A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix

Abstract

Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two thirds of preterm births occur after the spontaneous onset of labor, and the remaining one third after "indicated" preterm birth; however, the causes of spontaneous preterm labor and "indicated" preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identified in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at <33 weeks of gestation by 44%, along with the rate of admission to the neonatal intensive care unit, respiratory distress syndrome, requirement for mechanical ventilation, and composite neonatal morbidity/mortality score. There is no evidence that 17-α-hydroxyprogesterone caproate can reduce the rate of preterm delivery in women with a short cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and the implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (<25 mm).

Figure 1

Uterine components of the common pathway of parturition.

Figure 2

Normal spontaneous labor at term results from physiologic activation of the common pathway of parturition. In contrast, preterm labor begins because of a pathologic insult, resulting in the initiation of labor.

Figure 3

Clinical manifestations of preterm activation of the common pathway of parturition.

Figure 4

Pathological processes implicated in the preterm parturition syndrome.

Figure 5

Syndrome nature of a short cervix which is caused by multiple etiologies

Figure 6

Transabdominal sonogram performed in a patient with a full bladder. The bladder is causing compression and artificial lengthening of the uterine cervix.

Figure 7

Same patient as in Figure 6 but with the bladder emptied and transvaginal sonography performed. Note that the true cervical length is short (15.5 mm).

Figure 8

Transabdominal ultrasound when the fetus is in a vertex presentation. Note that the image quality of the uterine cervix is poor, because there is greater distance between the probe and the cervix, and there is shadowing from the fetal head.

Figure 9

Transvaginal ultrasound of the uterine cervix (cervical length 39.8 mm). This is the “gold standard” for the performance of cervical examinations during pregnancy. Note that the visualization of cervical anatomy and measurement of the cervical length is optimal.

Figure 10

In women with a short cervix, those receiving vaginal progesterone (vs. placebo) had a significant decrease in the rate of preterm delivery < 28, < 33, and < 35 weeks of gestation.

Figure 11

Patients with a short cervix allocated to receive vaginal progesterone (vs. placebo) had a significantly lower risk in the rate of preterm birth < 28, < 33, and <35 weeks of gestation.

Figure 12

Infants whose mothers (with a short cervix) received vaginal progesterone (vs. placebo) had a significantly lower risk of respiratory distress syndrome, composite neonatal morbidity and mortality, birthweight <1500 g, admission to neonatal intensive care unit, and requirement for mechanical ventilation