Placental characteristics and risks of maternal mortality 50 years after delivery

Yeung, Edwina; Saha, Abhisek; Zhu, Chunyan; Trinh, Mai-Han; Hinkle, Stefanie; Pollack, Anna Z.; Grantz, Katherine L.; Mills, James L.; Mumford, Sunni; Zhang, C.; Robinson, Sonia L.; Gillman, Matthew W.; Zhang, J; Mendola, Pauline; Sundaram, Rajeshwari

doi:10.1016/j.placenta.2021.12.014

Cited by 9 publications

(9 citation statements)

References 25 publications

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“…While the link between PW and paternal mortality has not been investigated previously, associations between increased offspring PW (and its ratio to BW) and maternal mortality were identified in a US cohort of over 33,000 pregnancies from the 1960s [ 36 ]. We also found associations between offspring PW and maternal mortality when adjusted for BW, with an 8.3% increase in the maternal risk of death for every increase of 1 SD in the PW Z score, for any given BW, which probably reflects placental inefficiency.…”

Section: Discussionmentioning

confidence: 99%

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort

2022

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Aims/hypothesis Low birthweight (BW) is associated with the development of type 2 diabetes. Genome-wide analyses have identified a strong genetic component to this association, with many BW-associated loci also involved in glucose metabolism. We hypothesised that offspring BW and placental weight (PW) are correlated with parental type 2 diabetes risk, reflecting the inheritance of diabetes risk alleles that also influence fetal growth. Methods The Walker cohort, a collection of birth records from Dundee, Scotland, from the 1950s and the 1960s was used to test this hypothesis by linking BW and PW measurements to parental health outcomes. Using data from SCI-Diabetes and the national death registry, we obtained health records for over 20,000 Walker parents. We performed Fine–Gray survival analyses of parental type 2 diabetes risk with competing risk of death, and Cox regression analyses of risk of death, independently in the maternal and paternal datasets, modelled by offspring BW and PW. Results We found significant associations between increased paternal type 2 diabetes risk and reduced offspring BW (subdistribution hazard ratio [SHR] 0.92 [95% CI 0.87, 0.98]) and PW (SHR 0.87 [95% CI 0.81, 0.94]). The association of maternal type 2 diabetes risk with offspring BW or PW was not significant. Lower offspring BW was also associated with increased risk of death in both mothers (HR 0.91 [95% CI 0.89, 0.94]) and fathers (HR 0.95 [95% CI 0.92, 0.98]), and higher offspring PW was associated with increased maternal mortality risk (HR 1.08 [95% CI 1.04, 1.13]) when adjusted for BW. Conclusions/interpretation We identified associations between offspring BW and reduced paternal type 2 diabetes risk, most likely resulting from the independent effects of common type 2 diabetes susceptibility alleles on fetal growth, as described by the fetal insulin hypothesis. Moreover, we identified novel associations between offspring PW and reduced paternal type 2 diabetes risk, a relationship that might also be caused by the inheritance of diabetes predisposition variants. We found differing associations between offspring BW and PW and parental risk of death. These results provide novel epidemiological support for the use of offspring BW and PW as predictors for future risk of type 2 diabetes and death in mothers and fathers. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort

2022

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“…As it will be subsequently discussed, there are different vascular disorders of pregnancy whose pathophysiological basis resides on altered placental perfusion, hence highlighting the importance of this organ for the maternofetal well-being. Moreover, a very recent longitudinal study of 33,336 women followed for 50 years showed that the placental weight to birthweight ratio was associated with long-term maternal mortality [96]. In other words, the status and development of the placenta are also crucial for maternal health during and after gestation, as well as to prevent long-term morbidity and mortality.…”

Section: Placenta and Maternofetal Programmingmentioning

confidence: 99%

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

Ortega

Fraile-Martínez

García-Montero

et al. 2022

Cells

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The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated.

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“…5 However, using a larger sample, Yeung et al found positive associations between offspring PW to BW ratio and maternal CVD mortality. 21 Apart from the correlation between placental size and fetal development, 22,23 suggesting similar genetic associations to those seen for BW, [24][25][26] the role of the placenta in the association between fetal growth restriction and parental health outcomes is not yet understood. A recent causal mediation analysis by Sato and colleagues 27 revealed that while maternal polygenic scores for blood pressure measurements are inversely associated with offspring BW, this effect was greatly mediated by placental weight, further adding to the complexity of the early determination of adult cardiometabolic disease.…”

Section: Introductionmentioning

confidence: 99%

Associations of offspring birthweight and placental weight with subsequent parental coronary heart disease: survival regression using the walker cohort

Sánchez-Soriano,

Pearson,

Reynolds

2023

J Dev Orig Health Dis

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Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring’s records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring’s BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88–0.95) and paternal (HR: 0.96, 95% CI: 0.93–1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08–1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

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Placental characteristics and risks of maternal mortality 50 years after delivery

Cited by 9 publications

References 25 publications

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

Associations of offspring birthweight and placental weight with subsequent parental coronary heart disease: survival regression using the walker cohort

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