The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy

Abstract: Introduction: Malaria in pregnancy contributes to significant adverse birth outcomes. This study is aimed to quantify the relationship between malaria in pregnancy and occurrence of adverse birth outcomes, including preterm delivery, low birth weight, small for gestational age, miscarriages, and stillbirth. Methods and analysis: Observational studies and Randomised controlled trials reporting data on selected birth outcomes separately for pregnancies, with or without malaria will be included. We will search for studies over various information sources and data extraction will be done from included studies. Pooled odds ratio (OR) will be calculated for each birth outcomes using fixed effect model or random effects models, based on the level of heterogeneity. Forest plot will be prepared with effect size (with 95 percent confidence interval) of each study and pooled effect size. The methodological quality will be assessed for included observational studies using the Newcastle-Ottawa scale (NOS). Cochrane Risk of Bias tool will be used to evaluate bias in randomised controlled trials. For publication bias, funnel plot will be prepared and assessed for asymmetry, along with Egger′s test. Discussion: This study will provide an estimate of the risk of adverse birth outcomes in pregnancies with malaria. Results of this study will contribute towards planning effective service delivery in areas with a higher risk of malaria transmission. Ethics and dissemination: The current study is a review of published literature, and it does not require ethical committee approval. Results of this review will be published in a peer-reviewed journal. PROSPERO registration number: CRD42020153009

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Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities

Trends in Parasitology ◽

10.1016/j.pt.2019.12.005 ◽

2020 ◽

Vol 36 (2) ◽

pp. 127-137 ◽

Cited By ~ 1

Author(s):

Michelle Ngai ◽

Andrea M. Weckman ◽

Clara Erice ◽

Chloe R. McDonald ◽

Lindsay S. Cahill ◽

...

Keyword(s):

Birth Outcomes ◽

Malaria In Pregnancy ◽

Adverse Birth Outcomes ◽

In Pregnancy

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Relationships Between Measures of Malaria at Delivery and Adverse Birth Outcomes in a High-Transmission Area of Uganda

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa156 ◽

2020 ◽

Vol 222 (5) ◽

pp. 863-870

Author(s):

John Ategeka ◽

Abel Kakuru ◽

Richard Kajubi ◽

Razack Wasswa ◽

Harriet Ochokoru ◽

...

Keyword(s):

Birth Outcomes ◽

Controlled Trial ◽

Intermittent Preventive Treatment ◽

Malaria In Pregnancy ◽

Adverse Birth Outcomes ◽

Adjusted Risk ◽

High Transmission ◽

Malaria Pigment ◽

Placental Blood ◽

In Pregnancy

Abstract Background Clinical trials of interventions for preventing malaria in pregnancy often use measures of malaria at delivery as their primary outcome. Although the objective of these interventions is to improve birth outcomes, data on associations between different measures of malaria at delivery and adverse birth outcomes are limited. Methods Data came from 637 Ugandan women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy. Malaria at delivery was detected using peripheral and placental blood microscopy, placental blood loop-mediated isothermal amplification (LAMP), and placental histopathology. Multivariate analyses were used to estimate associations between measures of malaria at delivery and risks of low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB). Results Detection of malaria parasites by microscopy or LAMP was not associated with adverse birth outcomes. Presence of malaria pigment detected by histopathology in ≥30% of high-powered fields was strongly associated with LBW (adjusted risk ratio [aRR] = 3.42, P = .02) and SGA (aRR = 4.24, P < .001) but not PTB (aRR = 0.88, P = .87). Conclusions A semiquantitative classification system based on histopathologically detected malaria pigment provided the best surrogate measure of adverse birth outcomes in a high-transmission setting and should be considered for use in malaria in pregnancy intervention studies.

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Association of Angiopoietin Dysregulation in Placental Malaria with Adverse Birth Outcomes

Disease Markers ◽

10.1155/2020/6163487 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Puspendra P. Singh ◽

Sneha Bhandari ◽

Ravendra K. Sharma ◽

Neeru Singh ◽

Praveen K. Bharti

Keyword(s):

Birth Outcomes ◽

Adverse Outcome ◽

Birth Outcome ◽

Placental Malaria ◽

Malaria In Pregnancy ◽

Adverse Birth Outcomes ◽

Peripheral Plasma ◽

Angiopoietin 2 ◽

In Pregnancy ◽

Angiopoietin 1

Malaria in pregnancy causes adverse birth outcomes due to sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Angiopoietins are critical regulators of vascular development and formation of placental villous vasculature. Angiopoietin-1 and Angiopoietin-2 concentrations were measured in peripheral and placental plasma samples from 70 malaria-infected and 216 control women using commercially available DuoSet ELISA development kit. Angiopoietins increased in placental plasma (ANG1-5833.5 pg/ml and ANG2-9580.6 pg/ml) as compared to peripheral plasma (ANG1-2293.1 pg/ml and ANG2-1198.9 pg/ml, p<0.0001). The concentration of placental and peripheral ANG1 (6099.23 pg/ml and 2320.5 pg/ml) was significantly lower (5013.5 pg/ml, 2208.5 pg/ml), and ANG2 (9553.3 pg/ml, 1180.92 pg/ml) was significantly higher (9664.6 pg/ml, 1254.4 pg/ml) in malaria-positive cases as compared to malaria-negative (p<0.0001). The association of dysregulated angiopoietins in malaria with adverse birth outcomes showed that the peripheral and placental ANG1 concentration was lower and ANG2 concentration was higher in low-birth-weight baby and stillbirth birth outcome as compared to normal deliveries among malaria-positive group. Therefore, ANG1 and ANG2 could be considered a biomarker for adverse outcome during malaria in pregnancy.

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