Placental inflammation and pregnancy outcomes: A prospective, observational study in South Asia: The PURPOSe study

Author:

Ahmed Imran1,Ghanchi Najia Karim1,Sunder Tikmani Shiyam1,Hwang Kay2,Zafar Afia1,Saleem Sarah1,Uddin Zeeshan1,Harakuni Sheetal3,Somannavar Manjunath S.3ORCID,Kulkarni Vardendra4,Guruprasad Gowder4,Goudar Shivaprasad S.3,Kim Jean2,McClure Elizabeth M.2ORCID,Goldenberg Robert L.56

Affiliation:

1. Aga Khan University Karachi Pakistan

2. RTI International Durham North Carolina USA

3. KLE Academy of Higher Education and Research's J N Medical College Belagavi Karnataka India

4. Bapuji Educational Association's J.J.M. Medical College Davangere Karnataka India

5. University of Utah School of Medicine Salt Lake City Utah USA

6. Columbia University New York New York USA

Abstract

AbstractObjectiveTo examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan.DesignProspective, observational study.SettingThree hospitals in India and a large maternity hospital in Pakistan.PopulationThe enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India.MethodsA prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards.Main outcome measuresAny placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens.ResultsIn the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000–2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions.ConclusionsChorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.

Funder

Bill and Melinda Gates Foundation

Publisher

Wiley

Subject

Obstetrics and Gynecology

Reference17 articles.

1. Stillbirths: rates, risk factors, and acceleration towards 2030

2. Causes of Death Among Stillbirths

3. World Health Organization.Newborn mortality.2022[cited 2022 July 1]. Available from:https://www.who.int/news‐room/fact‐sheets/detail/levels‐and‐trends‐in‐child‐mortality‐report‐2021#:~:text=Globally%202.4%20million%20children%20died in%20child%20survival%20since%201990

4. Trends and determinants of stillbirth in developing countries: results from the Global Network’s Population-Based Birth Registry

5. Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than chorioamnionitis displaying a maternal inflammatory response only

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