15th July 2024

Pre-eclampsia

Pre-eclampsia is a major contributor to global maternal morbidity and mortality. It occurs in around 5% of pregnancies.

Characterisation and diagnosis

Pre-eclampsia is a hypertensive disorder of pregnancy. It is defined as a new diagnosis of hypertension (systolic >= 140mmHg/diastolic >= 90mmHg) after 20 weeks of pregnancy, with organ dysfunction, manifested as one of:

• Proteinuria – detected via dipstick and confirmed by albumin: creatinine ratio above 8 mg/mmol or protein: creatinine creatinine ratio above 30 mg/mmol
• Maternal organ dysfunction
• Renal insufficiency – new rise in creatinine
• Hepatic impairment – increased liver transaminases
• Neurological complications – signs elicited on examination and the progression to eclampsia with seizures
• Uteroplacental dysfunction – foetal hypoxia, growth restriction, premature labour, placental abruption or in-utero demise caused by oxidative stress

For women with known CKD, diagnosing pre-eclampsia is more complicated.

• In cases where there is pre-existing non-proteinuric CKD, superimposed pre-eclampsia should be should be suspected after 20 weeks if new hypertension develops (systolic >= 140mmHg/diastolic >= 90mmHg) with new proteinuria or other evidence of maternal organ dysfunction.
• For women with CKD who have either pre-existing hypertension and/or proteinuria, there is no increase in either of these that are diagnostic for pre-eclampsia.
• However, women with chronic hypertension and proteinuria that develop severe, sustained hypertension (systolic >= 160mmHg/diastolic >= 1100mmHg) should be investigated for superimposed pre-eclampsia.
• Women with pre-eclampsia and CKD are at increased risk of pulmonary oedema peripartum.

Most cases of pre-eclampsia are based on the above clinical diagnostics. Increasingly, biomarkers also play a role in diagnosis. The National Institute for Health Care and Excellence (NICE) recommends offering tests for placental growth factor (PIGF) in suspected PET between 20 to 35 weeks’ gestation.

Clinical presentation

Patients with PET may complain of visual blurring, headaches, right upper quadrant pain and pedal oedema.

Risk factors

Although the aetiology of PET remains unclear, NICE guidelines outline the risks associated with development of PET. These can be divided into:

• History of previous hypertensive disorder during pregnancy
• Pre-existing hypertension – PET can be superimposed onto existing disease
• Concurrent maternal disease
• Chronic kidney disease
• Diabetes
• Maternal factors
• Nulliparity
• Increased maternal age (>40)
• High body mass index (BMI)
• Positive family history

Management

Women at high risk for pre-eclampsia, including women with chronic kidney disease, should start prophylactic aspirin (75-150mg) from 12 weeks’ gestation, reducing the risk of developing pre-eclampsia by 10%. Early detection of adverse foetal outcomes is monitored through increased frequency of antenatal scanning and obstetric clinics. Pre-eclamptic mothers should also monitor their blood pressures at home with pharmacological treatment started for blood pressure consistently 140/90mmHg or above. Renal and liver function tests should be measured two to three times per week, depending on the severity of hypertension.

Severe hypertension (>/=160/110 mmHg) should be treated in hospital under close obstetric monitoring and agents include oral nifedipine, methyldopa or oral/intravenous labetalol. Ultimately, timely delivery of the baby is the only curative management, balancing gestation for optimal in-utero development with maternal outcomes. Birth before 37 weeks is not indicated if blood pressure remains lower than 160/110 mmHg.

Follow-up

Blood pressure monitoring should continue after birth, daily for the first two days and once between day three and five. Anti-hypertensives should be continued postnatally for a similar time period. The adverse effects of pre-eclampsia have been shown to carry on into adult life, with a baby of a preeclamptic pregnancy having a higher relative risk of hypertension in later life. Key vascular changes lead to adverse cardiac remodelling and long-term cardiovascular morbidity. Future pregnancies should be closely monitored and other risk factors and concurrent diseases, such as diabetes, should be screened. Patients should have a follow up urine protein creatinine ratio to check for resolution of proteinuria. If it persists, patients should be referred to nephrology.

References

• Duhig KE, Myers J, Seed PT, Sparkes J, Lowe J, Hunter RM, Shennan AH, Chappell LC; PARROT trial group. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019 May 4;393(10183):1807-1818. doi: 10.1016/S0140-6736(18)33212-4. Epub 2019 Apr 1. PMID: 30948284; PMCID: PMC6497988
• Hypertension in pregnancy: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2019 Jun 25. PMID: 31498578
• Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007;369(9575):1791-8
• Davis EF, Lazdam M, Lewandowski AJ, Worton SA, Kelly B, Kenworthy Y, Adwani S, Wilkinson AR, McCormick K, Sargent I, Redman C, Leeson P. Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review. Pediatrics. 2012 Jun;129(6):e1552-61. doi: 10.1542/peds.2011-3093. Epub 2012 May 21. PMID: 22614768