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Bioengineering, Genetics, Neuroscience, Pregnancy, Research, Stanford News

Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health

Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health

blood on fingertip - 260

I read a lot of scientific papers. And while they’re all interesting, they don’t all make me snap to attention like the latest from Stanford bioengineer Stephen Quake, PhD. I even remarked to my husband that it’s rare to get the immediate sense that a discovery will significantly change clinical care.

If anyone’s going to shake up the status quo, however, it would be Quake. You may remember that Quake has made waves before with his pioneering discoveries involving the analysis of tiny bits of DNA circulating in our blood. His 2008 discovery that it’s possible to non-invasively detect fetal chromosomal abnormalities with a maternal blood sample has revolutionized prenatal care in this country. It’s estimated that, in 2013, hundreds of thousands of pregnant women used a version of this test to learn more about the health of their fetuses. And, in 2012, Quake showed its possible to sequence an entire fetal genome from a maternal blood sample.

Now he and his lab have gone one step further by turning their attention to another genetic material in the blood, RNA. Although information conveyed in the form of DNA sequences is mostly static (the nucleotide sequence of genes, for example), RNA levels and messages change markedly among tissues over time and at various developmental points. The difference in available information is somewhat like comparing a still photo with a high-resolution video when it comes to sussing out what the body is actually doing at any point in time.

The study was published today in the Proceedings of the National Academy of Sciences. As I explain in my release:

In the new study, the researchers used a technique previously developed in Quake’s lab to identify which circulating RNA molecules in a pregnant woman were likely to have come from her fetus, and which were from her own organs. They found they were able to trace the development of specific tissues, including the fetal brain and liver, as well as the placenta, during the three trimesters of pregnancy simply by analyzing blood samples from the pregnant women over time.

Quake and his colleagues believe the technique could also be broadly useful as a diagnostic tool by detecting distress signals from diseased organs, perhaps even before any clinical symptoms are apparent. In particular, they found they could detect elevated levels of neuronal-specific RNA messages in people with Alzheimer’s disease as compared with the healthy participants.

Quake and the lead authors, graduate students Winston Koh and Wenying Pan, liken their technique to a “molecular stethoscope.” They believe it could be broadly useful in the clinic. More from my release:

“We’ve moved beyond just detecting gene sequences to really analyzing and understanding patterns of gene activity,” said Quake. “Knowing the DNA sequence of a gene in the blood has been shown to be useful in a few specific cases, like cancer, pregnancy and organ transplantation. Analyzing the RNA enables a much broader perspective of what’s going on in the body at any particular time.”

Previously: Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies” and Better know a bioengineer: Stephen Quake
Photo by Alden Chadwick

Cardiovascular Medicine, Emergency Medicine, Patient Care, Pregnancy, Research, Stanford News

Cardiac arrest in pregnancy: New consensus statement addresses CPR for expectant moms

Cardiac arrest in pregnancy: New consensus statement addresses CPR for expectant moms

pregnantbelly2When a pregnant woman’s heart stops, two lives are threatened. Yet few caregivers know how to modify their cardiopulmonary resuscitation technique for the expectant mom and her fetus, and few hospitals are optimally prepared for such an event.

To fill the knowledge gap, the Society for Obstetric Anesthesia and Perinatology commissioned a Stanford-led team of experts from several medical disciplines to write a consensus statement of expert recommendations, publishing in the May issue of Anesthesia & Analgesia, that describes best practices for CPR on a pregnant patient. The new statement is one of many examples of Stanford leadership in helping to save the lives of pregnant women around the world; our experts have also helped to develop widely-adopted protocols for dealing with massive hemorrhage during delivery and for treatment of pre-eclampsia, for example.

I asked two Stanford scientists who helped prepare the statement, lead author Steven Lipman, MD, and senior author Brendan Carvalho, MD, for their perspectives on the challenges of resuscitation in pregnancy. Both are obstetric anesthesiologists at Lucile Packard Children’s Hospital Stanford, where Carvalho is chief of obstetric anesthesia.

“The good news is that cardiac arrest in pregnancy is very rare, and also that rates of survival are higher than for the non-pregnant population,” Lipman said. Only about one in every 20,000 women with access to modern obstetric care experiences cardiac arrest while pregnant. Higher survival among pregnant patients may be partly due, he said, to the fact that many maternal cardiac arrests are witnessed: They tend to occur during labor or delivery, when the woman is already in a hospital and being closely monitored by trained medical staff who can begin CPR right away.

But rarity creates challenges. Because maternal cardiac arrests happen infrequently, obstetric caregivers have less experience in performing resuscitation than people who work in other parts of the hospital, such as the emergency room or intensive care unit. And it’s impossible to conduct randomized clinical trials – usually considered the gold standard for evidence-based medicine – on these emergencies to determine what works best.

“Also, in pregnancy, there is an asymmetry between people’s expectations and the reality of the risk,” Lipman said. “People think, ‘Oh, I’m just having my baby, it’s just natural.’ But if you look at third-world countries with no developed medical infrastructure, the rates of maternal mortality are extremely high. Yes, it’s natural and people expect an easy delivery and a healthy baby, but the reality is that it can be a risky process, and people can become critically ill very quickly.”

The physiology of pregnancy also presents challenges for resuscitation. During the second half of pregnancy, when a pregnant woman lies flat on her back, the fetus and the enlarged uterus compress the large vein that returns most of the blood to her heart. This decreases the amount of blood available to the heart and makes it harder to provide effective chest compressions in CPR. And resuscitators also must think about how to balance the needs of the mother with those of the fetus.

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Ethics, Fertility, Genetics, In the News, Pregnancy, Stanford News

Daddy, mommy and ? Stanford legal expert weighs in about “three parent” embryos

Daddy, mommy and ? Stanford legal expert weighs in about "three parent" embryos

3519855504_9000d95a2aIt’s an interesting question that got a lot of traction in the media last week. Does the contribution of a tiny amount of DNA from a third person during in vitro fertilization really mean that the resulting child would have three genetic parents? Researchers in Oregon have proposed the technique as a way to avoid genetic diseases arising from faulty mitochondrial DNA by replacing an egg’s mitochondria with one from a second, healthy woman either before or after fertilization with a man’s sperm. They’ve shown that it works in monkeys, and the FDA met last week to consider whether the technique is safe enough to be used in humans.

Yesterday, Stanford law professor and bioethicist Hank Greely, JD, posted a great analysis of the topic on the university’s Law and Biosciences blog, complete with an elegant explanation of the problem for women with mitochondrial DNA mutations:

The mitochondria (high school biology’s “energy powerhouses of the cell”) have their own very short stretch of DNA, separate from the 6.8 billion base pairs found on 46 chromosomes in the cell’s nucleus (the nuclear DNA).  The 16,569 base pairs of the mitochondrial DNA (hereafter “mtDNA”) hold 37 (some say 38) genes, providing instructions for making 13 (or 14) proteins and another 24 RNA molecules.  The full importance of these genes is unknown, but it is clear that some (happily rare) variations in the mtDNA cause quite severe illnesses. Unfortunately, each child gets all of its mitochondria (and hence its mtDNA) in the egg from its mother; if the mother’s mtDNA is dangerously flawed, so will be the mtDNA of all her children. With almost all other genetic diseases, no matter how inevitably the “bad” genetic variation leads to a disease (how “penetrant” the genetic variation is), a woman will have only a 50% or 25% chance of passing on the condition.  With these, her genes can give rise to no healthy children.

Greely gets at the heart of the matter when he compares the statistically minute contribution from the donated mitochondria to a hypothetical child he calls Heather:

I have DNA from four people in each of my cells:  my mother’s mother, my mother’s father, my father’s mother, and my father’s father. Actually, my DNA really came from all eight of my great-grandparents, and all 1024 of my great great great great great great great great grandparents, and all roughly one million of my great (18) grandparents. Yes, all that DNA passed through my (genetic) parents before coming to me, but why does that matter?

Heather gets her DNA from more than two people a bit differently from the way the rest of us do, but so what? How does getting what is, in effect, “gene therapy,” where the gene is delivered in a natural package called the mitochondrion, turn our hypothetical (and healthy) child into a powerful argument against the procedure?

It shouldn’t.  Heather will not be getting superpowers, she will not be in any meaningfully way “designed” (except to avoid a nasty genetic disease), and she will not be given a newly made DNA sequence never before found in the human gene pool. She will get mitochondria with mtDNA that will allow her to have normal health, not a grave disease. That mtDNA will have been taken from a woman, who, though not a source of Heather’s nuclear DNA, is certainly a participant in the human gene pool.

“Heather has three parents” is NOT an argument. It is an irrelevant but attention-getting slogan that is uncritically put forward as, and sometimes mistaken for, a real argument. Yes, the proposed process is a way of bringing forth living and healthy babies that is somewhat new and different, but so were obstetric forceps, (safe) C-sections, and in vitro fertilization. Novelty is not, in itself, a respectable argument against it.

Previously: Medical practice, patents and “custom children”: A look at the future of reproductive medicine, Five million babies and counting: Stanford expert offers conversation on reproductive medicine and Stanford researchers work to increase the odds of in vitro fertilization success
Photo by Christian Pichler

Pregnancy, Stanford News, Women's Health

Attending to signs of preeclampsia in late-stage pregnancy

preeclampsiaAs recently written about on Scope, the California Quality Care Collaborative organized a task force and produced a toolkit of recommendations for treating preeclampsia, a pregnancy complication marked by hypertension that can kill pregnant women and new mothers.

An article in the San Francisco Chronicle details one woman’s health emergency and stillbirth experience owing to the condition. “I wish I had known more about preeclampsia,” Elizabeth Barnett, the 33-year-old mother, told Stephanie M. Lee. “Not that the outcome necessarily could have been that much different because of how severe I had it, but I definitely would have gone into the hospital earlier and would have been more on top of it.”

The piece emphasizes why recognizing and treating preeclampsia and eclampsia – which may induce deadly seizures – is paramount for expectant mothers and their health care providers.

From the Chronicle:

“Nobody realizes it’s a problem. Preeclampsia is the most common medical complication of pregnancy essentially,” said [Maurice Druzin, MD], an obstetrics and gynecology professor at Stanford University School of Medicine and an attending physician at Lucile Packard Children’s Hospital. Druzin helped lead the group of clinicians that wrote the guidebook.

From 2002 to 2004 in California, 25 women died of preeclampsia or eclampsia, making up 17 percent of all pregnancy-related deaths in the state during that time, according to an analysis of the most recent data. The number of maternal deaths in California, in general, is relatively small. The numbers had, in fact, been declining for years, but increased between 1999 and 2010 because of chronic conditions among pregnant women, variety in quality of pre- and postnatal care and other factors.

Previously: New preeclampsia toolkit will help prevent maternal deaths and Could exercise before and during early pregnancy lower risk of pre-eclampsia?
Photo by pumicehead

Health and Fitness, Pregnancy, Public Health, Research, Women's Health

Group sessions shown to help women maintain healthy pregnancy weight

Group sessions shown to help women maintain healthy pregnancy weight

pregnant_012214More than 50 percent of pregnant women, myself included, gain more weight than the recommended national guidelines. Personally, I had grand ambitions of maintaining my pre-pregnancy workout routine, or at least a modified version, and sticking to my usual healthy eating habits for the entire 40 weeks. But then I was sidelined for several months by unrelenting fatigue and an odd form of morning sickness where only Mexican cuisine agreed with my stomach. Although I resumed exercising and eating a more diverse diet, I wasn’t able to keep my weight gain within the suggested range.

Perhaps I would have been more successful if my prenatal check-ups had been structured as meetings with other women of similar gestational ages, rather than the traditional doctor visit. According to a growing body of research, women who received group prenatal care benefitted in a number of ways, including weight management. Futurity reports:

Researchers found that women who participated in prenatal care delivered in a group setting as opposed to the traditional approach—which typically involves a series of regular one-on-one visits with a healthcare provider—saw a 22 percent reduction in the risk of excessive gestational weight gain.

The beneficial effect of group prenatal care was even more pronounced for women who were overweight prior to pregnancy, who saw a 28 percentage points reduction in the risk of excessive gestational weight gain.

The post also notes that past studies have shown prenatal group check-ups can reduce the risk of infants being born with very low birth weights and increase the odds that  mothers will breastfeed their babies.

Previously: Eating nuts during pregnancy may protect baby from nut allergies, What’s in YOUR blood? A simple blood test may change the face of prenatal care and From womb to world: Stanford Medicine Magazine explores new work on having a baby
Photo by hugrakka

Patient Care, Pregnancy, Public Health, Stanford News, Women's Health

New preeclampsia toolkit will help prevent maternal deaths

New preeclampsia toolkit will help prevent maternal deaths

pregnant woman holding bellyCalifornia hospitals have a new tool to help reduce maternal deaths. Today, the California Maternal Quality Care Collaborative released a toolkit for the treatment of preeclampsia, a pregnancy complication that can kill pregnant women and new mothers. Although, fortunately, few women die in California during pregnancy or birth, preeclampsia is among the leading causes of such deaths. Importantly, many deaths caused by this disease can be prevented if doctors know what to do.

Preeclampsia is characterized by high blood pressure in late pregnancy. It can escalate without warning to full-blown eclampsia, in which the woman experiences potentially deadly seizures. The only cure is delivery of the baby.

To help California hospitals handle this obstetric emergency, the CMQCC convened a task force that reviewed scientific literature on the disease. The task force, c0-led by Stanford’s Maurice Druzin, MD, developed a package of materials that includes care guidelines, such as identification of clinical “triggers” that require immediate evaluation; a compendium of relevant research on the disease; and educational materials for physicians and patients.

From the CMQCC’s announcement about the toolkit:

The primary aim of the Toolkit is to guide and support obstetrical providers, clinical staff, hospitals and healthcare organizations to develop methods within their facilities for timely recognition and an organized, swift response to preeclampsia. “Every hospital that provides obstetric care should have current guidelines on early recognition and response to preeclampsia,” says Dr. Druzin. An expert in the field, Dr. Druzin also served on a national committee that made recommendations to the American College of Obstetrics and Gynecology on how to diagnose and treat preeclampsia.

I spoke with Druzin when the toolkit was in development, and he stressed that sharing this information could prevent tragic outcomes for women and their families. “The good news is that with a modern treatment approach, most women and their babies can have safe, healthy outcomes,” he said.

Previously: Could exercise before and during early pregnancy lower risk of pre-eclampsia?
Photo by nanny snowflake

Infectious Disease, Pregnancy, Public Health, Women's Health

Text message reminders shown effective in boosting flu shot rates among pregnant women

Text message reminders shown effective in boosting flu shot rates among pregnant women

pregnant_textingInfluenza is now widespread in 35 states across the country. Changes to the immune system during pregnancy make expectant moms more susceptible to the flu, and these women also face a particularly high risk for complications if they get sick. But despite this, roughly half of pregnant women fail to get a seasonal flu shot.

In an effort to increase adherence rates among moms-to-be, Columbia University researchers recently examined the effectiveness of using text message reminders. Psych Central reports:

Women in the intervention group received five weekly text messages about the importance of the vaccine starting in mid-September 2011 and two text message appointment reminders.

Both the intervention group and a control group received standard automated telephone appointment reminders.

The results showed that text messaging was successfully used to increase vaccination coverage.

Adjusting for gestational age and number of clinic visits, women who received the intervention were 30 percent more likely to be vaccinated.

A subgroup of women early in the third trimester had the highest intervention effect – 61.9 percent of the intervention group was vaccinated versus 49 percent for the control group.

The study adds to a growing body of work that shows how mobile health initiatives can help improve public health.

Previously: Ask Stanford Med: Answers to your questions about seasonal influenza, Flu shots for moms may help prevent babies from being born too small and Examining the effectiveness of text4baby service
Photo by niXerKG

Immunology, Nutrition, Pediatrics, Pregnancy

Eating nuts during pregnancy may protect baby from nut allergies

Eating nuts during pregnancy may protect baby from nut allergies

peanutbutterjelly.jpgThank goodness I ate so much peanut butter while I was pregnant.

That was my first reaction to new research, published today in JAMA Pediatrics, that found an association between higher nut consumption during pregnancy and lower rates of nut allergies in the baby. The researchers, at the Dana-Farber Children’s Cancer Center, Boston, asked women to record information about their diets during or soon after pregnancy, and came back later to find out whether their babies developed nut allergies. Among moms who were not themselves allergic to nuts, regular consumption of peanuts and tree nuts (almonds, walnuts and so on) was linked to reduced nut allergies in the babies. Women with the highest nut consumption, who ate nuts five times or more per week, had babies with the lowest allergy risk.

The finding helps clarify a debate about whether expectant women can do anything to reduce the risk of allergies in their babies. Previously, some experts have suggested that perhaps pregnant and breastfeeding women should avoid nuts to lower allergy risk. But the new findings contradict that recommendation. From a JAMA press release on an editorial about the new research:

…pregnant women should not eliminate nuts from their diet as peanuts are a good source of protein and also provide folic acid, which could potentially prevent both neural tube defects and nut sensitization. So, to provide guidance in how to respond to the age-old question “To eat or not to eat?” mothers-to-be should feel free to curb their cravings with a dollop of peanut butter!

Previously: Food allergies and school: One mom’s perspective, Ask Stanford Med: Pediatric immunologist answers your questions about food allergy research and A mom’s perspective on a food-allergy trial
Photo by Matias-Garabedian

Pregnancy, Research, Stanford News, Women's Health

Stanford-developed fertility treatment deemed a “top medical breakthrough” of the year

Stanford-developed fertility treatment deemed a "top medical breakthrough" of the year

‘Tis the season for end-of-the year top 10 lists. (Just wait – we have some of our own to post soon on Scope.)  TIME.com recently published its “Top 10 of Everything of 2013″ lists, and a Stanford fertility development was included as a top medical breakthrough.

From writer Alice Park:

Poor quality eggs are one of the reasons that some American women struggle to get pregnant. But researchers at Stanford University developed a technique that helps women with ovarian insufficiency to produce healthy, mature eggs again. The process, called in vitro activation, involves removing an ovary or piece of ovarian tissue and treating it in a lab with proteins and other factors that help the immature follicles it contains to develop into eggs. The recharged tissue is then reimplanted near the fallopian tubes. So far, of the 27 women who volunteered to test the technique, five produced viable eggs, one woman is pregnant and another gave birth to a healthy baby.

Previously: Image of the Week: Baby born after mom receives Stanford-developed fertility treatment, Oh, baby! Infertile woman gives birth through Stanford-developed technique and Researchers describe procedure that induces egg growth in infertile women

Emergency Medicine, In the News, Pediatrics, Pregnancy, Stanford News, Women's Health

Russian doctors visit Packard Children’s Hospital for childbirth-crisis training

Russian doctors visit Packard Children's Hospital for childbirth-crisis training

operationSome believe “The Trauma of Birth” is part of the human condition even during a healthy delivery. But sometimes entry into the world comes with unexpected medical complications – for mother as well as baby. Stanford’s Center for Advanced Pediatric and Perinatal Education at Lucile Packard Children’s Hospital trains health professionals on best practices for handling childbirth emergencies. An article in the San Francisco Chronicle spotlights experiences of the first Russian visitors to the center, which has been training medical experts from all over the world since 2002.

From the piece:

The simulation room looked a lot like a hospital room, with a couple of significant differences. Behind a two-way mirror, technicians sat in a control room video-recording the doctors’ every movement on seven cameras. They manipulated the vital signs shown on the bedside monitor of the mother, who was played by a hospital employee. They controlled the pumping lungs and warm breath of the baby mannequin.

After the childbirth simulation, the four Russian doctors involved in the scenario sat before a television and watched themselves on instant replay. Cringing a bit, the obstetricians admitted that they could have worked more efficiently by splitting up, with one monitoring the woman’s vital signs and the other guiding the delivery. One of the neonatologists who assisted with the newborn remarked that she should have called for help from a colleague sooner.

One of the participating doctors, Yulia Vorontsova, a neonatologist, said with the assistance of an interpreter, “When you look at a situation from the outside, it gives you a richer experience.”

Previously: “Preparation is everything:” More on how Stanford and Packard got ready for the Asiana crash, Whiz Kids: Research looks at handling pediatric crises effectively and Improving treatment for infant respiratory distress in developing countries
Photo by phalinn

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