Nadia M Ikumi1, Thokozile R Malaba2, Komala Pillay3,4, Marta C Cohen5,6,7, Hlengiwe P Madlala2, Mushi Matjila7, Dilly Anumba8, Landon Myer2, Marie-Louise Newell9,10, Clive M Gray1,4. 1. Division of Immunology, Institute of Infectious Disease and Molecular Medicine. 2. Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine. 3. Division of Anatomical Pathology, Department of Pathology, University of Cape Town. 4. National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa. 5. Department of Histopathology, Sheffield Children's NHS Foundation Trust. 6. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. 7. Department of Obstetrics and Gynaecology, University of Cape Town, Cape Town, South Africa. 8. Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield. 9. School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. 10. School of Public Health, Faculty of Medicine, University of Witwatersrand, Johannesburg, South Africa.
Abstract
OBJECTIVE: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology. DESIGN: A nested substudy in a larger cohort of HIV-infected women which examined the association between ART status and birth outcomes. METHODS: Placentas (n = 130) were examined for histopathology from two ART groups: stable (n = 53), who initiated ART before conception and initiating (n = 77), who started ART during pregnancy [median (interquartile range) 15 weeks gestation (11-18)]. Using binomial regression we quantified associations between ART initiation timing with placental histopathology and pregnancy outcomes. RESULTS: One-third of all placentas were less than 10th percentile weight-for-gestation and there was no significant difference between ART groups. Placental diameter, thickness, cord insertion position and foetal-placental weight ratio were also similar by group. However, placentas from the stable group showed increased maternal vascular malperfusion (MVM) (39.6 vs. 19.4%), and decreased weight (392 vs. 422 g, P = 0.09). MVM risk was twice as high [risk ratios 2.03 (95% confidence interval: 1.16-3.57); P = 0.01] in the stable group; the increased risk remaining significant when adjusting for maternal age [risk ratios 2.04 (95% confidence interval: 1.12-3.72); P = 0.02]. Furthermore, MVM was significantly associated with preterm delivery and low birth weight (P = 0.002 and <0.0001, respectively). CONCLUSION: Preconception initiation of ART was associated with an increased MVM risk, and may contribute to placental dysfunction. The association between MVM with preterm delivery and low birth weight suggests that a placenta-mediated mechanism likely links the putative association between long-term use of ART and adverse birth outcomes.
OBJECTIVE: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology. DESIGN: A nested substudy in a larger cohort of HIV-infected women which examined the association between ART status and birth outcomes. METHODS: Placentas (n = 130) were examined for histopathology from two ART groups: stable (n = 53), who initiated ART before conception and initiating (n = 77), who started ART during pregnancy [median (interquartile range) 15 weeks gestation (11-18)]. Using binomial regression we quantified associations between ART initiation timing with placental histopathology and pregnancy outcomes. RESULTS: One-third of all placentas were less than 10th percentile weight-for-gestation and there was no significant difference between ART groups. Placental diameter, thickness, cord insertion position and foetal-placental weight ratio were also similar by group. However, placentas from the stable group showed increased maternal vascular malperfusion (MVM) (39.6 vs. 19.4%), and decreased weight (392 vs. 422 g, P = 0.09). MVM risk was twice as high [risk ratios 2.03 (95% confidence interval: 1.16-3.57); P = 0.01] in the stable group; the increased risk remaining significant when adjusting for maternal age [risk ratios 2.04 (95% confidence interval: 1.12-3.72); P = 0.02]. Furthermore, MVM was significantly associated with preterm delivery and low birth weight (P = 0.002 and <0.0001, respectively). CONCLUSION: Preconception initiation of ART was associated with an increased MVM risk, and may contribute to placental dysfunction. The association between MVM with preterm delivery and low birth weight suggests that a placenta-mediated mechanism likely links the putative association between long-term use of ART and adverse birth outcomes.
Authors: Malango T Msukwa; Olivia Keiser; Andreas Jahn; Joep J van Oosterhout; Andrew Edmonds; Nozgechi Phiri; Ronald Manjomo; Mary-Ann Davies; Janne Estill Journal: Trop Med Int Health Date: 2019-04-01 Impact factor: 2.622
Authors: Aris T Papageorghiou; Stephen H Kennedy; Laurent J Salomon; Douglas G Altman; Eric O Ohuma; William Stones; Michael G Gravett; Fernando C Barros; Cesar Victora; Manorama Purwar; Yasmin Jaffer; Julia A Noble; Enrico Bertino; Ruyan Pang; Leila Cheikh Ismail; Ann Lambert; Zulfiqar A Bhutta; José Villar Journal: Am J Obstet Gynecol Date: 2018-02 Impact factor: 8.661
Authors: Nadia M Ikumi; Komala Pillay; Tamara Tilburgs; Thokozile R Malaba; Sonwabile Dzanibe; Elizabeth Ann L Enninga; Rana Chakraborty; Mohammed Lamorde; Landon Myer; Saye Khoo; Heather B Jaspan; Clive M Gray Journal: J Infect Dis Date: 2021-12-08 Impact factor: 7.759