In 1858 the visionary French physician, Victor-Louis Marcé, wrote a monograph titled Traité de la folie des femme enceintes (a treatise on the madness of pregnant women). During the early days of perinatal psychiatry in the 1980s and 1990s, clinicians and researchers focused largely on postpartum mental illnesses. The classical triad that is taught at an undergraduate and postgraduate level is that of postpartum blues, depression and psychosis. Marcé’s work, previously almost forgotten, anticipated the more recent rediscovery of the high risk of depression in pregnancy. 

Depressive symptoms are common during pregnancy and most women experience an increase in anxiety and depressive symptoms as pregnancy advances. These symptoms usually return to baseline by about six weeks postpartum.¹ Rates of clinical depression also increase as pregnancy advances, from about 7% – the normal rate in women in the non-perinatal period – in the first trimester; to 12% in the third trimester.² Postpartum rates reduce to about 10%. 

The perinatal period, in psychiatry, refers to the period from the onset of pregnancy up to one year postpartum. Perinatal depression (PD) is challenging clinically. Active management of PD is pivotal to the future mental health and wellbeing of the woman, her success as a parent, and the development and future wellbeing of her baby. This review will focus on the risk factors associated with PD, its consequences and its management.

PD may not present in the perinatal period and may not emerge until much later. A clear history about the timing of the onset of depression is valuable, as the vulnerability factors for the individual woman may be related to pregnancy, childbirth or motherhood. Another consideration is that depression in women outside the perinatal period is related to having three or more children and an early maternal age.³ Motherhood confers an increased risk of developing depression.

Aetiology of perinatal depression

Social and personal adversity

All of the risk factors for depression outside the perinatal period also pertain to PD. Some of these risks are amplified by pregnancy, particularly in the area of childhood sexual abuse (CSA);^4,5 and within this group adolescents may be even more vulnerable, particularly in the postpartum period.⁶ Another vulnerability factor amplified by pregnancy is socioeconomic deprivation. This is evident in the disparity in the rates of PD in economically developed countries compared to poorer nations;⁷ and also between different socioeconomic groups within the same country.⁸ Women who belong to racial minorities are recognised as being at an increased risk of developing PD.⁹

In my experience, domestic violence is common in women who suffer from PD. This year, the WHO published a document analysing global differences in the rates of violence against women, differentiating between intimate partner violence and sexual violence by a non-partner (www.who.int/reproductivehealth/publications). The prevalence of intimate partner violence is 25.4% in the WHO European region and should always be considered as a potential risk factor. The WHO findings indicate that the risk of depression is increased at least twofold in women subjected to domestic violence. This risk is amplified during the perinatal period. Howard et al (2013) estimate that there is a threefold increase in the odds of high levels of depressive symptoms in the postnatal period following partner violence during pregnancy.¹⁰

History of mood disorder

Some risk factors for PD are more biologically determined, such as a history of mood disorder, either recurrent depression or bipolar disorder type 1 or 2 (BD1 and BD2). BD1 is characterised by a pattern of manic and depressive episodes, whereas BD2 disorder is predominantly a depressive disorder with clinically insignificant episodes of hypomania. Overall, the risk of relapse is highest with BD1, followed by BD2 and then recurrent depression. For all these disorders, depression is the most common presentation, both during and following pregnancy. Mania is rare in the perinatal period.

Recurrent depression: There is a probable rate of relapse during pregnancy of about 40% in women with a history of recurrent depression.¹¹ The risk of relapse has been found to be significantly higher in women who discontinue antidepressant medication (68%), compared to women who remain on medication (26%).¹² A recent report of pregnant women who were being treated for depression prior to becoming pregnant indicates that about a half of these women discontinue medication on discovering that they are pregnant.¹³ Discontinuation of medication is more likely to occur in those who have unplanned pregnancies. Reinstatement of medication occurred in 58% of this sample later in pregnancy. Most women with a history of recurrent depression relapse postpartum, rather than during pregnancy.^11,14

Bipolar disorder: The risk of relapse in bipolar disorder is 50-78%, with the highest risk in the first month postpartum in women. There is convincing evidence that the rapid-onset, severe affective psychosis, usually called postpartum psychosis or puerperal psychosis, occurring in the first few weeks postpartum is related to the BD type 1 genotype.¹⁵ Women with a diagnosis of BD1 and a family history of postpartum psychosis have been found to have a 74% risk of developing this psychosis following the birth of their first child.¹⁵ The risk for women with a diagnosis of BD1, but who do not have a family history of postpartum psychosis, is 30%. This suggests that there is a specific vulnerability to postpartum psychosis transmitted within the BD1 genotype.

The clinical picture, mostly that of a pleomorphic psychosis with marked depressive or mixed affective experiences, is easily recognised in its most severe form. Less severe forms of psychosis may be difficult to recognise, and may be diagnosed as depression with fatal consequences.¹⁶ Any uncharacteristic behaviour during the puerperium should include the possibility of a psychotic illness in the differential diagnosis, as only 33% of women who develop postpartum psychosis have a psychiatric history.¹²

Specific risk factors associated with pregnancy

Unintended pregnancy: Unplanned pregnancy may lead to an unwanted pregnancy, which is a major risk factor for perinatal depression.¹⁷ Poor access to adequate reproductive healthcare, specifically contraception and abortion, leads to higher rates of unwanted pregnancies both in economically underdeveloped countries¹⁸ and cultures where there is endemic gender discrimination.¹⁷ Unwanted pregnancy is associated with a twofold increase in the rate of depression.¹⁸ This association is at least partly mediated by the increased exposure of women with unintended pregnancies to violence.¹⁹

Teenage pregnancy: Rates of depression are high among pregnant teenagers.²⁰ This is not surprising given the clustering of risk factors, including socioeconomic deprivation, poor education and sexual abuse in this group. 

Hormonal factors: There are huge shifts in concentrations of hormones during pregnancy, as well as exposure to pregnancy-specific hormones. Most of these hormones are steroids, and therefore lipophilic, and will modify brain function. In addition, a new endocrine system is created between mother and baby – the placental-adrenal system.²¹ The placenta produces corticotropin-releasing hormone (CRH), causing the synthesis and release of cortisol from both the maternal and foetal adrenal glands. Cortisol, in turn, causes the further release of placental CRH. There is thus a feed-forward drive between mother’s hypothalamo-pituitary-adrenal (HPA) and placental CRH, resulting in incremental increases in the concentration of maternal cortisol as pregnancy advances.²²

Circulating concentrations of cortisol in late pregnancy fall into the Cushingoid range.^18,23 This is relevant to the risk of developing PD because cortisol has mood altering properties, with depression outside of pregnancy being associated with a relative increase in the activity of the HPA axis.^24,25 This high concentration of cortisol may account for the high level of depressive symptoms found in pregnant women, especially in the more advanced stages of pregnancy.^23,26

The postpartum period is characterised by a rapid shift in the hormonal environment. Within the first 48 hours after delivery, oestrogen and progesterone concentrations fall dramatically, returning to normal levels within a week.²³ As these gonadal steroids modulate neurotransmitter systems involved in the regulation of mood, investigators have proposed a role for these hormonal changes in the emergence of postpartum affective illness.²⁷ The changes in the HPA axis following the abrupt withdrawal of placental CRH, and the re-equilibration of the maternal HPA axis is also a specific hormonal risk associated with the perinatal period.^21,28

A subgroup of women who experience postpartum, rather than antepartum, depression appear to have a specific biological vulnerability to hormonal shifts. These women often have a family history of postpartum depression and a personal history of premenstrual syndrome.²⁹ Another hormonal risk factor associated with postpartum depression is subclinical hypothyroidism.³⁰ Harris et al have recommended that thyroid peroxidase antibody (TPOAb) screening in early pregnancy could be a useful predictor of postpartum depression.³¹

Consequences of perinatal depression 

On mother

Ongoing depression: Unless depression is actively managed during pregnancy, it is unlikely to remit during the postpartum period. It is estimated that 50% of postpartum depression commences during pregnancy.³² The prognosis for PD depends at least partly on the persistence of psychosocial adversity, with women who have younger children being at a particularly greater risk.²⁷ Women with a history of depression remain at a high risk of relapse, and pregnancy should be considered as another, but not specific, risk factor in these high-risk women. 

PD can signal the beginning of lifelong depression in some women. This is usually understandable within the context of an individual’s history. For example, some women may have struggled with sub-clinical depression for years and are unable to cope with the additional burden of impending or actual parenthood. Others may have specific difficulties related to mothering, such as a history of CSA. 

PD and partnership difficulties, up to and including relationship breakdown, are closely associated.³³ Observation of either during the perinatal period should alert one to the possibility of the other. 

On baby

Birth outcome: There has been much investigation about the effects of antenatal stress and depression on birth outcome: specifically whether depression is associated with an increased risk of premature delivery, low birth weight or obstetric complications. This literature is confusing because antenatal stress is inconsistently defined – variably being measured by social adversity or life events, by perceived stress, by cut-off points of depression scales and less frequently by the only reliable method, clinical interview. However, a consensus seems to be that antenatal depression is associated with a small risk for premature delivery.^26,34

Animal work has demonstrated that antenatal stress in pregnancy increases cortisol production in the pregnant animal and that this hypercortisolaemia alters the behavioural responses and emotional areas of the brains in the offspring.³⁵ Major depression during pregnancy in humans has been found to be associated with increased activity of the HPA axis;²⁶ so that while all pregnant women are hypercortisolaemic, depressed pregnant women are even more so. The diurnal pattern of hypercortisolaemia in depressed pregnant women is similar to that seen in depression outside of pregnancy; with higher evening cortisol secretion in those with depression.³⁶ There is now considerable support for the hypothesis that it is the increased cortisol production in the pregnant woman that mediates the poor pregnancy outcome in depressed women.^26,37

Baby outcome: The consequences of this high-stress uterine environment for the foetus are probably long-lasting because of the programming effect of cortisol on the HPA axis of the baby.³⁸ Babies born to women who have had depression during or after pregnancy have a poorer cognitive and emotional developmental trajectory throughout childhood and into early adulthood;^39,40 being at a high risk of developing an affective disorder if female, and a conduct disorder if male.⁴¹ There are high rates of depression and anxiety disorders in women who present with ‘difficult to settle’ babies.⁴² With resolution of depression, mother-infant interactions improve, particularly mother’s sensitivity or ability to pick up cues from baby about his/her needs.

Management 

PD needs to be managed in the context of the family: the foetus or baby; and the partner and other children, if extant. Social inclusion and adversity are clear risk and perpetuating factors. Management needs to be directed at any aetiological factors that can be modified. Frequently there is a resistance on the part of individuals to address their areas of social and emotional vulnerability, particularly when heightened by a depressive mindset, so it is valuable to try and tease out these fears with individual women. Establishing this trust is fundamental to managing the depression. 

Problems can be compartmentalised and managed by specialist services. It is important to have multidisciplinary services available so that this approach can be implemented. 

Referral to the psychiatry services is advisable if the depression arises during pregnancy or within a month of delivery. Most maternity hospitals have a perinatal psychiatry service but this service may be poorly resourced. Local psychiatry services may be more accessible and will have home-based treatments. 

Antidepressant treatment and perinatal depression

Treatment with antidepressants has been shown to be effective, with similar indications for treating depression outside of the perinatal period. That is, antidepressant and psychotherapy treatments are probably equally effective in mild depression, and antidepressants are more likely to be effective, and psychotherapy less effective, in more severe depression.^43,44

While antidepressants have been demonstrated to be effective, there remains much controversy about their use during pregnancy. There is weak and inconsistent evidence that SSRIs may marginally, at most, increase the occurrence of cardiac malformations in the foetus.⁴⁵ There does not seem to be any effect on infant growth or development during the first year of life on SSRI exposure in utero.⁴⁶ The use of antidepressant medication during pregnancy is generally framed in the context of risk balance: possible risk to the foetus of exposure to antidepressants versus possible risk to the foetus of exposure to the harmful effects of depression.⁴⁷ Perinatal psychiatrists are more likely to advocate active and effective treatment of antenatal depression and see the alleviation of the mother’s depression as having significant merit. 

Fluoxetine is the most widely tested antidepressant used in the treatment of antenatal depression, but there is growing experience with citalopram. Paroxetine is contraindicated during pregnancy and treatment with SSRIs is preferable to treatment with venlafaxine. It is safe to breastfeed when taking SSRIs within an average dose range. Breastfeeding should be encouraged if the mother is taking SSRIs within an average dose range as it may reduce any withdrawal symptoms in baby.

Antipsychotics and mood stabilisers

Clinicians should be vigilant about the presence of psychotic symptoms. Any strange ideas about baby or family need to be seen as possibly psychotic. Alterations in behaviour or mien should be further investigated. A collateral history from someone who has closely observed the possibly psychotic woman is necessary. Admission to hospital for observation is advisable if this information is unavailable. Without excellent psychological support for mother, and 24 hour baby care being provided by another carer, admission is usually necessary if the woman is psychotic.

Olanzapine is very useful both during pregnancy and the postnatal period as it has not been demonstrated to be teratogenic, has been widely used and also has mood stabilisation properties. Potent dopamine-2 antagonists, such as haloperidol, amisulpride and risperidone, should be avoided. They promote the secretion of prolactin and interfere with the cessation of breastfeeding, which is usually necessary in psychotic affective disorder.

Lithium is very useful in the treatment of severe depression or mixed affective states during the perinatal period. Although there is a low risk of Ebstein’s anomaly if prescribed during the first trimester of pregnancy, it carries a reduced risk of associated major congenital malformations compared to sodium valproate, carbamazepine or lamotrigine.⁴⁸ The latter three mood stabilisers should only be prescribed in exceptional cases. 

Non-medical treatments

Although a multitude of studies has been published about non-medical interventions in the treatment of antenatal depression, most of the findings are equivocal. In a recent Cochrane review it is reported: “The evidence is inconclusive to allow us to make any recommendations for depression-specific acupuncture, maternal massage, bright light therapy, and omega-3 fatty acids for the treatment of antenatal depression”.²

There have been thousands of studies looking at non-medical interventions in PD during the postpartum period. The target groups in these studies vary, with some studies targeting women with high levels of depressive symptoms, but who are not necessarily depressed; and other studies targeting those who are at high risk of developing depression, for example, single, socioeconomically disadvantaged mothers. Many of these studies involve supportive or interpersonal psychotherapy with midwives. Not surprisingly, no definitive clinical guidelines have emerged. What is surprising is the emerging trend from these studies to demonstrate a lack of efficacy for non-specific supportive programmes.⁴⁹

Conclusion

Depression is common during the perinatal period because during this time there is a confluence of risk factors and a potential exposure to vulnerability factors leading to depression. Rates of depressive symptoms are high during pregnancy and rates of clinical depression increase from about 7% to 12% from the beginning to the end of pregnancy. Although the rates of depression reduce in the postpartum period, the incidence of severe or psychotic affective disorders increases, particularly in the first postpartum month. PD should be actively managed and ‘a-wait-and-see’ approach will probably lead to deterioration in mood, problematic attachment to baby, and impairments in baby development. SSRI antidepressants are the mainstay of treatment for PD. Baby attachment and development, family relationships and family planning issues should be given attention. Psychosocial problems should be targeted and actively managed, rather than intervening with non-medical non-targeted treatments.

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