Implications for clinicians of the Barker hypothesis

(what can we do about modifiable in utero risk factors?)

Professor Louise M Howard

Section of Women’s Mental Health

Institute of Psychiatry

King’s College London

Copyright restrictions may apply.

Grote, N. K. et al. Arch Gen Psychiatry 2010;67:1012-1024.

Effect of Antenatal Depression on Outcomes of PTB, LBW, and IUGR

Mental disorders and adverse fetal outcomes

Risk of LBW associated with antenatal depression sig larger in developing

countries (RR=2.05; 95% confidence interval, 1.43–2.93) compared with US

(RR=1.10; 95% confidence interval, 1.01–1.21) or European social democracies

(RR=1.16; 95% confidence interval, 0.92–1.47).

Meta-analysis in 1996 of OCs

Recent evidence from cohort studies:

• pregnancy complications incl gestational hypertension, placental

abruption, pre-eclampsia,

• preterm birth

• small for gestational age infants

• low APGAR scores in infants

Pregnancy and fetal outcomes and psychotic disorders Page 2

Bennedsen et al BJP 1998; Boden et al BMJ 2012; Jablensky et al Am J Psychiatry 2005; Lee

& Lin J Affect Disord 2010; Sacker et al Psychol Med1996; Vigod et al BJOG 2014

Meta-analysis of fetal death/stillbirth rate

in women with psychosis

Webb et al. American Journal of Psychiatry 2005

Neonatal deaths: relative risks of mortality for offspring of

mothers admitted with psychiatric illness vs Danish population

King-Hele S et al. Arch Dis Child Fetal Neonatal Ed 2009

Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

In utero environment associated with mental disorders –

potential risk factors and targets for intervention

• Psychiatric morbidity

• Other modifiable risk factors associated with mental

disorders

o medication

o smoking

o substance misuse

o nutritional deficiencies

o obesity

o domestic violence

Pregnancy and mental health Epidemiological studies - pregnancy generally not protective

Vesga-Lopez et al Arch Gen Psychiatry 20085.

Date of download: 6/26/2014 Copyright © 2014 American Medical

Association. All rights reserved.

From: Risks and Predictors of Readmission for a Mental Disorder During the Postpartum Period

Munk-Olsen et al. Arch Gen Psychiatry. 2009;66(2):189-195. doi:10.1001/archgenpsychiatry.2008.528

Relative Risks of First Readmission in Relation to Childbearing Among Danish Womena

Figure Legend:

Tertiary clinical sample - 22% with bipolar disorder relapse during pregnancy

Bipolar disorders greater risk than depression

Incidence rate ratio=4.85 (95% CI=3.32–7.23)

Impact of pregnancy on psychosis Page 8

Taylor et al In Prep; Viguera et al Am J Psychiatry 2011

Pregnant women in contact with SLAM

secondary mental health services

(CRIS 2007-11):

190 bipolar disorder – 15% relapsed in

pregnancy

236 non-affective psychosis – 26%

relapsed in pregnancy

Kaplan-Meier Survival Functions for Pregnant Patients With Bipolar Disorder Who Maintained or Discontinued Treatment

Viguera et al, Am J Psychiatry 2007

Mood stabilizer discontinuation ass with recurrence of BPD episode (RR 2) and shorter time to recurrence (adj HR 2.5)

Abrupt discontinuation vs gradual discontinuation

(RR=1.4)

Other predictors of relapse include bipolar II disorder

diagnosis, earlier onset,

more recurrences/year,

recent illness, use of

antidepressants, use of

anticonvulsants versus

lithium

CRIS study will investigate predictors of

relapse for bipolar disorder & schizophrenia

Study in community patients in antenatal care did not find antidepressants

reduced risk of depression (adj HR 0.88 [0.51—1.50] (Yonkers et al 2012)

Risk of relapse highest in women with h/o >4 depressive epsiodes

Risk of relapse if discontinue prophylactic medication Page 10

Cohen, L. S. et al. JAMA 2006;295:499-507

Impact of medication

Valproate – high rate of major malformations (10%), lowers IQ

Psychotropic Medication in pregnancy Page 12

Meador et al N Engl J Med 2009;

Smoking and adverse fetal outcomes Page 13

MacCabe et al Bipolar Disorders 2007

Mental disorders and smoking in pregnancy

• Leading preventable cause of fetal/infant morbidity & mortality in UK

• Pregnant women with mental disorders are more likely to smoke

• Cochrane SR (72 RCTs; n>25,000): Smoking cessation programmes in pregnancy reduce the proportion continuing smoke, improve birth outcomes

• Women with mental disorders may be less likely to be supported to stop smoking, but are likely to need intensive smoking cessation programmes

Nested qualitative study of 27 women – health professionals & women prioritised mental health over smoking

Some women thought stress may be worse for baby than smoking

“I think there are more harmful things than smoking. Like…..to take some medicaments or

even alcohol”.

Women reported health professionals also prioritised mental health over smoking

“don’t give up…we don’t want you getting anxiety or stressed”

Limited evidence on substance misuse

Howard et al BJOG 2013; Lumley et al 2009

One third of US women are overweight (BMI 25-30kg/m2) or obese (BMI >

30 kg/m2) when they become pregnant, with rising prevalence

UK - 16% women were obese at the start of pregnancy in 2004, 9.9% in

1990.

Obesity in pregnancy associated with adverse pregnancy outcomes incl

congenital neurological defects, childhood obesity, childhood ADHD

Systematic reviews:

• obesity associated with all categories of perinatal mental disorders

(50% pregnant women with psychosis on APs - overweight/ obese;

gestational diabetes)

• SMI child-bearing aged women more likely to have low folate and

B12; little research into other nutritional deficiencies

Some studies showing perinatal depression is associated with sub-

optimal diet

Obesity and nutrition Page 15

Barker et al 2013; Kulkarni et al 2014; McColl et al 2013; Molyneaux et al 2014;

Stothard et al JAMA 2009

Healthy dietary pattern scores by antenatal

depression status and BMI category (ALSPAC)

He

alth

y d

ieta

ry p

att

ern

sco

re

Normal weight Overweight Obese

Molyneaux et al In Prep

Domestic violence and birth outcomes Page 17

Shah and Shah J Women’s Hlth 2010

• Systematic review: high prevalence and increased odds (2-3) of

domestic violence among pregnant women across all diagnoses

studied

• CRIS SLAM data – 19% experienced domestic violence in pregnancy

• Identification of domestic violence by clinicians occurs in 10-30% of

cases

• Cochrane review– preliminary evidence on effectiveness of DV

interventions in pregnancy including advocacy

• Multi-faceted training and linked advocacy programmes effective in

improving identification and referral rates in primary care

• Pilot programme in secondary mental health care reduces abuse and

improves quality of life and social inclusion

• NICE (2014) guidance on identification and care pathways

Domestic violence & perinatal mental disorders Page 18

Feder et al 2011; Howard et al 2010; Howard et al 2013;

Jahanfar et al 2013; Trevillion et al 2013

Page 19

Characteristics of pregnant women on antipsychotics:

Australian cohort. Kulkarni et al PlosOne 2014

Page 20 Whole sample

N = 456

Non-affective

group, N=236

Affective

group, N=220

P*

Deprivation score, median(range)1 34.9 (3.8-77.2) 35.4 (3.8-77.2) 33.6 (6.8-9.7) 0.226

Maternal age at 1st index delivery,

mean(SD),

31.8 (6.2) 30.9 (6.4) 32.9 (5.8) <0.001

Partner during 1st index pregnancy

Yes 294 (71.5) 143 (68.1) 151 (75.1) 0.114

No 117 (28.5) 67 (31.9) 50 (24.9)

History of domestic abuse before

pregnancy

159 (34.9) 83 (35.2) 76 (34.6) 0.889

Domestic abuse in pregnancy 86 (18.9) 45 (19.1) 41 (18.6) 0.906

Smoking in pregnancy 79 (17.3) 51 (21.6) 28 (12.7) 0.012

Alcohol use in pregnancy 77 (16.9) 40 (17.0) 37 (16.8) 0.970

Substance use in pregnancy 61 (13.4) 39 (16.5) 22 (10.0) 0.041

Time since last admission (years)

1 year 104 (53.6) 65 (56.5) 39 (49.4) 0.326

2 years 90 (46.4) 50 (43.5) 40 (50.6)

Highest HoNOS total (range) 12 (0-36) 12 (0-36) 12 (0-28) 0.768

Taylor et al 2014 In Prep

Pregnant women with SMI under SLAM care 2007-11

Women with mental disorders are at risk of adverse

pregnancy, and longer term child, outcomes

Targeting of modifiable risk factors - ideally pre-conception

and during pregnancy - including optimal medication,

should improve outcomes for mother and child

Better understanding of how to optimise mental health and

associated physical health risks with tailored

interventions in the perinatal period is needed

Conclusions Page 21

Ackowledgements

Susan Bewley

Deborah Bekele

Jill Demilew

Theresa Marteau

Melissa Rowe

Clare Dolman

Ian Jones

Clare Taylor

Rob Stewart

Jack Ogden

Matthew Broadbent

Emma Molyneaux

Lucilla Poston

Gene Feder

Sian Oram

Kylee Trevillion

This presentation presents independent research funded by the National

Institute for Health Research (NIHR). The views expressed in this

publication are those of the author(s) and not necessarily those of the

NHS, the NIHR or the Department of Health.

Contact details:

louise.howard@kcl.ac.uk