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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 labor 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 detrimental 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.

SUBMITTER: Weckman AM

PROVIDER: S-EPMC10275952 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Weckman Andrea M AM Elphinstone Robyn E RE Ssenkusu John M JM Tran Vanessa V Zhong Kathleen K Madanitsa Mwayiwawo M Khairallah Carole C Kalilani-Phiri Linda L Mwapasa Victor V Conroy Andrea L AL Ter Kuile Feiko O FO McDonald Chloe R CR Kain Kevin C KC

iScience 20230519 6

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 labor 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 IL1 ...[more]

PMID: 37332611

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Project description:BackgroundPreterm delivery is a leading cause of neonatal mortality and morbidity. History of spontaneous preterm birth is the greatest risk factor for another preterm delivery. So, every effort should be made to prevent the recurrence of preterm delivery in this vulnerable group. This study aimed to evaluate the predictive ability of the anterior uterocervical angle and cervical length in preterm birth.Patients and methodsThis was a prospective cohort study that included 70 patients with a history of spontaneous preterm birth. Ultrasound measurements of cervical length and anterior uterocervical angle were set to be measured for each patient at three visits; first between 16 0/7 and 24 0/7 weeks, second between 24 1/7 and 32 0/7 weeks, and the third was between 32 1/7 and 36 6/7 weeks. The correlation between both measures and the prediction of preterm birth among study participants was the primary outcome of the study. Neonatal outcome among the study patients was a secondary measure of outcome.ResultsThe incidence of preterm birth among study participants was 31.41%. Cervical length and uterocervical angle showed progressive decrease and increase respectively throughout pregnancy. At the 2nd visit, the two measures were significantly different between those who delivered at term and those with preterm delivery with the cervical length being significantly shorter in the preterm arm (3.0 ± 0.49 versus 3.38 ± 0.36, p < 0.001) and uterocervical angle being significantly bigger among the same arm (110.1 ± 18.48 versus 84.42 ± 12.24, p < 0.001). A uterocervical angle > 89.8° at the second visit predicted preterm birth with 81.8% sensitivity and 70.8% specificity while cervical length ≤ 3.22 cm at the second visit predicted preterm birth with 68.1% sensitivity and 62.5% specificity. Multivariant logistic regression analysis showed that uterocervical angle > 89.8° at the second visit increased the odds ratio for preterm birth by 9.ConclusionUterocervical angle can be a useful ultrasound marker for the prediction of preterm birth among high risk patients. A cutoff value of 89.8° can be used as a threshold above which prophylactic measures such as cervical cerclage or progesterone therapy can be provided.Trial registrationNCT05632003 (First posted date: 30/11/2022).

Project description:BACKGROUND:Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally. METHODS:A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review. RESULTS:Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth (38/38, 100%), previous mid-trimester loss (34/38, 89%) and previous cervical surgery (33/38, 87%). All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs (16/28, 57%) and fetal fibronectin (8/28, 29%). The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12-16 weeks (30/35, 86%) and the frequency of review was usually determined by clinical findings (18/24, 75%). There was a wide variation in gestational age at clinic discharge between 24 and 37 weeks. CONCLUSIONS:There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes. TRIAL REGISTRATION:Systematic review registration number: CRD42019131470.

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

Publications

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

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