Scientific Duo Gets Back To Basics To Make Childbirth Safer

Feb 18, 2019
Originally published on February 22, 2019 1:18 am

Brittney Crystal was just over 25 weeks pregnant when her water broke.

It was her second pregnancy — the first had been rough, and the baby came early.

To try to avoid a second premature birth, Dr. Joy-Sarah Vink, an obstetrician and co-director of the Preterm Birth Prevention Center at Columbia University Medical Center, arranged for Crystal to be transported by ambulance from her local Connecticut hospital to New York City, where Vink could direct her care.

Two weeks later Crystal started having contractions. She was given magnesium sulfate to stop them, and made it through the night. Crystal believed there was a future for her coming baby, whom she had named Iris.

"I went to the mirror and I talked to Iris," Crystal says. "I said, 'you know, this was a rough day. ... You're going to have them. But then the next day comes and the sun comes up and we move forward.' "

That evening, however, the contractions started again. Crystal was whisked to an operating room for a Cesarean section. She was a little under 28 weeks pregnant.

"I think I knew before I opened my eyes that she had died," Crystal says, her voice cracking as she reaches for a tissue.

Afterward, as she was recovering in the hospital and mourning the loss of Iris, Crystal and her family asked a lot of questions. Why can't you seal up the amniotic sac if your water breaks early? Why can't you reliably stop preterm labor?

"And that's when Dr. Vink told us that, you know, rare diseases are being cured in this day and age, but we don't know what triggers full-term labor," Crystal recalls. "That just collectively blew away everyone in the room."

It was surprising but true. When it comes to pregnancy, research on some basic questions stalled decades ago, Vink says. If a pregnancy is normal, that doesn't matter much. But when things go wrong, those gaps in knowledge become issues of life and death.

"It's mind-boggling that in this day and age, we still don't understand [even] in a normal pregnancy how women go into labor — what triggers labor," Vink says. "Because we don't understand the normal fundamental mechanisms, we can't identify how things go bad — and then how we fix it when things go bad."

Crystal, for example, had undergone a procedure called cervical cerclage: Vink had stitched Crystal's cervix closed in hopes of preventing it from opening too soon. The technique has been around for more than 40 years, and it's about the only treatment available for what doctors call "an incompetent cervix." But much of the time, it's not enough to stop a premature birth.

Most basic knowledge about pregnancy comes from research performed in the 1940s, Vink says, and she's working hard to update that information.

She's focused first on the cervix, she says, because if doctors can get the cervix to stay closed in those final, crucial weeks of gestation, the baby won't be born too soon, even if the amniotic sac breaks.

"So, what is the cervix made out of? What proteins are there, what cells are there? How are all these things interacting? How do they change in pregnancy?" she asks, laying out some of the unknowns. By the end of pregnancy, a woman's cervix goes from being stiff, like the tip of a nose, to very soft. But how?

To help answer those questions, Vink and her graduate researchers are taking, for analysis, cervical tissue samples from women in her medical practice who are at different stages of pregnancy.

One of her first findings, she says, is that the cervix is not made mostly of collagen, as doctors long thought. It also has a lot of muscle, especially near the very top.

While Vink studies what the cervix is made of, one of her university colleagues, mechanical engineer Kristin Myers, is trying to determine how it works.

"I'm kind of an oddball in the department of obstetrics and gynecology," Myers says. "I teach mechanics classes and design classes here at Columbia."

Myers got her start as an undergraduate, doing materials research in the automobile industry. Back then she tested how tires respond to heat.

(Left) Myers shows Vink 3D computer simulations of the cervix. (Right) Vink pipettes solution into slides containing cervical smooth muscle cells. Understanding the forces that lead a healthy cervix to open and close at the right times may be key to preventing some premature births.
Adrienne Grunwald for NPR

"So if you take rubber and you heat it up and you pull on it, it gets really, really soft — and then it breaks," Myers says.

That reaction reminded her adviser of how a bulging aneurysm bursts. He suggested she focus her curiosity on the mechanics of the human body. When she arrived at MIT for her graduate studies, Myers worked with researchers who were interested in the mechanics of pregnancy.

"It's an important area — an understudied area — and a basic part of pregnancy physiology," says Dr. Michael House, an OB-GYN at Tufts Medical Center who also has a background in engineering. "There is just lots to learn."

House has been a mentor to Myers and continues to collaborate with her. He says the focus on the cervix is particularly important, "because a cervix problem can affect the pregnancy very early."

About 1 in 10 babies are born prematurely in the U.S. each year. If those babies are born close to term — after around 35 weeks — they can do quite well. But a woman with a problematic cervix can go into labor much sooner, which can lead to miscarriage or a baby born so early that the child may die or face lifelong health problems.

Myers is investigating several aspects of the biomechanics of pregnancy — from how much the uterus can stretch, to how much pressure pregnancy exerts on the cervix, to how much force a baby's kick puts on the whole system.

"We're building computational models of female pregnancy to answer those questions," Myers says.

She has two labs at Columbia — one at the hospital and one in the engineering school. In the lab at the engineering school there are a variety of microscopes and scalpels and slides. There's one machine that can inflate the uterine membranes like a balloon, and another, about the size of a microwave, that stretches uterine tissue between two grips.

"These [are] types of machines you'll see in all different kinds of material testing labs," Myers explains. "In civil engineering you can have one of these machines that is like two or three stories high and they're testing the mechanical strength of, [say], railroad ties."

She is measuring just how much the cervical tissue changes during pregnancy — starting out with the capability and consistency of a tendon, and becoming something more like a loose rubber band.

"We've mechanically tested various pregnant tissues and nonpregnant tissues of the cervix," Myers says, "and its stiffness changes by three orders of magnitude."

Vink reviews images of smooth muscle cells that her team isolated from cervical biopsies taken from pregnant women at different stages of pregnancy. The stiffness of the cervix changes by "three orders of magnitude" across nine months, Myer has found.
Adrienne Grunwald for NPR

All those measurements go into a databank. And when women in Vink's practice get an ultrasound, the technicians spend an extra few minutes measuring the mother's anatomy, as well as the baby's, and send that information to Myers, too.

Then the team uses their computer models to look at how the various factorsshape, stretch, pressure and tissue strength — interact as a woman moves toward labor and childbirth.

Their goal is to be able to examine a pregnant woman early on, and accurately predict whether she will go into labor too soon. It's a first step, Vink hopes, toward better interventions to stop that labor.

That's what Brittney Crystal is aiming for as well. After baby Iris died, Crystal started a foundation called The Iris Fund, which has raised more than $150,000 for Vink's and Myers' research.

"She didn't get to have a life," Crystal says. "But we really want her to have a very strong legacy."

Copyright 2019 NPR. To see more, visit https://www.npr.org.

DAVID GREENE, HOST:

This is the story about two women, a doctor and a mechanical engineer. They came together to study one of the most basic parts of human life - pregnancy and labor. That's because there's a lot we just don't know. NPR's Alison Kodjak reports on this unusual pair of researchers who are trying to learn more.

ALISON KODJAK, BYLINE: Dr. Joy Vink deals only with the hardest cases, cases like that of Brittney Crystal. Crystal was under Vink's care when she went into labor at just 28 weeks pregnant. She was rushed into an operating room at Columbia University Medical Center for an emergency C-section to try to save her baby, whom she had already named Iris.

BRITTNEY CRYSTAL: And I think I knew before I opened my eyes that she had died.

KODJAK: Afterward, as she was recovering in the hospital and mourning the loss of Iris, Crystal and her family asked Dr. Vink why there was no way to stop the premature labor.

CRYSTAL: And that's when Dr. Vink told us that actually, you know, rare diseases are being cured in this day and age, but we don't know what triggers full-term labor, which I think just collectively blew away everyone in the room.

KODJAK: Vink runs the Preterm Birth Prevention Center at Columbia. She says when it comes to pregnancy, basic research stalled decades ago. If a pregnancy is normal, that's not all that important. But when things go wrong, she says those gaps in knowledge become issues of life and death.

JOY-SARAH VINK: It's heartbreaking. It's heartbreaking to see patients who, either on their first or on their third, fourth, fifth time around, are losing a pregnancy right at that cusp of viability.

KODJAK: Crystal had what was called a short cervix, which put her at risk for going into labor early. She'd had a procedure called a cerclage, which is basically a stitch in her cervix to keep it closed and prevent an early birth. The technique has been around for more than 50 years. And while there's research to show it may help, the information is limited. Most of the basic knowledge about pregnancy comes from research performed in the 1940s, so Vink decided this time to learn more. She's starting by getting to know the cervix.

VINK: So what is the cervix made out of? What proteins are there? What cells are there? How are all these things interacting? How go they change in pregnancy? How does the cervix go from a stiff, sort of strong structure that's like the consistency of the tip of your nose to something that's as soft as butter by the end of pregnancy?

KODJAK: Her lab is full of graduate students.

VINK: We actually are taking tissue samples from the cervix from non-pregnant women as well as in pregnancy to understand what is a tissue made out of.

KODJAK: And while she's figuring out what it's made out of, she's teamed up with someone who can figure out what it can do - Kristin Myers.

KRISTIN MYERS: I'm kind of a oddball here in the Department of Obstetrics and Gynecology. I'm a mechanics person. I teach mechanics classes and design classes.

KODJAK: Myers got her start doing undergraduate research in the automobile industry looking at how rubber and tires degrades.

MYERS: So if you take rubber, and you heat it up, and you pull on it, it gets really, really soft. And then it breaks.

KODJAK: Her advisor suggested she could apply that kind of research to biology. And when she got to graduate school at MIT, she met Michael House, who was studying the biomechanics of pregnancy.

MICHAEL HOUSE: It's an important area, an understudied area and a basic part of pregnancy physiology. And I think that there's just lots to learn.

KODJAK: House, who's at Tufts, also has a background in engineering. He became a mentor to Myers and continues to collaborate with her today. He says Myers' and Vink's research on the cervix is particularly important.

HOUSE: A cervix problem is a tough one because a cervix problem can affect the pregnancy very early.

KODJAK: That means women with cervix problems are more likely to miscarry or give birth so early that their babies may die or face lifelong health problems. House says nailing down the mechanics of pregnancy is crucial to reducing premature birth. So Myers is laying the foundation - how much the uterus can stretch, how much pressure is on the cervix, what makes it open, how much force a baby's kick puts on the whole system. She has a lab next to Vink's at the medical center and another at Columbia's engineering school.

MYERS: So here's my lab.

KODJAK: There are four students sitting elbow to elbow at computers.

MYERS: So here in New York City, we run a tight, efficient ship. This is a 600-square-feet biomechanics lab.

KODJAK: On one screen, there's a multicolored three-dimensional image of the cervix that changes as the researchers add variables like a baby's kick. On the other side of a partition, there are microscopes and scalpels and slides.

MYERS: On this bench over here is a contraption we made to mechanically test thin membranes.

KODJAK: The machine inflates uterine membranes like a balloon. And there's another machine about the size of a microwave that stretches cervical tissue between two tiny grips.

MYERS: In civil engineering, you can have one of these machines that is, like, two, three stories high. And they're testing the mechanical strength of, like, railroad ties.

KODJAK: One of the most remarkable things about the cervix, Myers says, is how much it changes during pregnancy. Remember nose to butter?

MYERS: Pregnant tissue is really, really soft and squishy. So we've mechanically tested various pregnant tissues and non-pregnant tissues of the cervix, and its stiffness changes by three orders of magnitude.

KODJAK: Myers is also building an entirely new database of the anatomy of pregnant women using ultrasound images that measure the baby and the mother throughout pregnancy. She says she got the idea when she was pregnant and getting an ultrasound herself.

MYERS: Laying there on the bench, I was like, well, why can't we just measure the mom more?

KODJAK: The plan is to use that data to create a model that can predict how the uterus and cervix will react to various forces.

MYERS: What if the baby's kicking rigorously? How much mechanical force does it put on? What if the woman's at bed rest? How much does that take gravity off of her cervix? And, you know, we just don't know.

KODJAK: Vink and Myers are in constant contact. Myers' students observe Vink in the operating room as she collects tissue samples, and Vink reviews Myers' computer simulations. Their goal? To be able to look at a pregnant woman and predict accurately if she will go into labor prematurely. Only then can doctors find reliable interventions to stop it, which is what Brittney Crystal is aiming for as well. After Iris died, Crystal started a foundation called The Iris Fund, which has raised more than $150,000 for Vink's and Myers' research.

CRYSTAL: She didn't get to have a life, but we really want her to have a very strong legacy.

KODJAK: Alison Kodjak, NPR News, New York.

(SOUNDBITE OF DO MAKE SAY THINK'S "HERSTORY OF GLORY") Transcript provided by NPR, Copyright NPR.