Discussion
PTB, CL ≤, sPTB
PRETERM BIRTH, MISCARRIAGE
Our study identified a negative association between CL measured during the second trimester of pregnancy and the rate of sPTB. CL ≤ 31.7 mm is an important risk factor for PTB at ≤ 37 weeks and CL ≤ 25 mm is associated with extremely severe, severe, moderate and late PTB whereas CL of 25–30 mm is associated with late PTB. This study also confirms previous observational studies that found low BMI, previous miscarriage, previous PTB, CL ≤ 30 mm, funneling and sludge as predictors for PTB [The most relevant risk factor for PTB in a singleton pregnancy is a previous history of PTB; however, in nulliparous women this does not apply. We had almost half of the sPTB in nulliparous women and TVU is an important mean to identify nulliparous women at risk of PTB. In those women, except for BMI, the other important risk factors are directly connected to the second trimester TVU results. Thus, considering the higher incidence of sPTB in Brazil and globally [As a screening test for PTB, TVU did not present good performance to predict PTB at < 37 weeks. This result agrees with previous studies that did not find high sensitivity or acceptable specificity to consider TVU as a screening test to predict late PTB [There is an inverse correlation between long-term morbidity and adverse neurodevelopmental outcomes with gestational age at birth, which incurs higher medical costs and extrapolates this health problem to the economic sphere, generating a huge financial impact on the health system. The suggested NNS to identify a woman under real risk for an early preterm birth is very acceptable for a screening test. Thus, offering TVU as a screening test for women at risk of moderate and extreme sPTB would increase the reaching of optimal timing for antenatal corticosteroid administration [Recently, a multicenter Swedish cohort study involving 11,465 asymptomatic singleton pregnant women found that TVU ability to predict sPTB at < 37 weeks was poor: AUC of 0.63 (0.59–0.67) for measurement at 21–23 (+ 6) weeks with best cutoff point 35 mm; and the number needed to screen (NNS) to detect one true positive test result for sPTB at < 34 weeks considering CL ≤ 25 mm was 524. TVU demonstrated good performance (AUC > 0.75) for predicting sPTB at < 31 weeks’ gestation [The main strength of this study is that we have a considerably large sample of Brazilian women from 17 centers in three regions, thus covering possible internal population differences. In Brazil, previous TVU performance analyses to predict PTB were from single-center studies [The vaginal progesterone used for women with CL ≤ 30 mm is a limitation in our study because progesterone reduces the occurrence of PTB. Nevertheless, in our prenatal clinical assistance, women with CL ≤ 25 mm are encouraged to use progesterone, so maintaining this intervention in our sample allows the possibility to pragmatically infer the results to medical practice. Unfortunately, we cannot identify if progesterone has caused any reduction in PTB between women with CL 25– ≤ 30 mm, which could have underestimated PTB incidence in this subgroup. Another limitation is that some participating centers did not perform universal TVU screening, which could introduce some selection bias in our sample and the tendency to have a shorter CL. However, the mean CL identified was very similar to other previous Brazilian studies [Women with CL ≤ 25 mm had a significant association with sPTB < 34 weeks, which is an important clinical goal for preterm birth. Additionally, we found that the best cutoff points for all gestational ages outcomes (< 37, < 34, < 32 and < 28 weeks) are over 25 mm. Considering the feasibility to perform CL measurement following a standard technique and the capability to detect almost one third of all sPTB < 37 weeks, we suggest to use CL ≤ 30 mm as the cutoff for cervical length to identify women at risk of sPTB. This is easier to remember and is very similar to the best cutoff point identified in our study. Thus, women with CL ≤ 30 mm should be recognized as at higher risk for PTB and those with CL ≤ 25 mm should be recognized and treated properly to reduce sPTB < 34 weeks.It is important to highlight that although women with CL ≤ 30 mm are at higher risk for PTB, effective treatment for preventing PTB in women with 25–30 mm CL are not available [Considering the cutoff point where vaginal progesterone has demonstrated efficacy (25 mm), the NNS of 248 to detect 18 women with CL ≤ 25 mm is an acceptable number, which suggests the feasibility of implementing TVU for pregnant women in mid-trimester in settings like Brazil.As most PTBs worldwide are concentrated in low- and middle-income countries, this analysis is important to describe specific results for our population and stimulate new studies in other similar settings focused on strategies to reduce PTB. In such countries, where economical resources are considerably limited, it is important to define with precision the best strategies to reduce costs while improving health care. Nowadays, the national antenatal care for Brazil has not adopted routine TVU at mid-trimester screening based on studies developed in high-income countries with lower rates of sPTB. The NNS estimated in our study creates an opportunity to review the Brazilian and other countries’ protocols to deal with the PTB prevention. The estimated NNS is considered low and acceptable and should underpin the implementation of the TVU as a mid-trimester screening test.