Placental Pathology and Blood Pressure at Age 7: A Longitudinal Discordant Twin Analysis

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2024 Dec 19

PMID 39697173

Authors

Alexa A Freedman

Gregory E Miller

Andrew D Franklin

Lauren S Keenan-Devlin

Stephen E Gilman

Ann Borders

Sadiya S Khan

Linda M Ernst

Affiliations

Soon will be listed here.

Abstract

Background: Evidence suggests that the intrauterine environment shapes offspring cardiovascular disease risk. Although placental dysfunction may be an important pathophysiologic pathway, numerous parental and pregnancy characteristics that influence offspring blood pressure are strong confounders of the mechanistic role of the placenta in observational analyses of singletons. Therefore, we leverage twin- and sibling-based comparison designs to determine whether placental pathology is associated with offspring blood pressure at age 7 while mitigating major sources of confounding.

Methods: Data are from pregnant participants and their offspring in the Collaborative Perinatal Project, a longitudinal pregnancy cohort conducted from 1959 to 1965 in the United States. After delivery, placentas were systematically examined for lesions indicative of maternal vascular malperfusion (MVM) and acute inflammation. Blood pressure was assessed at a follow-up research visit when the offspring were 7 years old. Linear fixed-effects models were used to estimate associations between within-twin or sibling discordance in placental pathology and differences in blood pressure at age 7.

Results: Overall, 193 twin pairs were eligible for inclusion, and 23.3% had placentas discordant for MVM. In a fixed-effect analysis, a twin with high-grade MVM had a higher systolic blood pressure score by 0.56 SDs than their co-twin without MVM (95% CI, 0.06-1.05) or a 5.7-mm Hg difference (95% CI, 0.6-10.8). Associations were consistent in a sensitivity analysis restricted to dichorionic twins and in a secondary analysis of 759 MVM-discordant sibling pairs. Acute placental inflammation was not associated with blood pressure at age 7.

Conclusions: MVM in the placenta is associated with higher offspring blood pressure in mid-childhood, independent of parental and pregnancy characteristics that twins have in common. The findings support the role of the placenta and the intrauterine environment in the developmental origins of cardiovascular health.

References

Louey S, Jonker S, Giraud G, Thornburg K . Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes. J Physiol. 2007; 580(Pt. 2):639-48. PMC: 2075561. DOI: 10.1113/jphysiol.2006.122200. View

Arts N, Schiffer V, Severens-Rijvers C, Bons J, Spaanderman M, Al-Nasiry S . Cumulative effect of maternal vascular malperfusion types in the placenta on adverse pregnancy outcomes. Placenta. 2022; 129:43-50. DOI: 10.1016/j.placenta.2022.09.007. View

Lloyd-Jones D, Ning H, Labarthe D, Brewer L, Sharma G, Rosamond W . Status of Cardiovascular Health in US Adults and Children Using the American Heart Association's New "Life's Essential 8" Metrics: Prevalence Estimates From the National Health and Nutrition Examination Survey (NHANES), 2013 Through 2018. Circulation. 2022; 146(11):822-835. DOI: 10.1161/CIRCULATIONAHA.122.060911. View

Vishram-Nielsen J, Kristensen A, Pareek M, Laurent S, Nilsson P, Linneberg A . Predictive Importance of Blood Pressure Characteristics With Increasing Age in Healthy Men and Women: The MORGAM Project. Hypertension. 2021; 77(4):1076-1085. DOI: 10.1161/HYPERTENSIONAHA.120.16354. View

Romero R, Kim Y, Pacora P, Kim C, Benshalom-Tirosh N, Jaiman S . The frequency and type of placental histologic lesions in term pregnancies with normal outcome. J Perinat Med. 2018; 46(6):613-630. PMC: 6174692. DOI: 10.1515/jpm-2018-0055. View

Burton G, Fowden A, Thornburg K . Placental Origins of Chronic Disease. Physiol Rev. 2016; 96(4):1509-65. PMC: 5504455. DOI: 10.1152/physrev.00029.2015. View

Redline R, Vik T, Heerema-McKenney A, Jamtoy A, Ravishankar S, Nu T . Interobserver Reliability for Identifying Specific Patterns of Placental Injury as Defined by the Amsterdam Classification. Arch Pathol Lab Med. 2021; 146(3):372-378. DOI: 10.5858/arpa.2020-0753-OA. View

Rosner B, Cook N, Portman R, Daniels S, Falkner B . Determination of blood pressure percentiles in normal-weight children: some methodological issues. Am J Epidemiol. 2008; 167(6):653-66. DOI: 10.1093/aje/kwm348. View

Barker D, Osmond C, Golding J, Kuh D, Wadsworth M . Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298(6673):564-7. PMC: 1835925. DOI: 10.1136/bmj.298.6673.564. View

10.

Hemachandra A, Howards P, Furth S, Klebanoff M . Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project. Pediatrics. 2007; 119(6):e1264-70. DOI: 10.1542/peds.2005-2486. View

11.

Barker D, Thornburg K, Osmond C, Kajantie E, Eriksson J . The surface area of the placenta and hypertension in the offspring in later life. Int J Dev Biol. 2009; 54(2-3):525-30. PMC: 3923649. DOI: 10.1387/ijdb.082760db. View

12.

Redline R, Roberts D, Parast M, Ernst L, Morgan T, Greene M . Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease. Am J Obstet Gynecol. 2022; 228(2):187-202. PMC: 10337668. DOI: 10.1016/j.ajog.2022.08.010. View

13.

Greer C, Troughton R, Adamson P, Harris S . Preterm birth and cardiac function in adulthood. Heart. 2021; 108(3):172-177. DOI: 10.1136/heartjnl-2020-318241. View

14.

Abulikemu A, Zhang X, Su X, Meng T, Su W, Shi Q . Particulate matter, polycyclic aromatic hydrocarbons and metals, platelet parameters and blood pressure alteration: Multi-pollutants study among population. Sci Total Environ. 2024; 941:173657. DOI: 10.1016/j.scitotenv.2024.173657. View

15.

Barker D, WINTER P, Osmond C, Margetts B, Simmonds S . Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2(8663):577-80. DOI: 10.1016/s0140-6736(89)90710-1. View

16.

Murotsuki J, Challis J, Han V, Fraher L, Gagnon R . Chronic fetal placental embolization and hypoxemia cause hypertension and myocardial hypertrophy in fetal sheep. Am J Physiol. 1997; 272(1 Pt 2):R201-7. DOI: 10.1152/ajpregu.1997.272.1.R201. View

17.

Hardy J . The Collaborative Perinatal Project: lessons and legacy. Ann Epidemiol. 2003; 13(5):303-11. DOI: 10.1016/s1047-2797(02)00479-9. View

18.

Misra D, McNally S, Chen S, Salafia C . Placental infarcts in the collaborative perinatal project: Variable associations infer variable constructs. Placenta. 2020; 99:1-7. DOI: 10.1016/j.placenta.2020.06.004. View

19.

Sacha C, Mortimer R, James K, Harris A, Yeh J, Toth T . Placental pathology of term singleton live births conceived with fresh embryo transfer compared with those conceived without assisted reproductive technology. Fertil Steril. 2022; 117(4):758-768. DOI: 10.1016/j.fertnstert.2021.12.017. View

20.

Thornburg K, Marshall N . The placenta is the center of the chronic disease universe. Am J Obstet Gynecol. 2015; 213(4 Suppl):S14-20. PMC: 4593619. DOI: 10.1016/j.ajog.2015.08.030. View