Preconception counselling directed on nutrition and ... counseling nutrition...DHF TS THF Methyl...
Transcript of Preconception counselling directed on nutrition and ... counseling nutrition...DHF TS THF Methyl...
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Preconception counselling directed on nutrition and lifestyle
Research and practise
Régine P.M. Steegers-Theunissen, MD, PhDProfessor in Periconception Epidemiology
Erasmus MC: Departments of Obstetrics and Gynecology, Pediatrics, Epidemiology, and Clinical Genetics
P r ec o n c ep ti o n h ea l th a n d c a r e ex p er i en c es i n Th e Neth er l a n d s a n d I ta l y
R o m e, J a n u a r y 2 7, 2 0 11
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Conception Birth 1 5 10 20 40 80
Complex diseases:CardiovascularDiabetes type 2Metabolic syndrome…
Periconception period
Fertility disorderMiscarriageCongenital malformations Growith restrictionLow birth weight
Gene - environment: nutrition and lifestyle
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05
1015202530354045
2001 2003 2005 2007 0102030405060708090
100
2001 2002 2003 2004 2005 2006 2007vrouw 15-45 jr man 15-45 jr
>45%80%31%
Unhealthy nutrition and lifestylesMan and woman: 15 - 45 years
vrouw 15-45 jr man 15-45 jr vrouw 15-45 jr man 15-45 jr
Centraal Bureau voor de Statistiek 2009
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Woman OR (BI) Fertility disorder 1.6 (1.3 - 1.9) Congenital malformation: Heart 2.7 (1.7 - 4.5) Cleft lip- palate 2.4 (1.1 - 5.3) Miscarriage 2.3 (1.5 - 3.5) Birthweight < 300 - 500 gr
Man OR (BI) Semen < 12 - 15% Congenital malformation: Spina bifida 1.6 (1.0 - 2.5) Cleft lip- palate 1.4 (0.9 - 2.1) Miscarriage 1.8 (1.0 - 3.3)
Smoking and risks before and during pregnancy
Augood et al. 1998; Venners et al. 2004; Karatza et al. 2009; Shaw et al. 2009; Zhang et al. 2010
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Woman: Fecundity: >3 months 37%, >6 months 17%
Subfertility: 1.3 x increased (BMI 24-31), 2.7 increased (BMI >32)
Pregnancy: PIH, pre-eclampsia, Diabetes Gravidarum and
artificial delivery(Zaadstra et al., 1993; Norman et al., 1998; Bolumar et al., 2000; Rich-Edwards et al., 2002)
Man: BMI >25: 22% reduction semenconcentration and
more DNA damage (DFI)(Bolumar et al., 2000; Jensen et al., 2004)
Overweight and obesity and risksbefore and during pregnancy
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Quantitative undernutrition Reproductive and pregnancy failures
and diseases in later life
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Prof. R.W. Smithells 1924-2003
Periconceptional folate intake
Periconceptional folic acid use
reduces the risk of spina bifida, heart defects
and cleft lip- and or palate between 50% to 70%.
Folate sources
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Qualitative undernutritionReproductive failures and disease in later life
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Mediterranean
Traditional Dutch
Pregnancy chance OR 1.4 (1.0 - 1.9)
Growth restriction OR 2.8 (1.6 - 4.8)
Semen, number 37.106 - 62.106
Periconceptional Dietary patterns
Vujkovic et al. 2009; 2010; Timmermans et al. 2010
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Western
Spina Bifida OR 0.3 (0.1 - 0.9)
Congenital heart disease OR 0.4 (0.2 - 0.7)
Cleft lip- and/or palate OR 1.9 (1.2 - 2.9)
Vujkovic et al. 2007, 2008, 2009; Oberman-Borst et al. 2010
One carbon metabolism
Periconceptional dietary patterns and congenital anomalies
Mediterranean
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Mediterranean
Cardiovascular disease HR 0.41 (0.18-0.95)Metabolic syndrome << 22% Epithelial cancer <<
Cardiovascular disease OR 0.30 (0.12-0.71)
Dietary patterns in adulthood and disease in later life
Martinez-Gonzales et al, 2010; Runawas et al, 2009; Babio et al, 2009; La Vecchi, 2009; Weikert et al, 2005
One carbon metabolism
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5,10-methylene-THF
5-methyl-THF
MS
SAM
SAH
CBS
[vitamin B12]
[vitamin B6]
cystathionine
cysteine
DMG
Betaine
BHMT
dTMP
dUMP
MTHFR
homocysteine
methionineDHF
THFTS
Methyl acceptor
Methylated acceptor
[vitamin B6]
NO //
Derangements in one carbon pathwayHyperhomocysteinemia, DNA hypomethylation
and free radicals (oxydative stress)
FOLATE
HOMOCYSTEINE
NADPH
NADP++H+
Glutamate
Glutathione
GSSG
ROH
ROOH+
Free radicals
ROS
Proteins, LipidsCHROMATIN - DNA METHYLATIONNNMT
MTRRTC2
nicotinamide
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Periconceptional hyperhomocysteïnemiaReproductive and pregnancy failures
Homocysteïne
Folate
Oxidative stress
OR (CI) Congenital heart disease 4.4 (2.6 - 7.3) Cleft lip- and/or palate 2.3 (0.4 - 11.9) Spina bifida 2.1 (1.4 - 3.3) Miscarriage 2.7 (1.4 - 5.2) Growth restriction 0.4 (0.2 - 0.7)
Oocytes Semen Embryo quality Pregnancy chance 0.6 (0.3 - 1.0)
van der Put et al. 1997;Neelen et al. 2000;Verkleij-Hagoort et al. 2007;Timmermans et al. 2009;Boxmeer et al. 2008
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12-03-2010
3D ultrasound
Enables volume measurements
10+2 10+0
Rousian et al, BJOG 2008Verwoerd-Dikkeboom et al, Ultrasound Obstet Gynecol 2008
7+4
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ProgrammingEmbryo
8wk
Genetic programming in the periconception period
ProgrammingGametes
-10 wk
Conception Birth
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Low and high folic acid: Les and more markers
Waterland et al. Mol Cell Biol 2003
Dutch famine:Less markers
Heijmans et al. PNAS 2008
Folic acid use 0.4 mg\day: More markers
Steegers-Theunissen et al. PLoS One 2009
Epigenetics in animals and human: folic acid - IGF2
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Main conclusions
Periconception parental nutrition and lifestyles
seem to be environmental conditions that can cause
(epigenetic) changes in humans that persist throughout
life and may explain reproductive and pregnancy
outcome, and long term health and disease risks.
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Objective: to improve the use of healthy
nutrition, folic acid supplements and lifestyles in the preconception period.
Target population:couples planning pregnancy.
Tailored preconceptional dietary and lifestyle counselling in a tertiary centre
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Preconceptional tailored nutrition and lifestyle counselling in routine reproductive/obstetrical care
1e consultation Gynaecologist Letter+flyer
www.zwangerwijzer.nl
Questionnaires
Informed consent
Obstetrics
Prenatal Medicine
Reproductive Medicine
Preconceptional Nutrition and
Lifestyle Counselling
One stop shop
Referral to Gynaecologist
Blood test: Vitamin B12, Folate, Homocysteïne
Physical examination length, weight (BMI), RR, waist-to-hip ratio; Nutrition and Lifestyle advice; results of the web application
PatientLetter
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Preconceptional tailored Nutrition and Lifestyle counselling (PC): 419 couples planning pregnancy PC1 and PC2 (3 months)
Time Period: 10/2007 until 04/2009
Methods: general questionnaire 6-item food questionnaire (Dutch Dietary Guidelines, 2009)
Preconception Dietary Risk score (PDR), maximum PDR score= 6 (highly inadequate nutritional intake)
Evaluation
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Questionnaires
Rotterdam Reproduction Risk Score (R3-score): No folic acid supplement use
Medication, smoking, alcohol, caffeine (≥6 cups a day)Lack of physical activity, infection riskBMI (<20 of ≥30), waist circumference (woman:≥88 cm and man: ≥102 cm) waist to hip-ratio (≥0.8)blood pressure (systolic ≥160 en diastolic ≥90) Derangement homocysteine pathway (biomarkers)
R3-score maximum for woman: 13 and for man: 10
ASE model (Attitude, Social influence, Self-Efficacy ) (De Vries et al., 2000)
Lifestyle
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PC 1 (N=309)
PC 1 and PC 2(N=110)
Age (years) 31 (19 - 44) 32 (19 - 42)
BMI (kg/m2) 24.6 (17.0 - 43.2) 25.1(18.7 - 42.2)
Ethnicity:
Dutch 167 (54.0%) 56 (50.9%)European-others 29 (9.4%) 11 (10.0%)Non- European 109 (35.3%) 42 (38.2%)
Indication of referral
Subfertility 289 (93.5%) 104 (94.5%)High obstetrical risk 10 (3.2%) 1 (0.9%)Recurrent miscarriages 10 (3.2%) 5 (4.5%)
Educational Level: Low 41 (13.3%) 23 (20.9%)Intermediate 157 (50.8%) 42 (38.2%)High 111 (35.9%) 34 (30.9%)
Medication use 122 (29.1%) 39 (35.5%)
GZW vrouwen: AlgemeenWomen: Baseline Characteristics
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PC 1(N=306)
PC 1 and 2(N=103)
Age (years) 34.1 (22-63) 34.5 (22-60)
Ethnicity: Dutch-native 190 (58.5%) 55 (53.4%)European others 43 (7.2%) 10 (9.7%)Non-European 73 (30.8%) 38 (36.9%)
Educational Level:
Low 68 (21.5%) 22 (21.4%)Intermediate 118 (38.6%) 35 (34.0%)High 120 (39.5%) 37 (35.9%)
Medication use 94 (22.4%) 28 (27.2%)
Man: Baseline Characteristics
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% compliance to Dutch Dietary Guideline
0102030405060708090
100
Women PC1 36 86 26 65 85 39 67Women PC2 41 84 27 80 81 64 85
Bread Butter/Oils Vegetables Fruit ** Meat Fish ** Folic acid use **
Women: Dietary intake and Folic Acid use
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Man: Dietary Intake
% compliance according to Dutch Dietary Guideline
0102030405060708090
100
Men PC 1 65 87 19 49 86 45Men PC 2 66 84 22 68 87 54
Bread Butter/Oils Vegetables Fruit ** Meat Fish
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PDR-PC 1 median
(min-max)
PDR-PC 1 median
(min-max)
PDR-PC 2 median
(min-max)
p
Women 3.0 (0-6) 3.0 (0-6) 2.0 (0-6) ≤0.05
Ethnicity:
Dutch 3.0 (0-5) 3.0 (1-4) 2.0 (0-6) ≤0.05European others 2.5 (0-5) 2.5 (1-4) 2.8 (0-6) n.sNon-European 3.0 (0-6) 2.6 (0-6) 2.3 (0-6) n.s
Educational Level:
Low 2.8 (0-5) 3.0 (1-5) 2.3 (0-5) ≤0.05Intermediate 2.6 (0-6) 2.8 (1-5) 2.6 (0-6) n.sHigh 2.3 (0-6) 2.3 (1-4) 2.3 (0-6) n.s
BMI:
20-25 2.5 (0-6) 2.7 (0-6) 2.3 (0-6) n.s 25-30 2.4 (0-5) 2.3 (1-4) 2.3 (0-4) n.s >30 2.8 (0-6) 2.8 (0-5) 2.6 (0-6) n.s
Woman: Preconception Dietary Risk Score (PDR)
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PC1 median
(min-max)
PC1median
(min-max)
PC1median
(min-max)
p
Men 2.5 (0-6) 2.5 (0-6) 2.2 (0-6) ≤0.05
Ethnicity:
Dutch-native 2.3 (0-5) 2.3 (0-5) 1.9 (0-6) ≤0.01European Others 2.0 (0-4) 2.6 (1-4) 2.9 (0-4) n.sNon-European 2.7 (0-6) 2.6 (1-5) 2.4 (0-6) n.s
Educational level:
Low 2.5 (0-5) 2.5 (1-5) 2.3 (0-6) n.sIntermediate 2.3 (0-6) 2.3 (0-4) 2.0 (0-5) n.sHigh 2.3 (0-6) 2.5 (1-5) 2.4 (0-6) n.s
BMI:
20-25 2.3 (0-6) 3.0 (1-5) 2.2 (0-4) ≤0.05 25-30 2.3 (0-5) 2.3 (0-5) 2.0 (0-6) n.s >30 2.6 (0-5) 2.5 (0-5) 2.6 (0-6) n.s
Man: Preconception Dietary Risk Score
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1) Ineadequate dietary intake in women (99.1%) and men(97.3%).
2) Tailored PC is effective in women to improve fruit (+16%), fish (+25%) and folic acid
use (+17%) and in men to improve fruit (+20%) intake.
3) Also in low educated women.
Conclusions
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Woman: Lifestyle risk factors
PC 1(N=309)
PC 1(N=110)
p PC 2 (N=110)
p
BMI 26 (17.0-43.2) 25.1 (18.4-42.4) n.s 25.3 (18.8-40.3) n.s
25-30 50 (16.2%) 21 (19.1%) n.s 25 (22.7%) n.s
>30 89 (28.8%) 34 (34.0%) ≤0.05 31 (28.2%) ≤0.05
Folic acid use 192 (62.1%) 74 (67.3%) n.s 93 (84.5%) ≤0.01
Smoking 69 (23.3%) 18 (16.4%) n.s 17 (15.4%) n.s
Alcohol 136 (44.0%) 39 (35.5%) n.s 23 (20.9%) ≤0.01
Drugs 5 (1.6%) 4 (3.6%) n.s 4 (3.6%) n.s
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Man: Lifestyle risk factors
PC 1(N=306)
PC 1(N=103)
p PC 2(N=103)
p
BMI 26.9 (17.4- 46.8) 26.4 (18.5- 42.5) n.s 26.6 (19.1- 41.9) n.s
25-30 116 (37.9%) 40 (38.8%) n.s 50 (45.5%) n.s
>30 67 (21.9%) 20 (19.4%) n.s 18 (16.4%) n.s
Smoking 103 (33.7%) 21 (20.4%) ≤0.05 21 (20.4%) n.s
Alcohol 204 (66.7%) 61 (59.2%) n.s 48 (46.6%) ≤0.05
Drugs 25 (8.2%) 5 (4.9%) n.s 4 (3.9%) n.s
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0
5
10
15
20
25
30
35
40
1 2 3 4 5 6 7 8 9 10 11
%
R-3
vrouwen, bezoek 1
vrouwen, bezoek 2
mannen, bezoek 1
mannen, bezoek 2
Rotterdam Reproduction Risk score (R-3 score)Modifiable risk factors
Women visit 1
Women visit 2
Men visit 1
Men visit 2
R-3 score Women: 3.9 vs.2.8; p<0.01* R-3 score Men: 2.3 vs. 1.6; p<0.01*
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At PC1 women (100%) and men (98,5%) had =>1 lifestyle risk factor .
At PC2 R3-score 30% (women) and 45% (men) reduction.
Reduction also in high risk women (non-Western, low SES, living in
deprived neigbourhood).
Future studies should corroborate on the predictive value of the PDR and
R3-Score on reproductive performance and pregnancy outcome.
Cave selection: tertiaire medical hospital centre, RCT
Conclusions
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(E-)Healthcare programs
Development of tailored personalized tools to improve (pre)pregnancyHealth, nutrition and lifestyle of parents-to-be:1. inventarisation of risk factors2. risk profile3. advise4. support5. maintenance
Central Database (ErasmusMC - RijnmondZorgPortaal):1. Personal data, profiles, questionnaires, advises, compliance2. Safe, privacy3. Patients(users), Patientcare, Research and Healthcare providers
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E - Healthcare Tool 1: www.zwangerwijzer.nl
Screeningsinstrument
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E - Healthcare Tool 2: www.preconceptiewijzer.nl
Zorginstrument
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E - Healthcare Tool 3: Personal dietary measurement tool
Screening-, Care-, Intervention-, and Researchinstrument
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E - Healthcare Tool 3:Personal dietary measurement tool
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Women with overweight (BMI 28.5) following a diet to loose weight.
<many deficiencies, i.e., folate (B11): 52% RDA.
E - Healthcare Tool 3: Personal dietary measurement tool
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Tailored and personal interventionCombination of internet AND mobile phone
E - Healthcare Tool 3: Personal dietary measurement tool
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E - Healthcare Tool 4: Personal Mobile Pregnancy Program
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E - Healthcare Tool 4: Questions on nutritional intake
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E - Healthcare Tool 4: Personal feedback
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Periconceptional intakereduces the risk of birth defects
Voeding
Supplement Voeding
Supplement
E - Healthcare Tool 4: Folic acid intake
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Periconceptional intakereduces the risk of birth defects
E - Healthcare Tool 4: Personal feed back
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Automatic reminder to consult Personal Mobile Pregnancy Programme
!sms
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New life in a changing environment
Healthy periconceptional nutrition and lifestyles
improve health of parents, children and next generations!