Identifying novel prodromal symptoms of eclampsia: A two-country, case-control study

Magnesium sulphate halves the risk of eclampsia. There is no consensus on who to give magnesium sulphate prophylaxis because clinical tools are poor at identifying those at risk. Known prodromal symptoms such as headache, visual disturbance, or epigastric pain have modest associations with eclampsia. We set out to identify new prodromal symptoms of eclampsia.

This case-control study prospectively recruited participants in South Africa and Pakistan who had eclampsia, preeclampsia, or normotensive pregnancies. We asked whether they experienced 20 neurological symptoms, within 7 days of the seizure for those who had eclampsia. The primary analysis was the likelihood of symptoms occurring before eclampsia, compared to being present with preeclampsia. 341 participants were recruited with eclampsia, 1,355 with preeclampsia and 389 with normotensive pregnancies. When comparing symptoms among those who had eclampsia versus preeclampsia, the odds ratios (OR) were 2.56 (95% confidence interval (CI) [1.81,3.62]; p < 0.001) for headache, 5.73 (95% CI [4.44,7.39]; p < 0.001) for visual disturbances and 2.25 (95% CI [1.76,2.89]; p < 0.001) for epigastric pain. We identified 10 symptoms with odds ratios over 10 for eclampsia. Odds ratios were 42.03 (95% CI [23.66,74.68]; p < 0.001) for twitching/jerking limbs (30.5% eclampsia versus 1% preeclampsia); 36.00 (95% CI [18.34,70.65]; p < 0.001) for affected hearing (21.1% versus 0.7%)' 33.60 (95% CI [21.39,52.78]; p < 0.001) for affected mind state (38.7% versus 1.8%); 33.12 (95% CI [19.46, 54.37]; p < 0.001) for impaired speech; 23.71 (95% CI [16.49,34.10]; p < 0.001) for feelings of doom; 26.59 (95% CI [7.82,90.41]; p < 0.001) for severe vertigo; 20.52 (95% CI [14.22,29.63]; p < 0.001) for confusion; 18.16 (95% CI [10.76,30.66]; p < 0.001) for jitters; 15.18 (95% CI [11.34,20.33]; p < 0.001) for difficulty concentrating; and 10.49 (95% CI [6.76,16.27]; p < 0.001) for weakness/paralysis. These symptoms were rare among normotensive pregnancies. Only 2.4% of women with eclampsia did not experience any prodromal symptoms. This study is limited by the fact that we asked about prodromal symptoms after the seizure happened, and the potential for recall bias.

Ten prodromal symptoms exhibit far stronger associations with eclampsia than headache, visual disturbances, or epigastric pain. Eclampsia is uncommon without any prodromal symptoms. It may be useful to screen these symptoms among women with preeclampsia as part of clinical history taking to guide management. They could help direct magnesium sulphate prophylaxis to those with a higher risk of eclampsia.