Preterm delivery accounts for more than 75% of all neonatal deaths.1 Survival of preterm infants depends mainly on gestation at delivery; survival increases from less than 5% for those born at 23 weeks to more than 95% by 32 weeks.2,3 The risk of severe handicap in survivors decreases from more than 60% for those born at 23 weeks to less than 5% by 32 weeks.3–5
In singleton pregnancies, the rate of spontaneous delivery at or before 32 weeks is 1% to 2%. Recent evidence suggests that measurement of cervical length at 22–24 weeks' gestation sensitively and specifically predicts early preterm delivery.6,7 In a screening study involving cervical assessment at 23 weeks, the incidence of cervical length of up to 15 mm was 1.6%, and in that group 86%, 82%, 58%, and 38% delivered spontaneously at or before 28, 30, 32, and 34 weeks, respectively.7
In twin pregnancies, the rate of preterm delivery at or before 32 weeks is 5–10%.8 In a study of 26 women with twin pregnancies who presented with suspected preterm labor at 23–33 weeks' gestation, cervical length of less than 25 mm identified about 90% of those who delivered spontaneously at or before 33 weeks, with a false-positive rate of 45%.9 In a study of 85 women with twin pregnancies who were referred to a prematurity prevention clinic at 24–26 weeks, cervical length of less than 25 mm identified only 31% of those who delivered spontaneously at or before 33 weeks, with a false-positive rate of 18%.10 In a screening study of 147 women with twin pregnancies, cervical length was measured by transvaginal sonography at 22–24 weeks' gestation. Cervical length up to 25 mm was found in 18% of cases, and in that group 54% and 30% delivered spontaneously at or before 31 and 34 weeks, respectively.11
The aim of the present study is to examine the possible value of cervical assessment in twin pregnancies at 23 weeks in predicting risk of spontaneous preterm delivery.
Subjects and Methods
This was an observational study in women with twin pregnancies who presented to our unit at 10–14 weeks' gestation for assessment of risk of chromosomal abnormalities by maternal age and fetal nuchal translucency thickness.12 At the time of scans the junction of the intertwin membrane, with the placentas, was examined for a triangular piece of placental extension (the lambda sign); if it was present the pregnancy was classified as dichorionic.13 Women were offered the option of follow-up scans at 16, 20, and 23 weeks to examine fetal anatomy and growth. In monochorionic pregnancies the purpose was to make early diagnoses of possible twin-to-twin transfusion syndrome.14 At the 22–24 week scans, women were also offered the option of having transvaginal sonographic assessment of their cervices. The study was approved by the hospital ethics committee.
Women were asked to empty their bladders and were placed in the dorsal lithotomy position. Transvaginal sonography with a 5-MHz transducer (Aloka 1700; Aloka Co, Ltd, Tokyo, Japan) was done by one of four trained sonographers. The probe was placed in the anterior fornix of the vagina and a sagittal view of the cervix, with the echogenic endocervical mucosa along the length of the canal, was obtained. Care was taken to avoid exerting undue pressure on the cervix. Calipers were used to measure the distance between the triangular area of echodensity at the external os and the V-shaped notch at the internal os.15,16 Each examination was done for approximately 3 minutes to observe any cervical changes. Changes that might have been due to contractions were observed in less than 1% of women, and in such cases the shortest measurement was recorded.
Subject characteristics, including demographic data and obstetric and medical histories, were obtained from the women at their first visit to the hospital and were entered into a computer database. Ultrasound findings were recorded in the database at the time of the scans. Gestational age was determined from menstrual history and confirmed by measurement of fetal crown-rump length of the longer twin at first-trimester scan. Data on pregnancy outcomes were obtained from the computerized system in the delivery ward, or for those who delivered at home or in other hospitals, from the women themselves or their primary care physicians.
A computer search identified all twin pregnancies with live fetuses that had 23-week cervical assessments and known pregnancy outcomes. Excluded from the study were monochorionic pregnancies in which severe twin-to-twin transfusion syndrome developed (anhydramnios with anuria in the presumed donor and polyhydramnios with polyuria in the presumed recipient) requiring antenatal intervention, and pregnancies that had elective cervical cerclage before the 23-week scan because of history suggestive of cervical incompetence.
Distribution of cervical length was determined and normality was examined by the Kolmogorov-Smirnov test. Sensitivity and false-positive rate for spontaneous preterm delivery at or before 28, 30, 32, and 34 weeks for cut off cervical lengths of 15, 25, 35, and 45 mm were calculated. The χ2 test or Fisher exact test was used to calculate the significance of differences between subgroups in the percentage of spontaneous deliveries at or before 28, 30, 32, and 34 weeks, according to demographic characteristics, obstetric history, chorionicity, and cervical measurements.
The computer search identified 215 twin pregnancies with live fetuses that had cervical assessments at 22–24 (median 23) weeks' gestation; 133 (61.9%) pregnancies were dichorionic and 82 (38.1%) were monochorionic. There were 173 (80.5%) white, 34 (15.8%) black, and eight (3.7%) of other ethnicity. One hundred fifty (69.8%) subjects were aged 35 years or less and 65 (30.2%) were more than 35 years old. Twenty-six (12.1%) smoked cigarettes, none admitted to drinking more than the equivalent of five glasses of wine per week or taking recreational drugs, and one (0.5%) had a previous cone biopsy of the cervix. None of the fetuses had any major abnormalities. In terms of obstetric history, 63 (29.3%) women had no previous pregnancies, 69 (32.1%) had had one or more previous miscarriage or termination of pregnancy before 16 weeks' gestation, 62 (28.8%) had one or more term deliveries, with or without previous fetal losses before 16 weeks, 15 (7.0%) had at least one previous spontaneous preterm delivery, and six (2.8%) had at least one previous miscarriage or termination at 16–23 weeks.
Distribution of cervical length was skewed to the left. The median was 38 mm, and fifth and first centiles 19 mm and 7 mm, respectively (mean 36.8 mm, standard deviation [SD] was 10.5 mm) (Figure 1). The median and mean values were the same for monochorionic and dichorionic twin pregnancies. There was no significant association between cervical length and any demographic characteristics, obstetric histories, or chorionicity. In 4.2%, 11.2%, 40.0%, and 83.7% of cases, cervical lengths were up to 15 mm, 25 mm, 35 mm, and 45 mm, respectively. Three women with the shortest cervical lengths (1 mm, 6 mm, and 7 mm, respectively) had elective placement of cervical sutures and delivered at 36, 34, and 38 weeks, respectively. Those women were excluded from further analysis. All other subjects were managed expectantly without bed rest or prophylactic antibiotics or tocolytics.
The rates of spontaneous and iatrogenic delivery at or before 28, 30, 32, and 34 weeks are shown in Table 1. The sensitivity and false-positive rates for spontaneous delivery according to cervical length are shown in Figure 2. The sensitivity to predict spontaneous preterm delivery for cervical length up to 25 mm was 100%, 80%, 47%, and 35% for 28, 30, 32, and 34 weeks, respectively. The three women with the shortest cervical lengths (1–7 mm) had cervical sutures, so it was possible that the sensitivity of cervical lengths up to 25 mm was underestimated. All three other women with very short cervices (8 to 9 mm), who were managed expectantly, delivered spontaneously at or before 28 weeks. The rate of spontaneous preterm delivery at or before 28, 30, 32, and 34 weeks was not related significantly to any of the demographic characteristics, obstetric history, or chorionicity. The rate of spontaneous delivery at or before 32 weeks increased exponentially with decreasing cervical length at 23 weeks from 2.9% (95% confidence interval [CI] 1.9%, 3.8%) at 46 mm or longer, to 4.3% (95% CI 3.8%, 4.7%) at 36–45 mm, 6.7%(95%CI 5.7%,7.4%) at 26–35 mm,31%(95% CI 17%, 43%) at 16–25 mm, and 66% (95% CI 51%, 81%) at 15 mm or less (Figure 3).
This study showed that measurement of cervical length in twin pregnancies at 23 weeks' gestation sensitively predicted spontaneous, preterm delivery. Cervical length at 23 weeks was 25 mm or less in about 11% of the population, and in that group about 80% of the women delivered spontaneously at or before 30 weeks, and 45% delivered at or before 32 weeks. We provided a model for predicting individual risk for spontaneous delivery at or before 32 weeks, based on cervical length at 23 weeks. The estimated risk for preterm delivery increased exponentially with decreasing cervical length from about 2% at 55 mm to 4% at 40 mm, 30% at 20 mm, and 70% at 10 mm.
The median cervical length (38 mm) was the same as in a previous screening study in singleton pregnancies, but the fifth and first centiles were 19 mm and 7 mm, respectively, compared with 23 mm and 12 mm in women with singleton pregnancies. Cervical lengths were 25 mm or less in 11.2% of twin pregnancies, compared with 8.2% in singletons.7 In the only previous screening study in twins, the distribution of cervical lengths was not given, but the length was 25 mm or less in 17.7%.11 In the present study, we excluded pregnant women who presented with severe twin-to-twin transfusion syndrome, defined by polyhydramnios-anhydramnios sequence, because the natural history of the condition was altered by endoscopic laser coagulation of the communicating placental vessels.17 The extent to which those exclusions explain the lower percentage of women with short cervices in our study compared with that of Goldenberg et al11 is not certain because we could not ascertain whether they included pregnancies with severe twin-to-twin transfusion syndrome.
The incidence of preterm delivery at 24–32 weeks' gestation was twice as high in monochorionic compared with dichorionic twin pregnancies,8 a difference almost entirely due to polyhydramnios in severe twin-to-twin transfusion syndrome that complicates about 15% of monochorionic twin pregnancies.14 In our study, which excluded severe twin-to-twin transfusion syndrome, monochorionic and dichorionic twin pregnancies had similar cervical length at 23 weeks and similar incidence of spontaneous early preterm delivery (7.2% and 8.2%, respectively).
In the present study only cervical length was significantly associated with spontaneous early preterm delivery. Consequently, the well-described associations between certain demographic characteristics and obstetric history with preterm delivery might be mediated by cervical changes that are apparent as cervical shortening by 23 weeks' gestation.
The sensitivity of cervical length at 23 weeks predicting spontaneous preterm delivery of twin pregnancies (80% at or before 30 weeks and 47% at or before 32 weeks) was similar to that of singleton pregnancies (about 80% at or before 30 weeks and 58% at or before 32 weeks).7 Although those sensitivities were achieved with a much higher screen-positive rate in twin pregnancies (11% for cervical length up to 25 mm) compared with singleton pregnancies (1.6% for cervical length up to 15 mm),7 it was probably because the rate of early preterm delivery of twins was much higher than for singletons. Thus, the spontaneous preterm delivery rate at or before 32 weeks was 8% for twins and 1.5% for singletons. The risk of preterm delivery for cervical length of 25 mm or less in twin pregnancies (42%) was similar to that in singleton pregnancies with cervical length of 15 mm or less (52%).7
In singleton and twin pregnancies, the risk of preterm delivery increases exponentially with decreasing cervical length; however, the threshold for this increase is about 30 mm in twins and 20 mm in singletons (Figure 3).7 Several studies reported that prelabor uterine activity in twin pregnancies was significantly higher than in singleton pregnancies, from at least as early as 23 weeks' gestation, which might explain why with twins a longer cervix is needed to maintain its physiologic role as an effective barrier to early preterm delivery.18–20
Preliminary data suggest that in singleton pregnancies with short cervices at 23 weeks' gestation, the placement of a suture might be associated with a tenfold reduction in risk for early preterm delivery.21 The extent to which the same might be true for twin pregnancies remains to be determined.
1. Copper RL, Goldenberg RL, Creasy RK, DuBard MB, Davies RO, Entman SS, et al. A multicenter study of preterm birth weight and gestational age-specific neonatal mortality. Am J Obstet Gynecol 1993;168:78–84.
2. Guyer B, Martin JA, MacDorman MF, Anderson RN, Strobino DM. Annual summary of vital statistics—1996. Pediatrics 1997;100:905–18.
3. Tin W, Wariyar U, Hey E. Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. Northern Neonatal Network. BMJ 1997;314:107–11.
4. Rennie JM. Perinatal management at the lower margin of viability. Arch Dis Child 1996;74:214–8.
5. Robertson PA, Sniderman SH, Laros RK, Cowan R, Heilbron D, Goldenberg RL, et al. Neonatal morbidity according to gestational age and birth weight from five tertiary care centers in the United States, 1983 through 1986. Am J Obstet Gynecol 1992;166:1629–45.
6. lams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous delivery. N Engl J Med 1996;334:567–72.
7. Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Cervical length at 23 weeks of gestation: Prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol 1998;12:312–7.
8. Sebire NJ, Snidjers RJM, Hughes K, Sepulveda W, Nicolaides KH. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997;104:1203–7.
9. Crane JM, Van den Hof M, Armson BA, Listen R. Transvaginal ultrasound in the prediction of preterm delivery: Singleton and twin gestations. Obstet Gynecol 1997;90:357–63.
10. Imseis HM, Albert TA, lams JD. Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24 to 26 weeks' gestation. Am J Obstet Gynecol 1997;177:1149–55.
11. Goldenberg RL, lams JD, Miodovnik M, Van Dorsten JP, Thurnau G, Bottoms S, et al. The preterm prediction study: Risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1996;175:1047–53.
12. Snidjers RMJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Lancet 1998;351:343–6.
13. Sepulveda W, Sebire NJ, Hughes K, Odibo A, Nicolaides KH. The lambda sign at 10–14 weeks of gestation as a predictor of chorionicity in twin pregnancies. Ultrasound Obstet Gynecol 1996;7:412–23.
14. Sebire NJ, D'Ercole C, Carvelho M, Sepulveda W, Nicolaides KH. Inter-twins membrane folding in monochorionic pregnancies. Ultrasound Obstet Gynecol 1998;11:324–7.
15. Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol 1990;163:859–67.
16. Heath VC, Southall TR, Souka AP, Novakov A, Nicolaides KH. Cervical length at 23 weeks of gestation: Relation to demographic characteristics and previous obstetric history. Ultrasound Obstet Gynecol 1998;12:304–11.
17. Ville Y, Hyett J, Hecher K, Nicolaides K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995;332:224–7.
18. Newman RB, Gill PJ, Katz M. Uterine activity during pregnancy in ambulatory patients: Comparison of singleton and twin gestations. Am J Obstet Gynecol 1986;154:530–1.
19. Newman RB, Gill PJ, Campion S, Katz M. The influence of fetal number on antepartum uterine activity. Obstet Gynecol 1989;73:695–9.
20. Garite TJ, Bentley DL, Hamer CA, Porto ML. Uterine activity characteristics in multiple gestations. Obstet Gynecol 1990;76:56S–59S.
21. Heath VC, Souka AP, Erasmus I, Gibb DM, Nicolaides KH. Cervical length at 23 weeks of gestation: The value of Shirodkar suture for the short cervix. Ultrasound Obstet Gynecol 1998;12:318–22.