Impact of a high Edinburgh Postnatal Depression Scale score on obstetric and perinatal outcomes

The aim of this retrospective study was to characterise intrapartum and neonatal outcomes in women with an antenatally recorded Edinburgh Postnatal Depression Score (EPDS) ≤ 9 compared with women with a score of ≥12 at a major Australian tertiary maternity hospital. Women with scores ≥12 are at particularly high risk of major depressive symptomatology. There were 20512 (78.6%) women with a score ≤ 9 and 2708 (10.4%) had a score ≥ 12. Category 1 caesarean sections where there was immediate threat to life (maternal or fetal) were more common in women with EPDS scores ≥12 (5.2% vs. 4.3%, OR 1.24 95% CI 1.03–1.49, p = 0.024). Pre-term birth (<37 weeks) was also more common (11.7% vs. 8.6%, OR 1.38 95% CI 1.21–1.57, p < 0.001). Women with high scores had higher rates of babies with birth weights <5th centile (6.2% vs. 4.4%, p < 0.001). Apgar score < 7 at 5 minutes were more frequent in the high EPDS group (3.1% vs. 2%, OR 1.52 95% CI 1.18–1.93, p < 0.001). Resuscitation at birth (34.4% vs. 30.6%, p < 0.001) and neonatal death (0.48% vs. 0.13%, OR 2.52 95% CI 1.2–5.0, p < 0.001) were higher in babies of these women. These results suggest poorer intrapartum and neonatal outcomes for women with high EPDS scores.

non-anomalous pregnancies without documented pre-existing mental health issues were included in the study. The Mater Mothers' Hospital is one of the largest tertiary obstetric hospitals in Australia with almost 10000 births per year. Maternal demographic, intra-partum and neonatal outcome data were collected from the hospital's electronic maternity database. Gestational age was calculated from either the last menstrual period or earliest ultrasound examination. Maternal body mass index (BMI) was calculated based on measurement of height and weight recorded at the booking visit.
Demographic information collected included maternal age, body mass index (BMI), ethnicity, and country of birth, parity and maternal medical conditions (hypertension, gestational diabetes, thyroid disease). Intra-partum outcomes included mode of delivery, duration of labour and length of stay in hospital. Caesarean sections were categorised as planned or emergency including the degree of urgency. Classification of the degree of urgency of caesarean section is generally based on one of four categories 15 : Category 1 -immediate threat to life (maternal or fetal); Category 2 -maternal or fetal compromise that is not immediately life-threatening; Category 3 -needing early delivery but no maternal or fetal compromise; or Category 4 -delivery at the convenience of the patient or obstetric team. Professional bodies such as the American College of Obstetrics and Gynaecology, National Institute of Clinical Excellence in the United Kingdom and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists all have broadly similar recommendations in that the decision to delivery interval for Category 1 caesarean sections should be no longer than 30 minutes. Perinatal outcome data included gestation at delivery, birth weight, Apgar scores < 7 at 5 min, umbilical artery pH < 7.2 and/or lactate > 4 mmol/L, need for resuscitation at birth, respiratory distress, infection, admission to the neonatal intensive care unit (NICU) and neonatal death.
All women completed the EPDS questionnaire at their booking visit regardless of gestation. For the majority of women this took place at < 20 weeks gestation. Each of the 10 questions was scored by the patient on a 4-point scale from 0-3 with a possible total score ranging from 0 to 30. We stratified our study cohort into two groups: low score (≤ 9) and high score (≥ 12). This categorisation has been shown to be predictive of the severity of depression with scores ≥ 12 indicating particularly high risk of major depressive symptomatology 16 .
Statistical analysis for this study was performed using the R and the R commander program (R Foundation for Statistical Computing, Vienna, Austria). Categorical variables were compared using a Chi-squared test. Continuous normally distributed variables were compared using a two sample t test and non-normally distributed variables were compared using a Wilcoxon rank-sum test. Multivariate logistic regression, adjusted for maternal age, BMI and parity was used to examine the effect of EPDS scores on intra-partum and neonatal outcomes. The level of significance was set at 0.05. Summary statistics are reported as number (percentage) and median (inter-quartile range) as appropriate.
Ethical and governance approvals were granted by the Mater Human Research Ethics Committee and Research Governance Office respectively (Ref no: HREC/14/MHS/63).

Results
Over the study period there were 31071 non anomalous, public births at the Mater Mothers' Hospital. We excluded 4961 women who did not have a recorded EPDS score leaving a final study cohort of 26110. There were 2708 women (10.4%) with an EPDS score ≥ 12, 2890 women (11.1%) with a score of 9-11 and 20512 women (78.5%) with a score of < 9. The majority of women (88%) had the EPDS recorded at < 20 weeks gestation.
Maternal demographics. Women with EPDS scores ≥ 12 were younger, born outside Australia and be significantly more obese (BMI > 40 kg/m 2 ) compared to women with a score of < 9. There was also a higher prevalence of indigenous women in this group. Maternal medical diseases (hypertension and thyroid disease) were more common in women with high EPDS scores. These women also had a longer hospital stay Table 1.

Intrapartum outcomes.
There was no difference in the rates of normal vaginal deliveries, instrumental births or planned caesarean sections in women with high EPDS scores compared with women with low scores. Emergency caesarean section rates were however higher in women with scores > 12 compared to those with scores < 9 (19% vs. 17.5%, OR 1.16 95% CI 1.04-1.29, p = 0.006). Category 1 caesarean sections where there was immediate threat to life (maternal or fetal) were more common in women with EPDS scores ≥ 12 (5.2% vs. 4.3%, OR 1.24 95% CI 1.03-1.49, p = 0.024) Table 2.

Discussion
The results from this study demonstrate that women with high EPDS scores have higher rates of emergency caesarean section particularly for concerns of fetal wellbeing. Our results also indicate that these women were significantly obese (BMI > 40 kg/m 2 ), younger, of indigenous origin or more likely to have been born outside Australia. We also found a higher prevalence of maternal medical diseases (hypertension and thyroid disease) in women with high EPDS scores. We also found an association with low birth weight and pre-term birth and high maternal EPDS (≥ 12) scores. More worryingly however we demonstrate a higher prevalence of poorer newborn condition at birth, higher rates of NICU admission and neonatal death. To our knowledge some of these findings have not been previously reported.
Perinatal mental health disorders are important clinically, as up to 15-20% of women may be affected and this can impact maternal, fetal and neonatal outcomes. There is also a higher prevalence of depression and anxiety in women from low and middle income countries compared to those from high-income countries 17 . It is frequently unrecognized in pregnancy because depressive symptoms such as insomnia, poor appetite and decreased libido may be attributed to the normal physiological changes that occur during pregnancy and the puerperium. Furthermore, many women may be reluctant to report changes in their mood. Perinatal depression is often associated with poorer outcomes for mother-infant bonding and subsequent relationship and marital quality. There is good evidence that women with chronic psychotic conditions particularly schizophrenia are more likely to have adverse obstetric and neonatal outcomes including congenital malformations, preterm birth, fetal growth restriction, stillbirth, neonatal and sudden infant deaths. Some of these complications may however be related to the medication these women receive [18][19][20][21] .
In some other studies antenatal depression has not been shown (in contrast to our study) to be associated with hypertensive disorders, low Apgar scores or admission to NICU 22 . Although the risk of low birth weight and preterm birth may be increased in women with depression, the magnitude of this effect appears to be influenced to some degree by socioeconomic status and country of origin, with an increased risk seen in low and middle income countries (LMIC) 23 . Some researchers have attempted to correlate fetal and neonatal outcomes with the use of antidepressants in pregnancy rather than with an actual diagnosis of depression. Although this is usually because of the availability of data of prescribing trends, it is nevertheless difficult to disentangle the effect of antidepressants, life style confounders, and depression 24,25 .
Depression and anxiety are both associated with increased concentrations of stress hormones. In particular, norepinephrine can cause uterine artery constriction 5 which may reduce both antenatal and intrapartum utero-placental perfusion. This could potentially impair fetal growth and increase the risk of intrapartum fetal compromise precipitated by uterine contractions in labour. Another hormone released during stress is corticotrophin-releasing hormone (CRH) with higher concentrations found in women with depression and anxiety disorders. As CRH is a key modulator of parturition and cervical ripening its higher concentrations in the context of women with depression and anxiety could explain the increased risk of preterm birth seen in these women 26,27 . However, not all studies have shown an increase in CRH levels in women with depression 28 .
One possibility to explain the disparities in neonatal outcomes seen in our study is the "weathering hypothesis" 29 . In our study there were greater numbers of indigenous and Asian women as well as those born outside of Australia in the public cohort. Given that Australia accepts a large number of migrants and refugees from some of the most socially disadvantaged regions of the world, the psychosocial stress resulting from their cumulative experiences may prematurely "age or weather" the reproductive system, contributing to the increased rates of poorer outcomes seen in this study 29,30 . Although it may be speculative at this stage, it is possible that factors influencing perinatal outcomes may go beyond ethnicity, insurance status, maternal co-morbidities and age but may also include a woman's previous social and psychological experiences.
Health professionals should be cognizant of the perinatal complications of mental health disorders both in pregnant women as well as women contemplating pregnancy so that appropriate surveillance, both maternal and fetal can be instituted. Women also need to be counselled about some of the potential intrapartum and perinatal complications associated with mental health problems and this is particularly important in the context of those on psychotropic medication. Although there isn't robust evidence to suggest that preconception stabilisation of mental health improves perinatal outcomes, as a general principle this should be the aim. In addition, post conception professional and family support as well as optimisation of medication is critical in the management of these women.
The strengths of our study are the large sample size with prospectively collected EPDS scores at the booking visit and detailed perinatal outcomes. The limitations of our study include its retrospective nature, the lack of additional information on lifestyle, smoking, socioeconomic status, family support, substance abuse and use of non disclosed psychotropic or other medication, all of which could have influenced our results. Our results could also have been confounded if depression occurred after the initial EPDS screen. Nevertheless, our key findings particularly the increased risk of emergency caesarean section for fetal concerns and the adverse neonatal outcomes especially neonatal death are worrying and warrant further investigation.