Prevention of pre-eclampsia
There is a considerable literature devoted to the prevention of preeclampsia with the intention of avoiding the associated maternal and perinatal complications. However, preeclampsia, at least in its non-s evere form, may serve some adaptive function in terms of improved neonatal outcomes in the neonatal intensive care unit or neurodevelopmental outcome (67, 68).
Therefore, we have based our preventative recommendations on both the prevention of pre-eclampsia and/or the prevention of its associated complications where the literature permits. Preventative interventions may be best started before 16 weeks’ when most of the physiological transformation of uterine spiral arteries occurs, or even before pregnancy. Such early intervention has the greatest potential to decrease the early forms of pre-eclampsia that are associated with incomplete transformation of uterine spiral arteries (69).
Pregnant women can be classified as being at ‘low’ or ‘increased’ risk of pre-eclampsia most commonly by the presence or absence of one or more of the risk markers (Table 21.4). Widespread implementation of the following interventions is recommended to help prevent pre-eclampsia and its complications (15, 19).
Table 21.3 Investigations to diagnose and monitor women with a hypertensive disorder of pregnancy
| Investigations for diagnosis | Description in women with pre-eclampsia | Description in women with other conditions |
| Maternal testing | ||
| Uterine testing | ||
| Urinalysis (routine and microscopy with/ without additional tests for proteinuria) | Proteinuria (as discussed under Proteinuria) without RBCs or casts | Haemoglobinuria (dipstick 'haematuria' without RBCs): haemolytic anaemia RBCs alone: renal stones, renal cortical necrosis (also associated with back pain and oliguria/ anuria) RBCs and/or casts are associated with other glomerular disease and scleroderma renal crisis and (about half of) TTP-HUS Bacteria: UTI or asymptomatic bacteriuria Proteinuria is usually absent in secondary causes of hypertension such as phaeochromocytoma, hyperaldosteronism, thyrotoxicosis, coarctation of the aorta, and withdrawal syndromes |
| Oxygen saturation | ||
| Pulse oximetry | SpO2 bgcolor=white>Tests of coagulation | |
| INR and APTT | ↑ with DIC which is usually associated with placental | May be ↑ in APS, DIC from other causes including sepsis, amniotic fluid embolism, stillbirth, massive haemorrhage, haemangiomas, shock |
| abruption ↑ is associated with adverse maternal outcome | ↑ is prominent in AFLP | |
| Fibrinogen | θ | 4 with all causes of DIC including massive haemorrhage, genetic disorders |
| 4 more profound with AFLP than with HELLP | ||
| Usually normal in TTP-HUS (ADAMTS13 vWF cleaving protein may be moderately decreased in HELLP but ADAMTS13 antibody should be absent | ||
| Serum chemistry | ||
| Serum creatinine | ↑due to haemoconcentration and/ or renal failure ↑ associated with adverse maternal outcome | ↑ with other acute or chronic kidney disease. Rental failure prominent in malignant hypertension, TTP-HUS (along with thrombocytopenia), AFLP (along with liver dysfunction) |
| Serum uric acid | ↑ associated with adverse maternal and perinatal outcomes | ↑ with dehydration, medication (e.g. HCTZ), genetic causes |
| Glucose | θ | 4 with AFLP1 insulin therapy |
| AST or ALT | ↑ associated with adverse maternal outcome | ↑ with AFLP and other 'PET imitators' but to a lesser degree, and usually normal in TTP-HUS |
| May be increased in other pregnancy-related conditions (e.g. intrahepatic cholestasis of pregnancy) or conditions not associated with pregnancy (e.g. viral hepatitis or cholecystitis) | ||
| LDH | ↑ which may be prominent | ↑ with AFLP1 intravascular haemolysis |
| ↑ the is associated with adverse maternal outcome | ↑ LDH, AST ratio (>22) with TTP-HUS | |
(continued)
Table 21.3 Continued
| Investigations for diagnosis | Description in women with pre-eclampsia | Description in women with other conditions |
| Bilirubin | ↑ unconjugated from haemolysis or conjugated from liver dysfunction | (early) ↑ in AFLP1 ↑ with haemolytic anaemia, other liver disease with dysfunction, genetic disease |
| Albumin | f associated with adverse maternal and perinatal outcomes | f as negative acute phase reactant with acute severe illness, malnutrition, nephrotic syndrome, crystalloid infusion |
| Fetal testing | ||
| Abnormalities are not specific to the cause of poor placentation and/or placental dysfunction | ||
| Uterine artery Doppler velocimetry | Unilateral/bilateral notching, or elevated pulsatility index or resistance index may support a diagnosis of placental insufficiency including pre-eclampsia | |
AFLP1 acute fatty liver of pregnancy; APS, antiphospholipid syndrome; APTT, activated partial thromboplastin time; CBC, complete blood count; DIC, disseminated intravascular coagulation; HCTZ, hydrochlorothiazide; HUS, haemolytic uraemic syndrome; INR, international normalized ratio; ITP1 immune thrombocytopenic purpura; PET, pre-eclampsia; SpO2, oxygen saturation by pulse oximetry; RBC, red blood cell; TTP, thrombotic thrombocytopenic purpura; vWF, von Willebrand factor.
Source data from The FIGO Textbook of Pregnancy Hypertension (2016) p42-43,
Table 21.4 Prediction of pre-eclampsia
| Maternal | Paternal | |||||
| Demographics and family history | Past medical or obstetric history | Current pregnancy | ||||
| First trimester | Second or third trimester | |||||
| Previous pre-eclampsia | Multiple pregnancy | |||||
| Antiphospholipid antibody syndrome | ||||||
| Pre-existing medical condition(s) | ||||||
| • Pre-existing hypertension or booking DBP ≥90 mmHg | ||||||
| • Pre-existing renal disease or booking proteinuria | ||||||
| • Pre-existing diabetes mellitus | ||||||
| Afro-Caribbean or South Asian race | Lower maternal birth weight and/or preterm delivery | Short maternal stature ≤164 cm/5'5" | Excessive weight gain in pregnancy | Paternal age ≥45 years | ||
| Maternal age ≥35-40 years | Thrombophilias | Overweight/obesity | ||||
| Family history of pre-eclampsia (grandmother, mother or sister) | Increased pre-pregnancy triglycerides, total cholesterol and/ or non-HDL-cholesterol | Reduced physical activity | Mother had pre-eclampsia | |||
| Family history of early-onset cardiovascular disease | Non-smoking | First ongoing pregnancy | Fathered pregnancy complicated by pre-eclampsia with another partner | |||
| Rural location (LMICs) | Cocaine and/or methamphetamine use | New partner | ||||
| Previous miscarriage at ≤10 weeks with same partner | Short duration of, or reduced, exposure to sperm of current partner | |||||
| Previous pregnancy complicated by IUGR | Reproductive technologies | |||||
| Maternal uterine anomaly | Inter-pregnancy interval≥4 years | |||||
| Increased stress | Mental health (depression and/or anxiety) | |||||
| bgcolor=white>Booking SBP ≥130 mmHg | Elevated BP (gestational hypertension) | |||||
| Rural location (LMICs) | (Recurrent miscarriage) | Booking DBP ≥80 mmHg | Gestational proteinuria | |||
| Vaginal bleeding in early pregnancy | ||||||
| Gestational trophoblast disease | ||||||
| Anaemia with low vitamin C and E intake (LIMCs) | ||||||
| Severe anaemia (Hb It is our responsibility to ensure that we advocate for use of effective interventions whether we practice in well- or under-resourced settings. Fluids Plasma volume expansion is not recommended for women with pre-eclampsia, and, indeed, intravenous fluid intake should be minimized to 80 mL/hour in women with pre-eclampsia to avoid pulmonary oedema (14, 15, 76, 77). Fluid should not be routinely administered to treat oliguria (min | 4 h | Best avoided in women with asthma or heart failure Neonatology should be informed if the woman is in labour, as parenteral labetalol may cause neonatal bradycardia Parenteral therapy should be followed by ongoing oral therapy to maintain BP | ||||
| Nifedipine | Calcium channel blocker (vasodilator) | Capsule 5-10 mg to swallow without biting Repeat every 30 min | 5-10 min | 30 min | 6 h | There are three types of nifedipine preparations with which all staff must be familiar capsules, intermediate-release tables (PA, SR, or retard tablet) and slow-release tablets (XL, MR, or LA) Nifedipine may be given at the same time as MgSO4 |
| PA, SR. or retard tablet 10 mg to swallow | 30 min | 240 min | 6 h | |||
| Repeat every 30 min (max dosage 30 mg) | ||||||
| Hydralazine | Direct-acting vasodilator | Intermittent dosing 5 mg IV | 5 min | 30 min | 3-8 h | May increase the risk of maternal hypotension |
| Repeat 5-10 mg IV every 30 min (may be given IM but unusual) | ||||||
| Continuous infusion | ||||||
| 0.5-10 mg/h IV (max. dosage 45 mg) | ||||||
| Labetalol | Peripheralb alpha-1 and (non-selective) beta-1 and -2 receptor antagonist | 200 mg orally Repeat in 4 h (max. dosage 2400 mg/day in 4 divided dosesc) | 20-120 min | 1-4h | 8-12 h | Duration is dose dependent |
| Methyldopa | Centrally acting alpha-2 receptor agonist | 750 mg orally Repeat in 6 h (max. dosage 2000 mg/day in 4 divided dosesc) | Not known | 4-6 h | 24-48 h | Less effective than oral nifedipine |
| Clonidined | Centrally acting alpha-2 receptor agonist | 0.1-0.2 mg orally | 30-60 min | 2-4 h | 6-10 h | Clonidine therapy is not recommended during breastfeeding6 |
| Repeat in 1 h (max. dosage 0.8 mgc) | ||||||
| Captoprild only postpartum | Angiotensinconverting enzyme inhibitor | 6.25-12.5 mg orally Repeat in 1 h (max. dosage 75 mg) | 30 min | 60-90 min | ≥8 h | Captopril must NOT be administered before delivery, but it is acceptable for use during breastfeeding.0 Duration is dose dependent |
| Nitroglycerine infusion | Direct vasodilators that has its affects veins more than arterioles | 5 mcg/min, increased every 5 min (max rate 100 mcg/ min) | 2-5 min | 5 min | 5-10 min | Main side effects are headache (due to direct vasodilation) and tachycardia (from reflect sympathetic activation) |
Methaemoglobinaemia has been reported after 24 h of treatment
BP, blood pressure; IM, intramuscular; IV, intravenous; MgSO4, magnesium sulphate.
a General reference http://www.drugs.com.
b Beta-blockade is three to seven times more than alpha-blockade, especially at lower doses.
c Dosing of this drug may continue after the severe hypertension has resolved, as it is used for chronic treatment of non-severe hypertension.
d Captopril (25 mg) and clonidine (0.1 mg) are being compared in a postpartum randomized controlled trial (NCT01761916) based on the effectiveness of these medications for severe hypertension treatment outside pregnancy.
e http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm.
Source data from The FIGO Textbook of Pregnancy Hypertension (2016) p138-139.
Table 21.6 Antihypertensives for non-severe pregnancy hypertension
| Agent | I Mechanism of action | I Dosage | Comments |
| Methyldopa | Centrally acting alpha-2 receptor agonist → decreased sympathetic outflow → decreased peripheral vascular resistance | 250-500 mg PO BID-QID (max. dosage 2000 mg/day) | There is no evidence to support a loading dose of methyldopa |
| Psychological side effects (e.g. drowsiness or depression) may occur but women do not change drugs more frequently than with other medication Within first 6 weeks of therapy, >10% may develop hepatitis or cholestasis that can be detected by laboratory testing; abnormalities should reverse with discontinuation, but liver failure is rare. After 6 months of therapy, 10-20% develop a positive direct Coombs' test, but it does not interfere with typing or cross matching and associated haemolytic anaemia is rare | |||
| Labetalol | Peripheral3 alpha-1 and (non-selective) beta-1 and 2 receptor antagonist → decreased peripheral vascular resistance with no reflex increase in heart rate | 100-400 mg PO BID-QID (max. 2400 mg/day) | Some experts recommend a starting dose of 100 mg PO TID because the half-life of labetalol is shorter in pregnancy May be associated with postural hypotension, especially at higher doses |
| Nifedipine | Calcium channel blocker → vascular smooth muscle relaxation → decrease peripheral vascular resistance | PA, SR, or retard tablets 10-20 mg PO BID-TID (max. 180 mg/ day) | Peripheral oedema as a side effect may be more common at doses of 120 mg/day or more |
| XL, MR or LA preparation 20-60 mg PO OD-BID (max. 120 mg/day) | |||
BID, twice a day; PO, per os; QID, four times a day; TID, three times a day
a Beta-blockade is three to seven times more than alpha-blockade, especially at lower doses. Source data from The FIGO Textbook of Pregnancy Hypertension (2016) p 142.
The authors do not recommend corticosteroids for treatment of HELLP syndrome until they have been proven to decrease maternal morbidity through adequately powered randomized controlled trials (14, 15).
The authors recommend against plasma exchange or plasmapheresis for HELLP syndrome, particularly within the first 4 days postpartum (14, 15). These interventions can be important therapies for women with pre-eclampsia mimickers such as haemolytic uraemic syndrome.
Other therapies for treatment of pre-eclampsia
Women with pre-eclampsia before 35+0 weeks' gestation should receive antenatal corticosteroids for acceleration of fetal pulmonary maturity (14, 15). In addition, thromboprophylaxis may be considered antenatally among women with pre-eclampsia who have two or more additional thromboembolic risk markers, postnatally among women with pre-eclampsia who have at least one additional thromboembolic risk marker, or postnatally among women any HDP who were on antenatal bed rest for at least 7 days (14, 15).
More on the topic Prevention of pre-eclampsia:
- Arulkumaran S., Ledger W., Denny L., Doumouchtsis S. (eds.). Oxford Textbook of Obstetrics and Gynaecology. Oxford University Press,2020. — 928 p., 2020
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