Pediatrix Research in Maternal-Fetal Medicine: Improving Outcomes in High-Risk Pregnancies

October 17, 2023 | by Andrew Combs, M.D., Ph.D.
Pediatrix Research in Maternal-Fetal Medicine: Improving Outcomes in High-Risk Pregnancies

Pediatrix® Medical Group has sponsored several research studies on strategies to improve outcomes in high-risk pregnancies, publishing more than 30 peer-reviewed articles in medical literature since 2005.

Research is vital in obstetrics because it drives advancements in maternal and fetal care, enhances medical knowledge and improves overall outcomes. It helps identify best practices, refine medical procedures and develop new technologies to improve the health of both mothers and newborns.

The following are highlights of some of our studies that have had major impacts on the practice of obstetrics.

Antenatal Steroids

Preterm birth affects about 10.5% of pregnancies in the United States and is a major cause of newborn complications and infant mortality. When there is a threat that a pregnancy is likely to deliver preterm, a series of steroid shots given to the mother will reduce the chances of several newborn complications, including breathing problems, bleeding problems, intestinal injuries and death. However, the benefits of steroids dissipate after one to two weeks.

Before our study, if a pregnant person was given steroid shots and did not deliver for a week or more, doctors did not know whether to repeat the shots. A clinical trial by our network showed that a single “rescue” course of steroids given to such mothers will cut the rate of newborn complications in half.

A single rescue steroid treatment has since become the standard of care for patients with preterm labor who remain undelivered one to two weeks after initial steroid treatment and is endorsed by the American College of Obstetricians and Gynecologists (ACOG). Our 2009 article has been cited 158 times in medical literature.

Until recently, it has been unknown whether to give a booster course of steroids to mothers with leaking amniotic fluid (preterm rupture of membranes, or PROM) if they remain undelivered for a week or more after their initial steroid treatment. In the “rescue” trial above, we excluded patients with PROM because of concerns that steroids might increase their risk of infection. ACOG does not make a recommendation for or against rescue steroids for patients with PROM.

In May 2023, we published the results of a new clinical trial showing that booster steroids for women with PROM had no impact on the rate of newborn complications.

Preventing Preterm Birth

Two studies by other groups were published in 2003, finding that the rate of early preterm birth could be greatly reduced by the use of progesterone or a related drug, hydroxyprogesterone caproate (HPC), in people who had a preterm birth in a prior pregnancy.

Our network conducted several clinical trials to determine whether a weekly injection of HPC would help prevent early deliveries in patients at high risk for preterm birth because of twin pregnancy, triplet pregnancy or PROM. We found that HPC did not reduce preterm birth or improve any pregnancy outcome in these settings.

Although this was disappointing, these trials answered the important clinical question as to whether to use this expensive medication for patients with twins, triplets or PROM, and thereby saved the substantial costs, inconvenience and pain of weekly injections for those patients. These three trials have been cited 272 times in medical literature.

In May 2023, the U.S. Food and Drug Administration (FDA) removed its approval for HPC because of growing evidence that it is ineffective, even for patients with a previous preterm birth.


Some patients have early pregnancy loss due to the cervix silently opening. In the next pregnancy, these women have a “cerclage” procedure, which is a suture (stitch) in the cervix to help it stay closed. One complication of cerclage is PROM, which occurs in about one in 20 cerclages. Before our study, if PROM occurred after a cerclage, doctors did not know whether to leave the cerclage suture in place (to help keep the pregnancy inside) or remove the suture (to reduce the chance of infection).

We conducted the first and only clinical trial to address that question. We found that removing the suture not only reduced the infection risk but also tended to be associated with longer intervals to birth, so fears of the pregnancy delivering right away if the cerclage was removed are largely unfounded. Our 2014 article has been cited 35 times in medical literature.

Monoamniotic Twins

In most twin pregnancies, each twin is contained within its own amniotic sac. However, about 1% of twins are “monoamniotic,” meaning that both twins are in the same sac. This is a dangerous situation because their umbilical cords can become entangled and constricted, leading to stillbirth of one or both twins.

Because of this risk, doctors perform frequent fetal heart rate (FHR) monitoring on monoamniotic twins, hoping to detect early signs of cord constriction. We also deliver these pregnancies about two months before the due date, making a trade-off between complications from early delivery versus the risk of stillbirth if pregnancy were to continue.

Prior to our study, many physicians would perform the FHR monitoring several times a week on an outpatient basis but other physicians would admit patients to the hospital for monitoring once a day or more. Nobody knew whether the cost and inconvenience of hospitalization were rewarded with better outcomes.

Our study collected 96 pairs of monoamniotic twins from 11 maternal-fetal medicine (MFM) practices across the United States. Half were monitored as outpatients, and half were admitted to hospitals for monitoring. We found a stillbirth rate of 15% in those monitored as outpatients (about one in seven twins) versus 0% in those monitored in the hospital. It has since become more common to routinely admit monoamniotic twin patients for in-hospital monitoring. Our 2005 article has been cited 160 times in medical literature.

Vasa Previa

Vasa previa occurs when blood vessels from the umbilical cord pass directly over the cervix. It is dangerous because the vessels can rupture during labor or when the fetal membranes rupture, resulting in fetal bleeding. If vasa previa is not recognized before labor, fetal death from bleeding occurs in more than half the cases. If vasa previa is identified by ultrasound before labor, cesarean delivery about a month before the due date is recommended and fetal death occurs in less than one in 30 cases.

Our study of vasa previa collected 68 cases from nine MFM practices nationwide, one of the largest case series in the literature. We found that 96% of the cases were identified by prenatal ultrasound, and there were no fetal deaths. Our 2016 article has been cited 79 times in medical literature.

To learn more about Pediatrix research efforts, please visit the Pediatrix Center for Research, Education, Quality and Safety (CREQS) website. Also, learn how Pediatrix research has helped improve outcomes in neonatal intensive care.


by Andrew Combs, M.D., Ph.D.