perinatal complication increase the risk of postpartum depression

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Perinatal complications increase the risk ofpostpartum depression. The Generation R StudyEA Blom, a,b PW Jansen, b FC Verhulst, b A Hofman, c H Raat, d VWV Jaddoe, a,e M Coolman, f

EAP Steegers, f H Tiemeier c,d

a The Generation R Study Group b Department of Child and Adolescent Psychiatry c Department of Epidemiology d Department of PublicHealth e Department of Paediatrics f Department of Obstetrics and Gynaecology, Division of Obstetrics and Perinatal Medicine, Erasmus MCUniversity Medical Center Rotterdam, Rotterdam, the NetherlandsCorrespondence: Dr H Tiemeier, Department of Child & Adolescent Psychiatry, Erasmus MC Sophia, PO Box 2060, 3000CB Rotterdam,the Netherlands. Email [email protected]

Accepted 8 June 2010. Published Online 4 August 2010.

Objective To examine whether specic pregnancy and delivery

complications are risk factors for postpartum depression.Design A prospective longitudinal study.

Setting Rotterdam, the Netherlands.

Population A cohort of 4941 pregnant women who enrolled inthe Generation R Study.

Methods Information on perinatal complications was obtainedfrom the midwife and hospital registries or by questionnaire.Logistic regression analyses were used to calculate the risk of postpartum depression for the separate perinatal complications.

Main outcome measures Postpartum psychiatric symptoms wereassessed 2 months after delivery using the Edinburgh postnatal

depression scale.Results Several perinatal complications were signicantly associated with postpartum depression, namely: pre-eclampsia(adjusted OR, aOR 2.58, 95% CI 1.305.14), hospitalizationduring pregnancy (aOR 2.25, 95% CI 1.194.26), emergency caesarean section (aOR 1.53, 95% CI 1.022.31), suspicion of fetal

distress (aOR 1.56, 95% CI 1.082.27), a medically indicated

delivery provided by an obstetrician (aOR 2.43, 95% CI 1.563.78), and hospital admission of the baby (aOR 1.45, 95% CI1.101.92). Unplanned pregnancy, thrombosis, meconium-stainedamniotic uid, and Apgar score were not associated withpostpartum depression after adjustment for confounding factors,such as pre-existing psychopathological symptoms andsociodemographic characteristics. The risk of postpartumdepression increased with the number of perinatal complicationswomen experienced ( P < 0.001).

Conclusions We showed that several pregnancy and delivery complications present a risk for womens mental health in thepostpartum period. Obstetricians, midwives, general practitioners,and staff at baby well clinics should be aware that women who

experienced perinatal complicationsespecially those with anumber of perinatal complicationsare at risk for developingpostpartum depression.

Keywords Complications, delivery, depression, postpartum, preg-nancy, risk factors.

Please cite this paper as: Blom E, Jansen P, Verhulst F, Hofman A, Raat H, Jaddoe V, Coolman M, Steegers E, Tiemeier H. Perinatal complications increasethe risk of postpartum depression. The Generation R Study. BJOG 2010;117:13901398.

Introduction

Many women experience depressive symptoms during thepostpartum period, ranging from mild complaints such asmaternity blues to clinically diagnosed postpartum depres-sion. The prevalence of postpartum depression in thegeneral population is estimated at around 10%, with mostcases manifesting themselves in the rst 3 months postpar-tum. 1,2 The diagnosis is, however, often missed by health-care professionals3 because some symptoms of depressionaccording to the diagnostic criteria 4 are difcult to recog-

nise in postpartum women. If postpartum depression is leftuntreated it can persist for months to years, 1 and may

severely affect womens health and psychosocial wellbe-ing.5,6 In addition, there is ample evidence that postpartumdepression is associated with disturbances in the behaviouraland cognitive development of offspring. 5,7,8

Previous research reported that low socio-economicbackground, ethnic minority status, and a young age areassociated with a higher risk of postpartum depression. 5,913 Furthermore, various epidemiological studies identiedsocial and psychological risk factors, such as stress, marital

1390 2010 The Authors Journal compilation RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology

DOI: 10.1111/j.1471-0528.2010.02660.xwww.bjog.org

Epidemiology


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conict, maternal perfectionism, antenatal depression oranxiety, and lack of social support. 5,9,11,14,15 Althoughnumerous studies have described these sociodemographicand psychosocial determinants, little research has investi-gated whether complications during pregnancy or delivery predict postpartum depression. Moreover, the few studies onthis topic reported contradicting results. Whereas somestudies found no perinatal risk factors for postpartumdepression, 12,1618 another study characterised obstetric com-plications as modest but signicant risk factors. 13 The latterstudy, however, examined a composite score of obstetriccomplications, making it difcult to identify which speciccomplications predict postpartum depression.

Within a large birth cohort study in the Netherlands westudied a wide range of specic perinatal complications asrisk factors for postpartum depression. Several of thesecomplications are, to our knowledge, studied for the rsttime.

Methods

Design and study populationThis study was embedded in the Generation R Study, amulti-ethnic population-based cohort from fetal lifeonwards. It has previously been described in detail. 19

Briey, all women living in Rotterdam, the Netherlands,with an expected delivery date between April 2002 and Jan-uary 2006 were eligible for participation. Assessmentsincluded physical examinations and questionnaires duringand after pregnancy. The Medical Ethical Committee of theErasmus Medical Center, Rotterdam, approved the study.Written informed consent was obtained from all partici-pants.

Full consent for the postnatal phase of the Generation R Study was obtained from 7295 women. Women with miss-ing data on the Edinburgh postnatal depression scale(EPDS), either because of logistic problems at our researchcentre (14% received no questionnaire, n = 1051) orbecause of non-response (17.9%, n = 1303), were excluded.In total, 4941 women were included in the analyses. Assome women had missing data on one or more perinatalcomplications (maximum 14% per complication), thenumber of women included in the separate analyses variesper complication studied.

Outcome measuresPostpartum psychiatric symptoms were assessed 2 monthsafter delivery with the EPDS, a widely used self-report scalethat has been validated for the Dutch population. 20,21 TheEPDS assesses symptoms of postpartum depression in theprevious week and comprises ten statements, each withfour possible answers on a scale ranging from no, not atall (0) to yes, quite often (3). The EPDS sum score ranges

from 0 to 30, with higher scores indicating more depressivesymptoms. We classied women with a score of more than12 as having postpartum depression. Previous researchindicated that this cut-off score has a sensitivity of over80% and a specicity of 95% for identifying women withclinically diagnosed postpartum depression in a community sample.22

DeterminantsThe present study examined a wide range of perinatal com-plications as risk factors (indicated in italics) for postpar-tum depression. Information on the followingcomplications was obtained from midwife and hospital reg-istries (these complications were prospectively and rou-tinely registered for all women). Pre-eclampsia and pregnancy-induced hypertension were dened according tothe criteria described by the International Society for theStudy of Hypertension in Pregnancy. 23 Pregnancy-inducedhypertension was diagnosed if previously normotensive

women had a systolic blood pressure 140 mmHg and/ora diastolic blood pressure 90 mmHg after 20 weeks of gestation; if they additionally had proteinuria ( 300 mg/24 hour) they were diagnosed as pre-eclamptic. Gestational diabetes was diagnosed according to Dutch midwifery andobstetric guidelines using the following criteria: randomglucose level > 11.1 mmol/l or a glucose level > 7.0 mmol/lafter fasting, both in the absence of previously diagnoseddiabetes. Suspicion of fetal distress was diagnosed on thebasis of a fetal blood sample with a pH < 7.20 or a deviat-ing cardiotocogram (e.g. repetitive decelerations, loss of variability, or increased baseline fetal hart rate). Type of delivery was divided into four categories: (1) spontaneousdelivery; (2) instrumental delivery (including expression,forceps, and vacuum extraction); (3) elective caesarean sec-tion; (4) emergency caesarean section. Location of thedelivery was either at home or in hospital. Although rela-tively uncommon in most Western countries, in the Neth-erlands approximately 30% of pregnant women give birthat home. 24 This is the result of the Dutch system of obstet-ric care that is based on risk management. Women withlow-risk pregnancies remain in primary care and may choosewhether they want to deliver at home or in hospital: mid-wives provide the delivery in both places. Pregnant womenwith one or more risk factors (ranging from suspicion of

low fetal weight to an innate heart defect of the mother)get a medical indication for secondary care, which is pro-vided by obstetricians in hospital. We categorised locationof delivery as follows: (1) hospital delivery provided by anobstetrician; (2) hospital delivery provided by a midwife;(3) delivery at home provided by a midwife. Although thelocation of the delivery might not be a perinatal complica-tion in itself, it may be associated with postpartum depres-sion as it is a proxy for complications during pregnancy

Perinatal risk factors of postpartum depression

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and delivery. Information on meconium-stained amniotic uid (yes, no), Apgar score at 5 minutes after delivery (below seven; seven or higher), and birthweight of the child(


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pregnancy (P < 0.001). Women with postpartum depressionwere also younger (P < 0.001), were more often educated toa lower level (P < 0.001), and were more often of non-Wes-tern origin ( P < 0.001) than women with no postpartumdepression. The mean age of all pregnant women in the study population was 31.0 years (SD = 4.8); depressed womenwere on average 29.7 years old (SD = 5.7).

The frequencies of perinatal complications among

depressed and non-depressed women are presented inTable 2. In total, ten perinatal complications were signi-cantly associated with a high prevalence of postpartumdepression. For these complications, univariate regressionanalyses were used to calculate the corresponding unad- justed ORs for the risk of having postpartum depression(rst column of Table 3). Secondly, we adjusted the associ-ation between perinatal complications and postpartumdepression for maternal general psychopathological symp-

toms and family functioning (second column of Table 3).Thrombosis, meconium-stained amniotic uid, and Apgarscore at 5 minutes were no longer signicantly associatedwith postpartum depression after this adjustment. Finally,we additionally adjusted these analyses for sociodemo-graphic covariates (third column in Table 3). The followingrisk factors remained signicantly associated with anincreased risk of postpartum depression: pre-eclampsia

(aOR 2.58, 95% CI 1.305.14), hospitalization during preg-nancy (aOR 2.25, 95% CI 1.194.26), emergency caesareansection (aOR 1.53, 95% CI 1.022.31), suspicion of fetaldistress (aOR 1.56; 95% CI 1.082.27), delivery in a hospi-tal provided by an obstetrician or by a midwife (aOR 2.43,95% CI 1.563.78; aOR 2.23 95% CI 1.383.62, respec-tively), and hospital admission of the baby (aOR 1.45, 95%CI 1.101.92). The relationship between unplanned preg-nancy and postpartum depression was explained by both

Table 1. General population characteristics

Total study population Edinburgh postnatal depression scale

n * % % Normal(n = 4545)

% Clinicallyhigh ( n = 396)

Population characteristicsParity (% nullipara) 4869 57.9 58.1 55.6Twin birth (% yes) 4941 1.1 1.1 1.8Gender (% boys) 4887 49.7 49.4 53.5Psychosocial wellbeing characteristicsGeneral psychopathological symptoms, score (range)** 4078 0.13 (0.003.04) 0.13 (0.002.73) 0.39 (0.003.04)*****Fami ly functioning, score (range)*** 4046 1.42 (1.004.00) 1.42 (1.004.00) 1.50 (1.003.42)*****Sociodemographic characteristicsAge mother, years (SD) 4941 31.0 (4.8) 31.1 (4.7) 29.7 (5.7)*****Education level mother

High (%) 1438 29.1 30.4 14.1*****Mid-high (%) 1349 27.3 27.2 28.5*****Mid-low (%) 1359 27.5 27.0 33.3*****Low (%) 795 16.1 15.4 24.0*****

Ethnicity motherDutch (%) 3107 62.9 64.8 40.4*****Other Western (%) 924 18.7 18.8 17.9****Non-Western (%) 910 18.4 16.4 41.7*****

Family income>2000 euros (%) 3731 75.5 77.2 56.1*****12002000 euros (%) 665 13.5 12.9 19.7*****


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psychosocial wellbeing and sociodemographic characteris-tics: the OR was reduced by 79% from 2.12 to 1.24.

Finally, Table 4 shows the association between the numberof perinatal complications per participant and the risk of postpartum depression. The sum score was based on theperinatal complications that remained signicantly associ-ated with postpartum depression in the fully adjusted analy-ses (see also third column Table 3). The majority of theparticipants ( n = 3579, 74%) had none or just one complica-tion, whereas only 6% of the participants experienced threeor more complications. The risk of postpartum depressionincreased with a higher number of perinatal complications(P < 0.001, tested by including the number of risk factorsper participant as a continuous variable in the model). Nextto an accumulation of perinatal complications, psychopatho-logical symptoms during pregnancy are an important risk

factor for the development of postpartum depression. Low educational level and non-Western ethnicity were also inde-pendently associated with postpartum depression.

Discussion

This population-based study showed that various complica-tions during pregnancy and delivery predicted postpartumdepression in women 2 months after giving birth. Women

who experienced more than two perinatal complicationsare especially at high risk of developing postpartum depres-sion. Some perinatal factors, e.g. meconium-stained amni-otic uid, were associated with later postpartumdepression, but these associations were explained by prena-tal psychosocial wellbeing and the sociodemographic char-acteristics of the mother.

The strengths of the present study are the large number of women participating, the population-based design, and theavailability of detailed information on numerous perinatalrisk factors. We measured risk factors prospectively and rou-tinely, which limits potential bias of diagnosing more peri-natal complications in women at risk for postpartumdepression than in women with a low risk of postpartumdepression. Retrospective measurements have potentially limited previous research, and might explain the differences

between our ndings and other studies.12,13,18

A nalstrength of the study is that we controlled for several possi-ble confounding factors. Previous studies reported associa-tions between pregnancy complications and postpartumdepression that were only marginally adjusted, and thus may have resulted from confounding factors. 12,18,28,29 We showedthe extent of confounding, as several perinatal complicationswere initially associated with postpartum depression, butthese relations were explained by sociodemographic and

Table 2. Frequencies of perinatal complications by score on the Edinburgh postnatal depression scale

Perinatal complications Edinburgh postnatal depression scale

Normal ( n = 4545) Clinically high ( n = 396)

Unplanned pregnancy (% yes) 21.1 (n = 871) 36.2 ( n = 121)***Pre-eclampsia (% yes) 1.4 (n = 59) 3.2 (n = 12)**Pregnancy induced hypertension (% yes) 4.0 (n = 169) 3.8 ( n = 14)Gestational diabetes (% yes) 0.6 (n = 28) 1.0 (n = 4)Thrombosis (% yes) 0.6 (n = 27) 2.1 (n = 8)**Hospitalization during pregnancy (% yes) 1.8 (n = 70) 4.4 (n = 14)**Type of deliverySpontaneous delivery (%) 70.0 ( n = 2879) 69.8 ( n = 252)Instrumental delivery (%) 18.0 ( n = 742) 15.2 ( n = 55)Elective caesarean section (%) 5.1 ( n = 208) 4.7 ( n = 17)Emergency caesarean section (%) 6.9 ( n = 285) 10.2 ( n = 37)*Suspicion of fetal distress (% yes) 7.7 (n = 338) 10.8 ( n = 42)*Meconium-stained amniotic uid (% yes) 14.8 (n = 646) 18.8 ( n = 72)*Location of deliveryAt home, provided by midwife (%) 17.9 ( n = 808) 6.3 ( n = 25)***

Hospital, provided by midwife (%) 22.2 ( n = 1004) 27.4 ( n = 108)***Hospital, provided by obstetrician (%) 59.9 ( n = 2708) 66.2 ( n = 261)***Preterm birth (% yes) 4.6 (n = 207) 6.1 ( n = 24)Low birthweight (% yes) 3.9 (n = 168) 3.6 ( n = 13)Apgar score of


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prenatal psychosocial features. However, our thorough con-trol for possible confounding factors may have led to anoveradjustment of the associations, as some sociodemo-graphic variables, e.g. educational level, may partly act aspreceding factors in the relationship between perinatal com-plications and postpartum depression.

Some other limitations must also be discussed. The par-ticipants in this study represent a selection towards a morehealthy population. 30 Our non-response analyses showedthat the EPDS data was more complete for highly educated,Western women. This resulted in an under-representationof the most disadvantaged groups, who are most at risk of postpartum depression. 4,810,12 If similar effects were pres-

ent in these disadvantaged women, our results would be anunderestimation of the true associations. It is less likely that the selection led to spurious ndings. Secondly, despiteour large study population, the prevalence of some perina-tal complications was rather low, and may have limited ourpower. Finally, a limitation of our study is that the EPDSwas developed to screen for clinically relevant symptoms of postpartum depression, rather than for postpartum depres-sion itself. However, EPDS scores correspond closely to

clinical diagnoses, and are commonly used as a measure of postpartum depression. 22

We showed that various pregnancy and delivery compli-cations predicted postpartum depression in women. Severalmechanisms may explain these associations. Firstly, we hy-pothesise that the association between pre-eclampsia andpostpartum depression may be caused by physical and hor-monal changes. For example, serotonin levels in the bloodare known to be increased in women with pre-eclampsia. 31

This might lead to decreased levels of serotonin in thebrain, thereby causing depressive symptoms. 32

Another possible mechanism mediating the studied rela-tionship is physical health. Women who had pregnancy

complications or a troubled delivery, as indicated by anemergency caesarean section and fetal distress, are morelikely to experience physical morbidity in the postpartumperiod. 33 Physical morbidity can lead to higher rates of postpartum depression, as poor health is a well-knownstressor because of pain, tiredness and limitations.

Thirdly, psychological mechanisms might underlie theassociation between complications and postpartum depres-sion. Most women have particular expectations about their

Table 3. Perinatal complications and the risk of postpartum depression

Perinatal complications n Univariateanalyses*

Analyses adjustedfor prenatalpsychosocialwellbeing**

Analyses additionallyadjusted for

socio-demographiccharacteristics***

OR (95% CI) P OR (95% CI) P OR (95% CI) P

Unplanned pregnancy (yes) 4454 2.12 (1.682.68)


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pregnancy, delivery, and postpartum period. Sudden lifeevents, like a complex delivery or hospitalisation of thebaby, lead to worries and feelings of disappointment andfailure.4,8,10,13 This may affect a womans ability to adapt inthe postpartum months, and cause her to experiencedepressive symptoms.

Finally, personality differences might explain that womenwith a hospital delivery have a higher risk of developingpostpartum depression. We hypothesise that personality characteristics are associated with both choice of place of delivery and risk of postpartum depression. Presumably,women delivering at home are optimistic and self-con-dent, as they rely on having positive delivery outcomes,whereas it is known that self-condent women have alower risk of postpartum depression as compared with neu-

rotic women.5,8,14

Conclusions

Only a few studies have previously examined the relation-ship between perinatal complications and postpartumdepression. To our knowledge, this was the rst time thatsuspicion of fetal distress, meconium-stained amnioticuid, and thrombosis were studied as risk factors of post-

partum depression. Hence, further research is needed toconrm our ndings. These studies should have a prospec-tive design and consist of a large study population.

The detection and treatment of postpartum depression isimportant for both mothers and their children. It is impor-tant that obstetricians, midwives, general practitioners, andstaff at baby clinics are aware of the substantially increasedrisk of postpartum depression associated with complicatedpregnancies, difcult deliveries, and health problems of babies in the neonatal period. These healthcare workersmust be particularly attentive for depressive symptoms inwomen who experienced a number of perinatal complica-tions.

Disclosure of interestsThere are no potential conicts of interest.

Contribution to authorshipAll authors have signicantly contributed to this scienticwork and approved the nal version of the manuscript.EAB performed the data analyses and wrote the manu-script. PWJ was involved in the design of the paper, super-vised the data analyses, and co-wrote the manuscript. FCVand HT were involved in the conception of the project,

Table 4. Number of perinatal complications and the risk of postpartum depression (adjusted for prenatal psychosocial wellbeing andsociodemographic characteristics)

Variables included in the analyses n (total n = 4835)* OR (95% CI) P

Number of perinatal complications**0 770 Reference

1 2809 2.36 (1.453.83) 0.0012 956 2.93 (1.754.93)


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designing the paper, and provided nancial and materialsupport. HT supervised the drafting of the manuscript,whereas FCV revised the manuscript critically. HR wasinvolved in the conception of the project and revised themanuscript signicantly. AH and VWVJ were involved inthe conception of the project, provided nancial and mate-rial support, and helped to improve the manuscript. MCwas responsible for data gathering and revised the manu-script critically. EAPS was involved in the conception of the project, supervised the data gathering, and helpedimprove the text.

Details of ethics approvalThe Medical Ethical Committee of the Erasmus MedicalCenter, Rotterdam, approved the study (MEC 198.1782/2001/31 and MEC 217.595/2002/202). Written informedconsent was obtained from all participants.

Funding

The rst phase of the Generation R Study was made possi-ble by nancial support from: Erasmus MC University Medical Centre Rotterdam; Erasmus University Rotterdam;and the Netherlands Organization for Health Research andDevelopment (ZonMW). The present study was supportedby an additional grant from the Netherlands Organizationfor Health Research and Development (ZonMW Geestk-racht programme 10.000.1003). PWJ was nancially sup-ported by grant 602 from the Sophia Foundation forMedical Research SSWO.

AcknowledgementsThe Generation R Study is conducted by the Erasmus MC University Medical Center Rotterdam in close collaborationwith the Erasmus University Rotterdam, School of Law andFaculty of Social Sciences; the Municipal Health Service Rot-terdam area, Rotterdam; the Rotterdam Homecare Founda-tion, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. Wegratefully acknowledge the contribution of the participatingpregnant women and their partners, general practitioners,hospitals, midwives, and pharmacies in Rotterdam. j

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