Accepted Manuscript

Care of the Growth Restricted Newborn

B. Carducci, Z.A. Bhutta

PII: S1521-6934(18)30044-0
DOI: 10.1016/j.bpobgyn.2018.02.003
Reference: YBEOG 1802

To appear in: Best Practice & Research Clinical Obstetrics & Gynaecology

Received Date: 2 August 2017

Accepted Date: 15 February 2018

Please cite this article as: Carducci B, Bhutta Z, Care of the Growth Restricted Newborn, Best Practice &
Research Clinical Obstetrics & Gynaecology (2018), doi: 10.1016/j.bpobgyn.2018.02.003.

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Title: Care of the Growth Restricted Newborn Authors:

Carducci B1 and Bhutta ZA2.

1. Bianca Carducci
th
Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, 11 Floor,
Suite 11.9805, Toronto, ON, M5G 0A4. Canada.
Phone: (416) 813-7654 ext. 309515
bianca.carducci@sickkids.ca

2. Zulfiqar A. Bhutta
Correspondence to: Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay
th
Street, 11 Floor, Suite 11.9805, Toronto, ON, M5G 0A4. Canada.
Phone: (416) 813-7654 ext. 328532
zulfiqar.bhutta@sickkids.ca
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INTRODUCTION

Optimal growth and development during the first 1,000 days of life is central to neonatal

health and, ultimately, health throughout the lifespan. With growth dependent on many

direct and indirect factors such as maternal nutrition and the placental environment, it is

critical that prenatal monitoring and postnatal care are prioritized. However, if fetal growth

is insulted during pregnancy, it is hypothesized that growth restriction can occur causing

subsequent postnatal adverse health outcomes, as well as mortality [1]. Globally in 2015,

45% of all under-five deaths occurred in the first month of life, where the majority of these

deaths were due to preterm-birth and intrapartum-related complications [2]. In terms of

morbidity, growth restriction or growth failure can manifest itself as term or preterm

intrauterine growth restriction, small-for-gestational age or low birth weight. The

distinction between theses terms including timing of diagnosis is key for appropriate

neonatal care. Neonates can be classified by gestational age at birth (preterm, late

preterm, term and post-term), birth weight (extremely low birth weight [ELBW], very low

birth weight [VLBW], low birth weight [LBW]), and gestational age and birth weight

combined (small-for-gestational age [SGA], appropriate-for-gestational age [AGA], large-

for-gestational age [LGA]). Moreover, though it is often used interchangeably with SGA,

intrauterine growth restriction (IUGR) is a prenatal observation of growth restriction

confirmed either by a documented reduced fetal growth velocity and/or by the presence of

specific causes such as fetal infection, compromised placental blood flow, or toxic effects.

IUGR may be asymmetrical or symmetrical in nature, depending on the timing of the

prenatal insult and diagnosis. (Box 1 and Figure 1) [3-5].

Box 1. Key Definitions

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Preterm - Birth between 32 to less than 37 weeks of gestation

Very Preterm – Birth between 28 to less than 32 weeks of gestation
Extremely Preterm – Birth under 28 weeks of gestation

Low Birth Weight – Neonate weight under 2.5 kg at any gestational age
Very Low Birth Weight – Neonate weight under 1.5 kg at any gestational age
Extremely Low Birth Weight – Neonate weight under 1.0 kg at any gestational age

Small-for-Gestational Age –The birth-weight-for-gestational age, sex specific, single/twin curve, where
the 10th percentile of the curve should be used to classify SGA.

Intrauterine Growth Restriction/Retardation - A prenatal condition in which a fetus’ estimated weight

is below the recommended gender-specific weight for gestational age.
[Insert Figure 1 about here]

As shown in Figure 1, LBW can be a consequence of being premature, SGA or both, while

SGA can occur in both full-term (FT-SGA) and preterm (PT-SGA) infants [5]. This is

particularly relevant in terms of prognosis and morbidity management. Notably, a child

born SGA or LBW might have not suffered IUGR, and a baby born after a short span of

IUGR might not be SGA or LBW.

According to UNICEF estimates, approximately 16% of all newborns born globally in

2013 were LBW [7], while estimates of SGA are approximately 27% of all live births in

2010 [8]. Notably, LBW and SGA data remains limited or unreliable, as many deliveries

occur in homes or small health clinics and are not reported in official figures, which may

result in an underestimation of the prevalence. The association between growth restriction

and increased risk of mortality have been well documented. In fact, SGA infants are at a 2-

4 time higher risk of mortality compared to full-term infants and preterm non-SGA infants

[9]. With lack of data in the literature, IUGR is estimated to affect between 5-10% of all

pregnancies per year [10].

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ETIOLOGY

The etiology of all forms of growth restriction is multifactorial and complex in nature.

Though the pathophysiological mechanisms of maternal, fetal and uteroplacental risk

factors on growth-restriction differ, their mutual outcome of suboptimal placental

perfusion and fetal undernutrition have been widely studied. Selected risk factors are

presented in Box 2 [1, 7, 10-12].

Box 2. Etiology of Fetal Growth Restriction

Genetic & Anatomical

• Maternal height
• Maternal age
• Ethnicity
• Uterine or cervical anomalies
• Previous IUGR/SBW/LBW baby
• Congenital malformations
• Chromosomal abnormalities
• Inborn errors of metabolism

Nutrition
• Low pre-pregnancy BMI
• Micronutrient deficiencies
• Shorter inter-pregnancy intervals
• Multiple gestation
• Parity
• Insufficient utero-placental perfusion

Clinical Diseases
• Clinical or chronic disease (pregestational diabetes, hypertension,
preeclampsia, anemia, asthma, thyroid disease, kidney disease)
• Maternal mental health
•
Maternal infection (urinary tract infection, rubella, cytomegalovirus, malaria, bacterial
vaginosis, HIV, syphilis, Listeria monocytogenes, group B streptococcus,
chorioamnionitis)
• Placenta previa
• Abruption placentae
• Congenital infections
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Social & Environmental

• Low socioeconomic status

• Illicit drug use

Poor antenatal care

Excessive physical work
Stress

PROGNOSIS

Complications of fetal growth restriction can be immediate, intermediate and long-term

in nature. For growth-restricted infants, immediate consequences include persistent

pulmonary hypertension, hypothermia, hypoglycaemia, hyperglycaemia, pulmonary

haemorrhage, polycythemia, stillbirth, premature birth and intrapartum asphyxia [13,14].

Moreover, preterm infants are prone to multi-system complications, in combination with

the sequelae of IUGR, SGA and LBW, such as anemia, respiratory failure, necrotising

enterocolitis (NEC), retinopathy of prematurity, hyperbilirubinemia and patent ductus

arteriosus [13,14].

Intermediate and long-term outcomes have been well-documented and include stunting,

impaired cognitive and motor development, and susceptibility to developmental origins

of diseases (DOHaD). These are defined as adult chronic diseases such as metabolic

syndrome, obesity, hypertension, reduced glucose tolerance, increased insulin resistance,

• Smoking
• Alcohol abuse
• •
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dyslipidemia, type 2 diabetes, cardiovascular disease, and chronic lung and kidney disease

[7,9,13]. This ‘thrify phenotype’ hypothesis suggests that antenatal insults to the

intrauterine environment can disrupt hormones related to fetal insulin sensitivity and

consequently, predisposing the fetus to diabetes in later life [14].

Though treatment plans can be tailored to individual infants, the general priority of care is

to achieve growth velocity and optimal health similar to that of a normal infant. Balancing
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nutrient supply, such that benefits outweigh the risks of catch-up growth, is key. Too early

postnatal catch-up growth has been linked to an increased risk of adult life abdominal fat,

insulin resistance and increased fat mass, while poor catch-up growth is associated with

low IQ and short stature [14,15]. To circumvent this, preventive care, essential newborn

care, and the continuum of care for high-risk infants is compulsory. This review will focus

on preventive, essential and continuous care in terms of exclusive breastfeeding, nutrition

and fluid support, kangaroo mother care, and thermoregulation in the context of IUGR,

SGA, preterm and LBW neonates. Recommendations for extremely and very preterm or

LBW neonates will be integrated, though not emphasized.

DIAGNOSIS

Antenatal monitoring is critical for early detection of IUGR and improved neonatal

outcomes. Presently, there is no gold standard to diagnose IUGR as multiple modalities

including biochemical, histological and clinical features are currently practiced. Maternal

and familial risk factor assessments, maternal anthropometry (pre-pregnant and pregnant),

as well as maternal nutritional status are key screening tools for early indications of IUGR

in high-risk mothers. Additionally, the practice of ultrasonography to determine

appropriate gestational age through 1st trimester crown rump length (CRL) and last

menstrual period (LMP) is also used to identify slowed growth. If these preliminary

investigations warrant more intensive and sensitive tests, the Royal College of

Obstetricians and Gynaecologists recommend the use of various Doppler velocities

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(uterine artery, umbilical artery, middle cerebral artery, cerebro-placental ratio, ductus

venosus, and aortic isthmus), biometric measures, biophysical profile and

cardiotocography for diagnosis [7,12-19]. Taken together, these tests can inform IUGR

staging and timing of delivery [13].

At birth, infants can be further clinically examined and diagnosed as IUGR using the

Ponderal Index (PI), indicative of fetal malnutrition, as well the Cephalization Index (CI),
th
the ratio of head circumference to body weight [13]. A PI less than the 10 percentile

reflects fetal malnutrition, while a high CI indicates greater brain vulnerability.

Moreover, newborns may be additionally classified as preterm, LBW and or SGA, where

the latter is often associated with early-onset IUGR [7,12-19]. Notably,

st
INTERGROWTH-21 has developed the latest international fetal, newborn and postnatal

prescriptive standards. These are complementary to World Health Organization (WHO)

Child Growth Standards, which provide recommendations for growth and size and are

particularly important when diagnosing growth-restricted infants [20-22].

PREVENTIVE CARE

With recognition that maternal undernutrition and maternal infections increase the risk of

IUGR, LBW, SGA, there is significant opportunity to intervene with preconception

interventions [23, 24]. Preconception care, as defined by the WHO, is the ‘provision of

preventive, promotive or curative health and social interventions before conception occurs’

[25]. Preconception care for women is vital for promoting optimum nutrition, family

planning, infection assessment and appropriate inter-pregnancy intervals. Moreover, the

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prevention of early and adolescent pregnancies is integral to the prevention of

undernutrition in pregnant women [26, 27].

In terms of antenatal supplementation, the WHO recommends routine iron and folic acid

supplementation in pregnancy, where the dosage of iron is dependent upon the prevalence

of anemia [28]. However, over the past decade, a cost-effective multiplemicronutrient

supplement, UNIMMAP, has emerged to avert maternal micronutrient deficiencies during

pregnancy. The UNIMMAP supplement contains one recommended daily allowance of

vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C,

vitamin D, vitamin E, copper, selenium, and iodine with 30 mg of iron and 15 mg of zinc.

According to a recent Cochrane review, women who took UNIMMAP, compared to an

iron supplement with or without folic acid, had a reduced risk of infants born SGA, LBW

or stillbirth [29].

Finally, the prevention and treatment of malaria in pregnant mothers is a WHO priority in

malaria-endemic areas. WHO recommends a three-step approach including the use of

insecticide treated bed nets, intermittent preventive treatment of malaria with sulfadoxine-

pyrimethamine (IPTp-SP), and appropriate case management [30].

CARE AT CHILD BIRTH

At birth, resuscitation, timing of umbilical cord clamping, thermoregulation and initiation

of breastfeeding are key components of delivery room care. Once an infant is stabilized,

immunization and newborn screening are necessary to minimize infections and early

diagnosis of congenital disorders and medical conditions. In addition, it is prudent for each
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neonatal intensive care unit to reinforce and practice hygiene standards, especially with

families, as the susceptibility to infections is greater in high-risk, growth-restricted infants

[22]. Furthermore, an intramuscular dose of vitamin K is also administered in preterm

infants (0.4 mg/kg) to reduce the risk of vitamin K-deficiency bleeding [22].

Resuscitation

Though the majority of infants transition from the intrauterine to extrauterine environment

well, 5-10% of infants require active cardiorespiratory intervention. Neonatal resuscitation

and stabilization immediately after birth is critical in preventing brain damage. Guidelines

and steps in resuscitation include simultaneous rapid assessment and response to an

infant’s gestational age, airway, colour, muscle tone and heart rate, within the first 30

seconds of birth. Importantly, if an infant is identified as preterm, unable to breathe or cry

and or has poor muscle tone, immediate warming, drying, positioning to clear the airway

and stimulation should be completed. Subsequently, neonatal respirations and heart rate

should be assessed to determine if ventilation is required [22]. Re-evaluation, as well as 1-

minute and 5-minute Apgar scores should be obtained until the newborn is vigorous.

Delay of Umbilical Cord Clamping

Emerging evidence on the timing of umbilical cord clamping suggests a delay is

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favourable in both term and preterm infants [31]. WHO and Cochrane guidance on this

practice suggests the optimal timing of umbilical cord clamping is 1-3 minutes after birth,

as this allows for placental transfer of iron stores. Though this recommendation is

applicable for both term and preterm infants, preterm and LBW infants may experience

greater benefits immediately. Identified immediate benefits include increases in

haemoglobin, hematocrit and blood pressure, a decreased risk of NEC and

intraventricular haemorrhage, as well as a decreased need for blood transfusions,

surfactant and mechanical ventilation [32].

Thermoregulation

Supportive thermal care of growth-restricted newborns is particularly important soon

after birth, as these infants have increased insensible water loss and little capacity to

thermoregulate core body temperature given reduced brown fat and subcutaneous fat

mass, immature epidermal barriers and a larger surface area to body mass ratio.

Consequently, preterm, LBW and SGA infants are extremely vulnerable to hypothermia.

Interventions for thermal protection include warming the delivery room, immediate

drying, occlusive wrapping, appropriate clothing, KMC, and external heat sources such

as incubators or radiant warmers.

In preparation of birth, standard of care involves establishing a thermo-neutral environment

in the delivery room, with an air temperature of at least 25°C as recommended by the

WHO [33-35]. Moreover at birth, immediate drying of the neonate is essential to avoid
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first heat loss from evaporation of amniotic fluid, whereas bathing of neonates should be

postponed until ideally after 24 hours of life [22, 36]. While drying, infants should be

positioned on mother’s chest or abdomen, then subsequently wrapped or covered,

especially the head, while with the mother. KMC is crucial in thermal care of preterm and

or low birth weight infants who are stable, as it assists in preserving newborn body

temperature through SSC [35, 37]. The threshold and quantity of KMC to improve

outcomes has not been determined. Vigilant monitoring of growth-restricted and or

preterm infant’s core body temperature is essential. Methods of measuring temperature of

these infants includes axillary and rectal thermometry, where axillary temperature should

remain in the range of 36.0–37.0 °C (96.8–98.6 °F) or 36.5–37.5 °C (97.7–99.5 °F) for

rectal temperature [33, 34]. Axillary temperatures are commonly used over rectal

temperatures, as they are less invasive and correlate well with abdominal temperatures.

The use of occlusive wrapping, plastic bags plastic bags, hats and swaddling materials also

assist in maintaining infant body temperature, but are insufficient in doing so alone [35].

Additionally, it appears the benefits of plastic wrap or bags in combination with routine

thermal care, were more effective in preserving core body temperature in infants <28

weeks gestation, in comparison to infants 28-31 weeks gestation [35]. Radiant heaters or

incubators may also be necessary in caring for high-risk infants, if available.

Adjustment of air and radiating surface temperatures, as well as relative humidity is based

on infant clothing, weight, gestational age and insensible fluid loss (Table 3).

Abdominal skin temperatures should be in the range of 36.3-37.0 °C (97.3–98.6 °F) [34,
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38], which should be checked every half hour, in the first 24 hours of life. Importantly,

the use of sterile water for humidification and cleaning of incubators is of highest priority

to reduce the risk of hospital-acquired neonatal infections [27, 28]. Specific

thermoregulation care plans should be consulted [39].

[Insert Table 1 about here]

Emollient Therapy

While this is a common practice in both high-income and low- and middle- income

countries, the use of topical ointments and oils (vegetable, mustard, sunflower, coconut,

safflower, sesame or soybean) as a preventative treatment for infections in high-risk

infants is quite controversial in the literature [40-42]. Mechanistically, emollient therapy

is thought to provide a physical barrier on the skin to conserve heat, reduce

transepidermal water loss and susceptibility to infections. A review by Salam, Das,

Darmstadt and Bhutta (2013), reported a 27% significant reduction in neonatal mortality

and 50% risk reduction in hospital acquired infections in preterm infants as compared to

no intervention or control in LMICs. However, latest evidence from a Cochrane review

suggests topical ointments, creams and oils did not provide significant reductions in

invasive infections or mortality in preterm infants compared to routine skin care in both

high-income and LMICs. The heterogeneity within the literature has been attributed to

differential inclusion of studies, as well as methodological weakness of studies on

emollient therapy. Further research is necessary to understand how this low-cost, safe
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intervention can be utilized to reduce morbidity and mortality in newborns.

Initiation of Breastfeeding

With the goal to implement practices that promote, support and protect breastfeeding, the

World Health Assembly adopted the International Code of Marketing Breast-milk

Substitutes in 1981 and the WHO and United Nations Children’s Fund (UNICEF)

launched the Baby-friendly Hospital Initiative (BFHI) in 1991 [2]. Breast milk is widely

recognized as the primary nutrition source for both term and preterm infants, as well as

IUGR, SGA and LBW infants. High quality evidence suggests breast milk confers many

immunological, bioactive, psychological and environmental benefits for both mothers

and infants. Of these worth noting are the effects on neurological and gastrointestinal

maturation, as well as a reduction in the incidence of postnatal consequences such as

NEC, postnatal growth restriction and mortality. Standard practice of care advises the

initiation of breastfeeding within the first hour of birth, in order for newborns to receive

the colostrum or ‘first milk’ [13, 21, 22, 31, 33, 34, 38, 40, 43, 44].

CONTINUUM OF CARE

Immediate postnatal care is imperative following labour and birth as maternal and

newborn mortality is greatest in this period. Evidence continues to mount for exclusive

breastfeeding, kangaroo mother care and other forms of nutrition support such as human milk

fortifiers, as part of continuous care.

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Energy Requirements

Several groups have developed and published energy and nutrient intakes for preterm,

SGA and LBW infants, whereas available evidence on specific energy and nutrient intake

in term IUGR or SGA remains scarce. As seen in Table 2, based on an infant’s weight

and age at birth, energy and nutrient requirements vary. It is important to note that these

recommended intakes are for guidance, as individual absorption and bioavailability may

differ based on consumption of human milk or infant formula.

As nutritional status is often inferred from weight gain, healthy infant guidelines suggest

from birth to age 6 months, a neonate may grow ½ an inch to 1 inch (about 1.5 to 2.5

centimeters) a month and gain 5 to 7 ounces (about 140 to 200 grams) a week.

[Insert Table 2 about here]

Exclusive Breastfeeding

Exclusive breastfeeding from birth until 6 months of age, is strongly recommended by

WHO in FT-SGA, PT-SGA, LBW and preterm infants [43]. Infants who cannot

breastfeed, for instance in preterm or LBW infants, mothers are encouraged to feed

expressed breast milk with a cup and spoon [13, 21, 22, 31, 33, 34, 38, 40, 43, 44].

Expressed breast milk should be stored in a refrigerator and used within 72 hours. Feed

volumes should begin at 80 mL/kg/day on the first day of life and incrementally increase

by 10-20 mL/kg/day, until maximum (160-180 mL/kg/day) is reached at the end of the first
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week of life [34]. Decisions to enteral feed (i.e nasograstric, orogastric, gastrostomy,

transpyloric) should be based on oromotor abilities, gestational age and clinical condition.

While challenging and controversial, recent data suggests providing enteral nutrition

support to VLBW infants positively impacts feeding tolerance, maternal-infant bonding

and reduces the incidence of NEC. However, due to many other complications with

VLBW infants, mothers often encounter difficulties with lactation and experience

psychosocial issues. This frequently delays enteral feeding and subsequently the need for

parenteral nutrition [45-49]. Though delaying enteral feeding was previously thought to

decrease the risk of NEC in VLBW infants, latest Cochrane reviews have suggested that

both slow and delayed enteral feeding does not decrease the risk of NEC [49, 50]. WHO

guidelines for feeding VLBW should be consulted for specific feeding recommendations.

Notably, VLBW infants may require parenteral fluids and supplementation with iron,

vitamin D, calcium and phosphorus to reduce the likelihood of complications associated

with VLBW. With regard to iron supplementation, VLBW infants are recommended 2-4

mg/kg per day at 2 weeks until 6 months, while daily calcium and phosphorus should be

given at 120-140 mg/kg and 60-90 mg/kg respectively, in the first month of life. Vitamin D

is recommended daily for the first 6 months at a dose ranging from 400 to 1000 IU [43].

With recent updates to the BFHI and WHO guidelines for infant feeding in HIV, exclusive

breastfeeding is strongly encouraged for at least 12 months and up to 24 months of life in

HIV-positive mothers, while on effective antiretroviral therapy (ART)

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[51]. Mothers living with HIV and health-workers should be reassured that postnatal

transmission of HIV through breastfeeding is reduced with ART [51].

Alternative Milk Sources

In circumstances when an infant cannot be fed by a mother’s own milk and provided that

human milk banks are regulated, safe and affordable, WHO, American Academy of

Pediatrics and the European Society for Paediatric Gastroenterology Hepatology and

Nutrition recommend pasteurized donor milk as a first alternative milk source over

standard and preterm infant formula when feeding term, preterm, IUGR, SGA, LBW or

VLBW infants [52, 53]. In a Cochrane review, preterm infants fed donor milk were found

to have improved feeding tolerance, reduced delay to enteral feeding and a lower

incidence of NEC, when compared to preterm infants fed infant formula [54].

Importantly, administration of donor milk to preterm/LBW/VLBW infants should be

through cup and spoon, unless the neonate is sick or birth weight is under 1.0 kg [43].

Although there has been rapid expansion of human milk banks across the world, there are

several challenges which still exist, including a lack of infrastructure, guidance and

support politically, financially and within the community [55]. In resource-limited settings,

lack of regulatory and operational procedures including hazard analysis and critical control

processes to serologically screen donors and their milk, and further pasteurize, can

constrain the provision of donor milk [55].

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Human Milk Fortification

In preterm infants (with or without growth-restriction), evidence suggests human milk

alone may not be sufficient for growth. Given the higher nutrient requirements, coupled

with a rapid decline of protein and caloric composition of preterm human milk, preterm

infants may require expressed preterm milk or donor milk to be fortified [43, 47]. Human

milk fortifiers (HMF) are human milk-based or bovine milk-based sources of

macronutrients and or micronutrients, which can help meet preterm nutritional needs. In

the case of VLBW infants, WHO recommends the use of only human milk-based

In terms of fortification methods, there are three types when using HMF, namely standard

and individualized (targeted and adjustable) fortification. Standard fortification utilizes an

empirical dose of fortifier, which is added to expressed breast milk or donor milk.

Targeted fortification uses human milk analyses to inform the quantity of fortifier to meet

a specific nutritional requirement; whereas adjustable fortification uses blood urea

nitrogen levels to guide periodic and gradual increases in the amount of fortifier and extra

protein to breast milk [46, 56]. Data suggests compared to standard fortification,
fortifiers.
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adjustable fortification has been found to provide additional protein intake without volume

or caloric adjustments, leading to significantly higher length and head circumference

velocities in preterm very low birth weight infants [57].

Fortification preparations are available in powder and liquid forms, and can be

monocomponent (i.e. protein, fat, carbohydrate, sodium, calcium or phosphorus) or

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multi-component in composition. However, a recent Cochrane review found limited

evidence to support the use of multi-component HMF compared to unfortified breast milk

on important growth and development outcomes in preterm infants [58]. Consensus

recommendations and clinical guidance on HMF include [46, 56]:

HMF use only once the infant’s intake of expressed breast milk or pasteurized

donor milk has consistently reached 100 mL/kg/day

One powdered sachet (1 g) of HMF provides 4 g/kg/day of protein, 3.5-4 g/kg/day

of fats and 24 kcal/oz. This should be added to 20-25 mL of expressed breast or

pasteurized donor milk

Recommended protein intake is 3.5-4 g/kg/day, depending on birth weight and

age

Monitoring infant daily caloric and protein intake, as well as daily growth

velocities is important

Calcium and phosphorous levels should be monitored to prevent hypercalcemia

and osteopenia of prematurity respectively

Breast Milk Substitutes

•
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With lack of access to expressed or pasteurized donor milk, use of breast milk substitutes

and mixed feeding appears to be a widespread practice, especially in LMICs. However,

there are greater risks involved when artificial or mixed feeding growth-restricted infants

including a greater risk of developing NEC [54]. Sterilization of feeding and preparation

equipment is essential when artificial feeding preterm infants, as they are innately at a

higher risk of infection, in combination with the absence of immunological factors from

breast milk [43]. In circumstances where mothers plan to formula feed their SGA infant

(moderate-severe IUGR), they are encouraged to provide 60 mL/kg per day of formula on

the first day of life (80 mL/kg if <2.0 kg), 3 to 4 times per hour [13].

Glucose Monitoring

Blood glucose homeostasis in the first 48 hours of life is critical in growth-restricted

infants as they are at high risk for both hypoglycaemia and hyperglycaemia. Due to limited

stores of glycogen and fat, early reports have suggested hypoglycaemia in premature and
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LBW infants. Conversely, parenteral glucose infusion in preterm and LBW, VLBW

infants, who lack endogenous glucose production suppression and insulin secretion, is

associated with a high risk of neonatal hyperglycaemia and mortality [21]. According to

the American Academy of Paediatrics and WHO, normal blood glucose is approximately

30 mg/dL in all newborns 1-2 hours after birth and become relatively stable at 45 mg/dL

12 hours after birth. In high-risk infants (late-preterm and SGA) without any clinical signs,

initial feeding should be within the first hour after birth, and glucose levels should be

screened 30 minutes after. Subsequently, if blood glucose remains less than 25 mg/dL

(between birth to 4 hours) or less than 35 mg/dL (4–24 hours of age) after the initial feed

and check, the infant should be re-fed and glucose should be rechecked 1 hour after re-

feeding [22, 59]. If blood glucose continues to remain at these levels, appropriate

intravenous treatment is recommended. The target blood glucose level is 45 mg/dL after

every feed.
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In contrast, hyperglycaemia is defined as whole blood glucose concentration greater than

120 to 125 mg/dL (6.66 to 6.94 mmol/L) or a plasma glucose concentration greater than

145 to 150 mg/dL (8.05 to 8.33 mmol/L) regardless of the neonate’s gestational age,

weight, or postnatal age [60]. Optimal management strategies include reduction of IV

dextrose concentration or infusion rate and insulin treatment [22].

Kangaroo Mother Care

Kangaroo mother care (KMC) is an effective low-cost alternative to conventional

neonatal care for all growth-restricted infants, especially preterm and low birth weight

infants. Described in the 1970s, the WHO defines KMC as four components including

early, continuous skin-to-skin contact (SSC) between the newborn and mother, frequent

exclusive breastfeeding, early discharge from the hospital and close follow-up at home.

Immediate or early skin-to-skin contact begins at birth and involves placing the naked

baby, head covered with a dry cap and a warm blanket across the back, prone on the

mother's bare chest. Immediate SSC is initiated at birth, whereas early SSC begins within

the first day (birth to 24 hours). From a psychological perspective, postpartum SSC is

thought to prime an infant’s biological, mental and socio-behavioural strategies to their

environment through maternal contact, providing long-term benefits [61-63].

WHO guidance on interventions to improve preterm birth outcomes, strongly recommends

continuous KMC as routine care in stable infants under 2.0 kg at birth [37], as KMC has
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been associated with a 36% to 40% statistically significant risk reduction in mortality as

compared to conventional care, at discharge, 40-41weeks gestation or latest follow-up in

LBW infants [31, 61, 62, 64]. As well, the authors of both reviews reported a relative risk

reduction in hypothermia by 78% in all infants [47, 48], 88% reduction in hypoglycaemia

in LBW infants, and risk reduction of hospital readmission by 58% [61]. Furthermore, a

2016 Cochrane review found substantial evidence supporting KMC, especially in low- and

middle- income settings, as there was a positive association to increased infant growth

outcomes in LBW infants. KMC infants were found to gain more weight (mean difference

of 4.1 grams), had greater increases in length (mean difference of 0.21 cm) and increased

head circumference (mean difference of 0.14 cm), when compared to infants given

conventional care. In terms of promotion of breastfeeding, the authors also found an

increased likelihood of exclusive breastfeeding at discharge in KMC infants [62]. Thus,

KMC is protective for growth-restricted infants, and should be promoted immediately after

birth. It is with hope that future research will understand potential links between KMC and

early child development.

DISCHARGE CRITERIA & HOME CARE

Guidelines from the American Academy of Paediatrics state criteria necessary for

discharge of a high-risk infant. This includes an assessment of infant physiological state,

family and environmental readiness, and community and health-system preparedness to

ensure continuing care and follow-up. Infants should have steady weight gain of 30 g/day,

maintenance of a normal body temperature, cardiorespiratory stability, resolution of

medical complications and competent feeding through breast or bottle prior to discharge

[22, 38]. Importantly, the prescription and use of nutrient-enriched preterm formulas
 ACCEPTED MANUSCRIPT

following hospital discharge is not supported in the literature [65]. Conversely,

breastfeeding support and lactation consultation information should be provided.

Moreover, immunizations, metabolic screening, hearing and eye examinations should be

completed and individualized home care plans should be developed. Primary care

providers should offer parental education on home care including signs and symptoms of

illness, sleeping positions, medication administration, respiratory and nutrition support,

especially infants reliant on technology for parenteral feeding. Finally, follow-up care

within the home or arranged at a nearby health facility is key in providing continuum of

care. Growth-restricted infants should be timely monitored for neurological,

developmental, and behavioural status, to ensure appropriate referrals and early

intervention is made [22].

SUMMARY

Taken together, there is significant evidence to support essential newborn care and the

continuum of care tailored to growth-restricted infants in terms of resuscitation,

thermoregulation, delayed umbilical cord clamping, exclusive breastfeeding and Kangaroo

Mother Care. Specific guidelines to treat neonatal morbidities should be consulted, while

preventive strategies should be integrated in care packages across the life cycle. Discharge

decisions of high-risk infants should be dependent upon infant, family and community

readiness. Future research is warranted to understand the differences in care between term

and preterm IUGR/SGA infants, evaluating a possible dose-response relationship between

Kangaroo Mother Care and neonatal outcomes, as

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well as strengthening findings for the use of emollients for infection and mortality

CONFLICTS OF INTEREST: None.

PRACTICE POINTS

Preconception care should be provided to women of reproductive age, especially

expectant mothers in terms of promoting maternal nutrition, risk factor

assessment, and malaria treatment.

Rapid assessment and response to newborn airway, colour, muscle tone, and heart

rate should be initiated within 30 seconds after birth.

Delay umbilical cord clamping until 1 to 3 minutes after birth.

Delivery environments should be thermo-neutral (25°C) and use of appropriate

clothing or wrapping should be used in combination with maternal skin-to-skin

contact to maintain a neonate’s core temperature.

Exclusive breastfeeding should be initiated within the first hour after birth and

continuously until 6 months of age for stable small-for-gestational age, low birth

weight, very low birth weight and preterm infants. In some cases, human milk

fortifiers may be necessary.

prevention.

•
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• Pasteurized donor milk is the preferred alternative milk source standard and

preterm infant formula when feeding term, preterm, IUGR, SGA, LBW or VLBW

infants.
• Continuous Kangaroo Mother Care should be promoted immediately after birth for

stable small-for-gestational age, low birth weight and preterm infants.

RESEARCH AGENDA

• Determining specific postnatal management of term and preterm IUGR and or

SGA infants.

• Strengthening evidence for human milk bank models and integrating within

newborn care packages.

• Identifying the minimum threshold of KMC exposure needed to achieve an impact

on neonatal mortality and other important outcomes.

 ACCEPTED MANUSCRIPT

• Understanding the role of emollient therapy in reducing infections and mortality

among preterm infants.

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[65].
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Table 1. Suggested Incubator Air Temperatures of Newborns by Weight and Age. Adapted
from [39].

Table 2. WHO Recommended Daily Energy and Nutrient Intakes at Birth for Preterm
Infants (>1.0 kg). Adapted from Edmond, Karen and Bahl, (2006) [43]
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st
Figure 2: Intergrowth – 21 Birth Weight for Gestational Age Standard

Adapted from: Villar, J., L. Cheikh Ismail, C. G. Victora, E. O. Ohuma, E.

Bertino, D. G. Altman, A. Lambert, A. T. Papageorghiou, M. Carvalho, Y. A.
Jaffer, M. G. Gravett, M. Purwar, I. O. Frederick, A. J. Noble, R. Pang, F. C.
Barros, C. Chumlea, Z. A. Bhutta, and S. H. Kennedy. 2014. "International
standards for newborn weight, length, and head circumference by gestational
age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st
Project." Lancet 384 (9946):857-68. doi: 10.1016/s0140-6736(14)60932-6.
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HIGHLIGHTS

• Essential newborn care and the continuum of care tailored to growth-restricted

Preconception care packages should be integrated across the life cycle.

Breast milk is the preferred nutritional source for stable growth-restricted infants.
Kangaroo Mother Care is protective for growth-restricted infants.

infants is critical. • •
•