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Table 2 Mediation of the association between malaria in pregnancy and antepartum stillbirth or neonatal death

From: Mediation of the effect of malaria in pregnancy on stillbirth and neonatal death in an area of low transmission: observational data analysis

Mediating variable/s Natural indirect effect, risk ratio (95% CI) Natural direct effect, risk ratio (95% CI) Proportion indirect
Falciparum malaria and antepartum stillbirth
 SGA only 1.09 (1.05, 1.14) 1.61 (0.84, 2.67) 18%
 Maternal anaemia and SGA 1.23 (1.15, 1.34) 1.48 (0.77, 2.46) 42%
Symptomatic vivax malaria and antepartum stillbirth
 SGA only 1.10 (1.04, 1.17) 1.91 (0.65, 3.49) 16%
 Maternal anaemia and SGA 1.13 (1.06, 1.23) 1.73 (0.59, 3.20) 24%
Falciparum malaria and neonatal death
 Preterm birth only 1.25 (1.10, 1.43) 2.27 (1.29, 3.63) 26%
 SGA and preterm birth 1.30 (1.15, 1.49) 1.82 (1.07, 2.89) 40%
Vivax malaria and neonatal death
 Preterm birth only 1.20 (1.05, 1.37) 1.58 (0.94, 2.44) 31%
 SGA and preterm birth 1.25 (1.09, 1.44) 1.32 (0.81, 1.98) 50%
  1. Numbers are risk ratios (95% confidence interval). Natural direct effect (NDE, the effect of malaria on birth outcome, not mediated through the specified mediator/s); natural indirect effect (NIE, the effect of malaria on birth outcome, mediated through the specified mediator/s); SGA small-for-gestational-age. Note that total effects (NDE + NIE) from mediation analysis are not equivalent to the magnitude of associations obtained from Cox regression, which accounts for lost to follow-up and time-varying exposure and risk, because methods that incorporate time-to-event data in mediation analyses are limited. Maternal anaemia was defined as a final haematocrit during pregnancy of <30% (measured fortnightly throughout pregnancy). SGA was defined as a birthweight for gestational age below the 10th centile of INTERGROWTH-21st centiles. Maternal anaemia and SGA were included as binary variables because the association between the continuous variables, haematocrit and birthweight-for-gestational-age Z-score, and loge(odds) of stillbirth and/or neonatal death was non-linear. Maternal anaemia was not considered as a mediator of the association between malaria in pregnancy and neonatal death because <1% of women in this sub-set were anaemic. For further details on calculation and formal definitions of NDEs and NIEs, see Additional file 4
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