Preeclampsia prevention by timed birth at term

Delivery with PE as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) 2021.14. The definition of PE is chronic hypertension or new onset hypertension (systolic blood pressure (BP) should be ≥140 mm Hg and/or diastolic ≥90 mm Hg, on at least two occasions four hours apart BP >140/90 mm Hg) ≥ 20 weeks of gestation together with any of the following:
1. Proteinuria, defined as ≥300 mg in 24 hours or urinary creatinine ratio ≥30 mg/mmol (0.3 mg/mg) or two readings of at least ++ on dipstick analysis of midstream or catheter urine specimens if no 24-hour collection is available; or
2. Maternal organ dysfunction, defined as any one of the following:
2.1. Acute kidney injury with creatinine >90 μmol/l or
2.2. Liver involvement with elevated transaminases (alanine or aspartate aminotransferase [ALT or AST] >40 IU/L or twice the normal concentration) or
2.3. Haematological complications (thrombocytopaenia with platelet count <150 x 109/L), disseminated intravascular coagulation or haemolysis, or
2.4. Neurological complications, such as eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, or persistent visual scotomata, or
3. Uteroplacental dysfunction, defined as estimated fetal weight (EFW) <3rd percentile or EFW at the 3rd to 10th percentile in the presence of either of the following: uterine artery pulsatility index (UtA-PI) >95th percentile, umbilical artery PI (UA-PI) >95th percentile, or middle cerebral artery PI (MCA PI) <5th percentile

All outcome measures will be recorded during the routine care appointment and during childbirth. When the participants do not gIve birth at the chosen hospital, then the outcome is taken from their medical record.

All outcome measures will be recorded during the routine care appointment and during childbirth. When the participants do not gIve birth at the chosen hospital, then the outcome is taken from their medical record.

1. Emergency caesarean section, defined as any caesarean section after spontaneous onset or induction of labour. A caesarean section without prior labour will be considered as elective
2. Neonatal care unit stay for ≥48 consecutive hours up to primary hospital discharge home or 28 days of life, whichever is earlier

Other secondary outcomes:
1. GH, defined as systolic BP ≥140 mm Hg and/or diastolic ≥90 mm Hg, on at least two occasions 4 hours apart, and developing at ≥20 weeks’ gestation in previously normotensive women (i.e., BP <140/90 mm Hg)
2. Components of the 2021 ISSHP definition of PE (as above)
2.1. PE as defined by ACOG 201915:
2.2. GH (as above) or severe hypertension (as below), and either
2.3. Proteinuria (as above) or
2.4. In absence of proteinuria, one/more of:
2.4.1. Pulmonary edema
2.4.2. Platelet count <100 x 10e9/litre)
2.4.3. Serum creatinine >97 μmol/L or a doubling in its value
2.4.4. Abnormal liver enzymes (ALT or AST >67 IU/litre)
3. ‘Severe features’ of PE (one or more), and its components, according to ACOG 201915 and without alternative diagnoses:
3.1. Severe hypertension (as defined below)
3.2. Platelet count <100 x 10e9/L
3.3. ALT or AST raised to twice normal (>67 IU/L) and persistent severe right upper quadrant abdominal or epigastric pain unresponsive to medication and not otherwise accounted for by alternative diagnoses
3.4. Serum creatinine >97 μmol/L or a doubling of value in the absence of other renal disease
3.5. Pulmonary edema
3.6. New-onset headache unresponsive to medication
3.7. Visual disturbances
4. Preeclampsia Integrated Estimate of Risk Score (PIERS) combined adverse maternal outcome, and its components, derived from Delphi consensus (with the exception of the Glasgow coma score <13):
4.1. Maternal death
4.2. Central nervous system complications (one or more of):
4.2.1. Stroke (acute neurological event with deficits lasting > 24 hr, not due to a post-ictal state)
4.2.2. Eclampsia (generalized convulsion in the absence of a history of epilepsy)
4.2.3. Blindness (either retinal or cortical, defined as loss of visual acuity in the presence of intact pupillary response to light)
4.3. Cardiorespiratory complications (one or more of):
4.3.1. Uncontrolled hypertension (requiring administration of 3 or more different parenteral [intravenous or intramuscular] antihypertensive agents within a 12-hour period)
4.3.2. Inotropic support (use of vasopressors to keep systolic BP >90 mmHg or a MAP >70 mmHg)
4.3.3. Pulmonary oedema (diagnosed clinically with one/more of oxygen saturation < 95%, diuretic treatment or x-ray confirmation)
4.3.4. Respiratory failure (intubation, ventilation by endotracheal tube or non-invasively, or need for > 50% oxygen for > 1 hr which is not due to caesarean delivery)
4.3.5. Myocardial ischemia or myocardial infarction (by characteristic ECG changes and markers of myocardial necrosis)
4.3.6. SpO₂ <90%
4.4. Haematological complications (one or more of):
4.4.1. Platelet count <50 x 10e9/L
4.4.2. Transfusion (of any blood product)
4.5. Hepatic complications (one or more of):
4.5.1. Dysfunction (INR>1.2 in the absence of DIC or treatment with warfarin, OR, in the presence of DIC or treatment with warfarin: either mixed hyperbilirubinemia >17 μM or hypoglycemia <2.5 mM) in the absence of insulin)
4.5.2. Hepatic haematoma or rupture (presence of a blood collection under the hepatic capsule as confirmed by imaging or at laparotomy)
4.6. Acute kidney injury:
4.6.1. Acute serum creatinine >200 µM with pre-existing renal disease
4.6.2. Acute serum creatinine >150uM with no pre-existing renal disease
4.6.3. Dialysis
4.7. Placental abruption (clinically or on placental examination)
4.8. Other (as detailed, with appropriate information from hospital records)
5. Core maternal outcome set for PE17 (one or more of) and its components:
5.1. Maternal mortality
5.2. Central nervous system complications: eclampsia, stroke, blindness that is retinal or cortical (as defined for PIERS)
5.3. Cardiorespiratory complications: pulmonary edema, respiratory failure (as defined for PIERS)
5.4. Platelet count <100 x 10e9/L
5.5. Hepatic complications: AST or ALT raised to twice normal, or haematoma (as for PIERS)
5.6. Acute kidney injury (as for PIERS)
5.7. Placental abruption
5.8. Postpartum haemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth)
5.9. Maternal admission to intensive care or high dependency unit
6. Severe hypertension (defined as systolic BP ≥160 mm Hg and/or diastolic BP ≥110 mm Hg, on at least one occasion)
7. Caesarean section (any)
8. Labour onset, classified as spontaneous, induced, or no labour. (Spontaneous rupture of membranes without labour will be considered as spontaneous labour onset)
9. Maternal admission to intensive care or high dependency unit
10. Total number of nights in hospital
11. Gestational age at delivery
12. Stillbirth
13. Birthweight <3rd, <5th and <10th percentile for gestational age, calculated using the Fetal Medicine Foundation birthweight chart
14. Neonatal death (after birth or within the first 28 days of life)
15. Admission to neonatal care unit (for any duration)
16. Neonatal morbidity:
16.1. Intraventricular haemorrhage grade II or above, defined as bleeding into the ventricles
16.2. Neonatal sepsis (defined as confirmed bacteraemia in cultures)
16.3. Encephalopathy grade (mild, moderate, severe) requiring head cooling
16.4. Neonatal seizures
16.5. Anaemia defined as low haemoglobin and/or haematocrit requiring blood transfusion
16.6. Respiratory distress syndrome, defined as the need for ventilation with or without surfactant
16.7. Necrotising enterocolitis requiring surgical intervention
16.8. Composite of any of the above
17. Neonatal therapy:
17.1. Neonatal intensive care unit admission
17.2. Ventilation, defined as the need for positive pressure (continuous positive airway pressure) or nasal continuous positive airway pressure (NCPAP) or intubation
17.3. Composite of any of the above