Prenatal influences on fetal neurodevelopment: Can a person-centered approach help parse the complexity of maternal vulnerability and protective features and detect early alterations to fetal neurodevelopment trajectories related to prenatal distress?

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Prenatal influences on fetal neurodevelopment: Can a person-centered approach help parse the complexity of maternal vulnerability and protective features and detect early alterations to fetal neurodevelopment trajectories related to prenatal distress?

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Background: Prenatal maternal distress is associated with an at-risk developmental profile, yet there is little fetal evidence of this putative in utero process. Moreover, the biological transmission for these maternal effects remains uncertain. To advance our understanding of developmental pathways of early transmission of risk we must identify more homogenous profiles of maternal “distress signals” and detect and characterize neurodevelopmental sequelae of offspring risk beginning early in development. However, variability across the typical-to-atypical continuum of maternal experiences of distress, and heterogeneity within and across psychiatric disorders are fundamental challenges to overcome. Prior literature has focused primarily on psychosocial stress, negative mood, and symptoms of psychopathology, but has not yet considered key transdiagnostic vulnerability and protective factors central to the emergence and expression of prenatal distress, such as those related to emotion reactivity, emotion regulation, and coping in response to stress and adversity. Therefore, there are opportunities to advance our understanding of prenatal transmission of risk by: identifying multi-dimensionally-determined maternal profiles of risk that include vulnerability and protective factors, are agnostic to DSM categories, and derived via data-driven, person-centered approaches (i.e., “phenoscreening”); and investigating whether more comprehensive maternal phenotypes are associated with observable differences in fetal neurodevelopmental trajectories. Furthermore, while limited research has applied a person-centered approach to explore maternal features hypothesized to impact the in utero environment, person-centered statistical methods have not yet been used to identify data-driven fetal trajectories of risk. Maternal and fetal risk groups are hypothesized to overlap, since maternal and fetal risk indicators are associated in group-level (variable-centered) analyses. However, this hypothesis has not yet been tested using person-centered statistical methods. These results are needed as person-centered approaches continue to grow in popularity as a tool to detect and detail subpopulations. Central Aims: This study has three central aims. First: To identify high-risk maternal groups using a factor mixture model of maternal features. Second: To identify atypical groups of fetuses, using two well-established indices of fetal neurodevelopment, fetal heart rate (FHR) and fetal heart rate variability (FHRSD). Third: To test for evidence of maternal transmission of risk to offspring in putative in utero period, by investigating associations between maternal indicators of risk, fetal trajectories, and infant birth outcomes. These results are anticipated to inform our understanding of prenatal transmission of risk to offspring by identifying more homogenous “distress signals,” improving early identification efforts by detecting subpopulations of dyads in need of additional support or intervention, and increasing our understanding of explicit caveats and limitations of person-centered approaches applied to dyadic pairs. Methods: To detect subgroups of at-risk dyads, two person-centered statistical approaches were used in primary analyses to identify and characterize maternal and fetal risk groups in a community-based sample of pregnant women and fetuses (n = 108 dyads). First, factor mixture modeling (FMM) was used to identify subgroups of pregnant women and characterize phenotypic maternal risk profiles, derived from multiple self-report measures of distress and mood, psychopathology symptoms, pregnancy symptoms, personality, emotion reactivity, emotion regulation, and coping, collected at 8-16 and 20-24 gestational weeks. Analysis of maternal features focused on these time points because of interest in maternal experiences that may influence fetal trajectories prior to the occurrence of the fetal brain growth spurt hypothesized to fall at 28-32 GW. Second, latent class growth analysis (LCGA) was used to detect subgroups of fetuses who differed from one another in their initial level and/or trajectory of two indices of fetal neurodevelopment (fetal heart rate [FHR] and fetal heart rate standard deviation [FHRSD]). Third, to examine the utility of maternal and fetal risk profile classification, follow-up analyses were completed to test for predictive associations between maternal and atypical fetal groups and infant birth outcomes. Fourth, additional follow-up analyses examined associations between a high-risk maternal subgroup and atypical fetal subgroups, and differences in maternal measures and atypical fetal subgroups. Results: Aim 1: FMM results identified two asymmetrically sized maternal subgroups, including a putative high-risk phenotype comprising 9% of the sample characterized by elevated symptoms of anxiety and depression, high levels of negative and positive emotions and emotion reactivity, significant difficulties with emotion dysregulation, and poor coping abilities. Analyses to examine the utility of the FMM classification groups showed maternal subgroups differed significantly on a withheld measure frequently used to index prenatal distress (PSS). Additional analyses comparing the FMM classification groups to a “single-instrument, single-threshold” approach to identification of risk suggested significant overlap between women identified as high-risk by the FMM would likely also be identified as high-risk via use of a cutoff score on the CESD-R, but not the STAI. Aim 2: LCGA of FHR identified three asymmetrically sized fetal groups, including putative high- and moderate-risk groups that together comprised 26% (n=29) of the sample and were characterized by atypically high and low intercept coupled with flat slope across gestation. LCGA of FHRSD identified two asymmetrically sized fetal groups, including an “accelerated development” group comprising 15% (n=16) of the sample characterized by high intercept and steeper slope across gestation. Approximately 34% of fetuses were identified as exhibiting an atypical trajectory in one or both of the fetal indices. Aim 3: Fetuses in a combined “atypical” fetal subgroup (i.e., fetuses identified as having an atypical neurodevelopmental trajectory via FHR, FHRSD, or both indices) showed a ratio of high-risk women to low-risk women that was twice as high (13.5%) relative to the typical fetal subgroup (7%). However this proportion was not statistically significant (χ2 (1, N = 108) = .27, p = .31). Women in the high-risk group were more likely to have infants who were shorter at birth (F (1, 105) = 4.57, p = .03), although this significant difference did not survive correction for multiple comparisons. There were no other statistically significant differences in infant birth outcomes (gestational age at delivery, birthweight, ponderal index) based on maternal or fetal risk groups. Fetuses within the high-risk maternal subgroup did not show any significant differences in average FHR or FHRSD at any of the session time points (20-24, 25-29, 30-34, 35-39 gestational weeks). FHR and FHRSD subgroups differed significantly on multiple maternal measures of distress, mood, pregnancy symptoms, and transdiagnostic vulnerability and protective factors, including those indexing emotion reactivity, emotion regulation, and coping. Although fetal subgroups differed significantly on maternal measures at both session 1 (8-16 gestational weeks) and session 2 (20-24 gestational weeks), measures of mood and distress sampled at session 2 were more often associated with fetal subgroups than measures at session 1. Conclusions: This study used a data-driven approach to identify and characterize 2 maternal subgroups, and 5 fetal subgroups. A putative maternal high-risk group was characterized by elevated levels of distress, pregnancy symptoms, symptoms of psychopathology, high emotion reactivity in both negative and positive emotion, and poor emotion regulation and coping abilities. Maternal and fetal subgroups did not completely overlap, pointing to other important variables contributing to fetal neurodevelopment (genetics, nutrition). Following correction for multiple comparisons, there were no significant differences in infant birth outcomes based on maternal or fetal subgroup classification. Fetal groups were associated with differences in mean scores on maternal measures at session 1 and session 2, with more significant associations observed between fetal subgroups and maternal self-report at session 2 (20-24 gestational weeks). However, differences between fetal subgroups in FHR and FHRSD intercept values suggest alterations to neurodevelopmental trajectories associated with maternal distress phenotypes are already observable by 20 weeks, suggesting transmission of risk begins earlier in gestation. Although replication and extension of these results into the postnatal period is needed to contextualize, interpret, and strengthen the validation of fetal subgroups, findings suggest that data-driven and person-centered approaches hold promise for future efforts aimed toward early identification of at-risk maternal and fetal phenotypes associated with prenatal distress.


University of Minnesota Ph.D. dissertation. November 2021. Major: Child Psychology. Advisors: Megan Gunnar, Jed Elison. 1 computer file (PDF); x, 117 pages.

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Doyle, Colleen. (2021). Prenatal influences on fetal neurodevelopment: Can a person-centered approach help parse the complexity of maternal vulnerability and protective features and detect early alterations to fetal neurodevelopment trajectories related to prenatal distress?. Retrieved from the University Digital Conservancy,

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