Diagnosis and Prevalence During Pregnancy and Postpartum

In the DSM-V, a major depressive episode (MDE) is defined as at least a 2-week period of either persistent depressed mood or loss of interest or pleasure in daily activities, so-called gatekeeper symptoms, plus four associated symptoms (three if both gatekeeper symptoms are present; see Box 55-1 ). Persistent means the symptom must be present for most of the day nearly every day. The patient also must have impairment of function in interpersonal relationships or work. It is possible to have a diagnosis of MDE without the symptom of depression. A woman could have persistent loss of interest or pleasure but no sadness and yet have four other symptoms noted in the DSM-V criteria for major depressive disorder. Note that appetite, sleep, and motor activity can be either decreased or increased relative to the woman’s norm. A fatigued woman who derives no pleasure from previously enjoyable activities, sleeps 15 hours per day, sits immobile for long periods, and is gaining weight has MDE. A guilt-ridden woman with sadness, 4 hours of sleep nightly, weight loss of 15 pounds, and pacing also has MDE, which may be episodic or chronic.

Nearly twice as many women (12.0%) as men (6.6%) suffer from an MDE each year. Women are at the greatest risk for MDE between 25 and 44 years, the primary age for childbearing. The period prevalence of MDE is 12.7% during pregnancy (with 7.5% of women having a new episode), and 21.9% the year after parturition ; therefore, MDE is among the most common complications of childbearing. Mothers at increased risk are disadvantaged, have preterm infants, and are in adolescence. Depression persists from months to years after childbirth, with lingering limitations in physical and psychological functioning after recovery. Of women with postpartum MDE, 25% to 50% have episodes that last 7 months or more.

As predicted by the multiple determinants model (see Fig. 55-1 ), MDE has contributions from several risk factor domains. In women, the strongest predictors were stressful life events, genetic factors, history of an MDE, and high emotional sensitivity. Similarly, stressful life events and a history of MDE in the woman or her family are predictors of postpartum-onset MDE. Women with postpartum MDE are at increased risk (about 25% to 33%) for recurrence after a subsequent birth, and over 40% have nonpostpartum MDE.

The DSM-V allows the designation with peripartum onset to specify episodes that begin during pregnancy or within the first 4 weeks postpartum. Epidemiologists have defined the duration of postpartum based on data about the break point between elevated risk for psychiatric illness after birth and the baseline risk for episodes in childbearing-aged women. Kendell and Munk-Olsen and their colleagues found a significant peak in the rate of mood disorders in the 90-day period after childbirth. Although the definition of postpartum varies, the adverse effects of the disorder for the woman and her family are independent of time of onset.

The most commonly used measure to screen for MDE during childbearing is the Edinburgh Postnatal Depression Scale (EPDS; Fig. 55-2 ), which has been validated for use both during and after pregnancy. This self-report measure contains 10 items ranked from 0 to 3. Scored by simple addition, the EPDS is free to health care professionals and is available in 23 languages. A cutoff score of greater than or equal to 13 (the sensitivity for identifying MDE is 86%, specificity is 78%, positive predictive value is 73%) was recommended for screening for MDE in clinical settings. For pregnant women the recommended cutoff score is greater than or equal to 15. As with any screening tool, a positive test must be followed by diagnostic evaluation and treatment guidance. The differential diagnosis of MDE in the early postbirth period includes the “baby blues,” a transient syndrome that occurs in 80% of mothers that resolves by day 10 postpartum (see Chapter 23 ).

Edinburgh Postnatal Depression Scale.

(From Cox, JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psych. 1987;150:782-786.)

Natural History Across Childbearing

Periods of hormonal fluctuation—menstrual cycle, pregnancy, postpartum, and perimenopause—are associated with MDE. Investigators have suggested that the rapid change in gonadal steroid concentrations contributes to the etiology of postpartum-onset MDE. The neurobiology of women who develop postpartum depression (PPD) appears especially vulnerable to the mood-destabilizing effects of withdrawal from gonadal steroids.

Postpartum MDE does not differ from MDE at other periods during the childbearing years with respect to clinical presentation and duration of untreated episodes. However, aggressive obsessional thoughts occur more commonly in women who have postpartum-onset MDE compared with those whose depression falls outside the 1-year postbirth period. Delusions must be differentiated from the far more common obsessional thoughts in the context of depression. Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate and cause marked anxiety or distress. For example, some mothers have obsessional thoughts about drowning their baby and refuse to bathe the child. Women often have “what if” questions such as, What if I throw the baby over the banister? Obsessions differ from psychotic symptoms because the patient recognizes that the thoughts, impulses, or images are a product of her own mind (not imposed by an external force as might occur in psychosis). Additionally, obsessional visual images may occur but are brief and are perceived as being in the “mind’s eye” as opposed to an external hallucination. For example, a woman might have frightening images of her dead baby in a bathtub, but she is aware that the image does not reflect reality. The distinction is important clinically because women with obsessional thoughts are vigilant about preventing any action related to the thought content (e.g., insisting that all kitchen knives be locked away), whereas women with psychosis are at risk for taking action. Although these symptom sets are not mutually exclusive, co-occurrence is very rare.

The physiologic milieu created by MDE adversely impacts maternal function during pregnancy and postpartum. MDE is associated with poor prenatal care compliance, inadequate nutrition, obesity, smoking, alcohol and drug use, and suicide. A meta-analysis affirmed that MDE during pregnancy was associated with both low birthweight (LBW) and preterm birth (PTB). Offspring of pregnant women with MDE are at risk for insecure attachment and sleep and eating disorders. Children with in utero exposure to maternal MDE are four times more likely to be depressed at age 16 years.

Psychiatric illness during rapid development of the infant creates a new generation at risk. Maternal depression increases the risk for long-lasting adverse effects such as insecure attachment and poor cognitive performance. Other sequelae of maternal mental illness are increased rates of accidental injury, child abuse, neglect, and infanticide. Early identification and intervention for postpartum MDE has the potential to prevent negative sequelae for women and their families. The relationship between maternal MDE and multiple childhood problems is a continuum that often becomes apparent during pregnancy.

Treatment of Major Depressive Episode During Pregnancy

The emergence of MDE during childbearing compels a complete medical and family history, review of systems, and physical exam to assess for contributions to depressive symptoms, particularly thyroid abnormalities and anemia. Our experience is that MDE seldom remits with correction of hypothyroidism alone, and treatment for both is required. The use of prescribed and over-the-counter medications, herbal therapies, drugs, and alcohol must be assessed.

Although MDE is a highly prevalent condition, only 1 in 5 Americans receives any guideline-concordant intervention, and the rate is lower in pregnant women than in nonpregnant women. In nearly 6500 Medicaid recipients with established MDE treatment, women who became pregnant had a significantly greater drop in both outpatient psychotherapy visits and antidepressant prescription claims compared with matched nonpregnant women, and care did not resume after birth.

Evidence-based treatments for MDE are psychotherapy and antidepressants. Studies of interpersonal psychotherapy and pharmacotherapy document both reduced depressive symptoms and improved maternal function following treatment during pregnancy. Psychotherapy is the preferred treatment for most women ; however, it is not available in all practice settings, nor is it feasible for many mothers. Barriers to clinic-based depression care include the physical demands of pregnancy, transportation, childcare for other children, and cost. Adult outpatient settings do not typically offer flexible appointment schedules or allow children on site. If psychotherapy is not feasible, or the woman prefers pharmacotherapy, decision making tends to focus on the potential adverse effects of medication rather than the adverse effects of MDE. The result is often the choice by the woman or her physician to avoid or stop drug treatment to obviate fetal exposure without equal consideration of the risks of MDE to both the mother and fetus. For most pregnant women, the reality is that accessible and acceptable mental health treatment is very limited. Low treatment rates are a public health concern given accumulating evidence that MDE increases risk to the pregnant woman and fetus. Federally funded home visitation programs for disadvantaged women are potential adjuncts for collaborative care with obstetricians and mental health professionals to improve rates of depression treatment.

The risk-benefit decision-making process for treatment of MDE during pregnancy was described by representatives from the American Psychiatric Association. Individually tailored interventions are considered for their capacity to maximize maternal wellness while minimizing adverse effects for the maternal-fetal pair. The patient and physician both contribute expertise to the process, because the patient’s assignment of her own values dictates her choice. For example, some women will not consent to pharmacotherapy during pregnancy regardless of the impairment related to the MDE. Others choose pharmacotherapy because they are not confident that other treatments will be efficacious or because discontinuing medication invariably has been followed by recurrence with psychosocial consequences. The verbal informed consent process promotes the treatment alliance, recognizes the patient’s responsibility to make choices for herself and her baby, and provides an opportunity for ongoing assessment of the woman’s competence to make decisions.

Although used commonly, the word safe is problematic because it implies no possibility of an adverse effect. Confirming any exposure as harmless presents the impossible task of proving no effect on a monumental number of reproductive and developmental outcomes throughout the exposed offspring’s lifespan. What can be estimated from available studies is the magnitude of a subset of reproductive risks in antidepressant-treated women. The risks for multiple domains of reproductive toxicity considered in this chapter are miscarriage, intrauterine fetal demise, structural malformations, growth effects, neurobehavioral teratogenicity, and neonatal effects (see Chapter 8 ). A prominent observation from the literature is the methodologic difficulty of separating the reproductive effects of the drug exposure from the sequelae, both physiologic and psychosocial, of the underlying MDE.

Side Effects of Medical Treatment of Major Depressive Episode During Pregnancy

Recommendations for Treatment During Pregnancy

The American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association developed a consensus document for antidepressant treatment during pregnancy. For mild cases of MDE in pregnant women, psychotherapy is the treatment of choice as the initial intervention. Depressed pregnant women treated with interpersonal psychotherapy had a significant symptomatic improvement compared with a parenting education control group, and 60% of women achieved remission criteria. Other focused, short-term therapies such as cognitive behavioral therapy (CBT) are also effective options for MDE and may be delivered by nonphysician professionals such as psychologists, psychiatric nurse clinicians, or licensed clinical social workers. The cost and accessibility of depression treatment also impacts treatment selection.

For moderate to severe MDE with marked functional impairment, antidepressant pharmacotherapy or combination therapy (medication and psychotherapy) is appropriate. Established efficacy and tolerability of any antidepressant for the individual woman is a strong consideration in drug choice during the risk-benefit decision-making process. Women with chronic or highly recurrent MDE may be on main­tenance antidepressant medication when pregnancy occurs. Maintenance antidepressant treatment is recommended after three or more MDEs due to the near-certain likelihood of recurrence. For pregnant women studied in an academic setting, the risk of relapse for those who discontinued antidepressant usage proximate to conception was significantly greater than women who maintained treatment. Among 82 women who continued their medication, 21 (26%) relapsed compared with 44 (68%) of 65 women who discontinued medication. In contrast, Yonkers and colleagues found that pregnant women who continued antidepressants experienced the same rate of MDE recurrence as women who stopped in a community sample of obstetric patients. A predictive factor for recurrence in both studies were highly recurrent MDE (four or more episodes prior to pregnancy).

Treatment of Major Depressive Episode in the Postpartum Period

Medications effective for MDE in women outside of childbearing are effective during childbearing. In a randomized comparative efficacy trial, the tricyclic nortriptyline (NTP; n = 54) was compared with sertraline ( n = 55), and the response rates were equal. The dosing started with 10 mg for NTP and 25 mg sertraline for 2 days then 25 mg/day NTP and 50 mg/day sertraline thereafter, and it was increased every 2 weeks to a maximum of 150 and 200 mg/day, respectively. The total side effect burden for both drugs was similar, although the types differed for each drug. A major finding was that the dose of sertraline required for remission in this 8-week, double blind protocol was 100 mg/day or more, with many women requiring 150 to 200 mg/day. The starting dose of sertraline 50 mg/day was not efficacious in the majority of women, and dose adjustment should be anticipated approximately 2 weeks after treatment initiation. An RCT of sertraline versus placebo demonstrated efficacy for sertraline with a mean dose of 100 ± 54 mg/day.

In a small novel RCT of the efficacy of estradiol treatment, women with severe postpartum MDE were randomized to placebo or estradiol delivered by transdermal patch (200 µg/day) for 6 months. By 3 months, 80% of the estradiol-treated and 31% of the placebo-treated group responded. Endometrial changes were found in three participants at the end of the study, despite coadministration of dydrogesterone (10 mg/day, 12 days/month in the final 3 months of the RCT). The changes resolved at follow-up. The inclusion of women who took concurrent antidepressant medications limits the ability to discern an estradiol-specific effect. Little is known about estradiol secretion into breast milk; however, it was not detected in the milk of 18 women who used transdermal estradiol 50 to 100 µg/day for 12 weeks.

Prevention of Postpartum-Onset Major Depressive Episode

To reduce the risk for postpartum MDE, an interpersonal therapy-based group intervention was provided to pregnant women on public assistance. Within 3 months after delivery, 20% of the women in standard care developed postpartum MDE compared with 4% of women who received the intervention. Studies of antidepressants or hormones for the prevention of postpartum MDE are limited to three RCTs, with one small RCT demonstrating the efficacy of sertraline. Women with a history of MDE were treated with sertraline immediately following birth to prevent the onset of MDE. The dosing protocol was, in mg/day, 25 for 4 days, then 50 mg through week 4, and 75 thereafter. The duration of preventive treatment was a minimum of 6 months. The explanation for sertraline’s efficacy is based on its serotonergic impact; therefore, use of another serotonergic drug, particularly one to which the woman had previously responded, is appropriate. Although open studies supported that progesterone prevented recurrence, a placebo-controlled RCT of a synthetic progesterone increased the risk of depression after birth.

Treatment During Breastfeeding

The magnitude of antidepressant exposure through breast milk is substantially lower than during pregnancy ( Table 55-1 ). Comprehensive reviews of antidepressant drugs in maternal serum, breast milk, and infant serum have been published. Sertraline or paroxetine (among SSRIs) and nortriptyline (among TCAs) are agents of choice. These drugs are characterized by undetectable or very low breastfed-infant serum concentrations and no reports of adverse events. However, established efficacy of another drug for the woman must be considered strongly in the decision-making process. Although TCAs are reasonable treatments for postpartum MDE, they are second-line drugs due to their toxicity in overdose. More recently released antidepressants are second-line choices for breastfeeding women unless efficacy in prior episodes has been established.

The clinical condition of breastfed infants, particularly those who are sick or LBW, should be monitored to detect adverse effects that may be associated with the maternal drug (behavioral activation or sedation, new-onset feeding or sleeping problems; see Chapter 24 ). Routine laboratory measurement of serum drug levels in healthy full-term infants is not warranted; however, serum concentrations in preterm and sick infants have not been described and would be a welcome contribution to the literature.

Psychiatric Disorders and Suicidal Ideations

Oates performed an evaluation of the Confidential Enquiry into Maternal Deaths from the United Kingdom. Psychiatric disorder, and suicide specifically, was the leading cause of mortality and accounted for 28% of maternal deaths. Women also died of other complications related to psychiatric disorders and substance abuse, and they died violently. In a large scale study of 10,000 women screened with the EPDS, the proportions of response on item 10—“The thought of harming myself has occurred to me”—were for 0, or never, 96.81% ( n = 9681); for 1, or hardly ever, 2.46% ( n = 246); for 2, or sometimes, 0.65% ( n = 65); and for 3, or yes quite often, it was .08% ( n = 8). In this group of 10,000 women screened by phone, 3.2% of women had some degree of suicidal ideation.

Suicide assessment requires direct questioning of the patient about her desire to live or die, specific thoughts about killing herself, plans for carrying out the act, and access to and lethality of means. The American Psychiatric Association guidelines for the assessment of suicidal behaviors provide a comprehensive list of questions that help clinicians assess suicidal thoughts, plans, and behaviors. Initial questions address patients’ feelings about living (Have you ever thought that life was not worth living? Did you ever wish you could go to sleep and just not wake up?) and are followed by questions that address specific thoughts about death, self-harm, and suicide (Have things ever reached the point that you’ve thought of harming yourself?). If thoughts of self-harm are disclosed, clinicians should evaluate the details such as the intensity, frequency, timing, persistence, and circumstances. Physicians must also ask whether the patient has made a specific plan for self-harm. Ask about pills, household poisons, and firearms. Has the patient made preparations to enact the plan or for after her death (purchasing the means, writing a will, arranging for child care)? If the safety of the patient is at risk, emergency psychiatric consultation or involuntary commitment is indicated.

The practice guidelines identify situations in which suicide assessment is warranted: emergency department evaluation, an abrupt change in clinical symptoms, lack of improvement or worsening despite treatment, anticipation or experience of an interpersonal loss or stressor (divorce, loss of custody of children, financial loss, legal problems), or a physical illness associated with a threat to life, severe pain, or loss of function. Patients with increased risk are those with previous suicide attempts, major mood disorders (particularly bipolar disorder), schizophrenia, and substance use.

Diagnosis and Prevalence

The diagnosis of MDE is limited to the lifetime experience of normal mood with episodes of depression, whereas bipolar disorder (BD) includes normal, depressed, and elevated or irritable mood states (mania or its less intense form, hypomania). Changes in energy and activity levels parallel variations in mood. Mania is a persistent, abnormally euphoric, expansive or irritable mood state with inflated self-esteem, agitation, heightened energy, racing thoughts, pressured speech, impulsive behaviors, distractibility, and poor judgment for a minimum of 1 week. Impairment in function must be present. Hypomania is defined by a minimum of 4 continuous days of persistent increased creativity, productivity, and sociability or increased irritability that family or coworkers notice. The woman’s function may be enhanced by creativity and increased energy. In women, depression is the predominant mood state and is frequently mistaken for unipolar depression. Atypical depression—characterized by increased appetite, weight gain, hypersomnia, low energy, heaviness—is more common in women with BD and typically starts in the fall or winter and resolves in spring.

The lifetime prevalence of BD is 1% to 2%. BD type I, which affects women and men equally, is characterized by MDE and periods of mania or hypomania. Bipolar variants that are more common in women than men include BD type II (MDE and hypomania), mixed episodes (intermingled manic and depressive symptoms), and rapid cycling (four or more episodes of opposite polarity in one year). Women with BD often have comorbid anxiety disorders, alcohol or substance (especially Cannabis ) use disorders, bulimia nervosa, childhood or adult physical and/or sexual abuse, and medical problems that include migraines, metabolic syndrome, pain disorders, and hypothyroidism.

The differentiation of MDE from BD is a major challenge, and delays of 7 to 11 years until diagnosis of BD is common. Prescribing antidepressants without an antimanic drug can complicate treatment by increasing rapid cycling, mania, or mixed episodes. The most commonly used measure is the Mood Disorders Questionnaire (MDQ) shown in Figure 55-3 , which assesses lifetime history of mania with 13 yes/no symptoms and two questions: a yes/no query about whether symptoms occurred during the same time period and a designation of the magnitude of the resulting problems (none, minor, moderate, serious). A positive screen requires seven or more symptoms during the same period that caused moderate or serious problems. Our team studied use of the MDQ with the EPDS as a combined screening tool in a postpartum population with follow-up diagnosis by a research psychiatric interview. The addition of the MDQ to the EPDS identified BD in 50% of women with traditional scoring, and it reached almost 70% when the MDQ was scored without the impairment criterion. Based on this study, we recommend the MDQ or a diagnostic assessment for BD be given prior to prescribing antidepressants for a postpartum depressed woman.

Mood Disorder Questionnaire. This instrument is designed for screening purposes only and is not to be used as a diagnostic tool.

(Courtesy The University of Texas Medical Branch.)

Natural History Across Childbearing

The course of episodes is useful in evaluating recurrence risk during pregnancy. Women with episodes that occur only after delivery are not likely to relapse during pregnancy even without medication. However, women with a chronic course are likely to be symptomatic during pregnancy, and maintenance medication is appropriate. For women with chronic BD, discontinuation of drug treatment proximal to conception incurred a high risk for recurrence (86%) compared with patients who continued treatment (37%). After delivery, all women with BD are at high risk for recurrent mood episodes.

Postpartum psychosis is typically a manifestation of BD such as mania, mixed state, or depression with psychotic features . It occurs in 1 to 2 per 1000 births in the first month following delivery. Women are more vulnerable to psychosis in the post-birth period than at any other time during their lives. In the first 30 days after birth, a woman is 21.7 times more likely to develop psychosis than in the 2-year period prior to childbirth. If she has not had a child before, she is 35 times more likely to suffer psychosis than women who have children. The magnitude of these relative risks demonstrates that postpartum psychiatric morbidity is a major public health problem. The mechanism for the vulnerability of postpartum women with BD for decompensation and psychosis have not been elucidated. Sleep deprivation and marked interference with circadian rhythms related to labor are likely contributors to mood instability. Hormone elevations near the end of gestation and massive postpartum withdrawal also contribute to the risk. The clinical picture of postpartum psychosis is characterized by rapid onset of hectic mood fluctuations; marked cognitive impairment suggestive of delirium; bizarre behavior; insomnia; visual and auditory hallucinations, including unusual (tactile and olfactory) hallucinations; and impaired judgment and insight. Specific types of delusional thoughts are related to the risk for infanticide. Delusional altruistic homicide, often associated with maternal suicide, to save both mother and infant “from a fate worse than death” was reported in a review of filicides, that is, killing one’s son or daughter. Resnick observed that 40% of the perpetrators of filicide had seen physicians shortly before the tragedy. Sensitive, direct questions about thoughts of harm to the infant are imperative in the examination. Nonjudgmental inquiry can be made as follows: “Some new mothers have thoughts such as wishing the baby were dead or about harming the baby; has this happened to you?”

The risk for adverse pregnancy outcomes is increased in women with mental illness. A population cohort study demonstrated that women with BD had an increased frequency of placenta previa and antepartum hemorrhage compared with euthymic women.

Treatment of Bipolar Disorder During Childbearing

Medication maintenance is the mainstay of treatment for BD, although psychotherapy and education are also important. Early identification of BD and rapid initiation of treatment results in lower rates of relapse, increased time to recurrence, improved medication adherence, and better function. Because abrupt discontinuation of mood stabilizers increases the risk for recurrence, education about adherence and drug tapering for discontinuation is advisable.

Several classes of drugs are effective for the treatment of mania. Lithium, some antiepileptic drugs (AEDs), and atypical antipsychotic drugs are efficacious; however, these treatments provide response in only 36% to 50% of cases, and patients often receive more than one drug to manage their mood symptoms. To minimize fetal exposure, strategies include (1) use using the lowest effective doses, (2) minimizing the number of drugs taken, and (3) dividing daily doses to avoid high peak serum concentrations, unless compliance will be compromised.

Prevention of Bipolar Disorder Recurrence Postpartum

The risk for recurrence of mania, depression, or mixed states postpartum is the highest at any point in a woman’s life. In women who discontinued lithium therapy, the rates of recurrence in the postpartum period were almost three times that of the nonpregnant women over a similar time (70% vs. 24%). Moreover, among women who had previous postpartum psychosis, more than 40% experienced relapse after declining immediate postpartum lithium prophylaxis, and no woman who began medication immediately postpartum had a recurrence. The postpartum pharmacotherapy plan includes selection of the drug(s) of past response and educating partners to observe and report early symptoms to prevent episodes.

Breastfeeding for Women with Bipolar Disorder

The mother’s desire to breastfeed is an important consideration in the postpartum management (see Chapter 24 ). Successful lactation may be compromised by not breastfeeding through the night in the early postpartum period; however, sleep deprivation is a major factor in precipitating mania. If a partner or family member can provide support and feed the baby at night, sleep can be prioritized.

The American Academy of Pediatrics (AAP) and the AAN concluded that most medications used to treat BD produce breast milk concentrations less than 10% of the mother’s weight-adjusted concentrations. A multicenter longitudinal observational study of monotherapy of AEDs examined the impact of breastfeeding on IQ at 3 years age for CBZ, LTG, and VPA. Breastfed children did not differ from formula-fed children. However, the concentrations of LTG in breastfed infants averaged 30% to 35% of that of the mother. The risk for toxicity may be increased in breastfeeding infants of women who receive additional similarly metabolized agents such as lorazepam, aspirin, olanzapine, acetaminophen, and VPA.

Lithium treatment can be managed in breastfeeding women with education and close follow-up. In a case series of 10 mother-infant pairs, infant serum lithium concentrations were 25% of maternal levels. In another study of three infants, infant concentrations ranged from 10% to 17% of maternal levels. Caregivers should monitor the infant for signs of toxicity (poor feeding, lethargy, and hypotonia), especially in situations that increase the risk for dehydration (reduced feeding/oral intake, excessive fluid loss or fever). To avoid spuriously high levels of lithium, infant blood samples must be collected in tubes that do not contain lithium heparin as the stabilizing agent.

Fear of Labor and Delivery

Some women have intense fear of pregnancy and childbirth. About 5% to 10% of pregnant women have extreme fear of delivery, which may be considered a type of phobia. These women often request surgical deliveries to avoid labor. Risk factors for intense fear of delivery and requesting cesarean delivery include preexisting mental illness, history of abuse, poor social support, unemployment, and previous complicated delivery. Focused, short-term psychotherapy may enable these women to accept a vaginal delivery and improve the birth experience.