The Maternal-Fetal Dyad: Challenges and Adaptations

For additional material related to the content of this chapter, please see Chapter 2, Chapter 6, Chapter 49, Chapter 51 .

Vignette

Natalie is a partnered, 25-year-old woman, currently at 28 weeks of gestation with her third pregnancy. She brings her 4-year-old son, Jaxon, for an appointment with Dr. Greene, a clinician in a specialty clinic for children with developmental delays. Natalie appears to be sad and irritable, different from her presentation at prior clinic appointments. When Dr. Greene asks how she is doing, she responds, “Not great” and becomes tearful. Dr. Greene recalls that Jaxon was born at 35 weeks of gestational age and has been followed by the clinic since the age of 18 months for mild developmental delays in motor and language skills and sleep difficulties. Natalie had one pregnancy prior to Jaxon, which ended in a spontaneous loss at 12 gestational weeks. Natalie has a history of recurrent major depressive disorder and was treated with venlafaxine, a serotonin-norepinephrine reuptake inhibitor antidepressant, throughout her pregnancy with Jaxon. During his initial clinic visit, she had asked several questions about whether taking medication while pregnant with Jaxon could have contributed to her son’s difficulties .

Introduction

To understand child neurodevelopmental functioning, we must first understand the history of the maternal-child dyadic system from conception. Pregnancy is a dynamic system that comprises the physiologic, anatomic, and psychological components of the woman and her developing fetus within the context of their psychosocial and cultural environment (see Chapter 2 ). Pregnancy is a time of vast confluence of changes within and among these systems. These changes and the maternal-fetal adaptation to them are influenced by both preconception and current psychological, experiential, and physiologic factors. In this chapter we use the following terms when considering key aspects of maternal-child health: perinatal (the time from conception to 12 months postpartum), prenatal (conception through infant birth), and postpartum (after birth).

In our opening vignette, Natalie’s mental health during the current pregnancy may be impacted by her past pregnancy experiences. Inevitably her health status is shared with her fetus. We have yet to learn about Natalie’s experiences prior to her first pregnancy or the quality of her current social support; these factors are important to consider in this situation, as mounting evidence suggests that early life and adolescent experiences and current social support may play a significant role in both parental adjustment to pregnancy and parenthood ( ). Mental health, stress, and coping have been shown to impact pregnancy outcomes as well as long-term child outcomes (see Chapter 2 ). Understanding the impact of these adaptations, transactions, and conditions on the pregnant woman and her fetus is critical to health care during pregnancy and throughout the child’s development.

This chapter will provide an overview of the inherent adaptations and challenges that may occur in the perinatal period and their potential impact on child development. We focus our information on psychiatric disorders and adverse pregnancy-related events. We will briefly discuss available treatments and what is currently known about their potential impact, compared to the underlying condition, on fetal and child development. We conclude with assessment strategies and recommended actions for each condition in the form of clinical pearls.

Physiologic and Psychological Challenges in Pregnancy

Each phase of pregnancy presents ongoing challenges for the maternal-fetal dynamic system that may be met with varying degrees of successful adaptation. A summary of the major adaptations by pregnancy trimester is presented in Table 5.1 . This list of adaptations is not exhaustive but is meant to highlight those adaptations that may impact optimal fetal, infant, and child neurobehavioral development.

Table 5.1

Maternal-Fetal Changes Over Pregnancy and Associated Psychological and Social-Emotional Adaptations

System	First Trimester (0–13 wk)	Second Trimester (14–27 wk)	Third Trimester (28–40+ wk)
Physical/morphologic	Embryologic development evolves quickly, culminating in the fetal form ~13 wk gestation Primitive embryo movements begin by 7 wk gestation; larger, more frequent movements occur by week 12 No or minimal noticeable physical changes to woman’s outward physical form Absence of menses Increasing hCG levels Nausea and fatigue common Vomiting, less common Perception of poor perceived sleep quality with increased daytime sleepiness	Rapid fetal brain development; beginning of myelination Frequent spontaneous movements give way to increasingly stable rest-activity cycles by the end of the second trimester Growth of maternal uterine size, with expansion out of the pelvic cavity Maternal weight gain with altering center of gravity “Quickening”/maternal recognition of fetal movement usually occurs by week 26 Some women may continue to experience nausea and vomiting Blood volume increases, shifting abdominal structures to accommodate uterine size Changes in EEG sleep patterns possible	Accelerated fetal growth, fat stores, and brain development Increasing periods of quiescence as fetal behavioral states emerge Increasing size of the uterus, intermittent contractions of the uterus, and strengthening fetal movements may contribute to maternal physical discomfort Most large fetal movements can be felt by mother More pronounced changes in abdominal structures to accommodate uterine size Sleep becomes more fragmented with additional EEG changes; increased daytime fatigue
Social-emotional	Recognition of pregnancy Reorganization of sense of self, perceptions of others Pregnancy intention, preparation Social support needs increase Prior pregnancy experience, including past pregnancy loss, and psychiatric history and treatment may impact experience of a new pregnancy, increase anxiety, or precipitate changes in treatment due to concerns about taking medication in pregnancy Early mental representation of the fetus may begin	Increased maternal thoughts and images of the fetus; maternal-fetal attachment Most women feel physically well during this time compared to the first trimester Potential for exacerbation of underlying medical conditions or onset of pregnancy-related conditions (e.g., gestational diabetes) There is some evidence of increased onset of depressive mood episodes	Coping with impending delivery Preparation for newborn, transition to parenthood There is some evidence of increased onset of depressive mood episodes and or anxiety

EEG , Electroencephalogram; hCG , human chorionic gonadotropin.

Women most often suspect a pregnancy after the first missed menstrual period, about 2 weeks after conception, which is considered 4 gestational weeks, calculated as time since the last menstrual period. By the time a woman receives confirmation via a home or laboratory pregnancy test, she may already have begun to experience early physical changes alerting her to the possible pregnancy. Many factors may influence successful adaptation at this time, including an intention to become pregnant, positive social support, ongoing physical and emotional health, and past experiences with adverse pregnancy outcomes, loss, or trauma (Farren, Mitchell-Jones, Verbakel, Timmerman, Jalmbrant, & Bourne, et al., 2018). The recognition of pregnancy may be associated with changes in behavior to protect the fetus. While such changes may represent positive adaptations in the case of decreasing unhealthy habits, such as smoking or drinking alcohol, women may make other decisions, such as to forego needed medication or therapies, without prior consultation with health care providers. Then, changes may precipitate increased medical or psychiatric risk.

The early discomforts associated with the first trimester for some women typically resolve by the week 14 of gestation, which marks the onset of the second gestational trimester. While the second trimester is a time when most women report feeling physically well, it is also a time of vulnerability due to ongoing physiologic changes, including alterations in maternal sleep and circadian rhythms, physical changes in body size and shape, and hormonal and metabolic changes that occur throughout the second and third trimesters. Many women report varying mental representations of their fetus by the second trimester, which is thought to be the foundation for building an attachment to the fetus.

Maternal-fetal attachment is a term used to describe the emotional connection a woman develops with her fetus during pregnancy, expressed in feelings, cognitions, and behaviors. Establishing an emotional connection to the fetus is considered an important part of the process of identification with the maternal role and may lay the groundwork for the mother-infant relationship in the postpartum period. The strength of maternal-fetal attachment increases over the course of pregnancy, particularly after fetal movement can be physically experienced at about 18 weeks of gestation. Several factors may lower the strength of maternal-fetal attachment, including maternal depression and poor social support ( ). Maternal-fetal adaptation is critical as the early prenatal mother-infant relationship might influence future social, emotional, and cognitive development in the child.

The third trimester presents new challenges to the maternal-fetal dyad. The fetus is growing rapidly and has associated changes in physiology, increased fat distribution, and ongoing brain development. The mother may be experiencing increasing physical discomfort, sleep disturbance, and fatigue while preparing emotionally and otherwise for the impending delivery. Fathers and significant others may also be dealing with preparations and emotional adjustments in anticipation of birth, and this may impact the family’s overall relationships. Adapting to these changes successfully contributes to optimal birth outcomes.

While child-focused clinicians may have limited contact with the mother during pregnancy, it is important to understand the impact of maternal mental health on short- and long-term infant and child outcomes. Even in women who have high levels of depressive symptoms during pregnancy, children have better developmental outcomes when their mothers are adequately treated and have decreasing symptoms over time than when their mothers are untreated or undertreated ( ).

Perinatal Mental Health

A focus on mental health during the perinatal period, from pregnancy through 12 months postdelivery, is essential for all clinicians. A woman may experience psychiatric symptoms at any time in pregnancy, and the likelihood of occurrence is higher if such symptoms were present prior to the pregnancy ( ). In stark contrast to the prevailing belief that women were protected from mental illness during the perinatal period, recognition that pregnancy and postpartum may be a time of increased risk and vulnerability to mental health disorders is growing; during this time the risk of death by suicide in women is actually heightened ( ). Perinatal women may experience mood or anxiety symptoms for the first time, or the symptoms may be recurrences. Evidence of a direct causal pathway between prenatal maternal depression and child and adolescent behavior, emotional functioning, and psychopathology is compelling ( ). The psychological wellbeing of fathers during the pregnancy has also been examined. Men may have different experiences with depression than women and may not seek treatment; however, paternal depression also increases risk for poorer child outcomes after controlling for maternal mental health ( ). Prevention or treatment of psychiatric conditions remains a priority to promote optimal child development; however, consideration must be given to the potential risks and/or benefits that each treatment may confer.

Perinatal Mood and Anxiety Disorders

In a welcome expansion from a previously narrow focus on postpartum depression, there is growing awareness of the full breadth of mental health difficulties that women encounter throughout the perinatal period. Perinatal mood and anxiety disorder (PMAD) refers to several disorders that may cause distress during pregnancy and up to 12 months after delivery, including bipolar disorder, psychosis, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and panic disorder. A recent, large-scale study reported an increase in PMAD and serious perinatal mental illness from 2006 to 2015 ( ). Black, Indigenous, and people of color, women of lower socioeconomic status, immigrants and undocumented women, and women with disabilities are at elevated risk for PMAD. However, women from marginalized or disadvantaged communities may be particularly reluctant to disclose mental health concerns, given historical mistreatment and fear of negative consequences, such as involvement of child protective services.

Depressive Disorders

Depression is a leading cause of disability for women and the most common nonobstetric complication of the perinatal period. Perinatal depression can result in negative maternal and infant outcomes, with cognitive, emotional, and behavioral challenges for children of mothers with untreated depression. Prenatal depression occurs at a rate of 10% to 15% overall and appears to be more prevalent as pregnancy progresses. Rates of depression in the first trimester are equivalent to those in nonpregnant women (8%–10%). The prevalence increases in the second and third trimesters, with rates as high as 19% overall ( ). In the postpartum period, depression occurs at rates around 20%. However, Latina and Black women report early postpartum symptoms (between 2 and 6 weeks after delivery) at higher rates (47% and 44%, respectively) compared to White women (31%) ( ). Depression after delivery can be severe; 20% of women with postpartum depression report suicidal ideation ( ). Women with postpartum depression often have co-occurring anxiety, which may include anxious attachment or fear of being alone with the baby.

Perinatal depression should be differentiated from the baby blues, a dysphoric 5- to 10-day period that resolves on its own and affects up to 80% of postpartum women ( Table 5.2 ). The baby blues refers to increased tearfulness, anxiety, mood lability, and irritability, and resolves without treatment within a few days. In contrast, depressive disorders are more severe and of longer duration than baby blues, include impairment in functioning, and typically require treatment to resolve.

Table 5.2

Comparison of Baby Blues and Postpartum Depression

	Prevalence	Onset	Duration	Treatment
Baby blues	Up to 80%	3–4 days after delivery	<2 weeks	Support
Postpartum depression	20%	Within 12 mo postpartum	Weeks to months	Therapy, medication

It may be difficult to differentiate between an unremarkable pregnancy and postpartum symptoms of depression, especially changes in sleep, appetite and weight, and fatigue. Clinicians may minimize or dismiss signs of perinatal depression, assuring mothers their experiences are normal. However, the American Academy of Pediatrics (AAP) and other professional organizations recommend incorporating postpartum depression screening into pediatric well-child care. The identification of clinically significant depression may be facilitated using a self-report questionnaire. The Edinburgh Postnatal Depression Scale (EPDS) ( ) is widely used and well validated to identify depression and anxiety during pregnancy and postpartum. The EPDS has been translated into numerous languages and has been validated in pregnant and postpartum women across racial, ethnic, and cultural groups in both high- and low-income countries. Scores greater than 7 may indicate mild depression, scores of 13 to 18 suggest moderate depression, and scores above 18 should be considered severe depression ( ). Clinical judgment should always be used in conjunction with the scores obtained. Another screening option is the Patient Health Questionnaire, a two- or nine-item measure, which has also been validated in an obstetric-gynecologic context but may not be appropriate for all populations.

vignetteDr. Greene asks Natalie if she is feeling depressed, and she confirms that she is feeling sad and irritable most of the day, nearly every day, and has been sleeping less than 5 or 6 hours/night. She admits to feeling guilty because she no longer enjoys playing with Jaxon. Dr. Greene asks Natalie to fill out the EPDS survey to learn more about the severity of her symptoms, and her score is 15 .

Natalie is endorsing the two main symptoms of depression (depressed mood and anhedonia), and her EPDS score suggests that these symptoms are clinically significant. She is also reporting guilt and distress about her loss of enjoyment of her time with her son. This presentation is clinically significant and requires further assessment for suicidal ideations. It may also require treatment in the form of a referral, such as a “warm hand-off” to mental health care clinicians or trained community-based workers.

Risk and Protective Factors for Perinatal Depression

A history of depression is the most significant risk factor for perinatal depression, conferring a 20-fold increased risk for postpartum depression specifically ( ). Risk factors for depression in pregnancy include domestic violence, lack of support, life stress, maternal anxiety, unintended pregnancy, single status, and strained relationship with partner.

Predictors of postpartum depression include symptoms of depression or anxiety during pregnancy, a recent stressful event, perceived lack of support, and traumatic birth. Women with a positive screen for postpartum depression (using an EPDS score of ≥10) were more likely to be Black, single, and less educated than White, married, and highly educated ( ). Protective factors include perceived social support and resilience, defined as adaptation in the face of adversity.

Risks to Child Outcomes Associated With Perinatal Depression

Prenatal depression is associated with higher risk of obstetric complications, lower gestational age and birthweight, as well as long-term emotional, behavioral, and social problems in the child. Results from preclinical and human studies provide compelling evidence of a direct causal pathway between prenatal maternal depression and child and adolescent behavior, emotional functioning, and psychopathology ( ). A meta-analysis of 71 studies found that prenatal stress and depression were significant risk factors for child socio-emotional problems independent of other postnatal risk factors, however the effects were greater for those with additional socio-demographic risk ( ).

Postpartum depression is also linked to greater risks for children. found that children of mothers with depression were more likely to have behavior problems, including internalizing and externalizing behaviors and attention-deficit/hyperactivity disorder, than children of mothers with low or decreasing depressive symptomatology over time. A high relapse rate of maternal depression can be detrimental to child development, and prompt intervention is essential to avoid impacting the child’s pattern of stress responses via hypothalamus-pituitary-adrenal and cortisol reactivity ( ). In another recent study, children exposed to maternal depression before age 5 years had 17% greater odds of developmental vulnerability compared to those who were not exposed, with the strongest associations occurring in social-emotional domains ( ). Pediatric clinicians should be aware of maternal mental health and be prepared to refer women for appropriate treatment when possible.

Treatment for Perinatal Depression

vignetteNatalie reports that she stopped taking her antidepressant medication when she found out she was pregnant, as she feared the same medication was to blame for her son Jaxon’s preterm birth and developmental delays. When asked if she has been using alternate treatments for her depression, she reports that she has been using marijuana three to four times per week to relax and sleep better. She says she heard that marijuana is harmless during pregnancy. She recently signed up for prenatal yoga, and her first class is next week .

Natalie’s case is not uncommon. Many women fear the impact of medication on their unborn child and prefer nonpharmacologic treatments ( ). It is important for women who are contemplating pregnancy or those who are pregnant to have a discussion with their clinicians about benefits and risks associated with treatment and with nontreatment.

Approximately 13% of pregnant women have taken an antidepressant during their pregnancy; serotonin selective reuptake inhibitors (SSRIs) are among the most prescribed drugs in pregnancy. The American College of Obstetrics and Gynecology (ACOG) has published guidelines regarding the use of psychotropic medications in pregnancy as well as treatment recommendations for specific psychiatric conditions based on available data and clinical consensus ( ). Treatment advice needs to be based on careful consideration of the known risks and benefits of the treatment as well as the severity of the condition, stage of pregnancy, and preferences of the woman. Psychosocial approaches are recommended as a first-line treatment for depression in pregnancy unless the woman experiences suicidality or psychosis; psychotherapy, cognitive behavioral therapy, and interpersonal therapy are effective treatments for prenatal depression (see Chapter 49 ). For moderate to severe depression, medication may be considered in addition to psychotherapy if the depressive episode occurs after discontinuation of medication or if there is no response or worsening of symptoms to initial evidence-based nonmedication treatment.

Risks to Child Outcomes Associated With Treatment for Perinatal Depression

As indicated, SSRIs are the antidepressants prescribed most often in pregnancy. These inhibitors cross the placenta and affect fetal serotonin signaling, which affects brain development and modulates neurons involved in motor and social behaviors, emotional reactivity, and sleep. Prenatal SSRI exposure contributes to statistically significant adverse obstetric outcomes ( ). However, the clinical significance of the outcomes is not clear; they were limited to 1.5 times higher risk of preterm birth, half-week earlier gestational age at delivery, and less than 1-g lower birthweight. A meta-analysis of 30 studies showed that antidepressant use in pregnancy was associated with a significantly greater risk of adverse neonatal signs after delivery, specifically respiratory distress and tremors ( ). These adverse signs appear to be transient in the first postnatal month but may be more severe and prolonged with concomitant medication exposures such as benzodiazepines ( ). Evidence of the impact of prenatal SSRI exposure on the child after the first postnatal month is inconsistent and complicated by the potential confounding of the underlying maternal condition. However, there is some consistency in the finding of minor motor delays that appear to resolve by 36 months of age. Recent reports that controlled for potential confounding suggested that gastrointestinal complaints may be more common in prenatally SSRI-exposed children than unexposed children ( ) and that there may be some impact on specific aspects of social language development ( ). The benefits of treating PMAD must be considered for each woman individually.

Scientific evidence of the impact of alternative treatments for depression and anxiety on infant and later outcomes is limited. There is evidence of at least a small to moderate association with better outcomes for children of women who were adequately treated in pregnancy with nonpharmacologic options compared to those whose mothers were not treated ( ). Several promising nonpharmacologic self-management interventions have received attention for preventing or intervening with perinatal depressive symptoms (e.g., yoga, physical activity), particularly when they are used as adjuncts to usual care ( ).

ACOG guidelines apply to all psychotropic medications used to treat other PMADs. Infants may experience adverse effects from any psychotropic medication; however, the risks of these events may not outweigh the risks of not treating the underlying condition. Prenatal exposure to concomitant psychotropic medications may further increase risk of adverse neonatal signs and events; infants should be monitored closely in the first postnatal month.

Bipolar Spectrum Disorders

Women with a history of bipolar disorder have a recurrence rate of 71% in the perinatal period ( ). Women with bipolar disorder are more likely to experience a depressive rather than a manic or hypomanic episode during the perinatal period. They are 50% more likely to experience postpartum depression compared to women with a history of unipolar depression ( ). The Mood Disorder Questionnaire (MDQ) is a useful screening instrument for bipolar disorder and has been validated in postpartum women. A score of 7 or higher indicates a positive screen, in addition to functional impairment.

The decision to maintain or initiate medication for a pregnant or lactating woman requires a careful analysis of the risk of untreated illness compared to risk of medication effects on fetus/baby. Lithium, anticonvulsants, and second-generation antipsychotics are typically used to treat bipolar disorder; valproic acid is discouraged due to negative fetal effects, and carbamazepine is similarly avoided unless it was used pre-pregnancy and switching medications could prove harmful ( ). Women with bipolar disorder could utilize bright light therapy, if taking an antimanic agent, and if they are able to follow a specific protocol to avoid activation of mania.

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