Perinatal complications increase the risk of postpartum depression. The Generation R Study
Dr H Tiemeier, Department of Child & Adolescent Psychiatry, Erasmus MC – Sophia, PO Box 2060, 3000CB Rotterdam, the Netherlands. Email firstname.lastname@example.org
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 increase the risk of postpartum depression. The Generation R Study. BJOG 2010;117:1390–1398.
Objective To examine whether specific 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 in the Generation R Study.
Methods Information on perinatal complications was obtained from 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 were assessed 2 months after delivery using the Edinburgh postnatal depression scale.
Results Several perinatal complications were significantly associated with postpartum depression, namely: pre-eclampsia (adjusted OR, aOR 2.58, 95% CI 1.30–5.14), hospitalization during pregnancy (aOR 2.25, 95% CI 1.19–4.26), emergency caesarean section (aOR 1.53, 95% CI 1.02–2.31), suspicion of fetal distress (aOR 1.56, 95% CI 1.08–2.27), a medically indicated delivery provided by an obstetrician (aOR 2.43, 95% CI 1.56–3.78), and hospital admission of the baby (aOR 1.45, 95% CI 1.10–1.92). Unplanned pregnancy, thrombosis, meconium-stained amniotic fluid, and Apgar score were not associated with postpartum depression after adjustment for confounding factors, such as pre-existing psychopathological symptoms and sociodemographic characteristics. The risk of postpartum depression increased with the number of perinatal complications women experienced (P < 0.001).
Conclusions We showed that several pregnancy and delivery complications present a risk for women’s mental health in the postpartum period. Obstetricians, midwives, general practitioners, and staff at baby well clinics should be aware that women who experienced perinatal complications—especially those with a number of perinatal complications—are at risk for developing postpartum depression.
Many women experience depressive symptoms during the postpartum period, ranging from mild complaints such as ‘maternity blues’ to clinically diagnosed postpartum depression. The prevalence of postpartum depression in the general population is estimated at around 10%, with most cases manifesting themselves in the first 3 months postpartum.1,2 The diagnosis is, however, often missed by healthcare professionals3 because some symptoms of depression according to the diagnostic criteria4 are difficult to recognise in postpartum women. If postpartum depression is left untreated it can persist for months to years,1 and may severely affect women’s health and psychosocial wellbeing.5,6 In addition, there is ample evidence that postpartum depression is associated with disturbances in the behavioural and cognitive development of offspring.5,7,8
Previous research reported that low socio-economic background, ethnic minority status, and a young age are associated with a higher risk of postpartum depression.5,9–13 Furthermore, various epidemiological studies identified social and psychological risk factors, such as stress, marital conflict, maternal perfectionism, antenatal depression or anxiety, and lack of social support.5,9,11,14,15 Although numerous studies have described these sociodemographic and psychosocial determinants, little research has investigated whether complications during pregnancy or delivery predict postpartum depression. Moreover, the few studies on this topic reported contradicting results. Whereas some studies found no perinatal risk factors for postpartum depression,12,16–18 another study characterised obstetric complications as modest but significant risk factors.13 The latter study, however, examined a composite score of obstetric complications, making it difficult to identify which specific complications predict postpartum depression.
Within a large birth cohort study in the Netherlands we studied a wide range of specific perinatal complications as risk factors for postpartum depression. Several of these complications are, to our knowledge, studied for the first time.
Design and study population
This study was embedded in the Generation R Study, a multi-ethnic population-based cohort from fetal life onwards. It has previously been described in detail.19 Briefly, all women living in Rotterdam, the Netherlands, with an expected delivery date between April 2002 and January 2006 were eligible for participation. Assessments included physical examinations and questionnaires during and after pregnancy. The Medical Ethical Committee of the Erasmus Medical Center, Rotterdam, approved the study. Written informed consent was obtained from all participants.
Full consent for the postnatal phase of the Generation R Study was obtained from 7295 women. Women with missing data on the Edinburgh postnatal depression scale (EPDS), either because of logistic problems at our research centre (14% received no questionnaire, n = 1051) or because of non-response (17.9%, n = 1303), were excluded. In total, 4941 women were included in the analyses. As some women had missing data on one or more perinatal complications (maximum 14% per complication), the number of women included in the separate analyses varies per complication studied.
Postpartum psychiatric symptoms were assessed 2 months after delivery with the EPDS, a widely used self-report scale that has been validated for the Dutch population.20,21 The EPDS assesses symptoms of postpartum depression in the previous week and comprises ten statements, each with four possible answers on a scale ranging from ‘no, not at all’ (0) to ‘yes, quite often’ (3). The EPDS sum score ranges from 0 to 30, with higher scores indicating more depressive symptoms. We classified women with a score of more than 12 as having postpartum depression. Previous research indicated that this cut-off score has a sensitivity of over 80% and a specificity of 95% for identifying women with clinically diagnosed postpartum depression in a community sample.22
The present study examined a wide range of perinatal complications as risk factors (indicated in italics) for postpartum depression. Information on the following complications was obtained from midwife and hospital registries (these complications were prospectively and routinely registered for all women). Pre-eclampsia and pregnancy-induced hypertension were defined according to the criteria described by the International Society for the Study of Hypertension in Pregnancy.23 Pregnancy-induced hypertension was diagnosed if previously normotensive women had a systolic blood pressure ≥ 140 mmHg and/or a 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 and obstetric guidelines using the following criteria: random glucose level > 11.1 mmol/l or a glucose level > 7.0 mmol/l after fasting, both in the absence of previously diagnosed diabetes. Suspicion of fetal distress was diagnosed on the basis of a fetal blood sample with a pH < 7.20 or a deviating cardiotocogram (e.g. repetitive decelerations, loss of variability, or increased baseline fetal hart rate). Type of delivery was divided into four categories: (1) spontaneous delivery; (2) instrumental delivery (including expression, forceps, and vacuum extraction); (3) elective caesarean section; (4) emergency caesarean section. Location of the delivery was either at home or in hospital. Although relatively uncommon in most Western countries, in the Netherlands approximately 30% of pregnant women give birth at home.24 This is the result of the Dutch system of obstetric care that is based on risk management. Women with low-risk pregnancies remain in primary care and may choose whether they want to deliver at home or in hospital: midwives provide the delivery in both places. Pregnant women with 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 provided by obstetricians in hospital. We categorised location of delivery as follows: (1) hospital delivery provided by an obstetrician; (2) hospital delivery provided by a midwife; (3) delivery at home provided by a midwife. Although the location of the delivery might not be a perinatal complication in itself, it may be associated with postpartum depression as it is a proxy for complications during pregnancy and delivery. Information on meconium-stained amniotic fluid (yes, no), Apgar score at 5 minutes after delivery (below seven; seven or higher), and birthweight of the child (<2500 g; ≥2500 g) was also obtained from routine midwife and hospital registry records. Gestational age was determined by fetal ultrasound examination conducted at our research centre.25Birth was classified as preterm if it occurred before 37 weeks of gestation.
The following perinatal risk factors were obtained by questionnaire. Upon enrolment, women reported whether or not the pregnancy was planned. At 30 weeks of gestation, women answered a question about whether they had been admitted to hospital for more than 24 hours during the first two trimesters of pregnancy. Two months after delivery, the women reported retrospectively on the prevalence of thrombosis during pregnancy, and whether or not their baby was admitted to hospital in the first week after delivery.
Based on the literature, we considered the following non-obstetrical factors as possible confounders in the association between perinatal complications and postpartum depression: maternal educational level, ethnicity, age, and general psychopathological symptoms, as well as family income and family functioning.4,8–13 Information on educational level, ethnicity, and age was obtained by questionnaire upon enrolment. Educational level, defined by the highest attained education, was divided into four categories, ranging from low to high. We categorised ethnicity as: ‘Dutch’, ‘other Western’, and ‘non-Western’. The questionnaire at 30 weeks of gestation included questions about income, family functioning, and general psychopathological symptoms. Family income was defined by the total net monthly income of the household, and was categorised as ‘<1200 euros’, ‘1200–2000 euros’, and ‘>2000 euros’. Family functioning during pregnancy was measured by the ‘general family functioning’ measure of the McMaster family assessment device.26 This scale consists of 12 statements about support and stress within the family: higher scores represent poorer family functioning. Psychopathological symptoms during pregnancy, like anxiety, depression, somatisation, hostility, and psychoticism, were assessed using the brief symptom inventory. The sum score of the 53 items indicates general psychopathology, with higher scores representing more symptoms.27 We consciously chose to adjust for general psychopathological symptoms and not only for depression, because anxiety during pregnancy is also a risk factor for postpartum depression. Results were, however, essentially unchanged if corrected for depressive symptoms instead of general psychopathological symptoms (data not shown, adjustment for both scales not feasible because of colinearity).
All analyses were performed using the Statistical Package of Social Sciences v15.0 for Windows (SPSS Inc., Chicago, IL, USA). Chi-square tests were used to describe the association of general population characteristics (categorical variables) and perinatal risk factors with postpartum depression. The relationship between continuous population characteristics and postpartum depression was described with analysis of variance (ANOVA; normally distributed variables) or Kruskal–Wallis (non-normally distributed variables) tests. Using logistic regression analyses we calculated odds ratios (ORs) for the risk factors that were significantly associated with postpartum depression, as indicated by the chi-square tests. The associations were controlled for possible confounding factors. Missing data on the confounding factors were replaced by the median (categorical variables or non-normally distributed continuous variables) or the mean (normally distributed continuous variables). In the multivariable regression analyses, we firstly calculated ORs adjusted for family functioning and general psychopathological symptoms of the mother, as we considered these covariates to be important potential confounding factors. Additionally, the ORs were adjusted for sociodemographic covariates, which may be confounding factors but could also be anteceding factors, i.e. sociodemographic factors causing depression through their association with pregnancy complications. Finally, we calculated a risk score per participant by summing the number of perinatal risk factors that were significantly associated with postpartum depression in the fully adjusted analyses. We examined the association between the number of perinatal risk factors and risk of postpartum depression with logistic regression analyses.
For the non-response analyses, women with missing data on the EPDS were compared with women who filled out the EPDS. Women with missing data (n = 2266) reported more general psychopathological symptoms (F-test = 12; df = 1; P = 0.001), poorer family functioning (F-test = 12; df = 1; P = 0.001), and a lower family income (χ2 test = 42; df = 2; P < 0.001) than women who completed the EPDS. They were also more likely to be educated to a lower level (χ2 test = 227; df = 3; P < 0.001), to be of non-Western origin (χ2 test = 181; df = 2; P < 0.001), and younger (F-test = 109; df = 1; P < 0.001).
The characteristics of the study population are presented in Table 1. Of the 4941 women, 396 (8%) had postpartum depression. These women reported more psychopathological symptoms (P < 0.001) and poorer family functioning during pregnancy (P < 0.001). Women with postpartum depression were also younger (P < 0.001), were more often educated to a lower level (P < 0.001), and were more often of non-Western origin (P < 0.001) than women with no postpartum depression. The mean age of all pregnant women in the study population was 31.0 years (SD = 4.8); depressed women were on average 29.7 years old (SD = 5.7).
Table 1. General population characteristics
|Parity (% nullipara)||4869||57.9||58.1||55.6|
|Twin birth (% yes)||4941||1.1||1.1||1.8|
|Gender (% boys)||4887||49.7||49.4||53.5|
|Psychosocial wellbeing characteristics|
|General psychopathological symptoms, score (range)**||4078||0.13 (0.00–3.04)||0.13 (0.00–2.73)||0.39 (0.00–3.04)*****|
|Family functioning, score (range)***||4046||1.42 (1.00–4.00)||1.42 (1.00–4.00)||1.50 (1.00–3.42)*****|
|Age 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*****|
| Dutch (%)||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*****|
| >2000 euros (%)||3731||75.5||77.2||56.1*****|
| 1200–2000 euros (%)||665||13.5||12.9||19.7*****|
| <1200 euros (%)||545||11.0||9.9||24.2*****|
The frequencies of perinatal complications among depressed and non-depressed women are presented in Table 2. In total, ten perinatal complications were significantly associated with a high prevalence of postpartum depression. For these complications, univariate regression analyses were used to calculate the corresponding unadjusted ORs for the risk of having postpartum depression (first column of Table 3). Secondly, we adjusted the association between perinatal complications and postpartum depression for maternal general psychopathological symptoms and family functioning (second column of Table 3). Thrombosis, meconium-stained amniotic fluid, and Apgar score at 5 minutes were no longer significantly associated with postpartum depression after this adjustment. Finally, we additionally adjusted these analyses for sociodemographic covariates (third column in Table 3). The following risk factors remained significantly associated with an increased risk of postpartum depression: pre-eclampsia (aOR 2.58, 95% CI 1.30–5.14), hospitalization during pregnancy (aOR 2.25, 95% CI 1.19–4.26), emergency caesarean section (aOR 1.53, 95% CI 1.02–2.31), suspicion of fetal distress (aOR 1.56; 95% CI 1.08–2.27), delivery in a hospital provided by an obstetrician or by a midwife (aOR 2.43, 95% CI 1.56–3.78; aOR 2.23 95% CI 1.38–3.62, respectively), and hospital admission of the baby (aOR 1.45, 95% CI 1.10–1.92). The relationship between unplanned pregnancy and postpartum depression was explained by both psychosocial wellbeing and sociodemographic characteristics: the OR was reduced by 79% from 2.12 to 1.24.
Table 2. Frequencies of perinatal complications by score on the Edinburgh postnatal depression scale
|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 delivery|
|Spontaneous 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 fluid (% yes)||14.8 (n = 646)||18.8 (n = 72)*|
|Location of delivery|
|At 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 <7 at 5 minutes (% yes)||0.8 (n = 37)||2.4 (n = 9)**|
|Hospital admission of the baby (% yes)||16.5 (n = 731)||22.2 (n = 86)**|
Table 3. Perinatal complications and the risk of postpartum depression
|Unplanned pregnancy (yes)||4454||2.12 (1.68–2.68)||<0.001||1.38 (1.06–1.80)||0.02||1.24 (0.94–1.64)||0.1|
|Pre-eclampsia (yes)||4647||2.40 (1.28–4.50)||0.007||2.63 (1.33–5.21)||0.005||2.58 (1.30–5.14)||0.007|
|Thrombosis (yes)||4876||3.51 (1.58–7.78)||0.002||2.38 (0.99–5.74)||0.05||1.74 (0.71–4.27)||0.2|
|Hospitalization during pregnancy (yes)||4236||2.56 (1.43–4.60)||0.002||2.44 (1.29–4.61)||0.006||2.25 (1.19–4.26)||0.01|
|Type of delivery|
|Spontaneous delivery||3131||Reference|| ||Reference|| ||Reference|| |
|Instrumental delivery||797||0.85 (0.63–1.15)||0.3||1.01 (0.73–1.40)||0.9||1.07 (0.77–1.49)||0.7|
|Elective caesarean section||225||0.93 (0.56–1.56)||0.8||0.94 (0.53–1.66)||0.8||0.99 (0.56–1.75)||0.9|
|Emergency caesarean section||322||1.48 (1.03–2.14)||0.04||1.49 (0.99–2.23)||0.05||1.53 (1.02–2.31)||0.04|
|Suspicion of fetal distress (yes)||4793||1.46 (1.04–2.04)||0.03||1.55 (1.07–2.24)||0.02||1.56 (1.08–2.27)||0.02|
|Meconium-stained amniotic fluid (yes)||4746||1.33 (1.02–1.74)||0.04||1.12 (0.83–1.52)||0.5||1.09 (0.80–1.48)||0.6|
|At home, provided by midwife||833||Reference|| ||Reference|| ||Reference|| |
|Hospital, provided by midwife||1112||3.48 (2.23–5.42)||<0.001||2.69 (1.68–4.30)||<0.001||2.23 (1.38–3.62)||0.001|
|Hospital, provided by obstetrician||2969||3.12 (2.05–4.73)||<0.001||2.70 (1.74–4.18)||<0.001||2.43 (1.56–3.78)||<0.001|
|Apgar score of <7 at 5 minutes (yes)||4743||2.85 (1.36–5.94)||0.005||2.27 (0.96–5.35)||0.06||2.21 (0.92–5.31)||0.08|
|Hospital admission of the baby (yes)||4828||1.45 (1.12–1.86)||0.004||1.42 (1.08–1.88)||0.01||1.45 (1.10–1.92)||0.009|
Finally, Table 4 shows the association between the number of perinatal complications per participant and the risk of postpartum depression. The sum score was based on the perinatal complications that remained significantly associated with postpartum depression in the fully adjusted analyses (see also third column Table 3). The majority of the participants (n = 3579, 74%) had none or just one complication, whereas only 6% of the participants experienced three or more complications. The risk of postpartum depression increased with a higher number of perinatal complications (P < 0.001, tested by including the number of risk factors per participant as a continuous variable in the model). Next to an accumulation of perinatal complications, psychopathological symptoms during pregnancy are an important risk factor for the development of postpartum depression. Low educational level and non-Western ethnicity were also independently associated with postpartum depression.
Table 4. Number of perinatal complications and the risk of postpartum depression (adjusted for prenatal psychosocial wellbeing and sociodemographic characteristics)
|Number of perinatal complications**|
|4 or 5||59||5.47 (2.25–13.3)||<0.001|
|General psychopathological symptoms (per score point)||4835||9.73 (7.19–13.2)||<0.001|
|Family functioning (per score point)||4835||1.28 (0.99–1.66)||0.056|
|Age mother (per year)||4835||1.01 (0.99–1.04)||0.252|
|Education level mother|
|Other Western||924||1.12 (0.82–1.54)||0.476|
|>2000 euros||3731||Reference|| |
|1200–2000 euros||665||1.15 (0.83–1.61)||0.408|
|<1200 euros||545||1.19 (0.86–1.63)||0.291|
This population-based study showed that various complications during pregnancy and delivery predicted postpartum depression in women 2 months after giving birth. Women who experienced more than two perinatal complications are especially at high risk of developing postpartum depression. Some perinatal factors, e.g. meconium-stained amniotic fluid, were associated with later postpartum depression, but these associations were explained by prenatal psychosocial wellbeing and the sociodemographic characteristics of the mother.
The strengths of the present study are the large number of women participating, the population-based design, and the availability of detailed information on numerous perinatal risk factors. We measured risk factors prospectively and routinely, which limits potential bias of diagnosing more perinatal complications in women at risk for postpartum depression than in women with a low risk of postpartum depression. Retrospective measurements have potentially limited previous research, and might explain the differences between our findings and other studies.12,13,18 A final strength of the study is that we controlled for several possible confounding factors. Previous studies reported associations between pregnancy complications and postpartum depression that were only marginally adjusted, and thus may have resulted from confounding factors.12,18,28,29 We showed the extent of confounding, as several perinatal complications were initially associated with postpartum depression, but these relations were explained by sociodemographic and prenatal psychosocial features. However, our thorough control for possible confounding factors may have led to an overadjustment of the associations, as some sociodemographic variables, e.g. educational level, may partly act as preceding factors in the relationship between perinatal complications and postpartum depression.
Some other limitations must also be discussed. The participants in this study represent a selection towards a more healthy population.30 Our non-response analyses showed that the EPDS data was more complete for highly educated, Western women. This resulted in an under-representation of the most disadvantaged groups, who are most at risk of postpartum depression.4,8–10,12 If similar effects were present in these disadvantaged women, our results would be an underestimation of the true associations. It is less likely that the selection led to spurious findings. Secondly, despite our large study population, the prevalence of some perinatal complications was rather low, and may have limited our power. Finally, a limitation of our study is that the EPDS was developed to screen for clinically relevant symptoms of postpartum depression, rather than for postpartum depression 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 complications predicted postpartum depression in women. Several mechanisms may explain these associations. Firstly, we hypothesise that the association between pre-eclampsia and postpartum depression may be caused by physical and hormonal changes. For example, serotonin levels in the blood are known to be increased in women with pre-eclampsia.31 This might lead to decreased levels of serotonin in the brain, thereby causing depressive symptoms.32
Another possible mechanism mediating the studied relationship is physical health. Women who had pregnancy complications or a troubled delivery, as indicated by an emergency caesarean section and fetal distress, are more likely to experience physical morbidity in the postpartum period.33 Physical morbidity can lead to higher rates of postpartum depression, as poor health is a well-known stressor because of pain, tiredness and limitations.
Thirdly, psychological mechanisms might underlie the association between complications and postpartum depression. Most women have particular expectations about their pregnancy, delivery, and postpartum period. Sudden life events, like a complex delivery or hospitalisation of the baby, lead to worries and feelings of disappointment and failure.4,8,10,13 This may affect a woman’s ability to adapt in the postpartum months, and cause her to experience depressive symptoms.
Finally, personality differences might explain that women with a hospital delivery have a higher risk of developing postpartum 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-confident, as they rely on having positive delivery outcomes, whereas it is known that self-confident women have a lower risk of postpartum depression as compared with neurotic women.5,8,14
Only a few studies have previously examined the relationship between perinatal complications and postpartum depression. To our knowledge, this was the first time that suspicion of fetal distress, meconium-stained amniotic fluid, and thrombosis were studied as risk factors of postpartum depression. Hence, further research is needed to confirm our findings. These studies should have a prospective design and consist of a large study population.
The detection and treatment of postpartum depression is important for both mothers and their children. It is important that obstetricians, midwives, general practitioners, and staff at baby clinics are aware of the substantially increased risk of postpartum depression associated with complicated pregnancies, difficult deliveries, and health problems of babies in the neonatal period. These healthcare workers must be particularly attentive for depressive symptoms in women who experienced a number of perinatal complications.
Disclosure of interests
There are no potential conflicts of interest.
Contribution to authorship
All authors have significantly contributed to this scientific work and approved the final version of the manuscript. EAB performed the data analyses and wrote the manuscript. PWJ was involved in the design of the paper, supervised the data analyses, and co-wrote the manuscript. FCV and HT were involved in the conception of the project, designing the paper, and provided financial and material support. HT supervised the drafting of the manuscript, whereas FCV revised the manuscript critically. HR was involved in the conception of the project and revised the manuscript significantly. AH and VWVJ were involved in the conception of the project, provided financial and material support, and helped to improve the manuscript. MC was responsible for data gathering and revised the manuscript critically. EAPS was involved in the conception of the project, supervised the data gathering, and helped improve the text.
Details of ethics approval
The Medical Ethical Committee of the Erasmus Medical Center, Rotterdam, approved the study (MEC 198.1782/2001/31 and MEC 217.595/2002/202). Written informed consent was obtained from all participants.
The first phase of the Generation R Study was made possible by financial support from: Erasmus MC – University Medical Centre Rotterdam; Erasmus University Rotterdam; and the Netherlands Organization for Health Research and Development (ZonMW). The present study was supported by an additional grant from the Netherlands Organization for Health Research and Development (ZonMW “Geestkracht” programme 10.000.1003). PWJ was financially supported by grant 602 from the Sophia Foundation for Medical Research SSWO.
The Generation R Study is conducted by the Erasmus MC – University Medical Center Rotterdam in close collaboration with the Erasmus University Rotterdam, School of Law and Faculty of Social Sciences; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of the participating pregnant women and their partners, general practitioners, hospitals, midwives, and pharmacies in Rotterdam.