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A prospective cohort study to investigate parental stress and child health in low-income Chinese families: protocol paper

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      IntroductionChronic stress has adverse effects on health. Adults and children from low-income families are subject to multiple sources of stress. Existing literature about economic hardship mostly focuses on either adults or children but not both. Moreover, there is limited knowledge on the relationship between parental generalised stress and child health problems. This study aims to explore the bidirectional relationship between parental stress and child health in Chinese low-income families and to identify other modifiable factors influencing this relationship.Methods and analysisThis prospective cohort study will sample 254 low-income parent–child pairs and follow them up for 24 months with assessments at three time points (baseline, 12 and 24 months) on parental stress, health-related quality of life (HRQOL) and child health and behaviour using both subjective measures and objective physiological parameters. This study will collect data using standardised measures on HRQOL and behaviours of children as well as on HRQOL, mental health and stress levels of parents along with physiological tests of allostatic load and telomere length. The mediating or moderating effect of family harmony, parenting style and neighbourhood conditions will also be assessed. Data will be analysed using latent growth modelling and cross-lagged path analysis modelling to examine the bidirectional effect of parental stress and child health over time. Mediation and moderation analysis will also be conducted to examine the mechanism by which the variables relate.Ethics and disseminationThis study was approved by the institutional review board of the University of Hong Kong—the Hospital Authority Hong Kong West Cluster, reference no: UW 16-415. The study findings will be disseminated through peer-reviewed publications and international conferences.Trial registration numberNCT03185273; Pre-results.

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      The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories.

      The psychometric properties of the Depression Anxiety Stress Scales (DASS) were evaluated in a normal sample of N = 717 who were also administered the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). The DASS was shown to possess satisfactory psychometric properties, and the factor structure was substantiated both by exploratory and confirmatory factor analysis. In comparison to the BDI and BAI, the DASS scales showed greater separation in factor loadings. The DASS Anxiety scale correlated 0.81 with the BAI, and the DASS Depression scale correlated 0.74 with the BDI. Factor analyses suggested that the BDI differs from the DASS Depression scale primarily in that the BDI includes items such as weight loss, insomnia, somatic preoccupation and irritability, which fail to discriminate between depression and other affective states. The factor structure of the combined BDI and BAI items was virtually identical to that reported by Beck for a sample of diagnosed depressed and anxious patients, supporting the view that these clinical states are more severe expressions of the same states that may be discerned in normals. Implications of the results for the conceptualisation of depression, anxiety and tension/stress are considered, and the utility of the DASS scales in discriminating between these constructs is discussed.
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        The determinants of parenting: a process model.

         J Belsky (1984)
        This essay is based on the assumption that a long-neglected topic of socialization, the determinants of individual differences in parental functioning, is illuminated by research on the etiology of child maltreatment. Three domains of determinants are identified (personal psychological resources of parents, characteristics of the child, and contextual sources of stress and support), and a process model of competent parental functioning is offered on the basis of the analysis. The model presumes that parental functioning is multiply determined, that sources of contextual stress and support can directly affect parenting or indirectly affect parenting by first influencing individual psychological well-being, that personality influences contextual support/stress, which feeds back to shape parenting, and that, in order of importance, the personal psychological resources of the parent are more effective in buffering the parent-child relation from stress than are contextual sources of support, which are themselves more effective than characteristics of the child.
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          The Long-Term Health Consequences of Child Physical Abuse, Emotional Abuse, and Neglect: A Systematic Review and Meta-Analysis

          Introduction Child maltreatment is defined as all forms of physical and/or emotional ill-treatment, sexual abuse, neglect or negligent treatment, or commercial or other exploitation of children that results in actual or potential harm to a child's health, survival, development, or dignity in the context of a relationship of responsibility, trust, or power [1]. Four types of maltreatment are commonly recognised: sexual abuse, physical abuse, emotional abuse (also referred to as psychological abuse), and neglect (Table 1). 10.1371/journal.pmed.1001349.t001 Table 1 Definition of child maltreatment. Type of Maltreatment Description Physical abuse Physical abuse of a child is defined as the intentional use of physical force against a child that results in—or has a high likelihood of resulting in—harm for the child's health, survival, development, or dignity. This includes hitting, beating, kicking, shaking, biting, strangling, scalding, burning, poisoning, and suffocating. Much physical violence against children in the home is inflicted with the object of punishing. Sexual abuse Sexual abuse is defined as the involvement of a child in sexual activity that he or she does not fully comprehend, is unable to give informed consent to, or for which the child is not developmentally prepared, or else that violates the laws or social taboos of society. Children can be sexually abused by both adults and other children who are—by virtue of their age or stage of development—in a position of responsibility, trust, or power over the victim. Emotional and psychological abuse Emotional and psychological abuse involves both isolated incidents, as well as a pattern of failure over time on the part of a parent or caregiver to provide a developmentally appropriate and supportive environment. Acts in this category may have a high probability of damaging the child's physical or mental health, or his/her physical, mental, spiritual, moral, or social development. Abuse of this type includes the following: the restriction of movement; patterns of belittling, blaming, threatening, frightening, discriminating against, or ridiculing; and other non-physical forms of rejection or hostile treatment. Neglect Neglect includes both isolated incidents, as well as a pattern of failure over time on the part of a parent or other family member to provide for the development and well-being of the child—where the parent is in a position to do so—in one or more of the following areas: health, education, emotional development, nutrition, shelter, and safe living conditions. The parents of neglected children are not necessarily poor. Adapted from Butchart et al. [5]. There is a great deal of uncertainty around estimates of the frequency and severity of child maltreatment worldwide. Furthermore, much violence against children remains largely hidden and unreported because of fear and stigma and the societal acceptance of this type of violence [2]. Globally, prevalence of reported child sexual abuse varies from 2% to 62%, with some of this variation explained by a number of methodological factors including definition of abuse, method of data collection, and type of sample assessed [3]. In high-income countries, the annual prevalence of physical abuse ranges from 4% to 16%, and approximately 10% of children are neglected or emotionally abused [4]. Eighty percent of this maltreatment is perpetrated by parents or parental guardians [4], and poverty, mental health problems, low educational achievement, alcohol and drug misuse, having been maltreated oneself as a child, and family breakdown or violence between other family members are all important risk factors for parents abusing their children [5]. There is growing recognition that different forms of interpersonal violence have a large public health impact [6]. In children, the consequences of violence can vary widely. Physical injuries and, in extreme cases, death are direct consequences. World Health Organization (WHO) estimates of child homicide suggest that infants and very young children are at greatest risk, with rates for the 0- to 4-y age group about double those for 5- to 14-y-olds as a result of their dependency and vulnerability [5]. However, in the majority of non-fatal cases, the direct physical injury causes less morbidity to the child than the long-term impact of the violence on the child's neurological, cognitive, and emotional development and overall health [5]. Child maltreatment is a major public health problem, yet a lack of understanding of its serious lifelong consequences and of the cost and burden on society has hampered investment in prevention policies and programs. In order to effectively respond to the problem, the WHO 2006 report on prevention of child maltreatment [5] recommended expanding the scientific evidence base for the magnitude, consequences, and preventability of child maltreatment. The relationship between child sexual abuse and adverse psychological consequences in adults is well established [7]–[9], and in the WHO comparative risk assessment study, Andrews and colleagues [3] carried out a systematic review and meta-analysis summarising the evidence of a relationship between child sexual abuse and subsequent mental disorders. This review is currently being updated in the new iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study, aiming to provide global estimates of attributable burden for 1990 to 2010 [10], but other forms of child maltreatment have been omitted. Exposure to non-sexual child maltreatment, namely, physical abuse, emotional abuse, and neglect, is associated with increased risk of a wide range of psychological and behavioural problems, including depression, alcohol abuse, anxiety, and suicidal behaviour, and with increased risk of HIV and herpes simplex virus type 2 (HSV2) infection [11]–[14]. However, the long-term health consequences of these other forms of child maltreatment have not been systematically examined. To address these omissions, clarify the present state of empirical research, and enable the quantification of the health impacts of child neglect, physical abuse, and emotional abuse at the population level using burden of disease and comparative risk assessment methodology, we conducted a systematic review of the scientific literature and quantitative meta-analyses. To the best of our knowledge, this is the first meta-analysis to summarise the evidence for associations between individual types of non-sexual child maltreatment and outcomes related to mental and physical health. Methods General recommendations from the PRISMA 2009 revision [15], with regard to processing and reporting of results, were taken into account (Text S1). The meta-analysis conforms to the guidelines outlined by the Meta-analysis of Observational Studies in Epidemiology recommendations [16]. Methods and inclusion criteria were specified in advance and documented in a review protocol (Text S2). Inclusion and Exclusion Criteria This systematic review and meta-analysis incorporated retrospective and prospective cohort, cross-sectional, and case-control studies meeting the following inclusion criteria: (1) the study reported original, empirical research published in a peer-reviewed journal, (2) the study considered non-sexual child maltreatment as a potential risk factor for loss of health, and (3) the related health outcomes or behavioural risk factors were among those listed in the Global Burden of Diseases, Injuries, and Risk Factors Study [10]. Studies reporting exposure only to combined types of abuse were excluded. Included studies reported odds ratios (ORs) and confidence intervals (CIs) comparing those exposed and not exposed by type of abuse or, alternatively, provided the information from which effect sizes and confidence intervals could be calculated (Text S2). Search Strategy Three electronic databases (Medline, EMBASE, and PsycINFO up to 26 June 2012) were searched using full text and Medical Subject Headings (MeSH) terms to identify studies reporting an association between non-sexual child maltreatment and health outcomes (Text S2). Truncation of terms was used to capture variation in terminology. The search was not restricted to the English language, nor restricted by any other means. Searches were conducted using synonyms and combinations of the following search terms: “maltreatment”, “physical abuse”, “psychological abuse”, and “emotional abuse”, and automatic explosion of the terms “child abuse” and “child neglect”. The search was also not restricted to any particular health outcome. Instead, the broader terms “risk”, “adverse effect”, “consequences”, “harm”, and “association” were used to encompass all studies that investigated any adverse outcome of non-sexual child maltreatment. In addition, reference lists of selected studies were screened for any other relevant study, and additional studies were also identified through contact with study authors. Articles in languages other than English were translated. Data Collection and Quality Assessment The full-text article of any study that appeared to meet the inclusion criteria was retrieved for closer examination. Two reviewers (R. E. N. and M. B.) independently assessed articles for eligibility. Disagreements were resolved by consensus. The coders were not masked to the journals or authors of the studies reviewed. A standardised data extraction sheet was developed, and data retrieved included publication details, country where study was conducted, methodological characteristics such as sample size and study design, exposure and outcome measures, type of abuse, and health outcomes (Text S2). The data extraction sheet included a quality assessment tool (Table 2) to rate the methodological quality of each study based on the Newcastle-Ottawa Scale for assessing the quality of observational studies [17]. Quality assessment was completed independently by two reviewers, and disagreements were resolved by discussion. One author was contacted for further information. 10.1371/journal.pmed.1001349.t002 Table 2 Assessment of study quality. Quality Criteria Quality Score Representativeness of the population Population-based representative = 1 Not representative, selected group, volunteers, or no description = 0 Ascertainment of exposure to child abuse and neglect Data on child maltreatment collected prospectively = 1 Data on child maltreatment collected retrospectively = 0 Selection of the non-exposed cohort/controls Drawn from the same population = 1 Drawn from a different source or no description = 0 Assessment of child abuse and neglect Secure official record (court-substantiated abuse) = 1 Self-reported or structured interview or self-administered questionnaire or no description = 0 Case definition for child abuse and neglect Uses WHO definitions of child maltreatment or court-substantiated abuse or Barnett-Cicchetti Maltreatment Classification System = 1 Marks and bruises (physical abuse), questions from scales (e.g., Childhood Trauma Questionnaire), published surveys, or own system = 0 Assessment of outcome Use of structured clinical interview for DSM-III/IV (DIS, DISC, CIDI) (mental health); direct physical measurements or blood tests (physical health) = 1 Questions from published health surveys/screening instruments, own system, symptoms described, no system, not specified, or self-reported = 0 Adequacy of follow-up of cohorts (where relevant) or response rate Completeness good (≥80%), with description of those lost to follow-up = 1 Completeness poor ( 30 kg/m2 Obesity Prospective/cohort Abused youth Bonomi [99] 2008 US 3,568 100% Physical abuse Telephone interview Self-reported (CES-D for depression/presence-of-symptom surveys) Depressive disorders, back pain, headache/migraine, diarrhoea Retrospective/cross-sectional Insured women Boynton-Jarrett [100] 2011 US 68,505 100% Physical abuse Self-administered questionnaire with items from CTQ and CTS Hysterectomy/ultrasound confirmation Uterine leiomyoma Retrospective/cohort Pre-menopausal nurses Bremner [101] 1993 US 66 0% Physical abuse Self-reported, using CSTE SCID for DSM-III-R PTSD Retrospective/case-control Viet Nam combat veterans Brezo [27] 2008 Canada 1,684 47.2% Physical abuse Interview using CTS DIS-III-R, DISC-II, SSI Suicide ideation/attempt Retrospective/cohort Population-based Brown [102] 1999 US 639 47.7% Physical abuse and neglect Combined official records and self-reported abuse and neglect DISC-I Major depression, dysthymia, depressive disorders, self-inflicted injuries Retrospective/cohort Population-based Chapman [40] 2004 US 9,460 54% Physical and emotional abuse Self-administered ACE questionnairea Some questions from CES-D Depressive disorders Retrospective/cohort HMO members Chartier [103] 2009 Canada 8,116 50.2% Physical abuse Self-administered questionnaire CIDI structured face-to-face interview (alcohol abuse) and self-administered questionnaire Smoking, alcohol abuse, low exercise, obesity, risky sexual behaviour Retrospective/cross-sectional Population-based Cohen [104] 2001 US 664 50.3% Physical abuse and neglect Official records of abuse and neglect and self-reported abuse and neglect DISC-I and symptom scales Depressive disorders, anxiety, childhood behavioural disorders, substance abuse Retrospective/cohort Population-based Coid [105] 2003 UK 1,207 100% Beaten by parent Self-administered questionnaire Self-reported symptom scale (anxiety/depression), CAGE (alcohol problems) Anxiety, depression, PTSD, suicide attempt, self-inflicted injuries, drug use, alcohol problems Retrospective/cross-sectional Primary care patients Conroy [106] 2009 Australia 1,313 43.5% Physical and emotional abuse, and neglect Structured face-to-face interview History of opioid pharmacotherapy Opioid dependence Retrospective/case-control Not representative Cougle [73] 2010 US 4,141 56% Physical abuse Structured face-to-face interview CIDI Anxiety disorders Retrospective/cross-sectional Population-based Courtney [107] 2008 US 92 81.5% Emotional abuse Self-administered questionnaire using CTQ BDI-II Depressive symptoms Retrospective/cohort Adolescent primary care patients Dong [108] 2004 US 17,337 54% Physical and emotional abuse, and neglect Self-administered ACE questionnairea Self-reported Ischaemic heart disease Retrospective/cohort HMO members Draper [109] 2008 Australia 22,251 58.7% Physical abuse Self-administered questionnaire—own questions Self-reported Current smoking, alcohol problems, diabetes, cardiovascular disease, COPD, cancer Retrospective/cross-sectional Population-based Dube [110] 2001 US 17,337 54% Physical and emotional abuse Self-administered ACE questionnairea Self-reported Self-inflicted injuries Retrospective/cohort HMO members Dube [111] 2003 US 8,613 54% Physical and emotional abuse, and neglect Self-administered ACE questionnairea Self-reported Drug use Retrospective/cohort HMO members Dube [112] 2006 US 8,417 54% Physical and emotional abuse, and neglect Self-administered ACE questionnairea Self-reported Ever use of alcohol, early alcohol initiation (≤14 y) Retrospective/cohort HMO members Duke [28] 2010 US 136,549 50.2% Physical abuse Self-reported based on ACE questionnaire Self-reported Suicide ideation/attempt, self-harm Retrospective/cross-sectional Population-based Duncan [57] 1996 US 4,008 100% Physical assault Telephone interview ICI SCID for DSM-III-R Major depressive episode, PTSD, drug use Retrospective/cross-sectional Population-based Egeland [113] 2002 US 140 Not given Physical abuse and emotional neglect Official records (physical abuse); project staff assessment (neglect) K-SADS Conduct disorders Prospective/cohort High-risk youth Enns [114] 2006 Netherlands 7,076 Not given Physical and emotional abuse, and neglect Face-to-face interviews—standardised questions CIDI Self-inflicted injuries Retrospective/cohort Population-based Evans-Campbell [115] 2006 US 112 100% Physical abuse Face-to-face interviews—own questions Self-reported HIV risk behaviour Retrospective/cross-sectional Representative sample of American Indian/Alaska Native Fergusson [41] 2008 New Zealand 1,265 Not given Physical abuse/punishment Face-to-face interviews—own questions CIDI Major depression, mental disorders, substance abuse, self-inflicted injuries Retrospective/cohort Population-based Fergusson [116] 2008 New Zealand 1,265 Not given Physical abuse/punishment Face-to-face interviews—own questions CIDI Illicit drug use/dependence Retrospective/cohort Population-based Flisher [117] 1996 South Africa 7,340 54% Physical abuse/injury Self-administered questionnaire—own questions Self-reported Suicide attempt Retrospective/cross-sectional Students Fuemmeler [74] 2009 US 15,197 Not given Physical abuse and neglect Self-reported Height and weight measurements, BMI>30 kg/m2 Obesity Retrospective/cohort Population-based Fujiwara [118] 2011 Japan 1,722 49.4% Physical abuse and neglect Modified version of CTS CIDI Anxiety disorders, intermittent explosive disorder, substance abuse Retrospective/cross-sectional Population-based Fuller-Thomson [62] 2009 Canada 13,092 51.6% Physical abuse Self-reported Self-reported Cancer Retrospective/cross-sectional Population-based Fuller-Thomson [119] 2009 Canada 11,108 51.4% Physical abuse Self-reported Self-reported Osteoarthritis Retrospective/cross-sectional Population-based Fuller-Thomson [63] 2010 Canada 13,093 51.6% Physical abuse Self-reported Self-reported Heart disease Retrospective/cross-sectional Population-based Fuller-Thomson [61] 2010 Canada 13,089 56.1% Physical abuse Self-reported Self-reported Migraine Retrospective/cross-sectional Population-based Fuller-Thomson [120] 2011 Canada 13,069 56.1% Physical abuse Self-reported Self-reported Peptic ulcer Retrospective/cross-sectional Population-based Gal [121] 2011 Israel 4,859 50.8% Physical abuse Face-to-face interviews CIDI Anxiety disorders Retrospective/cross-sectional Population-based Goodwin [122] 2002 US 3,032 Not given Physical and emotional abuse Self-administered questionnaire using CTS Self-reported Type 2 diabetes Retrospective/cross-sectional Population-based Goodwin [65] 2003 US 3,032 Not given Physical abuse Self-administered questionnaire using CTS CIDI for mental disorders and self-reported for physical Migraine headache, ulcers Retrospective/cross-sectional Population-based Goodwin [68] 2003 US 5,877 Not given Physical abuse Self-administered questionnaire using CTS CIDI for mental disorders and self-reported for physical Major depression, alcohol dependence, hypertension Retrospective/cross-sectional Population-based Goodwin [66] 2004 US 5,877 Not given Physical abuse and neglect Self-administered questionnaire—own questions CIDI for mental disorders and self-reported for physical Self-reported arthritis, hypertension, ulcer, neurological disorders, diabetes Retrospective/cross-sectional Population-based Goodwin [64] 2005 NZ 983 Not given Physical abuse/punishment Face-to-face interviews—own questions CIDI Panic disorders Retrospective/cohort Population-based Goodwin [67] 2012 US 3,032 Not given Physical abuse Self-administered questionnaire Self-reported Respiratory disease Retrospective/cross-sectional Population-based Gould [123] 1994 US 292 71% Physical and emotional abuse Self-administered questionnaire Self-reported Suicide attempt Retrospective/cross-sectional Convenience sample, primary care Green [124] 2010 US 5,692 42% Physical abuse and neglect Face-to-face interviews with modified form of the CTS CIDI Anxiety, substance use, disruptive behaviour Retrospective/cross-sectional Population-based Griffin [75] 2010 US 290 100% Physical abuse Face-to-face interviews Self-reported Alcohol problem Retrospective/cross-sectional Non-probability sample Gunstad [125] 2006 Australia, US, UK, and the Netherlands 696 51.30% Emotional abuse Self-administered modified Child Abuse and Trauma Scale Self-reported height and weight BMI, obesity Retrospective/cross-sectional Not representative Hamburger [126] 2008 US 3,559 52% Physical abuse Self-administered questionnaire Self-reported Alcohol use/problems Retrospective/cross-sectional Students in high-risk community Hanson [127] 2001 US 4,008 100% Physical abuse (aggravated assault) Face-to-face interviews—own questions SCID for DSM-III-R Major depressive episode, PTSD Retrospective/cross-sectional Population-based Haydon [76] 2011 US 8,922 55.5% Physical abuse and neglect Computer-assisted self-interview Test-identified current STD Current STDs Retrospective/cohort Population-based Hillis [128] 2000 US 9,323 54.30% Physical and emotional abuse Self-administered ACE questionnairea Self-reported STDs Retrospective/cohort HMO members Hovens [22] 2010 Netherlands 1,931 Not given Physical abuse, emotional abuse, emotional neglect Face-to-face interviews CIDI Current depressive disorders, anxiety disorders Retrospective/cross-sectional Population-based Huang [129] 2011 US 4,882 49.3% Physical abuse and neglect Interview using items consistent with CTS and CTQ Self-reported Drug use Retrospective/cohort Population-based Jeon [130] 2009 South Korea 6,986 37.5% Physical and emotional abuse Self-administered questionnaire ETISR-SF Self-reported Suicide ideation/attempt Retrospective/cross-sectional Medical students Jewkes [13] 2010 South Africa 2,782 (1,367 men and 1,415 women) 50.9% Physical punishment, emotional abuse, emotional neglect Face-to-face interviews with modified form of the CTQ Self-reported using CES-D, blood test for HIV and HSV2 HIV and HSV2 infection, depressive disorders, alcohol/drug abuse, self-inflicted injuries Retrospective/cross-sectional for psycho-social outcome measures, longitudinal analysis for risk of HIV and HSV2 infection Volunteer sample Jirapramukpitak [77] 2005 Thailand 202 58% Physical and emotional abuse Self-administered questionnaire using CTS Lay-administered CIS-R for mental disorders, AUDIT for alcohol Drug use, alcohol problems Retrospective/cross-sectional Population-based Johnson [23] 2002 US 782 49% Physical neglect, harsh maternal punishment Maternal behaviour assessed by interviewer DISC-I Eating disorders, obesity Prospective/cohort Population-based Juang [131] 2004 Taiwan 116 67% Neglect Neglect assessed by teacher interviews (GFES) By neurologist using S-L criteria Chronic daily headache Case-control Convenience sample of students Jun [132] 2008 US 68,505 100% Physical abuse Self-administered questionnaire with items from CTQ Self-reported Adolescent smoking Retrospective/cohort Nurses Kaplan [133] 1998 US 99 abused and 99 non-abused adolescents 50% Physical abuse Official records SCID for DSM-III-R Depressive disorder, childhood behavioural disorders, drug use, cigarette use Retrospective/cross-sectional Abused youth Kerr [134] 2009 Canada 560 34% Physical abuse Interviewer-administered questionnaire using CTQ Self-reported Injection drug use Retrospective/cohort Street youth Lau [135] 2003 China 489 38.2% Physical abuse and punishment Face-to-face interview—own questionnaire Achenbach Child Behavior Checklist Substance use, smoking, self-inflicted injuries Retrospective/cross-sectional Population-based Levitan [136] 2003 Canada 6,597 61% Physical abuse Self-administered questionnaire—own questions CIDI Depressive disorders, anxiety, comorbid depressed and anxious Retrospective/cross-sectional Population-based Libby [69] 2004 US 3,084 (1,446 from southwest area and 1,638 from northern plains area) 57.3% in southwest; 51.75% in northern plains Physical abuse Face-to-face interviews—own questions CIDI Alcohol use/dependence, drug use/dependence Retrospective/cross-sectional Population-based Libby [137] 2005 US 3,084 (1,446 from southwest area and 1,638 from northern plains area) 57.3% in southwest; 51.75% in northern plains Physical abuse Face-to-face interviews—own questions CIDI Depressive disorders, anxiety, PTSD Retrospective/cross-sectional Population-based Lissau [138] 1994 Denmark 756 Not given Neglect School medical service answered a questionnaire about the hygiene of the child Height and weight measurements Obesity Prospective/cohort Population-based Logan [139] 2009 US 1,484 Not given Physical abuse Self-administered questionnaire Self-reported Suicide ideation/attempt, drug use Retrospective/cross-sectional High-risk youth Macmillan [70] 2001 Canada 7,016 52.4% Physical abuse Self-administered questionnaire using CTS CIDI Major depression, anxiety, alcohol abuse/dependence, drug abuse/dependence Retrospective/cross-sectional Population-based Mullen [29] 1996 New Zealand 497 100% Emotional abuse Face-to-face interviews—PBI PSE Eating disorder, suicide attempt, depression Retrospective/cross-sectional Population-based Nichols [71] 2004 US 722 100% Physical abuse Self-administered questionnaire—own questions derived from CTS Self-reported Smoking Retrospective/cohort Population-based Nikulina [140] 2011 US 1,005 47.3% Neglect Official record Diagnostic interview-DIS-III-R PTSD, major depression Prospective/cohort Abused youth Perkins [141] 2002 US 100,236 100% Physical abuse Self-administered questionnaire—own questions ABQ Bulimia (purging two or more times per week) Retrospective/cross-sectional Students, not representative Pillai [142] 2009 India 3,662 51.4% Physical abuse Face-to-face interviews Self-reported Suicide ideation/attempt Retrospective/cross-sectional Population-based Ramiro [143] 2010 Philippines 1,068 50.1% Physical and emotional abuse, and neglect Self-administered ACE questionnairea Self-reported Current smoking, alcohol, drug use, risky sexual behaviour, suicide attempt Retrospective/cross-sectional Population-based Rich-Edwards [78] 2010 US 67,853 100% Physical abuse Self-administered questionnaire with items from CTQ Self-reported Type 2 diabetes Retrospective/cohort Nurses Riley [144] 2010 US 68,505 100% Physical abuse Self-administered questionnaire with items from CTQ Self-reported Hypertension Retrospective/cohort Nurses Ritchie [145] 2009 France 942 58.1% Physical punishment and emotional abuse Self-reported MINI, CES-D, anti-depressant treatment Depressive disorders Retrospective/cross-sectional Elderly (65+ y) Roberts [32] 2008 US 11,394 Not given Physical abuse Self-administered questionnaire—own questions Self-reported smoking, CES-D for depression Ever regular smoking Retrospective/cross-sectional Population-based Rohde [146] 2008 US 4,641 100% Physical abuse Telephone interview based on CTQ Self-reported height and weight, depression Obesity, depression Retrospective/cross-sectional Health plan members Romans [147] 2002 New Zealand 477 100% Physical abuse Face-to-face interview—own questions Self-reported Headache/migraine, asthma, diabetes, CVD Retrospective/cross-sectional Population-based Rubino [148] 2009 Italy 788 56.5% for controls Physical and emotional abuse Self-reported SCID for DSM-IV Schizophrenia, depression Retrospective/case-control Voluntary inpatients Schneider [79] 2007 US 3,936 100% Physical and emotional abuse Self-administered questionnaire—TSS for physical abuse and CTS for emotional abuse CDC Healthy Days Measure, PC-PTSD Anxiety, PTSD Retrospective/cross-sectional Population-based Schoemaker [42] 2002 Netherlands 1,987 100% Physical and emotional abuse, and neglect Face-to-face interviews—own questions CIDI Bulimia nervosa Retrospective/cohort (uses cross-sectional data) Population-based Scott [149] 2008 Americas, Europe, Japan 18,303 52.7% Physical abuse and neglect Face-to-face interviews Self-reported Asthma Retrospective/cross-sectional Population-based Scott [150] 2011 Americas, Europe, Japan 18,303 52.7% Physical abuse and neglect Face-to-face interviews Self-reported Heart disease, diabetes, chronic spinal pain, headache Retrospective/cross-sectional Population-based Sidhartha [151] 2006 India 1,205 40% Physical abuse and neglect Self-administered questionnaire—AISS Self-reported Suicidal behaviour Retrospective/cross-sectional School students Silverman [30] 1996 US 375 50% Physical abuse Face-to-face interviews—own questions YSR and CDI (age 15 y), DIS-III-R (age 21 y) Major depression, PTSD, alcohol abuse/dependence, drug abuse/dependence, self-inflicted injuries Retrospective/cohort Population-based Smith [152] 2005 US 884 27.10% Physical abuse and neglect (adolescent) Official records (using Barnett-Cicchetti Maltreatment Classification System) Self-reported Drug use Prospective/cohort High-risk youth Springer [153] 2007 US 2,051 55.6% Physical abuse Self-administered questionnaire based on CTS Self-reported using CES-D (mental health), self-reported (physical) Depressive disorders, asthma, high blood pressure, allergies Retrospective/cohort Population-based Springer [154] 2009 US 3,317 52% Physical abuse Self-administered questionnaire based on CTS Self-reported Bronchitis/emphysema, ulcers Retrospective/cohort Population-based Stein [155] 1996 Canada 122 cases 124 controls 42.4% for controls Physical abuse Semistructured interview SCID for DSM-IV Anxiety disorders Retrospective/case-control Population-based Stein [156] 2010 Americas, Europe, Japan 18,630 52.8% Physical abuse and neglect Face-to-face interviews Self-reported Hypertension Retrospective/cross-sectional Population-based Straus [56] 1994 US 2,149 Not given Physical punishment (adolescent) Face-to-face interviews—CTS Four items from PERI Life Events Scale Depressive symptoms, self-inflicted injuries, alcohol abuse Retrospective/cross-sectional Population-based Strine [72] 2012 US 7,279 54% Physical and emotional abuse, and neglect Self-administered ACE questionnairea Self-reported Alcohol problems Retrospective/cohort HMO members Thomas [157] 2008 UK 9,310 Not given Physical and emotional abuse, and neglect self-administered questionnaire based on ACE questionnairea (retrospective); local authority health visitor interviewed parents at child ages 7, 11, and 16 y (prospective) Measured weight, height, and waist circumference, blood glucose levels Obesity, type 2 diabetes Prospective and retrospective/cohort Population-based Thompson [158] 2002 US 8,000 100% Physical victimisation Telephone interview—CTS Self-reported Drug use, alcohol use Retrospective/cross-sectional Population-based Thompson [159] 2004 US 16,000 50% Physical abuse Telephone interview—CTS Self-reported Drug use, alcohol use Retrospective/cross-sectional Population-based Thompson [160] 2012 US 740 52.6% Physical and emotional abuse, and neglect Official records (neglect); self-reported (physical/emotional) Self-reported Suicide ideation Retrospective/cohort High-risk youth Timko [161] 2008 US 6,942 100% Emotional abuse Self-reported Self-reported Binge drinking Retrospective/cross-sectional Population-based Trent [162] 2007 US 5,697 46.6% Physical abuse Self-administered questionnaire using CTS MAST Alcohol use, binge drinking Retrospective/cross-sectional Military personnel, not representative Turner [163] 2003 Australia 9,512 100% Physical and emotional abuse Self-administered questionnaire—own questions Self-reported Illicit drug use Retrospective/cohort Population-based Vander Weg [164] 2011 US 10,277 51.3% Physical assault and emotional abuse Telephone survey Self-reported Lifetime, current smoking Retrospective/cross-sectional Arkansas and Louisiana residents Von Korff [165] 2009 Americas, Europe, Japan 18,309 52.5% Physical abuse and neglect Face-to-face interviews Self-reported Arthritis Retrospective/cross-sectional Population-based Wainwright [166] 2002 UK 3,491 55.2% Physical abuse Self-administered questionnaire Structured self-assessment Major depression Retrospective/cohort Population-based Wan [167] 2010 Hong Kong 2,754 44.3% Physical abuse Self-administered questionnaire adapted from CTQ Self-reported+YSR Suicide ideation/attempt Retrospective/cross-sectional Population-based Welch [24] 1996 UK 306 100% Physical abuse investigator-based interview using own questionnaire EDE diagnostic interview Bulimia nervosa Retrospective/case-control Population-based Widom [168] 1995 US 1,068 49% Physical abuse and neglect Official record Diagnostic interview—DIS-III-R Alcoholism Prospective/cohort Abused youth Widom [169] 1996 US 1,187 49% Physical abuse and neglect Official record Self-report interview Risky sexual behaviour Prospective/cohort Abused youth Widom [170] 1999 US 1,196 48.7% Physical abuse and neglect Official record and self-reported using own questionnaire based on CTS Diagnostic interview—DIS-III-R Drug abuse/dependence Prospective and retrospective/cohort Abused youth Widom [171] 1999 US 1,196 49% Physical abuse and neglect Official record Diagnostic interview—DIS-III-R PTSD Prospective/cohort Abused youth Widom [43] 2007 US 1,196 48.7% Physical abuse and neglect Official record Diagnostic interview—DIS-III-R Major depression Prospective/cohort Abused youth Widom [33] 2012 US 754 52.9% Physical abuse and neglect Official record Mantoux test, blood tests, blood pressure measurements, height and weight measurements, eye and hearing (Weber and Rinne) tests, oral examination Tuberculosis, anaemia, malnutrition, hepatitis C, HIV, syphilis, hearing problems, vision loss, hypertension Prospective/cohort Abused youth Williamson [31] 2002 US 13,177 51% Physical and emotional abuse Self-administered ACE questionnairea Height and weight measurements Obesity (BMI≥30 kg/m2) Retrospective/cohort HMO members Wilson [172] 2008 US 630 55.2% Physical abuse and neglect Official record Diagnostic interview—DIS-III-R, blood tests HIV-positive status, risky sexual behaviours Prospective/cohort Abused youth Wilson [173] 2009 US 754 52.9% Physical abuse and neglect Official record Self-reported STDs Prospective/cohort Abused youth Wilson [174] 2011 US 800 52.9% Physical abuse and neglect Official record Self-reported Risky sexual behaviour Prospective/cohort Abused youth Wise [175] 2011 US 35,728 100% Physical abuse Mail questionnaire adapted from CTS Self-reported Breast cancer Retrospective/cohort Convenience sample of African-American women Yates [25] 2008 US 164 49% Physical abuse and physical neglect Official records (physical abuse); project staff assessment (neglect) SIBQ Self-inflicted injury Prospective/cohort High-risk youth Young [176] 2006 US 41,482 0% Physical and emotional abuse, and neglect Self-administered questionnaire—own questions based on ACE, CTS, and CTQ AUDIT-C questionnaire Risky drinking Retrospective/cross-sectional Military personnel a Some ACE questionnaire categories were defined using items adapted from other questionnaires. These were the Conflict Tactics Scale (physical abuse, witnessing interparental violence, and emotional abuse) and the Childhood Trauma Questionnaire (emotional and physical neglect). ABQ, Search Institute's Profiles of Student Life: Attitude and Behavior Questionnaire [177]; AISS, Adjustment Inventory for School Students [178]; AUDADIS-IV, Alcohol Use Disorders and Associated Disabilities Interview Schedule IV [179]; AUDIT, Alcohol Use Disorders Identification Test [180]; AUDIT-C, Alcohol Use Disorders Identification Test–alcohol consumption questions [181]; BDI-II, Beck Depression Inventory II [182]; CAGE, CAGE questionnaire [183]; CDC Healthy Days Measure, Centers for Disease Control and Prevention's Healthy Days Measure [184]; CDI, Children's Depression Inventory [185]; CES-D, Center for Epidemiologic Studies Depression Scale [186]; CIDI, Composite International Diagnostic Interview (a standardised diagnostic instrument) [187]; CIS-R, Clinical Interview Schedule–Revised [188]; COPD, chronic obstructive pulmonary disease; CSTE, Checklist of Stressful and Traumatic Events [189]; CTQ, Childhood Trauma Questionnaire [190]; CTS, Conflict Tactics Scale [191]; CVD, cardiovascular disease; DISC-I, National Institute of Mental Health Diagnostic Interview Schedule for Children I [192]; DISC-II, National Institute of Mental Health Diagnostic Interview Schedule for Children II [193]; DIS-III-R, National Institute of Mental Health Diagnostic Interview Schedule IIIR [194]; EDE, Eating Disorder Examination (a standardised investigator-based interview that operationalizes DSM-III-R criteria) [195]; ETISR-SF, Early Trauma Inventory Self Report–Short Form [196]; GFES, Global Family Environment Scale [197]; HMO, health maintenance organization; ICI, Incident Classification Interview [198]; K-SADS, Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children [199]; MAST, Michigan Alcoholism Screening Test [200]; MINI, Mini International Neuropsychiatric Interview [201]; PBI, Parental Bonding Instrument [202]; PC-PTSD, Primary Care PTSD Screen [203]; PERI Life Events Scale, Psychiatric Epidemiological Research Instrument Life Events Scale [204],[205]; PSE, Present State Examination [206]; SSI, Scale for Suicide Ideation [207]; SIBQ, Self-Injurious Behavior Questionnaire [208]; S-L criteria, Silberstein-Lipton criteria [209]; SCID for DSM-III-R, Structured Clinical Interview for DSM-III-R [210]; SCID for DSM-IV, Structured Clinical Interview for DSM-IV [211]; TSS, Traumatic Stress Schedule [212]; YSR, Youth Self-Report [213]. 10.1371/journal.pmed.1001349.t004 Table 4 Summary of primary meta-analyses on mental health consequences of child non-sexual maltreatment. Category Health Outcome and Type of Maltreatment Number of Data Points Pooled OR 95% CI Lower Bound 95% CI Upper Bound Cochran's Q I 2 (%) Test for Heterogeneity (p-Value) Mental disorders Depressive disorders Physical abuse 36 1.54 1.16 2.04 273.81 87.22 <0.01 Emotional abuse 9 3.06 2.43 3.85 21.99 63.63 <0.01 Neglect 14 2.11 1.61 2.77 45.33 71.32 <0.01 Anxiety disorders Physical abuse 59 1.51 1.27 1.79 592.99 90.22 <0.01 Emotional abuse 4 3.21 2.05 5.03 43.17 93.05 <0.01 Neglect 8 1.82 1.51 2.20 11.24 37.74 0.13 Eating disorders Physical abuse 6 2.58 1.17 5.70 43.66 88.55 <0.01 Emotional abuse 2 2.56 1.41 4.65 4.40 77.27 0.04 Neglect 2 2.99 1.53 5.83 2.14 53.33 0.14 Childhood behavioural/conduct disorders Physical abuse 12 2.29 1.76 2.97 15.83 30.53 0.15 Neglect 6 2.01 1.42 2.84 2.02 0.00 0.85 Substance abuse/alcohol and drug use Substance abuse Physical abuse 9 1.61 1.21 2.16 12.18 26.11 0.14 Emotional abuse 1 2.00 0.60 6.30 Not pooled Not pooled Not pooled Neglect 2 1.29 0.67 2.47 2.39 58.20 0.12 Alcohol use Physical abuse: any alcohol use 44 1.30 1.10 1.55 207.27 79.25 <0.01 Physical abuse: non-problem drinking 11 1.47 1.17 1.85 32.87 69.57 <0.01 Physical abuse: problem drinking 33 1.26 1.03 1.55 153.20 79.11 <0.01 Emotional abuse: any alcohol use 10 1.27 1.11 1.46 13.26 32.12 0.15 Emotional abuse: non-problem drinking 2 1.29 0.88 1.90 4.28 76.62 0.04 Emotional abuse: problem drinking 8 1.27 1.11 1.46 8.58 18.38 0.28 Neglect: any alcohol use 15 1.14 0.92 1.39 100.32 86.04 <0.01 Neglect: non-problem drinking 4 1.50 1.15 1.96 15.14 80.18 <0.01 Neglect: problem drinking 11 1.09 0.87 1.35 50.38 80.15 <0.01 Drug use Physical abuse 43 1.92 1.67 2.20 136.06 69.13 <0.01 Emotional abuse 8 1.41 1.11 1.79 30.51 77.06 <0.01 Neglect 41 1.36 1.21 1.54 180.81 77.88 <0.01 Suicidal behaviour Physical abuse 58 3.00 2.07 4.33 2,392.41 97.62 <0.01 Emotional abuse 11 3.08 2.42 3.93 32.36 69.10 <0.01 Neglect 15 1.85 1.25 2.73 19.43 27.94 0.15 10.1371/journal.pmed.1001349.t005 Table 5 Summary of meta-analyses on sexually transmitted infections and risky sexual behaviour as consequences of child non-sexual maltreatment. Health Outcome and Type of Maltreatment Number of Data Points Pooled OR 95% CI Lower Bound 95% CI Upper Bound Cochran's Q I 2 (%) Test for Heterogeneity (p-Value) STIs/risky sexual behaviour Physical abuse 33 1.78 1.50 2.10 49.12 34.85 0.03 Emotional abuse 5 1.75 1.49 2.04 2.96 0.00 0.57 Neglect 30 1.57 1.39 1.78 50.14 42.16 0.01 HIV infection Physical abuse 4 2.51 1.16 5.42 1.09 0.00 0.78 Emotional abuse 2 1.82 1.34 2.47 0.21 0.00 0.65 Neglect 2 2.50 0.77 8.15 0.29 0.00 0.59 Other STIs Physical abuse 12 1.53 1.13 2.07 17.27 7.65 0.10 Emotional abuse 2 1.56 1.26 1.93 0.76 0.00 0.38 Neglect 14 1.26 1.08 1.46 7.96 0.00 0.85 Risky sexual behaviour Physical abuse 17 1.95 1.58 2.40 23.37 31.54 0.10 Emotional abuse 1 2.10 1.50 3.00 Not pooled Not pooled Not pooled Neglect 14 1.80 1.52 2.13 27.74 53.14 0.01 10.1371/journal.pmed.1001349.t006 Table 6 Summary of primary meta-analyses on chronic diseases, lifestyle risk factors, and other physical health outcomes associated with exposure to child non-sexual maltreatment. Category Health Outcome and Type of Maltreatment Number of Data Points Pooled OR 95% CI Lower Bound 95% CI Upper Bound Cochran's Q I 2 (%) Test for Heterogeneity (p-Value) Chronic diseases Cardiovascular diseases Stroke Physical abuse 3 1.76 0.56 5.51 0.78 0.00 0.68 Neglect 2 3.00 0.99 9.10 0.57 0.00 0.45 Ischaemic heart disease Physical abuse 1 1.50 1.40 1.90 Not pooled Not pooled Not pooled Emotional abuse 1 1.70 1.50 1.90 Not pooled Not pooled Not pooled Neglect 2 1.35 1.17 1.55 0.28 0.00 0.60 Any cardiovascular disease Physical abuse 4 1.57 1.11 2.22 6.78 55.75 0.08 Neglect 1 1.37 0.99 1.91 Not pooled Not pooled Not pooled Type 2 diabetes Physical abuse 11 1.01 0.79 1.29 41.26 75.76 <0.01 Emotional abuse 3 1.19 0.74 1.93 10.45 80.86 0.01 Neglect 14 1.11 0.97 1.26 16.37 20.57 0.23 Respiratory diseases Asthma Physical abuse 2 1.74 1.15 2.62 0.14 0.00 0.71 Asthma (hazard ratio) Physical abuse 1 1.92 1.32 2.81 Not pooled Not pooled Not pooled Neglect 1 1.02 0.70 1.49 Not pooled Not pooled Not pooled Bronchitis/emphysema Physical abuse 3 1.39 1.19 1.62 0.91 0.00 0.63 Any respiratory disease Physical abuse (sometimes) 1 1.42 0.91 2.22 Not pooled Not pooled Not pooled Physical abuse (frequent) 1 1.09 0.78 1.52 Not pooled Not pooled Not pooled Other physical health outcomes Ulcers Physical abuse 7 1.71 1.44 2.02 5.69 0.00 0.46 Neglect 2 1.26 0.56 2.83 0.44 0.00 0.51 Headache/migraine Physical abuse 6 1.42 1.24 1.62 5.00 0.04 0.54 Emotional abuse 1 1.60 1.40 1.70 Not pooled Not pooled Not pooled Neglect 1 3.11 0.31 30.80 Not pooled Not pooled Not pooled Headache/migraine (hazard ratio) Physical abuse 1 1.64 1.44 1.88 Not pooled Not pooled Not pooled Neglect 1 1.21 1.02 1.43 Not pooled Not pooled Not pooled Neurological disorders Physical abuse 3 2.19 1.30 3.69 0.55 0.00 0.76 Neglect 3 2.07 0.99 4.32 0.08 0.00 0.96 Cancer Physical abuse 2 1.26 0.97 1.65 1.43 30.28 0.23 Arthritis Physical abuse 4 1.52 1.28 1.80 1.30 0.00 0.94 Neglect 2 1.70 1.06 2.73 0.06 0.00 1.00 Arthritis (hazard ratio) Physical abuse 1 1.42 1.22 1.66 Not pooled Not pooled Not pooled Neglect 1 1.29 1.08 1.55 Not pooled Not pooled Not pooled Lifestyle risk factors Tobacco smoking Physical abuse 19 1.55 1.09 2.21 161.75 88.87 <0.01 Emotional abuse 6 1.70 1.55 1.87 2.38 0.00 0.79 Neglect 2 1.20 0.98 1.48 0.63 0.00 0.43 Hypertension Physical abuse 6 1.16 0.94 1.44 5.64 11.33 0.34 Neglect 4 1.04 0.78 1.39 1.16 0.00 0.76 Obesity Physical abuse 11 1.32 1.06 1.64 37.54 73.36 <0.01 Emotional abuse 5 1.24 1.13 1.36 6.95 42.48 0.14 Neglect 18 1.07 0.97 1.19 44.68 61.95 <0.01 Low exercise Physical abuse 1 1.04 0.86 1.26 Not pooled Not pooled Not pooled 10.1371/journal.pmed.1001349.t007 Table 7 Summary of review findings on health consequences of child non-sexual maltreatment for disorders where data were insufficient to include in meta-analyses. Health Outcome and Type of Maltreatment OR 95% CI Lower Bound 95% CI Upper Bound Allergy [153] Physical abuse 1.38 1.06 1.78 Anaemia [33] Physical abuse 0.56 0.23 1.34 Neglect 0.59 0.37 0.95 Underweight/malnutrition [33] Physical abuse 3.16 1.53 6.50 Neglect 1.39 0.87 2.21 Hepatitis C [33] Physical abuse 0.99 0.30 3.26 Neglect 1.18 0.59 2.38 Tuberculosis [33] Physical abuse 0.75 0.07 8.58 Neglect 1.18 0.32 4.39 Hearing loss [33] Physical abuse 2.37 0.68 8.26 Neglect 1.72 0.74 4.01 Oral health [33] Physical abuse 0.70 0.37 1.35 Neglect 1.07 0.72 1.59 Vision problems [33] Physical abuse 0.58 0.29 1.17 Neglect 1.17 0.76 1.78 Diarrhoea (prevalence ratio) [99] Physical abuse 1.13 0.81 1.59 Uterine leiomyoma [100] Physical abuse—mild 1.09 1.03 1.15 Physical abuse—moderate 1.10 1.04 1.15 Physical abuse—severe 1.16 1.07 1.25 Back pain (prevalence ratio) [99] Physical abuse 1.03 0.84 1.26 Chronic spinal pain (hazard ratio) [150] Physical abuse 1.61 1.43 1.82 Neglect 1.33 1.15 1.34 Schizophrenia [148] Physical abuse 5.81 2.31 14.63 Emotional abuse 12.24 4.82 31.09 Breast cancer (incidence rate ratio) [175] Physical abuse 1.01 0.88 1.17 Mental Disorders Physically abused (OR = 1.54; 95% CI 1.16–2.04), emotionally abused (OR = 3.06; 95% CI 2.43–3.85), and neglected (OR = 2.11; 95% CI 1.61–2.77) individuals were found to have a higher risk of developing depressive disorders than non-abused individuals (Table 4; Figures S1, S2, S3). The test for heterogeneity was highly significant, with p<0.01 for both abuse types and neglect. Funnel plots indicate the possibility of publication bias for physical abuse, as it appears that some smaller, less precise studies have a greater effect size than the larger studies, and there are no smaller studies to the left (negative) side of the graph, suggesting that some negative studies may never have been published (Figure S4). For physical abuse, emotional abuse, and neglect, OR estimates in males were higher than in females, but the difference was not statistically significant (Table S1). The odds of developing depressive disorders with exposure to physical abuse were greatest in prospective studies. Although the OR point estimate was higher in subgroup analyses of studies where exposure to physical abuse was court-substantiated by official records—which would include the more severe cases of abuse (OR = 2.41; 95% CI 1.32–4.41)—compared with self-reported physical abuse (OR = 1.56; 95% CI 1.11–2.19) and physical punishment (OR = 1.20; 95% CI 0.88–1.61), the 95% CIs were overlapping, and these differences were not statistically significant. There was a stronger association between physical abuse and a diagnosis of major depressive disorder using structured interviews (OR = 1.82; 95% CI 1.44–2.30) than when depressive disorders were diagnosed by symptom scales (OR = 1.52; 95% CI 1.03–2.24), but again these differences were not statistically significant (Table S1). Restricting the physical abuse analysis to studies from high-income countries increased the odds of developing depressive disorders to 1.58 (95% CI 1.18–2.12), but the association was not significant in low-to-middle-income countries (Table S1). However, for neglect in childhood, similar odds of developing depressive disorders were observed in high- and low-to-middle-income countries. Data from two studies suggest a dose–response relationship, with depression more likely with frequent neglect compared with neglect that occurred only sometimes in childhood [13],[22]. A dose–response relationship was also reported for emotional abuse and depressive disorders, but not for physical abuse and depressive disorders (Table S1). Physical abuse (OR = 1.51; 95% CI 1.27–1.79), emotional abuse (OR = 3.21; 95% CI 2.05–5.03), and neglect (OR = 1.82; 95% CI 1.51–2.20) were associated with a significantly increased risk of anxiety disorders (Figures S5, S6, S7, S8). For physical abuse, significant associations were also observed with post-traumatic stress disorder (PTSD) and panic disorder diagnoses (Table S2). A dose–response relationship was observed with physical abuse but not with emotional abuse and neglect [22], with anxiety disorders more likely with frequent physical abuse than with abuse that occurred only sometimes in childhood (Table S2). Physical abuse, emotional abuse, and neglect were also associated with an almost 3-fold increased risk of developing eating disorders (Figures S9, S10, S11, S12), and physical abuse was associated with a 5-fold increased risk of developing bulimia nervosa meeting Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria. Most of the evidence came from retrospective studies, and only one prospective study [23] reported a strong association with neglect in childhood (Table S3). A dose–response relationship was also observed, with bulimia nervosa more likely with more severe and repeated physical abuse [24] (Table S3). Physical abuse and neglect were also associated with a doubling of the odds of childhood behavioural and conduct disorders (Figures S13, S14, S15). With respect to physical abuse, higher odds of developing conduct and childhood behavioural disorders were observed in prospective than in retrospective studies, but differences were not statistically significant. Studies with non-representative samples had significantly increased effect size for the association between physical abuse and childhood behavioural problems and conduct disorder (OR = 5.98; 95% CI 2.73–13.10) compared with population-based studies (OR = 2.02; 95% CI 1.58–2.58) (Table S4). Physical abuse significantly increased the risk of alcohol problem drinking (risky drinking, alcohol abuse/dependence, binge drinking) (OR = 1.26; 95% CI 1.03–1.55) (Figure S16) and non-problem drinking (current or ever alcohol use), but the effect did not persist in prospective studies (Table S5). In a subgroup analysis, physical abuse was also significantly associated with a diagnosis of alcohol abuse/dependence meeting DSM criteria (OR = 1.40; 95% CI 1.21–1.64) (Table S5). Alcohol problem drinking was also associated with emotional abuse (OR = 1.27; 95% CI 1.11–1.46) (Figure S17) but not with neglect in childhood (OR = 1.09; 95% CI 0.87–1.35) (Figure S18). For alcohol problems, there was no evidence of a dose–response relationship with respect to frequency of abuse and neglect (Table S5) [13]. Gender differences were observed, with the effect of physical abuse on alcohol problems stronger among males, and with females at an increased risk of alcohol problem drinking with exposure to neglect in childhood, but with overlapping confidence intervals (Table S5). Publication bias did not appear to play a role in the association between physical abuse and alcohol problem drinking (Figure S19). Although primary analyses suggest an increased risk of drug use associated with physical abuse (OR = 1.92; 95% CI 1.67–2.20), emotional abuse (OR = 1.41; 95% CI 1.11–1.79), and neglect (OR = 1.36; 95% CI 1.21–1.54) (Figures S20, S21, S22, S23), there was only borderline significance in prospective studies, with a stronger consistent association observed in retrospective studies, albeit with overlapping confidence intervals (Table S6). A dose–response relationship between emotional abuse and neglect and drug use was not consistently seen. Physically abused (OR = 3.00; 95% CI 2.07–4.33), emotionally abused (OR = 3.08; 95% CI 2.42–3.93), and neglected (OR = 1.85; 95% CI 1.25–2.73) individuals had a significantly increased risk of suicidal behaviour compared with non-abused individuals (Table 4). These significant associations continued in subgroup analyses by type of suicidal behaviour, with physically abused (OR = 3.40; 95% CI 2.17–5.32), emotionally abused (OR = 3.37; 95% CI 2.44–4.67), and neglected (OR = 1.95; 95% CI 1.13–3.37) individuals at a significantly increased risk of suicide attempt (Figures S24, S25, S26, S27) and suicide ideation (Table S7). There were no prospective studies investigating non-sexual child maltreatment and suicide attempt or ideation. Only one prospective study [25] was found investigating the association between self-inflicted injuries and exposure to physical abuse and neglect. Six studies [13],[26]–[30] presented the results by gender for physical abuse and suicide attempt and ideation, but no statistically significant differences were observed. One study showed that exposure to frequent childhood neglect was more strongly associated with suicidal behaviour than exposure to neglect that occurred sometimes [13] (Table S7). Sexually Transmitted Infections and Risky Sexual Behaviour Physically abused (OR = 1.78; 95% CI 1.50–2.10), emotionally abused (OR = 1.75; 95% CI 1.49–2.04), and neglected (OR = 1.57; 95% CI 1.39–1.78) individuals were found to have a significantly higher risk of sexually transmitted infections (STIs) and/or risky sexual behaviour than non-abused individuals (Table 5; Figures S28, S29, S30, S31). For physical abuse and neglect, the association with STIs and risky sexual behaviour was significant in prospective and retrospective studies (Table S8). HIV infection was about twice as common in physically abused (OR = 2.51; 95% CI 1.16–5.42), emotionally abused (OR = 1.82; 95% CI 1.34–2.47), and neglected (OR = 2.50; 95% CI 0.77–8.15) individuals as in controls, although for neglect the difference did not reach conventional levels of significance, probably because of weak statistical power. Physical abuse was also associated with an increased risk of other STIs (OR = 1.53; 95% CI 1.13–2.07) and risky sexual behaviour (OR = 1.95; 95% CI 1.58–2.40) (Table 5). A dose–response relationship was observed for HIV infection, with a larger effect size reported with more frequent physical and emotional abuse in childhood [13] (Table S8). Chronic Diseases, Lifestyle Risk Factors, and Other Physical Health Outcomes With regard to obesity, a significantly increased risk was observed for physical (OR = 1.32; 95% CI 1.06–1.64) and emotional abuse (OR = 1.24; 95% CI 1.13–1.36) but not for neglect (OR = 1.07; 95% CI 0.97–1.19) in the primary analysis (Figures S32, S33, S34, S35). Subgroup analysis by assessment of outcome indicated that neglect was associated with a higher risk of developing self-reported obesity, but there was no association with obesity defined by waist circumference or body mass index (BMI) measurements (Table S9). In the subgroup analysis by ascertainment of exposure to physical abuse, there was a strong association with obesity in one prospective study, but the magnitude of the effect was reduced in retrospective studies (Table S9). A dose–response relationship between physical and emotional abuse and obesity has been observed [31] (Table S9). Physical (OR = 1.78; 95% CI 1.26–2.52) (Figure S36) and emotional abuse (OR = 1.65; 95% CI 1.46–1.87) (Figure S37) were associated with a significantly increased risk of current smoking, but the association was not significant for neglect in childhood (OR = 1.20; 95% CI 0.98–1.48). One study showed a dose response, with smoking more likely with physical abuse that occurred 3–5 times than with abuse that occurred 1–2 times, but this relationship did not continue into those who had been abused more than six times compared with those who had been abused 3–5 times [32] (Table S10). Forty-two studies investigated the relationship between non-sexual child maltreatment and lifestyle risk factors, chronic diseases, and other physical health outcomes in adulthood. There is suggestive evidence of a significant association between child physical abuse and arthritis, ulcers, and headache/migraine in adulthood. However, for most other outcomes, including type 2 diabetes (Table S11; Figures S39, S40, S41, S42), hypertension, low exercise, cardiovascular diseases, respiratory diseases, neurological disorders, and cancer, these associations were mostly weak and inconsistent, with little adjustment for lifetime confounders. Pooled estimates were statistically significant in only a limited number of cases (Table 6). A recent prospective investigation of a group of individuals with documented histories of child abuse and neglect followed into middle adulthood provides some evidence that child abuse and neglect may increase the risk of a range of directly measured physical health outcomes after controlling for mental health problems, substance use, smoking, and BMI [33] (Table 7). However, there were insufficient studies examining the association between non-sexual child maltreatment and some of these health outcomes, including anaemia, underweight/malnutrition, hepatitis C, tuberculosis, hearing loss, vision loss, oral health, diarrhoea, allergies, uterine leiomyoma, back pain, breast cancer, and schizophrenia, to undergo meta-analysis (Table 7). Discussion To the best of our knowledge, this article presents the first systematic review and meta-analysis of published studies assessing the association between non-sexual child maltreatment and mental and physical health outcomes. We identified 124 studies that examined the association between physical abuse, emotional abuse, and neglect in childhood and various health outcomes. Does Non-Sexual Child Maltreatment Cause Adverse Health Outcomes? Evidence for a causal relationship between non-sexual child maltreatment and health outcomes was evaluated within the Bradford Hill framework on the grounds of the following important criteria: strength and consistency of the association, the temporal relationship of the association, evidence of a biological gradient or dose–response relationship, biological plausibility, and consideration of alternate explanations [34] (Table S12). Temporality Both prospective and retrospective studies consistently showed an association between exposure to child physical abuse, emotional abuse, and neglect and adverse health outcomes. The availability of prospective studies provides conclusive evidence of a temporal relationship between exposure to non-sexual child maltreatment and the later development of mental health outcomes, drug use, and STIs and risky sexual behaviour, as in these studies abuse and neglect preceded the onset of health problems in adulthood. However, only 16 studies were prospective, while the majority of the studies were cross-sectional and relied on adult retrospective report of abuse and neglect in childhood. By definition, these studies cannot prove a temporal relationship between exposure to child maltreatment and the onset of health outcomes. Furthermore, retrospective, self-reported information regarding abuse in childhood may be subject to recall bias, where those with adjustment problems may be more prone to recall or disclose exposure to abuse and neglect. In many cases participants were asked to report on events that would have occurred many years before, and the issue of potentially unreliable recall threatens the validity of the published literature on child maltreatment. At least with respect to child sexual abuse, evidence suggests moderate to good consistency of reports over time [35]. It has also been suggested that biases are probably towards under-reporting rather than over-reporting of abuse [36]. Nevertheless, given that retrospective reports were often the only measure of abuse available, particularly with regard to emotional abuse, we accepted these within the context of the limitations stated. Although the strength of prospective studies includes the temporal ordering of maltreatment and subsequent health outcomes, with an objective measurement of exposure to abuse, these studies are usually conducted in non-representative samples. Official cases of abuse may only detect those who come to professional attention, and this may alter the strength of the association between non-sexual child maltreatment and adult morbidity. These official cases are also generally skewed towards the lower end of the socioeconomic spectrum and may not be generalisable to child abuse and neglect cases that occur in middle- or upper-class children [33]. Those participants who have been identified by child protection agencies as having been exposed to physical abuse or neglect may have received interventions to prevent later pathology. Furthermore, some individuals in the “never maltreated” category may actually have experienced maltreatment, given that child maltreatment tends to be under-reported. The validity of the various study designs to investigate the long-term health consequences of child maltreatment has been a source of ongoing debate [37],[38]. In this meta-analysis we have included prospective and retrospective studies. The subgroup analyses show that with both methodologies there is robust evidence of a significant association between child non-sexual maltreatment and various health outcomes. Strength of the Association Associations between child physical abuse, emotional abuse, and neglect and mental disorders, drug use, and suicidal behaviour have been reported in prospective studies and/or large population-based studies. The strength of the relationship between abuse and mental disorders was generally reduced when the effects of important mediating variables were taken into account. Despite some variability, overall, child physical abuse, emotional abuse, and neglect were found to approximately double the likelihood of adverse mental health outcomes when combined in a meta-analysis. Consistency of the Association As shown in the forest plots of the effects by study, there was strong consistency and agreement in the estimated effect measures across studies, particularly for neglect and physical abuse, although we suspect publication bias for some of the outcomes. Risk estimates were comparable across different types of samples, for both non-representative and representative populations (Tables S1, S2, S3, S4 and S6, S7, S8). The findings persisted across different study designs, samples, and geographic regions investigated. It can be concluded that there is a highly consistent association between child physical abuse, emotional abuse, and neglect and adverse mental health outcomes, drug use, and STIs and risky sexual behaviour. We did not observe evidence of strong consistent associations for alcohol problems, chronic diseases, or lifestyle risk factors. Dose–Response Relationship We found evidence of a dose–response relationship between adverse health outcomes and non-sexual child maltreatment, such that those experiencing more severe abuse or neglect were at greater risk of developing mental disorders than those experiencing less severe maltreatment [39]. In the Chapman et al. [40] study, increasing severity of childhood adversity corresponded with poorer mental health outcomes. Consistent dose–response relationships with repeated, frequent, or severe abuse have been reported for mental disorders and physical abuse [13],[24],[41] and emotional abuse and neglect [13],[22]. Furthermore, there is evidence to suggest that experiencing multiple types of maltreatment may carry more severe consequences, with those exposed to multiple types of abuse at increased odds of developing mental disorders [42],[43], and the risk increases with the magnitude of multiple abuse [44]. Dose–response relationships with repeated frequent or severe abuse have also been reported for STIs and physical and emotional abuse [13], obesity and emotional and physical abuse [31], and smoking and physical abuse [32]. Plausibility With respect to biological plausibility, animal models of mental disorders do not exist, making it particularly difficult to understand the underlying biological mechanisms. Progress in understanding has to be made by association and inference rather than experimental data [3]. There are nevertheless several potential mechanisms that may explain the observed association between abuse and neglect in childhood and increased risk of mental health problems. Neurobiological development can be physiologically altered by maltreatment during a child's early years, which can in turn negatively affect a child's physical, cognitive, emotional, and social growth, leading to psychological, behavioural, and learning problems that persist throughout the life course [45],[46]. Moreover, cumulative trauma may further increase risk [47], and some victims of abuse may try to manage the subsequent distress through the use of alcohol, prescription medication, tobacco, or other drugs. There is emerging evidence that the origins of most adult disease are found among developmental and biological disruptions in childhood. These early life experiences can affect adult mental and physical health either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods [48]. There is generally a lag of many years before early adverse experiences are expressed in the form of disease [48]. Andrews and colleagues concluded that despite the lack of a biological link between child sexual abuse and mental disorders, a causal relationship was plausible [3], and that child maltreatment is most likely a contributory cause that acts via other intermediates. Consideration of Alternate Explanations It is important to note that the role of genes, environment, and gene–environment interactions in the causation of mental disorders is not well understood. Twin studies provide one of the best ways to examine the interplay between genetic and environmental influences [3], but to the best of our knowledge, these are only available for child sexual abuse. The relationship between abuse and neglect in childhood and subsequent health effects is complex. Although childhood abuse and neglect does result in adverse health outcomes, these outcomes are not independent of broader socioeconomic contexts. Lifestyle factors, access to health care, and neighbourhood characteristics may act as mediators between child abuse and neglect and long-term health consequences [49]–[51]. Exposure to child maltreatment often co-occurs within the context of other family dysfunction, social deprivation, and other environmental stressors that are also associated with mental disorders. Child maltreatment may be a marker of other family problems that together lead to the development of mental disorders. In addition, findings from many studies do not take into account the likely contribution of hereditary influences on the predisposition to mental disorders. Children of depressed parents may be at greater risk of depression through both exposure to maltreatment by their parents and genetic predisposition [43]. Hence, some of the effect of child abuse and neglect on mental disorders may still be explained by confounding. However, the effect of abuse on mental disorders remained significant in the majority of studies included in these meta-analyses after controlling for these co-occurring factors. Assessment of Causality In summary, there was robust evidence of significant associations between exposure to non-sexual child maltreatment and increased likelihood of a range of mental disorders, suicide attempts, drug use, STIs, and risky sexual behaviour. An increase in the likelihood of alcohol problem use was not consistently seen. There is weak to limited evidence suggesting a relationship between non-sexual child maltreatment and certain physical disorders and risk factors (Table 8), but more research is required to confirm these relationships. 10.1371/journal.pmed.1001349.t008 Table 8 Summary of the strength of the evidence for related health outcomes. Robust Evidence Weak/Inconsistent Evidence Limited Evidence Physical abuse Depressive disorders Cardiovascular diseases Allergies Anxiety disorders Type 2 diabetes Cancer Eating disorders Obesity Neurological disorders Childhood behavioural/conduct disorders Hypertension Underweight/malnutrition Suicide attempt Smoking Uterine leiomyoma Drug use Ulcers Chronic spinal pain STIs/risky sexual behaviour Headache/migraine Schizophrenia Arthritis Bronchitis/emphysema Alcohol problems Asthma Emotional abuse Depressive disorders Eating disorders Cardiovascular diseases Anxiety disorders Type 2 diabetes Schizophrenia Suicide attempt Obesity Headache/migraine Drug use Smoking STIs/risky sexual behaviour Alcohol problems Neglect Depressive disorders Eating disorders Arthritis Anxiety disorders Childhood behavioural/conduct disorders Headache/migraine Suicide attempt Cardiovascular diseases Chronic spinal pain Drug use Type 2 diabetes Smoking STIs/risky sexual behaviour Alcohol problems Obesity Study Limitations Although these findings and conclusions seem to be relatively consistent and robust, they should be interpreted in light of a number of limitations of our analysis. This meta-analysis may be subject to publication bias because non-significant findings are less likely to be published [52]. This problem is increased when statistical models are employed because often only significant estimates are reported in many studies. This may result in the association between child abuse and neglect and outcomes being overstated, particularly for depressive disorders and anxiety, where publication bias may have played a role. For some of the other conditions there were too few studies to make conclusions with respect to publication bias. The analysis also suffers from inconsistencies in how child abuse and neglect are defined and measured across the studies, as shown in Table 3. In studies using child protection records, exposure to physical abuse was defined to include injuries such as bruises, welts, burns, abrasions, lacerations, wounds, cuts, and fractures. Some studies used the Barnett-Cicchetti Maltreatment Classification System [53] which defines physical abuse as a caregiver or responsible adult inflicting physical injury upon a child by other than accidental means. In other studies physical abuse was defined as having been hit, kicked, or punched so hard that the individual had marks or bruising or needed medical attention. Some studies referred to physical punishment [13],[54],[55] and corporal punishment [56], which may exclude more severe physical abuse, as well as physical assault by caregivers [57]. Emotional abuse definitions also varied considerably and included verbal abuse and being humiliated by a caregiver. Most studies involving neglect referred simply to “neglect”, while others distinguished between physical and emotional neglect. Similarly, definitions of childhood were not consistent across studies. The complexity of defining and measuring child abuse has been noted in several studies [58]–[60]. Measurement bias with respect to health outcomes and the questionable reliability of self-reported data may also have affected the results. We dealt with this issue in the meta-analysis by adjusting the quality score and performing subgroup analyses. For mental disorders, studies using well-validated and standardised diagnostic instruments were assigned a higher quality score than studies using self-report symptom scales. Another limitation of meta-analyses of observational studies is that, since individuals cannot be randomly allocated to case groups, the influence of confounding variables cannot be fully evaluated. While most studies presented multivariable adjusted ORs controlling for a range of socio-demographic and study design variables, a few studies presented unadjusted associations between child maltreatment and health outcomes, or adjusted for age and sex only. We again dealt with this issue in our meta-analysis by adjusting the quality score of studies with inadequate control for confounding and by carrying out separate analyses depending on data availability. Some studies also statistically controlled for exposure to other forms of maltreatment by including the different types of abuse in the same model in order to determine the independent contribution of each abuse type. Generally, in studies presenting results from various unadjusted and adjusted models, the association between abuse and physical and mental health outcomes was attenuated when controlling for the effects of mediating variables [61]–[72] and other forms of abuse [73]–[79]. However, findings from a recent prospective cohort study indicate that for some physical health outcomes additional control for socioeconomic status, unhealthy behaviour, smoking, and mental health problems seems to play varying roles in attenuating or intensifying these complex relationships [33]. Furthermore, we cannot exclude that residual confounding or unmeasured potential confounders may still remain. Despite evidence of weak associations between non-sexual child maltreatment and chronic diseases, further studies are needed that ensure adequate adjustment for lifetime confounders, because the attributable burden would be appreciable. Significant heterogeneity exists in the primary analysis of physical and emotional abuse, even after our attempts to control for study quality in quality effects models, and the heterogeneity remained significant in most of the subgroup analyses. Given this situation, combining the effects may not be justified. With respect to neglect, pooled estimates in primary and subgroup analyses did not show significant heterogeneity for many outcomes. Recommendations Inconsistencies in the measurement and definition of child maltreatment highlight the importance of international efforts to standardise studies to enhance the comparability of findings. These include defining the cutoff age for childhood (0–18 y, as specified by the United Nations), and breaking this period into smaller age bands that can reflect age-specific patterns [5]. Researchers should select methodologies and instruments with international comparisons in mind. Identical questionnaires, research designs, and interviewing techniques should ideally be used for surveys in different countries [5]. In reality, however, all survey methods will require at least some adaptation to local conditions, and efforts to ensure comparability should involve choosing definitions of abuse and neglect, and questionnaire items, that represent an advanced level of knowledge [80]. To minimise how participants' subjective perceptions and definitions shape the answers, it is recommended that self-report studies clearly specify the behaviours and experiences being investigated, and that each sub-type of abuse and neglect is explored using multiple behaviourally specific questions, instead of a single-item “label question” [81]. Examples of international efforts to increase comparability across studies include the WHO's establishment of a global adverse childhood experiences research network, and the International Society for Prevention of Child Abuse and Neglect's Child Abuse Screening Tools (ICAST). The WHO network has developed an international version of the Adverse Childhood Experiences (ACE) questionnaire (the ACE International Questionnaire), for administration to people aged 18 y and older, which is currently being validated through trial implementation as part of broader health surveys in several countries [82]. The ICAST initiative has involved the development of three instruments that ask parents about their use of different behaviours for discipline, young adults (18–24 y) about their exposure to child abuse and neglect in childhood, and older children about their own recent experiences of violence [83]. Child maltreatment deserves increased investment in preventive and treatment strategies. Currently, there is a paucity of evidence-based interventions to reduce child maltreatment. Further research is urgently needed to identify programs that reduce the prevalence of child maltreatment, thereby alleviating an important risk factor for later health problems. Evidence-based systemic interventions that improve parenting strategies and family functioning may be more effective and economical than attempting to treat the wide-ranging deleterious health outcomes in adulthood that arise from maltreatment in the early years of life [48],[84]. A broad range of protective factors have been identified that assist in promoting resilience in children exposed to adversity. Self control, problem-solving skills, secure relationships with caregivers, and safe schools and neighbourhoods are known to reduce the risk of adverse consequences in children exposed to trauma [85],[86]. There is mounting evidence that exposure to childhood adversity interacting with particular genetic dispositions such as the short allele of the serotonin transporter gene [87] and genes involved in the regulation of the hypothalamic–pituitary axis [88],[89] can result in problems with stress regulation and increased risk of anxiety and depression. Epigenetic changes have also been postulated as a mechanism by which transgenerational resilience or vulnerability may occur [90]. In spite of the increased knowledge in this field, it remains a challenge to translate this research into interventions at a population level that can reduce the vulnerability of children exposed to maltreatment [91]. Conclusion This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. There is also emerging evidence that neglect in childhood may be as harmful as physical and emotional abuse. Although these conclusions have been drawn before from single empirical studies, in this article they are demonstrated in aggregate quantitative effects, to our knowledge for the first time. This review contributes to a better understanding and measurement of the non-injury health impacts of child maltreatment globally and enables quantification of the burden attributable to physical and emotional abuse and neglect at the population level using comparative risk assessment methodology [92]. All forms of child maltreatment should be considered as part of the cluster of interpersonal violence risk factors in future global comparative risk assessments. Attributable burden is likely to be substantial, given the high prevalence of these forms of child maltreatment, the strong associations reported in our analysis, and the fact that related health outcomes are among the leading causes of disease burden globally. Despite the magnitude of the problem and increasing awareness of its high social costs, preventing child maltreatment is not a political priority in most countries. It is imperative that epidemiology and public health approaches find their proper place at the forefront of national and international efforts to understand and prevent child maltreatment [93]. Supporting Information Figure S1 Forest plot for quality-effect meta-analysis of the association between physical abuse and depressive disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S2 Forest plot for quality-effect meta-analysis of the association between emotional abuse and depressive disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S3 Forest plot for quality-effect meta-analysis of the association between neglect and depressive disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S4 Funnel plots to aid assessment of publication bias for depressive disorders and physical abuse. (TIF) Click here for additional data file. Figure S5 Forest plot for quality-effect meta-analysis of the association between physical abuse and anxiety. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S6 Forest plot for quality-effect meta-analysis of the association between emotional abuse and anxiety. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S7 Forest plot for quality-effect meta-analysis of the association between neglect and anxiety. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S8 Funnel plot to aid assessment of publication bias for anxiety and physical abuse. (TIF) Click here for additional data file. Figure S9 Forest plot for quality-effect meta-analysis of the association between physical abuse and eating disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S10 Forest plot for quality-effect meta-analysis of the association between emotional abuse and eating disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S11 Forest plot for quality-effect meta-analysis of the association between neglect and eating disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S12 Funnel plot to aid assessment of publication bias for eating disorders and physical abuse. (TIF) Click here for additional data file. Figure S13 Forest plot for quality-effect meta-analysis of the association between physical abuse and conduct/childhood behavioural disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S14 Forest plot for quality-effect meta-analysis of the association between neglect and conduct/childhood behavioural disorders. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S15 Funnel plot to aid assessment of publication bias for childhood behavioural/conduct disorders and physical abuse. (TIF) Click here for additional data file. Figure S16 Forest plot for quality-effect meta-analysis of the association between physical abuse and alcohol problem drinking. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S17 Forest plot for quality-effect meta-analysis of the association between emotional abuse and alcohol problem drinking. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S18 Forest plot for quality-effect meta-analysis of the association between neglect and alcohol problem drinking. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S19 Funnel plot to aid assessment of publication bias for alcohol problem drinking and physical abuse. (TIF) Click here for additional data file. Figure S20 Forest plot for quality-effect meta-analysis of the association between physical abuse and drug use. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S21 Forest plot for quality-effect meta-analysis of the association between emotional abuse and drug use. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S22 Forest plot for quality-effect meta-analysis of the association between neglect and drug use. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S23 Funnel plot to aid assessment of publication bias for drug use and physical abuse. (TIF) Click here for additional data file. Figure S24 Forest plot for quality-effect meta-analysis of the association between physical abuse and suicide attempt. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S25 Forest plot for quality-effect meta-analysis of the association between emotional abuse and suicide attempt. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S26 Forest plot for quality-effect meta-analysis of the association between neglect and suicide attempt. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S27 Funnel plot to aid assessment of publication bias for suicide attempt and physical abuse. (TIF) Click here for additional data file. Figure S28 Forest plot for quality-effect meta-analysis of the association between physical abuse and sexually transmitted infections/risky sexual behaviour. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S29 Forest plot for quality-effect meta-analysis of the association between emotional abuse and sexually transmitted infections/risky sexual behaviour. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S30 Forest plot for quality-effect meta-analysis of the association between neglect and sexually transmitted infections/risky sexual behaviour. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S31 Funnel plot to aid assessment of publication bias for sexually transmitted infections/risky sexual behaviour and physical abuse. (TIF) Click here for additional data file. Figure S32 Forest plot for quality-effect meta-analysis of the association between physical abuse and obesity. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S33 Forest plot for quality-effect meta-analysis of the association between emotional abuse and obesity. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S34 Forest plot for quality-effect meta-analysis of the association between neglect and obesity. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S35 Funnel plot to aid assessment of publication bias for obesity and neglect. (TIF) Click here for additional data file. Figure S36 Forest plot for quality-effect meta-analysis of the association between physical abuse and current smoking. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S37 Forest plot for quality-effect meta-analysis of the association between emotional abuse and current smoking. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S38 Funnel plot to aid assessment of publication bias for current smoking and physical abuse. (TIF) Click here for additional data file. Figure S39 Forest plot for quality-effect meta-analysis of the association between physical abuse and type 2 diabetes. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S40 Forest plot for quality-effect meta-analysis of the association between emotional abuse and type 2 diabetes. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S41 Forest plot for quality-effect meta-analysis of the association between neglect and type 2 diabetes. Studies are represented by symbols, the area of which is proportional to the study's weight in the analysis. Output for ORs is set to the (natural) log scale. (TIF) Click here for additional data file. Figure S42 Funnel plot to aid assessment of publication bias for type 2 diabetes and neglect. (TIF) Click here for additional data file. Table S1 Depressive disorders subgroup analyses. (DOC) Click here for additional data file. Table S2 Anxiety disorders subgroup analyses. (DOC) Click here for additional data file. Table S3 Eating disorders subgroup analyses. (DOC) Click here for additional data file. Table S4 Childhood behavioural/conduct disorders subgroup analyses. (DOC) Click here for additional data file. Table S5 Alcohol use subgroup analyses. (DOC) Click here for additional data file. Table S6 Drug use subgroup analyses. (DOC) Click here for additional data file. Table S7 Suicidal behaviour subgroup analyses. (DOC) Click here for additional data file. Table S8 Sexually transmitted infections and risky sexual behaviour subgroup analyses. (DOC) Click here for additional data file. Table S9 Obesity subgroup analyses. (DOC) Click here for additional data file. Table S10 Tobacco smoking subgroup analyses. (DOC) Click here for additional data file. Table S11 Type 2 diabetes subgroup analyses. (DOC) Click here for additional data file. Table S12 Evaluation of the evidence for a causal relationship within the Bradford Hill framework for prospective and retrospective studies. (DOC) Click here for additional data file. Text S1 PRISMA checklist. (DOC) Click here for additional data file. Text S2 Review protocol. (DOC) Click here for additional data file.
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            Author and article information

            Affiliations
            [1 ] departmentDepartment of Family Medicine and Primary Care , The University of Hong Kong , Hong Kong
            [2 ] departmentDepartment of Paediatrics and Adolescent Medicine , The University of Hong Kong , Hong Kong
            [3 ] departmentSchool of Nursing , Hong Kong Sanatorium & Hospital , Hong Kong
            Author notes
            [Correspondence to ] Dr Esther Yee Tak Yu; ytyu@ 123456hku.hk
            Journal
            BMJ Open
            BMJ Open
            bmjopen
            bmjopen
            BMJ Open
            BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
            2044-6055
            2018
            22 February 2018
            : 8
            : 2
            29472262
            5855257
            bmjopen-2017-018792
            10.1136/bmjopen-2017-018792
            © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

            This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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            Funding
            Funded by: Health and Medical Research Fund of Hong Kong;
            Funded by: Kerry Group Kuok Foundation (Hong Kong) Limited;
            Categories
            Mental Health
            Protocol
            1506
            1712
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