This study expands ongoing inquiry and debates on the influence of single-parent households on child health outcomes, particularly in low- and middle-income countries (LMICs), where the phenomenon is rapidly increasing. It examines how conventional (i.e., access to money for children—conceived as experience of poverty—, family support, and experience of social isolation) and contemporary (i.e., health literacy) factors shape the health-related well-being of children in single-parent homes in Ghana in the short-, medium- (five years or less) and long-term (6 years +). It also investigates the extent to which health literacy explains how other factors influence their health-related well-being. Data was gathered through a cross-sectional survey conducted in Kumasi in the Ashanti region of Ghana (n = 337). Based on binary logistic regression and structural equation modelling analysis, health literacy (Odds Ratio, OR, = 1.086, p < 0.05) and social isolation (OR, = 0.584, p < 0.05) were associated with the health-related well-being of children who had been separated from a parent for five years or less while family support (OR = 1.592, p < 0.05) was associated with the health-related well-being of children separated from a parent for more than five years. Health literacy explained the association of experience of poverty (β = -0.012, p < 0.05) and experience of social isolation (β = -0.010, p < 0.10) with their health-related well-being. However, these significant relationships did not differ according to the duration of separation. The results underscore the need to invest in policies and programmes that can reduce exposure to health risks and empower children in single-parent households to contribute to protecting their health-related well-being.
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