Table 1.
A summary of the relationships we assessed between chemical or stress or both exposures and the comparisons group.
Table 2.
The inclusion and exclusion criteria used to determine study eligibility for inclusion in the systematic review.
Table 3.
A summary of the human stress exposure variables assigned to the “low” and “high” exposure groups.
A detailed description of the exposures can be found in the original studies which are listed by citation number.
Fig 1.
A flow diagram of the progression from the literature search to inclusion in the systematic review (n = 69 studies) and quantitative analysis (n = 39).
Table 4.
Chemical and stress exposures assessed included 69 human and animal studies on developmental outcomes from combined exposure.
The sum of the number of studies for either exogenous chemical or psychosocial stress is greater than 69 because some studies reported more than one stressor variable. Numbers in parentheses indicate the number of studies which were included in the quantitative review. Under the stress/stressor exposure, “multiple stressors” refers to a random schedule administered in two rat studies consisting of exposure to each of the following stressors: mouse cage, food & water deprivation, empty water bottle, damp bedding, cage tilting, noise, crowding, alone in cage, alone in cage, no bedding and new partner [92, 93].
Fig 2.
The number of studies reporting on each outcome category.
The vertical gray bar represents the cut-off for the number of human studies required to take the outcome forward to a quantitative analysis.
Fig 3.
A heat-map of the risk of bias for human and non-human studies on growth outcomes and combined chemical and psychosocial stress.
Fig 4.
Impact of stress and chemicals on fetal development.
The impact in humans of stress alone (green squares), chemicals in low stress (blue triangles) versus high stress (red diamonds) on birth weight (A) and odds of low birth weight (C) and their interaction (B and D respectively). Horizontal error bars represent 95% confidence intervals. Asterisks’ and letters denote the same population measured for more than one chemical or stress exposure.
Fig 5.
Impact of stress and chemicals on birth weight.
(A) and (C) Birth weight effects in humans of chemicals in low stress (blue triangles) versus high stress (red diamonds) groups; and (B) and (D) the interaction between stress and chemicals on relative reduction in birth weight. Horizontal error bars represent 95% confidence intervals. Asterisks’ represent the same population measured for more than one chemical or stress exposure.
Table 5.
A summary of the effects of combined exposure to high stress and high chemical in comparison to either one alone in 10 human studies.
To conclude that combined exposure is significantly associated with lower fetal growth than either exposure alone (high stress, low chemical & low stress, high chemical) we required a significant difference (denoted by “+”) between combined exposure and both individual exposures. Non-significant differences are denoted by “-“. Superscripts represent samples of the same population stratified by two chemical exposures.
Fig 6.
Meta-analysis of the effect of the low SES and smoking in high and low SES groups on odds of low birth weight (LBW) in humans.
(A) The effects of low SES alone (high stress; green squares) or smoking in high SES (low stress; blue triangles) and low SES groups (high stress; red diamond) are shown for each of four studies and their pooled random-effects estimate at the bottom of the figure; horizontal error bars represent 95% CI, symbol sizes represents the log of the precision of the estimate (i.e. weight in the meta-analysis). (B) the random-effects pooled interaction effect between low and high SES in smokers and non-smokers. Vertical error bars represent 95% CI and the horizontal grey bar represent the line of no effect.
Fig 7.
The effect of prenatal aluminum and restraint stress in rats and mice.
The impact of stress alone (green squares), chemicals in low stress (blue triangles) versus high stress (red diamonds) on postnatal weight at various times of assessment in rats (A) and mice (B) and their interaction (C and D respectively). Horizontal error bars represent 95% confidence intervals; the vertical grey bar represents the line of no effects. Letters denote the same stress control group used for multiple doses at the same time point. Figure legend is the same as Fig 4. Abbreviation: IP, intraperitoneal.