New approaches to preventing preterm birth and related complications were discussed by Roberto J. Romero, MD, here at the American Congress of Obstetricians and Gynecologists (ACOG) 59th Annual Clinical Meeting. In particular, Dr. Romero highlighted studies of cutting-edge technology that may lead to an approach for the prevention of cerebral palsy.
"Preterm birth is one of the most challenging problems," he said, and the frequency of preterm birth in the United States has remained unchanged over the past 2 decades, remaining at 12% overall and 20% in underserved populations. "Worldwide, 30 million preterm babies are born annually, with both short- and long-term complications," Dr. Romero told listeners at the Anna Maria D'Amico lecture. Dr. Romero is affiliated with the Perinatal Research Branch of the National Institutes of Health and is a professor at Wayne State University in Detroit, Michigan.
Preterm birth is a syndrome with multiple etiologies, Dr. Romero emphasized. No single test can predict all preterm births, and no singular treatment or prevention strategy will eradicate preterm birth. That being said, 2 factors are strongly associated with preterm birth: Short cervix (a cervix <15 mm in length) increases the risk for preterm birth by 50%, and progesterone deficiency is implicated in both preterm birth and short cervix. These 2 factors overlap and are amenable to treatment.
A study reported on last month by Medscape Medical News describes in detail the results of the PREGNANT trial, showing a significant 45% reduction in preterm birth (before 33 weeks' gestation) with the use of vaginal progesterone vs placebo (P = .02).
In that large, multicenter, randomized, placebo-controlled trial, 465 women with a singleton pregnancy and a short cervix on sonography (10 - 20 mm) were randomly assigned at 19 to 23 weeks of gestation to treatment with daily, self-administered vaginal progesterone or placebo. The rates of preterm birth at less than 28 weeks' gestation and 35 weeks' gestation were also significantly reduced with vaginal progesterone gel vs placebo, with a relative risk reduction of 50% (P = .04) and a relative risk reduction of 38% (P = .02), respectively.
Vaginal progesterone was also associated with a significantly reduced risk for respiratory distress syndrome (P = .03), any neonatal morbidity or mortality event (P = .04), and low birth weight (P = .01). No difference in adverse events was observed when vaginal progesterone was compared with placebo.
Dr. Romero commented on the implications of PREGNANT: "It is now possible to screen and assess risk delivery using cervical ultrasound [to measure cervical length,] and a simple intervention [ie, vaginal progesterone gel] can make a big difference."
He noted that before the results of PREGNANT were released online, a pharmacoeconomic analysis found that using ultrasound to measure cervical length could reduce the costs associated with preterm birth by $12 million, provided each scan cost $184 or less. For vaginal progesterone, the same analysis found that the number-needed-to-treat (NNT) to prevent 1 preterm birth was 14, and the NNT to prevent 1 case of respiratory distress syndrome was 22.
"These numbers compare favorably with other obstetrical interventions commonly used to prevent preeclampsia and respiratory distress syndrome," Dr. Romero stated.
"Vaginal progesterone gel will absolutely be used in clinical practice in women with short cervix. This treatment is of benefit for one of our biggest challenges in obstetrics — the high rate of premature delivery," stated ACOG's Scientific Program Committee Chair Raul Artal, MD, professor and chairman of the Department of Obstetrics, Gynecology, and Women's Health at St. Louis University in Missouri.
Dr. Romero focused the remainder of his talk on potential approaches to prevent cerebral palsy, which is associated with both preterm delivery and fetal infection.
Three large, randomized trials showed equivocal evidence for prevention of cerebral palsy using magnesium sulfate for neuroprotection. A meta-analysis of these 3 trials found that use of magnesium sulfate in patients at risk for preterm birth reduced the risk for cerebral palsy by 31%. The NNT was 52, and the cost to prevent 1 case of cerebral palsy was $10,000. This suggests that magnesium sulfate can protect against some cases of cerebral palsy, Dr. Romero said.
Another approach is aimed at the complications of infection, as in utero infection accounts for about 20% of cases of cerebral palsy, he continued. "Compelling evidence suggests that bacterial infections can activate the microglia and astrocytes [2 key cells implicated in cerebral palsy], injuring the myelin. Infection leads to periventricular leukomalacia, which leads to cerebral palsy. The presence of funisitis at birth suggests that the neonate was exposed to infection in utero, and this can be useful in the medicolegal setting [in proving that infection — not malpractice — caused cerebral palsy]," Dr. Romero said.
Cutting-edge technology is being studied in animals to prevent cerebral palsy. This approach uses dendrimers, which are tree-like plastics that can attach drug and target ligands and be viewed by imaging. In neonatal animals, intravenous dendrimers containing N-acetylcysteine (an anti-inflammatory) were found to target neural inflammation in the microglia and astrocytes, he explained.
Animals with endotoxin-induced neuroinflammation were divided into 2 groups. One group was injected on day 1 of life with dendrimers that release N-acetylcysteine, and the other group was untreated. The group receiving the dendrimer injections had improved motor coordination compared with their untreated counterparts, although their motor coordination was not as good as that of control animals.
"The use of nanotechnology to combat intrauterine infections is experimental at present. Although these results are exciting, this approach needs to be studied in humans to see if it translates to the clinical setting," Dr. Artal commented.
Dr. Romero and Dr. Artal have disclosed no relevant financial relationships.
American Congress of Obstetricians and Gynecologists (ACOG) 59th Annual Clinical Meeting. Presented May 1, 2011.
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