Lessons learnt from enrolment and follow up of pregnant women and their infants in clinical trials in South Africa, a low-middle income country

Abstract

Introduction: Infectious causes are a significant contributor to morbidity and mortality in neonates and young infants. Immunization of pregnant women to protect the mother and/or her infant is gaining momentum due to the benefits of this strategy demonstrated in numerous implemented strategies (Maternal and Neonatal Tetanus Elimination Initiative) and clinical trials. Reluctance by regulators, participants and healthcare providers to include pregnant women in clinical trials is considerable, but reducing. Infectious disease burden, and therefore need for interventions to reduce morbidity and mortality in mothers and infants, is highest in low-middle income countries (LMIC), however, reliable background data on adverse pregnancy outcomes and lack of experience in clinical trials and community opinions on immunization during pregnancy are not well documented.

Methods: We used our experiences in conducting two clinical studies in pregnant women in South Africa to illustrate the challenges experienced and lessons learnt which may benefit others working in the maternal immunization field.

Results: Accurate gestational age assessment, which is essential for clinical trials, is challenging in LMIC due to limited access to early ultrasound examinations, and unreliable assessment by history (last menstrual period date) and physical examination (symphyseal-fundal height). Concomitant administration of recommended vaccines has previously been avoided in clinical trials; however, this limitation could impact the potentially beneficial interventions that participants can access during antenatal care. Women in LMIC have a higher burden of concomitant illnesses (e.g. HIV infection, malaria and anaemia) and adverse pregnancy outcomes (e.g. stillbirth) than pregnant women in higher income countries. Availability of local data is essential for safety monitoring committees to identify vaccine-related adverse event triggers.

Conclusion: Immunization of pregnant women to reduce disease burden in them and their infants is promising, and women in high-risk settings should be included in trials (Clinical trial registry number: 'Study A': NCT01193920, 'Study B': NCT01888471).

Keywords: GBS: Group B Streptococcus; HIV: human immunodeficiency virus; Immunization in pregnant women; LMIC: low middle income countries; Neonatal morbidity and mortality.