Prevalence and Risk Factors for Infantile Bleeding and Mortality in Rural Bangladesh: Is Vitamin K Deficiency a Cause?
Authors: Thorne‐Lyman Andrew L , Rashid Mahbubur , Wu Lee , Schulze Kerry , Christian Parul , Labrique Alain B , Ali Hasmot , Mehra Sucheta , Shaikh Saijuddin , Klemm Rolf DW , West Keith P 
Published: November 2023

BACKGROUNDDespite growing attention to the importance of reducing neonatal mortality, little is known about the prevalence, types, severity, causes or case fatality of infant bleeding in rural South Asia. Vitamin K deficiency is a presumptive cause but this remains unknown.OBJECTIVEThe objectives of this study were to document the prevalence, severity, mortality case fatality rates and risk factors for infantile bleeding in rural Bangladesh.METHODSThis study was conducted within the JiVitA‐1 trial in northwest Bangladesh which tested effects of antenatal vitamin A or beta‐carotene supplementation on infant and maternal mortality. 59,756 pregnancies were detected through community surveillance from Aug 2001 to Oct 2006, resulting in 41,956 live births. Bleeding symptoms of bruising, and bleeding from the umbilicus and nose, were identified by parental recall at 3 and 6 months. Additionally, a verbal autopsy, administered to consenting parents of all deceased infants, included recall of the same bleeding symptoms. Mortality per 1000 live born infants and case fatality rate (CFR) per 1000 symptomatic cases were based on deaths within 7 days of incident symptoms. Risk ratios were estimated using log‐binomial regression for associations between different covariates and risk of bleeding and bleeding‐related mortality. Associations were examined between maternal PIVKA‐II levels in the 3rd trimester and 3 months postpartum from a subset of 62 cases and 216 controls, matched on gestational age at birth, using restricted cubic splines fit to conditional logistic regression models.RESULTSIncidence per 1000 [95% CI] of a 1st episode of any bleeding through 6 mo of age was 53.06 [50.64, 55.47], early bleeding (<48 hours of birth) was 11.15 [10.02, 12.28], classical bleeding (2–7 days) was 20.95 [19.38, 22.52], late bleeding was 22.62 [20.96, 24.29]. The CFR for any bleeding event under 6 mo was 216.5 [197.2, 235.7] per 1,000 cases. Nasal bleeding had a particularly high CFR of 605.3 [550.32, 660.2]. Significant risk factors for bleeding included maternal age, parity, accident in the 3rd trimester, gestational age at delivery, obstructed labor, and breech birth. No statistically significant linear or non‐linear associations were found between bleeding and maternal PIVKA‐II levels during the 3rd trimester or 3 mo post‐partum, times that may not reflect newborn vitamin K status.CONCLUSIONBleeding in early infancy is highly prevalent and fatal in rural Bangladesh. While several risk factors were identified, vitamin K deficiency remains a presumptive cause due widespread lack of supplementation at birth. In low resource settings where infant bleeding is observed, trials of oral VK supplementation may be warranted to evaluate its impact in reducing bleeding and infant mortality.Support or Funding InformationSupported by the Bill & Melinda Gates Foundation (GH614)