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Cited by 0Birth, Development, and HealthGestational Diabetes Research and ManagementPregnancy and preeclampsia studies

Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures

Open access
Panteris, Eleftherios, Kakatsaki, Ioanna, Koukou, Zoi, Kolvatzis, Charalambos, Papanikolaou, Styliani, Hatzidaki, Eleftheria·2026·Pathophysiology
DOI 10.3390/pathophysiology33030067PMC PMC13609975
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Abstract

Non-communicable diseases remain the dominant cause of adult morbidity and mortality, yet cardiometabolic, vascular and renal risk may originate before birth. This structured narrative review critically evaluates human evidence linking pregnancy-related exposures, placental pathophysiology and later offspring health within a maternal–placental–fetal–life-course framework. Evidence published from 2020 to 2026 was emphasised, while seminal earlier cohorts were retained when they provided uniquely long follow-up or direct placental measurements. The most consistent associations concern maternal obesity, gestational diabetes, excessive gestational weight gain and hypertensive disorders, which are linked with higher offspring blood pressure, greater adiposity and adverse glucose–insulin profiles. Human placental studies implicate vascular malperfusion, altered nutrient transport, inflammatory and oxidative signalling, endocrine function and epigenetic regulation. Few studies, however, have measured the prenatal exposure, a specific placental phenotype and a long-term offspring outcome within the same longitudinal design; most proposed placental pathways are supported by convergent evidence or biological plausibility rather than demonstrated mediation. Preterm birth and fetal growth restriction are clinically observable, etiologically heterogeneous sentinel phenotypes, not obligatory mediators. Placental and offspring epigenetic signatures, telomere biology and mitochondrial function represent distinct domains of biological embedding; their causal and prognostic significance remains uncertain. Longitudinal studies integrating maternal exposures, placental histopathology and molecular phenotypes, fetal organ development, childhood cardiometabolic trajectories and adult clinical outcomes are needed to determine whether, and under what circumstances, the placenta plays an intermediary role rather than merely serving as a marker of an adverse pregnancy environment.

AI snapshot

Written from the paper’s full text.

TL;DR

This structured narrative review evaluates human evidence linking pregnancy exposures, placental pathophysiology, and later offspring cardiometabolic risk within a maternal–placental–fetal–life-course framework. It finds the most consistent associations for maternal obesity, gestational diabetes, excessive gestational weight gain, and hypertensive disorders with higher offspring blood pressure, greater adiposity, and adverse glucose–insulin profiles, but few studies demonstrate placental mediation within the same longitudinal design.

Key findings

  • Maternal obesity, gestational diabetes/hyperglycaemia, excessive gestational weight gain, and hypertensive disorders are consistently associated with higher offspring blood pressure, adiposity, and adverse glucose–insulin traits. Examples include a 2025 meta-analysis reporting a mean offspring systolic blood pressure difference of 2.44 mmHg (95% CI 2.03–2.85) after hypertensive disorders of pregnancy, and an adult meta-analysis reporting systolic blood pressure differences of 3.40 mmHg (95% CI 2.44–4.37), diastolic differences of 2.19 mmHg, and higher odds of hypertension (OR 1.50, 95% CI 1.18–1.91).
  • Placental correlates are reported but rarely shown to mediate later outcomes. A meta-analysis of 10 cohorts comprising 2631 mother–infant pairs identified 27 placental CpG sites associated with maternal prepregnancy BMI, with DNA methylation differences up to 2.0% per 10-unit increase in prepregnancy BMI; a GDM-specific meta-analysis found higher odds of delayed villous maturation (OR 6.37, 95% CI 3.28–12.37), and placental villous and vascular lesions are reported four to seven times more often in preeclampsia than in normotensive pregnancies.
  • Some same-cohort studies provide more integrated evidence: placental weight statistically attenuated associations of gestational diabetes, excessive gestational weight gain, and prepregnancy BMI with childhood BMI by 52%, 25%, and 17%, respectively; greater second-trimester placental volume was associated with lower childhood systolic blood pressure. However, placental size and weight are crude proxies, and attenuation or prediction does not establish causal mediation.
  • Prenatal stress and preterm birth show long-term associations: in a Danish cohort of more than 2.6 million births followed up to 40 years, prenatal maternal bereavement was associated with CVD (HR 1.13, 95% CI 1.06–1.20), heart disease (HR 1.24, 95% CI 1.11–1.38), and hypertension (HR 1.27, 95% CI 1.01–1.60); prenatal stress was associated with higher offspring BMI (SMD 0.27, 95% CI 0.19–0.35). Preterm birth is linked to adult hypertension, heart failure, stroke, diabetes, and chronic kidney disease, but it is described as a clinically observable sentinel phenotype, not an obligatory mediator.

Methods

  • Structured narrative review using iterative, section-specific searches; PubMed/MEDLINE was the primary database, supplemented by Scopus. Evidence published from 1 January 2020 to 9 August 2026 was prioritised, while seminal earlier studies were retained when they provided uniquely long follow-up or direct placental measurements.
  • No PRISMA flow diagram, formal risk-of-bias assessment, or meta-analysis was undertaken. Evidence was classified into four interpretive categories: integrated longitudinal human evidence, convergent human evidence, exposure–outcome association, and biological plausibility.
  • Eligibility included systematic reviews and meta-analyses, population-based cohorts and register studies, pregnancy studies measuring maternal exposure plus a placental phenotype, longitudinal offspring studies, and same-cohort studies assessing at least two stages of the proposed pathway. Animal-only studies and reports limited to acute neonatal outcomes without relevant placental measurements were excluded.

Limitations

  • The paper states that exposure timing, biological matrices, placental sampling, histopathological definitions, and mixture methods differ widely; outcomes range from birth biomarkers to adult clinical events; molecular estimates depend on tissue, cell composition, assay platform, and algorithm; residual genetic, socioeconomic, behavioural, and familial confounding remains possible; differential loss to follow-up may select healthier participants; and many molecular studies are small and imprecise, increasing susceptibility to selective reporting and publication bias.
  • As a structured narrative review, it did not use a single deduplicated screening set, formal study-level risk-of-bias scoring, or certainty grading; evidence-strength categories were interpretive rather than equivalent to GRADE or a systematic-review framework.
  • The text makes evident that most proposed placental pathways are supported by convergent evidence or biological plausibility rather than demonstrated mediation, and few studies have measured the prenatal exposure, a specific placental phenotype, and a long-term offspring outcome within the same longitudinal design.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/pathophysiology33030067

Cites

143 of 143 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

59 of 103 cited sources checked · 31 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A meta-analysis of 10 cohorts comprising 2631 mother-infant pairs identified 27 placental CpG sites associated with maternal prepregnancy BMI, with DNA methylation differences of up to 2.0% per 10-unit increase in prepregnancy BMI.

    “A meta-analysis of 10 cohorts comprising 2631 mother–infant pairs identified 27 placental CpG sites associated with maternal prepregnancy body mass index (BMI), with DNA methylation differences of up to 2.0% per 10-unit increase in prepregnancy BMI [30].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [30] Fore, 2022, A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health, Commun. Biol. source
  • Premisecitation

    Higher average PM2.5 and NO2 exposure from pregnancy through age 18 is associated with higher peripheral and central diastolic blood pressure at age 18.

    “Direct adult-adjacent evidence is now available from a UK birth cohort that characterised air pollution exposure from pregnancy through age 18 and assessed cardiovascular markers at age 18, reporting that higher average PM2.5 and nitrogen dioxide (NO2) across this period were associated with higher peripheral and central diastolic BP.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [84] Tilling, 2025, Lifetime air pollution exposure from prenatal to 18 years and cardiovascular health in young adulthood: Findings from a UK birth cohort, Environ. Int. source
  • Interpretationcitation

    Exposure-associated differences in blood pressure persist at the transition to adult care.

    “this design strengthens the adult-health narrative by demonstrating that exposure-associated differences in BP persist at the transition to adult care [84].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [84] Tilling, 2025, Lifetime air pollution exposure from prenatal to 18 years and cardiovascular health in young adulthood: Findings from a UK birth cohort, Environ. Int. source

      The Abstract Results report associations between higher lifetime air-pollution exposure and higher diastolic blood pressure, and Methods > Cardiovascular health markers says blood pressure was measured at age 18 (no page numbers provided). The paper supports exposure-associated differences at that age, but a single age-18 assessment does not establish that blood-pressure differences persisted from earlier ages or assess a transition to adult care. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    Transplacental transfer of endocrine-disrupting compounds, including parabens and triclosan, has been demonstrated, confirming measurable fetal chemical burden during critical developmental windows of pregnancy.

    “Complementary biomonitoring investigations have demonstrated transplacental transfer of endocrine-disrupting compounds, including parabens and triclosan, confirming measurable fetal chemical burden during critical developmental windows of pregnancy [78].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [78] Karzi, 2021, Determination of prenatal exposure to parabens and triclosan and estimation of maternal and fetal burden, Toxicol. Rep. source
  • Premisecitation

    Higher maternal consumption of ultra-processed foods is associated with higher risk of offspring overweight or obesity through adolescence in three US prospective cohorts.

    “Across three US prospective cohorts, the Nurses’ Health Study II (NHSII) and the Growing Up Today Study (GUTS I and II) in the United States, higher maternal consumption of ultra-processed foods was associated with higher risk of offspring overweight or obesity through adolescence.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [95] Wang, 2022, Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: Results from three prospective cohort studies, BMJ source
    • Rests on an assumption: Maternal diet and the built environment shape fetal nutrient supply and maternal metabolic status.
  • May combine two claims. 63
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Interpretationcitation

    Because the exposure period in the ultra-processed food analysis was not limited to pregnancy and peripregnancy analyses were limited, the findings are better viewed as reflecting broader family dietary patterns and the link between pregnancy diet and the child's later food environment.

    “However, because the exposure period was not limited to pregnancy and analyses around the peripregnancy period were limited, these findings are better viewed as reflecting broader family dietary patterns and the link between pregnancy diet and the child’s later food environment [95].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [95] Wang, 2022, Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: Results from three prospective cohort studies, BMJ source

  • May combine two claims.

    Premisecitation

    Pregnancy-period environmental and dietary exposures are shaped by geography, occupation, housing, and socioeconomic position, and often co-occur with psychosocial stress and constrained access to health-promoting resources.

    “Pregnancy-period environmental and dietary exposures are shaped by geography, occupation, housing, and socioeconomic position, and they often co-occur with psychosocial stress and constrained access to health-promoting resources [71,72,73,74].”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [71] Zanini, 2020, Urban-Related Environmental Exposures during Pregnancy and Placental Development and Preeclampsia: A Review, Curr. Hypertens. Rep. source
    • cites [72] Sum, 2022, The socioeconomic landscape of the exposome during pregnancy, Environ. Int. source
    • cites [73] Eick, 2025, Psychosocial stressors as modifiers of the associations between well-studied and understudied chemicals and birth outcomes in the ECHO Cohort, Environ. Pollut. source

      The Introduction (page not supplied) says chemical exposures vary by sociodemographic group and describes evidence that environmental toxicants co-occur with psychosocial stress. The Methods > Covariates section mentions differences in diets and chemical exposure sources. Neither passage establishes the claimed roles of geography, occupation, or housing, or co-occurrence with constrained access to health-promoting resources. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [74] Kalligiannaki, A., Baliou, S., Vakonaki, E., Panteris, E., Hatzidaki, E., and Tzatzarakis, M.N. (2026). Dynamics of Endocrine Disruptor Exposure in Early Life: A Mother–Infant Hair Biomonitoring Study. Toxics, 14. source

      The Discussion links differences in pregnancy BPS exposure to occupation, and Results §3.3 identifies household water and plumbing as potential exposure sources. The Introduction also identifies diet as an exposure pathway. The paper does not establish that geography or socioeconomic position shapes these exposures, or that they often co-occur with psychosocial stress and constrained access to health-promoting resources. Page numbers are unavailable in our copy. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    The most consistent evidence base for pregnancy environmental exposures and later cardiometabolic risk relates to ambient air pollution, persistent pollutants such as PFAS, and selected EDCs, with diet and built-environment features as modifiers and correlated determinants.

    “The most consistent evidence base relates to ambient air pollution, persistent pollutants such as per- and polyfluoroalkyl substances (PFAS), and selected endocrine-disrupting chemicals (EDCs), with diet and built-environment features functioning as modifiers and correlated determinants of risk across the life course [75,76,77].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [75] Padmanabhan, 2021, Praegnatio Perturbatio—Impact of Endocrine-Disrupting Chemicals, Endocr. Rev. source
    • cites [76] Syama, 2025, Maternal mechanisms in air pollution exposure-related adverse pregnancy outcomes: A systematic review, Sci. Total Environ. source
    • cites [77] Ma, 2025, Endocrine-disrupting chemicals exposure: Cardiometabolic health risk in humans, Cardiovasc. Diabetol. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Prenatal and early-life PFAS exposure is associated with overweight/obesity in children older than 3 years, with effects varying by specific compound and sex.

    “For PFAS, a systematic review and meta-analysis reported associations between prenatal and early-life PFAS exposure and overweight/obesity in children older than 3 years, with effects varying by specific compound and sex.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [90] Frigerio, 2023, Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: A systematic review with meta-analyses, Environ. Health source

  • May combine two claims.

    Premisecitation

    Prenatal DEHP exposure has a significant inverse association with offspring BMI z-score, while no association is observed with body fat percentage.

    “A meta-analysis reported a significant inverse association between prenatal di(2-ethylhexyl) phthalate (DEHP) exposure and offspring BMI z-score, while no association was observed with body fat percentage.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [94] Lee, 2022, Prenatal exposure to phthalate and decreased body mass index of children: A systematic review and meta-analysis, Sci. Rep. source

  • May combine two claims.

    Premisecitation

    Persistent pollutants are important in developmental origins research because exposure often begins in utero, and several compounds can disrupt endocrine and metabolic regulation during critical developmental windows.

    “Persistent pollutants are important in developmental origins research because exposure often begins in utero, and several compounds can disrupt endocrine and metabolic regulation during critical developmental windows [88,89].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [88] Valvi, 2021, Prenatal exposure to persistent organic pollutants and markers of obesity and cardiometabolic risk in Spanish adolescents, Environ. Int. source
    • cites [89] Koshko, L., Scofield, S., Mor, G., and Sadagurski, M. (2022). Prenatal Pollutant Exposures and Hypothalamic Development: Early Life Disruption of Metabolic Programming. Front. Endocrinol., 13. source

      The Mechanisms section (page unavailable) identifies several pollutants that cross the placenta and discusses developmental effects on the hypothalamus and neuroendocrine system. The Conclusion and Future Perspectives section (page unavailable) links prenatal exposure to later metabolic impairment, but says the direct effect on hypothalamic development remains unclear. The paper does not establish that exposure to persistent pollutants often begins in utero or that several specific compounds directly disrupt endocrine and metabolic regulation. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Greater greenspace exposure is associated with lower odds of hypertension, obesity, and diabetes in a large meta-analysis.

    “For the built environment, a large meta-analysis reported that greater greenspace exposure is associated with lower odds of hypertension, obesity, and diabetes, but pregnancy-specific exposure definitions were not consistent, and the evidence should be positioned as contextual support rather than direct proof of effects limited to pregnancy [96].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [96] Sharifi, Y., Sobhani, S., Ramezanghorbani, N., Payab, M., Ghoreshi, B., Djalalinia, S., Ghonbalani, Z.N., Ebrahimpur, M., Eslami, M., and Qorbani, M. (2024). Association of greenspaces exposure with cardiometabolic risk factors: A systematic review and meta-analysis. BMC Cardiovasc. Disord., 24. source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    Pregnancy-specific greenspace exposure definitions were not consistent, so the evidence should be positioned as contextual support rather than direct proof of effects limited to pregnancy.

    “For the built environment, a large meta-analysis reported that greater greenspace exposure is associated with lower odds of hypertension, obesity, and diabetes, but pregnancy-specific exposure definitions were not consistent, and the evidence should be positioned as contextual support rather than direct proof of effects limited to pregnancy [96].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [96] Sharifi, Y., Sobhani, S., Ramezanghorbani, N., Payab, M., Ghoreshi, B., Djalalinia, S., Ghonbalani, Z.N., Ebrahimpur, M., Eslami, M., and Qorbani, M. (2024). Association of greenspaces exposure with cardiometabolic risk factors: A systematic review and meta-analysis. BMC Cardiovasc. Disord., 24. source

      The Discussion (Limitations and strengths; page not provided) says exposure definitions and measurements varied substantially across the included studies, and that only one blood-pressure study involved pregnant women. This supports treating the review as contextual rather than direct proof of pregnancy-specific effects, but it does not establish that exposure definitions were inconsistent specifically among pregnancy studies. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Adults born preterm have higher risks of stroke; within-family estimates are attenuated but remain above the null, suggesting that pregnancy-related factors contribute to risk beyond shared familial influences.

    “In a national cohort using a co-sibling design, adults born preterm had higher risks of stroke; although within-family estimates were attenuated, they remained above the null, suggesting that pregnancy-related factors contribute to risk beyond shared familial influences [104].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [104] Crump, 2021, Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study, Stroke source

  • May combine two claims.

    Premisecitation

    Telomere length reflects chromosome-end maintenance and accumulated cellular stress; mitochondrial DNA abundance or integrity reflects aspects of mitochondrial biology; and DNA methylation signatures capture tissue-, cell- and algorithm-specific epigenetic variation.

    “Telomere length reflects chromosome-end maintenance and accumulated cellular stress; mitochondrial DNA (mtDNA) abundance or integrity reflects aspects of mitochondrial biology; and DNA methylation signatures capture tissue-, cell- and algorithm-specific epigenetic variation [119,120].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [119] Nawrot, 2018, Telomere Length as Cardiovascular Aging Biomarker, J. Am. Coll. Cardiol. source
    • cites [120] Lynch, 2023, Evaluating genomic signatures of aging in brain tissue as it relates to Alzheimer’s disease, Sci. Rep. source

      Split into 3 atoms — 1 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Preterm birth is associated with higher blood pressure, altered vascular development, and distinct cardiac structure and function in adulthood.

    “Preterm birth has been associated with higher BP, altered vascular development, and distinct cardiac structure and function in adulthood, providing a coherent clinical narrative linking early delivery to later cardiovascular vulnerability [105].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [105] Lewandowski, 2020, Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk, Hypertension source

  • May combine two claims.

    Premisecitation

    Young adults born preterm have higher diabetes risk, with evidence of a gestational-age gradient.

    “A Swedish cohort study reported higher diabetes risk in young adults born preterm, with evidence of a gestational-age gradient, suggesting that early delivery may contribute to long-term metabolic vulnerability that may be evident by early adulthood [110].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [110] Crump, 2011, Risk of Diabetes Among Young Adults Born Preterm in Sweden, Diabetes Care source

      The Results report higher odds of diabetes medication prescription among young Swedish adults born preterm than among those born full term. They do not establish a consistent gestational-age gradient: odds were highest for the extremely preterm group but imprecise, and the authors report little difference between the 29–34- and 35–36-week groups. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Maternal-neonatal correlations in telomere length support an intrauterine and inherited component, but none of these measures is a clinical outcome or a validated individual predictor of adult cardiometabolic disease.

    “Maternal–neonatal correlations in telomere length support an intrauterine and inherited component, but none of these measures is a clinical outcome or a validated individual predictor of adult cardiometabolic disease [121].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [121] Vakonaki, 2025, Correlation of telomere length between full and preterm neonates and their mothers, Exp. Ther. Med. source

      The Discussion (page not provided) reports a weak-to-moderate, statistically significant correlation between maternal and neonatal telomere length; the Introduction describes telomere length as partly inherited and potentially influenced by intrauterine conditions. The study measured telomere length rather than adult clinical outcomes, but it does not assess whether these measures are validated individual predictors of adult cardiometabolic disease. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Reduced nephron endowment and altered renal development link preterm birth to later hypertension and cardiometabolic risk.

    “In another national cohort, preterm birth was associated with an increased risk of chronic kidney disease from childhood through mid-adulthood, supporting the link between reduced nephron endowment, altered renal development and later hypertension and cardiometabolic risk [111].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [111] Crump, 2019, Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: National cohort study, BMJ source

      The Introduction and Discussion say preterm birth interrupts kidney development, reduces nephron endowment, and may contribute to later hypertension. The Discussion also reports increased CKD risk from childhood into mid-adulthood in the national cohort. The proposed mechanism is not established by this cohort, and the paper does not substantiate the claim about later cardiometabolic risk. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Preterm birth and FGR are clinically observable sentinel phenotypes that may reflect several adverse maternal-placental-fetal pathways and are themselves associated with long-term cardiometabolic risk.

    “Preterm birth and FGR are clinically observable sentinel phenotypes that may reflect several adverse maternal–placental–fetal pathways and are themselves associated with long-term cardiometabolic risk [97,98,99,100,101].”
    Quote in the paperSubstantial claim4 of 5 sources checked
    • cites [97] Ahmed, 2024, Short-Term and Long-Term Mortality Risk After Preterm Birth, JAMA Netw. Open source

      The Discussion (page unavailable) associates preterm birth with later adiposity, cardiometabolic complications, diabetes, heart disease, and hypertension. It does not establish the same long-term risk for fetal growth restriction (FGR) or characterize preterm birth and FGR together as sentinel phenotypes reflecting maternal–placental–fetal pathways. Its discussion of fetal growth concerns how it contributes to low birth weight, not FGR's claimed role or risk. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [98] Crispi, 2018, Long-term cardiovascular consequences of fetal growth restriction: Biology, clinical implications, and opportunities for prevention of adult disease, Am. J. Obstet. Gynecol. source
    • cites [99] Crump, 2020, An overview of adult health outcomes after preterm birth, Early Hum. Dev. source

      The Endocrine/metabolic disorders > Lipid disorders section (page unavailable) links preterm birth to adult lipid disorders and cardiometabolic syndrome, supporting the long-term risk claim for preterm birth. The copy does not establish the corresponding cardiometabolic association for FGR or describe preterm birth and FGR as sentinel phenotypes of maternal–placental–fetal pathways. Its Kidney disease section mentions small-for-gestational-age birth, but in relation to renal disease, not cardiometabolic risk. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [100] Eleftheriades, 2006, Fetal Growth Restriction and Postnatal Development, Ann. N. Y. Acad. Sci. source
    • cites [101] Shah, 2024, Long-Term Neurologic Consequences following Fetal Growth Restriction: The Impact on Brain Reserve, Dev. Neurosci. source

      The Etiology of FGR section describes multiple causes of FGR, and its Fetal Programming subsection associates FGR with later cardiovascular disease and type 2 diabetes. The paper does not establish the same long-term cardiometabolic association for preterm birth, so it supports the FGR portion but not the claim about both phenotypes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Integrative placental omics in diabetes has highlighted recurrent RNA and protein pathways, although most evidence still ends at delivery and requires external replication.

    “Integrative placental omics in diabetes has highlighted recurrent RNA and protein pathways, although most evidence still ends at delivery and requires external replication [138].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [138] Fakonti, 2026, Decoding the molecular landscape of the placenta in maternal diabetes: A systematic review of high-throughput data, J. Mol. Endocrinol. source

  • May combine two claims.

    Interpretationreasoning

    These associations show that prenatal exposures can coincide with early differences in telomere biology; they do not establish that neonatal telomere length mediates adult disease.

    “These associations show that prenatal exposures can coincide with early differences in telomere biology; they do not establish that neonatal TL mediates adult disease.”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [122] Send, 2017, Telomere Length in Newborns is Related to Maternal Stress During Pregnancy, Neuropsychopharmacology source
    • cites [123] Mishra, 2023, Prenatal air pollution exposure in relation to the telomere-mitochondrial axis of aging at birth: A systematic review, Environ. Res. source
    • cites [124] Wai, 2023, Prenatal exposure to environmental heavy metals and newborn telomere length: A systematic review and meta-analysis, Environ. Pollut. source
    • cites [125] Moshfeghinia, R., Ghahremani, M., Ghasemi, A.R., Mostafavi, S., Mohagheghzadeh, H., Maharlouei, N., Ahmadi, J., and Vardanjani, H.M. (2025). Maternal smoking during pregnancy and newborn telomere length (TL): A systematic review and meta-analysis of observational studies. BMC Pregnancy Childbirth, 26. source
    • cites [126] Vakonaki, E., Vitiadou, M.T., Panteris, E., Tzatzarakis, M., Tsatsakis, A., and Hatzidaki, E. (2025). Maternal Lifestyle During Pregnancy and Its Influence on Offspring’s Telomere Length. Life, 15. source

  • May combine two claims.

    Premisecitation

    In adults, shorter leukocyte telomere length is associated with a higher risk of frailty independently of chronological age and other established risk factors, but this does not establish that neonatal telomere length predicts later frailty.

    “In adults, shorter leukocyte TL has been associated with a higher risk of frailty independently of chronological age and other established risk factors [127], but this observation does not establish that neonatal TL predicts later frailty.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [127] Bountziouka, 2022, Association of shorter leucocyte telomere length with risk of frailty, J. Cachex- Sarcopenia Muscle source

  • May combine two claims.

    Premisecitation

    A systematic review of 32 human placental metabolomics studies identified recurring perturbations in amino-acid, lipid and energy-related pathways across pregnancy complications, but outcomes were confined largely to pregnancy and birth.

    “A systematic review of 32 human placental metabolomics studies identified recurring perturbations in amino-acid, lipid and energy-related pathways across pregnancy complications, but the outcomes were confined largely to pregnancy and birth [136].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [136] Mercer, 2026, Placental metabolomics for assessment of pregnancy complications: A systematic review, Mol. Omics source

      The Abstract reports a systematic review of 32 human placental metabolomics articles and identifies amino-acid and lipid/phospholipid metabolism among the pathways associated with pregnancy complications. It does not identify recurring energy-related pathways or establish that the studies’ outcomes were confined largely to pregnancy and birth. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationreasoning

    This placenta-to-child evidence does not include a single defined maternal exposure and does not establish adult disease.

    “This is comparatively integrated placenta-to-child evidence, but it does not include a single defined maternal exposure and does not establish adult disease.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [139] Zhou, 2024, Associations of Placental Inflammation and Oxidative Stress Biomarkers with Glucolipid Metabolism in Children: A Birth Cohort Study in China, J. Am. Heart Assoc. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DNA methylation-based age estimates combine selected cytosine-phosphate-guanine sites using algorithms trained for particular ages and tissues.

    “DNA methylation–based age estimates combine selected cytosine–phosphate–guanine sites using algorithms trained for particular ages and tissues [132,133].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [132] Fang, 2023, Evaluation of pediatric epigenetic clocks across multiple tissues, Clin. Epigenet. source
    • cites [133] Musci, 2023, Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: A Systematic Review, Prev. Sci. source

  • May combine two claims.

    Premisecitation

    Oxidative and inflammatory stress can damage telomeric DNA and alter mitochondrial function, while mitochondrial reactive oxygen species may further affect telomere maintenance.

    “Oxidative and inflammatory stress can damage telomeric DNA and alter mitochondrial function, while mitochondrial reactive oxygen species may further affect telomere maintenance [128,129,130].”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [128] Coluzzi, E., Colamartino, M., Cozzi, R., Leone, S., Meneghini, C., O’Callaghan, N., and Sgura, A. (2014). Oxidative Stress Induces Persistent Telomeric DNA Damage Responsible for Nuclear Morphology Change in Mammalian Cells. PLoS ONE, 9. source

      The Discussion says oxidative stress damages telomeres and reports accelerated telomere shortening in cells with mitochondrial DNA mutations associated with increased reactive oxygen species. The Introduction also describes oxidative damage to telomeric DNA. These passages do not establish that inflammatory stress damages telomeres or that oxidative and inflammatory stress alter mitochondrial function. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [129] Opresko, 2025, Oxidative Stress and DNA Damage at Telomeres, Cold Spring Harb. Perspect. Biol. source

      The “Oxidative Stress and Telomere Maintenance” section (page not specified) says ROS damage telomeric DNA, inflammation is a source of ROS, and dysfunctional mitochondria produce ROS that can affect telomeres. It does not establish the claim’s additional direction—that oxidative or inflammatory stress alters mitochondrial function; it instead describes mitochondrial dysfunction as a source of oxidative stress. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [130] Fleming, 2025, Telomeric DNA damage landscapes distinguish oxidative from inflammatory cellular stress, Nucleic Acids Res. source

      The Introduction reports telomeric DNA lesions under oxidative and inflammatory stress and identifies mitochondria as a major source of reactive oxygen species. It also associates oxidative stress caused by mitochondrial dysfunction with telomere attrition. It does not say that oxidative or inflammatory stress alters mitochondrial function; that reverses the relationship described. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Pooled evidence supports shorter newborn telomere length after maternal smoking and an overall inverse association with prenatal metal exposure, with more consistent findings for cadmium and later-pregnancy exposure.

    “Pooled evidence supports shorter newborn TL after maternal smoking and an overall inverse association with prenatal metal exposure, with more consistent findings for cadmium and later-pregnancy exposure [124,125].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [124] Wai, 2023, Prenatal exposure to environmental heavy metals and newborn telomere length: A systematic review and meta-analysis, Environ. Pollut. source
    • cites [125] Moshfeghinia, R., Ghahremani, M., Ghasemi, A.R., Mostafavi, S., Mohagheghzadeh, H., Maharlouei, N., Ahmadi, J., and Vardanjani, H.M. (2025). Maternal smoking during pregnancy and newborn telomere length (TL): A systematic review and meta-analysis of observational studies. BMC Pregnancy Childbirth, 26. source

  • May combine two claims.

    Interpretationcitation

    Current studies support measurable biological embedding during fetal life, but they do not yet provide validated causal or prognostic markers for adult disease.

    “Current studies support measurable biological embedding during fetal life [73,80,115], but they do not yet provide validated causal or prognostic markers for adult disease.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [73] Eick, 2025, Psychosocial stressors as modifiers of the associations between well-studied and understudied chemicals and birth outcomes in the ECHO Cohort, Environ. Pollut. source

      The Results report measurable associations between prenatal chemical exposures, psychosocial stressors, and birth outcomes, including birthweight. That supports a narrower claim about fetal growth, but the paper does not establish biological embedding during fetal life or evaluate validated markers for adult disease. No page number was supplied for the indexed Results passage. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [80] Breton, C.V., Mack, W.J., Yao, J., Berhane, K., Amadeus, M., Lurmann, F., Gilliland, F., McConnell, R., Hodis, H.N., and Künzli, N. (2016). Prenatal Air Pollution Exposure and Early Cardiovascular Phenotypes in Young Adults. PLoS ONE, 11. source

      The Discussion (page not provided) reports that prenatal PM2.5 and PM10 exposure was associated with greater carotid artery stiffness measured in college students, supporting a measurable later-life correlate of prenatal exposure. It does not measure biological changes during fetal life, so that part of the cited claim is more specific than the evidence. The Discussion also says the implications for adult cardiovascular disease remain unclear. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [115] Luu, 2017, Long-Term Impact of Preterm Birth, Clin. Perinatol. source

  • May combine two claims.

    Interpretationcitation

    Links between maternal obesity, excessive GWG, GDM or hyperglycaemia and hypertensive disorders and offspring BP, adiposity and glucose-insulin traits are supported by systematic reviews and large cohorts, whereas evidence that a specific placental phenotype mediates the long-term association is more limited.

    “Their links with offspring blood pressure (BP), adiposity and glucose–insulin traits are supported by systematic reviews and large cohorts, whereas evidence that a specific placental phenotype mediates the long-term association is more limited [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Godfrey, 2010, Developmental origins of metabolic disease: Life course and intergenerational perspectives, Trends Endocrinol. Metab. source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Placental and offspring epigenetic signatures, telomere biology and mitochondrial function represent distinct domains of biological embedding; their causal and prognostic significance remains uncertain.

    “Placental and offspring epigenetic signatures, telomere biology and mitochondrial function represent distinct domains of biological embedding; their causal and prognostic significance remains uncertain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Maternal metabolic and vascular health during pregnancy can alter placental perfusion, nutrient transport, inflammatory signalling and endocrine function, with potential consequences for fetal growth and cardiometabolic development.

    “Maternal metabolic and vascular health during pregnancy can alter placental perfusion, nutrient transport, inflammatory signalling and endocrine function, with potential consequences for fetal growth and cardiometabolic development [25,26].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Gaillard, 2023, Maternal cardiovascular disorders before and during pregnancy and offspring cardiovascular risk across the life course, Nat. Rev. Cardiol. source
    • cites [26] Hivert, 2024, Pathophysiology from preconception, during pregnancy, and beyond, Lancet source

  • May combine two claims.

    Premisenone given

    Preterm birth and fetal growth restriction are clinically observable, etiologically heterogeneous sentinel phenotypes, not obligatory mediators.

    “Preterm birth and fetal growth restriction are clinically observable, etiologically heterogeneous sentinel phenotypes, not obligatory mediators.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The most consistent associations concern maternal obesity, gestational diabetes, excessive gestational weight gain and hypertensive disorders, which are linked with higher offspring blood pressure, greater adiposity and adverse glucose-insulin profiles.

    “The most consistent associations concern maternal obesity, gestational diabetes, excessive gestational weight gain and hypertensive disorders, which are linked with higher offspring blood pressure, greater adiposity and adverse glucose–insulin profiles.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Prenatal BPA exposure is associated with offspring obesity and related anthropometric outcomes in multiple cohorts, with sex- and age-related differences across studies.

    “A systematic review focused on prenatal bisphenol A (BPA) concluded that prenatal BPA exposure is associated with offspring obesity and related anthropometric outcomes in multiple cohorts, with evidence of sex- and age-related differences across studies [92].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Guo, 2024, The association between prenatal exposure to bisphenol A and offspring obesity: A systematic review, Environ. Pollut. source

  • May combine two claims.

    Interpretationnone given

    Evidence for PFAS, bisphenols, and phthalates is more heterogeneous and varies according to the specific compound, timing of exposure, offspring sex, and outcome assessed.

    “Evidence for PFAS, bisphenols, and phthalates is more heterogeneous and varies according to the specific compound, timing of exposure, offspring sex, and outcome assessed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Longitudinal studies directly linking a defined environmental exposure with a specific placental phenotype and subsequent adult disease remain scarce, and most proposed placental pathways rely on converging rather than direct evidence.

    “Longitudinal studies directly linking a defined environmental exposure with a specific placental phenotype and subsequent adult disease remain scarce, and most proposed placental pathways therefore rely on converging rather than direct evidence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Higher exposure to PM1, PM2.5, PM10, and NOx is associated with increased risk of overweight/obesity and elevated BMI in children and adolescents, with stronger associations at higher concentration levels and in Asian populations.

    “In a systematic review and meta-analysis, higher exposure to PM1, PM2.5, PM10, and nitrogen oxides (NOx) was associated with increased risk of overweight/obesity and elevated BMI in children and adolescents, with stronger associations observed at higher concentration levels and in Asian populations [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Zheng, 2023, Association of air pollution exposure with overweight or obesity in children and adolescents: A systematic review and meta–analysis, Sci. Total. Environ. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Studies of adiposity frequently combine prenatal and postnatal windows, limiting isolation of a fetal-life effect.

    “Studies of adiposity likewise frequently combine prenatal and postnatal windows, limiting isolation of a fetal-life effect.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Prenatal exposure to several phthalates is associated with markers of adiposity in offspring, whereas postnatal exposure appears more consistently linked to glycaemic traits.

    “For phthalates, a systematic review of metabolic syndrome components reported that prenatal exposure to several phthalates is associated with markers of adiposity in offspring, whereas postnatal exposure appeared more consistently linked to glycaemic traits, further supporting the importance of considering the timing of exposure [93].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Arrebola, 2023, Phthalate exposure and risk of metabolic syndrome components: A systematic review, Environ. Pollut.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Evidence for EDCs such as bisphenols and phthalates is heterogeneous, reflecting differences in biomarkers, timing, mixtures, and outcome definitions, but several reviews support pregnancy exposure as a contributor to later adiposity-related phenotypes.

    “Evidence for EDCs such as bisphenols and phthalates is heterogeneous, reflecting differences in biomarkers, timing, mixtures, and outcome definitions, but several reviews support pregnancy exposure as a contributor to later adiposity-related phenotypes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    FGR and preterm birth frequently overlap, and the combined phenotype may identify greater later vulnerability, but heterogeneity in aetiology and classification limits simple causal interpretation.

    “FGR and preterm birth frequently overlap, and the combined phenotype may identify greater later vulnerability, but heterogeneity in aetiology and classification limits simple causal interpretation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These molecular domains capture different biological processes and should not be treated as interchangeable measures of ageing.

    “These domains capture different biological processes and should not be treated as interchangeable measures of ageing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Evidence strength is highest for the association between gestational age and later clinical outcomes; it is weaker for any single upstream placental mechanism because the same birth phenotype can arise through different pathways, and long-term studies rarely include detailed placental histopathology or molecular phenotyping.

    “Evidence strength is highest for the association between gestational age and later clinical outcomes. It is weaker for any single upstream placental mechanism, because the same birth phenotype can arise through different pathways, and long-term studies rarely include detailed placental histopathology or molecular phenotyping (Table 4).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Preterm birth may follow infection and inflammation, cervical dysfunction, membrane rupture, maternal vascular disease, placental pathology, fetal disease or medically indicated delivery.

    “Preterm birth may follow infection and inflammation, cervical dysfunction, membrane rupture, maternal vascular disease, placental pathology, fetal disease or medically indicated delivery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    FGR is frequently associated with placental insufficiency but may also arise from fetal, maternal or environmental causes.

    “FGR is frequently associated with placental insufficiency but may also arise from fetal, maternal or environmental causes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Large register-based cohorts provide the strongest evidence linking preterm birth to adult outcomes, with risks varying systematically by gestational age.

    “Large register-based cohorts provide the strongest evidence linking preterm birth to adult outcomes, with risks varying systematically by gestational age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Adult echocardiographic and functional findings in individuals born preterm include smaller cardiac chamber size and altered ventricular function, which are clinically relevant substrates for heart failure risk later in life.

    “An additional review summarised adult echocardiographic and functional findings, including smaller cardiac chamber size and altered ventricular function, and positioned these phenotypes as clinically relevant substrates for heart failure risk later in life [106].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [106] Greer, 2021, Preterm birth and cardiac function in adulthood, Heart source

  • May combine two claims.

    Interpretationreasoning

    Neither preterm birth nor FGR is specific to placental dysfunction, and neither is an obligatory mediator between a prenatal exposure and adult disease.

    “Neither phenotype is specific to placental dysfunction, and neither is an obligatory mediator between a prenatal exposure and adult disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Individuals born preterm have increased risks of hypertension into adulthood, with the highest relative risks among those born at the lowest gestational ages and persistence into the fourth decade of life.

    “In a national Swedish cohort study, individuals born preterm had increased risks of hypertension into adulthood, with the highest relative risks among those born at the lowest gestational ages and with persistence into the fourth decade of life [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Crump, 2019, Risk of hypertension into adulthood in persons born prematurely: A national cohort study, Eur. Heart J. source

  • May combine two claims.

    Interpretationnone given

    mtDNA copy number is not equivalent to mitochondrial function, and cross-study comparison is limited by tissue selection, cell composition, extraction methods and adjustment for parental or maternal characteristics.

    “However, mtDNA copy number is not equivalent to mitochondrial function, and cross-study comparison is limited by tissue selection, cell composition, extraction methods and adjustment for parental or maternal characteristics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Algorithm choice, tissue source and cell composition remain major sources of variability in epigenetic age estimates, and their prognostic relevance for adult cardiometabolic disease has not been established.

    “These observations extend molecular associations beyond birth, but algorithm choice, tissue source and cell composition remain major sources of variability. Their prognostic relevance for adult cardiometabolic disease has not been established.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Standardisation, tissue and cell-type specificity, multiple-testing correction, experimental confirmation and independent replication remain important challenges.

    “Standardisation, tissue and cell-type specificity, multiple-testing correction, experimental confirmation and independent replication remain important challenges (Table 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Pregnancy exposures are socially patterned and often cluster with postnatal environmental and familial factors.

    “At the same time, pregnancy exposures are socially patterned and often cluster with postnatal environmental and familial factors [60,123].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [60] Meaney, 2017, Fetal Origins of Mental Health: The Developmental Origins of Health and Disease Hypothesis, Am. J. Psychiatry source
    • cites [123] Mishra, 2023, Prenatal air pollution exposure in relation to the telomere-mitochondrial axis of aging at birth: A systematic review, Environ. Res. source

  • May combine two claims.

    Interpretationreasoning

    Metabolomic, proteomic, lipidomic, inflammatory and immune signatures represent additional molecular dimensions of placental dysfunction, but their links with later offspring health remain comparatively underexplored.

    “Metabolomic, proteomic, lipidomic, inflammatory and immune signatures represent additional molecular dimensions of placental dysfunction, but their links with later offspring health remain comparatively underexplored.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Maternal metabolic and vascular exposures during pregnancy, including obesity, excessive GWG, gestational diabetes and hypertensive disorders, may alter placental perfusion, nutrient transport, endocrine and inflammatory signalling, oxidative balance and vascular function, with potential consequences for fetal growth and later cardiometabolic health.

    “Maternal metabolic and vascular exposures during pregnancy, including obesity, excessive GWG, gestational diabetes and hypertensive disorders, may alter placental perfusion, nutrient transport, endocrine and inflammatory signalling, oxidative balance and vascular function, with potential consequences for fetal growth and later cardiometabolic health.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Maternal metabolic, vascular, psychosocial and environmental exposures may alter fetal development through placental and non-placental pathways, while postnatal conditions influence whether early differences persist, diminish or become clinically apparent.

    “Maternal metabolic, vascular, psychosocial and environmental exposures may alter fetal development through placental and non-placental pathways, while postnatal conditions influence whether early differences persist, diminish or become clinically apparent.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The placenta regulates fetal exposure to inflammatory and oxidative mediators and is frequently sampled in these studies.

    “The placenta regulates fetal exposure to inflammatory and oxidative mediators and is frequently sampled in these studies [123,131].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Mishra, 2023, Prenatal air pollution exposure in relation to the telomere-mitochondrial axis of aging at birth: A systematic review, Environ. Res. source
    • cites [131] Cohen, 2025, Placental DNA methylation key topics: Sex- and cell-type specificity, mediation, multi-omics, and biomarker discovery, Epigenomics source

  • May combine two claims.

    Interpretationreasoning

    These associations support life-course surveillance but do not identify a single placental pathway or imply deterministic risk.

    “These associations support life-course surveillance but do not identify a single placental pathway or imply deterministic risk.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    In prenatal research, epigenetic measures indicate exposure-associated methylation patterns; they should not be interpreted as literal acceleration of whole-organism ageing or as evidence of causal mediation.

    “In prenatal research, these measures indicate exposure-associated methylation patterns; they should not be interpreted as literal acceleration of whole-organism ageing or as evidence of causal mediation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Preterm birth and FGR are clinically useful sentinel phenotypes but are neither specific to placental dysfunction nor obligatory mediators.

    “Preterm birth and FGR are clinically useful sentinel phenotypes but are neither specific to placental dysfunction nor obligatory mediators.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Many molecular studies are small and imprecise, increasing susceptibility to selective reporting and publication bias.

    “Many molecular studies are small and imprecise, increasing susceptibility to selective reporting and publication bias.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The principal knowledge gap is the scarcity of longitudinal human studies measuring a defined maternal exposure, a specific placental phenotype, fetal organ development, childhood cardiometabolic trajectories and adult clinical outcomes within the same design.

    “The principal knowledge gap is the scarcity of longitudinal human studies measuring a defined maternal exposure, a specific placental phenotype, fetal organ development, childhood cardiometabolic trajectories and adult clinical outcomes within the same design.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Outcomes range from birth biomarkers to adult clinical events, and molecular estimates depend on tissue, cell composition, assay platform and algorithm.

    “Outcomes range from birth biomarkers to adult clinical events, and molecular estimates depend on tissue, cell composition, assay platform and algorithm.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Biological embedding is supported by molecular associations, but the markers should remain conceptually distinct.

    “Biological embedding is supported by molecular associations, but the markers should remain conceptually distinct.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These molecular measures may capture exposure, susceptibility or response; they are not interchangeable indicators of ageing, and current evidence does not establish that they mediate adult disease or provide reliable individual risk prediction.

    “These measures may capture exposure, susceptibility or response. They are not interchangeable indicators of ageing, and current evidence does not establish that they mediate adult disease or provide reliable individual risk prediction.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Exposure timing, biological matrices, placental sampling, histopathological definitions and methods for mixtures differ widely between studies.

    “Exposure timing, biological matrices, placental sampling, histopathological definitions and methods for mixtures differ widely between studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Maternal metabolic and vascular disorders show the most consistent long-term associations, while environmental, psychosocial and molecular evidence is more heterogeneous.

    “Maternal metabolic and vascular disorders show the most consistent long-term associations, while environmental, psychosocial and molecular evidence is more heterogeneous.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    As a structured narrative review, this article did not use a single deduplicated screening set, formal study-level risk-of-bias scoring or certainty grading; evidence-strength categories were interpretive rather than equivalent to GRADE or a systematic-review framework.

    “As a structured narrative review, this article did not use a single deduplicated screening set, formal study-level risk-of-bias scoring or certainty grading; evidence-strength categories were interpretive rather than equivalent to GRADE or a systematic-review framework.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Pregnancy offers a distinctive opportunity for prevention because it is routinely monitored in clinical care, occurs within a defined time frame, and involves exposures that are often modifiable.

    “Nevertheless, pregnancy offers a distinctive opportunity for prevention because it is routinely monitored in clinical care, occurs within a defined time frame, and involves exposures that are often modifiable.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Pregnancy is routinely monitored in clinical care, occurs within a defined time frame, and involves exposures that are often modifiable.

  • May combine two claims.

    Premisenone given

    Prenatal smoking, air pollution and metal exposure have been associated with neonatal telomere length or mitochondrial indices, while selected chemical exposures have been associated with placental or childhood DNA methylation signatures.

    “Prenatal smoking, air pollution and metal exposure have been associated with neonatal TL or mitochondrial indices, while selected chemical exposures have been associated with placental or childhood DNA methylation signatures.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Across exposure domains, evidence is strongest when long-term offspring associations converge with measured placental abnormalities, but only a minority of studies assess these components within the same cohort.

    “Across exposure domains, evidence is strongest when long-term offspring associations converge with measured placental abnormalities, but only a minority of studies assess these components within the same cohort.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Residual genetic, socioeconomic, behavioural and familial confounding remains possible, even in sibling or family-based designs, while differential loss to follow-up may select healthier participants.

    “Residual genetic, socioeconomic, behavioural and familial confounding remains possible, even in sibling or family-based designs, while differential loss to follow-up may select healthier participants.”
    Quote in the paperNot a substantial claim
68 of 68

  • The paper relies on this without support.

    Placental 11β-HSD2 converts active cortisol to inactive cortisone and thereby limits fetal glucocorticoid exposure.

    “Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), encoded by HSD11B2, converts active cortisol to inactive cortisone and thereby limits fetal glucocorticoid exposure.”

  • The paper relies on this without support.

    Childhood adiposity and blood pressure are trajectories that often persist into adulthood.

    “childhood adiposity and BP are trajectories that often persist into adulthood and remain relevant endpoints within a life-course argument.”

  • The paper relies on this without support.

    Childhood profiles of adiposity and blood pressure are well-established precursors of adult cardiometabolic morbidity.

    “these childhood profiles are clinically relevant, as they are well-established precursors of adult cardiometabolic morbidity”

  • The paper relies on this without support.

    Maternal diet and the built environment shape fetal nutrient supply and maternal metabolic status.

    “Maternal diet and the built environment provide a complementary aspect because they shape fetal nutrient supply and maternal metabolic status”

  • The paper relies on this without support.

    Arterial stiffness is relevant to later cardiovascular risk at the population level.

    “Arterial stiffness is relevant to later cardiovascular risk at the population level”

  • The paper relies on this without support.

    Pregnancy is routinely monitored in clinical care, occurs within a defined time frame, and involves exposures that are often modifiable.

    “pregnancy offers a distinctive opportunity for prevention because it is routinely monitored in clinical care, occurs within a defined time frame, and involves exposures that are often modifiable.”
6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Plana-Ripoll study year differs between table and reference

    Minor

    Table 2 dates the cited study to 2020, but reference 56 lists it as 2015.

  • Burgueño study year differs between table and reference

    Minor

    Table 2 dates the cited review to 2020, but reference 64 lists it as 2019.

2 of 2

Cites

Flagged first, then by citations

Cited by

Still being checked.

Authors
Panteris, E., Kakatsaki, I., Koukou, Z., Kolvatzis, C., Papanikolaou, S., & Hatzidaki, E.
Affiliations
  • University of Crete (GR)
  • International Hellenic University (GR)
  • Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
ORCID
Venue
Pathophysiology
Publisher
MDPI AG
Published
2026-09-08
Volume
33
Issue
3
Pages
67
ISSN
  • 0928-4680 (ISSN-L)
  • 1873-149X
DOI
10.3390/pathophysiology33030067
PMC
PMC13609975
OpenAlex
W7211945282
Semantic Scholar
2e882925b8f5bb7268356653a51cf18f4216e5e0
Cited by
0
References
143
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Pathophysiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
placental pathophysiology, developmental programming, cardiometabolic risk, prenatal exposure, maternal obesity, gestational diabetes mellitus, gestational weight gain, hypertensive disorders of pregnancy, offspring blood pressure, offspring adiposity, glucose-insulin metabolism, placental vascular malperfusion, placental nutrient transport, placental inflammation, placental oxidative stress, placental endocrine function, epigenetic regulation, telomere biology, mitochondrial function, preterm birth, fetal growth restriction, biological embedding, non-communicable diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-20.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-20.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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