Series

Perinatal mental health 3

Effects of perinatal mental disorders on the fetus and child
Alan Stein*, Rebecca M Pearson*, Sherryl H Goodman, Elizabeth Rapa, Atif Rahman, Meaghan McCallum, Louise M Howard, Carmine M Pariante

Lancet 2014; 384: 1800–19 Perinatal mental disorders are associated with increased risk of psychological and developmental disturbances in
This is the third in the Series of children. However, these disturbances are not inevitable. In this Series paper, we summarise evidence for
three papers about perinatal associations between parental disorders and offspring outcomes from fetal development to adolescence in
mental health
high-income, middle-income, and low-income countries. We assess evidence for mechanisms underlying
*Joint first authorship
transmission of disturbance, the role of mediating variables (underlying links between parent psychopathology and
Section of Child and Adolescent
offspring outcomes) and possible moderators (which change the strength of any association), and focus on factors
Psychiatry, Department of
Psychiatry, University of that are potentially modifiable, including parenting quality, social (including partner) and material support, and
Oxford, Oxford, UK duration of the parental disorder. We review research of interventions, which are mostly about maternal depression,
(Prof A Stein FRCPsych, and emphasise the need to both treat the parent’s disorder and help with associated caregiving difficulties. We
R M Pearson PhD, E Rapa DPhil);
conclude with policy implications and underline the need for early identification of those parents at high risk and
MRC/Wits Rural Public Health
and Health Transitions for more early interventions and prevention research, especially in socioeconomically disadvantaged populations
Research Unit (Agincourt), and low-income countries.
School of Public Health,
University of the
Witwatersrand, Johannesburg,
Introduction risk is accentuated or ameliorated, is important to
South Africa (Prof A Stein); A substantial body of evidence now exists that shows understand. Most investigators have tried to answer
Elizabeth Blackwell Institute perinatal mental disorders are associated with an this question with attempts to elucidate possible
for Health Research, School of increase in a range of psychological and developmental mechanisms of transmission, that is, the role of
Social and Community
disturbances in children. However, disturbances are mediating variables underlying associations between
Medicine, University of Bristol,
Bristol, UK (R M Pearson); not inevitable and effect sizes for these associations parent psychopathology and outcomes in their
Department of Psychology, are mostly moderate or small. Therefore, why an children, and possible moderators that change the
Emory University, Atlanta, USA association exists between a particular parental strength of any association.
(S H Goodman PhD,
M McCallum MA); Institute of
disorder and child outcome, and in what situations the In this Series paper, we summarise the evidence
Psychology, Health and about the different domains of development that are
Society, University of affected by perinatal mental disorders, and describe
Liverpool, Liverpool, UK Key messages mediating and moderating variables, interventions, and
(A Rahman PhD); Health Service
and Population Research • Substantial global evidence exists that perinatal disorders implications of policies.
Department, Institute of are associated with risks for a broad range of negative We mainly focus on depression and anxiety disorders
Psychiatry, King’s College
child outcomes, which can persist into late adolescence during the perinatal period, but also assess the evidence
London, UK for bipolar disorder, other psychoses, personality
(Prof L M Howard MRCPsych); • However, risks are not inevitable and in the absence of
and Department of severe or chronic maternal disorder or other adversities, disorders, and eating disorders, although little research
Psychological Medicine, the effect sizes are generally small or moderate has been done about these disorders in relation to child
Institute of Psychiatry, King’s
• Most research has focused on mothers, but growing outcomes. We prioritise findings from longitudinal
College London, London, UK studies (especially meta-analyses of such studies) for
(C M Pariante FRCPsych) evidence suggests that the fathers’ mental health is also
associated with child developmental disturbances which, by contrast with cross-sectional designs, the
Correspondence to:
Prof Alan Stein, Section of Child • Mechanisms underlying associations are complex and temporal sequence of exposure and outcome is known.
and Adolescent Psychiatry, include a range of genetic, other biological, and This knowledge helps to increase the potential for causal
Department of Psychiatry,
environmental pathways inference, although still not as clearly as experimental
University of Oxford, Oxford designs. We report evidence from studies that use reliable
OX3 7JX, UK • Research should prioritise investigating the effectiveness
[email protected] of interventions in reducing risk to the child and reducing and valid measures of mental disorders of either
symptoms in the affected parent interviews (providing categorical clinical diagnoses) or
• Parenting is a key modifiable pathway to explain some of self-report symptom questionnaires. Questionnaires are
the risks of perinatal disorders to the child and should be feasible in large population-level studies, often have well
specifically targeted in interventions established thresholds to suggest clinically significant
• Interventions could be most important in the context of levels of symptoms, and can be used as continuous scales.
additional adversities, such as in socioeconomically We take a developmental perspective, report associations
disadvantaged populations, where risks to the child seem between perinatal disorders and offspring outcomes,
highest; where several risks are present and resources are beginning with fetal and proceeding through to adolescent
scarce, especially in areas in low-income and middle-income outcomes. Although the focus of this Series is maternal
countries, innovative strategies are needed disorders, when deeming the effect on the child, paternal
disorders also need to be taken into account.

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Fetal and neonatal outcomes

Two meta-analyses1,2 have assessed the association Search strategy and selection criteria
between antenatal depression and fetal and neonatal We searched in PubMed, Embase, PsycINFO, and the Cochrane Library without language
outcomes. Both reports showed that symptoms of restrictions using the search terms: “mothers” (exploded MeSH term), “fathers” (exploded
antenatal depression are associated with an increased MeSH term), “parents” (exploded MeSH term), “Mum”, “Mom”, and “Dad” in combination
risk for premature delivery (<37 weeks’ gestation). with “pregnancy”, “prenatal”, “antenatal”, “postnatal”, “postpartum”, “perinatal”,
One reported that studies controlling for women taking “puerperal”, “breastfeeding”, “birth”, “weaning”, “childbirth”, “trimester”, “peripartum”,
antidepressant drugs or smoking generated small (and “lactation”, “antenatal”, “postnatal”, “postpartum” and “mood disorder” (exploded MeSH
non-significant) odds ratios,1 whereas the second2 term), “anxiety disorder” (exploded MeSH term), “eating disorder” (exploded MeSH
concluded that “the summary relative risk was term), “psychotic disorders” (exploded MeSH term), “depression”, “anxiety”, “eating
comparable for depressed women treated and not disorder”, “psychotic disorders”, “psychoses”, “mania”, “Schizophrenia”, and “fetus”,
treated with antidepressants”.2 Antidepressants or “in-utero”, “child” (exploded MeSH term), “toddler”, “infant”, “adolescent” (exploded
smoking can be markers for more severe depression3 MeSH term), “offspring”, “boy”, or “girl”. We searched for systematic reviews (between
and the effects of antenatal depression on prematurity 1984–2014) and epidemiological or experimental studies (between 2009 and 2014 for
(and low birthweight) were strong in studies where studies of depression; between 1984 and 2014 for studies of other disorders, and from
depression was defined by a disorder,2 suggesting that low-income and middle-income countries) using the aforementioned search terms.
severity of disorder is important. Search terms (all Mesh terms were included where available for child development terms)
A discrepancy was noted between the findings relating were combined for sections about obstetric complications, prematurity or sudden infant
to depression and low birthweight; one meta-analysis2 death syndrome, stillbirth, childhood maltreatment, maternal care, or epigenetics with
reported a modest association whereas the other “cognition”, “cognitive”, “IQ”, “attention”, “memory”, “language” “ability”, “development”
reported a non-significant association.1 However, in the “learning”; or “emotion*, “affective”, “emotion-regulation”, “crying”, “internalizing”,
meta-analysis reporting no association,1 studies from “depression” “anxiety”, “mood” “temperament” “sad” “fearful” “mental health”
low-income and middle-income countries (LMICs) were “psychopathology”; or “attachment”, “secure”, “insecure”, “avoidant”, “anxious”,
excluded from analyses. In geographically diverse studies “resistant”, “bonding”, “relationships”, “strange situation”; or “behaviour”, “externalising”,
incorporated within the second meta-analysis,2 moderator “aggressive”, “angry”, “difficult”, “conduct disorder”, “oppositional”, “delinquent”,
analyses showed that the association with low birthweight “hyperactive”, “ADHD”, “attention deficit disorder”, “crime”, “anti-social”; or “nutrition”,
was higher in LMICs than in high-income countries “nutritional disorders”, “growth”, “nutritional status”, “body size”, “weight”,
(HICs). Low birthweight might therefore be a substantial “malnutrition”, “overweight”, “obesity”; or “treatment”, “intervention”, or “prevention”.
factor in LMICs, but not in HICs, except possibly in socio-
economically disadvantaged communities.2
Antenatal depression was not associated with Other mental health problems during pregnancy have
pre-eclampsia, Apgar scores, or admission to neonatal been associated with fetal and neonatal outcomes. Several
intensive-care units; for intrauterine growth restriction, studies suggest that maternal anorexia nervosa (active or
antenatal depression was associated with an increased past) is associated with low birthweight, although
risk but only in LMICs.1,2 Additional researchers in a associations are inconsistent with high rates of
meta-analytic review4 examined associations between prematurity.8 Schizophrenia has also been associated with
these outcomes and use of antidepressants during an increased risk of low birthweight, preterm delivery,
pregnancy, but reported weak associations after accounting stillbirth, and infant death within 1 year after birth.9–11 This
for confounding.4 risk might be partly attributable to environmental factors
Some fetal and neonatal outcomes have been investigated associated with adversity, including smoking, poverty, poor
mostly in association with the use of antidepressants nutrition, and substance misuse.11 Risks of such adverse
rather than with a diagnosis of depression4 usually because outcomes do not substantially differ between infants
of the availability of prescription data in large population according to whether their mothers had a history of a
databases studies,3 making it difficult to disentangle psychiatric admission for schizophrenia or affective
the effect of antidepressants, life style confounders, disorders. Risks for both groups with either schizophrenia
and depression. or affective disorders are lower than they are for infants of
Evidence is inconsistent for associations between mothers with substance misuse disorders.12
antenatal anxiety and adverse fetal outcomes. A
meta-analysis5 reported small, non-significant correlations Infant, child, and adolescent outcomes
for most outcomes other than pregnancy-related anxiety Overview
and young gestational age at birth. A meta-analysis6 in In view of the many studies that aim to examine associations
2014 showed slight associations between anxiety and both between perinatal disorders and offspring outcomes, we
preterm birth and low birthweight, although birthweight structure this section by domain of development, reviewing
was not significant when regarding adjusted findings.6 findings associated with different disorders within each
Both meta-analyses were limited by the paucity of studies domain. Only recent HICs studies (2009–13) are included;
and the frequent comorbidity of anxiety with depression however, in view of the paucity of LMICs studies, any study
and life stressors, which could confound associations.7 from these contexts were included (2000–13) in tables 1–5.

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) children at
exposure follow-up
Clinical Self-report Objective Questionnaire Confounding variables included Mediators or
interview or assessment or (parent moderators
objective of interview or child
assessment reported)
Gerardin 2011; Antenatal Clinical Not reported NBAS ITSEA 12 months Antenatal depression was None reported; however, Many
n=164; France13 interviews, associated with increased exclusions for at risk pregnancies associations
DSM-IV externalising and internalising were made limited to
symptoms on the ITSEA and poor boy infants
motor and regulation skills on
NBAS
Blair 2011; Antenatal Not reported STAI; PSA Not reported ECBQ 2 years Child negative affectivity was Postnatal anxiety, maternal age, Not reported
n=120; USA14 associated with both the initial education, ethnic origin, marital
intercept and the trajectory of status
maternal PSA in pregnancy
Velders 2011; Antenatal Not reported BSI Not reported CBCL (cutoff) 3 years Child internalising behaviour was Child sex, birthweight, birth Mediated by
n=2698; associated with antenatal order, ethnic origin, and age at maternal
Netherlands depression (OR 1·18 [95% CI questionnaire; maternal depression
(generation-R)15 1·08–1·29]; similar associations smoking and alcohol use during at age
reported for anxiety symptoms) pregnancy, parental age, and 3 years and
parental level of education parental
hostility
Davis 2012; Antenatal Salivary PSS; CES-D; Not reported CBCL anxiety 6–9 years Maternal antenatal pregnancy- Child sex, gestational age at Not reported
n=178; USA16 cortisol STAI; PSA scale specific anxiety score was birth, maternal level of
associated with child CBCL score education, and maternal
(β 0·22, p<0·05); maternal cortisol psychosocial stress at the time
concentration was associated with of child assessment
CBCL score (β 0·16, p<0·05)
Barker 2011; Antenatal Not reported EPDS; DAWBA; Not reported 8 years Child internalising behaviour was Adjusted for cumulative risk Not reported
n=3298; CROWN- internalising associated with antenatal anxiety score derived from SES, marital
UK (ALSPAC)17 CRISP index disorders (β 0·07, p<0·05) but not anetnatal status, teenage mother,
depression; postnatal depression substance use, criminal
(β 0·08, p<0·05); postnatal anxiety background, antenatal and
(β 0·17, p<0·05) postnatal anxiety and depression
were mutually adjusted
Leis 2013; Antenatal Not reported EPDS; Not reported SDQ mother 10–11 years Associations with total emotional Marital status, maternal age, Not reported
n=2891; CROWN- and teacher SDQ score in the child; antenatal birthweight, child sex, maternal
UK (ALSPAC)18 CRISP index report depression (β 0·22 [SE 0·07], education, alcohol use during
p<0·001); antenatal anxiety pregnancy, offspring smoking,
(β 0·43 [SE 0·11], p<0·001); depression and anxiety,
similar associations were noted mutually adjusted and later
for postnatal depression, but symptoms were controlled for
adjusted associations not given;
no associations were reported for
teacher-reported SDQ; similar
assocations reported for other
SDQ subscales
Pawlby 2009; Antenatal Pregnancy: Not reported Depression, Not reported 11 years and Antenatal depression was Family structure Mediated by
n=127; UK19 clinical diagnosis 16 years associated with increased risk later chronic
interview clinical of depression for child at age maternal
schedule; interview 16 years (OR 4·70 [95% CI depression
at age DSM-IV, CAPA 1·60–13·86]) after birth
16 years:
SADS-L
Korhonen 2012; Antenatal Not reported EPDS Not reported CBCL YSR 16 years or Antenatal and postnatal Later maternal depression at Association
n=192; Finland20 17 years depression symptoms were not child age 16–17 years between
associated with high internalising postnatal
scores on the YSR or CBCL; depression
however, antenatal and postnatal and social
depression were associated with competence
low social competence on CBCL was only
and YSR reported in
boys and not
in girls
(Table 1 continues on next page)

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) children at
exposure follow up
Clinical Self-report Objective Questionnaire Confounding variables included Mediators or
interview or assessment (parent moderators
objective of or interview or child
assessment reported)
(Continued from previous page)
Pearson 2013; Antenatal Not reported EPDS Depression Not reported 18 years Association between 1 SD Maternal age, social class, Maternal
n=8937; UK21 diagnosis increase in maternal EPDS score parity, history of depression education
clinical and child depression at age before pregnancy, smoking moderated
interview 18 years: antenatal EPDS (OR 1·23 during pregnancy, the effects of
CIS-R, ICD10 [95% CI 1·03–1·44]); postnatal breastfeeding in the first year, postnatal
EPDS in mothers with low use of non-parental child-care, but not
education (OR 1·26 [1·06–1·50]) later depression antenatal
or high education (OR 1·09 depression
[0·88–1·36])
Reck 2013; Postnatal Clinical Not reported Still Face Infant 3–8 months Postnatal anxiety was associated Sex of infant Not reported
n=82; interviews, Paradigm, behaviour with more distress to novelty and
Germany22 DSM-IV Cortisol questionnaire reported emotional problems
reactivity in temperament
response to
Still Face
procedure*
Bosquet Enlow Postnatal Not reported PTSD Observed ITSEA infant 6 months Maternal PTSD symptoms were Maternal age, educational Not reported
2011; n=52; symptoms; emotion behaviour and associated with infants’ emotional attainment, maternal
USA23 PCL-C; EPDS regulation, questionnaire 13 months regulation at age 6 months as depression, marital status,
still face assessed by infant ability to parity, financial strain, race,
recover from distress and maternal and ethnic origin, infant’s sex,
report; maternal PTSD symptoms birthweight, gestational age,
predicted maternal report of race, and ethnic origin
infant externalising, internalising,
and dysregulation symptoms at
age 13 months
Feldman 2009; Postnatal Depression Not reported Observed Not reported 9 months Compared with controls, None reported Effects on
n=22 depressed, and anxiety social engage- offspring of mothers with social
19 anxious, and clinical ment, fear depression showed reduced social engagement
59 controls; interviews, regulation, engagement, increased were
USA24 DSM-IV cortisol negativity, and poor fear moderated
regulation by maternal
sensitivity
Hartley 2010; Postnatal Not reported EPDS Not reported Modified 10–12 No association between postnatal None reported Sex of child,
n=83; alarm distress months depression and social withdrawal small sample
South Africa25 baby scale size with
depression
(n=26), HIV
sample
Conroy 2012; Postnatal Clinical Not reported Not reported ITSEA social 18 months Postnatal depression was Occupation, ethnic origin, Moderated
n=200; UK26 interview, and associated with child ITSEA partner status, and later by comorbid
DSM-IV SCID emotional subscores for internalising maternal depression, personality
(cutoffs) (OR 6·86 [95% CI 1·34–35·14]) sex of infant disorders
Kersten-Alvarez Postnatal Clinical Not reported Puppet CBCL, Early school No evidence that postnatal Child age, sex of child, maternal Moderated
2012; n=142 interviews, interview internalising; (children’s depression was associated with education, partner conflict, by sex of the
(29 with DSM-IV (used to PSBQ; teacher average age internalising or low self-esteem, stressful life events, separation child;
depression, assess self reported ego- of 5 years) but was associated with low peer from father associations
113 controls; esteem) resiliency: social competence and were
Netherlands27 California ego-resiliency stronger for
Child Q-set† girls than for
boys
Verbeek 2012; Postnatal Not reported Maternal Not reported CBCL (parents 10–15 years Postnatal depression was Smoking or drinking during Not reported
n=2729; report and teachers) associated with internalising pregnancy, social-economic
Netherlands28 interviewer symptoms (β 0·28 [95% CI position, and obstetric factors
led based on 0·14–0·41], p<0·001)
DSM-IV
(Table 1 continues on next page)

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) children at
exposure follow up
Clinical Self-report Objective Questionnaire Confounding variables included Mediators or
interview or assessment (parent moderators
objective of or interview or child
assessment reported)
(Continued from previous page)
Naicker 2012; Postnatal Not reported CES-D-12 Not reported Own scale 12–13 years Children exposed to maternal Life events, maternal alcohol Not reported
n=937; Canada based on depression were at an increased use, child and maternal chronic
(NLSCY)29 DSM-III risk of depression: first exposed to health problems, marital status,
maternal depression postnatally household income, sex of child,
(OR 1·36 [95% CI 0·80–2·32]) and later maternal depression
exposed at age 2–3 years
(OR 1·87 [1·05–3·53])
Murray 2011; Postnatal Clinical Not reported Interview Not reported 16 years Postnatal depression was Variables considered as Association
n=100; UK30 and after interviews, using KSADS associated with increased risk of mediators partly
SPI offspring depression (OR mediated by
4·99 [95% CI 1·68–14·70]) marital
conflict,
maternal
support,
continued
maternal
depression,
attachment
security, and
ego-
resilience

OR=odds ratio. DSM=diagnostic and statistical manual. NBAS=neonatal behavioural assessment scale. ITSEA=infant toddler social emotional assessment. STAI=state-trait anxiety inventory. PSA=pregnancy
related anxiety scale. ECBQ=early child behaviour questionnaire. BSI=brief symptom inventory (psychological symptoms). CBCL=child behavioural checklist (internalising and externalising symptoms).
PSS=perceived stress scale. CES-D=centre for epidemiologic studies depression scale. EPDS=Edinburgh postnatal depression scale. DAWBA=development and well-being assessment. ALSPAC=Avon longitudinal
study of parents and children (UK). SES=socioeconomic status. SDQ=strengths and difficulties questionnaire (internalising and externalising symptoms). SE=standard error. SADS-L=schedule for affective
disorders and schizophrenia-lifetime. CAPA=child and adolescent psychiatric assessment. PTSD=post-traumatic stress disorder. PCL-C=post-traumatic stress disorder checklist. LMIC=low-income and
middle-income countries. SCID=structured clinical interview for DSM-IV. PSBQ=preschool social behaviour questionnaire. SPI=standardised psychiatric interview. NLSCY=national ongitudinal survey of children
and youth (Canada). KSADS=kiddie-schedule for affective disorders and schizophrenia. *The mother is requested to stop responding and show a blank, unresponsive face to the infacnt for a short duration and
the infant’s reaction is noted. †Personality dimensions, in Kersten-Alvarez26 were used to assess ego-resiliency.

Table 1: Emotional outcomes

Emotional (internalising) difficulties and social age ranges, including internalising disorders, poor social
development competence in school years, and an increased risk of
Children’s emotional and behavioural difficulties are depression during adolescence (table 1).25,27,28,30,59 Risks are
often conceptualised as being either internalising or associated with both symptoms of depression and
externalising. Internalising difficulties include symptoms depressive disorder, although effect sizes are generally
or diagnoses of depression and anxiety (eg, separation large in children of mothers diagnosed with depressive
anxiety and phobias). By social development, we refer to a disorder (table 1).
child’s development of social skills, such as perspective In view of the high extent of the association between
taking, empathy, and cooperation. depression in the antenatal and postnatal periods, large
Longitudinal studies have shown that antenatal numbers of participants are required to provide sufficient
depression is associated with an increased risk for child power to assess whether the risks associated with antenatal
emotional problems;13,15,18 self-reported symptoms and and postnatal depression are independent of each other.21,32
depressive disorder are associated with an increased One study21 reported independent associations between
risk of clinical depression in late adolescence.19,21 symptoms of antenatal and postnatal depression and
Increased risks of emotional problems in children of offspring depression at age 18 years. Maternal level of
mothers with postnatal depression have long been education moderates the association between symptoms
noted.57 Detailed records of mother and infant behaviours of postnatal but not antenatal depression, and offspring
showed that infants of mothers with postnatal depression depression,21 suggesting different mechanisms of risk are
have an increased risk of difficulties in early emotional linked to antenatal and postnatal depression exposure.
regulation and social behaviour.58,59 Longitudinal studies Fewer investigations have been done to assess
provide evidence for associations between postnatal associations between antenatal and postnatal anxiety
depression and emotional outcomes across domains and and child emotional difficulties than have for perinatal

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) children at
exposure follow-up
Clinical Self-report Objective Questionnaire Confounding variables included Mediators or
interview assessment (parent moderators
or objective or interview or child
assessment reported)
Pemberton 2010; Antenatal Not BDI Not reported CBCL 27 months For the birth mother, prenatal– Openness in adoption, sex of Not reported
n=361; USA31 reported postnatal depressive symptoms child, parent age, prenatal
were associated with complications, birth; adoptive
externalising (β 0·09, p<0·10); parent antisocial behaviour, and
for an adoptive mother infant characteristics
postnatal depressive symptoms
associated with child
externalising (β 0·14, p=0·05)
Velders 2011; Antenatal Not BSI Not reported CBCL 3 years Evidence that child See table 1 Mediated by
n=2698; reported externalising difficulties were maternal
Netherlands associated with antenatal depression at age
(generation-R)15 depression (OR 1·19 [95% CI 3 years and
1·09–1·30]) parental hostility
Van Batenburg- Antenatal Not EPDS Not reported SDQ, CBCL 3 years Child attention problems were Sex of child, birthweight, birth After adjusting for
Eddes 2013; reported· associated with antenatal order, ethnic origin, and age at maternal
n=2280, depression: generation-R questionnaire; maternal symptoms after
Netherlands (OR 1·23 [95% CI 1·05–1·43]; smoking and alochol use during birth, antenatal
(generation-R); ALSPAC (OR 1·33 [1·19–1·48]); pregnancy, and maternal level maternal
n=3442, and antenatal anxiety: of education; family income; depression and
UK (ALSPAC)32 generation-R (OR 1·24 and adjusted for depression or anxiety were no
[1·06–1·46]); ALSPAC (OR 1·32 anxiety of a partner during longer associated
[1·19–1·47]) pregnancy with child
attention problems
in generation-R
Barker 2011; Antenatal Not EPDS DAWBA: Not reported 8 years Child externalising behaviour Adjusted for a cumulative risk Not reported
n=3298; reported CROWN- externalising was associated with antenatal score derived from SES, marital
UK (ALSPAC)17 CRISP index disorders depression (no association with status, teenage mother,
anxiety; β 0·09, p<0·05); and substance use, criminal
postnatal depression (β 0·09, background, and antenatal and
p<0·05) postnatal anxiety and
depression, mutually adjusted
Korhonen 2012; Antenatal Not EPDS Not reported CBCL, YSR 16–17 years Antenatal and postnatal Later maternal depression at Association
n=192; Finland20 reported depression was associated with child age of 16–17 years between postnatal
higher externalising score on but not antenatal
the YSR, but not the CBCL depression was
stronger in boys
than in girls;
prospective
Hay 2010; Antenatal Clinical Not DSM-IV; Not reported 16 years Associations between antenatal Associations were similar when Associations
n=120; UK33 interview, reported conduct depression and offspring including antenatal anxiety, between antenatal
ICD-9 CIS disorder or antisocial behaviour (OR 2·46 smoking, drinking, postnatal depression and
antisocial [95% CI 1·1–5·48]) and later depression, and social offspring antisocial
behaviour adversity behaviour were
reduced when
maternal conduct
disorder was
adjusted for
Conroy 2012; Postnatal Clinical Not Not reported ITSEA (SD 9) 18 months Postnatal depression was Occupation, ethnic origin, Moderated by
n=200; UK26 interview, reported associated with infant partner status, later maternal comorbid
DSM-IV dysregulated behaviour (β 5·12 depression, sex of infant, personality
[95% CI 1·49–8·75]) maternal sensitivity towards disorder
their infant
Galera 2011; Postnatal Not CES-D scale Not reported Not reported 17 months Postnatal depression was Prematurity and birthweight of Not reported
n=2057; reported to 8 years, associated with an increased child; prenatal smoking, drug
Canada34 trajectories risk of high trajectories of and alcohol use; family
of ADHD hyperactivity–impulsivity and structure, maternal age, income,
symptoms inattention symptoms through maternal education, parenting
childhood (OR 1·35 [95% CI factors, and paternal depression
1·18–1·54])
(Table 2 continues on next page)

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) children at
exposure follow-up
Clinical Self-report Objective Questionnaire Confounding variables included Mediators or
interview assessment (parent moderators
or objective or interview or child
assessment reported)
(Continued from previous page)
Avan 2010; Postnatal Not Pitt Not reported Richman child 2 years Postnatal depression was SES, ethnic origin, birthweight, Mediated by
n=1035; reported depression; behaviour associated with child gestational age, maternal age, stunted growth
South Africa35 inventory scale behavioural issues and growth (β 0·294, p=0·111)
(β 0·35, p=0·015)
Hanington 2012; Postnatal Not EPDS Not reported Rutter revised 4 years Postnatal depression was Maternal education, paternal Mediated by
n=8598; reported preschool associated with increased risk of depression marital conflict
UK (ALSPAC)36 scales conduct problems (OR 1·74
[95% CI 1·33–2·52]); and
emotional problems (OR 1·75
[1·36–2·52])
Kersten-Alvarez Postnatal Clinical BDI Not reported Teacher Early school Girls of mothers with postnatal Child age and sex, maternal Moderated by sex
2012; n=142 interviews; report social (child depression showed less education, partner conflict, of the child;
(29 with DSM-IV competence; average age externalising difficulties than stressful life event, and father associations were
depression); CBCL of 5 years) did controls absence stronger for girls
Netherlands27 than for boys
Letourneau Postnatal Not CES-D Not reported Physical 4–5 years Postnatal depression was SES, income adequacy, mothers’ Effects for
2013; n=10 033; reported aggression, associated with inattention years of education, family inattention
Canada inattention; (OR 1·53, p<0·05) and physical structure, and family function mediated by later
(NLSCY)37 NLSCY items aggression (OR 2·94, p<0·05) depression,
parenting style, and
family function
Fihrer 2009; Postnatal CIDI CES-D ADIS-P Parent and 6–8 years Postnatal depression was Maternal education, Associations
n=75; Australia38 teacher associated with child scores for non-English speaking mediated by later
reports; CBCL; internalising (β 0·35 maternal
maternal [standardised estimate 0·11]) depression, with
repots mainly and externalising (β 0·25 evidence for
used [standardised estimate 0·12]) significant indirect
difficulties effects by use of
path analysis

BDI=Beck depression inventory. CBCL=child behaviour checklist (internalising and externalising symptoms). BSI=brief symptom inventory (psychological symptoms). EPDS=Edinburgh postnatal depression scale.
SDQ=strengths and difficulties questionnaire (internalising and externalising symptoms). ALSPAC=Avon longitudinal study of parents and children (UK). DAWBA=development and well being assessment.
SES=socioeconomic status. YSR=youth self report (mental health). YSF=youth self report form. ICD=international classification of diseases. CIS=the clinical interview schedule. DSM=diagnostic and statistical
manual. ITSEA=infant toddler social emotional assessment. CES-D=centre for epidemiologic studies depression scale. ADHD=attention deficit hyperactivity disorder. LMIC=low-income and middle-income
countries. NLSCY=national longitudinal survey of children and youth (Canada). CIDI=composite international diagnostic interview. ADIS-P=anxiety disorders interview schedule for DMS-IV-parent version.

Table 2: Behavioural outcomes

depression. Depression and anxiety are substantially have an increased risk of difficulties in emotional
comorbid, and thus associations attributed to one, might regulation even after adjustment for symptoms
include causes associated with the other. Several studies of depression.23
showed self-reported symptoms of antenatal anxiety are Although research for other disorders is scarce,
associated with internalising symptoms in childhood14–17 one report62 shows that children of mothers admitted to
and adolescence.60 After symptoms of anxiety for both mother and baby units with severe postnatal disorders are
antenatally and postnatally were accounted for, no at an increased risk of a psychiatric (mainly emotional)
independent effect of antenatal depression occurred.17 disorder in adulthood compared with siblings who were
A systematic review61 reported associations between not exposed to a postnatal episode.62
postnatal symptoms of anxiety and child emotional
difficulties. Comparisons between depression and Behavioural (externalising) difficulties
anxiety disorders in a few studies were assessed by Externalising difficulties include attention deficit
diagnostic interviews; some specificity was noted in hyperactivity disorder, oppositional defiant disorder, and
the nature of the early effects of anxiety disorders on conduct disorder, or symptoms of any of these.
infant distress to novelty (which is linked to behavioural Several studies have reported associations between ante-
inhibition),22 but impairment in fear regulation was natal depression and a child’s externalising behaviour,15,17,20,32
restricted to infants of mothers with depression.24 including when a child is adopted.31 A small study33 reported
Infants of mothers with post-traumatic stress disorder an association between antenatal depressive disorder and

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Time Exposure measure (maternal) Outcome Age of Results Strengths and limitations
of first measure (child) children at
exposure follow-up
Clinical Interview Self-report Confounding variables Mediators or
or objective included moderators
assessment
Hayes 2013; Antenatal Diagnostic BDI-II Strange 12 months Antenatal depression was Sex of infant; parenting; Parenting warmth and
n=79; USA39 interview situation* associated with disorganised antenatal antidepressant sensitivity at child age
DSM-IV, SCID-IV attachment (β 0·21 [SE 0·09], drugs of 3 months reduced
p<0·05; OR 1·23) the association
Tharner 2012; Antenatal, Diagnostic BSI Strange 14 months Attachment insecurity was not Maternal age, parity, Not reported
n=627; postnatal interview (antenatal, situation* associated with antenatal maternal education, marital
Netherlands DSM-IV, CIDI postnatal) depression (BSI, Z score; status, sex of child,
(generation-R)40 (postnatally) EPDS OR 0·96 [95% CI 0·81–1·14]) gestational age at birth and
(postnatal) and postnatal depression (BSI, at assessment, paternal
Z score; OR 0·91 [0·75–1·10]) psychopathology
Tomlinson 2005; Postnatal Diagnostic Not reported Strange 18 months Postnatal depression was Partner support considered Some evidence for
n=147 (98 on interview situation* associated with insecure but not included in final mediation by maternal
18 month DSM-IV, SCID-IV attachment style (OR 2·98 model sensitivity or parenting
follow-up); [95% CI 1·26–7·01]) at child age of
South Africa41 2 months
Murray 2011; Postnatal Structured Not reported Strange 18 months Postnatal depression was Sex of infant, family Not reported
n=100; UK30 clinical interview situation* associated with insecure adversity
for DSM-IV attachment (OR 5·37 [95% CI
2·16–13·33])

DSM=diagnostic and statistical manual. SCID=structured clinical interview for DSM-IV. BDI=Beck depression inventory. CIDI=composite international diagnostic interview. BSI=brief symptom inventory.
EPDS=Edinburgh postnatal depression scale. *An observed experimental procedure where an infant’s reactions to separation and reunion with their mother are used to categorise so-called security of
mother-infant attachment.

Table 3: Attachment outcomes

antisocial behaviour in adolescence that was independent Antenatal depression is associated with disorganised
of postnatal depression. Several large longitudinal studies, attachment (a form of insecure attachment), independently
including from LMICs, provided supportive evidence that of postnatal depression.39 In two meta-analyses,65,66
symptoms and disorders of postnatal depression are postnatal depression was associated with an increased
associated with a child’s externalising behaviour, partic- risk of insecure (especially disorganised) mother–infant
ularly symptoms of attention deficit hyperactivity disorder, attachment. This association is low or non-significant in
up to age 16 years.20,34–38 In a large study of antenatal and community samples in relation to clinical samples and
postnatal maternal symptoms of depression, associations when depression is measured by self-report, in relation to
between antenatal symptoms and persistent childhood diagnostic interviews.40,66
attention deficit hyperactivity disorder symptoms were In a small sample of mothers with severe psycho-
diminished after postnatal symptoms were accounted for.32 pathology and admitted to hospital postnatally, infants
Self-reported symptoms of maternal anxiety both of mothers with unipolar depression, but not manic
antenatally15,63 and postnatally32 are associated with external- disorders, were more likely to show insecure attachment
ising disorders in childhood.61 We found no studies that at aged 12 months than were infants of mothers without
used clinical diagnostic interviews therefore associations a perinatal disorder.67
between specific anxiety disorders and children’s external-
ising difficulties remain to be established. Cognitive development
Few studies have investigated the effect of other perinatal Antenatal depression (both self-reported symptoms and
psychopathology on behavioural outcomes. Results of a the disorder) is associated with low levels of general
small study26 suggested that infants of mothers with cognitive development, including IQ scores in childhood.
comorbid postnatal depression and personality disorder However, effect sizes are generally small17,42,44 and not all
had reported dysregulated behaviour. studies showed a significant association.43 Postnatal
depression has shown consistent associations (including
Attachment studies from LMICs45–49) with a range of cognitive outcomes
Attachment is when a young child uses a caregiver as in early childhood, including infant ability to learn,
a secure base from which to explore and, when necessary, achievement of developmental milestones, and language
as a haven of safety and source of comfort.64 This and general cognitive development.26,37,50,51 Persistence of
attachment is based on early experiences with caregivers’ postnatal depression seems to be of particular importance
extent of responsiveness with the child. in relation to cognitive development (table 4).49–51

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Studies of the longer term effects of postnatal and concerns about body shape and weight and use of
depression on cognitive functioning have been dietary restraint at 10 years of age. The second study
inconsistent. Results from a large study44 showed an showed that eating disturbance at age 5 years was
association between symptoms of postnatal depression predicted by many postnatal maternal variables, such
and very small decreases in IQ scores at age 8 years, as body dissatisfaction and the internalisation of the
which became non-significant after accounting for thin ideal82 and at age 8 years, high postnatal maternal
maternal depressive symptoms after the postnatal period. dietary restraint predicted high body dissatisfaction and
Another large study37 reported no association between dieting behaviours only in girls.83
postnatal depression and low maths acheivement at age
11 years and a small UK study53 showed an association Fathers
between postnatal depressive disorder and academic Traditionally, the mother’s mental health received most
achievement in adolescence. attention. However, recognition of the importance of
Several studies have investigated perinatal depression father’s mental health is increasing.84 Fathers can affect
and anxiety by use of self-reporting. Associations with their children directly via quality of their interactions
poor child cognitive outcomes were specific to or genetic effects, or indirectly via their support to the
symptoms of depression; these included studies of mother and family environment. A large Norwegian
antenatal42 and postnatal42,45 symptoms. Other studies52 population study54 reported an association between
have reported that symptoms of antenatal anxiety, rather symptoms of paternal antenatal depression and poor
than depression, were associated with poor exam socioemotional and behavioural development of
achievements at age 11 years. An association was children at age 36 months;54 postnatal symptoms
reported between antenatal symptoms of anxiety and were not assessed. However, another study21 reported
impaired executive function abilities.68 no evidence that paternal symptoms of antenatal
We found no studies that reported associations depression were associated with child depression at
between other disorders in mothers during the perinatal age 18 years, rather only an association with paternal
period and their child’s cognitive development. symptoms of depression postnatally.21
Symptoms of paternal postnatal mental disorders are
Child physical growth and development associated with an increased risk of emotional and
Evidence is emerging that poor perinatal maternal behavioural disorders for young children,15,56 difficulties
mental health, especially in women at a socioeconomic with their language development,85 and depression at
disadvantage, is linked to poor infant growth. Although age 18 years.21 Paternal and maternal depression in the
some studies, especially those done in HICs, have not postnatal period seem to have similar effects on
noted such associations or only in subgroups,69–71 behavioural outcomes, whereas maternal depression has
increasing data from populations living in LMICs a greater risk for emotional difficulties.15,32,84,55 In a meta-
suggests that perinatal depression is associated with analysis86 of associations between both maternal and
underweight and stunting in infancy35,72–74 with effects paternal disorders and their child’s internalising or
persisting up to school age of 5 years.72,75 Children of externalising difficulties across childhood, the younger
mothers with chronic depression (multiple episodes) the age of the child at the time of study, the greater
might be particularly at risk of stunting or being the effect sizes for associations with maternal depression,
underweight in LMICs.76,77 By contrast, a systematic but the reverse was reported for paternal depression.86
review78 of studies in HICs reported chronic depression
after childbirth was associated with the child being Mechanisms
overweight.78 Postnatal depression in LMICs is associated Overview
with high rates of diarrhoeal diseases in children,79 The figure shows a model summarising possible
which could contribute to their poor growth. Of the few mechanisms underlying the associations between
studies of other perinatal disorders, some evidence parental psychiatric disorders and child outcomes.
exists that children of mothers with eating disorders, Biologically mediated effects of antenatal disorders
mainly those with anorexia nervosa, are at increased risk (through in-utero effects) would be specific to mothers,
of poor growth.80 whereas effects occurring postnatally and genetic
effects might occur if either parent is affected by
Feeding, eating habits, and attitudes a disorder.
Children of mothers who had an eating disorder during
pregnancy or in post partum are susceptible to Genetic factors
difficulties during infancy, such as mealtime conflict.80 Shared genetic risk factors probably account for part of the
Two longitudinal studies81,82 reported an increased risk association between parental mental disorders at any time
for negative outcomes in children of mothers with (including the perinatal period) and child susceptibilities.
postnatal eating psychopathology. One of these studies81 However, evidence exists for a substantial environmental
reported increased mealtime conflict at 5 years of age, contribution in the cause of mental disorders.88 Correlations

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Time Exposure measure Outcome measure (child) Age of Results Strengths and limitations
of first (maternal) child at
exposure follow-up
Clinical Self-report Objective Question- Confounding variables Mediators or
interview assessment naire (parent included moderators
or objective or interview or child
assessment reported)
Koutra 2012; Antenatal Not STAI-Trait Bayley III Not 18 months Lower cognitive Bayley score Maternal age, maternal Personality traits
n=223; reported EPDS, reported was associated with antenatal education, gestational age, associated with
Greece (Rhea personality depression (β –5·45 [95% CI quality of assessment, sex of infant neuro-
study)42 trait (EPQ-R) –10·44 to –0·46]); and child, and duration of developmental
postnatal depression (β –5·80 breastfeeding, parent scores
[–11·65 to –0·05]); no effect of employment status
trait anxiety for cognitive
development, no associations
with maternal symptoms and
Bayley language scores
Tse 2010; Antenatal Not EPDS PPVT (language) Not 3 years No evidence for an association Maternal race or ethnic origin, Not reported
n=1030; USA43 reported WRAVMA (visual reported between antenatal depression age, and education; parity,
motor) and PPVT score (β –0·7 [95% CI household income, pregnancy
–3·6 to 2·3]); WRAVMA intention, partnership status,
(β –0·5 [–3·0 to 2·1]) partner education, alcohol use
and smoking, birthweight for
gestational age
Barker 2011; Antenatal Not EPDS and WISC (IQ) Not 8 years Low IQ was associated with Adjusted for a cumulative risk Not reported
n=3298; reported Crown Crisp reported antenatal depression (β –0·05, score derived from SES,
UK (ALSPAC)17 index p<0·05), and postnatal marital status, teenage
depression (β –0·04, p<0·05); no mother, substance use and
association with anxiety history of criminal activities,
antenatal and postnatal
anxiety and depression,
mutually adjusted
Evans 2012; Antenatal Not EPDS WISC (IQ) Not 8 years Antenatal depression was Parity, maternal age smoking Accumulation
n=6735; reported reported associated with a small decrease and drinking, parental social of depression in
UK (ALSPAC)44 in IQ points, which attenuated class, maternal education, childhood best
after adjustments (β –0·64 disposable income, sex of child explained the
[95% CI –1·68 to 0·40]); no association with
association between postnatal low IQ points
depression independent of
other time periods
Hadley 2008; Postnatal Not HSCL Not reported Denver II 3 months Maternal total symptoms were Child age and sex, stunted Not reported
n=431; reported develop- and associated with low growth, maternal and
rural Ethiopia45 mental test 24 months developmental scores (β –0·003 paternal age, maternal and
[SE 0·001], p<0·001); separating paternal body–mass indexes,
symptoms into depression and household factors, paternal
anxiety, depression (p<0·01) and depression
not anxiety (p=0·51) was cause
of the noted association
Galler 2000; Postnatal Not Zung scale* Griffiths scale Not 6 months Negative correlation between Socioeconomic and home Not reported
n=226; reported (DQ) reported postnatal mood at age 7 weeks environment factors derived
Barbados46 and total Griffiths score at age from Socioeconomic and
6 months (r=–0·32, p<0·05) Home Environment
Questionnaire gestational age,
parity, and birth order; infant
weight at 3 months, length at
3 months and 6 months
Patel 2003; Postnatal Not EPDS DASII (develop- Not 6 months Postnatal depression was Birthweight and maternal Not reported
n=171; India47 reported mental reported associated with greater risk of education
assessment) poor development in infant
(OR 3·3 [95% CI 1·2–8·8])
Hamadani Postnatal Not EPDS Bayley (MDI) Not 6 months Weak correlations between Child age at the time of Association
2012; n=488; reported and reported reported and postnatal depression and assessment, socioeconomic attenuated once
Bangladesh48 milestones 12 months impaired mental development factors, nutritional status, and family care
(r=–0·04, p>0·05) and postpartum maternal indicators were
milestones (r=–0·08, p<0·05) morbidity included
(Table 4 continues on next page)

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Time Exposure measure Outcome measure (child) Age Results Strengths and limitations
of first (maternal)
exposure
Clinical Self-report Objective Question- Confounding variables Mediators or
interview assessment naire (parent included moderators
or objective or interview or child
assessment reported)
(Continued from previous page)
Quevedo 2012; Postnatal DSM-IV, Not Bayley III Not 12 months Postnatal depression duration Maternal age, sex of child, Duration of exposure
n=296; Brazil49 MINI reported language score reported (depressed on no, one, or parity, primary caregiver of postnatal
two occasions in first year) depression
associated with lower language associated with
Bayley scores (β –2·87 [95% CI more impaired
–5·01 to 0·64]) language
Kaplan 2011; Postnatal Clinical BDI-II Infant learning Not 12 months Infants aged 1 year of currently Not reported Duration of perinatal
n=134; USA50 interview, by observed reported depressed mothers with episode exacerbated
SCID, conditioned relatively longer-duration the association
DSM-IV attention task depressive episodes (ie,
perinatal onset) showed
significantly poorer learning
than infants aged 1 year of
currently depressed mothers
with relatively shorter duration
depressive episodes
(non-perinatal onset)
Conroy 2012; Postnatal Clinical Not Bayley II, MDI Not 18 months Postnatal depression was Occupation, ethnic origin, Not reported
n=200; UK26 interview, reported (mental reported associated with impaired partner status, later maternal
DSM-IV, subscale) ITSEA mental development (β –7·26 depression, sex of infant,
SCID-I, NP [95% CI –13·04 to –1·47], maternal sensitivity
p<0·05)
Sutter-Dallay Postnatal Clinical EPDS Bayley II (MDI) Not 2 years Postnatal depression associated Sex of child, maternal age, Mediated by later
2011; n=598; Interview reported with a low Bayley MDI score maternal education, income, depression in
France51 DSM-IV- (β –1·11 [95% CI –1·92 to –0·30], parity mother
MINI p<0·05)
Kersten- Postnatal Clinical BDI PPVT-R Teacher Early school See table 1; postnatal depression See table 1 Moderated by sex of
Alvarez 2012; interviews; report social (child was associated with low verbal the child;
n=142 (29 with DSM-IV competence; average intelligence only in girls associations were
depression); CBCL age of stronger for girls
Netherlands27 5 years) than for boys
Letourneau Postnatal Not CES-D Language, Not Between Association between postnatal SES, income adequacy, Mediated by later
2013; n=10 033 and later reported (12 items) maths reported 4–5 years depression and low language at mothers’ years of education, depression, family
(age 4–5 years), achievement and age 5 years (OR 1·39, p>0·05) family structure, and family functioning and
n=2427 11 years and low maths achievement at functioning parenting style
(age 11 years); age 11 years (OR 1·17, p>0·05)
Canada37
Galler 2004; Postnatal Not Zung scale* Exam scores at Not 11 years Maternal anxiety (not Socioeconomic and home Not reported
n=92; reported school entry reported depression) at 7 weeks environment factors derived
Barbados52 (Eleven-Plus correlated with overall exam from Socioeconomic and
examination) score (r=–0·25, p<0·05) Home Environment
Questionnaire, gestational
age, parity, and birth order
Murray 2010; Postnatal Clinical Not Bayley scales Not 16 years Postnatal depression associated Maternal IQ and cognitive Mediated by early
n=89; UK53 interviews reported MDI at reported with lower exam grade points support, social class cognitive
SPI, SADS-L 18 months, (GCSEs) in children, particularly considered but not included in impairments (on
McCarthy scale in boys whose mothers have final model Bayley scale) and
at age 5 years, postnatal depression than in cognitive support
WISC-III at age boys whose mothers did not from mother; effects
8 years, GCSE have postnatal depression limited to boys
exam results at postnatal depression
the end of school by interaction of the
age 16 years sex of the child
(p=0·03)

STAI=state-trait anxiety inventory. EPDS=Edinburgh postnatal depression scale. EPQ-R=Eysenck personality questionnaire revised. PPVT=peabody picture vocabulary test. WRAVMA=wide range assessment of
visual motor abilities. WISC=Wechsler intelligence scale for children. ALSPAC=Avon longitudinal study or parents and children (UK). SES=socioeconomic status. HSCL=Hopkins symptom checklist.
DASII=developmental assessment scales for Indian infants. DQ=development quotient. MINI=mini-international neuropsychiatric interview. SCID=structured clinical interview for DSM-IV. DSM=diagnostic and
statistical manual. BDI=Beck depression inventory. NP=non-patient edition. MDI=mental development index. ITSEA=infant toddler social emotional assessment. CES-D=centre for epidemiologic studies
depression scale. SPI=standardised psychiatric interview. SADS-L=schedule for affective disorders and schizophrenia-lifetime. *Self report for anxiety and depression.

Table 4: Cognitive outcomes

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(both passive and evocative) between genetic and variations in modifying environmental exposures is
environment factors89 could account for a proportion of likely to be very small and genetic susceptibility to
variance in associations between parental disorders environment will be defined by many, interactive
and child outcomes through genetic-confounding. Our variations in the genome.
knowledge of this genetic contribution remains restricted.
Children’s inherited genotype might also determine Epigenetics
individual differences in their susceptibility to environ- Epigenetic change (modification of gene expression,
mental effects. Interest has been shown in the possibility such as through methylation, without changing the
that gene polymorphisms can moderate the effect of genetic sequence) is a mechanism proposed to explain
many early-life adversities, including maternal mental the long-lasting effects of early life experiences,
disorders, on child development. Although including the perinatal environment, on biological and
some individual reports exist about effects of behavioural phenotypes.
gene-by-environment interactions when applied to both Investigations have mainly been derived from animal
antenatal90 and postnatal environment,91 results are studies; however, preliminary human studies report
often not replicated and the effect of single genetic that antenatal stress and anxiety increases glucocorticoid

Time Exposure Outcome measure (child) Age of Results Strengths and limitations
of first measure children at
exposure (paternal) follow up
Self-report Objective Questionnaire Confounding Mediators or moderators
assessment (parent or child variables included
or interview reported)
Kvalevaag 2013; Antenatal SCL-5 Not SDQ, ITSEA, CBCL 3 years Paternal antenatal depression was Paternal age, Not reported
n=31 663; reported (operationalised into associated with emotional problems education, marital
Norway three summary (OR 1·45 [95% CI 1·19–1·77]); status, somatic
(MoBa study)54 scores: behavioural behavioural problems (OR 0·13 conditions, lifestyle
difficulties, emotional [0·11–1·40]); and impaired social variables, use of
difficulties, and social functioning (OR 1·30 [1·06–1·59]) alcohol, cigarette
functioning) smoking, physical
activity
Velders 2011; Antenatal BSI Not CBCL (internalising 3 years Antenatal paternal depression was Maternal symptoms; Mediated by parental
n=2698; reported problem binary) associated with internalising (OR 1·15 see table 1 hostility and prenatal
Netherlands [95% CI 1·05–1·26]) and externalising family functioning
(generation-R)15 (OR 1·12 [1·02–1·23])
Pearson 2013; Antenatal EPDS CIS-R Not reported 18 years Antenatal paternal depression was not None (secondary Postnatal but not
n=2475; associated with offspring depression analysis only) antenatal paternal
UK (ALSPAC)21 (OR 0·9 [95% CI 0·7–1·1]); postnatal depression was
depression was associated with moderated by paternal
offspring depression in fathers with education
low education (OR 1·5 [1·1–2·0]) but
not high education (OR 1·0 [0·7–1·3])
Fletcher 2011; Postnatal K6 Not SDQ (binary) 4–5 years Paternal postnatal depression was Socioeconomic Paternal postnatal
n=2620, reported associated with behavioural problems position, maternal depression measured at
Australia55 (OR 1·93 [95% CI 1·75–2·14]); and low education, and child age of 2–3 years
development and wellbeing (OR maternal depression was more strongly
1·65 [1·48–1·85]) associated with
hyperactivity and
pro-social in boys than
with girls, and more
strongly associated with
emotional, conduct,
and overall problems in
girls than in boys
Ramchandani 2008; Postnatal EPDS DAWBA, Not reported 6 years Paternal postnatal depression was Maternal depression, Effects of paternal
n=10 975; DSM-IV and 7 years associated with any disorder (OR 1·72 paternal education, postnatal depression on
UK (ALSPAC)56 [95% CI 1·07–2·77]), behaviour or later paternal hyperactivity, and
oppositional defiant disorder (OR 1·94 depression emotional and
[1·04–3·61]) behavioural problems
were both stronger in
boys than in girls

SCL=symptom checklist. SDQ=strengths and difficulties questionnaire (internalising and externalising symptoms). ITSEA=infant toddler social emotional assessment. CBCL=child behaviour checklist
(internalising and externalising symptoms). OR=odds ratio. MoBa=Norwegian mother and child study. EPDS=Edinburgh postnatal depression scale. CIS-R=child interview schedule-revised. ALSPAC=Avon
longitudinal study of parents and children (UK). BSI=brief symptom inventory (psychological symptoms). DAWBA=development and well being assessment. DSM=diagnostic and statistical manual.

Table 5: Outcomes for fathers

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receptor (involved in stress responses) methylation (ie, infants independently of postnatal depression.97 In
silencing) in children.92 Postnatally, maternal mental rodents, antenatal stress reduces nurturing behaviour of
disorders might change maternal caregiving, which in maternal care.98 This disruption to maternal
animal studies lead to epigenetic changes in offspring.93 programming might account for evidence that antenatal
Thus, epigenetic pathways might mediate the depression is associated with insecure attachment styles
association between maternal disorders and child independently of postnatal depression39 and an increased
outcomes, although this hypothesis has not been risk of children being exposed to maltreatment.99
formally tested.
Chronic exposure
Timing of perinatal mental health problems Several studies have shown that effects of perinatal
Mental disorders or symptoms in pregnancy often mental disorders are mediated by continued or recurrent
continue after birth, thus raising questions about the exposure to the disorder during the child’s life
contribution of antenatal and postnatal exposure and the (tables 1–5).29,37,44,51 That is, some variance in the association
extent to which their contributions are distinct, interactive, between perinatal disorder and child outcomes results
or cumulative. In particular whether antenatal effects are from the persistence of the parent’s disorder.
due to the direct effect on fetal development or because
antenatal symptoms continue postnatally. Interparent conflict
Perinatal mental disorders are associated with an increased
Mediating and moderating factors risk of interparent conflict, relationship breakdown, and
Overview domestic violence100 which, in turn, negatively affects
A mediator is part of the causal pathway whereas children.101 Evidence shows that interparent and family
moderators change the strength of association between conflict mediates the association between symptoms of
exposure and outcome, which is sometimes referred to postnatal depression and child externalising behaviours.36
as effect modification.87 Some factors can act as either
mediators or moderators. Parenting
A body of evidence suggests that the most important
Fetal programming potential mediator is the quality of parenting. Data for
Animal studies provide evidence that antenatal stress each component of this mediating pathway shows first,
leads to maladaptive cognitive and behavioural changes perinatal disorders and symptoms can compromise the
in rodent offspring.94 Often these changes are attributed quality of parenting; second, compromised early parenting
to the effect of increased cortisol concentrations or other is associated with disturbances in child development; and
biological results due to stress on the offspring’s brain third, disrupted parenting mediates the association
development in utero.94 However, findings of positive between perinatal mental health and child outcomes.
associations are inconsistent in human beings between Symptoms of mental disorders can affect a person’s
antenatal depression or anxiety and increased cortisol ability to respond to their environment, and thereby
concentrations,16 implicating a more complex mechanism. their parenting capabilities. For example, rumination
For example, anxiety in pregnancy has been associated and mood disturbance make it difficult for parents to
with the downregulation of the enzyme that metabolises focus their attention on, and provide contingent
cortisol and protects the baby in utero from excessive responsiveness towards, their infant’s cues.102 Several
cortisol concentrations.94 Thus, decreased expression of aspects of parenting are associated with postnatal
this enzyme might be a mechanism by which antenatal disorders, including disengagement and withdrawal;
anxiety affects the fetus, even in the presence of normal missing of infant cues; poor responsiveness and
concentrations of maternal cortisol. Importantly, although particularly insufficient contingent responsiveness;
the present model is based on adverse effects of antenatal intrusiveness;58,103 and difficulty in thinking about and
stress, clinical data suggests the possibility of a non-linear appreciating their children’s perspectives, thoughts,
association between antenatal depression and fetal and feelings.103 Often, the term “lack of sensitivity” is
stress.95 This postulation is consistent with some animal used to incorporate these sometimes overlapping
models, which indicates that some exposure to stress parenting capacities.103 Most of this research has
might be advantageous, with levels at both extremes included maternal depression, but some evidence
leading to more negative fetal responses.96 shows that different disorders are associated with
specific disruption to maternal parenting. Mothers with
Maternal programming eating disorders are more likely to use over-controlling
Mental disorders during pregnancy might disrupt and intrusive parenting, especially during mealtimes80
neurocognitive changes in the mother that prepare and anxious mothers use more intrusive parenting24
women to respond towards their infants, known as than do mothers without a psychiatric disorder. Mothers
maternal-programming.97 Antenatal depression is assoc- admitted to psychiatric mother and baby units
iated with reduced maternal responsiveness towards (particularly those with either schizophrenia

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and personality disorder) often display practical

difficulties in baby care, poor emotional responsiveness, Genetic processes
and intrusive behaviour with their infants.67,104,105
Parental difficulties in focusing their attention to Diet; smoking; Fetus in utero; neurobiological
drugs processes in pregnancy
infant signals and poor contingent responsiveness have
been negatively associated with development of children’s
attention and cognitive functioning in studies with
mothers with depression.103 An infant’s ability to control
attention and thus effectively process information is, in Parental Child Child outcome
cognitions; cognitions; cognitive; emotional;
turn, predictive of intellectual abilities.106,107 Parental psychiatric
emotions; behaviour; emotions; behaviour; attachment;
disorder
An important task for a parent is to support their infant neurobiological neurobiological behavioural;
processes processes growth
when distressed, to maintain or recover their emotional
equilibrium. Insufficient parental warmth, difficulties in
regulation of an infant distress (so-called emotional
Parenting;
scaffolding), and intrusiveness during stressful situations interparental relationship;
are negatively associated with child emotional regulation home environment
and behaviour.103
Two aspects of parenting are associated with a child’s Figure: Possible mechanisms underlying the association of parental psychiatric disorders and child outcomes
attachment security. First, disruptions to parental Dotted lines show genetic processes. Solid lines show interactions. Orange colours refer to the child. Blue colours refer
to the parents. Green represents genetic processes. Figure is based on figure 1 from Stein and Harold.87
availability and appropriate responsiveness to attachment
cues108 and second, the parent’s capacity to treat their
child as a psychological agent with thoughts, feelings, partum.114 These infant characteristics might evoke
and intentions.109 mood changes in carers, potentially setting a cycle of
Disorder specific behaviours, such as speech and affect, bidirectional effects between mother and child.
manifested by a parent can be modelled by or transmitted
to the child, leading to outcomes in the child that Moderating factors
resemble the parent’s disorder. Infants of mothers with Moderation can occur at two levels: a variable can
depression are more likely to show sad affect and vocalise moderate the primary association—eg, sex of the child
less, although these behaviours are probably in part due can directly modify associations between postnatal
to infant distress as a result of the parent’s insufficent depression and child behaviour—or can occur at the level
appropriate responsiveness.58,59 Infants of socially anxious of the mediator. For example, the association between
mothers display similar responses to their mother, such perinatal disorders and parenting (the mediator) is often
as fear and avoidance of strangers.110 moderated by socioeconomic circumstances.
Observed parental sensitivity mediates the association Important potential moderators of associations between
between both antenatal and postnatal depressive disorders perinatal disorders and child outcomes relate to the
and attachment security,39,41,111 and the association between mother’s practical and financial support and socioe-
postnatal depressive disorder and child emotion regulation conomic status.115 Children whose mothers have the same
during infancy24 and depression at age 16 years.30 extent of postnatal depression, but who are from a higher
Furthermore, parental responsiveness, cognitive support, socioeconomic status, are less likely to be adversely
and book reading to the child mediates the association affected. For example, in a large longitudinal study,21
between symptoms of postnatal depression and poor maternal education moderated the association between
cognitive development.37,53,112 Experimental evidence symptoms of postnatal depression and offspring
suggests that activation of negative cognitions, both in the depression at age 18 years. Only children of mothers with a
context of postnatal anxiety and depressive disorders, low level of education showed an increased risk of
diminishes the quality of parenting, which is associated depression themselves.21 In a large community study,112
with negative infant behaviour.102 socioeconomic status moderated the association between
Consistent with a role of modelling of disorder specific postnatal depression and language development. Quality
behaviours, mother and offspring depressogenic cog- of parenting was also measured in this study, showing that
nitions are correlated and partly mediate the association the moderating effect occurred at the level of parenting.112
between perinatal maternal depression and the child’s Evidence shows that a high socioeconomic status is
depression at age 18 years.113 protective of parenting in postnatal schizophrenia.116 Social
Assumptions should not be made that the direction of and emotional support, including partner support, reduces
effects is only from parent to child (figure). For example, associations between postnatal depression and early
some children are more difficult to raise because they cognitive development.117
frequently cry, sleep poorly, and are emotionally reactive. In LMIC settings, the quality of parenting might have a
High irritability in young infants is strongly associated greater role in a child’s physical wellbeing, because the
with the onset of maternal depression by 8 weeks’ post environment is harsher in LMICs than in HICs. Poverty,

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overcrowding, and poor sanitation are common, and functioning than did infants of mothers assigned to
with suboptimum maternal care, these factors potentially supportive counselling. Furthermore, improvements in
increase the risk to physical health of children. depression symptoms in mothers treated with cognitive
Many additional factors accentuate the risk of poor behavioural therapy correlated with infants’ develop-
outcomes in children of parents with perinatal mental outcomes.128 Additional studies have also
disorders: single parenthood, teenage parenthood (in reported that antidepressant treatment in pregnancy
HICs), and family disharmony.57 The severity and might be associated with better infant developmental
duration of the disorder and particularly persistence outcomes.3,128 Overall, this understudied question of
after the postnatal period has consistently been shown associations has yielded a mixed pattern of results
to be an important moderator.49,116,118 Results of a suggesting additional investigations are needed.
moderating effect of sex are inconsistent although girls
have been suggested to be more susceptible to Parenting interventions
emotional outcomes57 and boys to poorer behavioural Interventions designed to provide parent education and
and cognitive outcomes.119 Children who have specific improve parent–infant interactions for women with
temperaments, those who show high levels of negative perinatal disorders have had some promising findings.
emotions, are more affected by the quality of maternal Most interventions focused on postnatal depression,
care and might also be more amenable to interventions with no reported studies on interventions delivered
to help them.120 prophylactically in pregnancy. Home-visiting programmes
improve the quality of maternal–infant interactions
Treatment and prevention in women with depression.129,130 Additionally, psycho-
Although promising findings are emerging for the therapeutic approaches for mothers who have depression,
treatment and prevention of mental disorders during the including a mother–infant psychotherapy group and
perinatal period, few have investigated the potential benefit interpersonal therapy, increases mother interactions with
of such interventions for the wellbeing of the children.3 The their infants compared with interactions of mothers with
extent to which children benefit from such interventions is their infants in a wait-list control group.131 A meta-analysis132
important. For example, although reliable evidence shows concluded that the most effective parenting interventions
that maternal depression can be successfully prevented and for mothers with depression included infant massage,
treated,121,122 amelioration of depressive symptoms alone has support groups, or interventions with more than
not been shown to improve mother–child interactions.123 one component.
Thus, in addition to provision of treatment for depression, Additional approaches have targeted mother–child
efforts need to directly target improving mother–child interactions, often by use of individualised
interaction to potentially improve child outcome, in view of video-feedback which focused on improving the
evidence for the mediating role of parenting. That is, mothers’ sensitivity to infant cues. In women with
ongoing stressors, poor parenting, or persistent parental depression, video-feedback interventions have been
symptoms might contribute to difficulties for children even associated with improvements in quality of interactions,
in the absence of the mother’s disorder. infants’ attachment security, and social competence
The few studies examining associations between compared with women who received little telephone
treatment of maternal perinatal disorders and infant parenting support.133 Video-feedback treatment provided
outcomes have reported the following findings. Mothers to mothers with eating disorders led to improvements
with postnatal depression who participated in psycho- in mother–infant interactions and increased infant
therapy (either non-directive supportive counselling, autonomy by comparison with women who received
cognitive behavioural therapy, or psychodynamic supportive counselling.134 An intensive (about once a
psychotherapy) were associated with fewer toddler week for 1 year) mother–toddler intervention for
behavioural problems when aged 18 months than mothers of 20-month-old toddlers, who had had at least
children of mothers assigned to routine care. However, one major depressive episode since their child’s birth,
no effect on cognitive development or attachment was was associated with improved cognitive development
noted.124 Mothers’ reduced levels of depression after and secure attachment when compared with mothers
12 weeks of antidepressant drugs were associated who had not had depression since birth.135,136
with improvements in the quality of mother–infant In women with schizophrenia, approaches focusing
interaction and infant play.125 Interpersonal therapy for on increasing maternal sensitivity are effective in
mothers with postnatal depression decreased their level improving mother–infant interactions.137 An assessment
of depression, but was not associated with significant of video-feedback for mothers with acute postpartum
improvements in parenting or child outcomes.126,127 psychiatric illness and their infants admitted to a mother
Finally, pregnant women with both diabetes and and baby unit, reported improvements in mother–child
depression who participated in cognitive behavioural interactions compared with mothers with psychiatric
therapy had 6-month-old infants with better child diagnoses living in the community who had not received
development in psychomotor and behavioural inpatient care or video-feedback.138

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Several randomised controlled trials in LMICs showed mechanisms, especially modifiable pathways, is key to
that psychological interventions delivered by local development of interventions and identification of at risk
community health workers can have a positive effect on groups. For example, the quality of parenting is important
parenting and aspects of child development. A study in and an understanding of the relationship between specific
Pakistan139 used a form of cognitive behavioural therapy parenting behaviours and different child outcomes is
together with parenting support that began during crucial. Furthermore, if researchers can clarify the process
pregnancy.139 Rates of postnatal depression were reduced, that environmental factors, such as education and social
but no effect was noted on child growth, the principal support, mitigate the effects of perinatal disorders on the
outcome. Parents reported a reduction in rates of children’s child, this knowledge could be used in prevention.
diarrhoea, increased rates of immunisation, and increased Development of evidence-based interventions and
play with children, although the quality of parent–child preventive strategies for these parents and children,
interaction was not measured.139 In a socioeconomically including routine involvement of the father, is urgently
disadvantaged South African community, although not needed. In view of increasing evidence that experiences
exclusively in the context of maternal depression, an in the early years of life are crucial for healthy development
intervention focused on helping mothers to attend to the and productivity later in life and the number of people
details of the infant’s communication and to respond affected,3 interventions and prevention strategies should
sensitively.111 This intervention led to improvements in the be a public health priority. Recognition is needed that
quality of mother–child interaction and increased rates of addressing perinatal mental disorders can contribute
secure attachment.111 In Jamaica, an intervention targeting substantially to the Millennium Development Goals
child rearing and parenting self-esteem led to and the post-2015 Millennium Development Goals
improvements in both maternal depressive symptoms and agenda, specifically those related to child nutrition and
infant global development compared with intervention of early development, education, and maternal health
standard care.140 Determination of whether any (including antenatal care).143
improvements in mother and infant outcomes are Although an association exists between children whose
sustained is an important question for future research. parents have mental disorders during the perinatal
period and an increased risk of a range of adverse child
Interventions involving fathers outcomes, such negative outcomes are not inevitable.
Preliminary evidence shows that psychological Most effect sizes for associations between disorders in
interventions, such as cognitive behavioural therapy, can parents and outcomes in children were moderate or
be effective in reducing symptoms of depression in small. Moreover, we identified evidence for moderation
fathers during the postnatal period.141 However, no trials whereby factors, such as low socioeconomic status,
have assessed the effect of these interventions on absence of social support (including partner support),
parenting or child outcomes. Rather than focusing on and persistence of the parental disorder, increased the
treatment of maternal or paternal mental health in child’s risk of adverse outcomes. Conversely, when
isolation, another approach is to move towards more disorders occur in the absence of social adversity and if
inclusive perinatal mental health care, whereby the they are of short duration, the risks to the child
wellbeing of both parents are regarded and fathers are are generally low. Children in socioeconomically
routinely involved.141 In view of the importance of the disadvantaged circumstances, especially in LMICs, are
interparental relationship, correlations between maternal more likely to be both exposed to parental disorders and
and paternal symptoms, and evidence that paternal if their parent has a disorder to be affected than in
involvement can buffer the effect of maternal disorder on children whose parents do not have a disorder,
the child,142 this inclusive approach could improve highlighting the need for global strategies that focus on
outcomes for the whole family. A preliminary assessment integration of perinatal mental health and public health.
suggested that father inclusive information about Nonetheless, despite adversity many children in such
perinatal mental health, provided by health-care systems, situations develop normally and remain healthy, showing
improved paternal response to the newborn baby.141 resilience of parental care and child development.
Contributors
Policy implications and conclusions AS and LMH developed the outline of this Review. RMP did the
From a policy perspective, an essential first step is to literature searches with ER and MMcC. RMP and MMcC created all
tables. All authors contributed to the writing and editing of the
identify both parents and children who are at an increased manuscript. AS, RMP, and ER prepared the final version of the Series
risk of adverse outcomes as a result of perinatal mental paper, which all authors approved.
disorders to enable early treatment and prevention. Declaration of interests
Children also have needs that are not necessarily met by AS has received several grants in relation to parental perinatal health
treating the parental disorder alone. Although much and child development from the Wellcome Trust (090139), Medical
progress has been made to understand the mechanisms Research Council UK, Barclay Foundation, Grand Challenges
(Canada), and The Department for Education (UK). RMP is supported
and pathways to both healthy and disturbed development by an early career fellowship funded by a Wellcome Trust Institutional
of children, much remains to be done. Understanding of Strategic Award. RMP has been supported by grants from the

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 Series

Wellcome Trust. ER was previously employed on a grant funded by the 15 Velders FP, Dieleman G, Henrichs J, et al. Prenatal and postnatal
Wellcome Trust. LMH is chair of the NICE (update) guideline on psychological symptoms of parents and family functioning: the
Antenatal and Postnatal Mental Health. LMH is chief investigator of impact on child emotional and behavioural problems.
an National Institute of Health Research (NIHR) Programme Grant Eur Child Adolesc Psychiatry 2011; 20: 341–50.
for Applied Research on the effectiveness of perinatal mental health 16 Davis EP, Sandman CA. Prenatal psychobiological predictors of
services (grant number RP-RP-DG-1108-10012) which also supports anxiety risk in preadolescent children. Psychoneuroendocrinology
CMP, and has received funding from an NIHR Research Professorship 2012; 37: 1224–33.
(NIHR-RP-R3-12-011) on maternal mental health, and a grant from 17 Barker ED, Jaffee SR, Uher R, Maughan B. The contribution of
Tommy’s baby charity (with the support of a corporate social prenatal and postnatal maternal anxiety and depression to child
responsibility grant from Johnson and Johnson) on antipsychotics in maladjustment. Depress Anxiety 2011; 28: 696–702.
pregnancy. LMH is also supported by the NIHR Mental Health 18 Leis JA, Heron J, Stuart EA, Mendelson T. Associations between
Biomedical Research Centre at the south London and Maudsley NHS maternal mental health and child emotional and behavioral
problems: does prenatal mental health matter?
Foundation Trust and King’s College London. The views expressed are
J Abnorm Child Psychol 2013; 42: 161–71.
those of the authors and not necessarily those of the NHS, the NIHR,
19 Pawlby S, Hay DF, Sharp D, Waters CS, O’Keane V. Antenatal
or the Department of Health. CMP has received research funding and
depression predicts depression in adolescent offspring: prospective
consultancy fees from Eli Lilly, Servier, and Janssen, which are longitudinal community-based study. J Affect Disord 2009; 113: 236–43.
pharmaceutical companies involved in the development of
20 Korhonen M, Luoma I, Salmelin R, Tamminen T. A longitudinal
antidepressants in the past 5 years. CMP is supported by the Medical study of maternal prenatal, postnatal and concurrent depressive
Research Council and the European Commission; the NIHR and the symptoms and adolescent well-being. J Affect Disord Feb 2012;
NIHR Biomedical Research Centre for Mental Health at the south 136: 680–92.
London and Maudsley NHS Foundation Trust and King’s College 21 Pearson RM, Evans J, Kounali D, et al. Maternal depression during
London; the Wellcome Trust, the NARSAD, and the Psychiatry pregnancy and the postnatal period: risks and possible mechanisms
Research Trust; and Eli Lilly, and Janssen. We declare no other for offspring depression at age 18 years. JAMA Psychiatry 2013;
competing interests. 70: 1312–19.
22 Reck C, Muller M, Tietz A, Mohler E. Infant distress to novelty is
Acknowledgments
associated with maternal anxiety disorder and especially with
We thank Elena Netsi, Valerie West, and Miguel Cordero Vega for their
maternal avoidance behavior. J Anxiety Disord 2013; 27: 404–12.
support with this Series paper.
23 Bosquet Enlow M, Kitts RL, Blood E, Bizarro A, Hofmeister M,
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