Psychological distress -- a term encompassing anxiety, stress, and depression -- was more prevalent than expected in a sample of healthy, well-educated pregnant women and was associated with impaired fetal brain development, a prospective study suggested. Among 119 pregnant women with uncomplicated pregnancies, 27% scored high on a perceived stress questionnaire, 26% had high scores for anxiety, and 11% had elevated symptoms of depression, according to Catherine Limperopoulos, PhD, of the Center for the Developing Brain at Children's National Hospital in Washington, D.C., and colleagues. Increases in trait anxiety scores were associated with reductions in left hemisphere fetal brain volume, and elevated maternal stress and anxiety levels were tied to increased fetal gyrification (cortical folding) in frontal and temporal lobes, they reported in JAMA Network Open. Elevated maternal depression scores also were associated with reductions in fetal creatine and choline levels. The study involved a group of well-resourced, well-educated women, and while the research is preliminary, "it points to prenatal psychological distress being alarmingly prevalent and clinically under-recognized," Limperopoulos said. "We did not expect these findings among women expecting normal babies. These women had no indication of any mental health disorder, which leads us to worry that many women with similar maternal distress are slipping below the radar during routine clinical encounters," she told MedPage Today. "Fetal brain development ramps up late in pregnancy, at the time when these women were recruited into the study," Limperopoulos added. "Introducing fetuses to this prenatal stressor at that vulnerable time has the potential to derail what should be a uniquely timed and organized program of fetal brain development." "Reduced brain volume and increases in gyrification could have profound implications for behavioral development," noted Charles Nelson III, PhD, of Boston Children's Hospital, in an accompanying editorial. "Although white matter is potentially malleable, a reduction in gray matter before birth could foreshadow potentially permanent consequences for behavioral development." In this study, Limperopoulos and colleagues followed 119 patients recruited from low-risk obstetric clinics in Washington from January 2016 to April 2019. These women had normal prenatal medical history, no chronic or pregnancy-related physical or mental illness, and normal fetal ultrasounds and blood tests. Fetal brain MRIs were performed at two time points between 24 and 40 weeks gestation. Researchers measured maternal distress with the Perceived Stress Scale (PSS), Edinburgh Postnatal Depression Scale (EPDS), and Spielberger State Anxiety Inventory (SSAI) and Spielberger Trait Anxiety Inventory (STAI) tests, which participants completed the same day as each MRI visit. The SSAI assessed state anxiety ("how you feel right now"), while the STAI assessed trait anxiety ("how you generally feel"). The average age of participants was about 34. Overall, 84% reported professional employment, 83% were college graduates, and 52% had a graduate degree. Most women (56%) were carrying male fetuses. Maternal trait anxiety (STAI) scores were negatively correlated with fetal left hippocampal volume on MRI (-0.002 cm3, P=0.004). Anxiety and perceived stress scores were tied to increased fetal cortical gyrification in the frontal lobe (β for SSAI score: 0.004, P=0.002; β for STAI score: 0.004, P<0.001; β for PSS score: 0.005, P=0.005). Anxiety scores also were linked to increased fetal cortical gyrification in the temporal lobe (β for SSAI score: 0.004, P=0.004; β for STAI score: 0.004, P=0.01). In addition, prenatal depression was negatively associated with fetal creatine levels (β for EPDS: -0.04; P=0.005) and choline levels (β for EPDS: -0.03, P=0.02) on magnetic resonance spectroscopy (MRS). The findings have "enormous scientific, clinical, and public health implications," Nelson observed. "It remains to be seen whether these prenatal effects are subsequently mitigated after birth, leaving little functional trace behind. "From a public health perspective, we know that anxiety, depression, and stress affect a huge percentage of the U.S. population," he continued. "Should we be doing a better job of screening pregnant women for psychological distress and mental health issues? If so, how early do we start, who do we target, and what resources can be offered to these women?" Earlier studies are needed to identify the timing and onset of maternal psychological distress and its association with fetal brain development, Limperopoulos and colleagues noted. The cohort was mostly educated and employed; findings might not apply to other populations. Challenges inherent in fetal imaging meant that 8% of MRI scans could not be used because of severe fetal motion and 19% of MRS scans were unsuccessful, they added. Source
