Testing a cascade model linking prenatal inflammation to child executive function

Camerota, Marie; Wylie, Amanda; Goldblum, Jessica; Wideman, Laurie; Cheatham, Carol L.; Propper, Cathi B.

doi:10.1016/j.bbr.2022.113959

Cited by 13 publications

(9 citation statements)

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“…The current study results are supported by previous research and add a further dimension, that is, it found that combined effects of lowered child health at birth mediated the negative effects of maternal metabolic syndrome on development. This is consistent with the inflammatory cascade hypothesis that postulates inflammation during pregnancy affecting not only early-life programming, but also subsequently showing negative effects on child development [46].…”

Section: Discussionsupporting

confidence: 90%

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

Kwok

Speyer

Soursou

et al. 2023

BMC Med

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Background There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators. Methods Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age. Results In mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models. Conclusions The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

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Section: Discussionsupporting

confidence: 90%

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

Kwok

Speyer

Soursou

et al. 2023

BMC Med

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“…Future exploration of the trajectory from PNMI to risk for adolescent psychopathology may identify intermediate phenotypes that serve as opportunities for early intervention. Recent studies demonstrate that sequelae related to PNMI are evident as early as infancy, including negative affect, heightened stress reactivity, and poor cognitive performance . Replication and expansion of these models using current cohorts, psychological assessments, and comprehensive demographic and early life adversity data could be used to inform a cascade model of adolescent affective disorders via other behavioral changes across the lifespan, beginning in utero .…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Lipner,

Mac Giollabhui,

Breen

et al. 2024

JAMA Psychiatry

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ImportancePrenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined.ObjectiveTo determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations.Design, Setting, and ParticipantsThis was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023.ExposuresLevels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy.Main Outcomes and MeasuresSelf-reported depressive symptoms at adolescent follow-up.ResultsA total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75).Conclusions and RelevanceIn this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

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“…High levels of IL-8 can lead to systemic inflammation which may disrupt the normal trafficking of neuronal processes, the formation of appropriate synaptic contacts and neural plasticity [ 4 , 6 , 13 , 36 ]. Accordingly, several studies have linked increased maternal inflammatory cytokines to increased risk of serious conditions including cerebral palsy, autism, schizophrenia, intellectual disability, depression and psychosis among offspring [ 1 , 4 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, to our knowledge this is the first study to specifically link prenatal IL-8 to fine motor and problem-solving skills in early childhood.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have linked prenatal measures of inflammatory biomarkers with adverse neurodevelopmental outcomes in offspring including cognitive ability [ 9 ], neurodevelopmental delay [ 1 ], psychomotor development [ 10 ], autism [ 11 , 12 , 13 , 14 , 15 ], neurologic abnormalities [ 4 ], depression [ 16 ], psychosis [ 17 ] and schizophrenia [ 6 ]. Although directions of effect have not always been consistent across these studies, there is a strong biological rationale for the involvement of the dysregulation of maternal immune function and maternal inflammatory biomarkers in childhood neurodevelopment [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

Kelly

Lee-Sarwar

Chen

et al. 2022

IJMS

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Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother–child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10–18 wks) and late (32–38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (β: −0.919, 95%CI: −1.425, −0.414, p = 3.9 × 10−4) and problem-solving skills at age two (β: −1.221, 95%CI: −1.904, −0.414, p = 4.9 × 10−4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women.

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Testing a cascade model linking prenatal inflammation to child executive function

Cited by 13 publications

References 50 publications

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

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