Learn about preeclampsia symptoms, signs, and the difference between preeclampsia and eclampsia. Discover effective eclampsia management at Meri Sehat.

Pre-eclampsia

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Ismail Munir

Overview

Pre-eclampsia is a pregnancy-specific condition characterized by new onset <a href="https://merisehat.pk/disease/hypertension-57">hypertension </a>and proteinuria. 
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Pre-eclampsia is a complex, multi-systemic condition that only affects pregnant women. It most commonly develops after the 20th week of gestation, but can occur after delivery.&nbsp; Approximately 10% of cases occur before 34 weeks of pregnancy<a href="#accordion">[1]</a>.

Previously called toxemia, this hypertensive disorder accounts for 2-8% of pregnancy-related complications worldwide<a href="#accordion">[2]</a>. Furthermore, in low-income countries, pre-eclampsia is responsible for 9-26% of all maternal deaths, and 16% in high-income nations<a href="#accordion">[2]</a>. This is due to the availability of limited sources and inferior access to appropriate obstetric care and services for family planning in low and middle-income countries (LMIC).

&nbsp;

The incidence of preeclampsia varies depending on ethnicity and race, with higher rates recorded among African-Americans and Hispanics<a href="#accordion">[1]</a>.

Pre-eclampsia is characterized by new-onset hypertension. This is defined as a systolic blood pressure of 140mmHg or more, or a diastolic blood pressure of 90mmHg or above, on 2 or more occasions at least 4 hours apart; or a systolic blood pressure of 160mmHg or more, or a diastolic reading of 110mmHg or above<a href="#accordion">[2]</a>. Women may also experience proteinuria, swelling in the extremities, and in severe cases, end-organ damage.

In severe cases, pre-eclampsia can progress to eclampsia which presents with seizures. Moreover, it can result in preterm delivery and other maternal and fetal complications. Globally, both pre-eclampsia and eclampsia account for more than 50,000 maternal deaths per year<a href="#accordion">[1]</a>. 
&nbsp;

Note: If you notice high blood pressure or increased swelling of the hands and feet during pregnancy, contact a healthcare professional immediately.&nbsp;

&nbsp;

Pre-eclampsia can be classified as mild or severe.These are including: 
&nbsp;

<ul>
	<li>Mild Pre-eclampsia: If a person has elevated blood pressure along with high amounts of protein in their urine, they might be given the diagnosis of mild pre-eclampsia.</li>
	<li>Severe Pre-eclampsia: This accounts for 25% of all pre-eclampsia cases<a href="#accordion">[2]</a>. Along with signs of mild pre-eclampsia, the women will have signs of liver or renal impairment, low levels of platelets, fluid in the lungs, disorientation and headaches, and visual disturbances. 
	&nbsp;</li>
</ul>

Signs and Symptoms

Most people do not experience any symptoms of pre-eclampsia. The condition is often discovered during regular prenatal appointments. 
&nbsp;

Other than elevated blood pressure, some common signs and symptoms of pre-eclampsia are:

<ul>
	<li>Swelling in the hands and feet (<a href="https://merisehat.pk/disease/edema">edema</a>)</li>
	<li>Severe and persistent headaches</li>
	<li>Pain in the right upper abdomen</li>
	<li>Unusual and sudden weight gain</li>
	<li>Nausea or vomiting</li>
	<li>Shortness of breath</li>
	<li>Blurry vision</li>
	<li>Seeing spots</li>
	<li>Decreased urine production</li>
	<li>Proteinuria 
	&nbsp;</li>
</ul>

Severe pre-eclampsia can cause the following symptoms:

<ul>
	<li>Hypertensive emergency (Blood pressure reading is 160/110mmHg or higher)</li>
	<li>Thrombocytopenia (Low levels of platelets in the blood)</li>
	<li>Fluid in the lungs</li>
	<li>Decreased urine production</li>
	<li>Impaired kidney or liver function 
	&nbsp;</li>
</ul>

Note: It is important to share all your pregnancy symptoms with your doctor. Look out for any of the above symptoms during pregnancy. 
&nbsp;

Causes

It is unclear as to what exactly causes pre-eclampsia. However, doctors propose that the placenta may play a role in the development of the condition. It is believed that abnormal placental implantation or a decreased blood supply to the placenta may result in pre-eclampsia. The reduced supply of blood and nutrients to the placenta then causes the release of distress markers, such as inflammatory cytokines and antiangiogenic factors. As a result, there is abnormal vessel formation and inadequate vascular accommodation in the renal, hepatic, and cardiovascular systems.

Genetic and environmental factors may also play a role in causing the condition.&nbsp; 
&nbsp;

Detecting pre-eclampsia in its early phases in healthy women has been very effective in reducing prenatal and perinatal issues. Pre-eclampsia is rare before 20 weeks of gestation, but as the pregnancy progresses toward maturity, it gradually becomes more prevalent. Therefore, tests are performed more frequently during the third trimester.

As per the U.S. Preventive Services Task Force (USPSTF), blood pressure measurements should be obtained on each prenatal care visit throughout pregnancy<a href="#accordion">[3]</a>.&nbsp; 
&nbsp;

Circulating indicators or a Doppler ultrasound analysis of the uteroplacental vasculature can both identify pre-eclampsia that is either impending or already present. This may be helpful for the early onset version of the condition but not the late-onset form. Maternal indicators of endothelial activation include new hypertension or proteinuria, whereas placental syncytiotrophoblast factors are more specific and occur earlier in the pathogenesis. A higher sFlt-1/PlGF ratio is a reliable indicator of placental toxemia and fetal development limitation brought on by placental malperfusion.

Pre-eclampsia must be ruled out to rule out the necessity for delivery within the next 2 weeks, and before 35 weeks. The PlGF number can do this with a 98% likelihood<a href="#accordion">[4]</a>. This rises to a chance of more than 99% within the next week when integrated with the sFlt-1/PlGF ratio<a href="#accordion">[5]</a>. The ratio does not accurately indicate late-onset pre-eclampsia, similar to uterine artery Doppler evaluation. The ideal time to decide is in the starting months of pregnancy when interventions can start even before the signs and symptoms appear. To increase the accuracy of prediction, combinations of demographic &amp; clinical variables with maternal BP, uterine artery Doppler readings, and blood biomarker evaluations have been put together<a href="#accordion">[6]</a>. In a study of prophylactic low-dose aspirin, a form of enhanced first-trimester screening was utilized, and the findings were promising, mainly detecting early onset pre-eclampsia. Whatever the result of these changes, quantitative predictions of the risk of pre-eclampsia should be reliable rather than subjective ones.

However, as per the USPSTF, there is inadequate evidence of the effectiveness of these risk prediction tools<a href="#accordion">[3]</a>. 
&nbsp;

Diagnosis

The diagnosis of pre-eclampsia is often made during routine prenatal appointments. During the physical examination, the doctor will assess the individual&rsquo;s blood pressure, weight gain, edema, and any other symptoms. Ideal conditions call for taking blood pressure while sitting and placing the proper-sized monitor on the upper arm just above the heart. Although auscultatory devices are commonly used and dependable, an approved automatic device computed for pregnancy and pre-eclampsia can be used<a href="#accordion">[7]</a>. 
&nbsp;

Most pre-eclamptic women have measurable proteinuria. The gold standard for detecting proteinuria has traditionally been a 24-hour urine sample, but it is difficult to perform properly and can be inaccurate. A spot protein to creatinine ratio of 30 mg/mol or more, or an albumin to creatinine ratio of higher than 8 mg/mol are fast and dependable alternatives to identify clinically relevant proteinuria and are now integrated into many guidelines definitions<a href="#accordion">[8]</a>. Only the diagnosis of a nephrotic range is now deemed to require a 24-hour urine sample.

&nbsp;A urinary dipstick value of 2+ or higher is highly indicative of clinically relevant proteinuria when laboratory estimation is not available<a href="#accordion">[9]</a>. Most international recommendations acknowledge that pre-eclampsia can be diagnosed by its extreme symptoms, and they advise that when certain symptoms and indications show, the patient should either deliver the baby or be admitted to the hospital for safety and close monitoring. Moreover, ultrasound and fetal monitoring are also conducted to assess the size of the fetus and amniotic fluid volume. 
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Treatment

Once identified, pre-eclampsia frequently worsens over time and affects the functioning of maternal organs. To avoid complications, the general management strategy is to deliver the infant and placenta at term gestation or, if pre-eclampsia is discovered, to attempt awaited management of the pregnancy until a more advanced gestation is achieved. If it is decided to keep going with the pregnancy, both the mother and the unborn child need to be carefully watched, and the infant needs to be delivered if there is proof that either is clinically impaired. 
&nbsp;

Pregnancy termination should be started if pre-eclampsia develops at 37 weeks or later because expectant care will raise the risk of unfavorable maternal outcomes with little to no fetal benefit<a href="#accordion">[10]</a>. A Cochrane evaluation of four studies found that expectant care may be linked to lowered morbidity for the infant at preterm gestations before 34 weeks<a href="#accordion">[11]</a>.

As a result, a frequent treatment approach is to keep the pregnancy going until the fetus is at a later stage of gestation. Pre-eclampsia is carefully monitored, and if clinically significant maternal organ failure or fetal compromise is present, delivery is accelerated. 
&nbsp;

In mild pre-eclampsia, the doctor will advise the following:

<ul>
	<li>Bed rest or hospitalization</li>
	<li>Frequent blood and urine tests to assess for proteinuria and low platelet levels</li>
	<li>Fetal monitoring</li>
	<li>Regular ultrasounds</li>
	<li>Anit-hypertensive medications, such as hydralazine, labetalol, and nifedipine</li>
	<li>Steroid injections to develop the baby&rsquo;s lungs</li>
</ul>

&nbsp;

At the hospital, the women may receive injections of magnesium sulfate to prevent eclampsia-related seizures. Intravenous magnesium may also be given during labor and following delivery.

As per the American College of Obstetricians and Gynecologists (ACOG), women at 37 weeks of gestation diagnosed with mild pre-eclampsia should undergo immediate delivery rather than expectant management<a href="#accordion">[1]</a>.

<div>
A 2019 systematic review looking at the timing of birth for pre-eclampsia diagnosed between 34- &amp; 37-week gestation found that women with a greater risk of developing pre-eclampsia complications, such as those women who are nulliparous, may benefit from an earlier delivery by 36 weeks gestation. Risks to the baby (such as respiratory distress syndrome) decrease to the point where the threshold for starting a planned delivery becomes lower than before 36 weeks gestation. Since the publication of this meta-analysis, a further study contrasting scheduled early birth with expectant management up until results showed that although the proportions of infants with neonatal morbidity had similarity between the 2 groups, immediate delivery increased admission to the neonatal unit, while it decreased the risk of a composite of adverse maternal outcomes<a href="#accordion">[12]</a>. Timing the delivery is a trade-off between maternal and fetal risk between 34- and 37 weeks gestation, and the woman should be informed of the choice. 
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<h5>Post-delivery Care</h5>

Symptoms of pre-eclampsia typically resolve within 48 hours of delivery. However, in some cases, people may develop pre-eclampsia or eclampsia after delivery. Therefore, patients suffering from pre-eclampsia need to be carefully watched for hypertension and other symptoms of pre-eclampsia after delivery. They should be informed before they leave the hospital when to call an ambulance if they experience postpartum pre-eclampsia symptoms like severe headaches, vision changes, severe abdominal pain, nausea, or vomiting. 
&nbsp;
</div>

Pre-eclampsia complications can include: 
&nbsp;

<ul>
	<li>Growth Restriction In Fetus - Pre-eclampsia impacts the arteries carrying blood to the placenta. Thus, the fetus might not get sufficient blood, oxygen, or nutrition. This can result in fetal growth restriction or slow growth. 
	&nbsp;</li>
	<li>Preterm Delivery - Pre-eclampsia can lead to an unplanned premature birth &mdash; delivery before 37 weeks. Pre-eclampsia&#39;s standard treatment is planned preterm birth. An infant who is delivered too soon is more likely to experience breathing and feeding issues, visual or hearing issues, cognitive disabilities, and cerebral palsy. Treatments before preterm delivery might well decrease some risks. 
	&nbsp;</li>
	<li>Cardiovascular Disease - Women with pre-eclampsia may have higher chances of developing heart and blood vessel disease (cardiovascular disease). 
	&nbsp;</li>
	<li>Placental Abruption - Pre-eclampsia raises the risk of placental abruption. The placenta gets separated from the innermost wall of the uterus before the delivery. Serious abruption can result in heavy bleeding, which can be fatal for the mother and baby both. 
	&nbsp;</li>
	<li>Eclampsia - Eclampsia is the emergence of seizures or coma in conjunction with pre-eclampsia signs and symptoms. It is difficult to predict if a patient with pre-eclampsia will eventually get eclampsia. Eclampsia can occur without any prior indications of pre-eclampsia. Severe headaches, visual difficulties, mental disorientation, or altered behavior are all signs and symptoms that may occur before seizures. However, there are frequently no signs or warning indications. Eclampsia may take place before, in between, or after delivery. 
	&nbsp;</li>
	<li>HELLP Syndrome - HELLP is the abbreviation for hemolysis (the destruction of red blood cells), elevated liver enzymes, and low platelet count. This complex type of pre-eclampsia impacts numerous organ systems. HELLP syndrome is life-threatening for the mother and baby and can cause lifetime medical issues for the mother. Vomiting and nausea, headache, upper right abdominal pain, and overall sentiment of illness or being unwell are the common signs and symptoms of HELLP syndrome. Occasionally, it develops unexpectedly, even before hypertension is identified. Moreover, it may advance without any indications. 
	&nbsp;</li>
	<li>Damage To Organs - Pre-eclampsia can damage the kidneys, liver, lungs, heart, and eyes, and can also cause a stroke as well as other brain injuries. The extent of injury to certain other organs depends on how serious the pre-eclampsia is. 
	&nbsp;</li>
</ul>

The following factors can increase one&rsquo;s risk of developing pre-eclampsia: 
&nbsp;

<ul>
	<li>Pre-gestational diabetes</li>
	<li>Nulliparity</li>
	<li>Maternal age &lt;20 years</li>
	<li>Multifetal pregnancy (e.g., twins or triplets)</li>
	<li>Family history of pre-eclampsia</li>
	<li>Antiphospholipid syndrome</li>
	<li>Pre-pregnancy body-mass index &gt;30 kg/m&sup2;</li>
	<li>Autoimmune disorders (e.g., Systemic lupus erythematosus)</li>
	<li>Pre-eclampsia in previous pregnancy</li>
	<li>Previous stillbirths</li>
	<li>Existing chronic disease, such as diabetes, chronic hypertension, or kidney disease</li>
	<li>Placental abruption in the past</li>
	<li>Maternal age &gt;35 years</li>
	<li>In-vitro fertilization (IVF) 
	&nbsp;</li>
</ul>

<ul>
	<li>
	<h5>Aspirin</h5>
	</li>
</ul>

Aspirin is the only effective evidence-based preventative drug therapy for pre-eclampsia.

A 2019 Cochrane study found high-quality evidence that low-dose aspirin if taken daily from the end of the first trimester until 36 weeks&#39; gestation lowers the risk of getting pre-eclampsia by around 18%<a href="#accordion">[13]</a>. Preterm pre-eclampsia is expected to have a higher risk reduction than pre-eclampsia in general. It is unknown how aspirin protects pre-eclampsia. Speculations include that aspirin promotes placental implantation, necessitating aspirin use early in pregnancy; and that aspirin protects the maternal vasculature by reducing platelet reactivity, lowering thromboxane concentration levels, and increasing prostacyclin production, necessitating aspirin use throughout pregnancy<a href="#accordion">[14]</a>.

The ASPRE trial enrolled 1776 women who were recognized as being at an elevated risk for pre-eclampsia during the first trimester. The study found that 150 milligrams of aspirin at night decreased their chance of preterm pre-eclampsia before 37 weeks gestation by 62%<a href="#accordion">[15]</a>.

&nbsp;

<ul>
	<li>
	<h5>Calcium</h5>
	</li>
</ul>

Calcium taken orally might prevent pre-eclampsia, particularly when dietary calcium consumption is insufficient. A meta-analysis found that 1 g of calcium every day decreased rates of pre-eclampsia. Calcium supplementation can be more beneficial in decreasing the risk of pre-eclampsia among women with poor dietary calcium consumption than in those with sufficient intake<a href="#accordion">[16]</a>.

&nbsp;

<ul>
	<li>
	<h5>Lifestyle And Healthful Decisions</h5>
	</li>
</ul>

It&#39;s an appreciable notion to be as healthy as possible before getting pregnant, particularly if the woman has a history of pre-eclampsia. 
&nbsp;

Note: Discuss with your provider how to manage any illnesses that raise your chance of pre-eclampsia. 
&nbsp;

Key Points

<ul>
	<li>Pre-eclampsia is a multifactorial disease prenatal condition defined by varying degrees of placental malperfusion.</li>
	<li>Pre-eclampsia is a leading cause of mother and perinatal death and morbidity, particularly in low- and middle-income nations.</li>
	<li>Delivery is timed to maximize fetal and maternal results.</li>
	<li>Women are often treated with intravenous magnesium sulfate to prevent the occurrence of seizures.</li>
	<li>Ongoing research is looking into the effectiveness, dose, and timing of aspirin and calcium to avoid pre-eclampsia, as well as other medications to manage high blood pressure or slow disease development. 
	&nbsp;</li>
</ul>

[1] Kee-Hak Lim MD. Preeclampsia. Practice Essentials, Overview, Pathophysiology.

[2] Karrar SA, Hong PL. Preeclampsia. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.

[3] Screening for preeclampsia: Recommendation statement. American Family Physician.

[4] Chappell LC, Duckworth S, Seed P, Griffin M, Myers J, Mackillop L. Diagnostic accuracy of placental growth factor in women with suspected pre-eclampsia: a prospective multicenter study. Circulation [revista en Internet]. 2013 [cited 14 ul 2019]; 128 (19):[aprox. 20p].

[5] Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P, Marti GE, Caporaso NE. B-cell clones as early markers for chronic lymphocytic leukemia. New England Journal of Medicine. 2009 Feb 12;360(7):659-67.

[6] McLaughlin K, Zhang J, Lye SJ, Parker JD. Kingdom JC. Phenotypes of pregnant women who subsequently develop hypertension in pregnancy. J Am Heart Assoc. 2018 Jul 14;7(14):e009595.

[7] Walker MG, Fitzgerald B, Keating S, Ray JG, Windrim R, Kingdom JC. Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery. Placenta. 2012 Jul 1;33(7):568-71.

[8] Côté AM, Brown MA, Lam E, von Dadelszen P, Firoz T, Liston RM, Magee LA. Diagnostic accuracy of urinary spot protein: creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. Bmj. 2008 May 1;336(7651):1003-6.

[9] Saudan PJ, Brown MA, Farrell T, Shaw L. Improved methods of assessing proteinuria in hypertensive pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology. 1997 Oct;104(10):1159-64.

[10] Koopmans CM, Bijlenga D, Groen H, Vijgen SM, Aarnoudse JG, Bekedam DJ, Van Den Berg PP, De Boer K, Burggraaff JM, Bloemenkamp KW, Drogtrop AP. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial. The Lancet. 2009 Sep 19;374(9694):979-88.

[11] Churchill D, Duley L, Thornton JG, Moussa M, Ali HS, Walker KF. Interventionist versus expectant care for severe pre‐eclampsia between 24 and 34 weeks' gestation. Cochrane Database of Systematic Reviews. 2018(10).

[12] Chappell LC, Brocklehurst P, Green ME, Hunter R, Hardy P, Juszczak E, Linsell L, Chiocchia V, Greenland M, Placzek A, Townend J. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. The Lancet. 2019 Sep 28;394(10204):1181-90.

[13] Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre‐eclampsia and its complications. Cochrane database of systematic reviews. 2019(10).

[14] Banala C, Moreno S, Cruz Y, Boelig RC, Saccone G, Berghella V, Schoen CN, Roman A. Impact of the ACOG guideline regarding low-dose aspirin for prevention of superimposed pre-eclampsia in women with chronic hypertension. American journal of obstetrics and gynecology. 2020 Sep 1;223(3):419-e1.

[15] Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS. Aspirin versus placebo in pregnancies at high risk for preterm pre-eclampsia. New England Journal of Medicine. 2017 Aug 17;377(7):613-22.

[16] Hofmeyr GJ, Lawrie TA, Atallah ÁN, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane database of systematic reviews. 2018(10).

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