Cerclage,progesterone and α-hydroxyprogeterone caproate treatment in women at risk for preterm delivery

Abstract

The most significant action of progesterone appears to be on the cervix and in prevention rather than on treatment of preterm delivery. In women with singleton gestations, no prior PTB, and CL <20?mm at <24 weeks, vaginal progesterone, either 90?mg gel or 200?mg suppository, is associated with reduction of both preterm birth (PTB) and perinatal morbidity/mortality. Cerclage is as effective as vaginal progesterone in women with CL <25?mm. Treatment of women with previous PTB with 17OHP-C from 16 to 20 weeks’ gestation until 36 weeks could reduce significantly both the risk of delivery at <37, <35 and <32 weeks’ gestation, as well as the rates of NEC, the need for supplemental oxygen and IVH. In women successfully treated with tocolytics progesterone combined with corticosteroid therapy lengthens pregnancy, reduces occurrence of respiratory distress syndrome and low birth weight. However, there is currently insufficient evidence on the role of progesterone after arrested preterm labor. It is reasonable to support an approach with CL screening of women with prior PTB starting at 16 to 19 weeks and administration of progesterone to women with a short cervix. Cerclage may be offered to those with a CL<25?mm. A combination of traditional tocolytics, corticosteroids and progesterone might be beneficial.     

Twin and Preterm Labor: Prediction and Treatment

Twin pregnancies are increasing. Preterm birth is a major health problem with high incidence all over the world. It is known to have a higher incidence in twin pregnancies as well as being higher in IVF/ICSI pregnancies. Prediction of preterm birth in twins through transvaginal cervical length measurement and vaginal fetal fibronectin measurement are good and well-documented methods. However, this could not be applied to IVF pregnancies. Prevention of preterm birth by administration of vaginal natural progesterone or IM synthetic progesterone injections is not effective in twins. The situation was similar with administration of progesterone to IVF twin pregnancies. Prophylactic cerclage for prevention of preterm birth in twins resulted in an increase of the incidence of preterm birth. Tocolytics also are ineffective, although nifedipine may have a role in treatment of threatened preterm birth in twins.     

疑似宫颈机能不全的保守治疗

超声检测宫颈长度可以辅助诊断宫颈机能不全,但是无统一标准,妊娠中期渐进性无痛性宫颈扩张或缩短为可疑宫颈机能不全, 同时伴有早产史或晚期流产史者更符合宫颈机能不全。妊娠中期宫颈长度<25 mm早产风险显著增加,为可疑宫颈机能不全。对于无早产史或晚期流产史者孕妇行环扎术无显著降低早产率的证据,但宫颈长度≤20 mm应用孕酮显著减少了不同孕周的早产率,显著改善了围产儿的结局。对于有早产史或晚期流产史伴宫颈长度<25mm者应用孕酮、环扎和宫颈托均有益处,可据患者意愿和医生的经验选择个体化处理方案。     

Clinical management of the short cervix

Cervical cerclage is associated with prolongation of gestation in singleton pregnancies with prior spontaneous preterm delivery and a short cervix on vaginal ultrasonography in the mid-trimester. Ultrasound screening of cervical length is not indicated in low-risk singleton pregnancies and in women with multiple gestations. 17α-Hydroxyprogesterone does not prevent preterm delivery in twin gestations with a short cervix. Cervical cerclage may cause detrimental effects in twin gestations. Vaginal pessary for the prevention of preterm birth in women with a short cervix is currently under active investigation.     

Long-term childhood outcomes after interventions for prevention and management of preterm birth

Globally, preterm birth rates are rising and have a significant impact on neonatal morbidity and mortality. Preterm birth remains difficult to prevent and a number of strategies for preterm birth prevention (progesterone, cervical pessaries, cervical cerclage, tocolytics, and antibiotics) have been identified. While some of these show more promise, there is a paucity of evidence regarding the long-term effects of these strategies on childhood outcomes. Strategies used to improve the health of babies if born preterm, such as antenatal magnesium sulfate for fetal neuroprotection and antenatal corticosteroids for fetal lung maturation, show evidence of short-term benefit but lack large-scale follow-up data of long-term childhood outcomes. Future research on preterm birth interventions should include long-term follow-up of the children, ideally with similar outcome measures to allow for future meta-analyses.     

Preterm premature rupture of membranes complicating twin pregnancy: management considerations

Preterm premature rupture of membranes (PPROM) is more prevalent in twin gestations and is major contributor to preterm birth. The management of PPROM in twin pregnancies does not differ significantly from that of singletons. In general, antenatal steroids, latency antibiotics, magnesium sulpfate for neuroprotection, and tocolysis are all potential interventions to consider when PPROM complicates a twin gestation. Certain circumstances, such as PPROM following an invasive procedure, at a previable gestational age, or in a monochorionic gestation, warrant special attention as the implications of PPROM and subsequent recommendations for these twin pregnancies may differ. In general, the approach to PPROM in twins should be individualized based on gestational age, and the maternal and neonatal risks of delaying delivery to prolong the pregnancy.     

Assessment of fetal growth in twins: Which method to use?

Fetal growth restriction contributes to the excess perinatal mortality and morbidity associated with twin pregnancies. Regular ultrasound monitoring for fetal growth restriction is an essential component of antenatal care of twin gestations. It is accepted that twins have divergent growth trajectories around 28–30 weeks’ gestation and are born smaller compared to singletons. Despite this well-established difference in fetal growth, twin pregnancies have been traditionally managed using growth standards developed for singleton pregnancies. Numerous recent studies have demonstrated a strong case supporting the use of twin-specific growth standards, but clinical implementation has been lacking. In this paper, we will review the evidence on factors affecting fetal growth, the rationale for twin-specific reference charts, clinical evidence for their use, and future direction of research. Applying singleton growth standards to twin pregnancies inflates the abnormal growth rate, and recent clinical evidence from several studies suggests that they are too stringent for classification of twins. The association of adverse perinatal and maternal outcomes such as perinatal death, preterm birth, neonatal care unit admission, hypertensive disorders of pregnancy, and composite neonatal morbidity is stronger when classification is made using twin-specific standards compared to singletons.     

Current Practice of Maternal–Fetal Medicine Specialists Regarding the Prevention and Management of Preterm Birth in Twin Gestations

ObjectiveTo investigate the current practices of maternal–fetal medicine (MFM) specialists regarding the prevention and management of preterm birth (PTB) in twin pregnancies.MethodsThis was a cross-sectional study of Canadian MFM specialists. Participants responded to an anonymous survey regarding the prevention and management of PTB in twins, including lifestyle and gestational weight gain recommendations, cervical length screening, PTB prevention, and labour and delivery practices.ResultsOf 137 MFM specialists surveyed, 95 (69%) responded. Most MFM specialists recommend against activity restriction (77.9%), avoidance of sexual activity (96.7%), routine progesterone (97.8%), routine prophylactic cerclage (98.9%), and routine administration of antenatal corticosteroids (95.6%). There were considerable inconsistencies with respect to gestational weight gain management. Despite lack of support by guidelines, most MFM specialists reported using routine cervical length screening (97.8%) and progesterone for short cervix (92.3%). Over half (52.7%) of MFM specialists recommend cervical cerclage when the cervix is <15mm. In cases of PTB, most MFM specialists recommend vaginal delivery when twins are in vertex presentation (63%–75%). MFM specialists are less likely to recommend vaginal delivery when twin B is non-vertex (35%–41%).ConclusionThere is a considerable variation among MFM specialists regarding the prevention and management of PTB in twins, and the practice of many MFM specialists differs from that recommended by professional societies’ guidelines. These findings underscore the necessity for high-quality studies and up-to-date recommendations.     

Quelle utilisation de la progestérone pour prévenir la prématurité ?

Widely prescribed in the years 1970–1980 to prolong gestation, progesterone has regained interest after the publication of randomized trials since 10 years. In women at increased risk of preterm birth with a history of preterm delivery or late miscarriage, the use of progesterone, especially intramuscularly may reduce the incidence of spontaneous preterm birth. In contrast, in cases of preterm labor or twin pregnancies, progesterone efficacy to reduce preterm birth has not been demonstrated. In women with asymptomatic midtrimester sonographic short cervix, randomized studies show conflicting results and new studies are necessary before its widespread utilisation.     

双胎妊娠早产的预防和治疗

双胎妊娠的早产发生率明显高于单胎,也是导致双胎妊娠新生儿死亡的主要因素之一。其确切的发病机制尚不明确。早产的预防和治疗有助于改善双胎妊娠的新生儿结局。超声测量宫颈长度和胎儿纤维连接蛋白检测对双胎早产均具有一定的预测价值。阴道用孕酮治疗、宫颈托及宫颈环扎术对于双胎早产具有一定的预防效果,但既往研究结论不一致,目前在临床中的应用仍有较大争议。     

The Principal Pregnancy Complications Resulting in Preterm Birth in Singleton and Twin Gestations

Preterm birth is the major cause of perinatal mortality for both singleton and twin gestations in the United States; most preterm birth prevention programs are primarily structured to detect and treat preterm labor. Most of these programs have had limited success, and the preterm birth rate for twins has remained well above that for singletons. Little attention has been paid to the question of whether the frequency of conditions that result in preterm twin delivery differs from those that result in the delivery of preterm singletons. Delivery records were reviewed for all 1,976 preterm (24–36 completed gestational weeks) singleton pregnancies and 221 preterm twin pregnancies delivered at the University of Connecticut Health Center, 1980–1989, to determine the primary complication that resulted in preterm delivery. Premature rupture of membranes was responsible for 46% of these singleton preterm deliveries, while the other causes were preterm labor with intact membranes (20%), pregnancy-induced hypertension (15%), antepartum hemorrhage (9%), and other maternal-fetal indications (10%). The five groups differed significantly in maternal and neonatal characteristics. The principal pregnancy complications resulting in preterm delivery of twins were preterm rupture of membranes (42%), preterm labor (31%), antepartum hemorrhage (4%), pregnancy-induced hypertension (11%), and other maternal-fetal indications (12%). Compared to preterm singletons, the preterm twins were significantly more likely to deliver because of preterm labor and less likely to deliver because of hemorrhage. Substantial reduction in the preterm birth rate requires programs tailored to the specific population and etiologies involved and should not solely address preterm labor.     

Prävention der Frühgeburt

Background

In recent years an improvement for the prevention of preterm birth has been achieved in evidence-based strategies by the use of progesterone with a proven prolongation of pregnancy and there is also an optimistic perspective for the use of vaginal pessaries; however, both interventions are only valid for singleton pregnancies. The most effective prevention of preterm birth was by reduction of multiple pregnancies in assisted reproductive techniques as well as the avoidance of elective deliveries in late preterm birth in 34 (0/7) to 36 (6/7) weeks of gestation.

Results

Prolongation of pregnancy by progesterone is achieved by the ability to modulate inflammatory mechanisms in cervical and myometrial tissue. Several studies showed a prolongation of pregnancy as well as improvement of perinatal outcome both in pregnancies after previous preterm births as well as in pregnancies with shortened cervix as assessed by sonography.

Discussion

The results on the indications for using cerclage for prevention of preterm birth are controversial. It is unclear where a cut-off for cervical length should be fixed for performing a cerclage to achieve a benefit. There are currently no relevant studies comparing the two methods of progesterone administration and cervical cerclage and no investigations on the combination of both methods. There is increasing discussion on whether routine sonographic assessment of cervical length should be carried out in all pregnancies including those women without previous preterm births.

Conclusion

Promising results have been obtained in a study assessing prolongation of pregnancy by prophylactic screening and treating vaginal infections; however, a meta-analysis failed to show any improvement in pregnancy duration. For more than half a century vaginal pessaries have been used to treat cervical incompetence. A recently conducted well-designed study using the Arabin pessary showed promising results both in prolonging pregnancy and improving perinatal outcome. The results of upcoming studies should be awaited before guideline recommendations for pessary use can be given.     

Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data

OBJECTIVE: Preterm birth is the main cause of perinatal morbidity and mortality. A short cervical length on transvaginal ultrasonography predicts preterm birth. Our aim was to estimate by meta-analysis of randomized trials whether cerclage prevents preterm birth in women with a short cervical length. DATA SOURCES: MEDLINE, PubMed, EMBASE, and the Cochrane Library were searched with the terms "cerclage," "cervical cerclage," "short cervix," "ultrasound," and "randomized trial." We included randomized trials involving the use of cerclage in women with short cervical length on transvaginal ultrasonography using patient-level data. TABULATION, INTEGRATION, AND RESULTS: Four properly conducted trials were identified. In the total population, preterm birth at less than 35 weeks of gestation occurred in 29.2% (89/305) of the cerclage group, compared with 34.8% (105/302) of the no-cerclage groups (relative risk [RR] 0.84, 95% confidence interval [CI] 0.67-1.06). There was no significant heterogeneity in the overall analysis (P = .29). There was a significant reduction in preterm birth at less than 35 weeks in the cerclage group compared with the no-cerclage groups in singleton gestations (RR 0.74, 95% CI 0.57-0.96), singleton gestations with prior preterm birth (RR 0.61, 95% CI 0.40-0.92), and singleton gestations with prior second-trimester loss (RR 0.57, 95% CI 0.33-0.99). There was a significant increase in preterm birth at less than 35 weeks in twin gestations (RR 2.15, 95% CI 1.15-4.01). CONCLUSION: Cerclage does not prevent preterm birth in all women with short cervical length on transvaginal ultrasonography. In the subgroup analysis of singleton gestations with short cervical length, especially those with a prior preterm birth, cerclage may reduce preterm birth, and a well-powered trial should be carried out in this group of patients. In contrast, in twins, cerclage was associated with a significantly higher incidence of preterm birth.     

The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies

The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection (ICSI) pregnancies. A single-centre prospective placebo-controlled randomized study was performed. A total of 313 IVF/ICSI pregnant patients were randomized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo, starting from mid-trimester up to 37 weeks or delivery. Amongst the patients, there were 215 singleton and 91 twin pregnancies. There was no significant difference in risk of preterm birth among all patients (OR 0.672, 95% CI 0.42–1.0. There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm (OR 0.53, 95% CI 0.28–0.97) and no significant difference between both arms in twin pregnancies (OR 0.735, 95% CI 0.36–2). In conclusion, the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton, but not in twin, IVF/ICSI pregnancies.Preterm labour is a major cause of perinatal and neonatal mortality and morbidity. It is defined as birth occurring prior to 37 weeks’ gestation; however, most damage occurs in infants born before 34 weeks. It was reported that pregnancies achieved by IVF or intracytoplasmic sperm injection (ICSI) are more liable to preterm labour. The objective of this study was to evaluate the effect of progesterone (given to the patient vaginally) on the prevention of preterm labour in IVF/ICSI pregnancies. Patients who became pregnant after IVF or ICSI were randomized into two groups. The first group was given 400 mg of vaginal progesterone starting from mid trimester until 37 weeks of pregnancy, and the second group received no treatment. The results showed that administration of 400 mg vaginal progesterone from mid trimester reduces the incidence of preterm labour in singleton, but not in twin, IVF/ICSI pregnancies.     

Preterm birth prevention

Preterm birth (PTB), which occurs in about 12% of pregnancies worldwide, is the main cause of neonatal morbidity and mortality. Symptomatic treatment of pregnancies presenting in preterm labor with corticosteroids and antibiotics has improved neonatal outcomes but has not reduced the incidence of PTB. Evidence suggests that the rate of PTB may be reduced by the prophylactic use of progesterone in women with a previous history of preterm delivery and in those with a short cervical length identified by routine transvaginal ultrasound. This review summarizes the evidence (level A evidence) of the effectiveness of progesterone on the rate of PTB.     

The impact of cerclage in twin pregnancies on preterm birth rate before 32 weeks

Purpose: To evaluate whether cerclage in twins reduces the rate of spontaneous preterm birth <32 weeks when compared to expectant management.

Methods: This is a retrospective cohort study of twin pregnancies with the following indications for cerclage from two institutions: history of prior preterm birth, ultrasound-identified short cervix ≤2.5?cm, and cervical dilation ≥1.0?cm. The “cerclage” cohort received a cerclage from a single provider at a single institution from 2003–2016. The “no cerclage” group included all patients with similar indications that were expectantly managed from 2010–2015, at a second institution where cerclages are routinely not performed in twin pregnancies. The primary outcome was the rate of spontaneous preterm birth at <32 weeks. Secondary outcomes were the rates of spontaneous and overall (including medically indicated) preterm births at <32 weeks, Results: In all, 135 women were included in two cohorts: cerclage (n?=?96) or no cerclage (n?=?39). The rates of spontaneous preterm birth <32 weeks were 10.4% (n?=?10) with cerclage versus 28.2% (n?=?11) without cerclage (OR 0.23, CI 0.08–0.70, p?=?.017). After adjusting for cerclage indication, clinical history, age, chorionicity, insurance type, race, BMI, in-vitro fertilization, and multifetal reduction, there remained a significant reduction in the cerclage group of spontaneous preterm birth <32 weeks (adjusted odds ratio (aOR) 0.24, CI 0.06–0.90, p?=?.035), spontaneous preterm birth <36 weeks (aOR 0.34, CI 0.04–0.81, p?=?.013) as well as in overall preterm birth <32 weeks (aOR 0.31, CI 0.1–0.86, p?=?.018), and overall preterm birth <36 weeks (aOR 0.37, CI 0.10–0.84, p?=?.030). When stratified by short cervix or cervical dilation in the cerclage versus no cerclage groups, there was a significant decrease in spontaneous preterm birth <32 weeks in the cerclage group with cervical dilation (11.1 versus 41.2%, p?=?.01) but not in the cerclage group with short cervix only, even for cervical length <1.5?cm. Pregnancy latency was 91 days in the cerclage group versus 57 days in the no cerclage group (p?=?.001), with a median gestational age at delivery of 35 versus 32 weeks (p?=?.002). There was no increase in chorioamnionitis in the cerclage group. Furthermore, there was a significant increase in birth weight (median 2278 versus 1665?g, p?p?=?.001).

Conclusions: Cerclage in twin pregnancies significantly decreased the rate of spontaneous preterm birth <32 weeks compared to expectant management. However, when stratified by cerclage indication, this decrease in primary outcome only remained significant in the group with cervical dilation.     

Nuchal translucency in pregnancies conceived after assisted reproduction technology

PURPOSE OF REVIEW: Nuchal translucency is one of the important markers in the first trimester during antenatal screening for fetal Down's syndrome. With the observation of alterations in biochemical markers in pregnancies conceived after assisted reproduction, this review presents current information related to the thickness of nuchal translucency in these pregnancies. RECENT FINDINGS: Early small studies did not demonstrate any discrepancy in the thickness of nuchal translucency in fetuses from assisted reproduction and from spontaneous pregnancies, but there has been recent evidence to suggest an increased level of nuchal translucency in singletons from various modes of assisted-reproduction technology. Nuchal translucency in twins following assisted reproduction did not, however, show a similar increase. Although the effect of chorionicity was not specifically addressed, nuchal translucency thickness in twins born after assisted reproduction was reported to be comparable to that in spontaneous singletons. It is possible that singletons and twins after assisted reproduction exhibit different antenatal behavior and pregnancy courses. SUMMARY: Similar to other biochemical markers of fetal Down's syndrome, nuchal translucency is increased in singletons after assisted-reproduction technology. Further studies on twin pregnancies, in particular dichorionic twins, are necessary before conclusive evidence can be drawn for multiple pregnancies.     

Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial

OBJECTIVE: The purpose of this study was to determine the efficacy of cerclage and bed rest versus bed rest-only for the prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination. STUDY DESIGN: Women with > or =1 of high-risk factors for preterm birth (> or =1 preterm birth at < 35 weeks of gestation, > or =2 curettages, diethylstilbestrol exposure, cone biopsy, Mullerian anomaly, or twin gestation) were screened with transvaginal ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23 weeks 6 days of gestation. Enrollment was offered to both asymptomatic women who were at high risk and who were identified to have short cervix (< 25 mm) or significant funneling (>25%) and nonscreened women who were at low risk and who were identified incidentally. The women who gave written consent were assigned randomly to receive either McDonald cerclage or bed rest-only. Both groups received similar counseling and treatment. Primary outcome was preterm birth at < 35 weeks of gestation. RESULTS: Sixty-one women were assigned randomly. Forty-seven pregnancies (77%) were high-risk singleton gestations. Thirty-one women (51%) were allocated to cerclage, and 30 women (49%) were allocated to bed rest. There were no differences between the groups in demographic characteristics, risk factors, and cervical variables. Preterm birth at < 35 weeks of gestation occurred in 14 women (45%) in the cerclage group and in 14 women (47%) in the bed rest group (relative risk, 0.94; 95% CI, 0.34-2.58). There was no difference in any obstetric or neonatal outcomes. A subanalysis of singleton pregnancies with previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm (n = 31 women) also revealed no significant difference in recurrent preterm birth at < 35 weeks of gestation (40% vs 56%; relative risk, 0.52; 95% CI, 0.12-2.17). CONCLUSION: Cerclage did not prevent preterm birth in women with a short cervix. These results should be confirmed by larger trials.     

Guideline No. 398: Progesterone for Prevention of Spontaneous Preterm Birth

ObjectivesTo assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth (SPB) and to make recommendations for the use of progesterone to reduce the risk of SPB and improve postnatal outcomes.OptionsTo administer or withhold progesterone therapy for women deemed to be at high risk of SPB.OutcomesPreterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes.Intended UsersMaternity care providers, including midwives, family physicians, and obstetricians.Target PopulationPregnant women at increased risk of SPB.EvidenceMedline, PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2018 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, short cervix, uterine anomalies, cervical conization, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review.Validation MethodsThis guideline was reviewed by the Maternal–Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors.Benefits, Harms, and/or CostsTherapy with progesterone significantly reduces the risk of SPB in a subpopulation of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other adverse effects to the mother or the baby have been identified.SUMMARY STATEMENTS (GRADE ratings in parentheses)

• 1Progesterone therapy reduces the risk of spontaneous preterm birth in women at an increased risk based on history of previous spontaneous preterm birth or in women with a short cervical length (moderate).
• 2There is insufficient evidence to support the use of progesterone for prevention of spontaneous preterm birth in women with a pregnancy in the absence of cervical shortening (moderate).
• 3There is insufficient evidence to support the use of progesterone for prevention of spontaneous preterm birth in women with a normal cervical length and a prior conization procedure on the cervix or abnormal uterine anatomy (low).
• 4Use of progesterone in women with arrested preterm labour is not associated with a reduced risk of spontaneous preterm birth or with improved postnatal outcomes (moderate).
• 5Use of vaginal progesterone for prevention of spontaneous preterm birth has not been associated with an increase in congenital malformations or with a worsening of postnatal neurodevelopmental outcomes (moderate).

RECOMMENDATIONS (GRADE ratings in parentheses)

• 1In women with a singleton pregnancy and a short cervical length (≤25 mm by transvaginal ultrasound between 16 and 24 weeks), vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate).
• 2In women with a previous spontaneous preterm birth, vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate).
• 3In women with a twin pregnancy (and by extrapolation of data, with a higher-order multiple pregnancy) and with a short cervical length (≤25 mm by transvaginal ultrasound between 16 and 24 weeks), vaginal progesterone therapy for prevention of spontaneous preterm birth is recommended (strong/moderate).
• 4In patients with a singleton pregnancy and a previous spontaneous preterm birth or a cervical length ≤25 mm between 16 and 24 weeks in the current pregnancy, if a cerclage is being considered, vaginal progesterone should be offered as an effective and potentially superior alternate therapy (strong/moderate).
• 5In patients using progesterone for prevention of spontaneous preterm birth, additional therapies such as a cervical cerclage (with exception of a rescue cerclage for an examination-based diagnosis) or a pessary are not recommended (strong/moderate).
• 6In patients at increased risk of spontaneous preterm birth due to a previous preterm birth, a short cervical length in the current pregnancy, or a multiple pregnancy, bed rest or reduced activity is not recommended (strong/moderate).
• 7When indicated for prevention of spontaneous preterm birth in a singleton pregnancy, vaginal micronized progesterone in a daily dose of 200 mg is recommended (strong/moderate).
• 8When indicated for prevention of spontaneous preterm birth in a multiple pregnancy, vaginal micronized progesterone in a daily dose of 400 mg is recommended (conditional [weak]/low).
• 9When indicated, vaginal progesterone therapy should be initiated between 16 and 24 weeks gestation, depending on when the risked factor is identified (strong/moderate).
• 10With consideration of individual patient risk factors, vaginal progesterone therapy can be continued up to 34–36 weeks gestation (strong/moderate).

     

Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies

Objective: To describe perinatal outcomes of twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP).

Methods: We conducted a retrospective cohort study of women delivered at a large tertiary obstetric center in Shanghai, China from January 2006 to May 2014. Delivery data were abstracted from medical records of all twin gestations delivered at the hospital.

Results: A total of 129/1922(6.7%) twin and 1190/92?273 singleton (1.3%) pregnancies were complicated by ICP. An increased risk of stillbirth among twin pregnancies was observed (3.9% and 0.8% in the ICP and non-ICP groups, respectively; aOR 5.75, 95% CI 2.00–16.6). Stillbirths with ICP and twins occurred between 33 and 35 weeks gestation compared to 36–38 weeks gestation among singletons. ICP in twins was also associated with an increased risk of preterm birth (<37 weeks) with an aOR of 4.17 (95% CI 2.47–7.04) and an aOR of 1.89 (95% CI 1.26–2.85) for delivery <35 weeks. Twin pregnancies complicated by ICP also had increased meconium staining of amniotic fluid and lower birth weight.

Conclusions: Twin pregnancies with ICP have significantly increased risks of adverse perinatal outcomes including stillbirth and preterm birth. Stillbirth occurs at an earlier gestational age in twin gestation compared to singletons, suggesting that earlier scheduled delivery should be considered in these women.