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Table 1 Effects of prenatal exposure to famine on mental disorders/symptoms in offspring

From: The association between prenatal famine, DNA methylation and mental disorders: a systematic review and meta-analysis

References

Cohort

Sample description of groups with prenatal, non-prenatal or non-exposure

Assessment of symptoms of psychopathology

Main results

Zhou et al. [42]

Chinese Famine*a

Prenatal exposure N = 1575, ♀ not stated, mean age 50

CES-D

Increased depressive symptoms after prenatal exposure and non-prenatal exposure compared to non-exposure***

Non-prenatal exposure N = 9138, ♀ not stated, age 57–69

Non-exposure N = 1968, ♀ not stated, mean age 47

He et al. [43]

Chinese Famine*a

Prenatal exposure N = 76, ♀ = 48, mean age not stated

GDS

Increased risk of depression after prenatal exposure compared to non-prenatal exposure*

Non-prenatal exposure N = 80, ♀ = 28, mean age not stated

Franzek et al. [57]

Dutch Famine*b

Prenatal exposure N = 5549

Case records of individuals with addictive behaviors in the database of the Dutch mental health care organizations

Increased risk of addictive behaviors after prenatal exposure during 1st trim (in men)*** and 3rd trim (in women)*** compared to non-exposure

1st trim = 1738, ♀ = 812

2nd trim = 568, ♀ = 287

3rd trim = 3243, ♀ = 1608

Non-exposure N = 11,630, ♀ = 5676

Age not stated

van den Broek et al. [38]

Dutch Famine*b

Prenatal exposure N = 23, ♀ = 11

MHI-5

Poorer mental health after prenatal exposure compared to non-prenatal exposure** and non-exposure*

Non-prenatal exposure N = 41, ♀ = 19

Non-exposure N = 83, ♀ = 34

Mean age of entire sample 57

Franke et al. [45]

Dutch Famine*b

Prenatal exposure N = 41, ♀ = 22, mean age 67

HADS-A/-D

No significant differences between prenatal exposure, non-prenatal exposure and non-exposure in anxiety and depressive symptoms

Non-prenatal exposure N = 35, ♀ = 21, mean age 69

Non-exposure N = 42, ♀ = 23, mean age 67

He et al. [50]

Chinese Famine*a

Rural population N = 239,055, ♀ = 119,217, mean age not stated

Diagnosis of schizophrenia with ICD-10 semi-structured symptom checklist for mental disorders

Only in rural population, increased risk of schizophrenia after prenatal exposure compared to non-exposure*

Urban population N = 148,038, ♀ = 73,471, mean age not stated

N for prenatal exposure, non-prenatal exposure and non-exposure not stated

Li et al. [40]

Chinese Famine*a

Prenatal exposure N = 996

CES-D

More depressive symptoms after prenatal exposure during 1st and 2nd trim compared to non-exposure*

Non-exposure N = 356

Trim and ♀ not stated

Age of entire sample > 45

Li et al. [39]

Chinese Famine*a

Prenatal exposure N = 1847, ♀ = 1019

CES-D

Only in women, more depressive symptoms after prenatal exposure compared to non-exposure (significant, but p not stated)

Non-exposure N = 2698, ♀ = 1671

Age of entire sample > 45

Wang et al. [47]

Chinese Famine*a

Prenatal exposure N = 81,279, ♀ = 40,509

Diagnosis of schizophrenia with ICD-10 semi-structured symptom checklist for mental disorders

Increased risk of schizophrenia after prenatal exposure compared to non-prenatal exposure*** and non-exposure***

Non-prenatal exposure N = 120,287, ♀ = 59,650

Non-exposure N = 150,429, ♀ = 75,470

Age not stated

Huang et al. [46]

Chinese Famine*a

Prenatal exposure N = 1477, ♀ = 752

GHQ-12 and the presence (yes/no) of eight additional risk factors for mental disorders

In women, increased GHQ-12 scores** and risk of mental disorders** and in men, decreased GHQ-12 scores** after prenatal exposure compared to non-exposure

Non-exposure N = 1029, ♀ = 514

Age not stated

de Rooij et al. [44]

Dutch Famine*b

Prenatal exposure N = 334

HADS-A/-D

Only in men, higher HADS-D and HADS-A scores after prenatal exposure during 1st trim compared to non-prenatal exposure* and non-exposure*

1st trim = 75, ♀ = 44, mean age 58

2nd trim = 121, ♀ = 76, mean age 58

3rd trim = 138, ♀ = 77, mean age 59

Non-prenatal exposure N = 253, ♀ = 136, mean age 59

Non-exposure N = 232, ♀ = 117, mean age 57

Song et al. [51]

Chinese Famine*a

Prenatal exposure N = 81,318, ♀ = 40,415

Diagnosis of schizophrenia based on CCMD with a semi- structured interview

Increased risk of developing schizophrenia after non-exposure compared to prenatal exposure*

Non-prenatal exposure N = 102,068, ♀ = 50,422

Non-exposure N = 110,970, ♀ = 56,706

Age of entire sample 22–32

Stein et al. [41]

Dutch Famine*b

Prenatal exposure N = 411, mean age 59

CES-D

Increased depressive symptoms after periconceptional and prenatal exposure compared to time and sibling controls (significant, but p not stated)

Periconceptional exposure N = 91

Time controls N = 218, mean age 59

Sibling controls N = 294, mean age 57

♀ not stated

Xu et al. [36]

Chinese Famine*a

Prenatal exposure N = 126,579

Case records (1971–2001) of schizophrenia patients from Longquanshan hospital

Increased risk of schizophrenia after prenatal exposure compared to non-prenatal exposure*** and non-exposure***

Non-prenatal exposure N = 329,189

Non-exposure N = 494,684

Age and ♀ not stated

Franzek et al. [56]

Dutch Famine*b

Prenatal exposure N = 2202, ♀ = 1055

Case records of addictive disorder patients in the database of the Dutch mental health care organization

Increased risk of addictive disorders, especially in men*, after prenatal exposure during 1st trim compared to non-exposure**

Non-exposure N = 5441, ♀ = 2753

Age not stated

St. Clair et al. [35]

Chinese Famine*a

Prenatal exposure N = 141,713

Case records (1971–2001) of schizophrenia patients from Fourth People’s hospital

Increased risk of schizophrenia after prenatal exposure compared to non-prenatal exposure*** and non-exposure***

Non-prenatal exposure N = 176,335

Non-exposure N = 243,647

Age and ♀ not stated

Brown et al. [52]c

Dutch Famine*b

Prenatal exposure N = 41,969

Case records of patients with major affective disorder from the Dutch national psychiatric registry from 1970 to 1996

Increased risk of major affective disorder requiring hospitalization after prenatal exposure during 2nd***and 3rd trim** for men and during 3rd trim* for women compared to non-exposure

1st trim = 9656, ♀ = 4672

2nd trim = 14,645, ♀ = 7185

3rd trim = 17,668, ♀ = 8727

Non-exposure N = 115,877, ♀ = 56,472

Age of entire sample ≥ 18

Neugebauer et al. [54]

Dutch Famine*b

Severe prenatal exposure N = 14,310

Non-standardized diagnosis of ASPD in men at time of medical examination for military induction

Increased risk of ASPD after severe prenatal exposure during 1st and/ or 2nd trim compared to non-prenatal and non-exposure (significant, but p not stated)

1st and/or 2nd trim = 9252, 3rd trim = 5058

Non-prenatal and non-exposure N = 45,007

Age of entire sample ≥ 18, ♀ not stated

Hoek et al. [55]

Dutch Famine*b

Prenatal exposure (Aug-Oct 1945) N = 2610

Diagnosis of schizoid personality disorder in men with ICD-6 and ICD-9

Increased risk of schizoid personality disorder after prenatal exposure (Oct-Dec) compared to non-prenatal and non-exposure*

Prenatal exposure (Oct-Dec 1945) N = 2056

Non-prenatal and non-exposure N = 64,265

Age of entire sample > 18, ♀ not stated

Susser et al. [48]c

Dutch Famine*b

Conception at peak N = 4190, ♀ = 2006

Case records of patients with schizophrenia from the Dutch national psychiatric registry from 1970 to 1992

Only for conception at peak of famine, increased risk of schizophrenia compared to non-prenatal and non-exposure**

Conception not at peak N = 5466, ♀ = 2666

Non-prenatal and non-exposure N = 136,691, ♀ = 66,748

Age of entire sample 24–48

Brown et al. [53]c

Dutch Famine*b

Prenatal exposure N = 41,969

Case records of patients with major affective disorders from the Dutch national psychiatric registry from 1978 to 1991

Only in men, increased risk of major affective disorders after prenatal exposure during 2nd trim compared to non-prenatal and non-exposure*

1st trim = 9656, ♀ = 4672

2nd trim = 14,645, ♀ = 7185

3rd trim = 17,668, ♀ = 8727

Non-prenatal and non-exposure N = 397,052

1st trim = 136,691, ♀ = 66,748

2nd trim = 131,702, ♀ = 64,235

3rd trim = 128,659, ♀ = 62,693

Age of entire sample 32–47

Susser et al. [49]c

Dutch Famine*b

Prenatal exposure 1st trim = 9656, ♀ = 4672

Case records of patients with schizophrenia from the Dutch national psychiatric registry from 1978 to 1989

Only in women, increased risk of schizophrenia after prenatal exposure during 1st trim compared to non-prenatal and non-exposure (significant, but p not stated)

Non-prenatal and non-exposure N = 116,934, ♀ = 57,034

Age of entire sample ≥ 19

  1. *aChinese Famine:1959–1961; *bDutch Famine:1944–1945; cpossible sample overlap between [48, 49] as well as [52, 53]; ASPD Antisocial Personality Disorder, CCMD Chinese Classification of Mental Disorders, CES-D Center for Epidemiologic Studies Depression Scale, GDS Geriatric Depression Scale, GHQ -12 General Health Questionnaire, HADS-A/-D Hospital Anxiety and Depression Scale, ICD International Statistical Classification of Diseases and Related Health Problems, MHI-5 Mental Health Inventory, trim Trimester; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001