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Table 3 Evidence for a causal relationship between low birth weight and preterm birth and hip osteoarthritis according to the Bradford Hill criteria

From: Could low birth weight and preterm birth be associated with significant burden of hip osteoarthritis? A systematic review

Bradford Hill criterion and description Hip osteoarthritis
Temporal relationship
This is an essential criterion. For a possible risk factor to be the cause of a disease, it must come before the disease. This is generally easier to establish from cohort studies than from cross-sectional or case-control studies, when measurements of the possible cause and the effect are made at the same time
Criterion met: Yes
Hussain et al. [32]
In a cohort study people born with low birth weight (LBW) or preterm underwent hip arthroplasty for hip osteoarthritis (OA) at an average age of 59.0 (standard deviation (SD) 9.5) years
Clynes et al. [34]
Participants of the Hertfordshire Cohort Study who were born LBW had more osteophytes in the hip joint detected by x-ray at the age median of 75 (interquartile range (IQR) 73–77) years
Plausibility
A risk factor associated with a disease is more likely to be the cause of the disease if the association found is consistent with knowledge obtained from other sources, such as animal experiments and experiments on biological mechanisms. However, this criterion must be used with care as a lack of plausibility may simply reflect a lack of scientific knowledge
Criterion met: No
Consistency
If similar results have been found in different populations using different study designs, the association is more likely to be causal as it is unlikely that all studies were subject to the same types of errors (chance, bias or confounding). However, a lack of consistency does not exclude a causal association, as different exposure levels and other conditions may reduce the impact of the causal factor in certain studies
Criterion met: Yes
Different stages of hip OA including hip arthroplasty for OA [32], osteophytes in hip joint [34], and hip shape deformity [36] were found in different populations using different study designs, including two cohort studies [32, 34] and a cross-sectional study [57]
Strength of an association
The strength of an association is measured by the size of the relative risk. A strong association is more likely than a weak association to be causal, as a weak association could more easily be the result of confounding or bias
Criterion met: Yes
A strong association was observed in one study [32]
Dose-response relationship
Further evidence of a causal relationship is provided if increasing levels of exposure lead to an increasing risk of disease
Criterion met: Yes
A dose-response relationship was observed in one study [34]
Specificity
If a particular exposure increases the risk of a certain disease but not the risk of other diseases, this is strong evidence in favour of a cause-effect relationship. However, one-to-one relationships between exposure and disease are rare, and lack of specificity should not be used to say that a relationship is causal
Criterion met: Yes
Low birth weight and preterm birth is associated with hip arthroplasty for OA [32] and hip osteophytes [34] but not knee arthroplasty for OA [32] or knee osteophytes [34]
Reversibility
When the removal of a possible risk factor results in a reduced risk of disease, the likelihood that this association is causal is increased. Ideally, this should be assessed by conducting a randomized intervention trial. For many exposures or diseases, such randomised trials are not possible in practice
Criterion met: Not applicable for this condition
Coherence
The suggested cause-effect relationship should essentially be consistent with the natural history and biology of the disease
Criterion met: No
Analogy
The causal relationship will be further supported if there are similarities with other (well-established) cause-effect relationships
Criterion met: Yes
Reduced bone mineral density [45] and bone mineral content [10] are found in preterm infants, even when age is corrected for term. Radiological changes, including characteristics of rickets, are identifiable in 23% of infants weighing < 1500 g [58]