweden.
79. Johnston, M.L. and Esposito, N. (2007) JOGNN, 36, 9–20.
80. Amir, L.H., Pirotta, M.V. and Raval, M. (2011) Austr. Fam. Phys., 40, 684–690.
81. Leung, A.K. and Sauve, R.S. (2005) J. Nat. Med. Assoc., 97, 1010–1019.
82. CDC (2016) Breastfeeding: disease. US Department of Health and Human Services, Atlanta, USA.
83. Fogel, J.M., Mwatha, A., Richardson, P., et al. (2013) Pediatr. Infect. Dis. J., 32, e164–169.
84. Hutchinson, S., Marmura, M.J., Calhoun, A., et al. (2013) Headache, 53, 614–627.
85. Newport, D.J., Pennell, P.B., Calamaras, M.R., et al. (2008) Pediatrics, 122, e223–231.
86. Chow, C.K. and Koren, G. (2015) Can. Fam. Phys., 61, 241–243.
87. Van Wegberg, A.M.J., MacDonald, A., Ahring, K., et al. (2017) Orphanet J. Rare Dis., 12, 162.
88. Banta-Wright, S.A., Press, N., Knafl, K.A., et al. (2014) Brestfeed. Med., 9, 142–148.
89. Banta-Wright, S.A., Shelton, K.C., Lowe, N.D., et al. (2012) J. Pediatr. Nurs., 27, 319–327.
90. Wingrove, B., Lowery, K. and Del Rorario, G. (2016) Pediatrics, an issue of physician assistant
clinics. Elsevier Health Sciences, Philadelphia.
91. Ryan, A.S. and Hay, W.W., Jr. (2016) Nutr. J., 15, 42.
92. CAC (2007) Standard for infant formula and formulas for special medical purposes intended
for Infants: Codex Stan, 72-1981 (REVISION 2007). Joint FAO/WHO Codex Alimentarius
Commission. http://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%
253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCODE
X%2BSTAN%2B72-1981%252FCXS_072e.pdf [accessed 31 August 2018].
93. FDA (2017) Infant formula: guidance for industry. Food and Drug Administration. https://
www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/
InfantFormula/default.htm [accessed 10 September 2018].
94. WHO (2009) Baby friendly initiative: revised, updated and expanded for integrated care. WHO
Press, Geneva, Switzerland.
95. Green Corkins, K. and Shurley, T. (2016) Nutr. Clin. Pract., 31, 723–729.
96. FDA (2017) Guidance for industry. Demostration of the quality factor reguirements under
21 CFR 106.96 (i) for ‘Eligible Infant Formulas’. https://www.fda.gov/downloads/Food/
GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/UCM400131.pdf [accessed
10 September 2018].
97. European Commission (2011) Regulation (EU) No. 1169/2011 Official Journal of the European
Union 304. https://www.fsai.ie/uploadedFiles/Consol_Reg1169_2011.pdf [accessed 10
September 2018].
98. CAC (1981) Standard for infant formula and formulas for special medical purposes intended
for infants: Codex Stan, 72-1981. Joint FAO/WHO Codex Alimentarius Commission. http://
www.fao.org/fao-who-codexalimentarius/sh-proxy/fr/?lnk=1&url=https%253A%252F%25
2Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCODEX%2BSTAN%
2B72-1981%252FCXS_072e.pdf [accessed 10 September 2018].
99. Heird, W.C. (2007) J. Nutr., 137, 499s–502s.
100. Qian, L., Zhao, A., Zhang, Y., et al. (2016) Int. J. Mol. Sci., 17, 2128.
101. Praveen, P., Jordan, F., Priami, C., et al. (2015) Microbiome, 3, 41.
102. Azad, M.B., Konya, T., Maughan, H., et al. (2013) CMAJ, 185, 385–394.
103. Yutin, N. and Galperin, M.Y. (2013) Enviro. Microbio., 15, 2631–2641.
104. Penders, J., Thijs, C., van den Brandt, P.A., et al. (2007) Gut, 56, 661–667.

105. WHO/FCH/CAH (2004) Feeding the non-breastefed child 6–24 months of age. CAH, WHO,
Geneva, Switzerland.
106. Hochwallner, H., Schulmeister, U., Swoboda, I., et al. (2014) Methods, 66, 22–33.
107. Johansson, S.G., Bieber, T., Dahl, R., et al. (2004) J. Allergy Clin. Immunol., 113, 832–836.
108. Committee on Nutrition, American Academy of Pediatrics (2000) Pediatrics, 106, 346–349.
109. Cabana, M.D. (2017) Ann. Nutr. Metab., 70 (Suppl. 2), 38–45.
110. Badger, T.M., Gilchrist, J.M., Pivik, R.T., et al. (2009) Am. J. Clin. Nutr., 89, 1668s–1672s.
111. Dinsdale, E.C. and Ward, W.E. (2010) Nutrients, 2, 1156–1187.
112. O’Connor, N.R. (2009) Amer. Fam. Phys., 79, 565–570.
113. Schneider, N. and Garcia-Rodenas, C.L. (2017) Nutrients, 9, 187.
114. Tudehope, D., Fewtrell, M. and Kashyap, S. (2013) J. Pediatr., 162, S72–S80.
115. Lakshman, R., Ogilvie, D. and Ong, K.K. (2009) Arch. Dis. Child., 94, 596–601.
116. Su, B.H. (2014) Pediatr. Neonatal., 55, 5–13.
117. Carver, J.D. (2003) Am. J. Clin. Nutr., 77, 1550s–1554s.
118. Martinez-Augustin, O., Boza, J.J., Del Pino, J.I., et al. (1997) Biol. Neonate, 71, 215–223.
119. Cosgrove, M., Davies, D.P. and Jenkins, H.R. (1996) Arch. Dis. Child. Fetal. Neonatal Ed., 74,
F122–F125.
120. Freitas, R.G., Nogueira, R.J., Antonio, M.A., et al. (2014) Rev. Paul. Pediatr., 32, 126–135.
121. Kent, R.M., Fitzgerald, G.F., Hill, C., et al. (2015) Nutrients, 7, 1217–1244.
122. Blanchard, E., Zhu, P. and Schuck, P. (2013) Infant formula powders. In: Bhandari, B., Bansal,
N., Zhang, M. and Schuck, P. (eds), Handbook of food powders, pp. 465–483. Woodhead
Publishing Ltd, Cambridge.
123. FAO (2004) Enterobacter sakazakii and other microorganisms in powdered infant formula.
World Health Organization, Food and Agriculture Organization of the United Nations, Geneva,
Switzerland.
124. Turck, D. (2012) Ann. Nutr. Metab., 60, 211–214.
125. Chenu, J.W. and Cox, J.M. (2009) Lett. Appl. Microbiol., 49, 153–159.
126. Norberg, S., Stanton, C., Ross, R.P., et al. (2012) J. Food Prot., 75, 607–620.
127. Feeney, A., Kropp, K.A., O’Connor, R., et al. (2014) Gut Micr., 5, 711–718.
128. Feeney, A. and Sleator, R.D. (2011) Bioeng. Bugs, 2, 260–270.
129. Collado, M.C., Isolauri, E. and Salminen, S. (2008) FEMS Microbiol. Lett., 285, 58–64.
130. Spalinger, J., Nydegger, A., Belli, D., et al. (2017) Nutrients, 9, 219–232.
131. Bier, D.M. (2012) Ann. Nutr. Metab., 60. 192–195.
132. Koletzko, B., Shamir, R. and Ashwell, M. (2012) Ann. Nutr. Metab., 60, 179–184.
133. EFSA (2013) EFSA Journal, 11, 3408.
134. Vilter, R.W. (1980) West. J. Med., 133, 485–492.
135. Carr, A.C. and Maggini, S. (2017) Nutrients, 9, 1211.
136. Covarrubias-Pinto, A., Acuna, A.I., Beltran, F.A., et al. (2015) Int. J.Mol. Sci., 16, 28194–28217.
137. Padayatty, S.J. and Levine, M. (2016) Oral Dis., 22, 463–493.
138. Chambial, S., Dwivedi, S., Shukla, K.K., et al. (2013) IJCB, 28, 314–328.
139. Devaki, S. and Raveendran, R. (2017) Vitamin C: sources, functions, sensing and analysis.
https://www.intechopen.com/books/vitamin-c/vitamin-c-sources-functions-sensing-and-
analysis [avaiable 30 August 2018].
140. Lynch, S.R. and Stoltzfus, R.J. (2003) J. Nutr., 133, 2978s–2984s.
141. Nyhus Dhillon, C., Sarkar, D., Klemm, R.D., et al. (2017) Mat. Child Nutr., 13 (Suppl. 1), e12493.
142. Ribeiro, D.O., Pinto, D.C., Lima, L.M., et al.(2011) Nutr. J., 10, 47.
143. Pisoschi, A.M., Danet, A.F. and Kalinowski, S. (2008) J. Autom. Methods Manag. Chem., 2008,
937651.
144. Nauta, A.J., Ben Amor, K., Knol, J., et al. (2013) Am. J. Clin. Nutr., 98, 586s–593s.
145. Mameli, C., Mazzantini, S. and Zuccotti, G.V. (2016) Int. J. Environ. Res. Public Health, 13,
838.
146. Stuebe, A.M. and Rich-Edwards, J.W. (2009) Am. J. Perinatol., 26, 81–88.
147. Rai, D. and Larson, B. (2009) Am. J. Clini. Nutr., 89, 1530s–1532s.
148. Ballard, O. and Morrow, A.L. (2013) Pediatr. Clin. North Am., 60, 49–74.
149. Andreas, N.J., Hyde, M.J., Gomez-Romero, M., et al. (2015) Electrophoresis, 36, 2269–2285.
150. Bardanzellu, F., Fanos, V. and Reali, A. (2017) Nutrients, 9, 843.
151. Rzehak, P., Oddy, W.H., Mearin, M.L., et al. (2017) Am. J. Clin. Nutr., 106, 568–580.
152. Yoo, J.Y. and Kim, S.S. (2016) Nutrients, 8, 173.
153. Donovan, S.M. and Comstock, S.S. (2016) Ann. Nutr. Metab., 69 (Suppl. 2), 42–51.
154. Nejrup, R.G., Licht, T.R. and Hellgren, L.I. (2017) Sci. Rep., 7, 3975.
155. Vandenplas, Y., De Greef, E. and Veereman, G. (2014) Gut Microbes, 5, 681–687.
156. Watkins, C., Stanton, C., Ryan, C.A., et al. (2017) Front. Nutr., 4, 48.
157. Vandenplas, Y., Analitis, A., Tziouvara, C., et al. (2017) Pediatr. Gastroenterol. Hepatol. Nutr.,
20, 167–177.
158. Bode, L. (2012) Glycobiology, 22, 1147–1162.
159. Arslanoglu, S., Moro, G.E., Schmitt, J., et al. (2008) J. Nutr., 138, 1091–1095.
160. Hill, D.R. and Newburg, D.S. (2015) Nutr. Rev., 73, 463–476.
161. Delplanque, B., Gibson, R., Koletzko, B., et al. (2015) J. Pediatr. Gastroenterol. Nutr., 61,
8–17.
162. Koletzko, B. (2016) Ann. Nutr. Metab., 69 (Suppl. 2), 28–40.
163. Gallier, S., Vocking, K., Post, J.A., et al. (2015) Colloids Surf. B, 136, 329–339.
164. Baars, A., Oosting, A., Engels, E., et al. (2016) Br. J. Nutr., 115, 1930–1937.
165. Timby, N., Domellof, M., Holgerson, P.L., et al. (2017) PloS One, 12, e0169831.
166. Mudd, A.T., Alexander, L.S., Berding, K., et al. (2016) Front. Pediatr., 4, 4.
167. Straub, N., Grunert, P., von Kries, R., et al. (2011) Am. J. Clin. Nutr., 94, 2030s–2035s.
168. Willatts, P., Forsyth, S., Agostoni, C., et al (2013) Am. J. Clin. Nutr., 98, 536s–542s.
169. Field, C.J., Van Aerde, J.E., Robinson, L.E., et al. (2008) Br. J. Nutr., 99, 91–99.
170. Donovan, S.M., Monaco, M.H., Drnevich, J., et al. (2014) J. Nutr., 144, 1910–1919.
171. Lonnerdal, B. (2014) Am. J. Clin. Nutr., 99, 712s–717s.
172. Trabulsi, J., Capeding, R., Lebumfacil, J., et al. (2011) Eur. J. Clin. Nutr., 65, 167–174.
173. Hadley, K.B., Ryan, A.S., Forsyth, S., et al. (2016) Nutrients, 8, 216.
174. Imdad, A., Yakoob, M.Y. and Bhutta, Z.A. (2011) BMC Public Health, 11 (Suppl. 3), S24.
175. Cow & Gate (2017) First infant milk 1: nutritional information. http://www.cowandgate.co.uk/
article/first-infant-milk#nutritional-information [accessed 3 August 2018].
176. Gidrewicz, D.A. and Fenton, T.R. (2014) BMC Pediatrics, 14, 216.
177. WHO/UNICEF (2017) Tracking breastfeeding policies and programmes. http://www.who.int/
nutrition/publications/infantfeeding/global-bf-scorecard-2017.pdf.[accessed 5 March 2018].

Early Life Nutrition: Susan Finn, Eamonn P. Culligan, William J. Snelling and Roy D. Sleator

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Science Progress (2018), 101(4), 332 – 359

Paper 1800265 https://doi.org/10.3184/003685018X15360040523721

Early life nutrition

Ms Susan Finn holds a BSc in Nutrition and Health Science

Dr Eamonn Culligan holds a PhD in Microbiology from

Dr William Snelling holds a PhD from the University of Ulster.

Keywords: infant, breastfeeding, formula, nutrition

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2. Evolution of infant nutrition

Figure 1 Louis XIV as an infant with his

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4. Why women may not breastfeed?

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6. Composition of infant formula

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7. Microbiological safety of infant formulas

9. Quality control of vitamin C content of infant formulas

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10. Exploring the future of early life nutrition

11. Advances in infant nutrition research

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Published online: 8 October 2018

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