Preventing Recurrent Preterm Birth

Preterm birth continues to be a leading cause of neonatal morbidity and mortality, with little progress made in reducing its frequency. Despite research efforts, scientists have little understanding of the causes of premature labor and rupture of membranes. However, in 2003, there appeared to be a breakthrough in prevention. An article in The New England Journal of Medicine described a randomized clinical trial showing a one-third reduction in preterm birth for women with a prior preterm delivery with weekly injections of a drug called 17-hydroxy-progesterone caproate, or 17P. This drug has been around for decades, with small studies showing mixed results for its efficacy. However, the 2003 study was sponsored by the NIH and performed with scientific rigor, and appeared to establish this medication as a huge step forward in treatment for the problem. And safety data showed no adverse side effects of this drug on the mother or the baby.

Upon publication of this article, clinicians quickly rallied behind this treatment for this vexing pregnancy condition. The only issue was that it was made by any drug company and was not on the market. So, clinicians went to pharmacies that could make drugs not currently available to begin making 17P. The American College of Obstetricians and Gynecologists recommended using 17P for patients with a prior preterm birth, and the March of Dimes advocated publicly for such patients to receive it. Patients with a previous preterm birth readily accepted this medication, not wanting to repeat the difficulties they had experienced, so the drug became increasingly used in this situation. Of note, trials using 17P for other risk factors (twins, triplets, short cervical length) did not find it to be effective for preventing preterm birth in any other situation.

After many years, a drug company applied for FDA approval to market 17P. Not often granting authorization based on a single trial, the FDA eventually gave consent for its marketing on the condition that the drug company perform another trial in women with a prior preterm birth to verify its effectiveness. There was trouble recruiting patients in the United States to participate in the trial, as very few women who had experienced this complication and could get access to 17P outside the trial were willing to risk being randomized to the placebo group. So, most women recruited for the study were recruited internationally. Published in 2020, the trial was four times larger than the original trial published in 2003. The results were very disappointing—there was no benefit with regard to the frequency of preterm birth, neonatal complications, or fetal/neonatal death.

Earlier this year, after considerable debate and consultation, the FDA withdrew approval for 17P, saying that it was ineffective, and the drug company stopped making it. The American College of Obstetricians now advises against prescribing it. It is unclear how the two very well-conducted trials came to such different conclusions, but it turns out that this is not uncommon at all in medicine. When studied in multiple trials, hardly any treatment shows universal agreement—researchers now routinely use a statistical technique called meta-analysis to combine data from various trials to see where the preponderance of the evidence lies.

We are back to where we started with preterm birth—no effective preventive treatments. It is most disappointing for the patients who have watched a child struggle in the neonatal ICU. But research continues, and hopefully, another treatment will come along with the promise of reducing the morbidity and mortality of preterm birth. With all of the advances being made in medicine, there is reason to be optimistic.

Advances in Fetal Surgery

One in every 40 babies is born with a major birth defect, much more common than most people realize. Most are related to malformations of the heart, brain, spine, or kidneys, but almost any body part can be affected. Some of these occur in combination as part of a syndrome, but most are isolated findings. These days, 80% or more of these defects can be identified by ultrasound in the middle of the pregnancy. Parents can benefit from this early detection by being referred to specialists who explain the nature of the condition, how it might affect the child, what further diagnostic testing may help to provide a prognosis, and how follow-up evaluations should occur. The couple may also be referred to a pediatric specialist who is more familiar with the condition and its long-term implications.

Some fetal heart defects will need surgery after the baby is born, but there are other types of birth defects that doctors can now operate on while the baby is still inside the uterus. The most common intrauterine surgery currently being performed is for open spina bifida. Spina bifida is a condition where the skin over the spine is open, exposing the spinal cord. This occurs in approximately one in every 1,000 pregnancies and can be associated with hydrocephalus (fluid buildup in the brain), weakness or paralysis of the legs, and loss of bowel or bladder control. When identified in the second trimester, in many cases, a surgeon can insert a scope through the mother’s abdomen and into the uterus, and close the skin over this defect. When this is performed, it can reduce the amount of disability for the child once it is born.

Some fetal surgery is performed for conditions other than birth defects. For example, if a fetus develops severe anemia, which used to be lethal, a needle can now be inserted through the mother’s abdomen and into the baby’s umbilical cord so that blood can be transfused. This is often a life-saving procedure.

In twin-twin transfusion syndrome (TTTS), which can occur among identical twins, the circulations of the two fetuses are interconnected through the placenta, with one getting more than half of the blood. This can lead to heart failure in the twin getting more of the blood and deterioration of the “donor.” A scope can now be inserted into the uterus, again through the mother’s abdomen, and a laser used to interrupt the blood connections in the placenta. In this way, the circulations of the twins are separated, and the condition often resolves.

These procedures, which once seemed like science fiction, are now being performed daily in the United States. Doctors can now help families have healthy outcomes for complications that used to be fatal or cause a severe disability. Every day, more advances are being made in the fields of fetal medicine and pregnancy care, giving peace of mind to mothers and improved health possibilities for developing babies.

Even a World-Class Athlete Can Die During Pregnancy

Tori Bowie was a world-class track and field athlete, having won 3 Olympic medals in the 2016 Olympics, including the gold medal in the 100 meters. But on May 2nd of this year, Ms. Bowie was found dead in her Florida home at age 32. Despite being in excellent physical condition, the recently released autopsy report stated that she died of complications from childbirth, possibly eclampsia. Little other information is available regarding the events surrounding her death. Eclampsia is a condition unique to pregnancy in which a woman develops severe hypertension (high blood pressure), seizures and sometimes coma. This condition is a medical emergency that requires intensive medical care to save the life of the mother and the baby.

Preeclampsia is a condition where a woman experiences an elevation of her blood pressure in the last trimester of pregnancy, often accompanied by passing large amounts of protein in the urine. It is not uncommon, being found in 5-10% of pregnancies, and is often asymptomatic and identified in routine office visits. When it is mild, the pregnancy can often be carried to term. But in some women, the preeclampsia progresses to a more severe form which can be dangerous for both the mother and fetus. There is no cure for preeclampsia other than delivery, and this may be necessary even if the pregnancy is far from the due date.

Preeclampsia can also come on quickly and progress in severity in a few hours, as it may have in the case of Ms. Bowie. Without medical care, patients in this situation can lose consciousness if seizures develop. This can lead to further severe complications, including bleeding in the brain, liver rupture, kidney failure, breathing difficulties, and even death. The key to survival is early recognition of the situation, prompt medical attention to stabilize the patient, and delivery of the baby.

Sadly, tragic events such as this do occur from time to time. More light has been shed in the media in the last few years regarding the much higher risk of maternal mortality in African American women, and much of this increase in mortality has been due to complications of hypertension. This racial disparity likely arises from many factors, including genetics, lifestyle, and access to care, all of which are difficult to address for an entire population. Many states have expanded access to Medicaid, and this may help. A valuable first step is awareness by both pregnant women and their healthcare providers. Women should be educated to recognize unusual or troublesome symptoms they may experience and then report them to their providers. In turn, providers must respond appropriately to these concerns. Hopefully, Ms. Bowie’s sudden and unfortunate passing will help bring the type of awareness that will lead to earlier recognition and treatment of serious complications before they become life-threatening.

We may never know the full story as to why Tori Bowie died from her complications. What is clear is that despite her excellent physical condition and notoriety, she was still vulnerable to dying during pregnancy. We need to continue to fight for all women to have a healthy pregnancy without endangering their lives or the lives of their unborn children.