The effect of gestational age and cervical length measurements in the prediction of spontaneous preterm birth in twin pregnancies: an individual patient level meta-analysis.

OBJECTIVE: To assess the effect of gestational age (GA) and cervical length (CL) measurements at transvaginal ultrasound (TVUS) in the prediction of preterm birth in twin pregnancy. DESIGN: Individual patient data (IPD) meta-analysis. SETTING: International multicentre study. POPULATION: Asymptomatic twin pregnancy. METHODS: MEDLINE and EMBASE searches were performed and IPD obtained from authors of relevant studies. Multinomial logistic regression analysis determined probabilities for birth at ≤28(+0) , 28(+1) to 32(+0) , 32(+1) to 36(+0) , and ≥36(+1) weeks as a function of GA at screening and CL measurements. MAIN OUTCOME MEASURES: Predicted probabilities for preterm birth at ≤28(+0) , 28(+1) to 32(+0) , and 32(+1) to 36(+0) . RESULTS: A total of 6188 CL measurements were performed on 4409 twin pregnancies in 12 studies. Both GA at screening and CL had a significant and non-linear effect on GA at birth. The best prediction of birth at ≤28(+0) weeks was provided by screening at ≤18(+0) weeks (P < 0.001), whereas the best prediction of birth between 28(+1) and 36(+0) weeks was provided by screening at ≥24(+0) weeks (P < 0.001). Negative prediction value of 100% for birth at ≤28(+0) weeks is achieved at CL 65 mm and 43 mm at ultrasound GA at ≤18(+0) weeks and at 22(+1) to 24(+0) weeks, respectively. CONCLUSION: In twin pregnancies, prediction of preterm birth depends on both CL and the GA at screening. When CL is <30 mm, screening at ≤18(+0) weeks is most predictive for birth at ≤28(+0) weeks. Later screening at >22(+0) weeks is most predictive of delivery at 28(+1) to 36(+0) weeks. In twins, we recommend CL screening in twins to commence from ≤18(+0) weeks. TWEETABLE ABSTRACT: An individual patient meta-analysis assessing gestation and CL in the prediction of preterm birth in twins.

Ovulation induction and small for gestational age neonates in twin pregnancies.

OBJECTIVE: To compare the incidence of small for gestation age (SGA) neonates in twin gestations conceived by ovulation induction or in vitro fertilization with that of twins conceived spontaneously. STUDY DESIGN: A retrospective cohort study was conducted. Subjects were delivered by a single obstetric practice between 2005 and 2011 at the Mount Sinai Medical Center. Maternal and neonatal data were recorded. Our primary outcome was the incidence of SGA, defined as birth weight <10th percentile, from the three modes of conception. Chi square, ANOVA, Fisher's exact test, the Kruskal-Wallis test, the Mantel-Haenszel test, and logistic regression were used in the analysis. RESULTS: In unadjusted analysis, using the records of 756 infants from 378 mothers of twin pregnancies, twins conceived by ovulation induction had an increased incidence of SGA (28.1%) compared to those conceived spontaneously (17.1%) and by in vitro fertilization (16.5%, p = 0.006). In a logistic regression model accounting for correlated responses between twins and adjusting for gestational age, gender, chorionicity, and maternal age, the odds ratio (95% confidence interval [CI]) of SGA for the ovulation induction group compared to the spontaneous conception group was 2.64 (1.38-5.05, p = 0.003). The odds ratio (95% CI) of SGA for the in vitro fertilization group compared to the spontaneous conception group was 1.51 (0.88-2.61, p = 0.135). CONCLUSIONS: When adjusted for gestational age, gender, chorionicity, and maternal age, twin neonates conceived by ovulation induction, but not those conceived by in vitro fertilization, had increased odds of SGA compared to those conceived spontaneously.

Rescue corticosteroids in twin pregnancies and short-term neonatal outcomes.

OBJECTIVE: To estimate the efficacy of a rescue course of antenatal corticosteroids in twin pregnancies. DESIGN: Retrospective cohort study. SETTING: Tertiary-care centre. POPULATION: Twins born from 24 to <34 weeks of gestation in a single maternal and fetal medicine practice from 2006 to 2011. METHODS: We compared neonatal outcomes in 88 twins exposed to a single course of corticosteroids with outcomes in 42 twins exposed to two courses of corticosteroids: the initial course and a single rescue course. Analyses were adjusted to control for correlation between twins born to the same mother. MAIN OUTCOME MEASURE: Short-term neonatal respiratory morbidity. RESULTS: Rescue corticosteroids were associated with fewer days of mechanical ventilation (7.3 ± 3.3 versus 33.9 ± 25.3 days, P = 0.003), fewer days with a fraction of inspired oxygen of >21% (6.3 ± 4.3 versus 33.3 ± 25.8 days, P = 0.003), a lower incidence of mechanical ventilation >14 days or death while on mechanical ventilation (0 versus 12.5%, P = 0.016), and a lower incidence of retinopathy of prematurity (0 versus 12.5%, P = 0.016). The proportion of neonates with respiratory distress syndrome did not differ between the groups (adjusted odds ratio 1.28, 95% confidence interval 0.50-3.26). There were no differences found for birthweight, head circumference and length. CONCLUSIONS: In twins born before 34 weeks of gestation, exposure to rescue corticosteroids may be associated with improved neonatal outcomes. Further studies are warranted to assess the effect of rescue corticosteroids in twin pregnancies.

Cervical length at 30-32 weeks and the risk of Cesarean delivery in twin pregnancies.

OBJECTIVES: To estimate the association between the cervical length (CL) measurement at 30-32 weeks and the mode of delivery in twin pregnancies. METHODS: This was a retrospective study of a cohort, from 2005-2010, of 265 twin pregnancies with a CL measurement at 30-32 weeks. We compared the CL measurement at 30-32 weeks based on mode of delivery. We then analyzed our data across four subgroups, based on the CL measurement quartiles at 30-32 weeks. We performed this analysis in all patients, and also performed a planned subgroup analysis of 130 patients who attempted a vaginal delivery. RESULTS: In all patients, including those who attempted a vaginal delivery, the mean CL at 30-32 weeks was significantly shorter in women who delivered vaginally compared with women who had a Cesarean section. The likelihood of Cesarean delivery increased significantly with increasing CL measurement across the groups defined by measurement quartiles. On adjusted analysis controlling for maternal age, race, in-vitro fertilization, chorionicity, induction of labor and prior vaginal delivery, the CL measurement at 30-32 weeks was independently associated with mode of delivery. CONCLUSIONS: In twin pregnancies, the CL at 30-32 weeks is significantly associated with the likelihood of Cesarean delivery. A longer CL may represent underdevelopment of the uterus, leading to a higher risk of Cesarean delivery in labor at term.

Intravaginal misoprostol versus Foley catheter for labour induction: a meta-analysis.

BACKGROUND: There are a number of agents used for cervical ripening prior to the induction of labour. Two commonly used agents are intravaginal misoprostol and a transcervical Foley catheter. OBJECTIVE: To review the evidence comparing misoprostol and transcervical Foley catheter placement for induction of labour, and perform a meta-analysis comparing these two induction agents. SEARCH STRATEGY: We conducted database searches of PubMed, Embase, the Cochrane Library Database, and the ClinicalTrials.gov website. Bibliographies of all relevant articles were reviewed. SELECTION CRITERIA: Prospective, randomised trials comparing the use of intravaginal misoprostol and transcervical Foley catheter for the purpose of cervical ripening and induction of labour were included. We excluded studies in which the patients in these two intervention groups also received other induction agents concurrently, such as oral misoprostol, oxytocin, or other prostaglandins. DATA COLLECTION AND ANALYSIS: The primary outcomes selected were time to delivery, and the rates of caesarean section, uterine tachysystole, and chorioamnionitis. Random-effects generalised linear models with a poisson distribution and log link function were used to compare the two induction agents across the studies. MAIN RESULTS: Nine studies (1603 patients) were identified as eligible to be included in this meta-analysis. There were no significant differences in the mean time to delivery (mean difference 1.08 ± 2.19 hours shorter for misoprostol, P = 0.2348), the rate of caesarean delivery (RR 0.991; 95% CI 0.768, 1.278), or in the rate of chorioamnionitis (RR 1.130; 95% CI 0.611, 2.089) between women who received misoprostol compared with transcervical Foley catheter. Patients who received misoprostol had significantly higher rates of tachysystole compared with women who received a transcervical Foley catheter (RR 2.844; 95% CI 1.392, 5.812). CONCLUSIONS: Intravaginal misoprostol and transcervical Foley catheter have similar effectiveness as induction agents. Transcervical Foley catheter is associated with a lower incidence of tachysystole.

Second-trimester fetal growth as a predictor of poor obstetric and neonatal outcome in patients with low first-trimester serum pregnancy-associated plasma protein-A and a euploid fetus.

OBJECTIVE: To examine if fetal growth during the second trimester predicts poor pregnancy and neonatal outcome in patients with low first-trimester serum pregnancy-associated plasma protein-A (PAPP-A) and a euploid fetus. METHODS: We identified all patients with first-trimester PAPP-A<5th centile who had undergone first- and second-trimester ultrasound examination. We excluded multiple pregnancies and those with aneuploidy or major anomalies identified before or after birth. We compared pregnancies with and without ultrasound markers for fetal growth restriction at 18-24 weeks. RESULTS: We identified 239 patients with low PAPP-A, 25 (10.5%) of whom had evidence of fetal growth restriction at 18-24 weeks. These 25 cases had significantly higher rates of third-trimester small-for-gestational age (SGA) fetus, gestational hypertension, preterm birth, indicated preterm birth, low birth weight and birth weight centiles, 1-min Apgar score<7, neonatal intensive care unit admission and fetal or neonatal death. CONCLUSION: Among patients with low first-trimester PAPP-A and a euploid fetus, fetal growth in the second trimester can predict poor obstetric and neonatal outcome.

Second-trimester fetal growth and the risk of poor obstetric and neonatal outcomes.

OBJECTIVE: To compare outcomes of fetuses with an estimated fetal weight (EFW) < 25(th) percentile in the second trimester to those in fetuses with EFW >or= 25(th) percentile in the second trimester. METHODS: We compared outcomes of 252 pregnancies with an EFW < 25(th) percentile at 18-24 weeks' gestation with those of 265 controls. All pregnancies had early dating by ultrasonography. We excluded fetuses with aneuploidy, major malformations, second-trimester rupture of membranes, and multiple pregnancies. RESULTS: Second-trimester EFW < 25(th) percentile was significantly associated with higher rates of fetal or neonatal death, third-trimester small for gestational age (SGA), Doppler abnormalities, indicated preterm birth, gestational hypertension or pre-eclampsia before labor, lower birth weight, birth weight < 10(th) percentile, birth weight < 5(th) percentile, and admission to the neonatal intensive care unit. Many of these associations remained even after excluding patients with oligohydramnios, fetal echogenic bowel, and growth asymmetry. CONCLUSION: Second-trimester SGA, as defined by an EFW < 25(th) percentile using current growth curves, is associated with poor obstetric and neonatal outcomes. Increased surveillance of such pregnancies may be necessary.

Short cervix: is a follow-up measurement useful?

OBJECTIVE: To study if a repeat cervical length (CL) measurement in the patient already diagnosed with a short cervix has any additional value in the prediction of preterm delivery. STUDY DESIGN: This was a retrospective study of singleton pregnancies with cervical lengths 1-25 mm at a gestational age of 16-28 weeks seen in our institution between 2002 and 2005. Patients who were managed expectantly and had a follow-up CL measurement within 3 weeks were included. Delivery data were obtained from the patients' computerized medical records. RESULTS: Sixty-eight patients met the inclusion criteria. 37% of the patients had a shorter CL on the second measurement. These patients delivered at an earlier gestational age (36+4 vs. 38+2 weeks, P=0.031) and were more likely to deliver at <37 weeks (60% vs. 26%, P=0.009). The change in the CL correlated with earlier gestational age at delivery and delivery at <37 weeks. CONCLUSION: In patients diagnosed with a short cervix, follow-up CL measurement is a strong predictor of preterm delivery. Greater change in the CL correlates with an earlier gestational age at delivery. In the patient diagnosed with a short cervix, a repeat measurement of CL gives additional predictive value.

The cellular repressor of E1A-stimulated genes mediates glucocorticoid-induced loss of the type-2 IGF receptor in ileal epithelial cells.

Glucocorticoids induce hypertrophy of the neonatal ileal mucosa but the molecular mechanisms behind this growth induction remain poorly understood. Ileal epithelial cells (IECs) are dependent upon IGF-II for proliferation both in vivo and in culture. The type-2 IGF receptor (IGFR-2) is a lysosomal transport protein that attenuates IGF-II-driven growth and is highly abundant in the ileum. The cellular repressor of E1A-stimulated genes (CREG) is a secreted phosphoglycoprotein that affects cell fate via ligand binding with IGFR-2, although the mechanism by which it does so is unknown. We hypothesized that glucocorticoids might facilitate IGF-mediated hypertrophy through CREG-mediated degradation of IGFR-2. To test this hypothesis, confluent rat IECs (IEC-18) were cultured for 72 h with or without dexamethasone (DEX) and harvested for Western blot, immunocytochemistry, gene array and CREG immunoneutralization experiments. IGFR-2 and CREG immunohistochemistry were also performed in archived ileal specimens from control and DEX-exposed newborn mice and extremely premature infants to investigate in vivo and clinical relevance. DEX exposure was found to diminish IGFR-2 immunolocalization in cultured rat IECs, newborn mouse ileal mucosa and human neonatal ileal mucosa. Gene array data indicated that IGFR-2 expression was unchanged with DEX treatment, suggesting a mechanism of protein degradation. CREG immunolocalization and abundance was found to be increased by DEX and immunoneutralization of CREG resulted in the abolition of IGFR-2 degradation. We have concluded that CREG is a secreted mediator by which DEX induces degradation of IGFR-2 and speculate that this is a fundamental mechanism of mucosal growth induction.