Addressing Knowledge Gaps About Mental Illness in Pregnancy and Postpartum

Although 10 percent to 16 percent of people who are pregnant are estimated to experience some form of mental illness, according to the World Health Organization, significant knowledge gaps remain about the impacts of these diseases and their treatments on the health and well-being of both the parent and child.

These are the gaps that Veerle Bergink, MD, PhD, and her colleagues are attempting to address. As Director of the Mount Sinai Women’s Mental Health Program, she is working with researchers in the Departments of Obstetrics, Gynecology and Reproductive Science, and Psychiatry, on studies focused on the role of medication in maintaining mood stability during pregnancy; the impact of parental mental illness on the brain and behavior of the child; and the etiology and treatment of severe mental illness immediately after delivery, such as postpartum psychosis.

“Individuals who are pregnant or postpartum have traditionally been excluded from most clinical studies to protect this population from any unforeseen risks,” says Dr. Bergink, Professor of Psychiatry, and Obstetrics, Gynecology, and Reproductive Science, at the Icahn School of Medicine at Mount Sinai.

“As a result, clinicians and pregnant individuals lack data to make informed health care decisions specifically related to mental health. Our diverse research program is intended to address that.”

Generation C and Beyond

The program launched Generation C, a large-scale, prospective, multidisciplinary study, in April 2020 to examine the impact of SARS-CoV-2 infection, and the ensuing immune response, during pregnancy on gestational parent and child health outcomes. Collected samples and established collaborations have spawned recent follow-up efforts.

The first follow-up effort to receive National Institutes of Health funding is “Cerebrospinal fluid (CSF) and peripheral markers of the neuropsychiatric sequelae of COVID-19: The Generation C-SF pregnancy study.” This study is using cerebrospinal fluid samples collected during epidurals to investigate the long-term impact of the immune response to SARS-CoV-2 infection on neuropsychiatric outcomes among 600 patients recruited from the Generation C cohort.

Obtaining brain fluid during delivery is notable, as it has not been routinely done during other studies in pregnancy, says M. Mercedes Perez-Rodriguez, MD, PhD, Associate Professor of Psychiatry and Director of the Affective and Cognitive Therapeutics Lab at Icahn Mount Sinai.

The team is also exploring the impact of immune expression in the placenta and is following children who were exposed to SARS-CoV-2 in utero to see if there are any differences in behavioral outcomes or brain development versus children who were not prenatally exposed to the virus. Anna-Sophie Rommel, PhD, Assistant Professor of Psychiatry, is leading the effort to study behavioral outcomes of children born into the Generation C cohort. She is assessing behavior based on 900 responses to caregiver questionnaires; in a subset of 300 children, she will conduct a clinical assessment involving electroencephalogram.

Dr. Rommel’s work creates the first time point for possible ongoing follow-ups with these children over the long term, while exploring the merit of future follow-ups. “My goal is to investigate whether these children are impacted in a similar way to what we have observed when we look at other types of infection during pregnancy,” she says.

Managing Medication During Pregnancy

The Women’s Mental Health Program also looked at the impacts of psychotropic medication on pregnancy and offspring. Dr. Bergink and her colleagues found that discontinuation of antidepressants before or during early pregnancy does not appear to be associated with an increased risk of adverse psychiatric outcomes and is beneficial for avoiding adverse outcomes such as postnatal adaptation syndrome and pulmonary hypertension among neonates—both of which are only associated with antidepressant use late in pregnancy. Findings were published in three journals in 2022.

While some individuals benefit from discontinuing medication, others who have a more severe mood disorder have a moderately increased risk for relapse.

For those who need to continue antidepressant use during pregnancy, the researchers quantified two important short-term outcomes:

There was also an observed significant increase in risk for moderately low birth weight, postnatal adaptation syndrome, and neonatal admission.

Dr. Bergink characterized long-term child outcomes as reassuring, with any adverse mental health outcomes in the child likely attributable to the underlying parental psychopathology rather than antidepressant exposure.

“Given that the use of antidepressants has significantly increased in recent years, these insights are vital in addressing questions about the impacts of continuing medication during pregnancy,” Dr. Bergink says, adding that her team is planning additional clinical studies and data collection focused on antipsychotics and stimulant medication.

Dr. Rommel is also conducting a study to assess whether acetaminophen use during pregnancy has any long-term behavioral impacts on children.

“Although this is the one pain medication that is allowed during pregnancy because it is thought not to cause any birth defects, acetaminophen is very similar to endocrine-disrupting chemicals,” Dr. Rommel explains. The study will examine the relationship of prenatal exposure to acetaminophen with inattention and social responsiveness among children ages three to four. The assessments will be based on caregiver reports and EEG data collection.

The program is generating vital guidance on best practices for mental health treatment during pregnancy, but the team hopes to make more headway, especially for individuals with severe mental illness, who have very high risk of relapse after delivery, or children at higher risk of developing illness.

“That is something that is really important to figure out in a targeted way,” says Thalia Robakis, MD, PhD, Associate Professor of Psychiatry at Icahn Mount Sinai. “The research on illness and therapeutic agents has largely been siloed. We are looking to secure funding so we can explore these things holistically and identify the relative risks versus benefits of medication among gestational parents and their children in a systematic and all-encompassing way.”