The impact of betel quid chewing during pregnancy on pregnancy outcomes in Bhutan

Betel (areca) nut is the fourth most widely used psychoactive substance globally, accounting for 10-20% of the world’s population. Its most basic form is betel ‘quid’ which consists of betel leaf, betel nut (the main psychoactive ingredient) and slaked lime. Evidence that betel quid and betel nut alone are associated with oral cancer has been established. Background: While there is a substantial body of evidence on the impact of health-risk behaviours including smoking and drinking alcohol on adverse pregnancy outcomes, studies on the impact of betel quid chewing on pregnancy outcomes are sparse and heterogeneous. Although several studies report the negative impact of betel quid chewing on pregnancy outcomes, the evidence is inconclusive. One of the challenges in understanding the impact of betel quid is to distinguish the impact of betel quid chewing from the impact of smoking. Bhutan, where low prevalence of smoking and high prevalence of betel-quid chewing are reported, provides a natural experimental environment for taking a close look at the impact of betel quid chewing alone. As a part of the global agenda to address preterm births (PTB) as a public health priority and in order to provide evidence to inform efforts to reduce neonatal morbidity and mortality in Bhutan, this study explores the impact of betel quid chewing on birth outcomes and its importance in relation to other risk factors. Methods: This study used a multi-centre case-control design. A case was defined as a mother of a singleton live born infant whose gestational age is less than 37 completed weeks and/or an infant whose birth weight is less than 2500 g. A control was defined as a mother of singleton live born term babies whose birth weight was more than 2500g and gestational age was greater than 37 weeks. Information was collected using a semi-structured questionnaire from February 2015 to the beginning of March 2016 at the three referral hospitals in Bhutan. Study participants were recruited by a trained interviewer during their post-delivery stay before discharge from each hospital. A statistical approach and a causal directed acyclic graph (DAG) approach were used for building logistic regression models. Results: Of the 669 study participants, 55% of the case mothers and 52% of the control mothers chewed betel quid during pregnancy. About 22% of cases and 22% of controls used commercial betel products during pregnancy. In total, 60% of the case mothers and 57% of the control mothers chewed either betel quid or packaged betel products during pregnancy. Neither the statistical approach nor DAG approach provided clear evidence of an association between betel quid use and low birth weight (LBW) or PTB. The adjusted odds ratio (aOR) of term LBW was 1.07 (95% CI: 8 0.54-2.13, p=0.845) in the statistical approach while the aOR of term LBW was 1.30 (95% CI: 0.74-2.27, p=0.439) in the DAG approach. Using the DAG approach, the aOR of PTB in association with betel quid chewing during pregnancy was 1.20 (95% CI: 0.72-2.00, p=0.614). When the total number of betel nuts consumed during the last three months of pregnancy was used as an exposure variable, the aOR for mothers who consumed more than one nut per day was 1.39 for term LBW (95%:0.52-3.68, p=0.514) and the aOR of PTB was 0.66 (95% CI: 0.27-1.66, p=0.383) compared to non-chewers. For a secondary outcome, the data suggest betel quid chewing is associated with increased odds of anaemia (aOR 2.09, 95% CI 1.27-3.43, p=0.004). Using the DAG approach, tobacco and alcohol use during pregnancy, low gestational weight gain, and urinary tract infection showed a clear association with term LBW and PTB. Conclusion: In the present study, the results provide no clear evidence of an association between term LBW or PTB and betel quid chewing during pregnancy. For a secondary outcome, the data suggest betel quid chewing is associated with increased odds of anaemia. The present study provides rich baseline data for mothers and established a cohort of cases and controls, which could be followed up to understand the short- and long-term effects of LBW and PTB and may help design effective interventions.