Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

Andrea M. Weckman; Robyn E. Elphinstone; John M. Ssenkusu; Vanessa Tran; Kathleen Zhong; Mwayiwawo Madanitsa; Carole Khairallah; Linda Kalilani-Phiri; Victor Mwapasa; Andrea L. Conroy; Feiko Ter Kuile; Chloe R. McDonald; Kevin C. Kain

doi:10.1016/j.isci.2023.106912

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

Andrea M. Weckman, Robyn E. Elphinstone, John M. Ssenkusu, Vanessa Tran, Kathleen Zhong, Mwayiwawo Madanitsa, Carole Khairallah, Linda Kalilani-Phiri, Victor Mwapasa, Andrea L. Conroy, Feiko Ter Kuile, Chloe R. McDonald, Kevin C. Kain

Clinical Sciences

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labour and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation, had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimnental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.

Original language	English
Article number	106912
Pages (from-to)	e106912
Journal	iScience
Volume	26
Issue number	6
Early online date	19 May 2023
DOIs	https://doi.org/10.1016/j.isci.2023.106912
Publication status	E-pub ahead of print - 19 May 2023

Keywords

Clinical finding
Health sciences
Pregnancy

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PIIS2589004223009896Final published version, 3.02 MBLicence: CC BY-NC-ND

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Weckman, A. M., Elphinstone, R. E., Ssenkusu, J. M., Tran, V., Zhong, K., Madanitsa, M., Khairallah, C., Kalilani-Phiri, L., Mwapasa, V., Conroy, A. L., Ter Kuile, F., McDonald, C. R., & Kain, K. C. (2023). Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women. iScience, 26(6), e106912. Article 106912. Advance online publication. https://doi.org/10.1016/j.isci.2023.106912

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title = "Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women",

abstract = "Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labour and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation, had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimnental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.",

keywords = "Clinical finding, Health sciences, Pregnancy",

author = "Weckman, \{Andrea M.\} and Elphinstone, \{Robyn E.\} and Ssenkusu, \{John M.\} and Vanessa Tran and Kathleen Zhong and Mwayiwawo Madanitsa and Carole Khairallah and Linda Kalilani-Phiri and Victor Mwapasa and Conroy, \{Andrea L.\} and \{Ter Kuile\}, Feiko and McDonald, \{Chloe R.\} and Kain, \{Kevin C.\}",

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month = may,

day = "19",

doi = "10.1016/j.isci.2023.106912",

language = "English",

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journal = "iScience",

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Weckman, AM, Elphinstone, RE, Ssenkusu, JM, Tran, V, Zhong, K, Madanitsa, M, Khairallah, C, Kalilani-Phiri, L, Mwapasa, V, Conroy, AL, Ter Kuile, F, McDonald, CR & Kain, KC 2023, 'Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women', iScience, vol. 26, no. 6, 106912, pp. e106912. https://doi.org/10.1016/j.isci.2023.106912

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T1 - Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

AU - Weckman, Andrea M.

AU - Elphinstone, Robyn E.

AU - Ssenkusu, John M.

AU - Tran, Vanessa

AU - Zhong, Kathleen

AU - Madanitsa, Mwayiwawo

AU - Khairallah, Carole

AU - Kalilani-Phiri, Linda

AU - Mwapasa, Victor

AU - Conroy, Andrea L.

AU - Ter Kuile, Feiko

AU - McDonald, Chloe R.

AU - Kain, Kevin C.

PY - 2023/5/19

Y1 - 2023/5/19

N2 - Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labour and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation, had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimnental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.

AB - Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labour and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation, had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimnental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.

KW - Clinical finding

KW - Health sciences

KW - Pregnancy

U2 - 10.1016/j.isci.2023.106912

DO - 10.1016/j.isci.2023.106912

M3 - Article

SN - 2589-0042

VL - 26

SP - e106912

JO - iScience

JF - iScience

IS - 6

M1 - 106912

ER -

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

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