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Table 3 Characteristics of included cohort studies examining the association between childhood adversity and child clinical outcomes

From: Systematic review of pediatric health outcomes associated with childhood adversity

First Author (year, setting) Sample description Exposuresa Outcomes Findings (95% CI)
Armitage (2009, USA) [56] 18 children aged 2 weeks, followed to age 6 months Maternal depression, assessed at enrollment or within 2 weeks postpartum Average sleep time in 24 hours, sleep distribution (nocturnal vs. day), nocturnal sleep latency, sleep efficiency (awakening from sleep), and number of daytime sleep episodes, assessed at 2 and 24 weeks Maternal depression was not associated with significant differences in average sleep time at 2 or 24 weeks, P < .13, but was associated with significantly shorter nocturnal sleep, P = .007, more awakenings during the night, P < .0001, longer nocturnal sleep latency, P < .0005, lower sleep efficiency, P < .0009, and more daytime sleep episodes of a shorter average duration, P < .0001
Ashman (2002, USA) [33] 72 children aged 14 months, followed to age 7–8 years Maternal depression (assessed retrospectively when child was aged 14 and 24 months, and 3.5, 4.5, 6.5, and 7–8 years) Salivary cortisol levels at age 7–8 years Maternal depression was nonsignificantly associated with salivary cortisol levels and diurnal rhythm of cortisol
Boynton-Jarrett (2010, USA) [46] Birth cohort, followed to age 60 months (N = 1595) Maternal intimate partner violence (IPV; physical, sexual, and restrictive abuse), categorized into early IPV (reported at baseline and/or the 12-month assessment only); late IPV (reported at the 36- and/or 60-month assessment only); or chronic IPV (reported both at baseline and/or the 12-month assessment and at the 36- and/or 60-month assessment) Obesity status at age 60 months Early and late maternal IPV were associated with a borderline, nonsignificant increase in risk for obesity, OR = 1.12 (0.67–1.85) and OR = 1.25 (0.88–1.77), respectively; maternal chronic IPV was associated with a significantly higher risk for obesity, OR = 1.80 (1.24–2.61); analyses stratified by sex indicated a significantly increased risk for obesity only among females exposed to maternal chronic IPV, adjusted OR = 2.21 (1.30–3.75), as compared with males, OR = 1.66 (0.94–2.93)
Caserta (2008, USA) [38] 169 children aged 5–10 years, followed for 3 years Parental psychiatric symptoms (including depression, anxiety, and psychoticism), assessed at the beginning of each 1-year period Number of illnesses and febrile illnesses in the 1 year following assessments 1, 3, and 5 Parental psychiatric symptoms were associated with a significantly increased rate of illness , RR = 1.40 (1.06–1.85), P = .02, as well as febrile illness, RR = 1.77 (1.00–3.13), P = .05
   Parental psychiatric symptoms in the previous month, ascertained at 7 assessments in 6-month intervals Natural killer cell function at each of the 7 assessments Parental psychiatric symptoms were associated with significantly enhanced natural killer cell function, P < .01
Copeland (2014, USA) [40] 3 cohorts of children aged 9, 11, and 13 years at risk for psychiatric problems, followed to age 21 years (N = 1420) Bullying in the 3 months prior to each assessment between ages 9 and 16 years (up to 9 waves) C-reactive protein (CRP) levels at each assessment between ages 9 and 16 years Bullying was not significantly associated with CRP levels when adjusted for either CPR-related covariates, P = .22, or bullying-related covariates, P = .10
Dreger (2010, Canada) [30] 315 children with asthma and 188 children without asthma, followed to age 7–10 years Maternal distress (at least 1 physician diagnosis of a depressive or anxiety disorder or at least 1 prescription for antidepressant, anxiolytic, or hypnotic medication), categorized into postnatal (first year only), late (2–7 years of age), or recurrent distress (first year and 2–4 and/or 5–7 years) Serum cortisol levels at age 7–10 years Postnatal and recurrent maternal distress were significantly associated with higher cortisol levels, P = .007 and .006, respectively, but late distress was not, P = .112; the interaction between asthma diagnosis and recurrent distress was significantly associated with lower cortisol levels, P = .012, in children with asthma, whereas postnatal and late distress were not, P = .666 and .345, respectively; among children without asthma, cortisol levels were 46%, 26%, and 11% higher in children exposed to postnatal distress, recurrent distress, and late distress, respectively, P < .05; among children with asthma, cortisol levels were 33% higher and 13% lower in children exposed to postnatal distress and recurrent distress, respectively, P < .05 (the predicted change for late distress was near 0%)
Essex (2002, USA) [31] 282 children aged 1 month, followed to age 4.5 years Clinically significant maternal depression in infancy (ages 1, 4, and 12 months), at age 4.5 years, or in both periods Salivary cortisol levels at age 4.5 years Maternal depression in both periods was associated with marginally significant, higher cortisol levels, P = .09, in comparison with no exposure or exposure at age 4.5 years; the association for exposure in infancy was not significant
Flaherty (2009, USA) [53] 805 children aged 4 or 6 years from 5 study sites, followed to age 12 years Number of adversities during the first 12 years of child's life: maltreatment (psychological maltreatment, physical abuse, sexual abuse, neglect) and household dysfunction (caregiver substance use/alcohol abuse, depressive symptoms, being treated violently; and criminal behavior in household), assessed at ages 4, 6, 8, and 12 years Somatic complaints at age 12 years (headaches, nausea, dizziness, tiredness, eye problems, aches, skin problems, stomach problems, vomiting, nightmares, and constipation) 5 or more adversities were not significantly associated with somatic complaints reported by child, OR = 1.87 (0.65–5.35), P = .24, but were significantly associated with somatic complaints reported by caregiver, OR = 4.26 (1.17–15.5), P = .03, and by either child or caregiver, OR = 2.72 (1.37–5.42), P = .01; with the exception of 3/4 adversities reported by either child or caregiver, OR = 2.38 (1.02–5.00), P = .04, fewer than 5 or more adversities reported by any source were not significantly associated with somatic complaints
   Number of adversities during the first 6 years of child's life (assessed at ages 4 and 6 years) and during the second 6 years (assessed at ages 8 and 12 years): maltreatment (psychological maltreatment, physical abuse, sexual abuse, and neglect) and household dysfunction (caregiver substance use/alcohol abuse, depressive symptoms, being treated violently; and criminal behavior in household) Somatic complaints at age 12 years (headaches, nausea, dizziness, tiredness, eye problems, aches, skin problems, stomach problems, vomiting, nightmares, and constipation) Adversity, particularly in the second 6 years of life, was associated with an increased risks of somatic complaints, but with differential effects by number of adversities and source of reporting: 5 or more adversities during the first 6 years of life were not significantly associated with child's report of somatic complaints, but were significantly associated with caregiver's report, OR = 3.31 (1.08–10.1), P = .04, and with either child's or caregiver's report, OR = 2.48 (1.05–5.87), P = .04; 5 or more adversities during the second 6 years of life were significantly associated with caregiver's report, OR = 3.37 (1.14–10.0), P = .03, but not with child's report of somatic complaints, OR = 0.70 (0.14–3.54), P = .67, or with either child's or caregiver's report, OR = 1.90 (0.73–4.96), P = .19
Flaherty (2013, USA) [54] 933 children aged 4 or 6 years from 5 study sites, followed to age 14 years Number of adversities during ages 0–6 years, 6–12 years, and 13–14 years: maltreatment (psychological maltreatment, physical abuse, sexual abuse, and neglect) and household dysfunction (caregiver’s substance use/alcohol abuse, depressive symptoms, being treated violently; and criminal behavior in household) Somatic concerns at age 14 years (headaches, nausea, dizziness, tiredness, eye problems, aches, skin problems, stomach problems, vomiting, nightmares, and constipation) Adversities across all ages had a graded relationship with somatic concerns: the ORs for somatic concerns were 4.19 (0.50–34.90), 8.91 (1.15–68.83), and 9.25 (1.25–68.23) for 1, 2, and =>3 adversities, respectively; for children experiencing adversities during ages 0–6 years, the ORs for somatic concerns were 1.90 (0.81–4.47), 1.29 (0.52–3.24), and 2.12 (0.90–5.00) for 1, 2, and =>3 adversities, respectively; for children experiencing adversities during ages 6–12 years, the ORs were 1.50 (0.74–3.02), 1. 46 (0.71–3.01), and 1.08 (0.51–2.31) for 1, 2, and =>3 adversities, respectively; for children experiencing adversities during ages 13–14 years, the ORs were 1.67 (0.92–3.03), 2.27 (1.13–4.59), and 3.47 (1.61–7.50) for 1, 2, and =>3 adversities, respectively
Frohlich (2011, Germany) [49] 95 children aged 7–15 years, followed for 24 months Maternal depression, assessed at baseline Success vs. failure in weight reduction between assessment at baseline and assessment at 24 months Psychosocial variables (family adversity index, maternal depression, and maternal attachment style) as a group were significantly predictive of weight reduction, P < .031, and maternal depression was the best predictor, P < .003
   Maternal depression, assessed at baseline Weight change (BMI) between assessment at 12 months and assessment at 24 months Psychosocial variables (family adversity index, maternal depression, and maternal attachment style) as a group were significantly predictive of weight change, P < .027, but maternal depression was not the best predictor, P = ns
Hairston (2011, USA) [57] Children of 83 mothers with a history of child abuse and PTSD, 38 mothers with a history of child abuse but no PTSD, and 63 mothers with no history of child abuse or PTSD, followed from either 14–28 weeks gestation or 6–8 weeks postpartum to age 18 months Maternal PTSD, assessed at intake and at age 4 months Infant sleep at age 4 months (number and duration of awakenings per night in the past week, wake after sleep onset) Maternal PTSD had a borderline, nonsignificant association with wake after sleep onset, P = .081, and a nonsignificant association with number and duration of awakenings per night in the past week
Halligan (2004, UK) [32] 48 children of mothers with postnatal depression and 39 children of nondepressed mothers, followed from age 2 months to 13 years Maternal postnatal depression, assessed at age 2 months 8:00 am salivary cortisol levels at age 13 years Maternal postnatal depression was significantly associated with 8:00 am cortisol levels over and above other factors (mean cortisol, P < .05; cortisol variability, P < .01)
Kozyrskyj (2008, Canada) [52] Birth cohort, followed to age 7 years (N = 13907) Maternal distress (physician visits, hospitalizations, or prescriptions for depression or anxiety), categorized into postpartum, short-term (at least 1 episode during year 1 and years 1 to 5 of child’s life), or long-term distress (from child’s birth to age 7 years (at least 1 episode during year 1, years 1 to 5, and years 5 to 7) Asthma at age 7 years (at least 2 physician visits for asthma, 1 asthma hospitalization, or 2 prescriptions for any asthma drug in the year after the child’s seventh birthday) Postpartum distress and short-term distress were not associated with a significant increase in risk of asthma, OR = 1.05 (0.79–1.41) and OR = 1.00 (0.72–1.37), respectively, but long-term distress was, OR = 1.25 (1.01–1.55)
Lange (2011, Puerto Rico) [51] 339 sets of twins, followed from birth to age 3 years (N = 678) Maternal depressive symptoms; paternal PTSD, antisocial behavior, and depression; parental depression(number of parents with depression), all within the first year of child's life Asthma symptoms in the previous 4 weeks and asthma hospitalizations in the previous year, both assessed at age 1 year Paternal PTSD, OR = 1.08 (1.03–1.14), P = .003, antisocial behavior, OR = 1.09 (1.04–1.15), P < .001, and depression, OR = 9.95 (1.38–71.59), P = .02, as well as maternal depressive symptoms, OR = 1.13 (1.02–1.25), P = .02, and parental depression, OR = 1.70 (1.14–2.53), P = .01, were all associated with a significant increase in risk of recent asthma symptoms; maternal depressive symptoms were associated with a borderline, nonsignificant increase in risk for asthma hospitalizations, OR = 1.14 (0.98–1.33), P = .09; no other exposure was significantly associated with hospitalizations
   Maternal depressive symptoms; paternal PTSD, antisocial behavior, and depression; parental depression (number of parents with depression), all within the first year of child's life Unplanned clinic or emergency department visit for asthma, use of oral steroids for asthma, asthma hospitalizations, and asthma diagnosis in the previous year, all assessed at age 3 years None of the exposures was significantly associated with unplanned clinic or emergency department visit; only maternal depressive symptoms were associated with a significant increase in risk of asthma diagnosis, OR = 1.13 (1.01–1.27), P = .03, and a borderline, nonsignificant increase in risk of asthma hospitalizations, OR = 1.16 (1.00–1.36), P = .05; paternal depression was associated with a borderline, nonsignificant increase in risk for use of oral steroids, OR = 3.03 (0.84–10.97), P = .09; parental depression was associated with a borderline, nonsignificant increase in risk of asthma hospitalizations, OR = 1.86 (0.98–3.56), P = .06
Lanier (2010, USA) [50]b 3845 maltreated children and 2417 nonmaltreated children (matched on birth year, region of residence) from families receiving public assistance, followed from birth to age 22 years Substantiated or unsubstantiated maltreatment report (neglect, abuse) prior to age 12 years First hospital treatment for asthma episode prior to age 18 years, but after maltreatment report Maltreatment was associated with a significantly increased risk for first hospital treatment for asthma, HR = 1.73 (1.47–2.04), P < .001
   Substantiated or unsubstantiated maltreatment report (neglect, abuse) prior to age 12 years First hospital treatment for a nonasthma cardio-respiratory disease episode (e.g. chronic pharyngitis) prior to age 18 years, but after maltreatment report Maltreatment was associated with a significantly increased risk for first hospital treatment for nonasthma cardio-respiratory disease, HR = 2.07 (1.87–2.29), P < .001
   Substantiated or unsubstantiated maltreatment report (neglect, abuse) prior to age 12 years First hospital treatment for an infection (e.g. mycosis) prior to age 18 years, but after maltreatment report Maltreatment was associated with a significantly increased risk for first hospital treatment for an infection, HR = 2.09 (1.85–2.36), P < .001
Lynch (2015, USA) [41] 93 maltreated children aged 4 years from an urban area and 93 nonmaltreated children of the same age from families receiving public assistance (demographically matched by gender, ethnicity, number of adults in the home, and family history of public assistance), followed to age 9 years Documented physical neglect, physical abuse, sexual abuse, or emotional maltreatment prior to age 4 years; living in neighborhood characterized by violent crime (rape, homicide, aggravated assault, and robbery) at age 4 years Change in respiratory sinus arrhythmia (RSA) at age 9 years Maltreatment status and neighborhood crime were not significantly associated with RSA, P = .66 and .20, respectively; the interaction between cognitive challenge, maltreatment, and neighborhood crime was significantly associated with change in RSA, P = .01; the interaction between cognitive challenge, GABRA6 genotype, maltreatment, and neighborhood crime was significantly associated with change in RSA, P = .003
Margolin (2010, USA) [55] 103 children aged 9–10 years, followed for 3 years Parent-to-youth aggression, marital physical aggression, and community violence in the previous 12 months, assessed across 3 waves approximately 1 year apart Somatic complaints assessed at wave 3 Parent-to-youth aggression was significantly associated with a slightly increased risk of experiencing somatic symptoms, RR = 1.03 (1.01–1.05), P < .05, whereas marital physical aggression and community violence were not, RR = 1.01 and 1.03 (0.99–1.03 and 0.99–1.08), respectively; analysis of cumulative violence exposure indicated that each unit increase on the cumulative violence exposure index (0–9) was associated with an increased risk of experiencing somatic symptoms, RR = 1.12 (1.003–1.24), P < .05
Morris (2015, UK) [45] Birth cohort, followed to age 17 years (N = 7021) Parental separation or death by age 4 years BMI trajectory from age 4 to 17 years Parental separation was associated with a BMI that was 1.1% (0.2–2.0) higher at age 4 years, but this diminished by age 9 years (1.1%, 0–2.2) and further by age 17 years (0.5%, -1.3 to 2.2); parental death was associated with lower BMI throughout childhood and adolescence (insufficient power to reliably determine associations)
Noll (2007, USA) [48] 84 sexually abused females aged 6–16 years and 89 nonabused females (matched on age, residing zip codes, race/ethnicity, predisclosure SES, family constellation, and other nonsexual trauma), followed for approximately 7 years Substantiated sexual abuse within 6 months of participation Obesity status in childhood/early adolescence (age 6–14 years) and in middle/late adolescence (age 15–19 years) Substantiated sexual abuse was associated with a nonsignificant increase in risk for obesity during childhood/early adolescence, OR = 1.25 (0.05–3.00), P = .52, and middle/late adolescence, OR = 2.03 (0.54–4.60), P = .09
Ouellet-Morin (2011, UK) [35] 30 pairs of 5-year-old identical twins, followed to age 12 years (N = 60), with co-twin never having experienced bullying victimization Bullying victimization experienced at least occasionally, assessed at ages 7, 10, and 12 years Salivary cortisol levels at age 12 years Bullying victimization was significantly associated with a blunted cortisol response after a stress test, P = .02
Ouellet-Morin (2011, UK) [36] 95 pairs of 5-year-old identical twins, followed to age 12 years (N = 190), with co-twin never having experienced childhood maltreatment or frequent bullying Childhood maltreatment (assessed at ages 5, 7, 10, and 12 years) or frequent bullying victimization (assessed at ages 7, 10, and 12 years) Salivary cortisol levels at age 12 years Maltreatment or frequent bullying was significantly associated with a blunted cortisol response following a stress test, P = .005
Peckins (2015, USA) [34] 303 maltreated children aged 9–12 years and 151 nonmaltreated children of the same age and residing in the same 10 zip codes, followed for 4.5 years New substantiated referral for any type of maltreatment (sexual abuse, physical abuse, emotional abuse, or neglect) in the month prior to recruitment Cortisol reactivity patterns at waves 2–4 Maltreatment was significantly associated with a blunted cortisol profile rather than a moderate or elevated profile at waves 2 and 3, but not wave 4 (moderate: Wave 2 OR = 0.44, P < .05; Wave 3 OR = 0.41, P < .01; Wave 4 OR = 0.87, P = ns; elevated: Wave 2 OR = 0.14, P < .01; Wave 3 OR = 0.31, P < .01; Wave 4 OR = 0.83, P = ns)
Rigterink (2010, USA) [42] 38 children aged 4–6 years, followed to age 9 years Domestic violence by husband or wife in the previous 12 months, assessed at ages 5 and 9 years Emotion regulation abilities at ages 5 and 9 years, measured via baseline vagal tone Husband’s report of own and wife’s aggression (HDV) at age 5 years was associated with a significantly smaller increase in baseline vagal tone from the first to the second assessment, P = .01, even when controlling for HDV at age 9 years, P = .01; wife’s report of own and husband’s aggression at age 5 years was not significantly associated with alterations in baseline vagal tone, P = .57
Schmeer (2012, USA) [44] Birth cohort from an urban area, followed to age 5 years (N = 1538) Parental separation or divorce between ages 3 and 5 years Change in overweight/obesity status between ages 3 and 5 years Parental separation or divorce was associated with a significantly higher risk of becoming overweight/obese, RRR = 1.83 (SE = 0.55), p < .05
Shalev (2013, UK) [43] 118 pairs of 5-year-old identical twins, followed to age 12 years (N = 236); twin pairs with no violence exposure were matched on sex and SES status Violence exposure (domestic violence, frequent bullying, and physical maltreatment) in one or both twins between ages 5 and 10 years Telomere length at age 10 years 2 or more types of violence exposure were significantly associated with accelerated telomere erosion, P = .015, even when controlling for poor health and asthma, P = .028
Shenk (2015, USA) [47] 266 maltreated females aged 14-17 years and 128 nonmaltreated females (matched on age, race, family income, and single-parent household), followed for 4 years or until age 19 years Substantiated maltreatment (physical abuse, sexual abuse, or physical neglect) within 12 months prior to recruitment Obesity (BMI score >=30), assessed annually Maltreatment was associated with a significantly increased risk for obesity, RR = 1.47 (1.03–2.08), P = .034
Wolf (2008, Canada) [39] 83 children aged 9–18 years, 50 with asthma and 33 medically healthy, followed for 6 months Parental depressive symptoms during the past week, assessed at baseline Interleukin-4 (IL-4) production at baseline and follow-up Parental depressive symptoms were not associated with changes over time in IL-4 production, P = .19, in either children with asthma or healthy children
   Parental depressive symptoms during the past week, assessed at baseline Eosinophil cationic protein concentrations (ECP) at baseline and follow-up Parental depressive symptoms were associated with increases in children's ECP levels over time, P = .046, in both children with asthma and healthy children
Wolke (2014, UK) [58] Birth cohort, followed to age 12 years (N = 6796) Repeated or frequent bullying victimization in the past 6 months, assessed at age 8 years, age 10 years, or both Parasomnias at age 12 years (nightmares, night terrors, and sleepwalking) Bullying victimization at age 8 years was associated with a significant increase in risk of nightmares, OR = 1.23 (1.05–1.44), night terrors, OR = 1.39 (1.10–1.75), and any parasomnias, OR = 1.28 (1.11–1.47), but not sleepwalking, OR = 1.22 (0.99–1.50); bullying victimization at age 10 years was associated with a significant increase in risk of nightmares, OR = 1.62 (1.35–1.94), night terrors, OR = 1.53 (1.18–1.98), sleepwalking, OR = 1.40 (1.11–1.76), and any parasomnias, OR = 1.75 (1.48–2.07); bullying victimization at both ages 8 and 10 years was associated with a significant increase in risk of nightmares, OR = 1.82 (1.46–2.27), night terrors, OR = 2.01 (1.48–2.74), sleepwalking, OR = 1.71 (1.31–2.25), and any type of parasomnia, OR = 2.10 (1.72–2.58)
Wyman (2007, USA) [37] 158 children aged 5–10 years, followed for 18 months Parental psychiatric symptoms (including depression and anxiety), ascertained at 4 assessments across 18 months Number of illnesses and febrile illnesses in the 1 year following the second assessment Parental psychiatric symptoms were associated with a significantly increased rate of illness, RR = 1.49 (1.12–1.97), P = .01, but not febrile illness, RR = 1.60 (0.94–2.73), P = .08
    Natural killer cell function at the fourth assessment and at all 4 assessments Parental psychiatric symptoms were not significantly associated with increased natural killer cell function at the fourth assessment, P = .13, but were significantly associated with higher natural killer cell function at all 4 assessments, P = .01
  1. Studies were prospective cohort unless otherwise noted. 95% CI 95% confidence interval, BMI body mass index, HR hazard ratio, PTSD posttraumatic stress disorder, OR odds ratio, RR risk ratio, RRR relative risk ratio, SES socioeconomic status
  2. aThe nonexposed comparison represents the absence of the examined exposure
  3. bRetrospective cohort study