Williams Obstetrics, 24th Edition

CHAPTER 61. Psychiatric Disorders

PSYCHOLOGICAL ADJUSTMENTS TO PREGNANCY

THE PUERPERIUM

PRENATAL EVALUATION

TREATMENT CONSIDERATIONS

DEPRESSIVE DISORDERS

BIPOLAR AND RELATED DISORDERS

ANXIETY DISORDERS

SCHIZOPHRENIA SPECTRUM DISORDERS

FEEDING AND EATING DISORDERS

PERSONALITY DISORDERS

Pregnancy and the puerperium are at times sufficiently stressful to provoke mental illness. Such illness may represent recurrence or exacerbation of a preexisting psychiatric disorder, or may signal the onset of a new disorder. Psychiatric disorders during pregnancy have been associated with less prenatal care, substance abuse, poor obstetrical and infant outcomes, and a higher risk of postpartum psychiatric illness (Frieder, 2008). Of pregnant women identified with psychiatric disorders, Andersson and colleagues (2003) in one Swedish study reported that more than 80 percent had a mood disorder. According to the Agency for Healthcare Research and Quality, the period prevalence of any depressive disorder during pregnancy in the United States is 18 percent (Yonkers, 2011). Unfortunately, most pregnant women with depressive disorders are not treated. In the Swedish study mentioned above, only 5 percent of women identified with psychiatric disorders received some form of treatment.

Suicide is the fifth leading cause of death in the United States among women during the perinatal period, and major depression is among the strongest predictors of suicidal ideation (Melville, 2010). In both the United Kingdom and Australia, psychiatric illness is a leading cause of mortality for late maternal deaths—those between 43 and 365 days postpartum (Austin, 2007). Suicide by violent means was responsible for 65 percent of these. In a 10-year case-control analysis of Washington state hospitalizations, Comtois and associates (2008) studied 355 women with a postpartum suicide attempt. Significant risk factors and their associated rates included prior hospitalization for a psychiatric diagnosis—27-fold, and for substance abuse—sixfold. These rates were further increased if there were multiple hospitalizations.

PSYCHOLOGICAL ADJUSTMENTS TO PREGNANCY

Biochemical factors—including hormonal effects—and life stressors can markedly influence mental illness. Thus, intuitively, pregnancy exacerbates some coexisting mental disorders. Indeed, pregnancy-related shifts in sex steroids and monoamine neurotransmitter levels; dysfunction of the hypothalamic-pituitary-adrenal axis; thyroid dysfunction; and alterations in immune response are all associated with an increased risk for mood disorders (Yonkers, 2011). These changes, coupled with evidence of familiality of depression, suggest that there may be a subgroup of women at risk for developing a unipolar major depressive disorder during pregnancy.

Women respond in a variety of ways to stressors of pregnancy, and some express persistent concerns regarding fetal health, child care, lifestyle changes, or fear of childbirth pain. Anxiety, sleep disorders, and functional impairment are common (Morewitz, 2003; Romero, 2014; Vythilingum, 2008). According to Littleton and coworkers (2007), however, anxiety symptoms in pregnancy are associated with psychosocial variables similar to those for nonpregnant women. The level of perceived stress is significantly higher for women whose fetus is at high risk for a malformation, for those with preterm labor or delivery, and for those with other medical complications (Alder, 2007; Ross, 2006). Hippman (2009) screened 81 women for depression who had an increased risk for a fetus with aneuploidy. Half of these women had a positive depression screening score, whereas only 2.4 percent of those with a normal pregnancy did so.

A number of steps can be taken to diminish psychological stress in the event of a poor obstetrical outcome. For example, following a stillbirth, Gold (2007) encouraged parental contact with the newborn and provision of photographs and other infant memorabilia. Addressing associated sleep disorders also seems reasonable (Romero, 2014).

image The Puerperium

The puerperium is a particularly stressful time and carries as increased risk for mental illness. Up to 15 percent of women develop a nonpsychotic postpartum depressive disorder within 6 months of delivery (Tam, 2007; Yonkers, 2011). A few have a more severe, psychotic illness following delivery, and half of these have a bipolar disorder (Yonkers, 2011). Depressive disorders are more likely in women with obstetrical complications such as severe preeclampsia or fetal-growth restriction, especially if associated with early delivery. However, among women with a history of bipolar disorder, these factors do not seem to play as great a role in the development of mania or depression (Yonkers, 2011).

Maternity Blues

Also called postpartum blues, this is a time-limited period of heightened emotional reactivity experienced by half of women within approximately the first week after parturition. Prevalence estimates for the blues range from 26 to 84 percent depending on criteria used for diagnosis (O’Hara, 2014). This emotional state generally peaks on the fourth or fifth postpartum day and normalizes by day 10 (O’Keane, 2011). The predominant mood is happiness. However, affected mothers are more emotionally labile, and insomnia, weepiness, depression, anxiety, poor concentration, irritability, and affective lability may be noted. Mothers may be transiently tearful for several hours and then recover completely, only to be tearful again the next day. Supportive treatment is indicated, and sufferers can be reassured that the dysphoria is transient and most likely due to biochemical changes. They should be monitored for development of depression and other severe psychiatric disturbances.

image Prenatal Evaluation

Screening for mental illness is generally done at the first prenatal visit. Factors include a search for psychiatric disorders, including hospitalizations, outpatient care, prior or current use of psychoactive medications, and current symptoms. Risk factors should be evaluated—for example, a prior personal or family history of depression conveys a significant risk for depression. Women with a history of sexual, physical, or verbal abuse; substance abuse; and personality disorders are also at greater risk for depression (Akman, 2007; Tam, 2007). Smoking and nicotine dependence have been associated with an increase in rates of all mental disorders in pregnancy (Goodwin, 2007). Finally, because eating disorders may be exacerbated by pregnancy, affected women should be followed closely.

According to the American College of Obstetricians and Gynecologists (2012a), there is currently insufficient evidence to make a firm recommendation for routine depression screening, either during or after pregnancy. At Parkland Hospital, all women are asked about depression and domestic violence at their first prenatal visit. They are also screened again during their first postpartum visit using the Edinburgh Postnatal Depression Scale (EPDS). In an analysis of more than 17,000 of these questionnaires, 6 percent had scores that indicated either minor or major depressive symptoms. Twelve of these 1106 women also had thoughts of self-harm (Nelson, 2013).

image Treatment Considerations

A large number of psychotropic medications may be used for management of the myriad mental disorders encountered in pregnancy. For treatment options that include psychosocial and psychological interventions, treatment decisions are ideally shared between patients and their health-care providers. Women taking psychotropic medication should be informed of likely side effects. Many of these drugs are discussed in Chapter 12 as well as by the American College of Obstetricians and Gynecologists (2012b). Additionally, these drugs are discussed subsequently in this chapter. Babbitt (2014) and Pozzi (2014) and their colleagues have recently reviewed principles of antenatal and intrapartum care of women with major mental disorders.

image Pregnancy Outcomes

There are only a few reports of psychiatric disorders and pregnancy outcomes. Some, but not all, link maternal psychiatric illness with untoward outcomes such as preterm birth, low birthweight, and perinatal mortality (Schneid-Kofman, 2008; Steinberg, 2014; Yonkers, 2009). In a population-based cohort of more than 500,000 California births, Kelly and colleagues (2002) assessed the perinatal effects of a psychiatric diagnosis that included all International Classification of Diseases 9th Edition Clinical Modification (ICD-9-CM) diagnostic codes. Women with these diagnoses had up to a threefold increased incidence of a very-low- or low-birthweight neonate or preterm delivery. In another study of more than 1100 women enrolled in a Healthy Start initiative, women with depression were found to be 1.5 times more likely to be delivered early compared with nondepressed women. Conversely, Littleton and associates (2007) reviewed 50 studies and concluded that anxiety symptoms—a common comorbidity in depression—had no adverse effect on outcomes.

CLASSIFICATION OF MENTAL DISORDERS

The Diagnostic and Statistical Manual-V is the most recent version by the American Psychiatric Association (2013). Its purpose is to assist in the classification of mental disorders, and it specifies criteria for each diagnosis. Shown in Table 61-1 are 12-month prevalences of mental disorders for adults.

TABLE 61-1. The 12-Month Prevalence of Mental Disorders in Adults in the United States

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image Depressive Disorders

According to the National Institute of Mental Health (2010), the lifetime prevalence of depressive disorders in the United States is 21 percent. Women are 50 percent more likely than men to experience a major mood disorder during their lifetime. Historically, these include major depression—a unipolar disorder—and manic-depression—a bipolar disorder with both manic and depressive episodes. It also includes dysthymia, which is chronic, mild depression. When concurrent with medical complications such as diabetes, heart disease, and asthma, major mood disorders worsen medical outcomes, and as a group, contribute to two thirds of all suicides (Yonkers, 2011).

image Major Depression

This is the most common depressive disorder, and an estimated 12 million women each year in the United States are affected (Mental Health America, 2013a). The lifetime prevalence is 17 percent, but only half ever seek care. The diagnosis is arrived at by identifying symptoms listed in Table 61-2.

TABLE 61-2. Symptoms of Depressive Illnessa


Persistent sad, anxious, or “empty” feelings

Feelings of hopelessness and/or pessimism

Feelings of guilt, worthlessness, and/or helplessness

Irritability, restlessness

Loss of interest in activities or hobbies once pleasurable, including sex

Fatigue and decreased energy

Difficulty concentrating, remembering detail, and making decisions

Insomnia, early-morning wakefulness, or excessive sleeping

Overeating or appetite loss

Thoughts of suicide, suicide attempts

Persistent aches or pains, headaches, cramps, or digestive problems that do not ease even with treatment

aNot all patients experience the same symptoms, and their severity, frequency, and duration will vary among individuals.

From the National Institute of Mental Health, 2010.

Major depression is multifactorial and prompted by genetic and environmental factors. First-degree relatives have a 25-percent risk, and female relatives are at even higher risk. One genome-wide linkage analysis of more than 1200 mothers suggests that variation in chromosomes 1 and 9 increases susceptibility to postpartum mood symptoms (Mahon, 2009). Families of affected individuals also often have members with alcohol abuse and anxiety disorders. Provocative conditions leading to depression include life events that prompt grief reactions, substance abuse, use of certain medications, and other medical disorders. Although life events can trigger depression, genes influence the response to life events, making the distinction between genetic and environmental factors difficult.

Pregnancy

It is unquestionable that pregnancy is a major life stressor that can precipitate or exacerbate depressive tendencies. In addition, there are likely various pregnancy-induced effects. Hormones certainly affect mood as evidenced by premenstrual syndrome and menopausal depression. Estrogen has been implicated in increased serotonin synthesis, decreased serotonin breakdown, and serotonin receptor modulation (Deecher, 2008). Concordantly, women who experience postpartum depression often have higher predelivery serum estrogen and progesterone levels and experience a greater decline postpartum (Ahokas, 1999).

Dennis and associates (2007) queried the Cochrane Database and reported the prevalence of antenatal depression to average 11 percent. Melville and coworkers (2010) found it in nearly 10 percent of more than 1800 women enrolled for prenatal care at a single university obstetrical clinic. Others have reported the incidence to be much higher (Lee, 2007; Westdahl, 2007). In another report, Luke and colleagues (2009) found major depressive symptoms in 25 percent of pregnant African American women. Hayes and associates (2012) reported that 13 percent of pregnant women in the Tennessee Medicaid program filled an antidepressant prescription either before or during pregnancy. In another report of almost 119,000 pregnancies in seven health plans, Andrade and coworkers (2008) found that only 6.6 percent received antidepressants at any time during pregnancy. These findings support to the notion that only half of pregnant women with depression receive treatment.

Postpartum depression—major or minor—develops in 10 to 20 percent of parturients (Centers for Disease Control and Prevention, 2008; Mental Health America, 2013b). Available data indicate that unipolar major depression may be slightly more prevalent during the puerperium than among women in the general population (Yonkers, 2011). In addition to antenatal depression, postpartum depression has been associated with young maternal age, unmarried status, smoking or drinking, substance abuse, hyperemesis gravidarum, preterm birth, and high utilization of sick leave during pregnancy (Endres, 2013; Lee, 2007; Marcus, 2009).

Depression is frequently recurrent. At least 60 percent of women taking antidepressant medication before pregnancy have symptoms during pregnancy. According to Hayes and colleagues (2012), approximately three fourths of women taking antidepressants before pregnancy stopped taking them before or during the first trimester. For those who discontinue treatment, almost 70 percent have a relapse compared with 25 percent who continue therapy. Up to 70 percent of women with previous postpartum depression have a subsequent episode. Women with both prior puerperal depression and a current episode of “maternity blues” are at inordinately high risk for major depression. Indeed, the need for postpartum depression help was the fourth most common challenge identified at 2 to 9 months postpartum by the Pregnancy Risk Assessment Monitoring System—PRAMS (Kanotra, 2007).

Postpartum depression is generally underrecognized and undertreated. Major depression during pregnancy or after delivery can have devastating consequences for affected women, their children, and families. Among new mothers, one of the most significant contributions to their mortality rate is suicide, which is most common among women with mental illness (Koren, 2012; Palladino, 2011). If left untreated, up to 25 percent of women with postpartum depression will be depressed 1 year later. As the duration of depression increases, so too do the number of sequelae and their severity. In addition, maternal depression during the first weeks and months after delivery can lead to insecure attachment and later behavioral problems in the child.

Treatment

Antidepressant medications, along with some form of psychotherapy, are indicated for severe depression during pregnancy or the puerperium (American College of Obstetricians and Gynecologists, 2012b). Shown in Figure 61-1 is one algorithm regarding initiation of treatment of mood disorders and management with a mental health professional. In women with severe depression a selective serotonin-reuptake inhibitor—SSRI—should be tried initially (Table 61-3). Tricyclic antidepressants and monoamine oxidase inhibitors are infrequently used in contemporary practice. If depressive symptoms improve during a 6-week trial, the medication should be continued for a minimum of 6 months to prevent relapse (Wisner, 2002). If the response is suboptimal or a relapse occurs, another SSRI is substituted, or psychiatric referral is considered. Mozurkewich and associates (2013) reported no salutary effects of docosahexaenoic acid (DHA) to prevent perinatal depression.

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FIGURE 61-1 Treatment algorithm of pregnant women with mood disorders. (Modified from Yonkers, 2011.)

TABLE 61-3. Some Drugs Used for Treatment of Major Mental Disorders in Pregnancy

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Importantly, in a recent metaanalysis by Huang and colleagues (2014), women using antidepressants during pregnancy were found to be at increased risk for preterm birth and low-birthweight neonates. Nevertheless, in their review of antidepressant medication use in pregnancy, Ray and Stowe (2014) concluded that the relative reproductive safety data is reassuring and that antidepressants remain a viable treatment option.

Recurrence some time after medication is discontinued develops in 50 to 85 percent of women with an initial postpartum depressive episode. Women with a history of more than one depressive episode are at greater risk (American Psychiatric Association, 2000a). Surveillance should include monitoring for thoughts of suicide or infanticide, emergence of psychosis, and response to therapy. For some women, the course of illness is severe enough to warrant hospitalization.

Fetal Effects of Therapy

Some known and possible fetal and neonatal effects of treatment are listed in Table 61-3. Studies implicating SSRIs with an increased teratogenic risk for fetal cardiac defects were isolated to paroxetine and were most consistent for ventricular septal defects (VSDs). It is estimated that the risk is no greater than 1 in 200 exposed infants (Koren, 2012). Nevertheless, the American College of Obstetricians and Gynecologists (2012b) has recommended that paroxetine be avoided in women who are either pregnant or planning pregnancy. Fetal echocardiography should be considered in women exposed to paroxetine in the first trimester.

In a case-control study, there was a sixfold increased risk of persistent pulmonary hypertension of the newborn (PPHN) in infants exposed to SSRIs after 20 weeks (Chambers, 2006). This translates to an overall risk of pulmonary hypertension that would be less than 1 in 100 exposed infants (Koren, 2012). In contrast, a population-based cohort study of 1.6 million pregnancies from Nordic countries identified a twofold increased risk in exposed neonates. It was estimated that this yields an attributable risk of 2 per 1000 births (Kieler, 2012). This marginally increased risk must be weighed against the risk associated with discontinuing or tapering medication during pregnancy.

Women who abruptly discontinue either serotonin- or norepinephrine-reuptake inhibitor therapy typically experience some form of withdrawal. Not surprisingly, up to 30 percent of exposed neonates may also exhibit withdrawal symptoms. Symptoms are similar to opioid withdrawal, but typically are less severe. This condition—neonatal behavioral syndrome—is self-limited, and the newborn rarely remains in the nursery more than 5 days. (Koren, 2009). Currently, convincing evidence of long-term neurobehavioral effects of fetal exposure to these medications is lacking (Koren, 2012).

Some psychotropic medications pass into breast milk. However, in most cases, levels are very low or undetectable. Importantly, the average amount of drug detected in breast milk is higher with fluoxetine than most other reuptake inhibitors (National Library of Medicine, 2012). Adverse effects include transient irritability, sleep disturbances, and colic. Agents with lower excretion into breast milk may therefore be preferred.

Electroconvulsive Therapy

This form of depression treatment is occasionally necessary during pregnancy for women with major mood disorders unresponsive to pharmacotherapy. With proper preparation, the risks to both mother and fetus appear to be reasonable (Pinette, 2007). O’Reardon and coworkers (2011) reported a woman who underwent 18 electroconvulsive therapy (ECT) sessions during the second and third trimesters. She was delivered of a normal child without evidence of developmental delay up to 18 months of age. That said, adverse maternal and perinatal outcomes have been described from complications of convulsive therapy. Balki and associates (2006) reported a pregnancy in which fetal brain damage likely was caused by sustained maternal hypotension associated with treatment of status epilepticus stimulated by electroshock.

Women undergoing ECT should be fasting for at least 6 hours. They should be given a rapid-acting antacid before the procedure, and their airway should be protected to decrease the likelihood of aspiration. A wedge should be placed under the right hip to prevent sudden maternal hypotension from aortocaval compression. Other important preparatory steps include cervical assessment, discontinuation of nonessential anticholinergic medication, uterine and fetal heart rate monitoring, and intravenous hydration. During the procedure, excessive hyperventilation should be avoided. In most cases, maternal and fetal heart rate and maternal blood pressure and oxygen saturation remain normal throughout the procedure.

There have been at least two reviews of ECT outcomes in pregnancy. In the earlier one, Miller (1994) found 300 cases and reported complications in 10 percent. These included fetal arrhythmias, vaginal bleeding, abdominal pain, and self-limited contractions. Women not adequately prepared had increased risks for aspiration, aortocaval compression, and respiratory alkalosis. In the more recent review, Andersen and Ryan (2009) described 339 cases, undoubtedly with some homology with the earlier study. In most cases, ECT therapy was done to treat depression, and it was 78-percent effective. They reported a 5-percent maternal ECT-related complication rate and a 3-percent associated perinatal complication rate that included two fetal deaths. For all of these reasons, we agree with Richards (2007) that ECT in pregnancy is not “low risk” and that it should be reserved for women whose depression is recalcitrant to intensive pharmacotherapy.

image Bipolar and Related Disorders

According to the National Institute of Mental Health (2010), the lifetime prevalence for manic-depression illness is 3.9 percent. There is no difference in the prevalence of bipolar disorder between pregnant women and nonpregnant reproductive-aged women (Yonkers, 2011). It has a strong genetic component and has been linked to possible mutations on chromosomes 16 and 8 (Jones, 2007). The risk that monozygotic twins are both affected is 40 to 70 percent, and the risk for first-degree relatives is 5 to 10 percent (Muller-Oerlinghausen, 2002). Periods of depression last at least 2 weeks. At other times, there are manic episodes, distinct periods during which there is an abnormally raised, expansive, or irritable mood. Potential organic causes of mania include substance abuse, hyperthyroidism, and central nervous system tumors. Importantly, however, pregnancy frequently prompts medication discontinuation, and this translates to a twofold increased risk for relapse during pregnancy (Viguera, 2007). Up to 20 percent of patients with manic-depression illness commit suicide.

Typical therapy for bipolar disorder includes mood stabilizers such as lithium, valproic acid, and carbamazepine, as well as antipsychotic medications (see Table 61-3). As depicted in Figure 61-1, treatment of bipolar disorder in pregnancy is complex and should be co-managed with a psychiatrist. Treatment decisions include risks versus benefits of using mood stabilizers, some of which are teratogenic. For example, lithium has been linked to Ebstein anomaly in exposed infants (Chap. 12p. 250). More recent data, however, suggest a lower risk of cardiac malformations than previously indicated (Reprotox, 2012). Nevertheless, fetal echocardiography is recommended by many for exposed fetuses. There is some limited evidence suggesting that lithium in breast milk can adversely affect the infant when its elimination is impaired as in dehydration or immaturity (Davanzo, 2011). Lithium use in mothers with a healthy term fetus, however, is considered moderately safe. A more detailed discussion of other mood stabilizers and antipsychotic medications side effects can be found in Chapter 12 (p. 250).

Postpartum Psychosis

This severe mental disorder is usually a bipolar disorder, but it may be due to major depression (American Psychiatric Association, 2013). Its incidence is estimated to be 1 in every 1000 deliveries, and it is more common in primiparas, especially those with obstetrical complications (Bergink, 2011; Blackmore, 2006). In most cases, illness manifests within 2 weeks of delivery. In a case-control study of postpartum women with their first lifetime episode of psychosis, the median onset of psychiatric symptoms was 8 days after delivery, and the median duration of the episode was 40 days (Bergink, 2011).

The most important risk factor for postpartum psychosis is a history of bipolar disease. These women typically exhibit symptoms sooner—1 to 2 days after delivery (Heron, 2007, 2008). Manic symptoms include feeling excited, elated, “high”; not needing sleep or unable to sleep; feeling active or energetic; and feeling “chatty.” Affected women have signs of confusion and disorientation but may also have episodes of lucidity. Because those with underlying disease have a 10- to 15-fold risk for recurrence postpartum, close monitoring is imperative. Postpartum psychosis has a 50-percent recurrence risk in the next pregnancy. As a result, Bergink and colleagues (2012) recommend initiating lithium therapy immediately postpartum in women with a history of postpartum psychosis.

The clinical course of bipolar illness with postpartum psychosis is comparable with that for nonpregnant women. Patients usually require hospitalization, pharmacological treatment, and long-term psychiatric care. Psychotic women may have delusions leading to thoughts of self-harm or harm to their infants. Unlike women with nonpsychotic depression, these women commit infanticide, albeit uncommonly (Kim, 2008). In most instances, women with postpartum psychosis ultimately develop relapsing, chronic psychotic manic-depression.

image Anxiety Disorders

These relatively common disorders–18 percent prevalence overall–include panic attack, panic disorder, social anxiety disorder, specific phobia, separation anxiety disorder, and generalized anxiety disorder. All are characterized by irrational fear, tension, and worry, which are accompanied by physiological changes such as trembling, nausea, hot or cold flashes, dizziness, dyspnea, insomnia, and frequent urination (Schneier, 2006). They are treated with psychotherapy and medication, including selective serotonin-reuptake inhibitors, tricyclic antidepressants, monoamine oxide inhibitors, and others.

Pregnancy

Despite their relative high prevalence in childbearing-aged women as shown in Table 61-1, little specific attention has been directed to anxiety disorders in pregnancy. Most reports conclude that there is no difference in rates in between pregnant and nonpregnant women. One recent analysis of 268 pregnant women with generalized anxiety disorder demonstrated that both symptoms and severity of anxiety decrease across pregnancy (Buist, 2011). Older studies indicate increased risks for adverse pregnancy outcomes with some of these disorders (American College of Obstetricians and Gynecologists, 2012b).

From their review, Ross and McLean (2006) concluded that some of the anxiety disorders may have important maternal-fetal implications. Some have been linked to preterm birth and fetal-growth restriction as well as poor neurobehavioral development (Van den Bergh, 2005). Children with a history of in utero exposure to maternal anxiety are felt to be at increased risk for a variety of neuropsychiatric conditions such as attention deficit/hyperactivity disorder (ADHD). Hunter and coworkers (2012) analyzed infants of 60 mothers with an anxiety disorder and found that auditory sensory gating—a reflection of inhibitory neurotransmission—was impaired, particularly in offspring of untreated women. Conversely, Littleton and associates (2007) found no excessive adverse pregnancy outcomes with “anxiety symptoms.” One important exception is their link with postpartum depression (Vythilingum, 2008).

Treatment

Mood and anxiety disorders coexist in more than half of women identified with either diagnosis (Frieder, 2008). Anxiety disorders can be effectively treated during pregnancy with psychotherapy, cognitive behavioral therapy, or medications. Antidepressants listed in Table 61-3 are often the first line of pharmacotherapy. Benzodiazepines are also commonly used to treat anxiety or panic disorders before and during pregnancy. Earlier case-control studies linked use of these central nervous system depressants to an increased risk for cleft lip and palate. However, a recent metaanalysis that included more than 1 million exposed pregnancies did not identify a teratogenic risk (Enato, 2011). Benzodiazepines, especially when taken during the third trimester, can cause neonatal withdrawal syndrome, which persists for days to weeks after delivery.

image Schizophrenia Spectrum Disorders

This major form of mental illness affects 1.1 percent of adults (see Table 61-1). Schizophrenia spectrum disorders are defined by abnormalities in one or more of the following domains: delusions, hallucinations, disorganized thinking, grossly disorganized or abnormal motor behavior, and negative symptoms. Brain-scanning techniques such as positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that schizophrenia is a degenerative brain disorder. Subtle anatomical abnormalities are present early in life and worsen with time.

Schizophrenia has a major genetic component, and there is a 50-percent concordance in monozygotic twins. If one parent has schizophrenia, the risk to offspring is 5 to 10 percent. Some data, including a strong association between schizophrenia and the velocardiofacial syndrome, suggest that associated genes are located on chromosome 22q11 (Murphy, 2002). But sophisticated gene mapping studies have shown clearly that schizophrenia is not related to a single gene or mutation. Instead, there are multiple DNA variants that likely interact to lead to schizophrenia (Kukshal, 2012). Other putative risk factors for subsequent schizophrenia in an exposed fetus include maternal iron deficiency anemia, diabetes, and acute maternal stress (Insel, 2008; Malaspina, 2008; Van Lieshout, 2008). These remain unproven, as does the association with maternal influenza A (Chap. 64p. 1241).

Signs of illness begin approximately at age 20 years, and commonly, work and psychosocial functioning deteriorate over time. Women have a slightly later onset than men and are less susceptible to autism and other neurodevelopmental abnormalities. Thus, many investigators theorize that estrogen is protective. Affected women may marry and become pregnant before symptoms manifest. With appropriate treatment, patients may experience a decrease or cessation of symptoms. Within 5 years from the first signs of illness, 60 percent have social recovery, 50 percent are employed, 30 percent are mentally handicapped, and 10 percent require continued hospitalization (American Psychiatric Association, 2013).

Pregnancy

There has been an apparent increase in relative fertility in schizophrenic women (Solari, 2009). Most studies have not found adverse maternal outcomes, although researchers in a Swedish study noted increased risks of low birthweight, fetal-growth restriction, and preterm delivery (Bennedsen, 1999). In an Australian study of more than 3000 pregnancies in schizophrenic women, Jablensky and colleagues (2005) reported that placental abruption was increased threefold and “fetal distress”—vaguely defined—was increased 1.4-fold.

Treatment

Because schizophrenia has a high recurrence if medications are discontinued, it is advisable to continue therapy during pregnancy. After 40 years of use, there is no evidence that conventional or “typical” antipsychotic drugs listed in Table 61-3 cause adverse fetal or maternal sequelae (McKenna, 2005; Robinson, 2012; Yaeger, 2006). Because less is known about “atypical” antipsychotics, the American College of Obstetricians and Gynecologists (2012b) recommends against their routine use in pregnant and breast-feeding women. In response to adverse event reports, the Food and Drug Administration (2011) issued a safety communication alerting health-care providers concerning some antipsychotic medications. These have been associated with neonatal extrapyramidal and withdrawal symptoms similar to the neonatal behavioral syndrome seen in those exposed to selective serotonin-reuptake inhibitors.

image Feeding and Eating Disorders

These severe disturbances in eating behavior largely affect adolescent females and young adults with a lifetime prevalence of 2 to 3 percent each (see Table 61-1). They include anorexia nervosa, in which the patient refuses to maintain minimally normal body weight. With bulimia nervosa, there usually is binge eating followed by purging or by excessive fasting to maintain normal body weight (Zerbe, 2008). Bulik and coworkers (2009) studied pregnancy outcomes in almost 36,000 Norwegian women screened for eating disorders. Approximately 0.1 percent—1 in 1025—had anorexia nervosa; 0.85 percent—1 in 120—had bulimia nervosa; and 5.1 percent reported a binge-eating disorder—a 6-percent pregnancy prevalence similar to the 6-month prevalence for nonpregnant individuals (see Table 61-1). The last subtype had a higher risk for large-for-gestational age infants with a concomitantly increased cesarean delivery rate. All eating disorders begin with the desire to be slim, and women with chronic eating disorders may migrate between subtypes (Andersen, 2009).

Pregnancy

As discussed in Chapter 18 (p. 352), there is an increased risk for pregnancy complications with both eating disorders, but especially in women with bulimia nervosa (Andersen, 2009; Hoffman, 2011; Sollid, 2004). Generally, eating disorder symptoms improve during pregnancy, and remission rates may reach 75 percent. In contrast, what may appear as a typical case of hyperemesis gravidarum could actually be a new or relapsing case of bulimia nervosa or of anorexia nervosa, binge-purge type (Torgerson, 2008). As perhaps expected, anorexia is associated with low-birthweight infants (Micali, 2007). Additional risks associated with eating disorders include poor wound healing and difficulties with breast feeding (Andersen, 2009). At a minimum, closely monitoring gestational weight gain in women with a suspected history of an eating disorder seems prudent.

image Personality Disorders

These disorders are characterized by the chronic use of certain coping mechanisms in an inappropriate, stereotyped, and maladaptive manner. They are rigid and unyielding personality traits. The American Psychiatric Association (2013) recognizes three clusters of personality disorders:

1. Paranoid, schizoid, and schizotypal personality disorders, which are characterized by oddness or eccentricity.

2. Histrionic, narcissistic, antisocial, and borderline disorders, which are all characterized by dramatic presentations along with self-centeredness and erratic behavior.

3. Avoidant, dependent, compulsive, and passive-aggressive personalities, which are characterized by underlying fear and anxiety.

Genetic and environmental factors are important in the genesis of these disorders, whose prevalence may be as high as 20 percent. Although management is through psychotherapy, most affected individuals do not recognize their problem, and thus only 20 percent seek help. In an observational study of 202 women with borderline personality disorder, De Genna and associates (2012) demonstrated that such women become pregnant during the most severe trajectory of their illness. They are at increased risk for teen and unintended pregnancies, however, it was not a risk factor for elective or spontaneous abortion.

Pregnancy

Personality disorders during pregnancy are probably no different than in nonpregnant women. Management of women with some of these disorders may be vexing. Akman and colleagues (2007) reported that avoidant, dependent, and obsessive-compulsive disorders are associated with an excessive prevalence of postpartum major depression. Magnusson and associates (2007) found a link between some personality traits—not disorders—and excessive alcohol consumption, but not necessarily addiction or dependence. Conroy and coworkers (2010) found that a mother’s ability to care for her newborn was obviously impaired only when a personality disorder was coupled with depression.

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