Completed Harm Worksheet for Evidence-Based Neonatal Medicine
Grether JK., Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997; 278:207-11.
Are the results of this harm study valid?
Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?
Yes. Cases were all singleton children born in 1983 through 1985 to residents of 4 San Francisco Bay-area counties and included all children who met the following criteria: weighed 2500 grams or more at birth, survived to age 3 years, were residents of California to that age, and had moderate or severe congenital CP. Control children were randomly selected from singleton children who met all the case criteria except for having CP.
Were treatment exposures and clinical outcomes measured the same ways in both groups (e.g., was the assessment of outcomes either objective (e.g., death) or blinded to exposure)?
Yes. Nurses masked to outcome of interest and to case or control status abstracted clinical data from maternal labor and delivery and newborn records.
Was the follow-up of study patients complete and long enough?
This is a case-control study. Case children were old enough to make an accurate diagnosis of CP.
Do the results satisfy some "diagnostic tests for causation"?
Is it clear that the exposure preceded the onset of the outcome?
Yes, but there are problems with the ascertainment of the exposure: Histologic diagnosis of inflammation of placental membranes was not consistently available, and therefore, some misclassification of exposure status may have occurred.
Is there a dose-response gradient?
Is there positive evidence from a "dechallenge-rechallenge" study?
N/A; the harm in question is permanent.
Is the association consistent from study to study?
Hard to say. You only found this one study in infants of normal birth weight. However, the findings are consistent with recent studies in infants of very low birth weight.
Does the association make biological sense?
It is uncertain why maternal infection is associated with CP. However, it is plausible that cytokines and other mediators may cross the placenta and the blood-brain barrier of the fetus, and disturb neuronal and glial development.
Are the valid results from this harm study important?
|Present (case)||Absent (control)|
|Exposed to the potential harm||Yes (Cohort)||
a + b
c + d
a + c
b + d
In a randomised trial or cohort study:
Relative Risk (RR) = [a/(a+b)]/[c/(c+d)]
In a case-control study:
Odds Ratio (or Relative Odds) (OR) = ad/bc
In this study, maternal infection was considered to be present, if at least one of the following had been documented: Fever>38 ºC in labour; Chorioamnionitis, clinical diagnosis; Histologic evidence of placental infection; Amniotic fluid foul; Maternal sepsis; Bladder or kidney infection.
OR = ad/bc
OR = (10x367)/(11x36)
OR = 9.3
Should these valid, potentially important results of a critical appraisal about a harmful exposure change the treatment of your patient?
The permanently disabling outcome of your patient cannot be reversed; however, the strong association between maternal infection and congenital CP provides an impetus for future research aimed at preventing and treating intrauterine inflammation.