Screening and Prevention of Preterm Birth in Twin Pregnancies.

Twins represent 3.2% of all live births. However, they account for 20% of all preterm deliveries, 60% delivering <37 weeks, 10.7% <32 weeks, and 5 times higher risk of infant death. Risk factors for preterm birth (PTB) include the history of preterm delivery, monochorionic twins, short cervical length, and cervical surgery. Transvaginal cervical length <24 weeks is the best tool to predict PTB. Only vaginal progesterone in women with transvaginal cervical length <25 mm and physical exam indicated cerclage in women with cervical dilation >1 cm have shown a significant decrease in PTB and improvement in neonatal outcomes.

Screening for preterm birth in twin pregnancies.

Twins represent 3.2% of all live births. However, they account for 20% of all preterm deliveries, with 60% delivered before 37 weeks and 10.7% before 32 weeks of gestation. Twin pregnancies have a 5 times higher risk of early neonatal and infant death related to prematurity. Monochorionic twins have a higher incidence of both indicated and spontaneous preterm delivery than dichorionic twins. Additional risk factors include a history of preterm delivery and cervical surgery. The transvaginal cervical length before 24 weeks is the best factor to predict preterm birth, independent of other risk factors.

Utility of follow-up cervical length screening in low-risk women with a cervical length of 26 to 29 mm.

BACKGROUND: In women with a previous preterm birth, a protocol for serial cervical length screening has been studied and recommended for the identification and treatment of a short cervix. Cervical length screening along with vaginal progesterone has been suggested for low-risk women with singleton pregnancies to treat a short cervix and reduce preterm birth. However, specific protocols for single vs serial ultrasound measuring cervical length in this population are not established. Cost-effectiveness of universal cervical length screening depends on the cost of screening; follow-up of borderline measurements can contribute to increased costs with uncertain benefit. OBJECTIVE: This study aimed to determine the utility of follow-up cervical length screening in otherwise low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm through the assessment of the rate of short cervix (≤25 mm) on follow-up ultrasound and subsequent delivery outcomes. STUDY DESIGN: This was a 2-year retrospective cohort study at a single urban institution of women with singleton pregnancies with no previous spontaneous preterm birth and an initial transvaginal ultrasound cervical length measurement of 26 to 29 mm identified during universal cervical length screening at time of anatomy ultrasound (18 0/7 to 22 6/7 weeks' gestation). The primary outcome was the rate of short cervix (defined as ≤25 mm on transvaginal ultrasound) on follow-up ultrasound at <24 weeks' gestation. Secondary outcomes included the rate of spontaneous preterm birth (<37 and <34 weeks' gestation). RESULTS: During the study period, there were 2801 women with singleton pregnancies at 18 0/7 to 22 6/7 weeks' gestation with transvaginal ultrasound cervical length screening at time of anatomy scan. Among those women, 201 had a cervical length of 26 of 29 mm, and 184 (7%) had no previous spontaneous preterm birth and were included in the study. Furthermore, 144 women (78%) had a follow-up cervical length completed before 24 weeks' gestation. The mean follow-up interval was 1.5±0.6 weeks. Overall, the percentage of short cervix (≤25 mm) on follow-up was 15% (n=21). Baseline characteristics were similar, but the initial cervical length measurement was shorter in women who subsequently developed a short cervix (26.7±0.8 vs 27.8±1.0; P<.01). Delivery outcomes were available for 126 patients. The rate of spontaneous preterm birth at <37 weeks' gestation in women with an initial cervical length 26 to 29 mm and subsequent short cervix was significantly higher than the rate of spontaneous preterm birth in a historical cohort of low risk women with an initial cervical length >25 mm (16% vs 3%; P=.03). The rate of spontaneous preterm birth at <34 weeks' gestation in women with a subsequent short cervix was 11% (2 of 19). CONCLUSION: Here, approximately 15% of low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm will experience cervical shortening of ≤25 mm before 24 weeks' gestation. Compared to women with singleton pregnancies without a history of preterm birth, the rate of spontaneous preterm birth (16%) in women with an initial cervical length of 26 to 29 mm and a subsequent cervical shortening of ≤25 mm is significantly higher. A total of 111 follow-up ultrasounds measuring cervical length would be required to prevent 1 early preterm birth at <34 weeks' gestation.

The compliance with a patient-safety bundle for management of placenta accreta spectrum†.

OBJECTIVE: Our objective was to evaluate the compliance with a patient-safety bundle for placenta accreta spectrum (PAS) by comparing the implementation of the components of the patient-safety bundle in the pre- and post-protocol time periods as a quality improvement project. STUDY DESIGN: This is a before and after retrospective cohort study as a quality improvement report examining compliance with a multidisciplinary delivery approach for patients with suspected PAS between 2007 and 2018. This bundle involved a multidisciplinary approach with maternal-fetal medicine, gynecologic oncology, intervention radiology, obstetric anesthesia, neonatology, and blood bank. The primary outcome was incorporation of all six of the components of the bundle into a PAS procedure: (1) betamethasone, (2) gynecologic oncology intraoperative consult, (3) preoperative balloon catheters, (4) cell salvage technology in the operating room, (5) vertical skin incision, and (6) fundal or high transverse hysterotomy. Demographic, delivery, and patient outcome data were also collected. RESULTS: There were 39 patients included in the study, 17 were pre-protocol and 22 were post-protocol. Patients were more likely to have a PAS suspected in the antenatal period during post protocol period (23.5 versus 90.9%, p < .0001), as well as having a placenta previa (35.3 versus 81.8%, p = .003), and receive betamethasone prior to delivery (23.5 versus 86.3%, p < .0001). Patients were delivered at an earlier gestational age in post protocol period (36.8 ± 2.52 versus 33.87 ± 2.4, p = .001). The primary outcome, adherence to all components of the patient-safety bundle, was more likely to occur in the post protocol period (0 versus 40.9%, p < .0001). Maternal and postoperative outcomes were not significantly different between groups. CONCLUSIONS: We have successfully implemented a patient-safety bundle for PAS and have standardized the execution of multidisciplinary management for PAS at our institution.

Predictors of Early Preterm Birth Despite Vaginal Progesterone Therapy in Singletons with Short Cervix.

OBJECTIVE: This study aimed to identify the incidence of and risk factors for early preterm birth (PTB) (delivery <34 weeks) in women without prior PTB and current short cervix (≤20 mm) prescribed vaginal progesterone. STUDY DESIGN: Retrospective cohort study of singletons without prior PTB diagnosed with short cervix (≤20 mm) between 180/7 and 236/7 weeks. Women who accepted vaginal progesterone and had delivery outcomes available were included. Demographic/obstetric history, cervical length, and pregnancy characteristics compared between women with early PTB versus delivery ≥34 weeks. Multiple logistic regression analysis used to identify predictors; odds ratio for significant factors used to generate a risk score. Risk score and risk of early PTB assessed with receiver operating characteristic curve (ROCC). Perinatal outcomes compared by risk score. RESULTS: Among 109 patients included, 29 (27%) had a spontaneous PTB <34 weeks. In univariate analysis, only gestational age at ultrasound, presence funneling, and mean cervical length were significantly different between those with and without early sPTB. With multiple logistic regression analysis, only gestational age at diagnosis (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p = 0.028) and index cervical length (OR: 0.84; 95% CI: 0.76-0.93; p = 0.001) remained significantly associated with early PTB. ROCC for the risk score incorporating cervical length and gestational age was predictive of early PTB with an AUC of 0.76 (95% CI: 0.67-0.86; p < 0.001). A high-risk score was predictive of early PTB with a sensitivity of 79%, specificity of 75%, positive predictive value of 54%, and negative predictive value of 91%. Women with a high-risk score had worse perinatal outcomes compared with those with low-risk score. CONCLUSION: A total of 27% of patients with short cervix prescribed vaginal progesterone will have a sPTB < 34 weeks. Patients at high risk for early PTB despite vaginal progesterone therapy may be identified using gestational age and cervical length at diagnosis of short cervix. Given the narrow window for intervention after diagnosis of short cervix, this has important implications for clinical care.

Genetic abnormalities seen on CVS in early pregnancy failure.

Objective: To determine the frequency and distribution of chromosome abnormalities in women with early pregnancy failure (EPF) detected by cytogenetic testing on chorionic villus sampling.Method: Retrospective observational cohort study of chromosomal analysis from transvaginal chorionic villus sampling (CVS) or reflex products of conception (POC) karyotype. CVS was offered as a training tool for Maternal Fetal Medicine fellows prior to manual vacuum aspiration for EPF 9-week gestation. POC were analyzed for cytogenetics if no results were obtained on CVS.Results: One hundred thirty samples were collected from December 2011 to April 2015. 33 (27.3%) cases had a normal karyotype and 88 (73.0%) cases had an abnormal karyotype. The most common group of abnormalities were trisomy, (n = 50, 41.3%), triploidy/tetraploidy, (n = 17, 14.0%), monosomy (n = 15, 12.4%), and structural rearrangements (n = 6, 5.0%). Nine (6.9%) samples were maternal decidua only. Abnormal karyotype in EPF was significantly increased in women by age group (p < .01) but not in women with a history of prior miscarriage (p = .5).Conclusion: Our cohort had a high detection rate of aneuploidy. The most common chromosomal abnormalities in EPF were: trisomy, followed by triploidy/tetraploidy, monosomy, and structural rearrangements. Maternal age had the strongest correlation with EPF associated with aneuploidy.

How many procedures does it take? Success of a CVS training program for Maternal Fetal Medicine fellows.

OBJECTIVES: To quantify the learning curve for a training program for Maternal Fetal Medicine (MFM) fellows in obtaining successful transvaginal chorionic villus sampling (CVS) results in women with early pregnancy failure (EPF). METHODS: Retrospective observational cohort study of transvaginal CVS and subsequent manual vacuum aspiration (MVA) performed by MFM fellows. CVS samples were sent for karyotype, and products of conception (POC) were sent if CVS sample did not yield a result. Success was defined as karyotype result on CVS specimen. RESULTS: A total of 130 women with EPF up to 9 weeks of gestation underwent transvaginal CVS and MVA from December 2011 to April 2015. CVS samples were successful in 53 (40.8%) cases, POC were analyzed for karyotype in 68 (52.3%) cases, and maternal decidua was obtained in 9 (6.9%) cases. Nine MFM fellows performed the CVS and MVA procedures. The mean number of procedures per fellow was 14 (5-24). The average success rate of transvaginal CVS sample was 33.3% after the first procedure and 50% at the 14th procedure. One procedure was performed per patient. CONCLUSIONS: Success increased over time from 33.3% to 50.0%. Given the gestational age and failed pregnancy status, this is a reasonable success rate for CVS at time of EPF. © 2016 John Wiley & Sons, Ltd.

Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome.

OBJECTIVE: Obesity and metabolic syndrome are associated with systemic inflammation and increased perinatal morbidity. Metformin improves metabolic and inflammatory biomarkers in nonpregnant adults. Using in vivo and in vitro models, we examined the effect of metformin on maternal and fetal inflammation. STUDY DESIGN: Female Wistar rats (6-7 weeks old) were fed a normal diet (NORM) or a high-fat/high-sugar diet (HCAL) for 5-6 weeks to induce obesity/metabolic syndrome. After mating with NORM-fed male rats, one-half of the HCAL-fed female rats received metformin (300 mg/kg, by mouth daily). All dams continued their respective diets until gestational day 19, at which time maternal and fetal outcomes were assessed. Maternal and fetal plasma and placentas were analyzed for metabolic and inflammatory markers. Cultured human placental JAR cells were pretreated with vehicle or metformin (10 µmol/L-2.5 mmol/L) before tumor necrosis factor α (TNF-α; 50 ng/mL), and supernatants were assayed for interleukin-6 (IL-6). RESULTS: HCAL rats gained more prepregnancy weight than NORM rats (P = .03), had higher levels of plasma insulin and leptin, and exhibited dyslipidemia (P < .05). Fetuses that were exposed to the HCAL diet had elevated plasma IL-6, TNF-α, and chemokine (C-C motif) ligand 2 levels (P < .05) and enhanced placental TNF-α levels (P < .05). Maternal metformin did not impact maternal markers but significantly decreased diet-induced TNF-α and chemokine (C-C motif) ligand 2 in the fetal plasma. Finally, metformin dose-dependently reduced TNF-α-induced IL-6 and IκBα levels in cultured placental JAR cells. CONCLUSION: Diet induced-obesity/metabolic syndrome during pregnancy significantly enhanced fetal and placental cytokine production; maternal metformin reduced fetal cytokine levels. Similarly, metformin treatment of a placental cell line suppressed TNF-α-induced IL-6 levels by NFκB inhibitor.

Maternal magnesium supplementation reduces intrauterine growth restriction and suppresses inflammation in a rat model.

OBJECTIVE: Intrauterine growth restriction (IUGR) is associated with increased inflammatory responses. We sought to investigate whether magnesium (Mg) attenuates inflammation and IUGR in a rat model. STUDY DESIGN: Pregnant Wistar rats (12 weeks, gestational day 18) were randomly assigned to 1 of 4 groups: normal diet with bilateral uterine artery ligation (BL) (n = 6) or sham surgery (SH) (n = 5); and Mg chloride (MgCl2) 1% (wt/vol) in the drinking water throughout gestation + BL (MgBL) (n = 6) or SH (MgSH) (n = 5). Dams were euthanized 24 hours postsurgery (gestational day 19). Maternal plasma, fetal plasma (pooled), individual amniotic fluid (AF) samples, and placentas (PL) were collected and assessed from live fetal pups only (BL, n = 36; SH, n = 20; MgBL, n = 20; MgSH, n = 20). All samples were analyzed for cytokines/chemokines (interleukin [IL]-6, IL-1ß, chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 2 [CCL2], and tumor necrosis factor [TNF-α] sensitivity <3 pg/mL) using a multiplex platform. Data were analyzed using Mann Whitney, analysis of variance, and Fisher exact tests. RESULTS: The incidence of IUGR (pup weight <10th percentile of SH) in the MgBL group was significantly lower (31%) than the BL group (86.3%) (relative risk, 0.36; 95% confidence interval, 0.2-0.6; P < .0001). BL significantly increased AF levels of IL-6, IL-1ß, TNF-α (P < .05), and CCL2 (P < .001) vs SH and PL levels of IL-6, IL-1ß, CCL2 and CXCL1 (P < .001), and TNF-α (P < .05) vs SH. Maternal MgCl2 supplementation significantly decreased IL-1ß, TNF-α, and CCL2 levels in AF and IL-1ß in PL tissues of MgBL vs BL rats (P < .0001). CONCLUSION: Maternal oral MgCl2 supplementation reduced BL-induced IUGR by 64% and suppressed cytokine/chemokine levels in the AF and PL.

Gestational age at cervical length measurement and incidence of preterm birth.

OBJECTIVE: To estimate the risk of spontaneous preterm birth based on transvaginal ultrasound cervical length and gestational age at which cervical length was measured. METHODS: Women at high risk for spontaneous preterm birth and with transvaginal ultrasound cervical length measurements between weeks 12 and 32 were identified at one institution between July 1995 and June 2005. Inclusion criteria for women at high risk for spontaneous preterm birth were prior spontaneous preterm birth at 14 to 35 weeks, cone biopsy, müllerian anomaly, or two or more dilation and evacuations. Women with multiple gestations, cerclage, indicated preterm birth, or fetal anomalies were excluded. Logistic regression was used to estimate the spontaneous preterm birth risk before 35, 32, and 28 weeks. RESULTS: Seven hundred five women received 2,601 transvaginal ultrasound measurements for cervical length. The incidences of spontaneous preterm birth before 35, 32, and 28 weeks were 17.7, 10.6, and 6.7%, respectively. The risk of spontaneous preterm birth before 35 weeks decreased by approximately 6% for each additional millimeter of cervical length (odds ratio 0.94, 95% confidence interval, 0.92-0.95, P=.001) and by approximately 5% for each additional week of pregnancy at which the cervical length was measured (odds ratio 0.95, 95% confidence interval 0.92-0.98, P=.004). Similar results were obtained for spontaneous preterm birth before 32 and 28 weeks. CONCLUSION: Gestational age at which transvaginal ultrasound cervical length is measured significantly affects the calculation of risk of spontaneous preterm birth. The spontaneous preterm birth risk increases as the length of the cervix declines and as the gestational age decreases. These spontaneous preterm birth risks are important for counseling and management for women with various degrees of short cervical length at different gestational ages. LEVEL OF EVIDENCE: II.