Studies Investigating The Barker Hypothesis

Large epidemiological studies of offspring of mothers exposed to malnutrition whilst pregnant include the Dutch Hunger Winter Study [16] and the Leningrad Siege Study [17].

The Dutch Hunger Winter Study (a cohort born between 1944 and 1946 in Amsterdam) demonstrated that first trimester exposure to intra-uterine malnutrition was associated with increased waist-hip ratio in adulthood but there was no effect on birth weight. In contrast, third trimester malnutrition reduced both birth weight and adulthood adiposity. A follow-up study of offspring of mothers from the original cohort demonstrated that infants born to these women did not show the expected increase in birth weight with increasing birth order [18]. This effect was observed in those offspring of mothers who were exposed to intra-uterine malnutrition during the first trimester and suggests that there are long-term biological effects that are independent of maternal birth weight which influence subsequent generations.

The Leningrad Siege Study compared two groups of offspring from Leningrad; those born during the siege (1941 - 1944) as an intra-uterine malnutrition group, those born before the siege as an infant malnutrition group; and a group from outside the city as an unexposed group. In contrast to Barker's studies there was no difference between the intra-uterine and infant groups with respect to the following: glucose intolerance, insulin concentration, blood pressure and lipid levels. Despite the problems of the lack of accurate birth weight data and low case ascertainment (only 44% of eligible subjects were screened) this study subjects that intra-uterine malnutrition does not have a major role in the pathogenesis of adulthood glucose intolerance and hypertension [17].

Extreme malnutrition may have little relevance to the general population and a number of studies have retrospectively examined the effects of birth weight on the development of chronic disease in adulthood using normal subjects. Results from large studies are shown in Table 1.

Table 1: Summary of large studies investigating the Barker Hypothesis

Study

Subjects and

Ascertainment

Source

Outcome

Conclusion

design

data

measures

Health

22,846 males

60%

Self

Self

LBW associated

Professionals

Postal

reported

reported

with

Follow-up Study

questionnaire.

BW.

BP

hypertension

USA [19]

Self

Diabetes

reported

Obesity.

DM

Self

reported

weight.

Nurses' Health

70,297

60%

Self

As above.

As above.

Study

Postal

reported

[20, 21]

questionnaire.

BW.

Uppsala

13,282

97%

Detailed

CV

LBW males have:

Sweden

singleton

maternity

mortality

Reduced fetal

[22]

births

Records

growth associated

surviving

Linkage

with:

beyond 1 yr.

and census

Increased CV

Born 1915 -

data.

mortality.

1929.

Helsinki

3,302 males

92%

Detailed

CV

LBW not

Finland

Born 1924 -

maternity

Mortality

associated with

[23]

1933.

records.

increased CV

mortality

Low ponderal

index and low

maternal BMI

associated with

increased CV

mortality.

Stockholm

2,237 males

79%

Self

DM

Association with

Sweden

Born 1938 -

reported

IGT

LBW strongest in

[24]

1957.

BW.

those with a

family history of

diabetes.

Israel

19,734 males,

95.2%

Maternity

Blood

Current BMI

[25]

12, 846 females.

records.

pressure

predicted BP.

Born 1964 -

1971.

Israel

6,684 males,

97.1%

As above

Blood

Low maternal

[26]

4,199 females.

Maternal

pressure

BMI correlated

Born 1974 -

BMI.

with BP.

1976.

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