Estimating baseline rates of adverse perinatal and neonatal outcomes using a facility-based surveillance approach: A prospective observational study from the WHO Global Vaccine Safety Multi-Country Collaboration on safety in pregnancy

Abstract

Background: Most perinatal and neonatal deaths occur in low- and middle-income countries (LMICs), yet, quality data on burden of adverse outcomes of pregnancy is limited in such countries.

Methods: A network of 21 maternity units, across seven countries, undertook surveillance for low birthweight, preterm birth, small for gestational age (SGA), stillbirths, congenital microcephaly, in-hospital neonatal deaths, and neonatal infections in a cohort of over 85,000 births from May 2019 - August 2020. For each outcome, site-specific rates per 1,000 livebirths (or per 1,000 total births for stillbirth) and 95% confidence intervals (CI) were calculated. Descriptive sensitivity analysis was conducted to gain insight regarding underreporting of four outcomes at 16 sites.

Findings: Estimated rates varied across countries and sites, ranging between 43·3-329·5 and 21·4-276·6/1000 livebirths for low birthweight and preterm birth respectively and 11·8-81/1,000 livebirths for SGA. No cases of congenital microcephaly were reported by three sites while the highest estimated rate was 13/1,000 livebirths. Neonatal infection and neonatal death rates varied between 1·8-73 and 0-59·9/1000 livebirths respectively while stillbirth rates ranged between 0-57·1/1000 total births across study sites. Results from the sensitivity analysis confirmed the underreporting of congenital microcephaly and SGA in our study.

Interpretation: Our study establishes site-specific baseline rates for important adverse perinatal and neonatal outcomes and addresses a critical evidence gap towards improved monitoring of benefits and risks of emerging pregnancy and neonatal interventions.

Funding: The study was sponsored by the World Health Organization with funding from the Bill and Melinda Gates Foundation.

Keywords: Baseline rates; Minimum detectable risk; Neonatal outcomes; Perinatal outcomes; Pharmacovigilance; Surveillance; Vaccines.

Figure 1

Map of study sites with status of protocol amendment. * St Francis Regional Hospital (United Republic of Tanzania) did not routinely assess births for SGA and congenital microcephaly, hence these two outcomes were not studied for this site. ** Data collection had to be terminated at 8 months at Grant GMC Hospital (India). At all other sites, data was collected for 12 months consecutively. # The registration and screening of individual births was not recorded in the SOMAARTH III application at the two sites in Spain due to lack of approval from EC. This information was submitted in aggregated format by the two sites and recorded in the study application by all other sites. Abbreviations- BP: BP Koirala Institute of Health Sciences; GH: General Hospital; GMC: Government Medical College; GUH: General University Hospital; H: Hospital; IMS SUM: Institute of Medical Science and Sum Hospital; MC: Medical College; PC: Polyclinic; PH: Provincial Hospital; RH: Referral/Regional Hospital; RRH: Regional Referral Hospital; SKIMS: Sher-i-Kashmir Institute of Medical Sciences; TH: Teaching Hospital; UH: University Hospital; ZRH: Zonal Referral Hospital.

Figure 2

Comparison of preterm birth, low birthweight, neonatal deaths and stillbirth rates from the literature and site-specific rates observed in the study, by country. The yellow bars represent rates from the literature and the blue bars represent rates from study sites, where each bar represents one site. From left to right the sites in Ghana are: 1) St Joseph's H; 2) Ejisu H; 3) Tema GH; 4) Eastern RH; Tanzania: 1) Mbeya ZRH; 2) St Francis RH; 3) Mbeya RRH; Zimbabwe: 1) Mbare PC; 2) Mutare PH; India: 1) JSS H; 2) Grant GMC; 3) IMS SUM H; 4) Kasturba MC; 5) MP Shah MC; 6) SKIMS; Islamic Republic of Iran: 1) Mahdieh H; 2) Shohada H. Nepal: 1) Patan H; 2) BP Koirala; Spain: 1) Castellon GUH; 2) Dr Peset UH (no cases of neonatal death and stillbirth reported by this site). ^aSource: Chawanpaiboon S, Vogel JP, Moller A-B, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. The Lancet Global Health 2019; 7(1): e37-e46. ^bSource: United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). Levels & Trends in Child Mortality: Report. New York, 2020. ^cSource: United Nations Children's Fund (UNICEF) & World Health Organization (WHO). Low birthweight estimates: levels and trends 2000-2015, 2019. ^dLow birthweight rates not available for India and Islamic Republic of Iran; hence, rates from South Asia and Middle East/North Africa regions were used for comparison ^eSource: United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). A neglected tragedy: the global burden of stillbirths 2020.