History of childhood and causation of health

Are lives programmed?

What is a child?

UN: 0-18 years

And what is health??

•WHO 1946:’Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity’ (later added: ’ability to lead a socially and economically productive life’)

•Sigmund Freud: ’You have health if you are able to work and love’

•Peter F Hjort: ’…Health is to master everyday’s demands’

Helse?• Samme kategori ord som kjærlighet,

lykke, kultur, bærekraftig• Alle har et forhold til begrepene,

ingen er enige om hvordan de skal defineres Hva lykke er? Det er å gå på en gressgrodd

setervei i tynne, tynne sommerklær klø sine første myggestikk med doven ettertenksomhet og være meget ung og meget rik på uoppplevet kjærlighet

(Inger Hagerup)

How can we measure health?Proxies (health indicators)

• MortalityMortalitet

• Morbidity

• Infant mortality (IMR)

• Life expectancy

• Under-5 mortality

• Birth weight

• Body height

All endpoints are proxies for what we call health

Quality of life model the different spheres(Lindstrøm, Allhardt)

• Global:macroenvironment, human rights

• Outer sphere:Socioeconomi

• Humen relations: Family, friends

• Personal: physical, mental, spiritual, activity, selfconfidence

What is mental health?

• (Meriam Webster):

• A state of emotional and psychological well-being in which an individual is able to use his or her cognitive and emotional capabilities, function in society, and meet the ordinary demands of everyday life”.

The three circles of social determinants of health

Family

Friends

Neighbours

Home

Norms

Expectations

Community

AreaLocal services

Naturalresources

Pollution

LocaleconomySchools

Macrosocial influences

Government

Laws

Economic system

Nationalpriorities

Welfare model

Justice

Equality

CHILD=child health indicators for life and development (EU)

• Demographic and socioeconomic determinants

• Health and disease (mortality, morbidity)

• Health determinants (positive,negative)

• Health policy

Children’s health and quality of life

Globalchanges

Technical changes

Economicalchanges

Societal changes

Educational changes

Populationchanges

Life style changes

Nutrition

Changes in disease panorama

?

?

??

?

?

What is epidemiology?

Basicly: The study of the origin of diseases

• Epidemiologiske undersøkelser dreier seg om undersøkelser av grupper av befolkningen, ikke av enkeltindivider

• Epidemiologi er grunnlaget for helseovervåkning og for å foreslå forebyggende tiltak i befolkningen

Eilert Sundt: Om dødeligheden i Norge (1855)

…”der er intet blindt tilfælde (av dødsfall). Det lære vi, naar vi ikke alene saaledes med bevæget sind betragte de enkelte dødsfald, som kunne være inntruffet i den snevrere kreds, men tillige med sindigt overlæg samle en større mengde erfaringer ved at tælle alle de dødsfald, som i et længere tidsrum ere intrufne i i en by, en egn eller i et helt land.”

Helsediktet fra Salerno - ca. 1300 e.Kr.

Om årsakene til sykdom:Årsakene til øresting:

• Sno, byld, sult, støt og hete, flere ting er nevnt som grunn til øresting. Samme skade kan det gjøre at folk skriker i ens øre.

Årsakene til sukkersyke:

• Er nyrene tørre, og sterkt opphetes, vil du få diabetes; også elskov, hopping og kappløp gjør sitt, og at en har slitt.

Hvordan skal vi måle sykdom eller helse?

• Forekomst (antall tilfeller, andel) må ha en teller (antall tilfeller) og en nevner (hele befolkningen, deler av befolkningen, aldersgrupper, osv.

• Vi må ha en kilde for å få frem tallene: register (dødsregisteret, kreftregisteret hvor alle tilfeller blir meldt), eller vi må gjøre spesielle undersøkelser, surveys

Examples (mortality)

• Number of deaths per 100 000 inhabitants• Infant mortality (IMR): number of deaths in first year

of life per 1000 live born• Deaths per 100 000 inhabitants in a county• Deaths per 1000 among people in certain

employments• Number of deaths per 100 000 of a specific

diagnose(cause specific mortality)

Target population, everyone ”at risk” must be stated.

Two types of epidemiological studies

• DescriptiveDescriptions of prevaence of illness(disease) in a

population (group) – nothing about causes

• AnalyticalTry to look for causal factors

Typer av epidemiologiske undersøkelser

• Hypotesegenererende• pasient• serier av pasienter• tverrsnittsstudier av befolkningen

• Hypotesetesting

Observerende: • pasient-kontroll (case-control)

• cohort

Eksperimentelle• Randomiserte(RTC)

Måling av sykelighet

• Forekomst/prevalens egner seg vesentlig for tilstander som er noenlunde stabile gjennom en tid (kroniske?). Uttrykkes i antall tilfelle per (for eksempel) 100 000 av målpopulasjonen

• For noen sykdommer er dette et uegnet mål, for eksempel ved akutte infeksjonssykdommer. Da kan vi måle insidens: antall nye tilfeller per 100 000

Letalitet

Det er også hensiktsmessig å kjenne uttrykket letalitet, som er antall døde per antall som er blitt

syke

Lif expectancy at birth, Norway 1900 -94

0

10

20

30

40

50

60

70

80

90

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 1994

boys girls

life

tim

e, y

ear

s

Cohort Studies – definition(R.Doll)

• ”…the delineation of a group of persons who are distinguished in some specific way from the majority of the population and observation of them long enough to allow any unusual morbidity or mortality to be recognised”.

”Case control”

• Compare exposure (risk factors) for people with a known endpoint (disease) with a control group without the disease

• The Norwegian Mother and Child Cohort Study studies cases and controls from the same set of data (”nested case control” )

Kohortdesignets fordeler:

• Man undersøker eksponeringsforhold (potensielle årsaksfaktorer) før utfallet er kjent

Assosiasjon mellom eksponering (risiko) og utfall

(sykdom)Risiko Sykdom

+ -

+ 201(a) 25(b)

- 20(c) 145(d )

Odds ratio= a x d/b x c

Association is not equivalent to causality!

• Criteria for associations= causes (Bradford-Hill):

• strength

• consistency

• specificity

• time sequence

• biological gradient (dose/response)

• plausibility

• coherence

• experimental proof

• analogy

Hvor kan vi hente data fra?Utfallsdata (sykdom,død): Registre (døds-,kreft-,fødsels-,diabetes-,pasi-entutskrivnings-)

Helseundersøkelser

(statens h.u.,CONOR, SSB, helsestasjonsdata, meldepliktige sykdommer)

Spesielle undersøkelser (surveys)

Hvor kan vi hente eksponeringsdata?

Eksempler:

• Kommunedata (luft,vann etc)

• Trafikketaten (trafikktetthet etc)

• Spesielle spørreundersøkelser til enkeltindivider

• Spesielle målinger (forurensning, støy etc)

• Biologiske prøver

• SSB (sosioøkonomi etc)

ER SYKDOMMEN ARVELIG?Design i genetisk epidemiologi

• Tvilling- og adopsjonsstudier• Segregasjonsstudier• Koplingsanalyse• ”Vanlig epidemiologisk design”: Ved

samspill mellom arv og miljø, behandler man de genetiske faktorene som en vanlig risikofaktor.

NB: de aller fleste sykdommer er styrt av mange gener, og av miljøpåvirkning!

IntervensjonsstudierVirker et tiltak?

• Randomiserte forsøk= RCT (randomized control trials

Ofte vanskelig design!

Alltid ved legemiddelutprøving

”Økologisk” (Ecological) design

Her sammenlignes hele grupper, ikke knyttet opp mot

enkeltindivider, eksempel er fra Forsdahl studie av hjerte-kar

dødsfall i Finnmark

New indicator for child health

(Student, Croatia):

”The proportion of children that smile to you when you meet them”

Health and Illness in Norwegian Childhood through 100 years-

from Poverty to Wealth

• Rannveig Nordhagen

• Norwegian Institute of Public Health

• Oslo, Norway

Ord om barn og barndom

• Barnets innebygde mål er å bli voksen, før dette eksisterer det bare som en mulighet, et potensial (Aristoteles)

• Barndommens historie er et langt mareritt, som vi bare langsomt holder på å våkne opp fra (Lloyd de Mause, am. psykoaanalytiker)

Scenario 1900:

Population 2,2 mill

Emigration 1901-10: 38 172

Infant mortality 1896-1900:

boys: 105,5/1 000,girls: 92/1000

Important diseases: Infections (Tbc)

Life expectancy:

0 år: 51,5

5 år: 55,5

20 år: 44,04

2007

• Folkemengde: 4 500 000

• Innvandrere: 8% (i 2060: 19-27%)

• Spedbarnsdødelighet: 3 per 1000

• Viktigste sykdommer: Hjerte-kar sykdommer, kreft (kroniske lidelser)

• Forventet gjenstående levetid (ved 0 år)

• Kvinner: > 82 år, menn: 78 år

Chr Krohg:Fighting for existence

Helene Scherfbeck

Spedbarnsdødeligheten

E.Munch: Fostermother

s in court

”Angel mothers”:

Fostermothers who starved the children to death

Infant mortality in Norway per 1 000 1905-1994

0

5

10

15

20

25

30

35

40

45

50

1905 1910 1915 1920 1925 1930 1935 1940 1945 1950 1950 1955 1960 1970 1975 1980 1985 1990 1994

boys girls

IMR and U5MR per 1 000 in some selected countries in 1960 and 2003

U5MR I MR

1960 2003 1960 2003

Niger 320 262 211 154

Pakistan 227 103 139 81

Turkey 219 39 163 33

Romania 82 20 69 18

US 30 8 26 7

UK 27 6 23 5

Norway 23 4 19 3

Life expectancy at birth, Norway 1900 -94

50

55

60

65

70

75

80

85

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 1994

boysgirls li

fe ti

me

, ye

ars

Tbc mortality, Norway, 1900-65, age 15-19 years

050

100150200250300350400450

1900

1905

1910

1915

1920

1925

1930

1935

1940

1945

1950

1955

1960

1965

Girls

Boys

Year

BCGChemotherapy

Mortality per 100

000

Mortality of tbc per 100 000

Age -1900 -1915 -1940

M F M F M F

0-4 345 339 180 156 38 37

10-14 145 223 87 154 20 27

15-19 319 375 272 333 27 81

Causes of infant mortality, Norway 2002

All 3.5/ per 1000

Per 100 000:Birth/perinatal complications: 153 Malformations: 108SIDS 31

Rate of low birthweight (< 2 500g) in the Nordic countries (NOMESCO 1997, %)

Denmark Finland Iceland Norway Sweden

1980-82 5,73 - 3,64 4,21 4,33

1983-85 5,78 - 3,82 4,50 4,42

1986-88 5,58 - 3,51 4,68 4,67

1989-91 5,36 3,84 3,33 4,87 4,54

1992-94 5,31 4,06 3,96 4,81 4,48

1980-94 5,53 3,93 3,65 4,63 4,49

Rate ratio(RR) of children with social support at the age of 7 in relation to

birthweight (Norway 1998)

Cause Weight groups

500-999 1000-1499

1500-1999

2000-2500

> 2500

Mentaldisorder

11,5 4,2 3,8 2,9 1

Nevrologicdisorder

53,0 36,9 13,6 3,5 1

CP 94,2 67,6 22,5 4,9 1

Eye disease 155,2 50,5 4,4 4,0 1

Ear disease 14,7 9,3 3,5 2,8 1

Malformat. 6,7 4,9 3,7 3,8 1

Mortality of tbc, Norway, 1900-65, age 0-4 years

0

100

200

300

400

1900 1905 1910 1915 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965

Mor

talit

y pe

r 10

0 00

0 Girls

Boys

Year

”Finsen-treatment” Hagavik hospital

Screening for tbc

Mortality rates and life expectancy (US)

1800 1850 1900 1950 2000

Infections

Chronic Disease

Life Expectancy

Tarlov 1996

Reported cases of invasive Hib infection, Norway, 1989-96

0

20

40

60

80

100

120

140

1989 1990 1991 1992 1993 1994 1995 1996Year

Nu

mb

er o

f re

po

rted

cas

es

3m-2years3-10 years>10 years

Vaccine

Kari Kveim Lie 1997

”The Oslo breakfeast”

Weight and hight screening

World war 2, 1940-45:

Food restrictions, undernutrition in towns

Mean hight for different age groups of girls, Oslo from 1920 to 1975. GH Brundtland et al 1980

Relation between height at the age of 7, and unemployment at age 22-32

0

0,5

1

1,5

2

2,5

3

3,5

114 119 122 124 126

Height at 7 years

Od

ds

ra

tio

fo

r u

ne

mp

loy

me

nt

crudeadjusted

Montgomery S et al. 1996

Parent reported overweight in Nordic children 1996,%

0

2

4

6

8

10

12

14

16

18

6 yrs 9 yrs 12 yrs 15 yrs 17 yrs

boys

girls

Chidren’s healthand quality of

life

Global changes

Technologicalchanges

Economical changes

Societalchanges

Educationalchanges

Changes inpopulation

Life stylechanges

Nutritionalchanges

Changes ofdiseasepattern

?

?

??

?

?

Infant mortality per 1 000 live born, Norway, 1901-63

0

20

40

60

80

100

120

140

160

Mor

tali

ty

MarriedUnmarried

Social class and infant mortality 1911-71, England & Wales

020406080

100120140160180

1911 1920 1931 1951 1971

Year

Infa

nt

mo

rtal

ity

per

100

0

IIIIIIIVV

Incidence of tye 1 diabetes in the Nordic countries 1995-2003, both

sexes, 0-14 yrs

0

10

20

30

40

50

60

1995 2000 2003

Inci

den

ce p

er 1

00 0

00

Denmark

Finland

Norw ay

Iceland

”Binge drinking” and problems associated with use of alcohol, both

sexes, 15-16 yrs

0

5

10

15

20

25

30

Denmark Faroe Islands Greenland Finland Iceland Norw ay Sw eden

Per

cen

t Binge drinking

Relationship problems

Delinquency problems

Mortality 1-17 years. Norway 2002,

per 100 000Total Infectious

diseases

Tumours Congenital

malformat.

21 0.9 3.4 2.4

The child’s century?(essay by RB, Norwegian school boy,

1999)

”…the developing countries seem to mirror the industrial countries a century ago, which should mean that the development goes in the right direction - which I believe. With an increased effort towards the developing countries towards year 2 000, I think we rightly might call this century the children’s century.”

The greatest threats for children in 2 000 (UNICEF):

• Wars

• AIDS/HIV infections

• Poverty

When are our lives determined?

Edvard Munch:Inheritance.

Why do we vaccinate against Rubella (German measels)?

Is this a clue??

Have we asked our questions at the right time?

Forsdahl/Bakketeig1991

Forsdahl/Bakketeig 1991

Anders Forsdahl :…”whereas the weaker of the cohort

die in infancy, the fit survive and carry with them a life-long

vulnerability”

Dødsårsaker, døde per 100 000, 2003

0 100 200 300 400

hjertekar

kreft

åndedrett

fordøyel

vold

trafikk

suicid

menn

kvinner

Standardised mortality ratios among men according to birthweight and weight at one year

Weight(lb)

Coronary All causes

Birth 5.5 102 93-7.5 82 80-9.5 56 68

1 year 18 105 89-22 85 82>26 42 62

Barker 1991

Hazard ratios for coronary heart disease in adult life among Finnish men according to birthweight and weight at 12

monthsBw (g) Hazard ratio (RR)

≤ 2500 3.63

-3000 1.83

-4000 2.08

>4000 1.00

P value for trend 0.006

Weight at 1 y (kg)

≤ 9 1.82

-10 1.17

-11 1.12

>12 1.00

P value for trend < 0.0001

Correlations of cause of death (SMRS) at ages 35-75 years and IMR

Cause of death Correlation coefficient

Ischaemic heart disease 0.73

Broncitis 0.82

Stomach cancer 0.79

Rheumatic heart disease 0.72

Stroke 0.54

Lung cancer 0.46

Barker 1986

Ethel Margaret Burnside, 17 yrs1877-1953

A pet child has many

namesForsdahl hypothesis??

Barker hypothesis?Fetal programming hypothesis?

Fetal origins hypothesis?

The concept of biological (fetal) programming (Lucas):

When an early stimulus or insult, operating at a critical or sensitive

period (infetal life), results in a permanent or long-term change in

the structure or function of the organism

Later programming hypothesis (Lucas 2):

If the fetus experiences undernutrition in fetal life, the fetus adopts to this state, and if a later

rapid overnutrition of the baby occurs, it can get out of balance- for instance what concerns the

tolerance of glucose (insulin resistence- diabetes 2).

”The growth accelaration hypothesis”

(Singhal & Lucas 2004)Hypothesis about rapid growth

very early in life

De viktigste assosiasjonene i de første Barker-studiene mellom fødselsvekt/vekt

ved ett år:• Hjerte-kar sykdommer,spesielt koronarlidelser• Diabetes II• Obstruktiv lungesykdom (KOLS)• Risikofaktorer for hjerte-kar sykdommer:

Hypertoni, koagulasjonsfaktorer, kolesterolnivå, overvekt

• Syndrom ”X”=diabetes2 +hypertoni+hyperlipidemi

Andre antropometriske mål ved fødselen som viser tilsvarende

assosiasjoner:Abdominal omkrets

HodeomkretsPlacental vekt/fødselsvekt

LengdePonderal index =kg/m³ (lengde³)

BMI =kg/m²(lengde²)

Low birthweight ”per se” is not the cause of later coronary

disease, but what has happened in intrauterine life

Three hypotheses (P. Magnus)

• The environmental model: Exposures, i.e. those related to poverty, have effects of the growing fetus, later leading to adult disease

• Genetic confounder model: the association between birth weight and later disease (coronary) is completely causes by genes influencing both factors

• Environmental confounder model: Same background factors can influence both early and late phenotypes, example is smoking..

”These diseases can best be focused on from a lifecycle

perspective(Erikson 2006)

Pathways from early life to later health

a)Programming

Programming in intrauterine life - Later illness/health (latency model)

b) Continuous life events

Parents’ SES - Childrens SES

Birth weight - Later illness

Foreslåtte mekanismer bark programmeringseffekten

(Lucas)

Cellulære mekanismer• Ernæringsforholdene (miljøet) endrer genetisk

ekspresjon permanent• Ernæringsforholdene virker inn på (reduserer) fosterets

cellemasse• Seleksjon av kloner av gener

• Ernæringsforholdet endrer organstrukturen• Ernæringsforholdene virker gjennom sensibilisering for

hormoner

Regression models (Lucas 1999)

- Early model: regression used simply to relate early size to later outcome

- Combined model: includes both early and later size, obtained by adding later size to the early model

- Interaction model: adds the interaction of early and later size to the combined model. The interaction terms

is calculated as the product of early and later size

- Late model: later size alone is related to outcome, which helps to interpret the relative importance of early

and later size separately and together

The fetal hypothalamic-pituitary- adrenal axis (DM Sloboda)

• …Programming of the fetal HPA axis during development appears to play a central role in the link between fetal growth and long-term disease in adulthood. Prenatal programming of HPA axis function may increase the the risk of developing cardiovascular and metabolic disease.Cognitive and behavioural modifications have also associated with fetal programming and linked to alterations in HPA axis activity ….

Mor Far

Barn

But what about genes??

• Single gene conditions (2% of the population in a life perspective)

• Chromosome anomalies (Down)

• Multifactorial conditions

Antenatal maternal anxiety and depression and infant development and

behaviour at 6 months

Rannveig Nordhagena Anne Inger Helmen Borgeb

aNorwegian Institute of Public Health, OslobInstitute of Psychology, University of Oslo

Leonardo da Vinci:Woomb

The hypothesis of fetal ”programming” (Forsdahl/Barker/Lucas)

• The intrauterin environment afforded by the mother at a critical period of development may permanently ”program” the structure and physiology of her offspring, and have a lasting or lifelong significance, for instance on the brain development.

Our hypothesis (slightly moderated from the title):

• Can the mother’s anxiety and depression in pregnancy affect the child’s behaviour at 6 months of age?

Rossetti: Ecce ancillaDomini(1850)

The Norwegian Mother and Child Cohort Study

• An ongoing cohort study starting in pregnancy, basicly a questionnaire study,but biological samples (blood, urine) are collected. Linking to health registries may be performed (Birth, Death,Cancer etc).

• Aim:

Recruitment of 100 000 pregnant women,

100 000 children, 80 000 fathers.

Status per 01012006: > 60 000 women included

Study progress:

• 1992: Project planned• 1995: Pilot project• 1999: Project start at first hospital• 2000: 2 752 women recruited• 2004: 40 000 women recruited• 2006: >60 000 women recruited• The participation rate is < 50% of all

invited women

Hospitals in Norway participating in the

MoBa Study

Time of questionnaires:

Q1: Week 17-18 of pregnancy (ultrasound)Q2: Week 24 of pregnancy (nutrition)Q3: Week 30 of pregnancyQ4: 6 months post partum Q5: 18 months post partum Q6: Child 3 yearsQ7: Child 7 years

Ca 100 Q in each questionnaire, and many subquestionsUsed in this study: Q1, Q3 and Q4 all reported by the mother

Included in this study:

• All mothers who had filled in Q1(week 17 in pregnancy), Q3 (week 30 in pregnancy) and Q4 (6 months post partum)

• Singleton births

All together: 37 011 women

Some missing on single questions!

Variables used in this study

• Outcome variable: Problematic child at 6 months

• Measure:

• 10 Q mainly from Infant characteristic questionnaire (ICQ) (Bates et al.)

• Items:crying, soothability, easily upset, intensity of protest, easy to get along with, smiles, very demanding, require attention, easy to put to sleep)

Exposure variables

• Mother’s general anxiety and depression week 30 in pregnancy and 6 months pp (short version of symptom check list (SCL). 8 questions: 4 for anxiety, 4 for depression)

• ”Specific” anxiety (week 30):Fear of giving birthWorries about the baby’s health

• Covariates/confounders:Maternal factors: Anxiety/depression 6 months pp, mother’s

education,mother’s age

Child factors: sex of baby, birth weight

E.Munch:Inheritance

Else Hagen: The Family

The results of this study cannot be published on the net, due to later

scientific publication.

Sorry!