1 Growth is a process Growth is a process Growth is a process - - PDF document

1 Nutritional Implications in Pediatric Pulmonary Hypertension Nutritional Implications in Pediatric Pulmonary Hypertension

Theresia Vissia-Kazemier, RN-MANP Dutch National Network for Pediatric Pulmonary Hypertension Center for Congenital Heart Diseases Department of Pediatric Cardiology Beatrix Children’s Hospital, UMCG

National Network for Pulmonary Hypertension at Childhood National Network for Pulmonary Hypertension at Childhood

UMCG, Groningen National Referral Center for Children with Childhood PH Collaboration with 9 Network Centers University Childrens Hospitals and/or Cardiology Childrens Hospitals

Amsterdam, The Hague, Leiden, Maastricht, Nijmegen, Rotterdam, Utrecht, Veldhoven

Standard Diagnostics and Treatment of Pulmonary Hypertension in Children, 2nd Edition, ‘Network for Pulmonary Hypertension in Childhood‘ http://www.kinderph.nl/professionals/ Two yearly PVD Conference

Nurses working group Pulmonary Hypertension Nurses working group Pulmonary Hypertension

Association for Nursing and Care Netherlands Task group pulmonary vascular disorders

https://longverpleegkundigen.venvn.nl/over-ons/taakgroepen/pulmonaal-vasculaire-aandoeningen

Sharing knowledge and exchange experiences Developing brochures, guidelines and protocols Case presentations Collaboration:

• Facility companies
• Patient association (eg, patient information, patient days)
• Pharmaceutical companies

No conflict of interest

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Growth is a process Growth is a process

Growth is a process Repeated growth measurements are important The most powerful tool in growth assessment is the growth chart Causes of growth impairment:

• Malnutrition
• Hormonal dysfunction or imbalance
• Genetic disorders
• Psychosocial factors
• Chronic diseases (eg, chronic renal failure, lung disease, chronic heart disease)

Malnutrition: imbalance between nutrient requirement and nutrient intake Malnutrition: imbalance between nutrient requirement and nutrient intake

SUPPLY PLY DEMAND Growth Development Outcomes: Morbidity Mortality Risk factors INTAK INTAKE LOSSES LOSSES NUTRITION BODY STORES

Definition of malnutrition Definition of malnutrition

Acute malnutrition (‘wasting’):

• > -2 SD weight for age (WFA) in children > 28 days and < 1 year
• > -2 SD weight-for-height (WFH) in children > 1 year or
• Deflecting growth curve of weight, height or WFH of > 1 SD in 3 months

Chronic malnutrition (‘stunting’):

• Height for age (HFA) ≥ -2 SD
• Deflection of the SD score with 0.5 - 1.0 SD or more in one year

(children < 4 years of age)

• Deflection of 0.25 SD or more in one year

(children > 4 years of age)

Overnutrition:

• BMI of WFH > 2 SD

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What is known ? What is known ?

During childhood adequate intake is of the utmost importance Rapid growth Development Recent data: low weight , height and body mass index Z-scores increases mortality Dat Data about about growth growth and nutr and nutrition in in childr children en with with PAH is PAH is lackin lacking

Moledina S, et al. Heart, 2010;96:1401-1406 Barst RJ, et al. Circulation. 2012;125:113-122 Ploegstra MJ, et al. The Lancet. 2016; 4: 241-336

Retrospective longitudinal study 53 centres in 19 countries 601 children Median follow up 2-9 years Mean height for age Z score was significantly lower than the reference (p<0·0001), as was body-mass index for age Z score (p=0·047). Height for age Z score was particularly decreased in young patients (aged ≤5 years) with idiopathic or hereditary PAH and in all patients with PAH associated with congenital heart disease Multivariable a analysis Associated with height for age Z-scores:

• Age
• Cause of PAH
• Exprematurity
• WHO functional class

Associated with BMI Z-scores:

• Age
• Ethnicity
• Trisomy 21
• Time since diagnosis

Associated with increases in height for Z-scores:

• Favourable WHO FC

Ploegstra et al. 2016

Nutrition & Growth Pilotstudy Nutrition & Growth Pilotstudy

A prospective cohort study 2009-2011 Prevalent pediatric patients idiopathic PAH or PAH/CHD pts Research questions

• 1. How is the nutritional status in children with PAH?
• 2. Does the severity of the disease and energy intake correlate with the nutritional status ?
• 3. Is an energy intake compared with required daily allowances enough to maintain growth or do

children with PAH need increased energy intake ?

• 4. Does have a structured nutritional advice have a positive impact on the nutritional status

children with PAH ?

Studypopulation Studypopulation Measurements an additional information Measurements an additional information

• Weight
• Height
• Weight for height
• BMI
• Mid-upper arm circumference (MUAC)
• Triceps skinfold thickness (TSF)
• 3-days dietary assessment (weekdays

/ 1 weekend day)

• Nutritional counseling by a dietician
• Patient characteristics:

age, gender, etiology of PAH, co-morbidity

• Related factors: WHO FC, exercise capacity

(6 MWT), NT-pro-BNP, uric acid, norepinephrine

Frederiks AM et al. Pediatric Res 2000;47:316-23 Gerver WJM and Bruin R. Universitaires Pers Maastricht, 2001

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Calculation of Individual Intake requirements (EIRc) Calculation of Individual Intake requirements (EIRc)

Using WHO (weight) equation of resting metabolic rate (RMR) Additional factors

• Physical activity level (PAL)

(consulting patient activity level parents opinion /set on normal activity 1.5)

• Ilnessfactor (IF)

(yet no evidence for increased energy requirement /set on 1.0)

• Growth factor (GF)

(range from 1.03-1.20 depending on age/growth spurt)

• Energy absorption coefficient (EAC)

(age dependent range 0,85-0.98)

Dutch Malnutrition Steering Group. Energy requirements in children.2010

EIRc = RMR x (PAL+IF) x G EAC

Calculations and comparisons Calculations and comparisons

Percentage Energy intake of Individual Requirement (%EIRc)

(measu (measured energy energy inta intake/EIR IR x x 100) 100)

Individual protein requirements (PIRc)

(multiplying tiplying childs’ w ds’ weight w ht with th r recommended pr ended protein ein intake) take)

Calculated Energy intake and intake of protein, carbohydrates and fat from 3-days dietary assessment Compared with recommended daily allowances (RDA) and data of Dutch Food Survey (DFS)

Dutch Malnutrition Steering Group. Energy requirements in children. 2010 Dutch Malnutrition Steering Group. Protein requirements in children. 2010 Health Council of The Netherlands. Dietary Reference Intake; energy, proteins, fat and digestible carbohydrates. Health Council of The Netherlands: The Hague, 2001 National institute for Public Health and Environment. Dutch National Food Consumption Survey young Children 2006/2006; 350070001 National institute for Public Health and the Environment. Dutch National Food Consumption Survey 2007-2010; Diet of children and adults aged 7 to 69 years. 2011; 350050006

Calculated energy: 1750 kcal Childs’ intake: 1500 kcal 1500 x 100 = 85,7% 1750

Results nutritional status Results nutritional status

Normal nutritional status in 5 children Acute malnutrition ‘wasting’

(WFH or BMI <- 2 SD) n= 2 (1 syndrome group and 1 non-syndrome group)

Chronic malnutrition height for age ‘stunting’ (HFA) of ≥-2 SD:

n=4 (3 syndrome/1 non-syndrome)

Two patients had both acute and chronic malnutrition

(n=1 syndrome, n=1 non-syndrome patient)

5 Nutritional Advice Nutritional Advice

After dietary assessment and this first measure point the dietician offered individual advice to promote growth n= 7 advice intake according recommended daily allowances (RDA) n=1 more calories to anticipate on growth spurt (adaptation of WHO equation) n= 1 extra calories because of individual severely low SD scores (adaptation of WHO equation to achieve catch up growth)

Energy intake: kcal and % calculated energy intake (%Eic) Energy intake: kcal and % calculated energy intake (%Eic) Energy intake (%EIc) Energy intake (%EIc)

%EIc Baseline Follow up Mean 102% (range 67‐129% Mean 105% (range 70‐139%) n= 3 > 110% n=4 > 110% n= 5 > 90 ‐110% n=3 > 90 ‐ 110% n=1 < 90% n=2 < 90%

Patients with normal nutritional status

Energy intake (kcal) compared with recommended daily allowances (RDA) Energy intake (kcal) compared with recommended daily allowances (RDA)

Both in normal and inpaired group

6 Energy intake (kcal) compared with Dutch Food survey (DFS) Energy intake (kcal) compared with Dutch Food survey (DFS)

Compared with DFS Baseline Follow up Mean 83 (range 68‐110%) Mean 91 (range 71‐135%) n= 1 > 110% n= 1 > 110% n= 1 90‐110% n= 4 90‐110% n= 7 < 90% n= 4 < 90%

Intake of protein Intake of protein

Recommended daily allowances protein intake boys/girls 1.2 g/kg/day Protein Compared with RDA Baseline Follow up Mean 180 % (range 125‐277 %) Mean 223 % (range 148‐341%) n=0 > 100‐150% n=2 > 100‐150% n=4 > 150‐200% n=2 > 150‐200% n=2 > 200‐300% n=3 > 200‐300% n=3 > 300% n=2 > 300% %PIRc Baseline Follow up Mean 198 (range 99‐ 321%) Mean 221% (range 115‐ 357 %) n= 1 < 100% n= 0 < 100% n= 0 > 100‐150% n= 2 > 100‐150% n= 4 > 150‐200% n= 1 > 150‐200% n= 3 > 200‐300% n= 5 > 200‐300% n= 1 > 300% n= 1 > 300%

Increase of protein intake during follow up Increase of protein intake during follow up

+ 6,9% + 15% + 8,6% Acute malnutrition Chronic malnutrition Normal nutritional status

Percentage protein intake of total energy intake Percentage protein intake of total energy intake

%EN Recommended daily allowances Boys Girls 1‐3 years 5 5 4‐8 years 5 5 9‐13 years 6 6 14‐18 year 7 8 Dutch Malnutrition Steering Group. Protein requirements in children, 2010. www.stuurgroepondervoeding.nl Health Council of The Netherlands. Dietary Reference Intakes: energy, proteins, fats and digestible carbohydrates. Health Council of The Netherlands. The Hague, 2001

7 Intake of carbohydrates Intake of carbohydrates

Decrease intake carbohydrates during follow up Decrease intake carbohydrates during follow up

• 1%
• 2%
• 3%

Intake of fat Intake of fat

Fats compared with DFS Baseline Follow up Mean 113% (range 93‐140%) Mean 113% (range 93‐134%) n=0 < 90% n=0 < 90% n=1 > 90‐100% n=2 > 90‐100% n=4 > 100‐110% n=2 > 100‐110% n=4 > 110‐130% n=5 > 110‐130% Fats compared with RDA Baseline Follow up Mean 92% (range 74‐119%) Mean 92% (range 77‐114 %) n=5 < 90% n=4 < 90% n=3 > 90‐100% n=3 > 90‐100% n=0 > 100‐110% n=1 > 100‐110% n=1 > 110‐130% n=1 > 110‐130%

Intake of fat during follow up Intake of fat during follow up

In children with acute malnutrition remained same level Slightly increase in children with chronic malnutrition 3% Slightly decrease In children with normal nutritional status 2%

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Influence on prognostic factors Influence on prognostic factors

Malnutrition ‘did not influence’ NT-pro BNP, uric acid or noradrenaline

Growth Growth Growth Growth

Both HFA and WFH decreased

• 2,6 to -2,8

Summary results Summary results

• 1. Calorie intake in children with PAH matched individual calculated energy intake
• 2. Calorie intake in children with PAH was below recommended daily allowances and intake of healthy

children

• 3. Protein intake exceeded individual calculated protein intake and RDA,

at baseline protein intake was below and at the end of the study slightly above that of healthy children

• 4. Protein intake in children with chronic malnutrition increased significantly during follow up
• 5. Intake of carbohydrates matched recommended daily allowances, but was lower than healthy children

and slightly decreased during follow up

9 Summary results Summary results

• 6. Intake of fats matched upper limit recommended daily allowances and slightly exceeded intake of

healthy children but slightly decreased during follow up

• 7. Children with acute and chronic malnutrition had higher intake than children with a normal

nutritional status

• 8. Although intake in children with PAH was sufficient compared to individual calculated energy

intake requirements normal growth or catch up growth could not be obtained, except in one patient

• 9. MUAC reflects nutritional status well

Discussion Discussion

If intake matches individual calculated energy intake why could normal Growth not be achieved?

• Higher demand due to increased cardiac and breathing function?
• Compensate for illness therefore taking a surplus factor instead of illness factor 1.0 ?
• Loss of muscle mass due to inactivity therefore loss of storage?
• Influences of medication? CCB (nifedipine) increases resting energy expenditure

Tian Z, Miyata K, Tabata M, et al. Nifedipine increases energy expenditure by increasing PGC-1alpha expression in skeletal muscle. Hypertens es 2011;34:1221–7

Which norms leads to adequate intake for growth?

• Calculated? RDA? Surpluss E+?
• Literature showed WHO and Schofield equations underestimate energy requirements in chronic sick children

Carpenter A. et al. Accurate Estimation of Energy Requirements of Young Patients. JPGN 2015;60: 4–10

• 3. Fully fletched RCT difficult to realize?
• Different age groups ? Heterogeneity of PAH groups ? Small numbers ?
• 4. Further research
• Use of indirect calorimetry to provide more accurate energy requirements ?
• Use of accelerometry to assess daily physical activity to better predict energy needs ?
• Access role of growht hormons ? Delayed puberty ?

Conclusion Conclusion

Energy intake in children with PAH was accurate compared to calculated requirements, but lower than recommend daily allowances and healthy children at baseline Although during follow up energy intake increased and matched all three norms, normal growth was compromised in nearly all patients (except for one), indicating that children with PAH need more energy for optimal growth It remains unclear if inaccurate energy intake in children with PAH solely leads to malnutrition or other factors also play a role We found no relation to severity of disease or prognostic factors in this small study group Literature MUAC correlates well with WFH or BMI MUAC can be used in children with severe edema or when weight or height otherwise cannot be obtained In future understanding the link between severity of the disease, nutrition and other related (growth)factors would be useful to identify patients who would benefit from early and aggressive nutritional intervention to improve nutritional status and outcome We recommend closely monitoring of the nutritional status and counseling by a dietician in daily practice

National Expertise Center for Children with PH Beatrix Childrens Hospital | University Medical Center Groningen | The Netherlands Pediatric PH team:

• Prof. dr. Rolf Berger

Paediatric cardiologist

• Dr. Marc Roofthooft

Paediatric cardiologist

• Drs. Brigitte Willemse

Paediatric pulmonologist

• Mw. Sira Baars

Social worker

• Drs. Marije Kort

Consultant education sick pupils

• Mw. Anneke Hegeman

Physiotherapist

• Drs. Carola Timmer

Physiotherapist

• Mw. Monique Klein

Child life specialist

• Mw. Manon Groenewold

Dietician

• Mw. Jannie IJbema

Dietician Mw G. Venema Dietician

• Drs. Kim van der Schoot

Psychologist

• Drs. Jeffrey Looijestijn

Psychologist

• Mw. Theresia Vissia-Kazemier, MANP

Paediatric nurse practitioner (email: t.kazemier@umcg.nl) PH Research group led by Prof. dr. Rolf Berger:

• Dr. Mirjam van Albada MD, PhD
• Dr. Menno Douwes MD, PhD
• Dr. Beatrijs Bartelds MD, PhD
• Dr. Marc-Jan Ploegstra MD, PhD
• Dr. Michael Dickinson MD, PhD
• Dr. Willemijn Zijlstra MD, PhD
• Dr. Laura van Loon MD, PhD

Diederik van Veen PhD student

• Dr. Mieke Kerstjens-Frederikse MD, PhD

Guido Bossers PhD student

• Dr. Jan Renier Moonen MD, PhD

Sanne Arjaans PhD student

• Dr. Reinout Borgdorff MD, PhD

Marlies Haarman PhD student