Simplified treatment for eclampsia prevention using magnesium sulfate

Maternal eclamptic seizure: occurrence of first onset of convulsions in a woman with features of pre-eclampsia that is unrelated to other neurological conditions; as documented on a participants trial chart or medical records from the time of randomization until day 7 after birth, hospital discharge, transfer to higher-level/another facility, withdrawal from study, or maternal death; whichever is first.

1. Composite endpoint describing events related to maternal toxicity and consisting of one or more of the following – absent/reduced tendon reflexes, respiratory depression, use of calcium gluconate to counteract perceived/confirmed maternal toxicity, or stopping/reduced magnesium sulfate treatment in the event of perceived/confirmed maternal toxicity: the occurrence of any of the above events related to maternal toxicity, individually documented on the participant’s STEPMag chart- which documents hourly assessments for these events.
1.1 Patella reflexes as assessed by the obstetric care provider during magnesium sulfate treatment; as documented on a scale from 0 to +4; where 0 is absent reflexes, +2 is normal, and + 4 is a sustained response. Tendon reflexes are assessed from randomization until 24 hours after start of treatment and recorded in the participant STEP-Mag chart.
1.2 Respiratory depression, defined as a respiratory rate of less than 16 respirations/minute as assessed by the obstetric care provider during magnesium sulfate treatment and recorded in the participant STEP-Mag chart.
1.3 Use of calcium gluconate, defined as the use of calcium gluconate given at any time during treatment to combat perceived or confirmed magnesium sulfate toxicity and recorded in the participant STEP-Mag chart.
1.4 Stopping/reduced magnesium sulfate treatment due to perceived/confirmed magnesium toxicity; as documented in the participant STEPMag chart as the rationale for the obstetric provider to lower (e.g., halving) the dose of magnesium sulfate treatment regimen, as defined in the protocol.
2. Maternal death (all-cause and cause-specific): the death of a woman and the underlying cause, measured using a review of patient notes for events up to day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
3. Death of baby before hospital discharge (stillbirth, perinatal death or neonatal death, for women enrolled before giving birth):
3.1. Stillbirth: defined as death of a fetus after documented evidence of fetal heart beats prior to randomization and showing no signs of life at time of birth. This outcome is documented at the time of delivery. In the case of participants enrolled with an intrauterine fetal demise prior to randomization, defined as absence of fetal heart beats, as confirmed by the obstetric provider and documented on the participant’s baseline information sheet.
3.2. Perinatal death: This is defined as the occurrence of stillbirth, stillbirth or neonatal death, or neonatal death following randomization in a woman enrolled prior to birth, measured using a review of patient notes from admission to day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
3.3. Neonatal death: This is defined as death of a live birth before the completion of 168 hours (7 days) after birth; as measured using a review of patient notes from admission to day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
4. Indicators of severe maternal morbidity (respiratory arrest, cardiac arrest, coagulopathy, renal failure, liver failure, pulmonary oedema, and stroke): the occurrence of any of the above severe maternal morbidity events, individually measured using a review of the participant STEPMag chart and patient notes from admission until day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
4.1. Respiratory arrest: woman not breathing or not able to breath
4.2. Pulmonary oedema: liquid accumulation in the tissues and airspaces of the lungs, diagnosed as based upon clinical auscultation or on chest X-ray
4.3. Cardiac arrest: no evidence of heart function or in setting of arrhythmia such as ventricular fibrillation
4.4. Renal failure: loss of kidney functions as a result of ischaemic injury, typically due to acute tubular necrosis in the context of pre-eclampsia
4.5. Liver failure: evidence of liver dysfunction due to severe spontaneous bleeding into the liver with haemorrhagic liver cell necrosis and rupture, haematoma, or infarction, hepatic encephalopathy or coma
4.6. Disseminated intravascular coagulopathy: This is an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. In pregnancy, diagnosis is based upon platelet count, fibrinogen and differences in prothrombin time.
4.7. Stroke: a serious life-threatening medical condition that happens when the blood supply to part of the brain is cut off. It could be ischaemic due to decreased blood flow to areas of the brain, or haemorrhagic due to bleeding into the brain by the rupture of a blood vessel. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side.
5. Maternal intensive care unit (ICU) admission: admission of a woman for intensive care in the hospital, measured using a review of patient notes from admission to day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
6. Recurrence of seizures (for women with eclampsia): the occurrence of the second or further episodes of generalized tonic clonic convulsion, measured using a review of patient notes from admission to day 7 after birth, or hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
7. Maternal side effects of magnesium sulfate (nausea or vomiting, flushing of the skin, drowsiness, confusion, muscle weakness, problem at injection site – pain, injection abscess with IM or IV administration): the occurrence of any of the above side effects, individually measured using a review of the participant STEPMag chart and patient notes.
7.1. Nausea or vomiting, flushing of the skin, drowsiness, confusion, muscle weakness recorded hourly for the 24 hours (on magnesium treatment)
7.2. problem at injection site – pain, injection abscess with IM or IV administration), as recorded hourly for the 24 hours (on magnesium treatment) or until transfer to higher level of care, death, withdrawal from the study, or 7 days after birth if the woman remains admitted; whichever is first.
8. Mode of birth (caesarean section or vaginal birth): the final mode of birth for a woman who was randomized prior to giving birth, measured using a review of the patient notes at the time of birth.
9. Induction of labour: the artificial initiation of labour in a woman who was randomized prior to giving birth, measured using a review of the patient notes from the time of birth.
10. Augmentation of labour: the artificial stimulation of labour in a woman who was randomized prior to giving birth, measured using a review of the patient notes from the time of birth.
11. Abruptio placenta: the occurrence of premature separation of the placenta in a woman who was randomized prior to giving birth, measured using a review of the patient notes from the time of birth.
12. Postpartum haemorrhage: the occurrence of postpartum blood loss estimated at ≥ 500 mL following a vaginal birth or ≥ 1000 mL following a caesarean birth within 24 hours after birth (i.e. primary postpartum haemorrhage) in a woman who was randomized prior to giving birth, measured using a review of the patient notes at 24 hours after birth.
13. Treatment with additional uterotonics for postpartum haemorrhage: the use of additional uterotonic(s) for therapeutic treatment of primary postpartum haemorrhage (in addition to any prophylactic uterotonics) in a woman who was randomized prior to giving birth, measured using a review of the patient notes from 24 hours after birth.
14. Blood transfusion: the use of any blood or blood products (i.e., no minimum volume) in a woman who was randomized prior to giving birth, measured using a review of the patient notes from admission to day 7 after birth, hospital discharge, transfer to higher level of care, maternal death, or withdrawal from the study; whichever is first.
15. Retained placenta: as placenta or membranes that have not been expelled from the uterus during the third stage of labour and up to 30 minutes following childbirth in a woman who was randomized prior to giving birth, measured using a review of the patient notes up to 24 hours after birth.
16. Indicators of severe neonatal morbidity (Apgar <7 at 5 minutes, need for intubation at birth, ventilation, seizures, admission to neonatal intensive care or special care unit): the occurrence of any of the above severe neonatal morbidity events in a woman who was randomized prior to giving birth.
16.1. Apgar < 7 at 5 minutes: Apgar score of the baby at 5 minutes of life lower than 7 out of 10; individually measured using a review of patient notes from the time of birth.
16.2. Need for intubation at birth: Intubation received at time of birth. This outcome relates specifically to intubation at the time of birth; individually measured using a review of patient notes from the time of birth.
16.3. Ventilation: Any ventilation received by the infant from time of birth (mechanical ventilation, use of supplemental oxygen, or CPAP); individually measured using a review of patient notes from the time of birth.
16.4. Neonatal seizures: Any neonatal convulsion experienced between time of birth and until day 7 after birth, maternal discharge, transfer to higher level care, death, or withdrawal from the study (whichever is earliest). A convulsion can be any of the following signs, criteria are listed below:
16.4.1 Generalized convulsion (repetitive jerking movements of limbs or face; continuous extension or flexion of arms and legs, either synchronous or asynchronous: apnoea (spontaneous cessation of breathing for more than 20 seconds); or the baby may appear unconscious or awake but unresponsive.
16.4.2 Subtle convulsion (Repetitive blinking, eye deviation, or staring; repetitive movements of mouth or tongue; purposeless movement of the limbs, as if bicycling or swimming; or apnea: the baby may be conscious .
17. Gestational age at birth: the gestational age (in weeks ± days) at which the baby of a woman randomized was born, measured using a review of the patient notes at the time of birth (for women randomized prior to birth).
18. Birthweight: the birthweight of the baby (in grams) of a woman randomized, measured using a review of the patient notes at the time of birth for women randomized prior to birth)
19. Small-for-gestational age: an infant with birth weight less than 10th centile for the gestational age, based on obstetric assessment of gestational age, birthweight, and the neonatal growth chart (length vs weight), measured using a review of patient notes at the time of birth for a woman randomized prior to birth.
20. Maternal satisfaction: satisfaction of a woman with magnesium sulfate regimen received, measured using a modified treatment satisfaction for medication questionnaire at the time of discharge.