Handbook of Consultation-Liaison Psychiatry

23. Obstetrics and Gynecology Patients: Menstrual Cycle, Pregnancy, and Postpartum-Related Psychiatric Disorders

Beena Nair

CONTENTS

23.1 Do Hormones Have a Role in Affective State?

23.1.1 Case Example

23.1.2 Discussion

23.2 Menstrual Cycle-Related Affective Illness

23.2.1 Premenstrual Dysphoric Disorder

23.2.2 Perimenopause-Related Affective Illness

23.2.3 Relationship Between Women's Reproductive Cycle and Mood Disorders

23.3 Psychiatric Disorders During Pregnancy

23.3.1 General Considerations

23.3.2 Negative Consequences of Untreated Psychiatric Illness

23.3.3 Mechanisms of Adverse Outcome Secondary to Maternal Psychiatric Illness

23.3.4 Risk Factors for the Emergence or Exacerbation of Psychiatric Disorders During Pregnancy

23.3.5 Prevalence and Clinical Features of Psychiatric Disorders During Pregnancy

23.3.6 Diagnosis and Treatment of Psychiatric Disorders During Pregnancy

23.3.7 General Guidelines for Treatment During Pregnancy

23.4 Postpartum Psychiatric Disorders

23.4.1 Postpartum Blues, Also Called "Baby Blues"

23.4.2 Postpartum Depression

23.4.3 Psychotropic Medication and Lactation

23.4.4 Postpartum (Puerperal) Psychosis

23.5 Special Topics

23.5.1 Hyperemesis Gravidarum

23.5.2 Fetal Demise

23.1 Do Hormones Have a Role in Affective State?

23.1.1 Case Example

A 40-year-old woman who is 15 weeks pregnant and has gestational diabetes was referred for psychiatric evaluation for increasing anxiety and depression. During the psychiatric interview the patient reported feeling very depressed, anxious, restless, confused, and somewhat agitated for the last several weeks, worried that something bad was going to happen to her fetus and her three older children. She also reported racing thoughts, palpitation, feeling very hot and sweaty, and weight loss. The patient denied any past psychiatric history or treatment and denied any alcohol or illicit substance use. On further workup, the patient had a thyroid-stimulating hormone (TSH) of <0.004. She was diagnosed with thyrotoxicosis, and treatment started with propylthiouracil. The patient was also started on an antidepressant and a low dose of antipsychotic to control her agitation.

23.1.2 Discussion

Women have a significantly higher risk for developing mood disorders than men. The lifetime prevalence of mood disorders in women is approximately twice that of men. Sex difference in the rates of depression begins to appear in adolescence. Although reasons for this gender difference are not fully understood, the changing level in reproductive hormones throughout women's life cycles can have direct or indirect effects on mood. Reproductive hormones modulate neuroendocrine, neurotransmitter, and circadian rhythm, all of which have been implicated in the pathophysiology of mood disorder.

Euphoria is seen during the late follicular (periovulatory) phase of menstrual cycle when the estradiol level is increasing, and depression is most likely during the late luteal phase (premenstrual phase) when the hormone levels are declining. Pregnancy is associated with an increase in the hormone levels, which results in improved mood. During the postpartum period, sudden withdrawal of hormones results in affective instability and even psychosis in some women. Studies on bipolar disorder suggest that women are more likely than men to be rapid cyclers (Arnold, 2003). The higher prevalence of rapid cycling in women could be attributed to increased occurrence of hypothyroidism or menstrual cycle irregularities. Also women with bipolar disorder report significant mood changes across the menstrual cycle. Oral contraceptives, hormone replacement therapy, and menopause dampen the cyclicity of ovarian function and can cause mood symptoms.

23.2 Menstrual Cycle-Related Affective Illness

23.2.1 Premenstrual Dysphoric Disorder

Twenty to eighty percent of women report mild to minimal somatic symptoms premenstrually, and 5% experience severe, disabling symptoms and meet the criteria for premenstrual dysphoric disorder (PMDD)-a constellation of mood, behavior, and somatic symptoms with a regular cyclical relationship to the luteal phase of the menstrual cycle, present in almost all the cycles, which remit by the end of menstrual flow with a symptom-free interval of at least 1 week per cycle.

Diagnosis of PMDD requires the presence of five of the following 11 symptoms, with one severe mood symptom causing functional impairment: (1) depressed mood, feelings of hopelessness, or self deprecating thoughts; (2) marked anxiety, tension, feelings of being "keyed up" or "on edge"; (3) marked affective lability, such as feeling suddenly sad or tearful, or increased sensitivity to rejection; (4) persistent marked anger or irritability or increased interpersonal conflicts; (5) decreased interest in usual activities (work, school, friends, hobbies); (6) subjective sense of difficulty in concentration; (7) lethargy, easy fatigability, or marked lack of energy; (8) marked change in appetite, overeating, or specific food cravings; (9) hypersomnia or insomnia; (10) subjective sense of being overwhelmed or out of control; (11) other physical symptoms such as breast tenderness, swelling, headache, joint or muscle pain, sensation of "bloating" or weight gain.

The cause of these symptoms is not fully understood. Symptoms could be the result of exaggerated or abnormal response to normal hormonal changes in susceptible women. Reproductive hormones-estrogen, progesterone and their metabolites alter the noradrenergic, serotonergic, and y-aminobutyric acid (GABA) systems and symptoms could be the effect of central neurotransmitter dysregulation caused by these hormones. An elevated level of serum testosterone during the luteal phase has been suggested to contribute to the symptoms of irritability.

Symptoms may start during the teens or early 20s and worsen with age. Symptoms may vary from cycle to cycle. Premenstrual exacerbation of other mood or anxiety disorders should be ruled out. Symptoms should be assessed prospectively over two consecutive cycles to ensure that symptoms are indeed premenstrual. It is important to rule out other medical or gynecologic causes for the symptoms. Patients' dietary habits, amount of physical activity, and drug/alcohol use should be determined as part of the initial evaluation.

Women who experience PMDD have a greater risk of future depression during pregnancy, postpartum, and the perimenopausal period.

Treatment involves education, lifestyle changes, support, and pharmacologic management of symptoms.

Nonpharmacologic measures include education; support groups; aerobic exercise; stress management; relaxation training; and dietary modifications, such as reducing the intake of caffeine, salt, and refined sugars, eating frequent small meals, and increasing the intake of complex carbohydrates. Cognitive-behavioral therapy (CBT) has been shown to be effective in randomized controlled trials.

Pharmacologic treatments include vitamin and mineral supplementation: B6, 50 to 100 mg/day; calcium carbonate 1200 mg/day in divided doses; magnesium; vitamin E 400 units/day. L-Tryptophan, 6 g per day, has been found to be effective in some studies. For physical symptoms, nonsteroidal antiinflammatory drugs (NSAIDs) and diuretics, especially spironolactone, has been found to be helpful. For mood symptoms, selective serotonin reuptake inhibitor (SSRIs) has been found to be effective in multiple controlled trials. Continuous dosing and intermittent late luteal phase dosing have both been shown to be effective. With intermittent dosing the antidepressant is started approximately 14 days before the onset of menses and continued until the onset of menses or shortly thereafter. Benzodiazepines can be effective for severe anxiety symptoms. Oral contraceptives containing progestins derived from 19-nortestosterone has not been found to be effective, and the side effects could be similar to premenstrual syndrome (PMS). Newer oral contraceptives containing low-dose estrogen and progestin drospirenone, a spironolactone analogue, has been found to be effective in preliminary studies. Gonadotropin-releasing hormone agonists leupro- lide and buserelin, which suppress the menstrual cycle and cause "medical oophorectomy," have been shown to be effective. They should be used only in patients who are resistant to other forms of treatment as they induce menopause and the side effects related to it, including hot flushes, vaginal dryness, depression, headache, osteoporosis, and increased risk for cardiovascular disease. Danazol, a gonadotropin inhibitor has been found to be effective in treating premenstrual mastalgia and migraine. The higher dose required to suppress ovulation is associated with weight gain, mood changes, fluid retention, and acne.

23.2.2 Perimenopause-Related Affective Illness

Perimenopause is associated with physical and psychological symptoms in many women. The physiologic hallmark of the transition into menopause is gradual cessation of ovarian function and estrogen depletion. Estrogen has complex central nervous system (CNS) effects. Estrogen receptors are concentrated in the limbic system, which modulates emotions. It also modulates the synthesis, release, and metabolism of monoamines. It increases the number of 5-hydroxytryptamine (5-HTzA) receptor binding sites in areas that modulate mood and cognition.

During the years leading to menopause the estrogen level changes rapidly with decreasing levels of estradiol production by the ovaries, declining levels of androgens and increasing levels of pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The menopausal transition is frequently accompanied by vasomotor symptoms including hot flushes, night sweats, sleep disturbances, and changes in sexual function. These changes may play a role in the development of mood symptoms in vulnerable women. Community- and clinic-based studies have identified several potential antecedents of perimenopausal depression including past episodes of depression, the presence of PMS, prolonged perimenopause, and hot flushes. It is also a period of increased susceptibility to new-onset depression (Schmidt, 2004). Patients with bipolar disorder may have rapid cycling during this time. Psychosocial factors may play a role in causing the mood symptoms during this period. "Empty nest syndrome," changing roles, and loss of parents and partners may increase the vulnerability to affective illness. The most prevalent mood symptoms during this period include irritability, tearfulness, anxiety, depressed/labile mood, lack of motivation and energy, poor concentration, and interrupted sleep.

23.2.2.1 Treatment

23.2.2.1.1 Pharmacologic Treatment

23.2.2.1.1.1 Antidepressants: The SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) have been found to be effective to treat depression as well as the some of the physical symptoms like hot flushes.

23.2.2.1.1.2 Hormone Replacement: Estrogen therapy has been shown to be especially effective in improving the mood and in alleviating hot flushes, improving psychological well-being, and promoting better quality of life in symptomatic peri- and postmenopausal women, but its use may be accompanied by increased risk of stroke, cardiovascular events, breast cancer and pulmonary embolism. Certain subpopulations of women might preferentially benefit from hormonal interventions such as women with other clinical indications for the use of estrogen replacement therapy (ERT), or women with preexisting clinical conditions such as sexual dysfunction, which could get worse with the isolated use of antidepressants. Transdermal testosterone has been found to be effective in improving mood, anxiety, psychological well-being, and sexual functioning in postmenopausal women.

Cognitive and supportive psychotherapy as well as referral to support groups help women deal with the associated psychosocial stressors.

23.2.3 Relationship Between Women's Reproductive Cycle and Mood Disorders

The pattern of neuroendocrine events related to female reproduction is vulnerable to change and is sensitive to psychosocial, environmental, and physiologic factors. Mood disorders first triggered by hormonal events may later generalize, becoming progressively more severe through the lifetime course of affective illness.

Premenstrual mood symptoms may predispose to the development of severe maternity blues, and postpartum depression can exacerbate premenstrual mood symptoms.

Women with a history of mood disorder have a 10% to 40% risk of having an episode of mood disorder in the postpartum period. Women with a history of postpartum psychosis are at high risk for subsequent puerperal psychotic episodes. Puerperal psychosis is the first illness for over one third of women with bipolar disorder, and the risk of recurrence with subsequent childbirth in women with history of bipolar mood disorder is 25% to 40%.

High levels of prenatal depression are associated with elevated levels of depressive symptoms at 6 weeks postpartum; 30% of women with postpartum affective illness may later develop nonpuerperal affective illness. The episodes tend to become more severe, more frequent and more spontaneous not only with age but also as a function of the number of prior episodes. Untreated episodes lead to greater degrees of behavioral pathology and to episodes that are less responsive to treatment. Untreated postpartum episodes sensitize women to the development or exacerbation of other affective illness. Postpartum state may worsen the course of rapid cycling bipolar disorder, premenstrual syndrome, and menopause.

Changes or variability in reproductive hormones rather than absolute level increases the risk for symptoms in vulnerable individuals. Depression occurring in association with the reproductive cycle may sensitize a woman to further depression.

23.3 Psychiatric Disorders During Pregnancy

23.3.1 General Considerations

23.3.1.1 Case Example

A 32-year-old woman who was 22 weeks pregnant was admitted for fetal monitoring for twin pregnancy complications. Patient had a history of bipolar disorder and borderline personality disorder and had been on Depakote, Seroquel, Klonopin, and Zoloft in the past but discontinued all her medications after she found out that she was pregnant around 7 weeks. This was her seventh pregnancy and was unplanned. She had been feeling increasingly emotional and tearful and occasionally suicidal. She had a history of repeated suicide attempts in the past. During psychiatric interview she reported feeling overwhelmed, depressed, anxious, crying a lot, having insomnia, loss of appetite, and occasional suicidal thoughts, but no psychotic symptoms. When restarting her medications was discussed, the patient adamantly refused to take her psychotropic medications. She stated that she had been on psychotropic drugs during her last pregnancy, and her now 2-year-old son from that pregnancy was recently diagnosed with autism.

Pregnancy has been historically considered a safe period for psychiatric illness. But recent studies have shown increased incidence of relapse or emergence of new psychiatric disorders during pregnancy. Many women are advised to stop psychotropic medications during pregnancy or before conception because of our limited knowledge of their safety during pregnancy. Acute affective or psychotic disorders during pregnancy can have adverse outcome on the pregnancy, fetus, and the family as a whole.

23.3.2 Negative Consequences of Untreated Psychiatric Illness

Maternal negative consequences of untreated psychiatric illness during pregnancy include lack of self care; poor compliance with prenatal care (Zuckerman et al., 1989); lower than expected weight gain; use of tobacco, alcohol, and illicit substances; increased risk of being a victim of violence; decision to abort due to depression; and increased risk for self injurious behavior and suicide (although risk may be lower than in nonpregnant women).

Obstetric and neonatal complications of untreated psychiatric illness includes placental abruption, preeclampsia, higher need for epidural anesthesia, higher incidence of operative deliveries, preterm birth, low birth weight, smaller head circumference, lower Apgar score at birth, higher incidence of neonatal intensive care unit (NICU) admissions, and impairment in neonatal neurobehavioral functioning such as irritability in newborn, unconsolability, and excessive crying (Zuckerman et al., 1990).

Long-term effects on infants of mothers with untreated psychiatric illness Childhood behavioral problems have been reported through animal and human studies in infants of mothers with untreated psychiatric illness. A British, prospective, community-based study found that children whose mothers experienced high levels of anxiety in late pregnancy exhibited higher rates of behavioral and emotional problems during early childhood, which persisted at least through middle childhood, after controlling for obstetric risks, psychosocial disadvantage, and postnatal anxiety and depression (O'Connors et al., 2003). Offspring of mothers who have suffered antenatal stress are overreactive to stress and hypersecrete cortisol compared to controls.

Negative consequences of maternal psychiatric illness on the family unit includes interpersonal problems, marital discord, disruption in the mother-child interaction, and attachment problems.

23.3.3 Mechanisms of Adverse Outcome Secondary to Maternal Psychiatric Illness

The exact mechanism or cause of the adverse outcome is not clear. Some of the hypotheses include increased serum cortisol and catecholamine levels associated with stress. Stress and depression may adversely affect the placental function, which may explain the increased incidence of uterine irritability, preterm labor, and low birth weight. Maternal anxiety in pregnancy has shown to increase the uterine artery resistance index (Teixeira et al., 1999). Placental transmission of stress hormones to the fetus could affect fetal development and increase the risk of behavioral/emotional problems in childhood, perhaps persisting to adulthood.

23.3.4 Risk Factors for the Emergence or Exacerbation of Psychiatric Disorders During Pregnancy

include a history of affective illness, a family history of affective illness, discontinuation of maintenance psychotropic medications during pregnancy, marital discord, recent adverse life events, inadequate psychosocial support, lower socioeconomic status. and unwanted pregnancy.

23.3.5 Prevalence and Clinical Features of Psychiatric Disorders During Pregnancy

23.3.5.1 Unipolar Depression

There is a significant overlap between prepartum and postpartum depression. A study on the prevalence rates and demographic factors associated with depression during pregnancy and postpartum in a heterogeneous sample of 360 pregnant women concluded that approximately 25% of the sample reported elevated levels of depressive symptoms, 10% met diagnostic criteria for depression during pregnancy, and 6.8% were depressed postpartum (Gotlib et al., 1989). Only half of the cases of postpartum depression were new onset (3.4%). The remaining women receiving the diagnosis of postpartum depression were also depressed during pregnancy. Some of the demographic factors that increased the risk of depression during pregnancy included younger age, low education level, greater number of children in the household, and occupation of housewife.

Diagnosis of depression during pregnancy can be complicated by the significant overlap of the neurovegetative symptoms of depression with pregnancy, such as sleep disturbance, low energy, appetite change, and decreased libido. The clinical features that would help to make the diagnosis of depression include anhedonia, feelings of guilt, hopelessness, and suicidal thoughts. Suicidal behavior or a suicide attempt in women with clinical depression during pregnancy is found to be relatively lower compared to that in nonpregnant women (Appleby, 1991; Marzuk et al., 1997).

Women with a history of recurrent major depression who are on maintenance antidepressant medication and who discontinue their medication either before conception or during pregnancy are at significantly high risk for relapse. A prospective study (n = 32) assessing the risk of relapse in women following antidepressant discontinuation during pregnancy found that 75% of the women relapsed during pregnancy, mostly during first trimester. Relapse was more prevalent in women with a history of chronic depression (Cohen et al., 2004).

23.3.5.2 Bipolar Disorder

Pregnancy is now considered a time for an increased risk of relapse of bipolar depressive and manic episodes, especially following rapid discontinuation of mood stabilizing maintenance treatment. In a retrospective study, the risk of recurrence of bipolar disorder in pregnant women after discontinuing lithium maintenance during the first 40 weeks after lithium discontinuation was similar for pregnant and nonpregnant women (52% vs. 58%) but had been much lower for both groups in the year before treatment was discontinued (21%). The risk increased sharply during the postpartum period (2.9 times). Recurrence risk was greater after rapid than after gradual discontinuation of lithium and for patients with more prior affective episodes but was similar for diagnosis (of type I and II Bipolar disorder) (Viguera and Nonacs, 2000).

Physicians managing pregnant women with bipolar disorder who are receiving maintenance psychotropic medications should consider the rate of drug discontinuation as an important risk factor for relapse.

23.3.5.3 Anxiety Disorders

The prevalence of anxiety disorders during pregnancy is unclear. Mild to moderate anxiety symptoms are common during pregnancy, but severe anxiety symptoms need prompt diagnosis and treatment, as anxiety can have a deleterious effect on pregnancy and fetus and increase the risk for postpartum anxiety and depression.

A recent study on assessing the course of depression and anxiety through pregnancy and postpartum in a community sample concluded that antenatal anxiety occurs frequently (21.9%), overlaps with depression, and increases the likelihood of postpartum anxiety (64%) and depression, even after controlling for antenatal depression (Heron et al., 2004).

23.3.5.4 Panic Disorder

Some reports suggest a reduction in panic symptoms during pregnancy but other more recent prospective studies reported recurrence of panic symptoms during pregnancy in women with a history of panic disorder. Women who discontinued antipanic treatment during pregnancy were three times more likely to relapse compared to those who maintained treatment during pregnancy (Roy-Byrne et al., 1989).

23.3.5.5 Obsessive-Compulsive Disorder

Several studies indicate women may be at increased risk for the onset of obsessive-compulsive disorder (OCD) during pregnancy and postpartum. Women with a history of OCD are at risk for recurrence of symptoms during pregnancy especially with discontinuation of maintenance treatment.

23.3.5.6 Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) has been reported in women with traumatic birth experience including prolonged labor, severe pain during childbirth, and loss of control during delivery. It can affect a woman's decision on future pregnancy and ability to breast-feed, and impair parent-child bonding. Comorbid disorders are common. Women with PTSD are five times more likely to have major depression and three times more likely to have generalized anxiety disorder.

23.3.5.7 Psychotic Disorders

Psychotic disorder during pregnancy is associated with significant maternal and fetal morbidity and mortality. A new onset of psychosis during pregnancy requires systematic diagnostic evaluation to rule out secondary causes of the symptoms. It also increases the risk for postpartum psychosis. Acute psychosis during pregnancy is both an obstetric and a psychiatric emergency and needs prompt evaluation and treatment to reduce the morbidity and mortality associated with it.

23.3.6 Diagnosis and Treatment of Psychiatric Disorders During Pregnancy

Appropriate management of psychiatric disorder during pregnancy involves prompt diagnosis, collaboration between the primary physician and psychiatrist, and discussion with patient and family on the morbidity and mortality associated with untreated psychiatric illness, on the risk of discontinuation of psychotropic medication, and on the risk and benefit of medication and alternative treatments.

The detection rates for depressive disorder in the obstetric setting is low (26'V) and is lower in the primary care setting. Consequently a large proportion of pregnant women continue to suffer silently with depression throughout their pregnancy. As mentioned above this may have a profound impact on both pregnancy and the fetus.

Discussion on the impact of pregnancy on psychiatric illness should be initiated even before conception in a woman with a history of psychiatric disorder. Pregnancy may cause exacerbation of symptoms especially following discontinuation of treatment. Also the physiologic changes in a woman's body during pregnancy can alter the pharmacokinetics and pharmacodynamics of drug treatment.

Clinicians face specific challenges in treating pregnant women with psychiatric illness. All medications readily cross the placenta. It is common for women to avoid or discontinue psychotropic agents either before conception or during pregnancy. Discontinuation of psychotropic medications including antidepressants, mood stabilizers, anxiolytics, and antipsychotics is associated with a high risk of relapse of symptoms. Thus clinicians face the challenge of minimizing the risk to the fetus while limiting the morbidity of untreated psychiatric illness in the mother. The threshold for treating a psychiatric condition during pregnancy tends to be higher compared to a nonpsychiatric medical illness, and treatment with psychotropic medications is usually reserved for psychiatric conditions that cause severe impairment in maternal functioning. Treatment should be individualized after a collaborative and ongoing discussion with the patient and her partner on the risk and benefit of psychotropic medications and the risk of untreated psychiatric condition on pregnancy and fetus. Even if the decision is made to discontinue treatment, patients should be followed closely during pregnancy and in the postpartum period for early detection of relapse and rapid intervention, which may significantly reduce the morbidity.

23.3.7 General Guidelines for Treatment During Pregnancy

The choice of treatment with psychotropic medication during pregnancy is based on the following factors: severity of symptoms, level of functioning, period of clinical stability with and without treatment, past history of treatment discontinuation and time to relapse, time to recovery with reintroduction of treatment, previous medication trials and responses, risk and benefits of treatment, and wishes of the patient.

Nonpharmacologic interventions such as cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) have proven efficacy for mild to moderate depression and anxiety and should be considered as a first-line treatment for these conditions whenever possible (Spinelli, 1997). Both IPT and CBT can also be used to taper the dose of antidepressant or antianxiety medications prior to conception to decrease the risk of relapse.

23.3.7.1 Pharmacologic Management of Psychiatric Illness During Pregnancy

Recurrent severe depression or new-onset severe depression, anxiety, or psychosis during pregnancy calls for initiation or continuation of psychotropic medications. If medications are required during pregnancy, follow these general guidelines: (1) select the safest medication with documented safety; (2) use the minimum effective dosage; (3) avoid abrupt discontinuation of medication, as it would increase the risk of relapse; (4) simplify the medication regimen to reduce the potential side effects on pregnancy and fetus; and (5) if medications were discontinued during pregnancy, consider restarting them postpartum, as this is the period of high risk for relapse.

None of the psychotropic medications are Food and Drug Administration (FDA) approved for use during pregnancy.

Most psychotropic medications are class C (human fetal teratogenicity cannot be ruled out) or class D (positive evidence of human teratogenicity has been demonstrated). Factors affecting the decision to initiate or continue psychotropic medications during pregnancy include (1) risk of fetal exposure to the medication; (2) risk of untreated psychiatric illness on the patient, fetus, and family; and (3) risk of relapse associated with discontinuation of maintenance treatment.

Use of psychotropic medications during pregnancy can result in four types of problems: (1) risk of pregnancy loss or other obstetrical complications, including preterm labor and low birth weight; (2) risk of teratogenicity; a drug is considered to be a teratogen if exposure to it during pregnancy significantly increases the risk of congenital deformities over the baseline, which is about 2% in the United States; risk of teratogenicity occurs in the first 12 weeks of gestation as organs are formed; formation of heart and great vessel takes place between 4 and 9 weeks, formation of lip and palate is completed by weeks 8 to 14, and neural tube folding and closure occur within the first 5 to 7 weeks of gestation; (3) risk of perinatal syndrome or neonatal toxicity; these are physical and behavioral symptoms noticed shortly after birth in a newborn exposed to psychotropics around the time of delivery; (4) risk of long-term neurobehavioral sequelae in the exposed infant, including cognitive, emotional, and behavioral problems in children who were exposed to psychotropics in utero.

23.3.7.1.1 Antidepressants

23.3.7.1.1.1 SSRIISNRI: Exposure to SSRIs in general during the first trimester has not been reported to cause major congenital malformations. A robust report on safety is available for fluoxetine through prospective studies (2500 cases) and citalopram (375 cases). Reproductive safety of other SSRIs and SNRls including sertraline, paroxetine, fluvoxamine, and venlafaxine is gradually emerging but limited in terms of sample size.

One study reported increased incidence of three or more minor anomalies in the fluoxetine-exposed infants. No specific pattern was recognized (Chambers et al., 1996). A prospective controlled study on 150 pregnant women exposed to venlafaxine during the first trimester suggested no increase in the rates of major malformation above the baseline (1-2%) (Einarson et al., 2001). One prospective study on use nefazodone (n = 89) and trazodone (n = 58) suggested no increase in risk of major malformations above the baseline rate. The study also measured pregnancy outcome and found no increase in the rate of premature labor or effect on birth weight but a slight increase in the incidence of spontaneous abortion in the treatment group (Einarson et al., 2003). Prospective studies on the reproductive safety of bupropion, mirtazapine, and duloxetine are lacking.

Recent studies have suggested that exposure to SSRI during the third trimester may be associated with poor perinatal outcomes such as preterm labor, low birth weight, and poor neonatal adaptation. Symptoms appear to be relatively benign and transient, resolving 1 to 4 days after birth without specific medical interventions. A study on the neurobehavioral outcome in newborn from SSRI exposure in utero (n = 17) suggested SSRI-exposed infants had a shorter mean gestational age, increased tremulousness, less flexible and dampened state regulation, increased startle or sudden arousals, more rapid eye movement (REM) sleep, more generalized motor activity, and greater autonomic dysfunction (Zeskind and Stephens, 2004). SSRI use in late pregnancy [up to 20 weeks] has been linked to persistent pulmonary hypertension in 1% of exposed newborn in a recent case control study (Chambers et al., 2006).

Fluoxetine and citalopram seem to cause serotonergic overstimulation, while paroxetine seems to cause discontinuation syndrome. Maternal depression and anxiety may play a role in some of the perinatal symptoms.

23.3.7.1.1.2 Tricyclic Antidepressants: Early case reports suggested a possible association between first-trimester exposure to tricyclic antidepressants (TCAs) and limb malformations. Recent prospective and retrospective studies that examined over 400 cases of first-trimester exposure to TCAs failed to show a risk for any major congenital anomaly. Among TCAs, desipramine and nortriptyline are preferred since they have less anticholinergic and postural hypotensive effects. There are several case reports of perinatal syndrome with exposure to TCAs in utero. Withdrawal symptoms including jitteriness, irritability, feeding problems, respiratory distress, and hypotonia, and in rare cases seizures have been reported. Withdrawal seizure with clomipramine has been reported. Transient anticholinergic symptoms including functional bowel obstruction and urinary retention have been reported in neonates.

Scant information is available regarding the reproductive safety of monoamine oxidase inhibitors (MAOIs). These agents are generally avoided during pregnancy because they may interact with medications used to prevent premature labor like terbutaline, resulting in hypertensive crisis.

23.3.7.1.1.3 Long-Term Neurobehavioral Sequelae from Antidepressants: Animal studies demonstrate changes in behavior and neurotransmitter function after prenatal exposure to a variety of psychotropic agents. Three human studies to date have not shown significant differences in cognition, language development, or temperament of preschool and early school children exposed to fluoxetine or TCA in utero (Nulman and Rovet 2002; Numlan et al., 1997).

23.3.7.1.2 Antianxiety Medications: Abrupt discontinuation of antianxiety medication during pregnancy can result in rebound anxiety symptoms and potentially serious withdrawal symptoms. If patient and clinician decide to stop antianxiety medication during pregnancy, it has to be gradually tapered in over 2 weeks. Adjunctive CBT could be helpful to prevent relapse of symptoms.

For severe anxiety symptoms or for relapse following discontinuation of antianxiety medications, patient and clinician may decide to resume the anxiolytics. The SSRIs and TCAs are used as first-line agents for treatment of anxiety disorders, but if the patient does not respond to these antidepressants, benzodiazepines should be considered.

23.3.7.1.2.1 Teratogenic Effect of Benzodiazepines: Although there are a number of studies and individual case reports concerning the use of benzodiazepines in human pregnancy, the data concerning teratogenicity and effects on postnatal development and behavior are inconsistent. Earlier reports suggested an association of use of benzodiazepine especially diazepam and chlordiazepoxide during the first trimester and increased incidence of cleft lip and/or cleft palate (Safra and Oakley, 1975). More recent studies and meta-analysis suggest a very modest increase in risk of oral cleft, 0.6%, which represents a tenfold increased risk in relation to general population (Altshuler et al., 1996).

23.3.7.1.2.2 Perinatal Toxicity: Late-trimester use and exposure during labor seems to be associated with much greater risks to fetus/neonate. Some exposed infants exhibit either the floppy baby syndrome or marked neonatal withdrawal symptoms. Symptoms include mild sedation, hypotonia, neonatal apnea, reluctance to suck, low Apgar score, cyanosis, and temperature dysregulation. These symptoms have been reported to persist for hours to months after birth. Infrequent use of benzodiazepines does not seem to cause this problem. Intravenous use of lorazepam has been reported to increase the risk of perinatal toxicity especially in preterm infants with significantly low Apgar score, need for ventilation, hypothermia, and poor suckling. A case series study on 38 women with a history of panic disorder treated with clonazepam during pregnancy reported no adverse outcome on pregnancy or perinatal toxicity (Weinstock et al., 2001).

Using the lowest effective dose, using the shorter-acting agents, and discontinuing the use of benzodiazepine prior to delivery can help to reduce the risk of fetal and neonatal toxicity.

23.3.7.1.2.3 Neurobehavioral Sequelae: Data on neurobehavioral sequelae following exposure to benzodiazepines in utero are scant and reports are mixed. In 550 children exposed to benzodiazepines and followed up to 4 years of age, there was no adverse effects on neurobehavioral development and IQ (McElhatton, 1994).

Currently no systematic data are available on the reproductive safety of nonbenzodiazepine anxiolytics such as buspirone or the newer hypnotic agents zolpidem and zaleplon, and therefore these medications are not recommended for use in pregnancy at this time.

23.3.7.2 Management of Bipolar Disorder During Pregnancy

It is challenging for clinicians to treat patients with a history of bipolar disorder who plan to conceive. Mood stabilizers and antipsychotic medications readily cross the placenta. Most mood stabilizers and atypical antipsychotic drugs have been identified by the FDA as category C (human fetal teratogenicity cannot be ruled out) or category D (positive risk of human fetal teratogenicity has been demonstrated). Relative risk associated with the use these medications should be weighed against potential benefits and the likely morbidity and mortality associated with untreated psychiatric illness. Treatment should be individualized with collaborative discussion with the patient and her partner and making an informed decision.

23.3.7.2.1 Lithium

23.3.7.2.1.1 Teratogenic Effect: The risk of major congenital anomalies in lithium-exposed babies is about 4% to 12% compared to 2% to 4% in the general population. The use of lithium during the first trimester is associated with the risk of Ebstein anomaly, which is characterized by right ventricular hypoplasia and congenital downward displacement of the tricuspid valve into the right ventricle. Initially this risk was thought to be approximately 400 times higher than in the general population, but recent epidemiologic data point to a risk of 0.05% to 0.1%, which is 10 to 20 times higher than observed in the general population (1 in 20,000). Report from the registry on 225 lithium babies identified 25 cases of congenital anomalies (11.1%) of which 18 babies (8%) had cardiovascular defects and six (2.7%) had Ebstein anomaly.

Prenatal screening with high-resolution ultrasound and fetal echocardiography is recommended at around 16 to 18 weeks of gestation to screen for cardiac anomalies.

Lithium use during the second and third trimesters of pregnancy has been reported to cause polyhydramnios, premature delivery, thyroid abnormalities including nontoxic goiter and hypothyroidism, nephrogenic diabetes insipidus, and floppy baby syndrome, with lethargy, muscular hypotonia, impaired breathing, and cyanosis in lithium-exposed infants. The higher the maternal lithium level, the greater the fetal complications detected.

To minimize lithium-induced fetal complications, prescribe the minimum effective dose, use sustained-release lithium in divided doses to avoid peak concentrations, avoid diuretics with lithium, discontinue use of lithium 24 hours before delivery, and resume use after delivery to prevent postpartum decompensation and intravenous hydration during labor and delivery.

Limited data are available on the neurobehavioral sequelae from lithium exposure during pregnancy. A 5-year study of 60 children exposed to lithium in utero found no significant behavioral problems (Schou, 1976).

Recent guidelines on the use of lithium during pregnancy suggest gradual tapering of lithium over a period of 2 weeks prepregnancy in patients with mild and stable forms of bipolar disorder. In patients with a moderate risk for relapse, tapering and discontinuing lithium during embryogenesis at 4 to 12 weeks can be tried. In patients with severe form of illness with multiple episodes of affective instability or who relapse on medication discontinuation, maintaining lithium throughout pregnancy is recommended, as the risk associated with lithium teratogenicity is outweighed by the risk associated with lithium discontinuation and relapse. Appropriate reproductive risk counseling and prenatal diagnosis should be offered in such cases. Relapse of bipolar disorder during pregnancy is potentially dangerous to both mother and fetus, as it would require aggressive treatment that includes hospitalization and exposure to multiple psychotropic agents at higher dosages.

23.3.7.2.2 Anticonvulsants

23.3.7.2.2.1 Valproate: Valproate readily crosses the placenta. It is an FDA class D medication. It confers approximately five times increased risk of major malformation or other substantial pregnancy complications. The incidence of major congenital malformation is about 11%. The rates of neural tube defect range from 3% to 5%, which is about 50 times above the base rate of 0.05% in the general population. This is of particular concern because the formation of neural tube occurs during the first month of pregnancy, even before the diagnosis of pregnancy is made. So women in their reproductive years who are on valproate should have reproductive counseling before deciding to get pregnant.

Other congenital anomalies associated with exposure to valproate include craniofacial abnormalities, cardiovascular malformation, skeletal abnormalities, limb defects, genital anomalies, and CNS structural abnormalities including hydrocephalus. There is also an increased risk for minor malformations with exposure to valproate including rotated ears, flat nasal bridge, fingernail hypoplasia, which tend to disappear over time (Jager-Roman et al., 1986).

Specific risk factors for teratogenesis include high maternal daily dosage or serum concentrations of anticonvulsant, low folate level, and exposure to multiple anticonvulsants. Perinatal complications reported with valproate exposure include intrauterine growth retardation, neonatal hypoglycemia, coagulopathies, neonatal hepatotoxicity, and hyperbilirubinemia and neonatal withdrawal syndrome, with irritability, jitteriness, hypertonia, feeding difficulties, seizures, and vomiting (Ebbesen et al., 2000; Thisted and Ebbesen, 1993).

Knowledge of any neurobehavioral sequelae with anticonvulsant exposure is limited, but there are reports of subtle cognitive effects even with second- and third-trimester exposure.

The use of valproate in pregnancy is relatively contraindicated, and pregnant women with first trimester exposure to valproate should have a high-resolution fetal sonogram and echocardiogram performed at 16 to 18 weeks of gestation along with a serum a-fetoprotein level to detect neural tube defects followed by amniocentesis if necessary to detect spina bifida. Supplementation with folic acid 4 mg daily is recommended. Prophylactic vitamin K supplementation 10 to 20 mg/day in the last month before delivery as well as 1 mg IM vitamin K administered to neonates is recommended because of the potential for valproate-induced coagulopathies. Lower doses of valproate (<1000 mg/day) with serum levels <70 µg/mL and divided doses may reduce the risk of teratogenicity.

23.3.7.2.2.2 Carbamazepine: Carbamazepine has been associated with about a 0.5% to 1.0% risk of spina bifida. The overall incidence of congenital malformation is about 5.7%. Common teratogenic effects include microcephaly and other craniofacial defects, fingernail hypoplasia, cardiac abnormalities, coagulopathies, growth retardation, and possible developmental delays (Jones et al., 1989). A higher frequency of congenital anomalies is reported when carbamazepine is administered with valproate.

Carbamazepine is relatively contraindicated during the first trimester of pregnancy and it is an FDA class D medication.

23.3.7.2.2.3 Other Anticonvulsants: Information on the reproductive safety of newer anticonvulsants including gabapentin, lamotrigine, and topiramate in human is limited. The risk of malformation with lamotrigine monotherapy during the first trimester, based on data from the lamotrigine pregnancy registry established by the manufacturer, is about 2.5%. There has been recent reports of increased prevalence of cleft up and/or cleft palate in infants exposed to lamotrigine during the first trimester of pregnancy. Lamotrigine has been shown to decrease fetal folate concentration in rats. Folate supplementation should be considered for all women of reproductive age who are taking lamotrigine. Preclinical studies on the use of gabapentin and topiramate suggest potential fetotoxicity. The human teratogenic effect is unknown.

23.3.7.2.3 Antipsychotics: Meta-analysis of available studies noted an elevated risk of congenital malformation following first trimester exposure to lowpotency neuroleptics. High-potency agents may be preferable to low-potency agents or newer atypical antipsychotics for use during pregnancy. There are several case reports of transient extrapyramidal side effects (EPSs) including motor restlessness, tremor, and difficulty with oral feeding, hypertonicity, dystonic movements, and parkinsonism in neonates exposed to neuroleptics in utero. But these symptoms were short lived, and infants were noted to have normal motor development. Available data on the long-term neurobehavioral consequences of exposure to antipsychotics is limited and inconclusive.

Studies on the reproductive safety of atypical antipsychotics are limited. In a recent prospective comparison study (Mckenna et al., 2005) on pregnancy outcome in 151 women exposed to the atypical antipsychotic drugs olanzapine (n = 60), risperidone (n = 49), quetiapine (n = 36), or clozapine (n = 6), there were 110 live births (72.8%), 22 spontaneous abortions (14.6%), 15 therapeutic abortions (9.9%), and four stillbirths (2.6%). There was no statistically significant difference in any of the pregnancy outcomes between the exposed and comparison groups, with the exception of the rate of low birth weight, which was 10% in exposed babies compared with 2% in the comparison group, and the rate of therapeutic abortions, which was 9.9% in the exposed group and 1.3% in the comparison group. Outcome from 23 prospectively ascertained olanzapine exposed pregnancies from the Lilly pharmacovigilance safety database reported spontaneous abortion in 13%, stillbirth in 5%, major malformation in 0%, and prematurity in 5%, all within the normal control rates. There are several case reports of healthy infants born without complications despite prenatal exposure to olanzapine.

23.3.7.2.3.1 Clozapine: Case reports of pregnant women maintained on clozapine during pregnancy showed no evidence of congenital malformation. Of the 29 exposed neonates from the clozapine registry of babies exposed to clozapine, 25 were noted to be healthy, while four showed one or more problems including neonatal convulsions, Turner's syndrome, collar bone fracture, facial deformity, congenital hip dislocation, and blindness. The significance of these findings is unclear. The potential for clozapine-induced agranulocytosis warrants monitoring of the white blood count (WBC) in exposed newborns, although there have been no reports of leukopenia or agranulocytosis in such infants.

23.3.7.3 Electroconvulsive Therapy During Pregnancy

Electroconvulsive therapy (ECT) is a relatively safe and effective treatment during pregnancy when done in collaboration with a multidisciplinary team and taking steps to minimize potential risks. It is indicated for severe psychotic depression and agitated mania with risk of impulsivity and self-harm.

A study that reviewed 300 case reports from 1942 to 1991 reported complications in 28 of the 300 cases who underwent ECT during pregnancy. These complications included transient benign fetal arrhythmias (n = 5), mild vaginal bleeding (n = 5), abdominal pain (n = 3), self-limited uterine contractions (n = 2), premature labor (n = 4), miscarriage (n = 5), stillbirth and neonatal death (n = 3), neonatal respiratory distress (n = 1), and teratogenicity (n = 5) (Miller, 1994). Transient hypertension during seizures may increase the risk of abruption (Sherer et al., 1991). Without proper preparation there was also an increased likelihood of pulmonary aspiration from delayed gastric emptying during pregnancy, aorto- caval compression during later stages of pregnancy, and fetal hypoxia from respiratory alkalosis. Pregnancy may alter the seizure threshold in unpredictable ways. Progesterone-driven hyperventilation with compensatory alkalosis, electrolyte disturbances, sleep disturbance, fatigue, and stress can lower seizure threshold.

23.3.7.3.1 Effects of Medications Used in ECT

23.3.7.3.1.1 Muscle Relaxants: Succinylcholine, which is used most commonly as a muscle relaxant during ECT, in ordinary doses does not cross the placenta in detectable amounts.

23.3.7.3.1.2 Anticholinergic Agents: Atropine or glycopyrrolate is administered before ECT to prevent excessive vagal bradycardia and to decrease oropharyngeal and tracheal secretions. Atropine and to a lesser extent glycopyrrolate quickly cross the placenta and can cause fetal tachycardia and decreased heart rate variability. Glycopyrrolate, because of its minimal effect on fetal heart rate, is preferred during pregnancy. Also these drugs can reduce lower esophageal sphincter tone, thus increasing the risk of regurgitation and aspiration.

23.3.7.3.1.3 Barbiturates: Short-acting barbiturates in doses administered during ECT have no known adverse effect unique to pregnancy. In women with a history of porphyria, the use of barbiturates can trigger an acute attack.

Preparation for ECT during pregnancy should include a pelvic exam, discontinuation of nonessential anticholinergic medication, monitoring for uterine contractions, intravenous hydration, and administration of nonparticulate antacid. During ECT, elevation of the pregnant woman's right hip, external fetal cardiac monitoring, intubation (if beyond first trimester), and avoidance of excessive hyperventilation are recommended. Recheck for uterine contraction and vaginal bleeding after ECT is administered.

Informed consent for ECT should include the patient's capacity to understand and rationally evaluate risks and benefits to herself and fetus.

23.4 Postpartum Psychiatric Disorders

The postpartum period is a time of increased vulnerability to psychiatric illness in the life cycle of women. About 85% of women experience some kind of mood symptoms during this period, but in most cases symptoms are transient and mild; 10% to 15% of women experience more severe and disabling symptoms, which, if unrecognized and untreated, would place both the mother and the newborn at risk, have a negative impact on the family as a whole, and have been associated with long-term effects on child development and well being.

Postpartum affective illness is clinically indistinguishable from affective illness occurring at other times during a woman's life. The risk for postpartum psychiatric illness is highest during the first 3 months after delivery, but the risk remains high during the first year after delivery.

The types of postpartum psychiatric disorders include the following:

• Postpartum "blues": incidence 50% to 85%

0 Postpartum depression: incidence 10% to 15%

• Postpartum psychoses: incidence 0.1% to 0.2%

23.4.1 Postpartum Blues, Also Called "Baby Blues"

This is a common benign, transitory, and self-limited condition occurring during the first 10 days postpartum; it peaks between days 3 and 5. Postpartum blues appears to be a specific affective syndrome associated with childbirth and not just a nonspecific response to a major stressor. Symptoms include rapidly fluctuating mood, tearfulness, irritability, anxiety, somatic symptoms, and sleeplessness. The central feature of postpartum blues is the marked lability of mood with increased emotional reactivity to stimuli, such as crying or becoming irritable, profoundly joyful, or sad, in response to stimuli that would normally not provoke such intense reactions.

23.4.1.1 Relationship to Other Affective Illness

A history of depressive episodes is a major predictive factor for postpartum blues. Women who had higher levels of depressive symptoms during pregnancy, who had at least one previous episode of depression, and who had experienced premenstrual depression are all at increased risk for postpartum blues. A family history of depression also increases the risk for postpartum blues. Women who experience severe postpartum blues have three times greater likelihood of developing postpartum depression (Henshaw et al., 2004).

23.4.1.2 Etiology

23.4.1.2.1 Psychosocial Factors: The role of demographic variables, current stressors, obstetric complications, and social support appears to be minimal. Psychosocial factors have been shown to influence the intensity of blues. It occurs across all social classes and cultures even though the incidence may vary. No marked difference has been demonstrated between home and hospital deliveries.

23.4.1.2.2 Biologic Factors: The presence of postpartum blues in a variety of cultures, unrelated to psychosocial factors, and the timing of symptoms, coinciding with a period of dramatic drop in the hormonal level, point to a physiological cause.

23.4.1.2.2.1 Hormonal Withdrawal Hypothesis: The abrupt withdrawal of the hormones estrogen and progesterone in the immediate postpartum period may have a direct or indirect effect via neurotransmitters in causing the mood symptoms. It is the magnitude of drop rather than the absolute levels that causes the symptoms. One study found a greater drop in free estriol levels in women who developed postpartum blues compared to women who did not (O'Hara et al., 1991).

Postpartum blues are hypothesized as essentially withdrawal symptoms resulting from the precipitous drop in hormonal level. Ovarian steroid receptors are heavily concentrated in the limbic system. Neuroactive steroids are also synthesized de novo in the brain tissue and have direct agonist effect on GABA receptors and may cause withdrawal symptoms with the rapid drop in the hormonal levels postpartum. Mood symptoms may be related to the large drop in the (3-endorphin causing an endogenous opioid withdrawal state (Brinsmead et al., 1985). There is evidence of lower levels of free plasma tryptophan, a precursor of serotonin, in the early postpartum period that may trigger the blues in vulnerable women (Bailara et al., 2005).

23.4.1.3 Treatment

No specific treatment is indicated as symptoms are benign and resolve spontaneously.

Support and reassurance could help. It usually does not affect the mother's functional ability to care for self and her newborn. If symptoms are severe or prolonged over 2 weeks, patient should seek professional help. In patients with a history of recurrent affective illness, the blues may indicate the onset of a significant postpartum depression.

23.4.2 Postpartum Depression

The prevalence of postpartum depression (PPD) is 10% to 15%. The diagnostic criteria for PPD include symptoms of major depression lasting for more than 2 weeks with postpartum onset.

23.4.2.1 Risk Factors

Risk factors for PPD include women in lower socioeconomic bracket, financial stress, marital discord, inadequate social and spousal support (both emotional and instrumental support), child care stress, stressful life events during pregnancy, or early puerperium. Immigrant women who are culturally and physically separated from their support system are at risk for postpartum depression.

Other risk factors include very young or older age, having twins, a history of premenstrual dysphoric disorder, severe postpartum blues, depressive symptoms during pregnancy, anxiety symptoms during pregnancy, a personal history of mood disorder especially bipolar disorder (risk of recurrence is 30-50%), a history of postpartum depression [rates of recurrence is as high as 40% (Cooper and Murray, 1995)], a family history of mood disorder, history of recurrent episodes of depression, and discontinuation of antidepressant maintenance during pregnancy.

23.4.2.2 Clinical Features

Onset of symptoms of PPD is insidious within the first 3 months after delivery. Symptoms are more pervasive and interfere with the mother's ability to care for self and her newborn. Symptoms includes depressed mood, irritability, tearfulness, emotional lability, sleep disturbance, fatigue, loss of appetite, poor concentration, feelings of inadequacy, guilt, lack of pleasure, lack of interest in the baby, and ambivalent or negative feelings toward the infant. Suicidal ideation is common but suicide attempt is relatively infrequent in women with nonpsychotic depression. Anxiety symptoms are prominent and may present with generalized anxiety disorder, panic disorder, or hypochondriasis. Patients may experience intrusive obsessive ruminations involving the child, often violent in nature, such as thoughts about smothering the infant, dropping the baby down the stairs, or throwing the baby out of the window. These thoughts are ego-dystonic and very distressing, and women appear to go out of their way to ensure their child's safety. Reality testing is intact. Severity of depression may decrease over time, but in 30% of women symptoms could persist for as long as 2 years. Depression history, lower overall social support, higher parental distress, and stressful child care events are associated with more severe symptoms at 2 years.

23.4.2.3 Etiologic Factors

Etiologic considerations of general depression (see Chapters 6 and 9) hold in addition to the biology and psychology of the postpartum period.

23.4.2.4 Biologic Factors

During pregnancy, levels of estrogen, progesterone, (3-endorphin, human chorionic gonadotropin (HCG), and cortisol rise steadily, peaking near term. There is a rapid decline in the levels with the removal of the placenta. Estrogen and progesterone levels drop 200-fold, reaching prepregnancy levels by the fifth postpartum day. Estrogen and progesterone are known to influence neurotransmitter functions in the brain. Data on the effect of estrogen and progesterone causing PPD is conflicting. The sudden drop in hormones may increase the risk of developing mood symptoms in a subpopulation of women who are vulnerable to changes in hormonal state.

Seven percent of women develop abnormal thyroid function in the postpartum period, compared to 3% to 4% in the general population. Approximately 12% of postpartum women have thyroid antibodies, which may be due to a rebound immune phenomenon after the sharp drop in the cortisol levels after delivery. In one study 43% of antibody-positive women developed depressive symptoms compared to 28% of antibody negative women (Harris et al., 1992). Antibody-positive women should be followed with thyroid function testing beyond the postpartum period, as many patients with antithyroid antibodies go on to develop overt hypothyroidism within 4 years. Diminished thyroid function may affect postpartum mood through its association with diminished central serotonin activity.

23.4.2.5 Psychosocial Factors

Psychosocial variables appear to play a major role in the etiology of postpartum depression. Inadequate social support, marital discord, and stressful life events during pregnancy and around the time of delivery appear to increase the likelihood of postpartum depression.

23.4.2.6 Cultural Influences

Culture influences identity, expression of symptoms, the nature of the individual's social support and stressors, and the treatment relationship between the patient and the clinicians. Different cultures follow different rites of passage to parenthood, including ceremonies, cleansing rituals, seclusion, rest, solicitude, and return to the home of origin. A major function of these rituals is to provide mutual support during times of emotional and physical vulnerability. This protective barrier of social support lessens the likelihood of developing depressive symptoms during the vulnerable period. Migration, individuation, and separation from the family of origin reduce the social support and increase the emotional burden on both partners in the postpartum period. In immigrants, acculturation and the necessity of individuals from different ethnic groups raising children together may result in fewer shared traditions and rituals, which may cause a diminution of the supportive rites of passage to parenthood. Clinicians during assessment should ask patients about cultural background, social support network, and traditional antepartum and postpartum practices.

23.4.2.7 Consequences of Untreated Postpartum Depression

Untreated postpartum depression can result in a disturbed mother-infant relationship, psychiatric morbidity in children later (depression, conduct disorder, lower IQ), marital tension, vulnerability to future depression, and suicide/homicide.

A disturbed mother-infant relationship as a result of postpartum depression can result in both short- and long-term consequences. Maternal characteristics including emotional availability, accepting attitude, and responsiveness and sensitivity to the infant's signals and needs are critical during the first year of life. These characteristics result in a secure mother-infant bond that is associated with a positive outcome in the child.

If the mother has postpartum depression, she may have difficulty in engaging in interaction with her infant, or it may present as a lack of interest, neglect, negativity toward the infant, and less sensitivity and responsiveness to the infant's needs. Infants of mothers with PPD show decreased eye gaze during feeding, less reciprocity and playfulness with their mothers, limited engagement with the environment, and more muted affective expressions.

Long-term effects on children of mothers with postpartum psychiatric illness include behavioral problems, sleep disturbances, eating problems, and temper tantrums, which may persist over time. Several studies have documented less optimal cognitive development in offspring of mothers with postpartum mood disorder, including lag in developing the concept of object permanence and developmental delays in intellectual functioning. It can also cause social and interpersonal functional impairment, including reduced quality of interaction with their mothers, less sociability with strangers, and insecure attachment patterns (Cicchetti et al., 1998). Exposure to maternal stress, especially postpartum depression early in infancy, predisposes children to increased hypothalamicpituitary-adrenal (axis) (HPA) function with an increase in cortisol level during a period of concurrent stress. These children were found to be at increased risk for emotional and behavioral difficulties at the end of the first grade in school (Essex et al., 2002).

23.4.2.8 Treatment

23.4.2.8.1 Primary Prevention: Primary prevention involves identifying risk factors and taking measures to prevent these factors from causing or contributing to postpartum depression. It includes the following steps:

• Screening for antenatal depression and a history of postnatal depression

• Screening for family history of affective disorder

• Screening for other risk factors, such as age, social support, financial status, negative life events

• Screening for thyroid antibodies and thyroid function

Providing continuity of care, education, support groups, continuous early and late antenatal care with additional focus on psychosocial issues, and timely postnatal counseling can help reduce the risk of postpartum depression. Brief, group psychotherapy for pregnant, socially disadvantaged women who possessed one or more risk factors of depression, a single individual psychotherapy session shortly after birth for women who had elevated depressive symptoms, and extended home visits by nurses/midwifes to vulnerable families have all been found to be effective strategies for preventing postpartum depression.

For women with history of recurrent major depression or postpartum depression or depression during pregnancy, prophylactic antidepressant treatment has been found to reduce the recurrence of postpartum major depression.

Interpersonal therapy has proven efficacious in the prevention of postpartum depression, with focus on role transition, conflict with other role interests, and maladaptive interpersonal patterns.

23.4.2.8.2 Secondary Prevention: Secondary prevention involves early diagnosis and treatment to minimize the consequences of postpartum depression. It can be managed from a primary care perspective with occasional referral to the psychiatrist.

Most women do not report their symptoms to health care providers, and less than one third of women with PPD receive any type of intervention. Symptoms of depression may remit spontaneously, but many women are still depressed at 1 year after childbirth without intervention. Screening all women for depression during the postpartum period is advisable. The Edinburgh Postnatal Depression Scale is a 10-item self-rated questionnaire that has been used extensively for detection of PPD (Cox et al., 1987) (see Appendix at end of chapter). A score of 12 or more on this scale or an affirmative answer on question 10 (presence of suicidal thoughts) raises concern and indicates the need for more thorough evaluation. It can be integrated in the follow-up obstetric visit at 6 weeks and subsequent pediatric well-baby visits, which can significantly improve the detection of women with PPD.

Treatment for postpartum depression involves psychological interventions for mild to moderate depression, which includes IPT, CBT, self-help networks, peer and partner support, and nondirective counseling. Other interventions, such as relaxation/massage therapy, exercise, and mother-infant relationship therapy, have also been found to be helpful.

Biologic interventions for moderate to severe depression include antidepressant medications, hormone therapy, and ECT.

23.4.2.8.3 Interpersonal Therapy: Evidence supports the effectiveness of interpersonal psychotherapy in treating mild to moderate postpartum depression (O'Hara et al., 2000). It also improves social adjustment in these patients and represents an alternative to pharmacotherapy, particularly for women who are breast-feeding. Interpersonal therapy has been found to be effective in both individual and group settings. It is time limited and focuses on role transition, integrating a new role with the established roles, exploring feelings and ambivalence about these roles, assessing satisfaction with relationships, defining patient's expectations of others, and renegotiating relationships.

23.4.2.8.4 Cognitive-Behavioral Therapy: Cognitive-behavioral therapy in individual or group settings has been shown to be effective in treating mild to moderate postpartum depression. It is time limited and focuses on negative thoughts, negative perceptions of self and infant, cognitive restructuring, and behavioral modification.

23.4.2.8.5 Other Psychosocial Interventions: Companionship and belonging to a support group have a protective effect on postpartum depression. Support groups, peer and partner support (Dennis, 2003), telephone-based peer support, and nondirective or supportive counseling administered by public health nurses and social workers have all been found to be effective in reducing the depressive symptoms of PPD. Similarly, maternal/infant massage therapy, exercise, infant sleep interventions, and mother-infant therapy all hold promise in reducing the symptoms of postpartum depression.

23.4.2.8.6 Pharmacotherapy: Pharmacotherapy is indicated for moderate to severe depression. Antidepressant medication, especially SSRIs and some SNRIs, has been shown to be effective in treating postpartum depression in randomized controlled and open-label studies. Women with postpartum depression may take longer to respond to treatment and may require more antidepressant agents at the time of response to treatment (Hendrick et al., 2000). The use of psychotropic medications during breast-feeding should be considered on an individual basis, weighing the risk and benefit of nursing and exposure of the infant to these medications. There are no controlled studies on the safety of these medications in nursing mothers. Treatment guidelines for psychiatric disorders in breast-feeding mothers is based on case reports and small case series for each of the different psychotropic medications.

In non breast-feeding mothers, any of the antidepressants could be used. The SSRIs and the newer antidepressants (venlafaxine, nefazodone, mirtazapine, bupropion) are well tolerated and are recommended as first-line agents. In breast-feeding mothers little is known on the effects of antidepressants on the developing infant brain. Studies so far are encouraging, and no serious side effects have been reported.

23.4.3 Psychotropic Medication and Lactation

Most psychotropic medications pass into breast milk to some degree, mostly through the process of passive diffusion. Factors that determine the amount of diffusion into breast milk include maternal dosing and frequency, and the drug's protein binding, lipid solubility, degree of ionization, and molecular weight. The less protein bound, more lipid soluble and more weakly alkaline the drug, the more likely it is to diffuse into breast milk. The higher lipid content of hind-milk makes it likely that the second half of breast milk will have a higher concentration of maternal medication than the first half.

Infant physiology that would determine the bioavailability of the drug includes absorption, metabolism, and elimination of drugs. Infants have higher gastric pH, which increases the absorption of basic compounds. They have low serum protein, which would increase the amount of free drug in circulation. Full-term neonatal cytochrome P-450 activity is approximately one half of that found in adults, decreasing the rate of degradation of the medications. Hepatic enzyme immaturity is even more pronounced in premature infants. The newborn kidney is functionally immature, with a glomerular filtration rate (GFR) of 20% to 30% and tubular secretion of 20% to 30% of adult function, which result in decreased renal clearance. Medications eliminated through the kidneys tend to accumulate in the infant, causing toxic exposure over time. For full-term infants the GFR seen in adults is achieved between the second and fifth months of life. The newborn blood-brain barrier is not fully developed, and lipidsoluble agents can be 10 to 30 times more concentrated in the cerebrospinal fluid (CSF) than in the serum.

23.4.3.1 Milk to Plasma Ratio

The milk to plasma (M/P) ratio is the ratio of medication concentration in milk to the concentration in maternal serum. Compounds that are weakly protein bound, highly lipid soluble, weakly alkaline, and small in molecular size have a higher M/P ratio. Ratios greater than 1 indicate higher milk level than serum level. The higher the M/P ratio, the greater will be the infant's exposure to the medication. A clear correlation between M/P ratio and clinical status has not been established.

23.4.3.2 Antidepressants and Lactation

23.4.3.2.1 Tricyclic Antidepressants: Infant serum levels of TCAs and their active metabolites in different studies ranged from nondetectable to less than 30 ng/mL. With amitriptyline, nortriptyline, imipramine, and desipramine, there are no reports of adverse effects in the breast-fed infants. With Doxepin, respiratory depression occurred in one case, which reversed with discontinuation of breast feeding.

23.4.3.2.2 Selective Serotonin Reuptake Inhibitors: No clear association is established among levels in infant serum, maternal dose, and infant age. No adverse effects were noted in 180 of the 190 cases reported. In one study (n = 4), normal neurobehavioral development of infant was reported at 1 year of age (Yoshida et al., 1998). Adverse effects from fluoxetine exposure during late pregnancy and through breast milk, including excessive crying, decreased sleep, vomiting, diarrhea, somnolence, and lethargy, have been reported, which decreased upon discontinuation of nursing (Hale et al., 2001). One retrospective study (n = 64) indicated poor weight gain in fluoxetine-exposed infants (Chambers, 1999). Another prospective study (n = 78) indicated no change in weight in infants exposed to antidepressants (Hendrick et al., 2003). A study to determine serotonin blockade in nursing infants exposed to sertraline concluded that platelet 5-HT uptake in nursing infants of treated mothers is unaltered even when the mothers experience substantial blockade of platelet 5-HT transporter (Epperson et al., 2001). A prospective study (n = 11) on citalopram use during pregnancy and lactation reported normal pregnancy outcome and normal neurodevelopment of all infants up to the age of 1 year (Heikkinen et al., 2002).

23.4.3.2.3 Other Antidepressants: Five case reports on venlafaxine exposure reported detectable amount of the drug or its metabolite in the infant serum without any adverse effects. Similarly, one report on bupropion exposure did not reveal any adverse effects. More data are needed before conclusions can be reached regarding their safety in breast-feeding.

From the available data, SSRIs comprise a relatively safe group of medications that can be used during lactation for postpartum depression and anxiety. Among the SSRIs, sertraline and paroxetine have a uniformly low or nondetectable infant serum level and a lack of reported adverse effects, which makes them good choices for nursing mothers. In the case of sertraline, serum levels peak in infants between 7 and 11 hours after maternal dosing, and refraining from breast-feeding during this time may significantly reduce infant exposure. Similar peak levels have not been reported for paroxetine or fluoxetine. Rather than relying on lab values, it is important to clinically monitor the infants through close follow-up.

23.4.3.2.4 Anxiolytics: With clonazepam, there is one case report of cyanosis, decreased respiratory rate, decreased tone, and lethargy with prenatal and postnatal exposure. Symptoms resolved at 10 days, and normal milestones were achieved at 5 months. One case report described a lactating mother who was treated with 0.5 mg of alprazolam two or three times a day through pregnancy and breast-feeding, which was discontinued when the infant appeared restless and irritable at day 7. Withdrawal symptoms appeared in the infant within 2 or 3 days and was treated with phenobarbital elixir. With diazepam, no adverse events were reported in three cases, and one case of sedation and another case of lethargy and weight loss were reported, which reversed with discontinuation of nursing. No adverse events were reported in 10 cases of temazepam exposure. In five women exposed to zolpidem 20 mg, most of the zolpidem excretion in the breast milk took place within 3 hours after the maternal dose, and no adverse effects were reported in the infants.

Mild to moderate postpartum anxiety could be managed with nonpharmacologic interventions such as CBT, relaxation techniques, and environmental stress reduction. If medications are indicated, occasional low doses of short-acting benzodiazepines such as temazepam or oxazepam are probably safe. Reports of adverse effects from diazepam and withdrawal effects from alprazolam make them less optimal choice. The TCAs, except for doxepin, and the SSRIs are good options for treatment of panic disorders in breast-feeding mothers.

23.4.3.2.5 Antipsychotics: Ten reports of infant exposure to antipsychotics through breast milk included 34 cases, of which 25 showed no adverse effects. Lethargy was reported in one case of a chlorpromazine-exposed infant, and a decline in developmental scores was observed at 12 to 18 months of age in three infants exposed to a combination of haloperidol and chlorpromazine. One case of clozapine exposure revealed a high concentration of the drug in breast milk. A study on the exposure of breast-fed infants to olanzapine concluded nondetectable infant plasma olanzapine level with no adverse effects in the exposed infants (Gardiner et al., 2003).

Postpartum psychosis requires pharmacologic interventions. The infant's clinical status should be regularly monitored for side effects like somnolence, muscle rigidity, or tremors in case of infant exposure to antipsychotics through breastfeeding. A monotherapy regimen should be maintained if possible to minimize side effects and to reduce delayed development from combination treatment. Infants exposed to clozapine should be monitored for agranulocytosis.

23.4.3.2.6 Mood Stabilizers: Twenty-eight reports on the use of mood stabilizers during breast-feeding included 79 infants exposed to lithium, carbamazepine, valproate or lamotrigine through breast-feeding. Of the 25 cases of carbamazepine exposure, two cases of transient hepatic dysfunction have been reported. There are reports of seizure-like activity, drowsiness, irritability, and abnormal crying with exposure to combination of agents. Of the 36 valproateexposed infants, no adverse effects were reported in 19 cases and clinical status was not reported for 16 exposed infants. Thrombocytopenia and anemia were reported in a 3-month-old infant that reversed upon cessation of nursing.

Serum concentration was found to be high in 13 infants exposed to lithium. Two cases reported symptoms consistent with lithium toxicity in the infants. One infant with a congenital heart murmur, cyanosis, and hypotonia had been exposed to lithium in utero and through breast milk. No adverse effects were reported in four other infants and clinical status was not reported for eight. In five cases of lamotrigine exposure, no adverse effects were reported in the nursing infants.

Treatment of bipolar disorder invariably requires mood stabilizers. Maternal use of lithium increases the risk of thyroid dysfunction, cyanosis, poor muscle tone, and electrocardiogram changes in infants. Renal clearance is decreased in infants up to 5 months of age and can result in lithium toxicity. Since discontinuation of lithium in bipolar patient can result in serious risk of relapse especially during postpartum period, an individualized approach to nursing mothers receiving lithium is warranted with careful monitoring of the infant clinical status and careful monitoring of infant serum lithium level.

The use of carbamazepine and valproate during breast-feeding requires careful monitoring of infant liver enzymes, bilirubin, WBC, platelet count, and drug level in the infant.

23.4.3.3 Treatment Guidelines During Lactation

The decision to start psychotropic medication in breast-feeding mothers is complicated by a number of factors, including potential benefits of breast-feeding to the infant, mother-infant bonding, the wishes of the mother, the risk of infant exposure to the medication, and the consequence of untreated psychiatric illness on the mother, infant, and family.

Before starting psychotropic medication. the following steps should be taken:

1. Explain the potential risks and benefits, ideally to both parents.

2. Refer for a pediatric evaluation to assess the baby's baseline behavior sleep, feeding, and alertness.

3. Collaborate with the pediatrician and provide education regarding possible infant side effects and interaction with other medications.

The choice of medication is affected by a number of factors, including diagnosis of psychiatric illness, a past history of treatment response, the side-effect profile of the medication, dosing flexibility, and pharmacokinetic characteristics that minimize accumulation of the medication in milk and infant serum.

Factors that minimize infant exposure include minimum effective dose, shortacting agents, medications without active metabolites, timing the breast-feeding for when the drug levels in milk are lowest, formula supplementation reducing infant exposure while retaining some breast-feeding benefits, and monitoring infant clinical status monthly to ensure general health and normal pediatric development.

23.4.3.4 Hormonal Interventions

Progesterone use has not been supported by randomized controlled studies. Some reports suggest worsening of mood symptoms with synthetic progesterone (Lawrie et al., 1998). Naturally occurring progesterone has shown some beneficial effect in uncontrolled studies.

Postpartum estrogen treatment has shown some beneficial effect. Transdermal patch of 17(3-estradiol was found to be effective in one doubleblind placebo-controlled trial (n = 61) (Gregoire and Kumar, 1996) and sublingual 17(3-estradiol was found to be effective in one open-label study (n = 23) (Ahoka et al., 2001). Effective dosing and the route of administration include using 200 tg as a transdermal patch, changed twice weekly, or I mg sublingually four times a day. Side effects include changes in breast milk production, thromboembolic events, and endometrial hyperplasia. Efficacy and safety relative to antidepressants have not been established.

23.4.3.5 Electroconvulsive Therapy

No randomized controlled trials exist on the use of ECT in postpartum women. It has been advocated by several researchers as an effective treatment option. It is used more commonly in severe drug-resistant depression. It also has a positive advantage in breast-feeding mothers who do not want to expose their infants to antidepressant medications.

23.4.3.6 Course and Prognosis

The duration of postpartum illness is variable. Episodes are often short lived and may last no more than 3 months. Women with a history of recurrent major depressive disorder (MDD) and with severe symptoms can have a more protracted course. Postpartum depression has a good prognosis with early diagnosis and treatment. There is a 40% risk of recurrence with subsequent childbirth. There is also risk of recurrence of episodes unrelated to pregnancy and childbirth.

Exposure to maternal depression in the early postpartum months may have an enduring influence on the child's psychological development and can cause emotional, behavioral, cognitive, and interpersonal problems later in life.

23.4.4 Postpartum (Puerperal) Psychosis

Postpartum psychosis is a psychotic disorder occurring after childbirth. It is primarily manic-depressive illness (bipolar affective disorder) or a variant of it. Evidence from studies of women with a history of bipolar disorder, longitudinal studies of women with puerperal episodes of psychosis, and family studies support a link between postpartum psychosis and bipolar disorder (Chaudron and Pies, 2003).

23.4.4.1 Epidemiology

One to two per 1000 postpartum women are affected. A constant incidence rate is reported transculturally.

23.4.4.2 Risk Factors

The risk factors are as follows:

1. Primiparity (70% to 80% of index cases occur after first childbirth, 35 times more common in primipara)

2. Family and personal history of manic depressive illness

3. Women with history of bipolar disorder or postpartum psychosis

4. First-degree relatives of women with bipolar disorder

5. Women with a history of schizophrenia have a 24% chance of developing postpartum psychosis

6. Perinatal mortality

7. Lack of partner

23.4.4.3 Etiology

Transcultural prevalence and occurrence in primipara suggest that biologic or physiologic factors contribute to the onset of postpartum psychosis.

Genetic Factors

Genetic factors include a strong family history of affective illness.

Biologic Factors

Estrogen can lead to an increase in dopamine receptor binding, and estrogen withdrawal can lead to dopamine receptor supersensitivity. Sleep deprivation in the postpartum period may trigger manic and hypomanic state in vulnerable women.

Psychosocial Factors

Some association with psychosocial stressors, including marital status, social support, and obstetrical complications, has been reported.

23.4.4.4 Clinical Presentation

Postpartum psychosis is the most severe form of postpartum psychiatric illness. The presentation of postpartum psychosis is often abrupt and dramatic, with onset of symptoms during the first 48 to 72 hours after delivery. The majority of women with postpartum psychosis develop symptoms within the first 2 weeks postpartum. Symptoms resemble those of a rapidly evolving mania or mixed state. The earliest signs are restlessness, agitation, irritability, and insomnia. The symptoms are characterized by a mixture of delirium, psychosis with confusion and perplexity, emotional lability, delusions, and hallucinations.

In psychotic depression the woman is depressed (the depression is worst in the morning), tearful, has significant psychomotor retardation, has sleep disturbances with early morning awakenings, has appetite disturbances, is preoccupied with feelings of guilt and worthless, may have delusions of the infant being dead or defective, and may have hallucinations commanding her to harm the baby.

In postpartum mania, the woman is excited, euphoric, grandiose, irritable, and hyperactive; she requires little sleep and may have grandiose delusions about her baby, such as having special powers or that the child is either Satan or God.

Compared with episodes of nonpsychotic depression, women with postpartum psychosis who have thoughts of harming their infants are more likely to act on them, as their reality testing is impaired.

Differential diagnosis includes exacerbation of primary psychiatric disorder; toxic, metabolic, or neurologic causes, such as tumors, head trauma, infection, cerebral embolism, seizures, electrolyte disturbances, anoxia, vitamin deficiencies, thyroiditis; and drugs, such as high doses of metronidazole, bromocriptine, or recreational drugs.

23.4.4.5 Treatment

Postpartum psychosis is a psychiatric emergency and requires major intervention and in most cases hospitalization. Both psychosocial and pharmacologic interventions are necessary. In most cases symptoms should be treated as an affective psychosis. Acute treatment with a mood stabilizer in addition to antipsychotic medication is indicated. Treatment with a mood stabilizer should extend beyond the resolution of active symptoms to reduce the risk of relapse. Electroconvulsive therapy is well tolerated and can work more rapidly than medication in the cases of more severe postpartum depression and postpartum psychosis. It also has a positive advantage in breast-feeding mothers who do not want to expose their infants to psychotropic medication.

In women with a history of postpartum psychosis or bipolar disorder, prophylactic treatment with lithium or other mood stabilizers instituted either prior to delivery (at 36 weeks' gestation) or no later than the first 48 hours postpartum is found to significantly reduce the relapse rates as well as to diminish the severity of illness (Cohen et al., 1995; Stewart, 1988).

23.4.4.6 Prognosis

Rates of infanticide associated with untreated postpartum psychosis have been estimated to be as high as 4%; 95% of adequately treated women improve within 2 to 3 months and have a good functional outcome. A 23-year follow-up study showed an increased risk of subsequent episodes in 75% of patients with an index puerperal episode, most of them unrelated to childbirth. The risk of puerperal recurrence is as high as 30% (Robling et al., 2000). Medicolegal issues from infanticide secondary to postpartum psychosis can be complicated, as symptoms may remit by the time patient goes for trial.

23.4.4.7 Conclusion

The postpartum period increases vulnerability for the development of major psychiatric illness in some women. The consequences of untreated postpartum depression and psychosis can be devastating for the mother, the newborn, and other family members. Screening for risk factors and symptoms can be incorporated into the already existing prenatal and postnatal clinic visits. Instituting effective pharmacologic and nonpharmacologic interventions may limit both maternal and infant morbidity and mortality.

23.5 Special Topics

23.5.1 Hyperemesis Gravidarum

Nausea and vomiting symptoms affect 70% to 85% of pregnant women during early pregnancy. Symptoms may persist throughout pregnancy in about 10% of pregnant women. Hyperemesis gravidarum is a severe form of nausea and vomiting seen in 1 in 200 pregnant women and is associated with intractable vomiting associated with weight loss (more than 5% of body weight), dehydration, ketosis, and electrolyte imbalance. It can result in negative pregnancy outcome and can cause considerable distress and disability to the pregnant woman and her family. Multiple gestation, gestational trophoblastic disease, triploidy, Down syndrome, and hydrops fetalis have been associated with an increased incidence of hyperemesis gravidarum. Multiple medical conditions have been found to play a role in causing or contributing to hyperemesis gravidarum, including gastrointestinal disorders, genitourinary tract diseases, metabolic disorders, neurologic disorders, pregnancy-related conditions like acute fatty liver of pregnancy and preeclampsia, and drug toxicity or intolerance.

Referral for psychiatric consultation is usually made in cases of repeated hospitalization, multiple medication failures, presence of significant psychosocial stressors, and for the emotional support of the patient and her family. Some of the psychological factors that have been found to be associated with hyperemesis gravidarum include the mother's excessive dependence on her mother, hysteria, and infantile personality.

Negative maternal outcome associated with hyperemesis gravidarum includes splenic avulsion, esophageal rupture, Mallory-Weiss tears, pneumothorax, peripheral neuropathy, and preeclampsia. Negative fetal outcome includes fetal growth retardation and mortality.

Management of the nausea and vomiting of pregnancy depends on the severity of symptoms and can range from dietary modifications, acupressure, vitamin supplements (pyridoxine), and herbal remedies (ginger), to more aggressive treatment including hospitalization, intravenous fluids, antiemetics, antihistamines and anticholinergics, motility drugs, and steroids, to total parenteral nutrition.

The role of the psychiatric consultant involves evaluation of the underlying psychosocial stressors, depression, anxiety, or other psychiatric conditions that could be contributing to or worsening the physical symptoms. Appropriate management of the psychiatric comorbidity with medications, weighing the risks and benefits, facilitating support from the staff, family, friends, and support network, and working collaboratively with the treating primary physician can help to alleviate the symptoms.

23.5.2 Fetal Demise

Miscarriage is the most common complication of pregnancy, and about one fifth of clinically confirmed pregnancies abort spontaneously. Most women react to this unexpected loss with sorrow and grief. Studies have shown that 22% to 44% of these women develop clinically significant levels of depression and anxiety. About 50% of women continue to be depressed 1 to 3 months after the miscarriage. Anxiety symptoms were found to persist at 6 months postmiscarriage.

Women may have the following physical symptoms and psychological feelings after experiencing a miscarriage:

1. Physical pain and bleeding.

2. Miscarriage may represent loss of a pregnancy, a baby, a future child, loss of motherhood, loss of self-esteem, and doubts regarding ability to reproduce.

3. Self-accusation. Some women feel responsible for the miscarriage, blame themselves for the loss, and feel excessive guilt and shame.

4. Depression. Studies have shown that women who had a miscarriage have significantly more anxiety and depressive symptoms compared to control pregnant women, and these symptoms persisted at 6 weeks. A majority of women have intense feelings of grief, guilt, and anxiety immediately following miscarriage, which wanes within 4 to 6 weeks, but some symptoms may persist for longer periods.

Clinicians should be aware of the psychological sequelae associated with miscarriage and should provide support and follow-up, as well as access to formal counseling when necessary. Intervention should be focused on grief counseling, support to patients and families, and providing them access to resources in the community. Screening for depression and anxiety initially and at follow-up visits using a general health questionnaire or the Edinburg Postnatal Depression Scale would help early diagnosis of major psychiatric illness and prompt intervention (Lee et al., 1997).

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