Gabriele Saccone

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.

Tranexamic acid for preventing postpartum blood loss after cesarean delivery: a systematic review and meta-analysis of randomized controlled trials

There are several published clinical trials of the use of tranexamic acid (TXA) in an obstetric setting, but no consensus on its use or guidelines for management.

Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.

OBJECTIVE DATA Fetal fibronectin is an extracellular matrix glycoprotein that is produced by amniocytes and cytotrophoblasts and has been shown to predict spontaneous preterm birth. STUDY The aim of this systematic review and metaanalysis of randomized clinical trials was to evaluate the effect of the use of fetal fibronectin in the prevention of preterm birth in singleton pregnancies with threatened preterm labor. STUDY APPRAISAL AND SYNTHESIS METHODS The research was conducted with the use of MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library as electronic databases from the inception of each database to February 2016. Selection criteria included randomized clinical trials of singleton gestations with threatened preterm labor that were assigned randomly to management based on fetal fibronectin results (ie, intervention group) or not (ie, comparison group). Types of participants included women with singleton gestations at 23 0/7 to 34 6/7 weeks with threatened preterm labor. Studies that included management that was also based on the use of sonographic cervical length were excluded. The primary outcome was preterm birth at <37 weeks of gestation. The summary measures were reported as relative risk or as mean differences with 95% confidence interval. RESULTS Six trials that included 546 singleton gestations with symptoms of preterm labor were included in the metaanalysis. The overall risk of bias of the included trials was low. Women were eligible for the random assignment in case of symptoms that suggested preterm labor at 23-34 weeks of gestation. During admission, before digital examination, a Dacron swab was rotated in the posterior fornix for 10 seconds to absorb cervicovaginal secretions that were then analyzed for the fetal fibronectin qualitative method, with results reported as either positive or negative. Women who were assigned randomly to the fetal fibronectin group had a similar incidence of preterm birth at <37 weeks of gestation (20.7% vs 29.2%; relative risk, 0.72; 95% confidence interval, 0.52-1.01), at <34 weeks of gestation (8.3% vs 7.9%; relative risk, 1.09; 95% confidence interval, 0.54-2.18), at <32 weeks of gestation (3.3% vs 5.6%; relative risk, 0.64; 95% confidence interval, 0.24-1.74), and at <28 weeks of gestation (1.1% vs 1.7%; relative risk, 0.74; 95% confidence interval, 0.15-3.67) compared with the control group. No differences were found in the number of women who delivered within 7 days (12.8% vs 14.5%; relative risk, 0.76; 95% confidence interval, 0.47-1.21), in the mean of gestational age at delivery (mean difference, 0.20 week; 95% confidence interval, -0.26 to 0.67), in the rate of maternal hospitalization (27.4% vs 26.9%; relative risk, 1.07; 95% confidence interval, 0.80-1.44), in the use of tocolysis (25.3% vs 28.2%; relative risk, 0.97; 95% confidence interval, 0.75-1.24), antenatal steroids (29.2% vs 29.2%; relative risk, 1.05; 95% confidence interval, 0.79-1.39), in the mean time in the triage unit (mean difference, 0.60 hour; 95% confidence interval, -0.03 to 1.23) and in neonatal outcomes that included respiratory distress syndrome (1.3% vs 1.5%; relative risk, 0.91; 95% confidence interval, 0.06-14.06), and admission to the neonatal intensive care unit (19.4% vs 8.1%; relative risk, 2.48; 95% confidence interval, 0.96-6.46). Management based on the fetal fibronectin test required higher hospitalization charges (mean difference,

Prior uterine evacuation of pregnancy as independent risk factor for preterm birth: a systematic review and metaanalysis

153; 95% confidence interval, 24.01-281.99). CONCLUSION Fetal fibronectin testing in singleton gestations with threatened preterm labor is not associated with the prevention of preterm birth or improvement in perinatal outcome but is associated with higher costs.

Omega-3 long-chain polyunsaturated fatty acids and fish oil supplementation during pregnancy: which evidence?

BACKGROUND Preterm birth (PTB) is the number one cause of perinatal mortality. Prior surgery on the cervix is associated with an increased risk of PTB. History of uterine evacuation, by either induced termination of pregnancy (I-TOP) or spontaneous abortion (SAB), which involve mechanical and/or osmotic dilatation of the cervix, has been associated with an increased risk of PTB in some studies but not in others. OBJECTIVE The objective of the study was to evaluate the risk of PTB among women with a history of uterine evacuation for I-TOP or SAB. DATA SOURCES Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, and Sciencedirect) were searched from their inception until January 2015 with no limit for language. STUDY ELIGIBILITY CRITERIA We included all studies of women with prior uterine evacuation for either I-TOP or SAB, compared with a control group without a history of uterine evacuation, which reported data about the subsequent pregnancy. STUDY APPRAISAL AND SYNTHESIS METHODS The primary outcome was the incidence of PTB < 37 weeks. Secondary outcomes were incidence of low birthweight (LBW) and small for gestational age (SGA). We planned to assess the primary and the secondary outcomes in the overall population as well as in studies on I-TOP and SAB separately. The pooled results were reported as odds ratio (OR) with 95% confidence interval (CI). RESULTS We included 36 studies in this metaanalysis (1,047,683 women). Thirty-one studies reported data about prior uterine evacuation for I-TOP, whereas 5 studies reported data for SAB. In the overall population, women with a history of uterine evacuation for either I-TOP or SAB had a significantly higher risk of PTB (5.7% vs 5.0%; OR, 1.44, 95% CI, 1.09-1.90), LBW (7.3% vs 5.9%; OR, 1.41, 95% CI, 1.22-1.62), and SGA (10.2% vs 9.0%; OR, 1.19, 95% CI, 1.01-1.42) compared with controls. Of the 31 studies on I-TOP, 28 included 913,297 women with a history of surgical I-TOP, whereas 3 included 10,253 women with a prior medical I-TOP. Women with a prior surgical I-TOP had a significantly higher risk of PTB (5.4% vs 4.4%; OR, 1.52, 95% CI, 1.08-2.16), LBW (7.3% vs 5.9%; OR, 1.41, 95% CI, 1.22-1.62), and SGA (10.2% vs 9.0%; OR, 1.19, 95% CI, 1.01-1.42) compared with controls. Women with a prior medical I-TOP had a similar risk of PTB compared with those who did not have a history of I-TOP (28.2% vs 29.5%; OR, 1.50, 95% CI, 1.00-2.25). Five studies, including 124,133 women, reported data about a subsequent pregnancy in women with a prior SAB. In all of the included studies, the SAB was surgically managed. Women with a prior surgical SAB had a higher risk of PTB compared with those who did not have a history of SAB (9.4% vs 8.6%; OR, 1.19, 95% CI, 1.03-1.37). CONCLUSION Prior surgical uterine evacuation for either I-TOP or SAB is an independent risk factor for PTB. These data warrant caution in the use of surgical uterine evacuation and should encourage safer surgical techniques as well as medical methods.

Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials

Abstract Objective: The aim of this study was to provide evidence-based recommendations for omega-3 supplementation during pregnancy through a systematic review of level-1 data published on this topic. Methods: We reviewed all randomized-controlled trials (RCTs) including women who were randomized to treatment with either omega-3 supplementation or control (placebo or no treatment) during pregnancy and analyzed all the outcomes reported in the trials, separately. We planned to evaluate the effect of omega-3 on: preterm birth (PTB); pre-eclampsia (PE) and intrauterine growth restriction (IUGR); gestational diabetes; perinatal mortality; small for gestational age (SGA) and birth weight; infant eye and brain development; and postpartum depression. Results: We identified 34 RCTs including 14 106 singletons and 2578 twins. These level-1 data showed that omega-3 was not associated with prevention of PTB, PE, IUGR, gestational diabetes, SGA, post-partum depression or better children development. Data about birth weight, perinatal mortality and childhood cognitive outcome were limited. Women with gestational diabetes who received omega-3 had significantly lower serum C-reactive protein concentrations, low incidence of hyperbilirubinemia in newborns and decreased newborns’ hospitalization rate. Conclusions: There was not enough evidence to support the routine use of omega-3 supplementation during pregnancy. Given the 73% significant decrease in perinatal death in the singleton gestations who started omega-3 supplementation ≤ 20 weeks, further research is needed. Large RCTs in multiple gestations and longer follow-up are also required.

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

Objective To evaluate the effectiveness of antenatal corticosteroids given at ≥34 weeks’ gestation. Design Systematic review with meta-analysis. Data sources Electronic databases were searched from their inception to February 2016. Eligibility criteria for study selection Randomized clinical trials comparing antenatal corticosteroids with placebo or no treatment in women with a singleton pregnancy at ≥34 weeks’ gestation. Trials on antenatal steroids in women expected to deliver late preterm (340-366 weeks) and trials given before planned cesarean delivery at term (≥37 weeks) were included. Data synthesis The primary outcome was the incidence of severe respiratory distress syndrome (RDS). The summary measures were reported as relative risks or mean differences with 95% confidence intervals. Results Six trials, including 5698 singleton pregnancies, were analyzed. Three included 3200 women at 340-366 weeks’ gestation and at risk of imminent premature delivery at the time of hospital admission. The three other trials included 2498 women undergoing planned cesarean delivery at ≥37 weeks. Overall, infants of mothers who received antenatal corticosteroids at ≥34 weeks had a significantly lower risk of RDS (relative risk 0.74, 95% confidence interval 0.61 to 0.91), mild RDS (0.67, 0.46 to 0.96), moderate RDS (0.39, 0.18 to 0.89), transient tachypnea of the newborn (0.56, 0.37 to 0.86), severe RDS (0.55, 0.33 to 0.91), use of surfactant, and mechanical ventilation, and a significantly lower time receiving oxygen (mean difference −2.06 hours, 95% confidence interval −2.17 to −1.95), lower maximum inspired oxygen concentration (−0.66%, −0.69% to −0.63%), shorter stay on a neonatal intensive care unit (−7.64 days, −7.65 to −7.64), and higher APGAR scores compared with controls. Infants of mothers who received antenatal betamethasone at 340-366 weeks’ gestation had a significantly lower incidence of transient tachypnea of the newborn (relative risk 0.72, 95% confidence interval 0.56 to 0.92), severe RDS (0.60, 0.33 to 0.94), and use of surfactant (0.61, 0.38 to 0.99). Infants of mothers undergoing planned cesarean delivery at ≥37 weeks’ gestation who received prophylactic antenatal corticosteroids 48 hours before delivery had a significantly lower risk of RDS (0.40, 0.27 to 0.59), mild RDS (0.43, 0.26 to 0.72), moderate RDS (0.40, 0.18 to 0.88), transient tachypnea of the newborn (0.38, 0.25 to 0.57), and mechanical ventilation (0.19, 0.08 to 0.43), and significantly less time receiving oxygen (mean difference −2.06 hours, 95% confidence interval −2.17 to −1.95), lower percentage of maximum inspired oxygen concentration (−0.66%, −0.69% to −0.63%), shorter stay in neonatal intensive care (−7.44 days, −7.44 to −7.43), and a higher APGAR score at one and at five minutes. Conclusions Antenatal steroids at ≥34 weeks’ gestation reduce neonatal respiratory morbidity. A single course of corticosteroids can be considered for women at risk of imminent late premature delivery 340-366 weeks’ gestation, as well as for women undergoing planned cesarean delivery at ≥37 weeks’ gestation. Systematic review registration PROSPERO CRD42016035234.

Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta‐analysis

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

Depression is a prevalent condition in pregnancy affecting about 10% of women. Maternal depression has been associated with an increase in preterm births (PTB), low birthweight and fetal growth restriction, and postnatal complications. Available treatments for depressive disorders are psychotherapeutic interventions and antidepressant medications including selective serotonin inhibitors (SSRIs). SSRI use during pregnancy has been associated with several fetal and neonatal complications; so far, however, the risk of PTB in women using SSRIs during pregnancy is still a subject of debate.

Omega-3 supplementation to prevent recurrent preterm birth: a systematic review and metaanalysis of randomized controlled trials

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.