Pregnancy, Hypertension, and Preeclampsia: Advancing Understanding of a Complex Relationship

At a Glance

  • Preeclampsia is one of the most common medical disorders of pregnancy and affects between 3 to 10 percent of pregnancies.
  • The relationship between kidney function and pregnancy outcomes and overall maternal health requires a more encompassing understanding from all those who treat women with preeclampsia.
  • Although a lot is known about preeclampsia, there remain important gaps in medical knowledge.

"Acknowledging that while the obstetricians and nephrologists may have different perspectives about preeclampsia, at NewYork-Presbyterian, the ongoing collaboration and communication has resulted in unique opportunities to make scientific discoveries and translate these discoveries to render excellent care for patients."

Phyllis August, MD, MPH

The obstetrician and the nephrologist see patients with preeclampsia through different lenses, Phyllis August, MD, MPH wrote in a 2013 article published in Advances in Chronic Kidney Disease. The article, which emphasized the complex and multifaceted features of preeclampsia, proposed physicians move past their focus on single attributes of preeclampsia to reduce the risk of harm to mother and baby.

“We have a holistic view of preeclampsia and a true interdisciplinary approach to treatment at NewYork-Presbyterian,” emphasizes Dr. August. “A very close research and clinical collaboration with obstetricians, neonatologists, and researchers has ensured that patients seeking care at our hospital have unprecedented access to a team of specialists. Acknowledging that while the obstetricians and nephrologists may have different perspectives about preeclampsia, at NewYork-Presbyterian, the ongoing collaboration and communication has resulted in unique opportunities to make scientific discoveries and translate these discoveries to render excellent care for patients.”

Dr. August believes that the interesting relationship between kidney function and pregnancy outcomes and overall maternal health requires a more encompassing understanding from all those who treat women with preeclampsia.

“You have young women in the prime of their lives, and you don’t want to permit them to get into a situation that would be life-threatening — for them or their babies,” says Dr. August. Her work has focused on the interrelationships of kidney function, blood pressure regulation, and pregnancy, particularly in women with hypertension and those at risk for preeclampsia.

Significance of Hypertension to Preeclampsia

Preeclampsia is a syndrome of gestation diagnosed after 20 weeks and characterized by mild to severe hypertension, proteinuria equal to or more than 300 mg/day, or evidence of organ dysfunction — particularly in the kidney. “An absorbing and unique relationship exists between kidney function and having a healthy pregnancy,” says Dr. August, who is one of only a handful of nephrologists in the country with a major clinical focus on gestational hypertension.

“If kidney function is impaired at all, a pregnant woman is at risk for a myriad of complications. In addition to causing high blood pressure, abnormal kidney function may result in early delivery or a smaller than normal newborn. The other interesting aspect is that it’s a bidirectional relationship.”

Preeclampsia is one of the most common medical disorders of pregnancy and affects between 3 to 10 percent of pregnancies. Preeclampsia profoundly affects the kidney, causing, in addition to proteinuria, reduced function and other more subtle defects, such as impaired calcium excretion by the kidney, first reported by Dr. August and her colleagues in the New England Journal of Medicine in 1987.

“Elevated blood pressure is often the first clinical sign that preeclampsia is present,” says Dr. August. “It is a clinical feature that often leads to preterm deliveries and an important risk factor for one of the most lethal sequelae of preeclampsia – maternal intracerebral hemorrhage. Subtle increases in blood pressure are detectable weeks before preeclampsia is diagnosed.” Dr. August’s research has also focused on why blood pressure is elevated in women with preeclampsia and has found that alterations in the renin-angiotensin system, a key hormonal system that regulates blood pressure and kidney function, are routinely present in women with hypertension in pregnancy and preeclampsia.

Dr. August appreciates the older name for preeclampsia – toxemia – as it implies that the cause is a circulating toxin in the blood, a theory that persists to this day. “Although we have learned a lot about this disorder, there remain important gaps in our knowledge.

“We don’t yet know what causes the abnormalities in the placenta that ultimately lead to preeclampsia,” says Dr. August. While the condition generally improves after the baby is delivered, one of the important features of toxemia that Dr. August and others have reported is that the women who have had this disorder in pregnancy are at increased risk for cardiovascular disease, and possibly kidney disease later in life. “We are very interested in why this is the case.”

The Challenges of Treatment

“One of the more challenging aspects of preeclampsia — whether you take the obstetric or nephrocentric perspective — is that despite considerable understanding regarding some of the key pathogenetic features, treatment options are fairly limited,” says Dr. August, who served on the 2013 Task Force on Hypertension in Pregnancy convened by the American Congress of Obstetrics and Gynecology. “Antihypertensive therapy can prevent severe maternal hypertension, but not preeclampsia. We have become somewhat better at predicting who is at higher risk and can thus implement closer surveillance for women with a history of preterm preeclampsia and those with multiple gestations, chronic hypertension, diabetes, preexisting kidney disease, and obesity.”

The early pregnancy identification of women with chronic hypertension – which alone is a major risk factor for preeclampsia – would permit more intensive surveillance, more aggressive care, and hopefully better maternal and fetal outcomes.”

So how should the treatment of hypertension be approached in women who are or may become pregnant? In young women considering pregnancy, identifying and treating hypertension is important. Dr. August notes that although most women with hypertension at the beginning of gestation have what is known as essential hypertension, and do quite well during pregnancy, the experience of her and her colleagues, supported by limited published evidence, suggests that identification of secondary causes of hypertension is important and often overlooked. These conditions — pheochromocytoma, renovascular hypertension, obstructive sleep apnea, Cushing’s syndrome, and primary aldosteronism — are not common, but they are associated with considerable risks to the expectant mother with hypertension and the unborn fetus who is at risk for preterm birth, morbidity due to prolonged hospitalization associated with prematurity, and death. If appropriately diagnosed, they can be cured, and subsequent pregnancy outcomes much improved – and often quite healthy.

According to the ACOG guidelines, a blood pressure greater than or equal to 160/105 should be treated. For women with chronic hypertension whose delivery is imminent, safe medications include IV labetalol, IM or IV hydralazine, calcium channel blockers, or diazoxide. Those with a delayed delivery can be prescribed methyldopa, labetalol, calcium channel blockers, alpha or blockers, or hydralazine. “In women who have a history of preterm preeclampsia and want to have another baby, we consider recommending low-molecular-weight heparin and baby aspirin to prevent complications.”

Important Lines of Investigation

Dr. August and her colleagues – maternal-fetal medicine specialist Daniel W. Skupski, MD, and third-year fellow Line Malha, MD– continue to pursue research to expand the understanding and treatment of hypertension and preeclampsia further. “We are collaborating with the Suthanthiran laboratory and beginning to look at biomarkers in women who are at risk for but have not yet developed preeclampsia to identify the microRNAs that determine who will get into trouble as the pregnancy progresses,” says Dr. August.

“We have previously established clinical markers and related tests that are useful for predicting who will get preeclampsia, but we are interested in looking at the genetic basis with the hope that this will point us in the direction of understanding more about the mechanism of preeclampsia and, in particular, defining treatments to prevent recurrent preeclampsia in subsequent pregnancies.

“Our evidence base to guide our use of the antihypertensive treatment in women with preeclampsia can be improved, and important questions regarding thresholds for beginning anti-hypertensive therapy and treatment targets remain,” continues Dr. August. “For the nephrologist, preeclampsia is an exciting field. There are significant opportunities for progress as the disorder encompasses many aspects of nephrology and obstetrics, and despite the sometimes dramatic presentations accompanied by maternal and fetal morbidity and mortality, overall the outcomes are generally happy ones."

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