14 Joanna V. MacLean1,2 and Teri B. Pearlstein1,2 1 Department of Psychiatry and Human Behavior and Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA 2 Women’s Behavioral Medicine, Women’s Medicine Collaborative, Providence, Rhode Island, USA It is important to identify prenatal mood and anxiety disorders in the mother since untreated disorders can have negative effects on fetal development, birth outcome and child development. As such, it is important for clinicians to have an understanding of identification and treatment options for the most common disorders. It is difficult to distinguish the effects of untreated prenatal depression, anxiety and stress since so many studies examine them together. Depression, anxiety and stress during pregnancy can lead to poor health behaviours including inadequate prenatal care, poor nutrition, lack of exercise, poor compliance with prenatal vitamins and prescribed medications, and increased alcohol, smoking and drug abuse. A recent systematic review and meta‐analysis reported that untreated depression was associated with a 1.56 odds ratio (OR) of preterm birth (PTB) and a 1.96 OR of low birthweight (LBW) [1]. Given the high infant morbidity and mortality associated with PTB and LBW, these increased risks with untreated prenatal depression have large public significance. Untreated prenatal depression, anxiety and stress have also been linked to increased maternal cortisol levels, spontaneous miscarriage, pre‐eclampsia, caesarean section, lower Apgar scores and placental abruption. Studies have reported associations between untreated depression and anxiety and adverse outcomes on child development, such as decreased grey matter density, disrupted sleep, developmental delay and autism, cognitive impairment, internalizing and externalizing behaviours (such as attention deficit disorder, conduct disorders, antisocial behaviour), depression, anxiety and psychotic disorders, as well as obesity and metabolic dysfunction [2]. It is difficult to separate the prenatal exposure from the postnatal exposure to maternal depression, as well as other postnatal environmental factors. Proposed mechanisms underlying maternal prenatal stress and child outcomes include the direct and indirect effect on health behaviours, maternal physiology, placenta and the postnatal environment [2]. Psychosocial stress in pregnancy can negatively impact maternal behaviours, such as smoking, substance use, unhealthy eating, sleep disturbances and physical activity, which may increase adverse pregnancy and child outcomes. Maternal exposure to stress activates the hypothalamic–pituitary–adrenal (HPA) axis and subsequent release of cortisol. Cortisol may enter the fetal circulation through direct transport across the placenta. It can also increase production of placental corticotrophin releasing hormone (CRH), which stimulates the fetal HPA axis. High cortisol concentration in utero influences fetal behavioural, immunological and brain development, and placental CRH concentration has been associated with decreased fetal growth and size at birth. The role of placental 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) is to convert cortisol to inactive cortisone, a built‐in protection against heightened maternal cortisol concentrations. However, maternal prenatal anxiety may downregulate the 11β‐HSD2 enzyme and allow more cortisol to cross into fetal blood. Catecholamines may also play a role in maternal stress, influencing infant outcomes. For example, catecholamines in maternal blood result in constriction of placental blood vessels, which can decrease the supply of nutrients and oxygen to the fetus and increase fetal catecholamine release. Chronic prenatal stress may negatively impact maternal immunity, resulting in increased risk of infections, increased proinflammatory cytokines (which may affect the developing fetal brain) or immune alterations in the offspring. The postnatal environment also plays a central role in child development and can be difficult to control for when assessing the impact of prenatal stress. Often, prenatal psychosocial stress is a predictor for the postnatal environment. It has been suggested that the fetal programming that occurs as a result of prenatal stress may be protective, equipping the child for the postnatal environment, and it is only when there is a mismatch between the prenatal and postnatal environments that problems in health and behaviour may be anticipated [2]. Depression has been reported in up to 10–15% of pregnant women. This prevalence reflects major depressive disorder (MDD) and less severe depression. MDD is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) by at least 2 weeks of low mood, or loss of interest or pleasure, associated with at least five other symptoms such as change in appetite or weight, insomnia or hypersomnia, psychomotor agitation or retardation, decreased energy or fatigue, sense of worthlessness or guilt, difficulty concentrating or making decisions, and recurrent thoughts of death, dying or suicide [3]. The prevalence of MDD in perinatal women is similar to that in women of reproductive age outside the perinatal period, but some women may be at risk during pregnancy. Risk factors for having MDD during pregnancy include being adolescent, poor socioeconomic status, having a prior MDD, current anxiety, comorbid medical problems, life stress, intimate partner violence, poor social support and unintended pregnancy. Screening guidelines for depression in adults were updated in early 2016, which included screening recommendations for pregnant and postpartum women [4]. Screening pregnant and postpartum women was reported to have ‘small to none’ harms, and the process of screening could reduce depressive symptoms. It is recommended that screening takes place in healthcare settings with ‘adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow‐up’. The most widely used screening measure utilized in perinatal women is the Edinburgh Postnatal Depression Scale (EPDS), where a score greater than 10 suggests a possible depression. The Patient Health Questionnaire (PHQ‐9) is a widely used screening measure for depression that can be applied to perinatal women [4]. Postpartum ‘blues’ occur in up to 80% of newly postpartum women. Common symptoms include mood lability, low mood, tearfulness, irritability, interpersonal sensitivity, anxiety, fatigue and confusion. The incidence of symptoms peaks in the first 3–5 days after delivery, and symptoms generally resolve spontaneously by 2 weeks. Support and reassurance are generally helpful. Although the expression of the symptoms is presumed to be related to the rapid decrease in hormone levels after delivery, this association has not been unequivocally demonstrated. The clinical significance of postpartum blues is that in up to 25% of women the symptoms do not resolve spontaneously and a full depressive episode may develop. Postpartum depression (PPD) occurs in 10–15% of new mothers. As mentioned in the section about depression during pregnancy, the prevalence of PPD is similar to that in women of reproductive age outside the perinatal period, but some women may be at particular risk during the postpartum period. Risk factors for PPD are similar to the risk factors for developing MDD during pregnancy, and include prior MDD, current depression or anxiety, poor partner and other social support, preterm infant or complicated delivery, being adolescent, poor socioeconomic status, psychosocial stressors and marital conflict. The EPDS and other depression rating scales can screen for the presence of PPD. Ruling out thyroid dysfunction and anaemia is indicated. As with postpartum blues, studies have failed to unequivocally find an association between hormone concentrations and PPD. It has been postulated that there may be multiple PPD phenotypes. Within the ‘hormone‐sensitive’ phenotype, the normal perinatal fluctuations of reproductive hormones potentially lead to abnormal responses in neurotransmitters (serotonin, monoamine oxidase), HPA axis function, allopregnanolone responsivity, thyroid function, immune function, oxytocin function and genetic expression [5]. In this group of sensitive women, hormonal fluctuations trigger affective dysregulation with the expression of depressive and anxiety symptoms. The DSM‐5 definition of PPD is MDD that has onset within 1 month of childbirth [3]. In reality, many women who are depressed in the postpartum period had depression during pregnancy, or develop it beyond the first postpartum month. A large‐scale study administered the EPDS to 10 000 postpartum women 4–6 weeks following delivery and identified that 14% of them had an EPDS score above 10. Of these women, the onset of the MDD was prior to pregnancy in 27%, during pregnancy in 33%, and developed after delivery in 40% [6]. This study also demonstrated the high psychiatric comorbidity with PPD. Approximately two‐thirds of the women who had an EPDS score above 10 had a comorbid anxiety disorder, 23% had bipolar disorder, and 19% endorsed self‐harm ideation [6]. Maternal suicide is a leading cause of death in postpartum women in some countries and is often by violent means. Severe PPD can also be a risk factor for infanticide. Suicidal and infanticidal ideation should be inquired about at postnatal visits. It is important to treat PPD due to the well‐established negative effects on infant and child development, in addition to negative effects on the mother and family. PPD can lead to decreased mother–infant attachment and decreased initiation and maintenance of breastfeeding. Children of depressed mothers have been reported to have temperament difficulties, sleep problems and poor self‐regulation. Young children may have delayed motor development, behavioural inhibition, externalizing disorders (such as conduct problems), poor emotion regulation and altered cognitive function. Older children and adolescents exposed to PPD have increased prevalence of depressive disorders, anxiety disorders, attention deficit disorder, conduct disorders and medical illnesses. Eight randomized controlled trials have been published involving antidepressant medications for PPD, including a total of 715 postpartum women. In a pooled analysis of three of these studies, sertraline and paroxetine were found to be more effective than placebo for reducing depressive symptoms in women with PPD [7]. More studies are needed to compare the efficacy of antidepressant medications with psychotherapy, to examine the efficacy of combined antidepressants and psychotherapy, and to confirm that improvement of symptoms after treatment with antidepressant medications also leads to improvement in maternal functioning and infant and child development. Anxiety disorders are defined in DSM‐5 as disorders of excessive fear, which is an emotional response to a perceived or real threat, and anxiety, which is anticipation of future threat [3]. While anxiety disorders are often comorbid with one another, they differ with regard to the stimulus or scenario that induces the fear or anxiety, as well as the associated belief. With all the disorders, a defining feature is that the fear or anxiety is excessive, out of proportion or persisting beyond the appropriate periods, taking cultural contextual factors into consideration. The symptoms may not be attributable to the physiological effects of a substance, medication, another medical condition or mental disorder. Approximately 30% of women experience an anxiety disorder during their lifetime. As anxiety disorders often have a relatively early and chronic course, many women will experience symptoms during the peripartum period, with prevalence estimates for any anxiety disorder ranging from 4.4 to 39% [8]. Generalized anxiety disorder (GAD) is the most common perinatal anxiety disorder, diagnosed by having excessive anxiety and worry that occurs more days than not and can cause functional impairment. DSM‐5 criteria for GAD requires symptoms for at least 6 months, so if the onset occurs during pregnancy it may exclude those with excessive worries for less than 6 months and may be difficult to differentiate new‐onset GAD from an adjustment disorder with anxious mood. The worries include a number of events or activities, and feel difficult to control. Associated symptoms include restlessness, easy fatiguability, difficulty concentrating, irritability, muscle tension and sleep disturbance, often symptoms that may be considered normal in pregnancy and post partum. In the general population, prevalence ranges from 1.2 to 6.4%, with higher rates in pregnancy ranging from 8.5 to 10.5% [9]. The worries often involve pregnancy complications and fetal well‐being, maternal wellness and partner illness. A previous history of GAD is the strongest predictor of GAD in pregnancy, with additional risk factors including personal or family history of anxiety disorder, lower social support, childhood abuse and lower education. Postpartum, the anxious thoughts often involve mothering skills and the transition to motherhood, breastfeeding, finances, and change in partner relationship, with prevalence rates between 4.4 and 10.8% [9]. GAD is highly comorbid with MDD, often resulting in a more severe and protracted course of illness. GAD can also predict an increase in the development of PPD. In one study, pregnancy anxiety was the strongest predictor of alcohol consumption in the prenatal period. Maternal anxiety during pregnancy has been associated with an increased risk of PTB and LBW. Research has suggested that GAD and recurrent negative thinking has resulted in less responsive and engaged maternal interactions with their infants. These infants were withdrawn with lowered emotional tone. As a result of excessive maternal worry, mothers may be less able to identify happy infant faces. Maternal GAD during pregnancy was found to result in lower levels of fetal brain‐derived neurotrophic factor in cord blood of newborns, suggesting a potential negative impact on the neurodevelopment of the fetus [9]. The mainstays of treatment are individual psychotherapy and selective serotonin reuptake inhibitors (SSRIs) or serotonin–noradrenaline reuptake inhibitors (SNRIs). Cognitive behavioural therapies (CBT) are the first‐line choice for mild to moderate perinatal GAD, with the goal of reducing worries to a more reasonable level, lessen the mothers concern over her worries, and reducing autonomic arousal. Additional therapeutic techniques include mindfulness training, relaxation techniques and psychoeducation. SSRIs/SNRIs should be considered in moderate to severe cases, weighing the risk of untreated maternal anxiety and its consequences for the developing infant against the potential risks of medication treatment [9]. Panic disorder is diagnosed when an individual experiences recurrent unexpected panic attacks, and persistent worry about additional panic attacks or their consequences. A panic attack is defined by an abrupt surge of intense fear or discomfort, along with at least four other symptoms such as accelerated heart rate, sweating, sensation of shortness of breath, chest pain, nausea, feeling dizzy or light‐headed, paraesthesias, fear of dying or losing control, and derealization or depersonalization. Agoraphobia, defined as excessive fear or anxiety about being in a situation where escape may be difficult or help not available in the event of developing panic‐like or embarrassing symptoms, is often comorbid with panic disorder [3]. In the general population, the 1‐year prevalence rate for panic disorder is 2–3%, with a 0.2–5.7% prevalence during pregnancy, decreasing to 0.5–2.9% prevalence at 6–10 weeks post partum. The onset of panic disorder during pregnancy ranges between zero and 54%, with unpredictable courses (worsening, improving or staying the same) that vary widely among studies. There is a risk of onset of panic disorder post partum and after weaning, which is hypothesized to occur due to fall in progesterone levels. Panic disorder in pregnancy may have 4.2 times greater risk of PPD (during the first year postpartum) than those without [8]. Medical conditions that should be considered in the differential for new‐onset perinatal panic attacks include thyroid dysfunction, anaemia, pre‐eclampsia and phaeochromocytoma. Case–control studies have reported that untreated panic disorder during pregnancy has been associated with PTB, LBW, shorter gestational age, small for gestational age, anaemia, isolated cleft lip with or without cleft palate and other congenital abnormalities [10]. CBT is the treatment of choice for panic disorder, and has been demonstrated to decrease panic symptoms. Antidepressant medications are considered the first‐line pharmacotherapy option, with the goal of reducing panic symptoms and number of attacks. Benzodiazepines are also effective, but have an increased risk of abuse and dependence. Obsessions are recurrent persistent thoughts, urges or images that are experienced as unwanted and intrusive, causing marked anxiety or distress. Compulsions are repetitive behaviours or mental acts that one feels driven to complete. The behaviours or acts are clearly excessive, and are not connected in a realistic way to their goal of preventing a dreaded event or situation. The obsessions or compulsions must be time‐consuming or cause clinically significant distress or impairment, which helps differentiate the disorder from occasional intrusive thoughts or behaviours that may be common during the perinatal period [3]. In pregnancy, the prevalence of obsessive compulsive disorder (OCD) ranges from zero to 5.2%, and studies show that the course of illness is variable. One meta‐analysis showed that prevalence increases as women progress from pregnancy to the postpartum period, and that pregnant or postpartum women are approximately 1.5–2 times more likely to experience OCD compared with the general population [11]. Up to 47% of women retrospectively date their first onset of OCD in the peripartum period. During pregnancy, the obsessions or compulsions often involve contamination fears and cleaning rituals. During the postpartum period there are often intrusive ego‐dystonic obsessional thoughts of intentionally or accidentally harming the infant, fears of contaminating the infant resulting in repetitive washing, fears of infant death, compulsive checking, compulsive ordering and avoidance of being alone with the infant. Postpartum OCD appears to be characterized by the rapid onset of obsessional symptoms after the birth, with onset as early as the second postpartum day [12]. It is important to recognize that most postpartum women, greater than 65%, experience intrusive thoughts of harm coming to their infants, but it is unlikely they will act on those thoughts or develop OCD. Aggressive thoughts related to the child are perceived as distressing to mothers, and women with OCD are not at increased risk of harming their infants [11]. This is important to differentiate from postpartum psychosis, in which the thoughts are not distressing to the mother and the risk of actual harm is increased. OCD in pregnancy has been associated with lower quality of life in pregnant women, and increased likelihood of PPD [8]. Maternal OCD may have negative impacts on the infant’s development. A mother’s fear of harming her infant and subsequent avoidance may hinder a secure mother–child relationship, and may also cause the infant to receive inadequate care. Increasing data show that a poor early interaction between the mother and infant can have long‐term detrimental effects on the child, such as increased vulnerability to stress and increasing risk for later development of psychiatric disorders [12]. Non‐pharmacological options that are effective for treating OCD include CBT and the specific behavioural therapy technique, exposure and response prevention. SSRIs and the tricyclic antidepressant (TCA) clomipramine are the first‐line pharmacological treatments, often requiring dosages higher than those used for MDD. As many as 78% of women experience some fear of childbirth, such as pain, health complications, death of fetus or loss of control. In a subset of women (5–6%), this fear is persistent and causes significant distress, often associated with previous traumatic delivery, anxiety and depressive symptoms during pregnancy, lack of support, dissatisfaction with partners, advanced maternal age and previous caesarean section. The fear may result in less tolerance of pain during childbirth, increased elective and emergency caesarean section rates and increased intrusive memories of childbirth [13]. Post‐traumatic stress disorder (PTSD) follows exposure to actual or threat of death, serious injury or sexual violence, accompanied by recurrent intrusive symptoms for over a month that include avoidance of stimuli associated with the event, negative alterations in cognitions and mood associated with the event, and marked alterations in arousal and reactivity. There is high comorbidity with MDD, GAD and substance misuse [3]. Prevalence rates among women are around 5% for current PTSD and range from 10 to 20% for lifetime PTSD. During pregnancy, the prevalence may be as high as 24% for women at high risk (racial minorities, teens, less educated, or poor) [14]. Women who have experienced a previous trauma, especially childhood or reproductive trauma, may be at increased risk for exacerbation of symptoms during the peripartum period. Prevalence rates of PTSD during the first year post partum range from 0.9 to 4.6%, with PTSD symptoms found in up to 24% [15]. Risk factors associated with postpartum PTSD include previous traumatic life events, sexual abuse, previous depression or psychiatric treatment, previous traumatic births, pregnancy complications, labour anxiety and traumatic experiences during the birth process [15]. Preventive strategies may include providing psychoeducation, extra support, improving coping strategies and increasing the woman’s sense of control. One example could include establishing a care plan for delivery, which is shared with the care team, and includes her desires for pain control and medications and immediate post‐birth wishes. Perinatal PTSD increases adverse pregnancy and birthing outcomes, including poor prenatal care, high‐risk health behaviours, miscarriage, ectopic pregnancy, PTB and LBW [14]. Perinatal PTSD has been associated with postpartum depression and bonding impairment with the infant, impaired relationship with partner, sexual dysfunction, as well as negatively impacting future reproductive choices [14]. Psychotherapeutic treatment options for PTSD include CBT, exposure therapy and eye movement desensitization. SSRIs are considered first‐line pharmacotherapy. Prazosin has an off‐label role in treating nightmares.
Psychiatric Problems in Pregnancy and Post Partum
Effects of untreated prenatal depression, anxiety and stress
Depression during pregnancy
Postpartum blues
Postpartum depression
Anxiety disorders
Generalized anxiety disorder
Panic disorder
Obsessive compulsive disorder
Fear of childbirth
Post‐traumatic stress disorder
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