The cycle of under detection and under treatment of prenatal depression, anxiety, and stress
To date, perinatal mental healthcare has focused almost exclusively on preventing and treating postpartum depression. This paradigm does not reflect current evidence that 50 to 70% of postpartum anxiety and depression begin  and frequently co-occur [15–17] in pregnancy, nor does it reflect the enduring effects of poor prenatal mental health on child health [11, 18, 19]. Prenatal depression, anxiety, and stress are severely under detected and under treated, and two-thirds of women with substantial symptoms remain unidentified by most obstetrical providers [20, 21]. A number of barriers prevent women from seeking mental healthcare during the perinatal period, including stigma, fear of being prescribed medication, lack of knowledge about whether their symptoms are ‘normal’ or ‘abnormal’, and fear that their concerns will be dismissed [22–24]. However, despite recommendations [25, 26] and acceptance by both healthcare providers [27–30] and women [31–33], psychosocial assessments are routinely conducted by fewer than 20% of prenatal care providers . In systems without linkages between assessment, referral, and mental healthcare, only 18% of pregnant and postpartum women who are assessed as having mental health problems actually follow up with a referral that they have been given , and fewer than 15% of those needing care receive some form of treatment [35, 36]. The problem is further complicated by evidence that most women do not voluntarily disclose mental health concerns [22, 37, 38] (despite the fact that <4% refuse provider-initiated assessment) [39, 40]. The cycle of under detection and under treatment is perpetuated by a ‘catch 22’ where providers do not assess women because no follow-up services exist , and because women are not assessed, they are not referred and treated. Targeting the individual components of assessment, referral, or treatment in isolation will not address the need in that it is not feasible to enhance psychosocial assessment without simultaneously increasing service capacity to receive referrals. Improvements in psychosocial care can only be addressed as an integrated process of assessment-referral-treatment.
Integrated perinatal mental healthcare
Integrated perinatal mental healthcare - the systematic linkage of assessment, referral, and treatment  - has been recommended by national bodies . Integrated care is a more efficient approach to primary care management of depression and anxiety in that it improves access, adherence, and treatment response while being cost-effective [41–44]. Very few studies have evaluated integrated psychosocial care during the perinatal period [40, 45, 46]. In these studies, the high prenatal ‘screening’ rates of 95%  and 62.5%  and low refusal rates (<4%) demonstrate women’s acceptance of routine screening and follow-up care . The predominant limitations of existing studies of integrated perinatal mental care (and areas we aim to improve upon) are: 1) all lacked a comparison group; 2) all primarily targeted depression without addressing stress and anxiety; 3) most conducted a minimal feasibility assessment, providing little guidance for improving the intervention or understanding its most effective components; 4) none evaluated clinical outcomes; 5) none used technological (for example, web-based) approaches to support integrated care, although recommended as a key element of success of integrated care ; and 6) none targeted the most prominent barriers to mental healthcare reported by providers (for example, lack of time to screen, lack of screening tools and knowledge regarding their use, lack of referral mechanisms, unavailable and inaccessible non-pharmacological therapies) [28, 47, 48] or by pregnant/postpartum women (lack of time, preference for working through their symptoms on their own, stigma associated with treatment, inability to find/access/afford nonpharmacologic therapy) [22, 24, 37]. Together, these limitations highlight the lack of utility that current research offers in terms of implementing integrated psychosocial care in clinical settings. There is a need to design and rigorously evaluate integrated interventions that reduce barriers and promote access to mental healthcare by linking standardized psychosocial assessment to effective mental healthcare.
Standardized psychosocial assessment
Psychosocial assessment comprises the use of a standardized screening tool (for example, Edinburgh Postnatal Depression Scale, EPDS) in addition to a holistic assessment of psychosocial risk factors (for example, Antenatal Risk Questionnaire, ANRQ-R) . Standardized psychosocial assessment is feasible [31, 35, 49, 50], improves detection [51, 52] and facilitates triaging of women by symptom severity to ensure that women receive appropriate services . However, serious resource limitations (for example, lack of time and assessment tools) constrain many primary care providers from routine assessment of mental health problems. Computer-based psychosocial assessment conducted in primary care can address such limitations. Evidence exists that patients and providers find the use of computer-based screening acceptable and feasible for inquiring about sensitive issues, including prenatal  and postnatal intimate partner violence  and mental health [55, 56]. It is also well-suited for busy clinical settings in that it offers consistency, is resource-sparing, can be tailored to meet the needs of patients, can be used with audio/video for low literacy, easily provides a real-time summary for patients/providers [56, 57], achieves similar rates of disclosure to written- or interview-based screening, and is preferred by patients due to its perceived anonymity [56, 58, 59]. However, a recent systematic review demonstrated that, on its own, assessment is ineffective in preventing or treating depression  and others have shown that it does not improve linkage with healthcare in the form of follow-up assessment or treatment [21, 61]. Thus, in order for mental healthcare to be effective, psychosocial assessment must be systematically linked to treatment.
Cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a highly effective treatment for depression and anxiety [62, 63]. Since prenatal mental health problems are characterized by the co-occurrence of anxiety and depression [3, 16, 17], CBT (including online CBT) is recommended in national guidelines as an early intervention for improving maternal-child outcomes . Randomized controlled trials (RCTs) of group-based CBT for new mothers [64–68] and pregnant women [69, 70] demonstrate that group CBT is acceptable and efficacious in reducing risk and symptoms of postpartum depression [64–68].
However, individual- and group-based CBT are frequently inaccessible by pregnant women due to long wait times (groups often small; number of therapists limited) and expense (that is, often not covered by health insurance) . Barriers that are unique to childbearing families (for example, care of other children) can also hinder sustainability of women’s attendance at individual- and group-based CBT sessions [69, 72]. Furthermore, pregnant women with mild and moderate symptoms may not be offered CBT due to resource constraints within the healthcare system that restrict these limited services to women with severe symptoms who present with the greatest need at the current time. Consequently, women with mild and moderate symptoms are underserved. Without treatment, there is evidence that 48% of pregnant women with anxiety and 71% of those with depression continue to experience symptoms throughout the postpartum period , with as many as one-third of new mothers experiencing symptoms up to 4 years postpartum [73, 74]. As such, the delay in not treating pregnant women with mild or moderate symptom severity can lead to substantial personal, societal, and system costs if their symptoms become chronic or more severe over time . Accessible and available mental healthcare is a priority for this vulnerable population.
Few trials have evaluated CBT in pregnancy [66, 69, 70, 76, 77]. Pilot testing of a prenatal workbook-based CBT plus telephone coaching by members of our research team revealed four key findings: 1) pregnant women found the program acceptable and helpful; 2) they wanted CBT earlier in pregnancy; 3) they wanted an online format; and 4) they recommended shorter modules . The proposed trial incorporates these pilot results by using six, 30-minute modules (versus the original three), delivering the intervention early in pregnancy (first and second trimester), and adapting the CBT workbook for online use without the use of a telephone coach.
Online CBT is resource-sparing, clinically and cost-effective, acceptable [79–82], and accessible , and has been recommended for treatment of anxiety and depression in primary care . A meta-analysis reported that online CBT produces moderate to large effects, is as effective as face-to-face CBT, and has lower attrition rates (20%) than group-based CBT (40 to 50%) [7, 84]. Although not tested in pregnant women, online CBT is an ideal treatment because it can overcome major deterrents to mental healthcare cited by pregnant/postpartum women, including: long wait times , inaccessibility , lack of time , finding childcare [24, 85], stigma of attending care , and treatment expense . Online CBT satisfies the majority (93%) of distressed women’s preference for self-help  and should improve aspects of psychological health (for example, mastery, resilience) related to poor pregnancy outcomes . Importantly, online CBT can be embedded in current delivery systems, creating a sustainable approach to effective perinatal mental healthcare. Finally, evidence exists that online CBT and online CBT plus telephone  or email  support by a psychologist are equally efficacious in reducing depression and promoting adherence. Thus, online CBT, as a stand-alone intervention, offers a highly cost-effective approach to mental healthcare that is independent of limited human resources.
The cost-effectiveness of integrated perinatal mental healthcare has not been evaluated [68, 89]. However, an economic evaluation of the cost of treating postpartum depression demonstrated that public health costs were twice as high in women with postpartum depression compared to those without depression . At a prevalence rate of 25% among childbearing women, prenatal mental health problems pose a substantial economic and human resource burden to the healthcare system. However, widespread implementation of integrated prenatal mental healthcare (even resource-sparing approaches) will require a substantial commitment of resources, and an economic evaluation that considers the individual (maternal, family, child), local (clinic-and community-based), and societal implications of early, prenatal intervention compared to usual prenatal care is essential.
Mechanisms of integrated psychosocial care
Integrated prenatal psychosocial care is a complex intervention with several components. We found no studies that described mechanisms by which prenatal intervention led to improved outcomes . As noted in the Medical Research Council Framework for Complex Interventions, without this knowledge it is difficult to define which components (for example, program content, intervention characteristics, method of delivery, assessment approach, referral processes) of an intervention contribute to its impact and should be replicated in other settings. Given the need for widely accessible interventions across a diverse spectrum of perinatal care providers and settings (midwives, nurses/nurse practitioners, family physicians, obstetricians), it is critical to identify the key components of the integrated intervention that contribute to its effectiveness and facilitate successful implementation across settings. In practice, a pregnant woman would complete the brief online psychosocial assessment while waiting for her clinic appointment, and her perinatal provider would access these results in ‘real time’ online (for example, a summary of psychosocial risk plus question responses). A decision-making algorithm would provide guidance on the most appropriate referral options for the provider to discuss with the woman. Thus, a key aspect of this study is to understand what aspects of the intervention enhance or deter from its implementation success and integration into routine clinical practice.
Strong evidence exists supporting a deleterious, enduring effect of poor prenatal mental health on adverse fetal  and child outcomes [11, 18]. Two decades of longitudinal research have demonstrated a clear, independent association between maternal prenatal distress and neurodevelopmental outcomes in children [11, 18, 92] and adolescents . Although well established in animal research, early human studies provide evidence of various biological pathways underlying the link between prenatal distress and infant/child outcomes, including epigenetic mechanisms (that is, fetal DNA methylation, placental gene expression [91, 94]), impaired neurogenesis , and dysregulation of the fetal hypothalamic-pituitary-adrenal (HPA) axis [96, 97]. However, the interplay of influences in the prenatal and postnatal environments and, in particular, the extent of the moderating effect of postnatal intervention on fetal development that has been impacted by prenatal depression, anxiety, or stress is largely unknown. Together, this evidence implies that early prenatal intervention should be explored as a means to interrupting the risk of prenatal distress on infant and child well-being.
Very few studies have evaluated the impact of prenatal CBT on infant outcomes [76, 98], and none have determined the influence of integrated perinatal mental healthcare on infant or child well-being, maternal early caregiving practices, or the maternal-child relationship. Furthermore, a recent Cochrane review recommended a RCT to explore the value of integrated prenatal psychosocial care on maternal-child outcomes . This is an important line of inquiry, given that symptoms of prenatal depression, stress, and anxiety tend to continue into the postnatal period, influencing the quality of the child’s postnatal environment [7, 8, 73]. From a healthcare system and societal perspective, the costs associated with poor pregnancy outcomes are substantial [11, 18, 75, 100–102], and treatment options for postpartum mental health  and child developmental problems  are severely limited. Thus, there is a need to evaluate whether early prenatal intervention can prevent or lessen the risk of adverse maternal-child outcomes.