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Neonatal and Infant Nutrition Dr Russell Peek Paediatric HST Core Training Day Gloucester, 4 Neonatal and Infant Nutrition Dr Russell Peek Paediatric HST Core Training Day Gloucester, 4 th October 2007

Introduction • What does ‘nutrition’ mean to you? Introduction • What does ‘nutrition’ mean to you?

The OED definition Nutrition (noun) 1. the process of taking in and assimilating nutrients. The OED definition Nutrition (noun) 1. the process of taking in and assimilating nutrients. 2. the branch of science concerned with this process. DERIVATIVES nutritional adj. nutritionist noun. ORIGIN Latin, from nutrire ‘nourish’.

Textbook answer • Nelson’s Textbook of Paediatrics – achievement of satisfactory growth and avoidance Textbook answer • Nelson’s Textbook of Paediatrics – achievement of satisfactory growth and avoidance of deficiency states.

Aims • To explore the knowledge base behind key competencies in nutrition for paediatricians Aims • To explore the knowledge base behind key competencies in nutrition for paediatricians • Reference: A Framework of Competences for Core Higher Specialist Training in Paediatrics (RCPCH, 2005. )

Objectives • By the end of this morning, you will – understand the effects Objectives • By the end of this morning, you will – understand the effects of fetal growth restriction on short- and long-term health – understand the principles and importance of nutrition in the neonatal period including assessment of nutritional status – be able to make appropriate recommendations to address feeding problems and faltering growth

‘Normal’ Nutrition ‘Normal’ Nutrition

Fetal nutrition • Parenteral (mostly!) • Stores are laid late in gestation • At Fetal nutrition • Parenteral (mostly!) • Stores are laid late in gestation • At 28 weeks, a fetus has: – 20% of term calcium and phosphorus stores – 20% of term fat stores – About a quarter of term glycogen stores

Adaptation to nutrition after birth • Gut adaptation is regulated by – Endocrine factors Adaptation to nutrition after birth • Gut adaptation is regulated by – Endocrine factors – Intraluminal factors – Breast milk hormones and growth factors – Bacteria

Breast is best Breast is best

Feeding the term infant • Breast feeding achieves – Nutrition – Immunological and antimicrobial Feeding the term infant • Breast feeding achieves – Nutrition – Immunological and antimicrobial protection – Passage of breast milk hormones and growth factors – Provision of digestive enzymes – Facilitation of mother-infant bonding

Supplementing breast milk • Should be unnecessary, but – Vitamin K levels are low Supplementing breast milk • Should be unnecessary, but – Vitamin K levels are low – Vitamin D levels are low in areas of little sunlight – Iron levels are low (but very well absorbed)

Artificial Feeds • Term formulas are broadly similar – May be whey or casein Artificial Feeds • Term formulas are broadly similar – May be whey or casein based – International agreed standards for constituents

Artificial feeding • Practical considerations for making up feeds – Water softeners increase sodium Artificial feeding • Practical considerations for making up feeds – Water softeners increase sodium content – Repeated or prolonged boiling can increase sodium content of water – Bottled water can contain high levels of carbon dioxide, sodium, nitrate and fluoride.

Monitoring feeding • Maternal sensation of engorgement and emptying • Frequency of feeding • Monitoring feeding • Maternal sensation of engorgement and emptying • Frequency of feeding • Wet nappies • Stools • Jaundice • Weight

Normal output Daily stool and urine output guidance Day 0 1 wet nappy and Normal output Daily stool and urine output guidance Day 0 1 wet nappy and meconium at least once a day Day 1 2 wet nappies and meconium at least once a day Day 2 & 3 3 or 4 wet nappies and changing stools at least once a day Day 4+ 5 or 6 heavy wet nappies and yellow stools at least once daily A baby who is passing meconium at 3 or 4 days old may not be getting enough milk. A baby who does not have yellow stools by day 5 may not be getting enough milk. A baby who is not doing as many wet nappies each day as expected may not be getting enough milk.

Support for breast feeding mothers • • Midwife Infant feeding specialist Breast feeding support Support for breast feeding mothers • • Midwife Infant feeding specialist Breast feeding support groups National Childbirth Trust

Nutrition for the preterm or sick baby Nutrition for the preterm or sick baby

From little acorns… • The obstetric team ask you to talk to a mother From little acorns… • The obstetric team ask you to talk to a mother who is being induced at 31 weeks gestation as she is ‘small for dates’. • What further information would you like?

Mrs Oak • • • 28 year old primigravida 5’ 2, 80 kg Smokes Mrs Oak • • • 28 year old primigravida 5’ 2, 80 kg Smokes 5 cigarettes daily Concerns about growth from 20 weeks Latest ‘dopplers’ show absent EDF Proteinuria and hypertension

In groups, plan your chat • How will you counsel the family? • Consider In groups, plan your chat • How will you counsel the family? • Consider particularly: – Risks of preterm delivery vs risk of continuing pregnancy – Short term risks – Approach to feeding – Long term outcome

Short term risks of IUGR • Obstetric – Intrauterine death – Intrapartum asphyxia Short term risks of IUGR • Obstetric – Intrauterine death – Intrapartum asphyxia

Short term risks of IUGR • Paediatric – Hypoglycaemia – Necrotising enterocolitis – Increased Short term risks of IUGR • Paediatric – Hypoglycaemia – Necrotising enterocolitis – Increased risk of problems of prematurity – (hypothermia) – (polycythaemia)

NEC and IUGR • Case-control study (n=74) – at 30 -36 weeks GA, birth NEC and IUGR • Case-control study (n=74) – at 30 -36 weeks GA, birth weight <10 th centile is a significant risk factor – OR 6 (1. 3 -26)1 • Observational study (n= 69) – At 30 -36 weeks 71% of cases were <10 th centile 2 • 1 • Beeby and Jeffrey. 1991, ADC: 67: 432 -5 2 Mc. Donnell and Wilkinson. Sem Neonatol 1997

NEC and IUGR: Why? • Pathogenesis of NEC requires – enteral feeding – gut NEC and IUGR: Why? • Pathogenesis of NEC requires – enteral feeding – gut ischaemia – bacterial infection • Abnormal gut blood flow recognised in IUGR • Ischaemic damage or reperfusion injury?

Normal doppler flow in umbilical artery Normal doppler flow in umbilical artery

Absent end diastolic flow Absent end diastolic flow

Reversed end-diastolic flow Reversed end-diastolic flow

Abnormal dopplers and NEC • In 9 of 14 studies, AREDF led to an Abnormal dopplers and NEC • In 9 of 14 studies, AREDF led to an increased risk of NEC • OR 2. 13 (95%CI 1. 49 to 3. 03) • Dorling J, Kempley S, Leaf A. Feeding growth restricted preterm infants with abnormal antenatal Doppler results. Arch. Dis. Child. Fetal Neonatal Ed. 2005; 90: F 359 -F 363

So how to feed? • • Delay start? Use non-nutritive feeds? Increase slowly? Use So how to feed? • • Delay start? Use non-nutritive feeds? Increase slowly? Use friendly bacteria?

Cochrane review: early vs late feeding • 72 babies in 2 studies • Early Cochrane review: early vs late feeding • 72 babies in 2 studies • Early feeders had – Fewer days parenteral nutrition – Fewer investigations for sepsis • No difference in – NEC – Weight gain

Cochrane review: rapid vs slow increase • • 369 babies in 3 studies Rapid: Cochrane review: rapid vs slow increase • • 369 babies in 3 studies Rapid: 20 to 35 ml/kg/day Slow: 10 to 20 ml/kg/day Rapid group: – reached full enteral feeds and regained birthweight faster – No difference in NEC rate or length of stay

Cochrane review: minimal enteral nutrition • 380 babies in 8 studies • 12 to Cochrane review: minimal enteral nutrition • 380 babies in 8 studies • 12 to 24 ml/kg/day for 5 to 10 days • MEN group – Faster to full enteral feeds – Shorter length of stay – No difference in NEC

Probiotics for preventing NEC • Systematic review of 1393 VLBW infants treated with a Probiotics for preventing NEC • Systematic review of 1393 VLBW infants treated with a variety of organisms • Reduced risk of – NEC (RR 0· 36, 95% CI 0· 20– 0· 65) – Death (RR 0· 47, 0· 30– 0· 73) • Achieved full feeds faster • No difference in rates of sepsis – Deschpande et al, Lancet 2007

Preventing NEC: what works? Strategy Absolute RR NNT Enteral antibiotics 0. 089 11 Judicious Preventing NEC: what works? Strategy Absolute RR NNT Enteral antibiotics 0. 089 11 Judicious fluid administration 0. 084 12 Human milk feeds 0. 069 15 Enteral Ig. G and Ig. A 0. 066 15 Enteral Probiotics 0. 025 40 Antenatal corticosteroids 0. 019 54 Delayed or slow feeding Not effective - Enteral Ig. G only Not effective -

Feeding small or preterm infants: Choices • Human milk – Mother’s own – Banked Feeding small or preterm infants: Choices • Human milk – Mother’s own – Banked donor milk – Fortified • Artificial – Term formula – Preterm formula • Parenteral Nutrition

Parenteral Nutrition Parenteral Nutrition

Parenteral Nutrition • If an infant can’t, won’t or shouldn’t be fed enterally • Parenteral Nutrition • If an infant can’t, won’t or shouldn’t be fed enterally • What’s in the bag? – – – Fluid Carbohydrate Protein Fat Minerals and Trace Elements

Energy • Requirements – Basal metabolic rate – Physical activity – Specific dynamic action Energy • Requirements – Basal metabolic rate – Physical activity – Specific dynamic action of food – Thermoregulation – Growth

Energy • Requirements kcal/kg/day – Basal metabolic rate – Physical activity – Specific dynamic Energy • Requirements kcal/kg/day – Basal metabolic rate – Physical activity – Specific dynamic action of food – Thermoregulation variable – Growth 40 4+ (10%) 70 (To match in-utero growth of 15 g/kg/day)

Protein • With glucose infusion alone, infants lose 1 -2% of endogenous protein stores Protein • With glucose infusion alone, infants lose 1 -2% of endogenous protein stores daily • 1 g/kg/day gives protein balance • 2. 5 to 3. 5 g/kg/day allows accretion – nb energy requirement • Safe to start soon after birth

Fat • Energy source • Essential fatty acid source (intralipid) • Cell uptake and Fat • Energy source • Essential fatty acid source (intralipid) • Cell uptake and utilisation of free fatty acids is deficient in preterm infants • Start at max 1 g/kg/day, increasing gradually to 3 g/kg/day (less if septic)

Benefits of PN • Earlier, faster weight gain • Avoidance of problems associated with Benefits of PN • Earlier, faster weight gain • Avoidance of problems associated with enteral feeds

Risks of PN • Line associated sepsis • Line related complications (eg thrombosis) • Risks of PN • Line associated sepsis • Line related complications (eg thrombosis) • Hyperammonaemia • Hyperchloraemic acidosis • Cholestatic jaundice • Trace element deficiency

Milk Feeds Milk Feeds

Human milk advantages • • • Protection from NEC Improved host defences Protection from Human milk advantages • • • Protection from NEC Improved host defences Protection from allergy and eczema Faster tolerance of full enteral feeds Better developmental and intellectual outcome

Human milk shortcomings if preterm • Human milk may not provide enough – Protein Human milk shortcomings if preterm • Human milk may not provide enough – Protein – Energy – Sodium – Calcium, phosphorus and magnesium – Trace elements (Fe, Cu, Zn) – Vitamins (B 2, B 6, Folic acid, C, D, E, K)

Breast milk fortifiers • Improved – short term growth – nutrient retention – bone Breast milk fortifiers • Improved – short term growth – nutrient retention – bone mineralisation • Concerns – trend towards increased NEC

Term vs preterm formulas • Term formulas do not provide for preterm protein, calcium, Term vs preterm formulas • Term formulas do not provide for preterm protein, calcium, sodium and phosphate requirements, even at high volumes • Term formula (vs preterm formula) fed infants – Grow more slowly – Have lower developmental score and IQ at follow up

Feeding preterm infants: aim “To provide nutrient intakes that permit the rate of postnatal Feeding preterm infants: aim “To provide nutrient intakes that permit the rate of postnatal growth and the composition of weight gain to approximate that of a normal fetus of the same gestational age, without producing metabolic stress” American Academy of Pediatrics Committee on Nutrition

Evidence Based Nutrition • RA Ehrenkranz, Seminars in Perinatology 2007 (31): 48 -55 Evidence Based Nutrition • RA Ehrenkranz, Seminars in Perinatology 2007 (31): 48 -55

Post-Discharge Nutrition Post-Discharge Nutrition

Post discharge nutrition • Preterm infants tend to be small at discharge, and remain Post discharge nutrition • Preterm infants tend to be small at discharge, and remain small into adolescence • Limited evidence for what rate of growth is optimal

The evidence • Comparison of ‘post-discharge’ formula with standard term formula – No consistent The evidence • Comparison of ‘post-discharge’ formula with standard term formula – No consistent difference in growth parameters or body composition – Z-score reduces in both groups – Term formula needs supplementing with vitamins and iron to achieve targets

The evidence • Comparison of breast milk with term formula – Calcium and phosphate The evidence • Comparison of breast milk with term formula – Calcium and phosphate deficiency in breast milk fed infants in first year resolves by age two – Little difference in growth (although small numbers)

Outcomes Outcomes

Catch-up Growth • Enhanced nutritional intake sufficient to allow ‘catch-up’ growth improves long term Catch-up Growth • Enhanced nutritional intake sufficient to allow ‘catch-up’ growth improves long term neurodevelopmental outcome

Body composition differences • Compared to term infants, ex-preterm infants fed at 120 kcal/kg/day Body composition differences • Compared to term infants, ex-preterm infants fed at 120 kcal/kg/day – Have more body fat – Have a different fat distribution

The long range forecast with IUGR • Does the in-utero environment or early feeding The long range forecast with IUGR • Does the in-utero environment or early feeding permanently change organ structure, function and metabolism?

Developmental Origins theory • Humans demonstrate ‘developmental plasticity’ in response to their environment • Developmental Origins theory • Humans demonstrate ‘developmental plasticity’ in response to their environment • Part of cardiovascular risk may be explained by in-utero and postnatal growth

Developmental Origins theory • Geographically, coronary heart disease correlates with past neonatal mortality • Developmental Origins theory • Geographically, coronary heart disease correlates with past neonatal mortality • In epidemiological studies, adult cardiovascular disease is associated with: – low birthweight – rapid early postnatal growth

Is rapid catch-up growth bad? • Postnatal weight gain is associated with BMI and Is rapid catch-up growth bad? • Postnatal weight gain is associated with BMI and waist circumference at 19 years • IUGR infants are at increased risk of the metabolic syndrome • Preterm infants fed breast milk rather than preterm formula – had lower BP at 13 -16 yrs – were less insulin resistant – had a better LDL: HDL ratio

Nutrition Assessment Nutrition Assessment

How best to assess growth and nutrition? • Weight – Reflects mass of lean How best to assess growth and nutrition? • Weight – Reflects mass of lean tissue, fat, intra- and extracellular fluid compartments • Length – More accurately reflects lean tissue mass • Head circumference – Correlates well with overall growth and developmental achievement

Laboratory assessment • TPN requires regular monitoring of acid base status, liver function, bone Laboratory assessment • TPN requires regular monitoring of acid base status, liver function, bone profile and electrolytes • In enterally fed infants, monitoring albumin, transferrin, total protein, urea, alkaline phosphatase and phosphate may be useful

Infant Feeding Infant Feeding

Task • Read the GP referral letter • In pairs: – Pick out the Task • Read the GP referral letter • In pairs: – Pick out the important aspects of the referral – Decide what further questions you’d like to ask the family – What sort of investigations (if any) might you consider?

Faltering Growth Faltering Growth

‘Failure to Thrive’ • Term first used to describe delayed growth and development, – ‘Failure to Thrive’ • Term first used to describe delayed growth and development, – also called maternal deprivation syndrome. • “A failure of expected growth and well being” • Only growth can be objectively measured

Crossing centiles? • 5% of normal infants cross 2 intercentile spaces from birth to Crossing centiles? • 5% of normal infants cross 2 intercentile spaces from birth to 6 weeks. • 5% of normal infants cross 2 intercentile spaces from 6 weeks to 1 year. • Infants regress to the mean • Hence development of ‘thrive lines’

Causes and correlates • Organic disease • Abuse and Neglect • Deprivation • Undernutrition Causes and correlates • Organic disease • Abuse and Neglect • Deprivation • Undernutrition

Causes and correlates • Organic disease – <5%, usually suggestive symptoms and signs • Causes and correlates • Organic disease – <5%, usually suggestive symptoms and signs • Abuse and Neglect – increased risk, but a small proportion • Deprivation – may influence referral • Undernutrition

The Energy Balance Equation The Energy Balance Equation

Undernutrition • Most are underweight for height • Fastest decline in weight gain when Undernutrition • Most are underweight for height • Fastest decline in weight gain when energy needs are highest • Poor appetite • Delayed progression to solid foods • Limited range of foods

Faltering Growth over time Faltering Growth over time

Consequences • • Lasting deficit in growth Lasting effects on appetite and feeding Low Consequences • • Lasting deficit in growth Lasting effects on appetite and feeding Low maternal self esteem Developmental delay at 1 year – 7 -10 DQ points • Small (not statistically significant) IQ difference at 8 -9 years

Management • Few trials of intervention • One RCT found health visitor led intervention Management • Few trials of intervention • One RCT found health visitor led intervention useful • One non randomised trial found dietary advice useful • Management is therefore based on ‘accepted best practice’

Screening or Case Finding? • Up to 50% of children with FTT are never Screening or Case Finding? • Up to 50% of children with FTT are never identified • Recommendations for frequency of weighing suggest paying more attention to fewer weights.

Growth Monitoring Growth Monitoring

Primary or Secondary care? • Common problem, often resolves with simple interventions • Ill Primary or Secondary care? • Common problem, often resolves with simple interventions • Ill children or those losing weight need referral • Home visitor assessment – Dietary history – Simple explanation and advice • Second port of call should be dietician

Strategies Strategies

The Role of the Paediatrician • Investigations (if necessary) should be completed promptly • The Role of the Paediatrician • Investigations (if necessary) should be completed promptly • FBC, ferritin, U+Es, TFTs, TT glutaminase, MSU • Chromosome analysis in girls • CXR and sweat test in young infants or history of respiratory infections.

Pathway of care Pathway of care

If not improving? • Nursery nurse involvement or nursery placement • Help with other If not improving? • Nursery nurse involvement or nursery placement • Help with other behavioural problems • Treat illness in mother • Social work input • Almost never need food supplements or hospital admission

Task • One volunteer to play the part of Neil’s parent • A second Task • One volunteer to play the part of Neil’s parent • A second volunteer to be the registrar in clinic • Others to observe and be prepared to give feedback at the end

Question • What are the agendas of the health professionals and the parent? • Question • What are the agendas of the health professionals and the parent? • How will you address the different priorities? • Where will you take things from here?

Feeding difficulties in ex-prems • Feeding issues are common, especially in those born before Feeding difficulties in ex-prems • Feeding issues are common, especially in those born before 28 weeks • Risk of – Disordered oral-motor functioning – Significant gastro-oesophageal reflux – Oral hypersensitivity – Neurological impairment affecting feeding

Colic Colic

What is Colic? • “excessive bursts of crying in an otherwise healthy infant not What is Colic? • “excessive bursts of crying in an otherwise healthy infant not relieved by routine comfort” • ‘Colic’ crying is said to be of higher amplitude, greater intensity, more frequent, and of longer duration

Problems in Evaluation • Poor case definition • Few controlled studies • Little evidence Problems in Evaluation • Poor case definition • Few controlled studies • Little evidence base for management or investigation

The Classic Definition • “crying lasting 3 or more hours per day, on more The Classic Definition • “crying lasting 3 or more hours per day, on more than 3 days a week, for at least 3 weeks and resolving around 3 months”. – Wassell, Pediatrics 1954

Study Results • Quantifying colic – scoring scales – acoustic cry assessments • No Study Results • Quantifying colic – scoring scales – acoustic cry assessments • No effect of sex, birth order, social class, ethnic origin. • Vagal tone and cortisol levels are the same as in non-colicky babies

The impact on parents • Resistance to soothing causes anxiety • Learned helplessness, causing The impact on parents • Resistance to soothing causes anxiety • Learned helplessness, causing anxiety and depression • Stress can cause parental coping crises • 10% of mothers experience a depressive disorder postnatally

Temperament • Some reports link excessive crying to later difficult behaviours – few studies Temperament • Some reports link excessive crying to later difficult behaviours – few studies only – based on maternal recall – possible that quality of care in later childhood is influenced by early patterns of behaviour

Colic and difficulties with feeding • 19 with colic v 24 without • Assessment: Colic and difficulties with feeding • 19 with colic v 24 without • Assessment: – colic symptom checklist – neonatal oral assessment score – clinical feeding evaluation

Outcomes • Colic group showed: – more disorganised feeding behaviours, – less rhythmic nutritive Outcomes • Colic group showed: – more disorganised feeding behaviours, – less rhythmic nutritive and non-nutritive sucking, – more discomfort during feeds, – lower responsiveness during feeding interactions. • Miller-Loncar, Arch Dis Child 2004; 89 908 -12

Organic causes of a ‘colicky’ baby • congenital heart disease • CNS abnormalities • Organic causes of a ‘colicky’ baby • congenital heart disease • CNS abnormalities • NAI • fever eg UTIs • maternal drug ingestion • gastro-oesophageal reflux • cows milk protein intolerance • malabsorption • gut dysmotility

Gut hormones • Motilin initiates migrating motor complexes • Vagus stimulation increases number and Gut hormones • Motilin initiates migrating motor complexes • Vagus stimulation increases number and force of contractions • Raised motilin in 2 small studies of infantile colic • Smokers have higher motilin levels

Systematic review of treatment • Lucassen et al, BMJ, 1998 • 50 complete studies, Systematic review of treatment • Lucassen et al, BMJ, 1998 • 50 complete studies, 27 controlled reviewed.

Treatments for colic • Results as effect size – Behavioural: (reducing stimulation) 0. 48 Treatments for colic • Results as effect size – Behavioural: (reducing stimulation) 0. 48 – Dicycloverine: 0. 46, but serious side effects – Hydrolysate milks: 0. 22 – Herbal tea: 0. 32 (single small study) – Low lactose and soya milks: no effect – Simethicone: no effect

Treatments for colic Treatments for colic

Any Questions? Any Questions?

Summary • Optimal growth for neonates and infants requires careful thought about nutrition • Summary • Optimal growth for neonates and infants requires careful thought about nutrition • Interventions (or lack of them) may have long term consequences • There is a limited evidence base to guide current practice • Colic is common • Feeding difficulties post SCBU are common