First medical device developed to filter blood to treat preeclampsia

courtesy: APT

The U.S. Food and Drug Administration (FDA) granted a Breakthrough Device Designation for the Advanced Prenatal Therapeutics, Inc. (APT) Targeted Apheresis Column for Preeclampsia (TAC-PE) in the treatment of preeclampsia.

Currently, the therapeutic options for preeclampsia are limited and include bed rest, anti-hypertensive medications and induction of preterm labor if needed.

The TAC-PE column is an apheresis device that works like kidney dialysis in selectively removing the harmful substances from the blood. While the exact cause of preeclampsia is not known, several biomarkers have been identified that are responsible for life-threatening preeclampsia symptoms like kidney and liver dysfunction and high blood pressure.

The apheresis procedure resembles voluntary blood donation. The woman’s blood is pumped through the apheresis machine to separate it into plasma and blood cells. The plasma then passes through the TAC-PE device, where the toxic substances are captured. The toxin-free plasma is mixed with the cells and returned to the patient.

APT first therapeutic target is soluble fms-like tyrosine kinase-1 (sFlt-1). The circulating sFlt-1is made by the placenta and antagonizes the action of Vascular endothelial growth factor (VEGF), that triggers new vessel formation and vasodilatation in normal pregnancies. Pre-eclampsia occurs when the relative functional activity sFlt-1 exceeds that of VEGF resulting in vasoconstriction in important organs like kidney, liver, and brain (the organs most affected by preeclampsia).

Removal of sFlt-1 from blood helps to restore the vascular homeostasis by alleviating the endothelial dysfunction. This eliminates the need for premature termination of pregnancy, helps stabilize the mother and baby to let the pregnancy proceed naturally to term.

“We were navigating virtually uncharted waters in 2005 when we first proposed that preeclampsia could be treated using an apheresis column to remove pathogenic factors such as sFlt-1,” said Dr. James Smith, President/CEO of APT. “Now that we are preparing for initial clinical studies, we are very pleased that the Breakthrough Designation will help provide a clear and efficient pathway to market.”

APT is a Laguna Hills, California based company involved in developing an effective treatment that will safely prolong pregnancy, allowing babies more time to develop in the womb in patients with preeclampsia.

TAC-PE: TARGETED APHERESIS COLUMN FORPREECLAMPSIA

Advanced Prenatal Therapeutics PressRelease…

Here is a video from APT

News from ACOG 2018: Aspirin cuts down the risk of superimposed preeclampsia in women with chronic hypertension

Keeping up with the American College of Obstetricians and Gynecologists (ACOG) 2016 practice guideline of supplementing low-dose aspirin to pregnant women with chronic hypertension was associated with a 57% decrease in superimposed preeclampsia.

Investigators at Thomas Jefferson University presented the results of this retrospective study in a poster presentation at the ACOG 2018 annual meeting (April 27–30, 2018, Austin, Texas).

The study participants included 715 women with chronic hypertension carrying singleton pregnancy, who delivered at Thomas Jefferson University Hospital between January 2008 to July 2017.

The women were divided into 2 groups based on whether they delivered before and after ACOG recommendations. The pre-ACOG group included 635 women while the post-ACOG group had 80 women.

The cohort was further stratified based on additional risk factor for the development of superimposed preeclampsia (SIP) like a previous history of preeclampsia or pregestational diabetes. The primary outcome of interest was the development of preeclampsia, while the secondary outcomes studied were the incidence of SIP with severe features (SIPSF), small for gestational age, and preterm birth was also studied.

The incidence of SIP was dramatically reduced by 57% in women with chronic HT who received low dose aspirin (OR 0.43 (95% CI 0.26-0.73).

Women who had no other risk factor for the development of SIP, the incidence of SIP and SIP with severe features decreased by 75% and 77% respectively.

The incidence of secondary outcomes did not show any significant changes. Aspirin showed the highest benefits in women with chronic hypertension who did not have any additional risk factor for preeclampsia.

Hence the authors concluded that this study showed that ACOG guidelines have a significant positive impact on bringing down the incidence of superimposed preeclampsia in patients with chronic hypertension.

Abstract

ACOG Practice Advisory on Low-Dose Aspirin and Prevention of Preeclampsia

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Purdue develops at home wearable preeclampsia testing device

supine pressor test

Researchers at Purdue University are working on an app-based preeclampsia testing that enables pregnant women to use a smartphone to detect her risk of developing preeclampsia.

The team, led by Craig Goergen, an assistant professor in Purdue’s Weldon School of Biomedical Engineering is modifying the way the underused tool called the supine pressor test records the Blood Pressure for a pregnant woman.

“We hope this will allow us to predict and prevent preeclampsia and reduce the number of children born prematurely each year. This could also reduce the long-term health complications for mothers,” Goergen said.

Other team members include George Wodicka, the Dane A. Miller Head of Biomedical Engineering at Purdue, and Kirk Forster, a senior research engineer at the Weldon School.

The supine pressor test measures a woman’s blood pressure in two different positions and the difference predicts her risk of developing the disease. But, to carry out the test, a woman must go visit the hospital or other healthcare providers, not an easy task in some parts of the world.

The researchers are working to combine available existing technologies such as smartphones, a conventional inflatable blood pressure cuff, and a wireless accelerometer (which measures body position) to build an innovative prototype that will detect preeclampsia before it develops.

  

A supine pressor test is an old, valuable tool that assesses blood flow through the kidney, and 90 percent of women with a positive test eventually develop preeclampsia. The women can send the test results to a doctor's office, a health-care system or a centralized network for the results to be read.

Based on the results the women can receive advice about prevention and early management to avoid the development of terminal consequences.

The World Health Organization estimates that nearly 10 percent of all maternal deaths in Africa and Asia are associated with hypertensive disorders during pregnancy and 25 percent of all maternal deaths in Latin America. Most of those deaths are avoidable, according to the WHO.

The American Journal of Obstetrics & Gynecology issued a report last year estimating the costs to the U.S. health-care system for preeclampsia at $2.18 billion for the first 12 months after birth  — $1.03 billion for mothers, and $1.15 billion for babies.

The researchers received a $100,000 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation in November.

While the Gates Foundation’s goal is to help women in developing countries, Goergen said the device the Purdue researchers are working on also could help women in inner cities and rural areas of the United States and other developed countries.

Here is video by the lead scientist Craig Goergen about the app and wearable device

Purdue News Release

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In case you missed it: Here are the top 5 posts this month

September was a very busy month with lots of good research papers and systematic reviews published on various topics. We also saw many guidelines and recommendations updates from ACOG, ASRM and USPSTF. Here are the top 5 most read posts for the month of September.

USPSTF simplifies cervical cancer screening recommendations: Dual testing no longer advised

The US Preventive Services Task Force (USPSTF) has issued new draft recommendations for cervical cancer screening with a major change that it recommends either cervical cytology (CC) or high-risk HPV (hrHPV) test as a screening procedure every 3 years for women aged 30-65 years, and not both ( Grade A)  

https://obgynupdated.blogspot.com/2017/09/uspstf-simplifies-cervical-cancer.html

ACOG issues clinical practice guidelines for Gestational Diabetes Mellitus

The American College of Obstetricians and Gynecologists (ACOG) has issued clinical practice guidelines for the diagnosis and treatment of gestational diabetes mellitus (GDM).

Although prevalence of GDM is directly proportional to prevalence of type 2 DM in a given population, it is estimated that GDM accounts for 90% of cases diabetes in pregnancy. The prevalence of DM in pregnancy is around 6-9%.

https://obgynupdated.blogspot.com/2017/09/acog-issues-clinical-practice.html

ASRM guidelines update: Metformin alone is not the first line of treatment for ovulation induction in women with PCOS

Practice Committee of the American Society for Reproductive Medicine does not recommend Metformin alone for ovulation induction as a first line therapy in women with PCOS. The guidelines were published in Journal Fertility and Sterility Epub ahead of print.

Metformin is a biguanide used as an oral insulin lowering agent in type2 diabetes, but also used enthusiastically in women with PCOS because of shared pathophysiology of insulin resistance in both.

https://obgynupdated.blogspot.com/2017/09/asrm-guidelines-update-metformin-alone.html

Oral Nifedipine parallels IV hydralazine in lowering down BP in acute hypertensive emergency in pregnancy

Intravenous hydralazine and oral nifedipine both exhibit the same efficacy in lowering the blood pressure in acute hypertensive emergency of pregnancy reports the results of small randomized trial published online in journal American Journal of Obstetrics and Gynecology.

https://obgynupdated.blogspot.com/2017/09/oral-nifedipine-parallels-iv.html

Oral diclofenac potassium plus cervical lidocaine cream eases the pain during hysterosalpingography

Oral diclofenac potassium tab 30 minutes before hysterosalpingography (HSG) and cervical lidocaine cream 5% significantly relieves pain and eases patient anxiety during the procedure and for half an hour after reports the results of a randomized trial published in September issue of journal Fertility and Sterility.

https://obgynupdated.blogspot.com/2017/09/oral-diclofenac-potassium-plus-cervical.html 

Any type of hypertension in pregnancy incurs high future risk of cardiovascular disease

courtesy: indiatimes.com

Women presenting with any subtype of hypertensive disorders of pregnancy (HDP) are at increased risk of developing future hypertension, Ischemic Heart Disease (IHD), stroke and renal disease reports the results of a large retrospective cohort study epub ahead of print in journal Hypertension.

The results demonstrate that women with any type of hypertension during pregnancy are 2.78 times the risk of future hypertension, nearly twice the risk of IHD and stroke and 2.76 times the risk of renal disease as compared to women who were normotensive during pregnancy.

Contrary to popular belief, the highest risk is faced by women with gestational hypertension (OR, 4.08; CI,3.23–5.10) and not by women with preeclampsia during pregnancy (OR,3.06; CI,2.18–4.29).

Women with preeclampsia in pregnancy are nearly 5 times at risk of developing renal disease as compared to their normotensive counterparts during pregnancy (OR, 4.74; CI, 2.19 –10.20).

This retrospective study was conducted at a metropolitan tertiary hospital in Sydney, Australia, across a period of nine years. Data was extracted from medical records. A total of 31 656 deliveries took place during the study period out of which HDP was diagnosed in 4387 (13.8%) women, whereas 27262 (86.2%) of the women remained normotensive in their pregnancy.

The time to develop CVD from index pregnancy varied between 3 to 29 years, the median being 20 years. Future risk of developing CVD also increased proportionately as the severity of HDP increases. Women with preeclampsia also had more severe hypertension as compared to women with gestational hypertension. Women with severe HDP were older, deliver early in pregnancy and have babies that are small for gestational age.

Women who delivered ≤34 weeks gestation also are at increased and early risk of future CVD and as compared to women who delivered >34 weeks gestation. Receiving anti-hypertensive medication during pregnancy did not alter the future risk of developing CVD, although it benefited maternal and fetal outcome.

Under-reporting of chronic hypertension in young women might have limited some aspects of data analysis.

Hence, these women who have history of HDP should be explained in detail about their future risk of CVD and renal diseases. They should be advised a lifelong close monitoring for B.P and other modifiable risk factors for the development of CVD.

Cardiovascular risk assessment should also include obstetric history of women.

Further research is warranted to look into prevention of CVD after the risk is identified early in disease course.

 Abstract, Full Text

Use of β-Blocker in pregnancy and risk of fetal cardiac anomalies.

The use of β-Blocker in pregnancy does not increase the risk of fetal congenital cardiac anomalies after adjusting for maternal co-morbidities says the results of a large population basedcohort study conducted by department of research and evaluation at Kaiser Permanente Southern California.

The study was reported as a research letter online April 17, 2017 in JAMA Internal Medicine.

Lewei Duan and colleagues from Kaiser Permanente, California note, “Beta-blockers are the most commonly used class of medication for treating cardiac conditions in pregnant women. Despite the common use of this class of medication, data that support its safety are limited.”

“A recent meta-analysis reported an association between beta-blocker exposure and fetal congenital cardiovascular defects, raising a concern regarding potential teratogenic effects of this class of medication.”

The authors identified 379,238 women through birth records who delivered at Kaiser Permanente, Southern California through a period of 11 years (2003-2014). Of these, 4847 women (1.3%) received β-Blocker during pregnancy as identified by pharmacy dispensing records.

And, 2,628 (0.7%) were exposed during the first trimester of pregnancy.

Most common beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489) and metoprolol (n = 324). The most common indication for prescribing beta-blockers was hypertension.

Data analysis revealed that women on beta-blockers were older and had higher body mass index(BMI). They also had higher prevalence of chronic comorbidities like hyperlipidemia, diabetes, hypertension, heart failure, a history of arrhythmia and pregnancy complications like preeclampsia and eclampsia.

They also delivered about a week early than those not taking beta-blockers (mean 37.4 weeks vs. 38.9 weeks).

In unadjusted analyses, women on beta-blockers were significantly more likely to have a baby with congenital cardiac malformation as compared to those not taking the drug (P < 0.001).

When after taking into account the confounders like maternal age, BMI, and comorbidities and gestational age at delivery, there was no longer any association between the exposure and the outcome (P = 0.32).

This suggests that the association seen in unadjusted analyses was caused by maternal demographics and other chronic co-morbidities and not due to beta-blockers.

“The previously reported association between beta-blocker use and fetal cardiac anomalies in other studies may be attributed to confounding,” Duan and colleagues concluded. “While these findings do not definitively rule out the possibility of fetal congenital defects in association with beta-blocker use, these results do provide reassurance regarding the use of this class of medication for the treatment of cardiac conditions in pregnant women.”

Access the Abstract here 

Primary source: Duan L, Ng A, Chen W, Spencer HT, Nguyen J, Shen AY, Lee M. β-Blocker Exposure in Pregnancy and Risk of Fetal Cardiac Anomalies. JAMA Intern Med. 2017;177(6):885-887. doi:10.1001/jamainternmed.2017.0608

USPSTF final recommendation statement favor screening for preeclampsia throughout pregnancy.

The US Preventive Services Task Force (USPSTF) today issued its final recommendations for preeclampsia screening by monitoring the blood pressure throughout pregnancy with grade B, meaning there exists substantial net benefit for the mother and infant because of screening.

The recommendations, accompanying editorial and systematic review evidence was published online 25 April 2017 in JAMA.

USPSTF has earlier released a draft recommendation on September 27, 2016 which was open to public comments till October 2017.

The task force last full review of this topic was in 1996. The topic was again reviewed recently in light of new evidence and change in definition of preeclampsia.

The current recommendation states that Blood Pressure measurement should be done at each antenatal visit. No timing interval is mentioned.

The screening applies to all pregnant women without a known diagnosis of preeclampsia or being at high risk for the disease.

Conditions associated with increased risks are previous history of eclampsia or preeclampsia (particularly early-onset preeclampsia), medical morbidities associated includes DM 1 or 2, GDM, chronic hypertension, renal disease, and autoimmune diseases), previous history of adverse pregnancy outcome and multifetal gestation.

Other risk factors include nulliparity, obesity, African American race, low socioeconomic status, and advanced maternal age.

Evidence did not suggest point of care urine testing when screening for preeclampsia because it alone could not predict the health outcome.

Recently revised criteria for the diagnosis of preeclampsia include:

• elevated blood pressure (≥140/90 mm Hg on 2 occasions 4 hours apart, after 20 weeks of gestation)
• and either proteinuria (≥300 mg/dL on a 24-hour urine protein test, protein to creatinine ratio of ≥0.3 mg/mmol, or urine protein dipstick reading >1 if quantitative analysis is not available)
• or, in the absence of proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms.

The USPSTF further recommends low dose aspirin (81 mg/d) after 12 weeks of gestation for all women at high risk for preeclampsia.

Other Obstetrics and Gynecology societies like The Society of Obstetricians and Gynecologists of Canada, The National Institute for Health(NIH) and Care Excellence recommends urinalysis for proteinuria at each antenatal visit.

The ACOG only recommends B.P. measurements at every visit with detailed history to evaluate the risk.

“Preeclampsia and CVDs including hypertension are bound not only by common pathophysiology but also epidemiology” said Nisha I. Parikh, MD, and Juan Gonzalez, MD, PhD, from the University of California, San Francisco, in an accompanying editorial published simultaneously in JAMA Internal Medicine.

"Pregnancy is essentially a cardiovascular stress test, and the development of preeclampsia among other pregnancy complications is the earliest marker of patients at risk for future [cardiovascular disease].” They further added.

The full text of recommendation statement in JAMA can be assessed here.

The accompanying editorial in JAMA can be accessed here.

The accompanying editorial in JAMA cardiology can be accessed here.

The accompanying editorial in JAMA Internal Medicine can be accessed here.

ACOG releases recommendations for management of acute onset, severe hypertension in pregnancy and postpartum period.

It is estimated that ten million women develop preeclampsia each year around the world, with 76,000 deaths due preeclampsia and related hypertensive disorders.  It is also responsible for 50,000 stillbirths and early neonatal deaths in developing nations.

A woman in developing country is seven times more likely to develop preeclampsia than a woman in a developed country, contributing to 10-25% of all Maternal mortality.

In the United States, preeclampsia complicates approximately 3-5% of pregnancies, accounting for 10-15% of maternal deaths and 3% of perinatal deaths.

ACOG says “Introducing standardized, evidence-based clinical guidelines for the management of patients with preeclampsia and eclampsia has been demonstrated to reduce the incidence of adverse maternal outcomes.”

ACOG committee opinion was published online ahead of print in Journal of Obstetrics and Gynecology.

Women who are pregnant or postpartum presenting with acute onset severe systolic (greater than or equal to 160 mm Hg) as well as severe diastolic hypertension (greater than or equal to 110 mm Hg) require urgent antihypertensive therapy.

Hospitals, doctor’s office and other institutions handling emergencies should initiate treatment with first line drugs within 30-60 minutes of confirming the diagnosis to prevent maternal stroke.

Intravenous labetalol and hydralazine have long been used as the first line drugs in managing hypertensive emergencies in antenatal and postnatal women.

Recent available evidence suggests that immediate release oral nifedipine may also be considered an alternative first line therapy, especially in circumstances when an IV line is not secured. Some studies in recent time have shown that it brings down BP faster than labetalol and hydralazine. Concurrent use of Nifedipine and Magnesium Sulfate requires tertiary care setup and close monitoring of mother’s vital signs.

Use of all these three drugs does not requires cardiac monitoring.

In rare cases all the three drugs, labetalol, hydralazine and nifedipine may fail to relieve acute hypertensive emergency. In such circumstances, expert opinion of maternal-fetal medicine specialist, anesthesiologist and critical care subspecialist is sought. The second line alternative to be considered are nicardipine or esmolol by infusion pump.

Once the blood pressure is stabilized, detail evaluation of maternal and fetal well-being is carried out to make plans for long term drug therapy and timing of delivery.

The American College of Obstetricians and Gynecologists has identified additional resources on topics related to this document that may be helpful for ob-gyns, other health care providers, and patients. It may be viewed at www.acog.org/More-Info/Hypertension In Pregnancy.

The full text of the ACOG recommendations and suggestions can be accessed here. 

ACOG supports the USPSTF’s broader list of risk factors for supplementing low dose aspirin in preeclampsia risk reduction.

low dose aspirin 

The current ACOG recommendation for supplementing low dose aspirin for reducing the risk of developing preeclampsia is based on report by Task Force on Hypertension in Pregnancy in 2013.

The task force recommended 60-80 mg of aspirin started late first trimester for all women who are at risk by their obstetric history:

• history of preeclampsia in more than one prior pregnancy.
• history of early onset preeclampsia with preterm delivery at <34 weeks' gestation.

The U.S.Preventive Services Task Force (USPSTF) conducted a systematic review and meta-analysis of several good quality RCTs and published the results as clinical guidelines. It expanded its list of high risk pregnancies at risk for developing preeclampsia in 2014.[1]  The list was divided into 3 categories: high, medium and low risk for developing preeclampsia.

1) Women are considered at high risk if one or more of the following factors are present:

• History of preeclampsia, especially when accompanied by an adverse outcome
• Multifetal gestation
• Chronic hypertension
• Type 1 or 2 diabetes
• Renal disease
• Autoimmune disease such as systemic lupus erythematous, antiphospholipid syndrome.

2) Women are considered at moderate risk if they have several of these moderate-risk factors:

• Nulliparity
• Obesity (body mass index >30 kg/m²)
• Family history of preeclampsia (mother or sister)
• Sociodemographic characteristics (African American race, low socioeconomic status)
• Age ≥35 years
• Personal history factors (e.g., low birthweight or small for gestational age, previous adverse pregnancy outcome, >10-year pregnancy interval)

3) Women are considered at low risk if they have:

• A history of uneventful term delivery.

ACOG issued a practice advisory in July 2016[2] supporting  the recommendation by USPSTF to consider the use of low-dose aspirin (81 mg/day), initiated between 12 and 28 weeks of gestation, for the prevention of preeclampsia, and recommends using the high-risk factors as recommended by the USPSTF and listed above.

Supplementing the low dose aspirin reduced the reduced the risk for preeclampsia by 24% in clinical trials and reduced the risk for preterm birth by 14% and IUGR by 20%.

In a meta-analysis of RCTs and observational studies, USPSTF did found any evidence of increased risk of placental abruption, postpartum hemorrhage, or fetal intracranial bleeding even in moderate to low risk patients.

It is estimated that ten million women develop preeclampsia each year around the world, with 76,000 deaths due preeclampsia and related hypertensive disorders.  It is also responsible for 50,000 stillbirths and early neonatal deaths in developing nations.

A woman in developing country is seven times more likely to develop preeclampsia than a woman in a developed country, contributing to 10-25% of all Maternal mortality.

In the United States, it affects 5-8% of all pregnancies.

Establishing casualty, early detection and prevention of preeclampsia along with identifying the women at risk has been the mainstay of preeclampsia research in the last decade.

Link to USPSTF complete final recommendation  can be found here. 

Link to ACOG practice advisory can be found here. 

  

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[1] https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

[2] http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations

Maternal death: a century of getting it wrong | Basky Thilaganathan | TEDx Talk..

Basky's research interests are focused on obstetrics and high risk pregnancies with a interest in pre-eclampsia which accounts for 40% of maternal deaths worldwide and contributes to 25% of overall neonatal morbidity. During the last decade, substantial progress has been made towards understanding its causes. In this talk, Basky will reveal emerging evidence that pre-eclampsia is a cardiovascular disorder that effects some of its actions through the placenta.

It is estimated that over 300,000 women will die in childbirth in coming year. It has decreased by 40% in last 20 years.

Majority of the deaths are due to infection, but preeclampsia also is responsible for a massive share. 1 in 5 women will die of preeclampsia that is one maternal death every 12 minutes.

We have believed since centuries that placenta is at the root of all symptoms of preeclampsia.

But how it is that placenta which we disposed off20 years ago, is having an effect on woman’ heart now.

So, we challenge the centuries old belief and research on maternal hemodynamic alteration in pregnancy will be critical to progress further in this arena.

Basky Thilaganathan was appointed in 2008 as Professor of Fetal Medicine at St George’s, University of London. Before that, he was Reader in Fetal Medicine since 2005 and appointed Director of Fetal Medicine at St George’s Hospital in 1999. His research interests are focused on obstetrics and high-risk pregnancies (Materno-Fetal medicine), with a particular interest on maternal cardiac function, placental function, fetal growth and pre-eclamspsia. 

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

Hypertension in pregnancy nearly doubles the risk autism spectrum disorder and intellectual disability.

A recent study presented at the International Meeting of Autism Research (IMFAR) 2016 shows a significant association between any form of hypertension during pregnancy, particularly in the presence of placental insufficiency and the risk of developing ASD in the offspring.

"Children born to women with preeclampsia, or placental insufficiency, or both are at risk for adverse neurodevelopmental outcomes, including intellectual disability and autism," principal investigator Cheryl Walker, MD, MIND Institute, University of California, Davis, in Sacramento told news media.

"Identification of these children might facilitate very early interventions and improved developmental outcomes at a time when the brain is most responsive to modification," she added.

The current research is an extension of Childhood Autism Risk from Genetics and Environment (CHARGE) study published in Published in JAMA Pediatrics in 2014.

Results of the CHARGE study shows that children who were diagnosed with ASD were twice as likely to be exposed to preeclampsia as compared to controls who showed a typical development(TD).

In the current study also conducted at University of California, Davis, the researchers Paula Krakowiak, PhD and her colleagues decided to dig deeper and study the effects of specific categories of hypertension with and without the presence of placental insufficiency.

The study subjects were drawn from large cohorts of children born in California from 1991 to 2008.

The different types of hypertension studied were chronic hypertension, preeclampsia, and hypertension superimposed on preeclampsia. Presence of Placental insufficiency was determined by signs of intrauterine growth restriction, inadequate amniotic fluid, and small-for-gestational-age birthweight.

Dr Krakowiak opined "Women with any type of hypertensive disorder had approximately a 20% increased risk for having a child with autism relative to the general population." While placental insufficiency alone was modestly associated with ASD risk.

In contrast, women with placental insufficiency and any type of preeclampsia or chronic hypertension has almost 40% increased risks of having a child with ASD.

Association were stronger between intellectual disabilities and preeclampsia. Women had twofold the risk of bearing a child with intellectual disability if she has hypertension and superimposed preeclampsia and the risk rises to threefold in placental insufficiency alone.

Dr Krakowiak observed that the association between hypertensive disorders and intellectual disability was stronger than that for ASD, noting that there is overlap between autism and intellectual disability in real life.

"Many children with autism have varying levels of cognitive impairments, and some children with intellectual disability have mild behavioral symptoms reminiscent of autistic features," she said.

It is postulated that the developing fetus falls short on oxygen and other nutrients in an environment complicated by placental insufficiency and inflammation leading to poor neurodevelopmental outcomes.  

Dr Cheryl Walker advises women to maintain a healthy weight and daily physical activity to improve placental function. Maternal supplementation with low dose aspirin and statins, have shown some promising results in recent studies in diminishing the cellular and end organ damage due to placental insufficiency probably due to improving perfusion.

References:

http://archpedi.jamanetwork.com/article.aspx?articleid=2020784

https://imfar.confex.com/imfar/2016/webprogram/Paper23118.html

Two blood tests to rule out pre-eclampsia approved by The National Institute for Health and Care Excellence (NICE), UK.

According to an estimate by NHS mild pre-eclampsia affects up to 6% of pregnancies, while 1-2% of patients develop severe preeclampsia.  Data Centre for Maternal and Child Enquiries Mission statement shows pre-eclampsia, and associated eclampsia, are the second leading cause of direct maternal deaths in the UK.

NICE have approved and recommended two blood tests Triage PlGF test (Alere) and the Elecsys immunoassay sFlt-1/PlGF ratio (Roche Diagnostics) to help rule-out pre-eclampsia between 20^th and 35^th week of pregnancy.

The tests detect changes in the blood indicating that the placenta is not developing properly.

The tests however are not meant for diagnosing preeclampsia.

The tests were approved by NICE after the groundbreaking PROGNOSIS study results were published in New England Journal of Medicine in January,2016. 

The PROGNOSIS study has demonstrated that low ratios of the proteins sFlt-1 and PlGF in the blood of women at high risk of developing of preeclampsia can predict the absence of the condition within a period of one week (the rule-out claim). The data published today show that an sFlt-1/PlGF ratio of 38 and below can rule out the development of preeclampsia within the next week with a very high confidence level of 99.3%.

PROGNOSIS was a multi-center, prospective, double-blind, non-interventional trial evaluating the short-term prediction of preeclampsia, eclampsia and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome in pregnant women with suspected preeclampsia. Sponsored by Roche, the PROGNOSIS study aimed to address the limitations of the traditional clinical parameters used to predict preeclampsia, and to demonstrate the utility of the Elecsys® preeclampsia ratio test in this context.

Identifying women who are unlikely to develop preeclampsia in the short term will save them from the stress of monitoring and the disruption to their home life caused by a stay in hospital.

The test is available in all countries accepting the CE mark in Europe, Latin America, Middle East, Africa and Asia. The test is currently not available in the United States and Japan.

PROGNOSIS also demonstrated that an sFlt-1/PlGF ratio greater than 38 may help predict whether women with suspected preeclampsia will develop the condition within four weeks (the rule-in claim), allowing doctors to identify at-risk patients who need close monitoring.

Dr Jenny Myers, who is also Senior Lecturer and Consultant Obstetrician, Maternal and Fetal Health Research Centre, Central Manchester Foundation Trust said “At the moment women with suspected pre-eclampsia often have to come into hospital for 24 to 36 hours so we can make a diagnosis, but now, for women between 20^th and 35^th week of their pregnancy, these new tests may avoid the need for admission to hospital.”

“The tests will be extremely valuable to help rule out pre-eclampsia before the 35^th week of pregnancy, when approximately 1/3 of women with pre-eclampsia are diagnosed.

“Doctors will need to be clear with patients, depending on which test is used, the result is only valid for 7 to 14 days and neither test definitively rules out pre-eclampsia for the rest of the pregnancy.

“However these tests represent a great stride forward in the management and treatment of pre-eclampsia.”

The cause of preeclampsia is not fully understood; many factors have been implicated in the development of this life threatening disease. Recent research provides evidence that angiogenic factors such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) play a major role in the development of the disease.

It is postulated that preeclampsia is caused by an imbalance of angiogenic factors of sFlt-1 (anti-angiogenic protein) and PlGF (pro-angiogenic protein). During normal pregnancy both these proteins are involved in placental vascular remodeling.

In normal pregnancy, PlGF levels rise and peak at 26 to 30 weeks, so when PlGF levels do not rise during pregnancy this may be an indicator that the placenta is not developing properly, predict subsequent development of preeclampsia.

The Elecsys immunoassay sFlt-1/PlGF ratio also measures a protein called soluble FMS-like tyrosine kinase-1 (sFlt-1). The protein sFlt-1 stops other proteins that help to form blood vessels, like PlGF, from working. In pre-eclampsia if sFlt-1levels are higher than those seen in normal pregnancy it could be an indicator the placenta is not developing properly.

The sFlt-1/PlGF ratio measurement in combination with proteinuria, blood pressure and Doppler ultrasound gives better prediction of preeclampsia.

Professor Carole Longson, director of Centre for Health Technology at NICE added “Until now there have been no tests which doctors can use to confidently rule-out pre-eclampsia. This has meant women with suspected pre-eclampsia often need increased monitoring or have to stay in hospital. Apart from being inconvenient, this can increase anxiety at what might already be a stressful time.

“In recommending these tests the committee highlighted the importance of making sure laboratories explain to clinicians if a test result doesn’t rule-out pre-eclampsia they should not automatically diagnose women with pre-eclampsia.

Instead doctors should follow existing NICE guidelines to make such a diagnosis. This is so that babies aren’t delivered unnecessarily early as a result of these tests.”

Two other tests were also considered initially but later not included in the guidelines.

NICE recommends further research and trials to be carried out using these tests in women with suspected preeclampsia.

References:

http://www.cobas.com/content/dam/cobas_com/pdf/product/Elecsys%20Preeclampsia%20assays%20sFlt-1%20PlGF/Preeclampsia%20Abstract%20Booklet.pdf

http://www.1000livesplus.wales.nhs.uk/sitesplus/documents/1011/CMACE%20Saving%20mothers%20Lives%202011.pdf

http://www.nhs.uk/conditions/pre-eclampsia/pages/introduction.aspx

https://www.nice.org.uk/news/press-and-media/nice-guidance-recommends-new-tests-to-help-rule-out-pregnancy-complication-and-avoid-unnecessary-hospital-admissions

http://www.nejm.org/doi/full/10.1056/NEJMoa1414838

Preconception Cardiometabolic risk factors differs for preeclampsia and gestational hypertension.

It is estimated that ten million women develop preeclampsia each year around the world, with 76,000 deaths due preeclampsia and related hypertensive disorders.  It is also responsible for 50,000 stillbirths and early neonatal deaths in developing nations.

A woman in developing country is seven times more likely to develop preeclampsia than a woman in a developed country, contributing to 10-25% of all Maternal mortality.

In the United States it affects 5-8% of all pregnancies.

According to the World Health Organization, among women who have had preeclampsia, about 20% to 40% of their daughters and 11% to 37% of their sisters also will get the disorder.

Establishing casualty, early detection and prevention of preeclampsia along with identifying the women at risk has been the mainstay of preeclampsia research in the last decade.

Preconception maternal risks for cardiovascular disease, maternal insulin resistance and diabetes in their ability to predict preeclampsia have been the subject of speculation since long. Only two studies have so far evaluated these risk factors, but their small sample size lead to discrepancy.

A recent study published April 25, 2016 in Hypertension, by Norwegian researchers evaluated the extent of similarities and differences in preconception cardiometabolic risk factors associated with gestational hypertension, preeclampsia, and preterm preeclampsia. 

It was a prospective cohort study that followed participants by linking Cohort Norway (CONOR) health surveys (1994–2003) to the Medical Birth Registry of Norway for births subsequent to CONOR participation (through to December 31, 2012).

The study confirms that pregnancy is a stressor and unmasks predisposing familial and modifiable cardiometabolic risk factors. More risk factors predicted the development of preeclampsia than gestational hypertension. Study results show that:

• A family history of diabetes mellitus and women’s preconception diabetes mellitus predicted both gestational hypertension and preeclampsia.
• A family history of myocardial infarction before 60 years of age predicted preeclampsia, but not gestational hypertension.
• A family history of stroke predicted the combined outcome of gestational hypertension or preeclampsia.
• BMI and preexisting hypertension predicted both.
• A high total cholesterol/HDL cholesterol ratio predicted both gestational hypertension and preeclampsia. In contrast, an elevated triglyceride level only predicted preeclampsia.
• Alcohol once a week as compared to none or less than one serving per month was associated with lower risks of preeclampsia in contrast to binge drinking, a strong predisposing factor for preeclampsia.
• Physical exercise 3 hours a week or more was protective for preeclampsia, but not for gestational hypertension. The protective mechanism goes beyond simple weight management and also includes reduced inflammation and oxidative stress, improved endothelial function, placental growth and vascular development.

Odds of developing gestational HT and preeclampsia according to risk factors 

These findings have important implications in preventive medicine, as it is seen that if a woman can bring down her BMI pre pregnancy than she has pretty much good chances of being protected from preeclampsia and gestational hypertension.

These results are intriguing because it could help us preventing the long term cardiovascular morbidities of preeclampsia.

So,to conclude gestational hypertension and preeclampsia have several common baseline risk factors: a family history of diabetes mellitus, preconception diabetes mellitus, hypertension, obesity, a high total cholesterol/HDL cholesterol ratio, and a family history of stroke. But, preeclampsia additionally was also predicted by a family history of myocardial infarction before 60 years of age, physical inactivity, an elevated triglyceride level, and binge drinking.

References:

Grace Egeland, Kari Klungsoyr, Nina Oyen, et al. Preconception cardiovascular risk factor differences between gestational hypertension and preeclampsia. Cohort Norway Study. Hypertension 2016; DOI:10.1161/HYPERTENSIONAHA.116.07099.

http://www.acog.org/About-ACOG/News-Room/News-Releases/2013/Ob-Gyns-Issue-Task-Force-Report-on-Hypertension-in-Pregnancy

http://www.preeclampsia.org/health-information/149-advocacy-awareness/332-preeclampsia-and-maternal-mortality-a-global-burden

https://www.nichd.nih.gov/health/topics/preeclampsia/conditioninfo/Pages/risk.aspx#f5

World Health Organization Fact Sheet, May 2012

Lim, K.-H., & Ramus, R. M. (2011). Preeclampsia. Retrieved May 02, 2016, from http://emedicine.medscape.com/article/1476919-overview