Center for Neuroscience in Women's Health

Pregnancy and Mental Health

A common myth states that hormones released during pregnancy protect women from psychiatric disorders and foster a period of emotional well-being.  Recent studies, however, have shown that up to 20% of women suffer from mood or anxiety disorders during the gestation and postpartum periods.  Whether the symptoms develop at the onset of pregnancy or are a continuation of a previous history, women face a difficult decision about how to manage their illness during pregnancy.

It is common for women to discontinue or avoid pharmacologic treatment in order to decrease the risks of prenatal exposure to medications.  This is not always the safest option, however, as psychiatric illness in the mother can in some cases cause significant morbidity for the mother and child.  It is important for the patient to be well informed about the risks involved on both sides and take into account her specific diagnosis and the recommendations of her health care provider.

Common Psychiatric Disorders

              Given the numerous physiological and hormonal changes the body undergoes and the stressors involved in pregnancy, anxiety and depression are the most common emotional disturbances during the perinatal period.  Reported rates of depression in pregnant women have ranged from 5% to almost 30%.  In very mild cases, symptoms are usually manageable with counseling, support groups, environmental manipulation, and diversions such as walking, warm baths, and keeping up social contacts.  When the depression and anxiety does not respond to these approaches, professional psychotherapy is recommended.  Brief hospital stays, intensive outpatient programs, or, for more severe cases, medication may effectively treat the illness. 

Major depression, a mood disorder that affects a person’s ability to experience normal mood states, affects up to 10% of pregnant women.  Symptoms include a depressed mood most of the day, nearly every day, for two weeks or longer and/or the loss of interest or pleasure in activities that the person usually enjoys.  Other symptoms can include:

Untreated major depression has serious potential risks for mother and fetus.  Symptoms may develop and worsen into the postpartum period.  Continued depression may lead to poor nutrition, smoking, drinking, suicidal behavior, prolonged or premature labor, and low birth weights.           

Anxiety disorders can also be stimulated or compounded by pregnancy.  Panic disorder, obsessive compulsive disorder, and generalized anxiety disorder appear to be as common as depression.  Perinatal anxiety symptoms can include:

The Risks of Fetal Medication Exposure

              The Food and Drug Administration has not approved any psychotropic drug during pregnancy.  Because medications diffuse across the placenta, one must consider the risks associated with prenatal exposure, including the risk of teratogenesis, the risk of neonatal toxicity, and the risk of long-term neurobehavioral effects.            

Teratogenesis is the development of congenital malformations.  These include gross morphological abnormalities, such as cleft lip or palate, but may also include phenomena such as increased risk of cervical cancer.  The formation of major organ systems in the fetus takes place within the first twelve weeks after conception.  Each organ or organ system has a critical period during development when it is susceptible to the effects of a toxic agent.  Teratogenesis does occur naturally in 2 to 4% of births in the U.S.             

Neonatal toxicity or perinatal syndromes refer to the physical and behavioral symptoms observed in the first month of life that can be attributed to drug exposure near the time of delivery.  In some cases, a range of neonatal distress syndromes have been associated with exposure to or withdrawals from medications the child absorbed in the uterus, but larger studies have not yet established clear links between particular medications and perinatal syndromes.

There have been few studies regarding the long-term effects of prenatal exposure to psychotropic medications, and thus our knowledge is incomplete.  Because of the complex and continuing development of the central nervous system during and after pregnancy, it is particularly vulnerable to toxic agents.  Exposure to these agents after 32 days of gestation may produce subtle changes in behavior and functioning that appear later on in the child’s life.

Antidepressants

              A relatively small number of cases of first trimester exposure to antidepressants have been reported, but these reports have suggested no increased risk of birth defects.  Since there have probably been millions of cases of accidental first trimester exposure in the over thirty years of treatment with tricyclic antidepressants, the lack of reports suggesting teratogenicity is encouraging.  Several studies that compared tricyclic antidepressants and SSRIs did not demonstrate an increased risk of congenital malformation.  Prozac is the most prescribed antidepressant in the United States and has been the most researched.  Data collected from over 2500 cases indicate no increase in risk of major congenital malformation in exposed infants.  Studies of other specific SSRI medications carry the same results but have not been researched as extensively.  MAOIs are generally not used during pregnancy because they require dietary restrictions which can compromise the mother’s nutritional status, can affect blood pressure, and adversely react with terbutaline, which is used to suppress premature labor.

              Recent studies have suggested that exposure to SSRIs at the time of delivery may be associated with poor perinatal outcomes.  Several studies have reported increased rates of admission to the special care nursery among SSRI-exposed infants.  The most commonly reported symptoms in the newborns include tremor, restlessness, increased muscle tone, and increased crying.  These symptoms, however, resolve within 1 to 4 days after birth without any specific medical intervention.

              The best long-term study of antidepressant-exposed fetuses followed 80 cases up to age seven.  When compared to a control group without any exposure to antidepressants during pregnancy, the exposed children showed no significant differences in IQ, temperament, behavior, reactivity, mood, distractibility, or activity level. 

Mood Stabilizers

              Maintenance treatment with a mood stabilizer can significantly reduce the risk of relapse in pregnant women with bipolar disorder.  However, many of the medications commonly used carry some teratogenic risk.  First trimester exposure to lithium has been associated with an increased risk of cardiovascular malformation between .05% and .1%.  Prenatal exposure to valproic acid can increase the risk of fetal malformation by up to 4%.  There is limited information on the reproductive safety of other newer anticonvulsants. 

              There is however, increased support for the reproductive safety of lamotrigine (Lamictal).  Of 360 children exposed to lamotrigine alone, 2.8% had a major malformation, which is within the range of 2 to 4% observed in women with no exposure to toxic agents. 

Anti-Anxiety Medications

              Benzodiazepines are commonly prescribed to people suffering from anxiety disorders.  Older studies suggest that there may be an increased risk of cleft lip and palate amounting to .7%, but these results have been widely debated.  If correct, the likelihood that a woman exposed to benzodiazepines during the first trimester will give birth to a child with this congenital anomaly remains less that 1%.  Benzodiazepines are also associated with prenatal syndrome, including feeding problems, hypothermia, and deficiency in baby’s muscle tone.  No systematic data are available on the reproductive safety of other, non-benzodiazepine anxiolytic agents and hypnotic agents, therefore their use during pregnancy is not recommended. 

Anti-Psychotic Medications

              High-potency antipsychotics, like Haldol, are effective schizophrenia and bipolar medications.  Recent studies have shown no increased risk to fetus or baby and are recommended for used during pregnancy for high-risk patients.  Low-potency neuroleptic agents, however, are associated with higher risks of congenital malformations after first trimester exposure and are not recommended.  There is not enough data to identify the effects of atypical antipsychotics on the fetus and are not recommended.

SSRIs and Persistent Pulmonary Hypertension of the Newborn

              A recent study has linked SSRI use during late pregnancy to an increased risk of persistent pulmonary hypertension in the newborn. Persistent pulmonary hypertension of the newborn (PPHN) is a cardiovascular syndrome typically seen shortly after birth, usually within 12 hours of delivery.  After birth, the infant’s pulmonary vascular resistance does not decrease as it should and blood is shunted away from the lungs.  The blood, therefore, is not fully oxygenated and causes respiratory distress in the infant, which may require assisted ventilation.  PPHM occurs in approximately one in 700 births. 

              A study conducted in 1996 compared 377 infants with PPHN with a control group of 836 infants.  The study found that SSRI-exposure after the 20th week of gestation was significantly associated with PPHN.  Only this study, however, has associated this severe condition with SSRI-exposure.  Almost all other studies have found associations with only mild, transient symptoms.  Further investigation is needed to clarify the relationship between SSRI use and PPHN.

Psychiatric Medications and Breastfeeding

              Given the incidence of psychiatric illness during the postpartum period, especially postpartum depression, a significant number of women may need to take psychiatric medications while nursing.  The safety of infant exposure to medications through the mother’s breast milk has been a question of concern.  Current research indicates that all medications are secreted into the breast milk but adverse events in nursing infants are not common.  Whether or not the infant experiences toxicity depends on the medication, amount of exposure (maternal dosage, frequency of dosing, rate of maternal drug metabolism), and how well the medication is metabolized in the infant’s liver.  During the first few weeks of a full-term infant and even longer for premature infants, the capacity for metabolism is much lower than adults.  The infant’s capacity increases until the second or third month of age when their liver metabolism surpasses that of adults. 

 

For more information, visit:

http://womensmentalhealth.org/topics/pregnancy.html

http://www.athealth.com/Practitioner/particles/Guest_Rathbun.html

 

Stanford Medicine Resources:

Footer Links: