Transcript Maternal PKU - the dietitians perspective

Maternal PKU – dietary
management
Fiona White
Chief Metabolic Dietitian
Manchester Children’s Hospitals
NSPKU Conference 3/3/07
look at ……..
• history of maternal PKU
• evidence for guidelines for management
of maternal PKU
• dietary management
• outcome
• Manchester experience
history of maternal PKU
1957 – first description by Prof Charles Dent
• mother, mentally handicapped, with PKU
• 3 mentally retarded children, non PKU
• was PKU the cause?
history of maternal PKU
1980 – Lenke & Levy (USA)
• published survey of 524 pregnancies in 155
women with PKU
– 34 pregnancies a low phe diet preconception or
started after
maternal PKU
100
90
mental retardation
microcephaly
heart disease
b wt <2500g
% of offspring
80
70
60
50
40
30
20
10
0
1200
Lenke and Levy (1980)
1000
850
phe µmol/l
600
normal
population
maternal PKU - clinical presentation
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•
•
•
•
•
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microcephaly (small head,>70%)
low birth weight / poor growth (50%)
dysmorphic features
slow development (>90%)
congenital heart disease (15–20%)
other malformations
behavioural problems
‘maternal PKU syndrome’
evidence for dietary management guidelines
- from maternal PKU outcome studies
2 major studies
• International maternal PKU collaborative study
(MPKUCS), 1984 – 2002
• UK MRC/DHSS PKU registry, 1978-97
cognitive outcome
maternal PKU outcome - IQ
Platt et al, 2000
(MPKUCS)
• best IQ outcome occurred when
• maternal blood phenylalanine level <600 µmol/l
by 8-10 weeks gestation
• and maintained throughout pregnancy
maternal PKU outcome - IQ
140
R2=0.5742
120
IQ
100
80
60
40
0
500
1000
1500
2000
mean phe 1st trimester (µmol/l)
(MPKUCS)
2500
birth head circumference
I – strict diet at conception
II – relaxed diet at conception
III – diet started in 1st trimester
IV - diet started in 2nd or 3rd trimester
V – no diet
36
n = 17
35
p < 0.001
n = 12
cm
34
p < 0.001
n=9
p < 0.001
n=8
p < 0.001
n = 18
33
32
31
30
50th centile
I
II
III
IV
V
group
Drogari et al (1987)
UK MRC/DHSS PKU Registry
heart
maternal PKU outcome
– congenital heart disease
• Levy et al 2001 (MPKUCS)
– 14% risk of heart defect if phe >900 µmol/l at
conception & poor control by 8th week
• Matalon et al 2003 (MPKUCS)
– heart disease also increased where <50%
recommended protein intake consumed in first
trimester
growth
maternal PKU outcome
– effect of maternal nutrition
• Acosta et al, 2000 (MPKUCS)
– highest protein intake (>RDA) &
– achieving recommended energy intake associated with
• best phe control
– phe<360µmol/l by 10 weeks
– maintained between 120 - 360µmol/l for rest of
pregnancy
• best growth measurements at birth
maternal PKU outcome – growth
Lee et al,2005
(UK MRC/DHSS PKU Registry)
• preconception diet
– better birth weight & head circumference
summary of evidence
• high maternal phenylalanine levels are toxic
• preconception diet, good phe control & good nutrition
throughout pregnancy produces best outcome
• if pregnancy unplanned start diet as soon as possible
– phe control by 8-10 weeks
• reduces risk heart defects
• improves IQ outcome
• improves growth
maternal PKU –management aims
•
control of blood phe within acceptable limits
throughout pregnancy
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•
•
MRC 1993: 60 - 250mol/l
our unit currently 100 - 250 mol/l
? 150 - 300 mol/l
– preconception control is the ideal
•
4 weeks of consecutive levels within desired range before
stopping contraception
– if pregnant with higher levels - to achieve control within 1st
trimester
•
good nutrition
dietary requirements in maternal PKU
5 key areas:
• phenylalanine
• protein
• tyrosine
• energy
• micronutrients
dietary requirements in maternal PKU
1 - phenylalanine
• phenylalanine requirements - exchanges
based on blood phe level
– individual tolerance
– use 50mg phe exchange system
– initially number of exchanges small
–
• distribute evenly throughout day
• tolerance should increase later
– may need to use high protein foods (6g
exchanges)
phenylalanine tolerance - BE
30
25
20
1st pregnancy
2nd pregancy
3rd pregnancy
15
10
5
40
36
32
28
24
20
16
12
8
4
0
0
dietary requirements in maternal PKU
2 - protein
• protein requirements
– approx. RNI for pregnancy + 15% (total 60g)
– initially all from phe free protein substitute
– may give extra to improve phe control
1992 – 3 protein substitutes
suitable for maternal PKU
• XP Maxamum
• PK Aid 4
• Aminogran
2007 – 12 protein substitutes suitable
for maternal PKU
• Powders
2007 – 12 protein substitutes suitable
for maternal PKU
• Liquids
2007 – 12 protein substitutes suitable
for maternal PKU
• tablets
improving tolerance of
protein substitute
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•
•
•
•
•
disguising smell
chilling
flavouring
alter dilution
increase frequency
alternative product - tablets
Dietary requirements in maternal PKU
3 - tyrosine
– essential amino acid in PKU (added to
supplements)
– may require additional supplement in
pregnancy
dietary requirements in maternal PKU
4 - energy
• energy requirements
– vary widely (2000 - 3000kcals/day)
• preconception - sufficient to maintain appropriate weight
• during pregnancy - sufficient to promote appropriate
pregnancy weight gain
• non protein sources - low protein products,
free foods, energy supplements
free foods
calorie supplements
dietary requirements in maternal PKU
5 - micronutrients
• micronutrients
– to provide RNI + monitor at risk nutrients
– folic acid
• provided in protein substitute, if not separate
supplement
vitamins & minerals
+calcium
maternal PKU diet - difficulties
• may have been off diet for many years
• little awareness of managing the diet
– now up to them not their parents
• accustomed to normal food
• poor cooking & organisational skills
• satisfying appetite
• lack of support
maternal PKU diet - difficulties
• problems during pregnancy
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•
•
•
•
•
nausea & vomiting
severe hyperemesis
weight loss
inadequate protein substitute
illness
poor compliance (lack of support)
maternal PKU - monitoring
• blood phenylalanaine & tyrosine – twice weekly
• maternal weight
• twice weekly / more frequent contact with
dietitian
• monthly clinic review - Dr & dietitian
• monthly monitoring of Ferritin, B12, folate, FBC
• foetal monitoring
Pregnancy - outcome
1 - planned pregnancy
LE
• Bwt - 25th centile
• length - 75th centile
• OFC - 25th centile
2500
Phe µmol/l
2000
1500
1000
500
0
26
26.5
27
age (yr)
27.5
• normal developmental
progress
• DQ 111 age 4
2 - conception on a normal diet
JV
• presented 8/40
• preconception diet until
just prior to conception
• weight loss affecting phe
control
• coarctation of the aorta
• ? normal development
700
600
500
400
300
200
100
35
32
29
24
21
16
13
9
0
-4
Phe mol/l
TO
• Bwt - 25th centile
• OFC - 3rd centile
3 – poor compliance
LR dob 27/6/62
• diagnosed age 35 - maternal
screening
• 3 previous miscarriages
• pregnancy terminated as unable to
control phe levels
• preconception diet
SR
• bwt - 3rd centile
• length - < 3rd centile
• OFC - << 3rd centile
1400
• microcephaly
• severe learning
difficulties
1000
800
600
400
200
weeks
34
31
28
26
23
20
17
15
14
12
10
8
6
3
0
0
Phe mol/l
1200
Post birth
• infant feeding advice
– breast feeding OK whether mum on or off PKU diet
• record birth information
– gestational age
– birth wt, length, head circumference
– any medical problems
• routine newborn screening
• follow up by metabolic paediatrician
– DQ at 2, 4, 8, 14, 18years
• regular follow up of mother even if not on diet
maternal PKU – why be concerned?
• screened & treated PKU women - good outcome
• to prevent adverse outcome of pregnancy from high
maternal phe levels
•  number of women of child bearing age
- many lost to follow up
• unplanned pregnancies despite pre -conceptual advice
Manchester - size of the problem
Female PKU Patients
no of patients
30
25
children (n=66)
20
adults (n=98)
15
10
5
0
0-5
6-10
11-15
16-20
21-25
26-30
31-35
36-40
41-45
age of patients (years)
46-50
51-55
56-60
61-65
66-70
maternal PKU births in Manchester
10
9
8
7
6
Total
5
planned
unplanned
4
3
2
1
06
05
20
04
20
03
20
02
20
01
20
00
20
99
1983 - 2006 = 80 (44 planned - 55%)
20
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
89
19
88
19
87
19
86
19
84
19
19
19
83
0
successful management of maternal PKU
• commitment from patient, Dr & dietitian
• family support
• communication between agencies
• metabolic team
• GP
• maternity services
• frequent biochemical monitoring
• reliable, quick laboratory service
• inpatient facilities
conclusions
• good dietary control in maternal PKU
• normal outcome
• encourage female PKU’s to
• maintain regular contact with metabolic clinic
• maintain diet?
• continue protein substitute?