Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study.

BACKGROUND: Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth. METHODS: This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks' gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy. RESULTS: 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02). CONCLUSION: Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

The impact of COVID-19 on psychiatric clinical encounters among low-income racially-diverse children.

BACKGROUND: There is a lack of longitudinal data to examine the impact of COVID-19 on all types of clinical encounters among United States, underrepresented BIPOC (Black, Indigenous, and people of color), children. This study aims to examine the changes in all the outpatient clinical encounters during the pandemic compared to the baseline, with particular attention to psychiatric encounters and diagnoses. METHOD: This study analyzed 3-year (January 2019 to December 2021) longitudinal clinical encounter data from 3,394 children in the Boston Birth Cohort, a US urban, predominantly low-income, Black and Hispanic children. Outcomes of interest were completed outpatient clinical encounters and their modalities (telemedicine vs. in person), including psychiatric care and diagnoses, primary care, emergency department (ED), and developmental and behavioral pediatrics (DBP). RESULTS: The study children's mean (SD) age is 13.9 (4.0) years. Compared to 2019, psychiatric encounters increased by 38% in 2020, most notably for diagnoses of adjustment disorders, depression, and post-traumatic stress disorders (PTSD). In contrast, primary care encounters decreased by 33%, ED encounters decreased by 55%, and DBP care decreased by 16% in 2020. Telemedicine was utilized the most for psychiatric and DBP encounters and the least for primary care encounters in 2020. A remarkable change in 2021 was the return of primary care encounters to the 2019 level, but psychiatric encounters fluctuated with spikes in COVID-19 case numbers. CONCLUSIONS: Among this sample of US BIPOC children, compared to the 2019 baseline, psychiatric encounters increased by 38% during 2020, most notably for the new diagnoses of adjustment disorder, depression, and PTSD. The 2021 data showed a full recovery of primary care encounters to the baseline level but psychiatric encounters remained sensitive to the pandemic spikes. The long-term impact of the pandemic on children's mental health warrants further investigation.

Posttraumatic Stress Symptoms and the Quality of Maternal-Child Interactions in Mothers of Preterm Infants.

OBJECTIVE: The purpose of this study was to examine associations between maternal trauma exposure, posttraumatic stress symptoms, and directly observed maternal-child interactions among a diverse cohort of mother-preterm infant dyads at 12-month corrected age. METHODS: We conducted a retrospective cohort study. Maternal trauma exposure and posttraumatic stress symptoms were measured using the Modified Posttraumatic Stress Disorder Symptom Scale at baseline and 6 and 12 months. The primary outcome was directly observed maternal-child interactions at 12-month corrected age using the Coding Interactive Behavior Manual. We used linear regression models to estimate the associations between trauma exposure, posttraumatic stress symptoms (and symptom clusters), and observer-rated maternal-child interactions. RESULTS: Among the 236 participants, 89 (37.7%) self-reported as Black and 98 (41.5%) as Latina; mean gestational age of the infants was 31.6 weeks (SD 2.6). Mothers with posttraumatic stress symptoms demonstrated greater maternal sensitivity (ß = 0.32; 95% confidence interval [CI], 0.06-0.58; standardized effect size = 0.39) and greater dyadic reciprocity (ß = 0.39; 95% CI, 0.04-0.73; standardized effect size = 0.36) compared with those not exposed to trauma; however, we did not observe significant differences between trauma-exposed but asymptomatic women and those not exposed to trauma. Across symptom clusters, differences in maternal sensitivity and dyadic reciprocity were most pronounced for mothers with avoidance and re-experiencing symptoms, but not hyperarousal symptoms. CONCLUSION: Maternal posttraumatic stress symptoms seem to be associated with the quality of maternal-child interactions at age 1 year among a cohort of urban, mother-preterm infant dyads. These findings have implications for strength-based intervention development.

Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism.

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs). In both samples, predicted pathogenic (PP) heteroplasmies in children are associated with ASD risk (Meta-OR = 1.56, P = 0.00068). Inter-generational transmission of mtDNA reveals attenuated effects of purifying selection on maternal heteroplasmies in children with ASD relative to controls, particularly among males. Among children with ASD and PP heteroplasmies, increased mtDNA content shows benefits for cognition, communication, and behaviors (P ≤ 0.02). These results underscore the value of exploring maternal and newborn mtDNA in ASD.

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder.

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.

Small Moments, Big Impact: Pilot Trial of a Relational Health App for Primary Care.

OBJECTIVE: To conduct a pilot trial of Small Moments, Big Impact: a relational health app. METHODS: Low-income mothers with 1 or no prior children, a full-term birth, above 18 years old, and without substance abuse were recruited. The control group was recruited prior to the intervention group to avoid contamination. Of the 117 mothers enrolled, 29 intervention and 29 control mothers completed the study. Five questionnaires were administered at baseline and 6-months to measure maternal depression, empathy, beliefs about children's emotions, intelligence mindsets, and app use. At 6 months, questionnaires assessing parenting stress, reflective functioning, and perceived value of app were also administered. RESULTS: Mothers in the final sample were similar to those who did not complete the study, except more mothers who dropped out were recruited during COVID-19 and had a lower empathetic subscale score. No differences were found between groups at pre- or post-test. However, because of skewed outcome variables which violated normality principles and the small sample size, quantile regression analyses were performed comparing the 25th, 50th, and 75th percentiles for each outcome. Controlling for pretest and potential confounders, subsets of SMBI mothers reported lower parental stress, more growth mindset and increased effort to understand their child's feelings. Ninety percent of mothers reported using SMBI at least once per week. Eighty percent of mothers would recommend the SMBI app to new mothers. CONCLUSIONS: Most mothers used SMBI weekly, rated it highly and reported less stress, more growth mindset, and more positive child rearing beliefs.

Effects of Stress and Nativity on Maternal Antenatal Substance Use and Postnatal Mental Disorders.

Background: Maternal substance use and common mental disorders (CMDs) during or after pregnancy can lead to negative health outcomes among mothers and infants. We examined whether nativity (US-born versus foreign-born) and stress levels during pregnancy were associated with antenatal substance use and postnatal CMDs. Methods: We analyzed the Boston Birth Cohort, a racially diverse cohort recruited at birth with rolling enrollment since 1998. Information on antenatal substance use (tobacco and/or alcohol use) was obtained using an in-person postpartum questionnaire (n = 6,514). Information on postnatal CMDs (depression and/or anxiety) was obtained from medical records (n = 2,052). Nativity and stress during pregnancy were self-reported. We performed multivariate logistic regression to examine how nativity and stress levels were jointly associated with antenatal substance use and postnatal CMDs. We further investigated if blacks, Hispanics, and whites were differentially at risk. Results: We found that US-born mothers were at higher risk of substance use and CMDs than their foreign-born counterparts. In analyses combining nativity and stress, being US-born with high stress was associated with increased odds of antenatal substance use (adjusted odds ratio [aOR] = 14.91, 95% confidence interval [CI]: 12.09-18.39) and postnatal CMDs (aOR = 4.09, 95% CI: 2.72-6.15) compared with foreign-born mothers with low stress. The results of the subanalyses limited to black and Hispanic women separately were similar; high stress alone was associated with fourfold increased odds of CMDs among foreign-born Hispanic mothers (aOR = 4.27, 95% CI: 1.96-9.33). Conclusions: Findings suggest that identifying and alleviating high stress among pregnant women may reduce their risk of antenatal substance use and postnatal CMDs.

Maternal Stress and Early Neurodevelopment: Exploring the Protective Role of Maternal Growth Mindset.

OBJECTIVE: The purpose of this study was to test associations between maternal stress, maternal mindset, and infant neurodevelopment at 12 months of age. Specifically, we sought to examine the extent to which maternal growth mindsets may serve to attenuate the negative associations between maternal stress and infants' neurodevelopment. METHODS: The current exploratory study leverages data from a longitudinal cohort study following mother-infant dyads. Maternal-perceived stress, maternal mindset, and infant electroencephalography (EEG) recordings were collected when infants were 12 months of age. The final analytic sample included 33 dyads. RESULTS: Results revealed no statistically significant main effects of maternal stress or maternal mindset for any of the infant EEG frequency band outcomes. After including interactions between maternal stress and mindset, statistically significant positive interactions were detected for all EEG frequency bands. Simple slope tests revealed significant negative associations between maternal stress and each of the 6 EEG frequency bands for mothers with more fixed-oriented mindsets. Associations between maternal stress and infant EEG outcomes for mothers with more growth-oriented mindsets did not differ from 0. CONCLUSION: These findings suggest that infants raised by mothers with growth mindsets may be protected against the neurodevelopmental consequences of higher maternal stress.

Anti-Poverty Medicine Through Medical-Financial Partnerships: A New Approach to Child Poverty.

Poverty threatens child health. In the United States, financial strain, which encompasses income and asset poverty, is common with many complex etiologies. Even relatively successful antipoverty programs and policies fall short of serving all families in need, endangering health. We describe a new approach to address this pervasive health problem: antipoverty medicine. Historically, medicine has viewed poverty as a social problem outside of its scope. Increasingly, health care has addressed poverty's downstream effects, such as food and housing insecurity. However, strong evidence now shows that poverty affects biology, and thus, merits treatment as a medical problem. A new approach uses Medical-Financial Partnerships (MFPs), in which healthcare systems and financial service organizations collaborate to improve health by reducing family financial strain. MFPs help families grow assets by increasing savings, decreasing debt, and improving credit and economic opportunity while building a solid foundation for lifelong financial, physical, and mental health. We review evidence-based approaches to poverty alleviation, including conditional and unconditional cash transfers, savings vehicles, debt relief, credit repair, financial coaching, and employment assistance. We describe current national MFPs and highlight different applications of these evidence-based clinical financial interventions. Current MFP models reveal implementation opportunities and challenges, including time and space constraints, time-sensitive processes, lack of familiarity among patients and communities served, and sustainability in traditional medical settings. We conclude that pediatric health care practices can intervene upon poverty and should consider embracing antipoverty medicine as an essential part of the future of pediatric care.

Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways.

Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother-child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, p < 0.001), serine (R = 0.30, p < 0.001), glycine (R = 0.34, p < 0.001), and glutamate (R = 0.16, p < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, p = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, p = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted.

A prospective cohort study on the intersectionality of obesity, chronic disease, social factors, and incident risk of COVID-19 in US low-income minority middle-age mothers.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has disproportionally affected communities of color. We aimed to determine what factors are associated with COVID-19 testing and test positivity in an underrepresented, understudied, and underreported (U3) population of mothers. METHODS: This study included 2996 middle-aged mothers of the Boston Birth Cohort (a sample of predominantly urban, low-income, Black and Hispanic mothers) who were enrolled shortly after they gave birth and followed onward at the Boston Medical Center. COVID-19 testing and test positivity were defined by the SARS-CoV-2 nucleic acid test. Two-probit Heckman selection models were performed to identify factors associated with test positivity while accounting for potential selection associated with COVID testing. RESULTS: The mean (SD) age of study mothers was 41.9 (±7.7) years. In the sample, 1741 (58.1%) and 667 (22.3%) mothers were self-identified as Black and Hispanic, respectively. A total of 396 mothers had COVID-19 testing and of those, 95 mothers tested positive from March 2020 to February 2021. Among a multitude of factors examined, factors associated with the probability of being tested were obesity (RR = 1.27; 95% confidence interval (CI): 1.08-1.49); and presence of preexisting chronic medical conditions including hypertension, asthma, stroke, and other comorbidities (coronary heart disease, chronic kidney disease, and sickle cell disease) with a corresponding RR = 1.40 (95% CI: 1.23-1.60); 1.29 (95% CI: 1.11-1.50); 1.44 (95% CI: 1.23-1.68); and 1.37 (95% CI: 1.12-1.67), respectively. Factors associated with higher incident risk of a positive COVID-19 test were body mass index, birthplace outside of the USA, and being without a college-level education. CONCLUSIONS: This study demonstrated the intersectionality of obesity and social factors in modulating incident risk of COVID-19 in this sample of US Black and Hispanic middle-aged mothers. Methodologically, our findings underscore the importance of accounting for potential selection bias in COVID-19 testing in order to obtain unbiased estimates of COVID-19 infection.

The Influence of Health Mindset on Perceptions of Illness and Behaviors Among Adolescents.

BACKGROUND: Health mindsets can be viewed on a continuum of malleability from fixed (health cannot be altered) to growth (health can be affected by behavior). We propose that mindsets may influence the health perceptions of healthy adolescents as well as the health behaviors of adolescents with a chronic illness. METHODS: In Study 1, we surveyed healthy adolescents about their health mindsets and their judgments of illness in response to vignettes of fictional others. In Study 2, we measured the health mindsets and health behaviors of adolescents with type 1 diabetes RESULTS: In Study 1, healthy adolescents with a fixed health mindset were more likely to rate fictional others as being less healthy, less likely to recover, and more vulnerable to additional diseases. In Study 2, a growth mindset was associated with a greater frequency of glucose monitoring among younger, but not older, adolescents with type 1 diabetes. Further, growth mindset was associated with lower HbA1c levels for younger adolescents. CONCLUSIONS: Health mindsets may shape views of the implications of illness or injury for overall health and, in adolescents with a chronic condition, may interact with age to influence health behaviors and outcomes.

Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder: a prospective birth cohort study.

BACKGROUND: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. METHODS: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups - ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography-tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. RESULTS: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p = .032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p = .002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. CONCLUSIONS: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions.

Genome-wide association study identifies a novel maternal gene × stress interaction associated with spontaneous preterm birth.

BACKGROUND: Maternal stress is potentially a modifiable risk factor for spontaneous preterm birth (sPTB). However, epidemiologic findings on the maternal stress-sPTB relationship have been inconsistent. METHODS: To investigate whether the maternal stress-sPTB associations may be modified by genetic susceptibility, we performed genome-wide gene × stress interaction analyses in 1490 African-American women from the Boston Birth cohort who delivered term (n = 1033) or preterm (n = 457) infants. Genotyping was performed using Illumina HumanOmni 2.5 array. Replication was performed using data from the NICHD genomic and Proteomic Network (GPN) for PTB research. RESULTS: rs35331017, a T-allele insertion/deletion polymorphism in the protein-tyrosine phosphatase receptor Type D (PTPRD) gene, was the top hit that interacted significantly with maternal lifetime stress on risk of sPTB (PG × E = 4.7 × 10-8). We revealed a dose-responsive association between degree of stress and risk of sPTB in mothers carrying the insertion/insertion genotype, but an inverse association was observed in mothers carrying the heterozygous or deletion/deletion genotypes. This interaction was replicated in African-American (PG × E = 0.088) and Caucasian mothers (PG × E = 0.023) from the GPN study. CONCLUSION: We demonstrated a significant maternal PTPRD × stress interaction on sPTB risk. This finding, if further confirmed, may provide new insight into individual susceptibility to stress-induced sPTB. IMPACT: This was the first preterm study to demonstrate a significant genome-wide gene-stress interaction in African Americans, specifically, PTPRD gene variants can interact with maternal perceived stress to affect risk of spontaneous preterm birth. The PTPRD × maternal stress interaction was demonstrated in African Americans and replicated in both African Americans and Caucasians from the GPN study. Our findings highlight the importance of considering genetic susceptibility in assessing the role of maternal stress on spontaneous preterm birth.

Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health.

BACKGROUND: Preeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. METHODS: This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. RESULTS: A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. CONCLUSION: In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.