Smoking Pot While Pregnant is a No-No
Mom, Don’t Think Smoking Pot When Pregnant is Harmless for your Child
In a new article in Science, Jasmine Hurd reports on a large sample of mothers who smoked pot while pregnant. Their offspring were more anxious, hyperactive, and aggressive and had higher levels of the stress hormone cortisol in their hair at ages 3-6.
When Superstorm Sandy hit, mothers who were stressed and smoked pot while pregnant had children 31 times more like to have oppositional defiant disorder and 7 times more likely to have an anxiety disorder. Stress may interact negatively with the effects of pot.
In fetuses aborted after being exposed to pot while in utero had decreased dopamine receptors in the their amygdala and n. accumbens, a reward center in brain. In animal studies, pregnant mother rodents who were exposed to THC had offspring more likely to use heroin.
DADS’ BEHAVIOR COUNTS TOO. Dad’s exposure to THC as an adult also led to offspring who preferred opiates. This was based on epigenetic changes passed on in the sperm. To the extent that this also happens in humans, one could ask how much of the current opiate epidemic is based on parental use of marijuana. Mom’s and dad’s smoking pot could make their offspring more vulnerable to opiate addiction.
Bipolar Disorder in Pregnancy and the Postpartum Period
At the 2020 meeting of the International Society for Bipolar Disorders, researcher Veerle Bergink reported several findings from a recent meta-analysis of articles on pregnancy and bipolar disorder. Bergink and colleagues found that pregnant women with bipolar disorder have a 37% risk of a postpartum relapse, more than twice the risk of postpartum mental disorders in the general population.
Using lithium as a treatment in the first trimester of pregnancy increased risk of congenital malformations in the fetus, but the risk was much smaller than previously thought and could be monitored by ultrasound.
Bergink and colleagues also reported that in a sample of 645 women with first-onset postpartum psychosis who received followup over a period of 7 to 25 years, 43% had no subsequent severe episodes outside of the postpartum period.
Another finding was that women with postpartum severe depression or mania had abnormalities in T cells, which are important in immune response.
Prenatal Prevention of Psychiatric Illness with Nutritional Supplements
In a 2018 article in the American Journal of Psychiatry, researcher Robert Freedman and colleagues shared the results of a systematic review of data on nutritional supplements during pregnancy for the primary prevention of psychiatric illness in the child. Freedman and colleagues concluded that the evidence is robust that prenatal folic acid supplementation plus multivitamins not only can prevent birth defects such as cleft palate, spina bifida, and microcephaly, but also social withdrawal, decreased attention, and aggression at age 18 months. They wrote, “Supplements of up to 4 mg [of folic acid] before 12 weeks gestation have been found to be safe and effective.”
The effects of omega-3 fatty acid supplementation depended on when the supplements were taken. Taking omega-3 fatty acid supplements early in pregnancy was linked to an increase in schizophrenia and more symptoms of attention deficit hyperactivity disorder (ADHD) in the offspring. However, supplementation after 20 weeks of pregnancy decreased preterm delivery, low birth weight, and asthma.
As of 2017, choline supplementation during pregnancy is recommended by the American Medical Association. Their recommendation is based on research in which the choline precursor phosphatidylcholine (5,000-6,300 mg/day) was given to mothers beginning in the 18th week of pregnancy and continued in the newborn for two weeks to three months after birth in the form of 100mg of liquid phosphatidylcholine. This supplementation regimen normalized the P50 auditory evoked potential, a measure of inhibitory sensory gating that is abnormal in patients with schizophrenia and bipolar disorder and infants whose parents had psychosis, depression, or smoked (all risk factors for a later diagnosis of schizophrenia).
Healthy individuals show a reduced response to an auditory cue when it is repeated 50 milliseconds after the initial cue. In people with schizophrenia, response to the repeated cue is not suppressed. Not only did the P50 auditory evoked potential normalize with phosphatidylcholine supplementation, but at 3.5 years of age, those who received phosphatidylcholine supplements in utero and as newborns had fewer problems with attention and social interactions. The findings were even more robust in those with the CHRNA7 genotype (a genetic variation in the alpha 7 nicotinic receptor), which is a risk factor for schizophrenia.
Supplementation with vitamins A and D during gestation also decreased the risk for schizophrenia and autism spectrum disorders in offspring. Recommendations include Vitamin D at doses of 600 to 4,000 IU for pregnant mothers and 400 to 1,000 IU for infants. Because of potential toxicity, vitamin A should be limited to 8,000 units from diet and supplements combined. (Supplements typically contain 2,500 units.)
While there are some methodological limitations to the findings, Freedman and colleagues conclude, “As part of comprehensive maternal and fetal care, prenatal nutrient interventions should be further considered as uniquely effective first steps in decreasing risk for future psychiatric and other illnesses in newborn children.”
Editor’s Note: Given the high risk of psychiatric illness (74%) in the offspring of a parent with bipolar disorder and the finding of abnormal P50 auditory evoked potential in patients with bipolar disorder, the recommended nutritional supplements should be given special consideration during gestation of a child who has a parent with bipolar disorder. According to the 2018 article by Freedman and colleagues, this would include folate, phosphatidylcholine, vitamin A and vitamin D.
In Animals, Exposure to High Fat Diet During Pregnancy Can Affect Offspring’s Neurological Development
New research in non-human primates suggests that exposure to a high fat diet during pregnancy and in early development prior to weaning can increase the offspring’s propensity for anxiety later in life.
The new research echoes 2010 findings about rats. Researcher Staci D. Bilbo and colleagues reported in the journal of the Federation of American Societies for Experimental Biology that in rats, a high fat diet during pregnancy and lactation led to offspring with greater body weight, increased inflammation, and problems with anxiety and spatial learning. Switching to a standard diet after weaning did not eliminate these outcomes.
The recent research by Jacqueline R. Thompson and colleagues, published in the journal Frontiers in Endocrinology in July 2017, suggests that maternal nutrition in the primate during pregnancy and lactation can have long-lasting effects on offspring’s neurological development, altering the brain and endocrine system. These changes occurred even if the offspring began a normal diet after weaning.
65 female Japanese macaques were divided into two groups, one that received a high-fat diet and one that received a normal diet. In the offspring of mothers who ate a high-fat diet, the researchers found impaired development of neurons containing serotonin. The offspring of the high-fat diet group also showed behavioral alterations such as increased anxiety.
The high rates of obesity in the US and other developed nations make these findings particularly important. The researchers suggest that 64% of women in the US who are of reproductive age are overweight, and 35% are obese. Co-author Elinor Sullivan suggested that the findings from the study could motivate mothers to make healthy nutritional decisions, not only for themselves but for their children as well.
Using Antidepressants During Pregnancy Likely Does Not Increase Autism Risk
In the past year or so, several meta-analyses have analyzed data from numerous studies of a possible link between antidepressant use in pregnancy and autism in the offspring. In a 2017 article in the Journal of Clinical Psychiatry, researcher Chittaranjan Andrade offers a meta-analysis of these previous meta-analyses, and determines that while there is a small link between antidepressant use in pregnancy and autism in the offspring, it is most likely the mother’s depressive illness rather than the medications that is responsible for this link.
Andrade found that antidepressant exposure was linked to an increased risk of autism spectrum disorders in the offspring even when the antidepressant use occurred only before conception occurred, when it could not possibly have affected the future fetus’ physiology. This implies that it is the mother’s illness rather than the antidepressant treatment that is a determinant of autism risk.
Atypical Antipsychotic Drug Aripiprazole Appropriate for Pregnancies
A 2017 systematic review in the Journal of Affective Disorders found that the atypical antipsychotic medication apripiprazole (Abilify) was relatively safe for use during pregnancy and lactation. Researcher Alessandro Cuomo and colleagues reviewed 93 articles from the last two decades of research.
Placebo-controlled research on medications used during pregnancy are uncommon, due to ethical reservations about assigning women randomly to each group when their fetus may be affected. However, Cuomo and colleagues were able to find some large prospective studies and large database studies that shed light on aripiprazole’s safety during pregnancy. They concluded that the data on aripiprazole during pregnancy and breastfeeding were “relatively reassuring” and that the benefits of aripiprazole outweigh the potential risks.
Risks of relapse upon discontinuing a mood stabilizer can be as high as 80%. Illness in the mother conveys risks to the fetus, so the risk-benefit ratio may suggest that staying on effective aripiprazole treatment during pregnancy and lactation makes sense for many patients.
In a comment on the study reported by Reuters Health, Dr. Jennifer L. Payne of the Johns Hopkins School of Medicine said, “The main reason to discontinue aripiprazole for pregnancy…would be if it is not working and the mother is actively ill, or if she insisted on doing so. In my mind, the literature supports the use of aripiprazole during pregnancy in mothers with serious mental illness who are responding well to the medication.”
Folate Supplements Reduce Autism Rates in Offspring of Women Taking Anti-Epileptic Drugs During Pregnancy
A 2017 study form Norway suggests that the offspring of women taking anti-epileptic drugs during pregnancy are less likely to develop autism if the women also take folic acid supplements.
The study by Marte Bjørk and colleagues in the journal JAMA Neurology used data from 104,936 children aged 18 to 36 months. Those whose mothers took anti-epileptic drugs during pregnancy had elevated autism rates, but only if their mothers did not use folic acid supplements. The mothers’ folate levels in weeks 17 to 19 of their pregnancies were inversely related to the degree of autistic traits in their offspring.
Women without epilepsy and women whose epilepsy went untreated during pregnancy had children with similarly low rates of autism to those whose mothers supplemented their anti-epileptic medications with folic acid during pregnancy.
Several Studies Find Lamotrigine is Safe in Pregnancy
Several studies have now suggested that lamotrigine is safe to use during pregnancy. In June 2017, researcher Gali Pariente and colleagues published a systematic review and meta-analysis in the journal CNS Drugs in which they reported that across 21 studies, lamotrigine use during pregnancy was not linked to an increase in birth defects.
In November 2017, a small study from an Israeli medical center reported data from 83 women who received lamotrigine during their first trimester of pregnancy. The study by Merav Cohen-Israel and colleagues in the British Journal of Clinical Pharmacology found that lamotrigine use was not linked to congenital malformations, neurodevelopmental disorders, or withdrawal symptoms in the offspring.
Of the 83 women, 76 received lamotrigine alone, four received it in combination with clonazepam, two with carbamazepine, and one in combination with both levetiracetam and phenytoin.
Management of Unipolar and Bipolar Depression During Pregnancy
At the Maryland Psychiatric Research Society’s continuing medical education conference in November, Lauren Osbourne, Assistant Director of the Women’s Mood Disorders Clinic at Johns Hopkins Hospital, gave a presentation on the management of mood and anxiety during pregnancy and lactation. She had a number of important ideas for physicians and patients to consider in their decision-making process.
According to Osbourne, 60%-70% of pregnant women with unipolar depression who discontinue their antidepressants relapse. Of those with bipolar disorder who discontinue their mood stabilizers, 85% relapse, while 37% of those who stay on their medications relapse.
Something to consider when deciding whether to continue medication while pregnant is that depression in pregnancy carries its own risks for the fetus. These include preterm delivery, low birth weight, poor muscle tone, hypoactivity, increased cortisol, poor reflexes, and increased incidence of attention deficit hyperactivity disorder (ADHD) and other behavioral disorders.
The placenta makes an enzyme 11-BHSD2 that lowers the stress hormone cortisol in the baby. However, this enzyme is less active in depression, exposing the fetus to higher levels of cortisol.
Thus, the decision about whether to continue medications during pregnancy should consider the risks to the fetus of both the mother’s depression and the mother’s medications.
Most antidepressants are now considered safe during pregnancy. There have been reports of potential problems, but these data are often confounded by the fact that women with more severe depression are more likely to require antidepressants, along with other risk variables such as smoking or late delivery (after 42 weeks). When these are accounted for by using matched controls, the apparent risks of certain antidepressants are no longer significant. This includes no increased risk of persistent pulmonary hypertension, autism, or cardiac malformations.
There may be a possible increased risk of Neonatal Adaption Syndrome (NAS) in the first weeks of life in babies who were exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants in the third trimester. This syndrome presumably results from antidepressant withdrawal, and can include respiratory distress, temperature changes, decreased feeding, jitteriness/irritability, floppiness or rigidity, hypoglycemia, and jaundice. There is not yet a robust literature on the syndrome, but Osbourne suggested that it disappears within 2 weeks of birth.
In her practice, Osbourne prefers to prescribe sertraline, which has the best safety data, along with fluoxetine. Sertraline is also OK for breastfeeding. There is less data on bupropion, but it also appears to be safe during pregnancy. Endocrine and enzyme changes in pregnancy typically cause a 40% to 50% decrease in concentrations of antidepressants, so doses of antidepressants typically must be increased in order to maintain their effectiveness.
Osbourne ranked mood stabilizers for bipolar disorder, from safest to most worrisome. Lamotrigine is safest. There is no evidence linking it to birth defects, but higher doses are required because of increased clearance during pregnancy. Lithium is next safest. There are cardiac risks for one in 1,200 patients, but these can be monitored. Carbamazepine is third safest. One percent of babies exposed to carbamazepine will develop spina bifida or craniofacial abnormalities. Valproate is least safe during pregnancy. Seven to ten percent of babies exposed to valproate will develop neural tube defects, other malformations, or developmental delay, with a mean decrease of 9 IQ points. The atypical antipsychotics all appear safe so far.
Alternatives and Adjuncts to Medications in Pregnancy
Safety of Atypical Antipsychotics in Pregnancy
A 2017 article in the Journal of Clinical Psychiatry systematically reviewed data on the risks related to schizophrenia, bipolar disorder, and treatment with atypical antipsychotic medication during pregnancy. The article by researcher Sarah Tosato and colleagues suggests that a mother’s illness may be more harmful to a fetus than treatment for that illness is.
The review analyzed 49 articles about illness-related and atypical antipsychotic–related risks in bipolar disorder and schizophrenia. Tosato and colleagues found that abrupt discontinuation of treatment led to a high risk of relapse in pregnant women with bipolar disorder or schizophrenia.
Schizophrenia was linked to a slight increase in obstetric complications for mothers, while both bipolar disorder and schizophrenia were linked to a slight increase in complications for newborns. Mothers ill with schizophrenia had the highest risk for serious complications, including stillbirth, neonatal or infant death, and intellectual disability in the child.
The researchers reported that untreated bipolar disorder and schizophrenia are risk factors for birth defects, but use of atypical antipsychotics is not. Children’s neurodevelopment also does not seem to be affected by mothers’ use of atypical antipsychotics during pregnancy.
The authors suggest that, given parents agree and understand any risks involved, the least harmful choice of action is to maintain treatment of women with bipolar disorder and schizophrenia during pregnancy at the safest minimum dosage to keep their illness at bay.
