Table 2.

Summary of quality and strength of evidence for metals and neural tube defects.

	Mn	Pb	Cd	Hg	As
Quality factor
Downgrade factors
Risk of bias across studies	$-1$	$-1$	$-1$	$-1$	$-1$
Imprecision	0	0	0	0	0
Publication bias	0	0	0	0	0
Upgrade factors
Large magnitude of effect	1	0	1	1	0
Dose response	1	1	1	1	0
Confounding minimizes effect	0	0	0	0	0
Overall quality of evidence	1	0	1	1	$-1$
Strength considerations
Quality of body of evidence	High	Moderate	High	High	Low
Direction of effect	Increase	Increase	Decrease	Increase	Null
Confidence in estimates of association: “Is it likely or unlikely that a new study would change the trend/pattern observed in the high quality literature at the moment?”	Likely	Likely	Likely	Likely	Likely
Other compelling attributes of the data that may influence certainty	There are three studies that demonstrate a monotonic dose response. If you remove the study using hair as the exposure, the studies are very consistent.	None	Although one study did demonstrate a monotonic dose response, this is not consistent across studies.	There are three studies that demonstrate a monotonic dose response.	None
Overall strength of evidence (“sufficient,” “limited,” “inadequate,” or “evidence of lack of effect”)	Limited	Inadequate	Inadequate	Limited	Inadequate

Note: decrease, increasing exposure levels/decreasing risk; high, sum of quality factors is $\ge 1$; increase, increasing exposure levels/increasing risk; low, sum of quality factors is $\le -1$; moderate, sum of quality factors is 0.