Amanda Roman

Cerclage for short cervix in twin pregnancies: systematic review and meta-analysis of randomized trials using individual patient-level data

To evaluate the efficacy of cerclage for preventing preterm birth in twin pregnancies with a short cervical length.

Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: The PREGNANTS study

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti‐&bgr;2 glycoprotein‐I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well‐established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti‐&bgr;2 glycoprotein‐I, and/or lupus anticoagulant), and were treated with low‐dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti‐&bgr;2 glycoprotein‐I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti‐&bgr;2 glycoprotein‐I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51–0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22–1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19–2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17–2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22–2.94). In women with only 1 positive test result, women with anti‐&bgr;2 glycoprotein‐I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P<.01) and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; P<.01) and with severe features (17.2% vs 14.4% vs 0%; P=.02), intrauterine growth restriction (48.4% vs 40.1% vs 25.9%; P<.01), and stillbirth (29.7% vs 21.2% vs 7.4%; P<.01) compared with women with anticardiolipin antibodies and with women with lupus anticoagulant present alone, respectively. In the group of women with >1 antibody positivity, triple‐positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22–0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15–2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti‐&bgr;2 glycoprotein‐I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when <1 antiphospholipid antibody is present. Despite therapy with low‐dose aspirin and prophylactic low molecular weight heparin, the chance of a liveborn neonate is only 30% for triple‐positive women.

Efficacy of ultrasound-indicated cerclage in twin pregnancies

OBJECTIVE We sought to compare the perinatal outcomes in twin pregnancies with short cervical length (CL) with ultrasound-indicated cerclage (UIC) vs no cerclage (control). STUDY DESIGN This was a retrospective cohort study of asymptomatic twin pregnancies with transvaginal ultrasound (TVU) CL ≤25 mm at 16-24 weeks from 1995 through 2012 at 4 separate institutions. Exclusion criteria were: genetic or major fetal anomaly, multifetal reduction >14 weeks, monochorionic-monoamniotic placentation, or medically indicated preterm birth (PTB). Primary outcome was spontaneous PTB (SPTB) <34 weeks. Secondary outcome was SPTB <28, <32, and <37 weeks. We also planned to evaluate primary and secondary outcome for the subgroup of twin pregnancies with CL ≤15 mm. RESULTS In all, 140 women with twin pregnancy and TVU-CL ≤25 mm were managed with either UIC (n = 57) or no cerclage (n = 83). Demographic characteristics were not significantly different except women who underwent UIC presented at an earlier gestational age (GA) at diagnosis of short CL. After adjusting for GA at presentation, there were no differences in GA at delivery or SPTB <28 weeks: 12 (21.2%) vs 20 (24.1%) (adjusted odds ratio [aOR], 0.3; 95% confidence interval [CI], 0.68-1.37), <32 weeks: 22 (38.6%) vs 36 (43.4%) aOR, 0.34; 95% CI, 0.1-1.13), or <34 weeks: 29 (50.9%) vs 53 (63.9%) (aOR, 0.37; 95% CI, 0.16-1.1). In the subgroup of women with CL ≤15 mm (32 with UIC and 39 controls) the interval between diagnosis to delivery was significantly prolonged by 12.5 ± 4.5 vs 8.8 ± 4.6 weeks (P < .001); SPTB <34 weeks was significantly decreased: 16 (50%) vs 31 (79.5%) (aOR, 0.51; 95% CI, 0.31-0.83) as was admission to neonatal intensive care unit: 38/58 (65.5%) vs 63/76 (82.9%) (aOR, 0.42; 95% CI, 0.24-0.81) when the UIC group was compared with the control group, respectively. CONCLUSION UIC in asymptomatic twin pregnancies with TVU-CL ≤25 mm was not associated with significant effects on perinatal outcomes compared to controls. However, in the planned subgroup analysis of asymptomatic twin pregnancies with TVU-CL ≤15 mm before 24 weeks, UIC was associated with a significant prolongation of pregnancy by almost 4 more weeks, significantly decreased SPTB <34 weeks by 49%, and admission to neonatal intensive care unit by 58% compared with controls.

Exercise during pregnancy and risk of gestational hypertensive disorders: a systematic review and meta-analysis

Gestational hypertensive disorders, including gestational hypertension and preeclampsia, are one of the leading causes of maternal morbidity and mortality. The aim of our study was to evaluate the effect of exercise during pregnancy on the risk of gestational hypertensive disorders.

Cerclage for sonographic short cervix in singleton gestations without prior spontaneous preterm birth: systematic review and meta‐analysis of randomized controlled trials using individual patient‐level data

The aim of this systematic review and meta‐analysis was to quantify the efficacy of cervical cerclage in preventing preterm birth (PTB) in asymptomatic singleton pregnancies with a short mid‐trimester cervical length (CL) on transvaginal sonography (TVS) and without prior spontaneous PTB.

5-Methyl-tetrahydrofolate in prevention of recurrent preeclampsia

Abstract Objective: To evaluate the efficacy of 5-methyl-tetrahydrofolate (5-MTHF) supplementation in prevention of recurrent preeclampsia. Methods: Retrospective cohort of women who received daily oral 5-MTHF 15 mg supplementation as prophylactic treatment since first trimester for recurrent preeclampsia were compared with women who did not. All asymptomatic singleton gestations with prior preeclampsia (in the previous pregnancy) were included. Women with chronic hypertension were excluded. The primary outcome was the incidence of preeclampsia. Results: Three hundred and three singleton gestation met the inclusion criteria: 157 received 5-MTHF, while 146 did not (control group). Women who received 5-MTHF had a significantly lower incidence of recurrent overall preeclampsia (21.7% versus 39.7%; odds ratio (OR) 0.57, 95% confidence interval (CI) 0.25, 0.69), severe preeclampsia (3.2% versus 8.9%; OR 0.44, 95% CI 0.12–0.97) and early-onset preeclampsia (1.9% versus 7.5%; OR 0.34, 95% CI 0.07–0.87) compared to control. The intervention group delivered about 10 d after the control and had higher birth weight. Conclusion: This retrospective study showed that women with prior preeclampsia who received daily oral 5-MTHF 15 mg supplementation had a significantly lower incidence of overall preeclampsia, severe preeclampsia and early-onset preeclampsia. Randomized controlled trials are needed to confirm our findings.

Pessary versus cerclage versus expectant management for cervical dilation with visible membranes in the second trimester

Abstract Objective: We evaluated pessary for dilated cervix and exposed membranes for prolonging pregnancy compared to cerclage or expectant management. Methods: Multicenter retrospective cohort study of women, 15–24 weeks, singleton pregnancies, dilated cervix ≥2 cm and exposed membranes. Women received pessary, cerclage or expectant management. Primary outcome was gestational age (GA) at delivery. Secondary outcomes were time until delivery, preterm premature rupture of membranes (PPROM) and neonatal survival. Results: About 112 women met study criteria; 9 – pessary, 85 – cerclage and 18 – expectant management. Mean GA at delivery was 22.9 ± 4.5 weeks with pessary, 29.2 ± 7.5 weeks with cerclage and 25.6 ± 6.7 weeks with expectant management (p = 0.015). Time until delivery was 16.1 ± 18.9 days in the pessary group, 61.7 ± 48.2 days in the cerclage group and 26.8 ± 33.4 days in the expectant group (p < 0.001). PPROM occurred less frequently and neonatal survival increased in women with cerclage. There was a significant difference in all the perinatal outcomes with cerclage compared with either pessary or expectant management. Conclusions: Perinatal outcomes with pessary were not superior to expectant management in women with dilated cervix with exposed membranes in the second trimester in this small retrospective cohort.

Blood loss at cesarean delivery in women on magnesium sulfate for preeclampsia

Abstract Objective: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD). Methods: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were “magnesium sulfate”, “preeclampsia” and “randomized”. Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia. Results: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88–1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28–0.57). Conclusions: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage.

Decrease in the incidence of threatened preterm labor after implementation of transvaginal ultrasound cervical length universal screening

Abstract Background: It is unknown if universal second-trimester transvaginal ultrasound (TVU) cervical length (CL) screening in asymptomatic women with singleton gestations and no prior spontaneous preterm birth (SPTB) affects the incidence of symptoms of preterm labor (PTL) later in pregnancy. Objective: To evaluate the incidence of threatened PTL before and after the implementation of universal second trimester TVU CL screening. Study design: This was a retrospective cohort study of all consecutive singleton gestations without prior SPTB presenting to obstetric triage for threatened PTL between 23 0/7 and 33 6/7 week in 2011 (1 January–31 December), and in 2014 (1 January–31 December) at Thomas Jefferson University Hospital (TJU) (Philadelphia, PA). These 2 years were chosen as a new protocol for universal TVU CL screening was started on 1 January 2012. This protocol involved one measurement of TVU CL in all singleton gestations without a prior SPTB at 18 0/7 − 23 6/7 week, the time of the “anatomy” scan. Women with prior SPTB were excluded from this study. The primary outcome included the incidence of threatened PTL, defined as the number of women with singleton gestations without prior SPTB who presented with threatened PTL to our labor and delivery (L&D) triage unit annually, divided by the total number of annual deliveries of women with singleton gestation without prior SPTB. Secondary outcomes were the incidence of PTL, defined as the number of women with singleton gestations without prior SPTB admitted for PTL annually divided by the total number of annual deliveries of women with singleton gestation and without prior SPTB; and length of stay in the hospital. We aimed to compare primary and secondary outcome in the “2011” versus the “2014” group. Results: In 2011, there were a total of 1745 deliveries at TJU, of which 1550 (88.8%) were singletons without prior SPTB. In 2014, there were a total of 1924 deliveries at TJU, 1751 (91.0%) were singletons without prior SPTB who were offered universal TVU CL screening. One hundred and seventy-two women with singletons without prior SPTB presented in L&D triage unit in 2011; and 118 women with singletons without prior SPTB presented in L&D triage unit in 2014. There were significant decreases in the incidence of threatened PTL from 11.1% (172/1550) in 2011 to 6.7% (118/1751) in 2014 (p < .001), as well as in the rate of admission for PTL from 2.3% (35/1550) to 1.4% (24/1751), respectively (p = .04). Length of stay was not significantly different between the two groups. Conclusion: The introduction of a universal TVU CL screening program in women with singleton gestations without a history of SPTB is associated with a reduction in the frequency of threatened PTL and admission for PTL. Key Message The introduction of a second trimester universal transvaginal ultrasound (TVU) cervical length (CL) screening program in women without a history of spontaneous preterm birth (SPTB) is associated with a reduction in the incidence of threatened preterm labor (PTL) and admission for PTL.

Risk of spontaneous preterm birth in IVF-conceived twin pregnancies

Abstract Objective: To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester in screening for preterm birth in in vitro (IVF)-conceived twin pregnancies versus spontaneously-conceived twin pregnancies. Methods: This was a retrospective cohort study. Potential study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7 to 23 6/7-week gestation. All women with twin diamniotic pregnancies screened with a single TVU CL for this trial were included. Mean TVU CLs were compared between IVF-conceived twin pregnancies and spontaneously-conceived twin pregnancies. The relationship of TVU CL with gestational age at delivery was assessed. Incidence of short TVU CL, defined as TVU CL ≤30 mm, was also calculated in the two groups. The primary outcome was the mean of TVU CL. Distribution of CL was determined and normality was examined in both groups Results: A total of 668 women with diamniotic twin pregnancies who underwent TVU CL screening between 18 0/6 and 23 6/7 weeks were included. 158 (23.7%) were IVF-conceived pregnancies, and 510 (76.3%) were spontaneously-conceived pregnancies. No women received progesterone, pessary, or cerclage for preterm birth prevention during pregnancy. The mean TVU CL was significantly lower in the IVF-conceived group (32.2 ± 10.5 mm) compared to the spontaneously-conceived group (34.1 ± 9.1 mm) (mean difference (MD) − 1.90 mm, 95%CI −3.72 to −0.08). The incidence of TVU CL ≤30 mm was 30.4% in the IVF-conceived group and 21.6% in the spontaneously-conceived group (adjusted odds ratio (aOR) 1.59, 95%CI 1.06–2.37). IVF-conceived twins had a significantly higher risk of spontaneous preterm birth <34 weeks (32.9 versus 21.2%; aOR 1.83, 95% confidence interval (CI) 1.23–2.71) and higher rate of delivery due to spontaneous onset of labor (64.5 versus 54.9%; aOR 1.50, 95%CI 1.03–2.17). For any given TVU CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for IVF-conceived twins was earlier by about 1 week on average compared with spontaneously-conceived twins. Conclusions: The higher rate of spontaneous preterm birth in IVF-conceived twin pregnancies is predicted by lower midtrimester TVU CL, as well as by the lower gestational age at birth per any given CL in the IVF-conceived compared to the spontaneously-conceived twin pregnancies.