Prevention of spontaneous preterm birth in singleton pregnancies
Although prediction is key, prevention remains the true goal. Prevention can be classified into primary and secondary preventative strategies. The aim of primary prevention is to lower the incidence of PTB by improving physical and mental well-being and avoiding modifiable behavioural factors associated with PTB.
For example, smoking cessation lowers the risk of sPTB by 16% (OR 84%; 95% CI 72-98%) (44). Secondary prevention includes interventions targeted to an at-risk population identified from the general population. At present there are only effective preventative treatments for women identified with a short cervix. As a result, screening clinics have been set up across the United Kingdom to perform TVUS for women at high risk of PTL (45).17α-hydroxyprogesterone caproate
Progestogens are a class of steroid hormones that bind and activate the progesterone receptor. The role of progestogens in uterine quiescence was first reported in 1954, and they can be classed as natural or synthetic. 17α-hydroxyprogesterone caproate (17-OHPC, often shortened to 17P) is the most investigated synthetic progestogen in the prevention of sPTB. However, the term ‘progesterone’, a type of natural progestogen, has been erroneously used interchangeably with ‘progestogen’ for many years. Natural vaginal progesterone and synthetic 17-OHPC (delivered intramuscularly) have very distinct pharmacological and biochemical properties and are not considered to be the same drug (46).
No prior history of PTB, with short or unknown CL
In a low-risk population, with or without a short cervix, no randomized controlled trial (RCT) of 17-OHPC has shown benefit above placebo or a cerclage (short cervix only).
Prior PTB, unknown cervical length
In 463 women with a singleton pregnancy and a history of previous PTB between 20 and 36+6 weeks, 17-OHPC 250 mg intramuscularly weekly from 16 weeks was associated with a reduction in incidence of PTB at less than 35 weeks (relative risk (RR) 66%; 95% CI 5481%), PTB at less than 37 weeks, PTB at less than 32 weeks, as well as intraventricular haemorrhage when compared to placebo (47). Since 2003, 17-OHPC has been recommended routinely for pregnant women in the United States with a singleton gestation (48). In 2011, the US Food and Drug Administration (FDA) approved the use of 17-OHPC during pregnancy to reduce the risk of recurrent PTB in women with a history of prior sPTB. However, the FDA has requested that a second RCT of 17-OHPC versus placebo be conducted before granting full marketing approval under the Food, Drug and Cosmetic Act 505(b).
Prior PTB and short cervical length
In this population, 17-OHPC has only been evaluated in one RCT, which was discontinued after interim analysis (n = 105) showed futility in continuing. The PTB rate at less than 37 weeks was 45% in the 17-OHPC arm and 44% in the placebo arm (P >0.99) (49).