Fetal fibronectin testing for reducing the risk of preterm birth.

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for preterm birth. This is an update of a review first published in 2008. OBJECTIVES: To assess the effectiveness of management based on knowledge of FFN testing results for preventing preterm birth. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth\u27s Trials Register (7 September 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials of pregnant women screened with FFN for risk of preterm birth. Studies included are based exclusively on knowledge of FFN results versus no such knowledge, and we have excluded studies including women with only positive or only negative FFN results. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We identified 16 trials, of which six were eligible for inclusion. The six included studies randomized 546 women with singleton gestations and threatened preterm labor (PTL) at 23 0/7 to 34 6/7 weeks. A total of 277 women were randomized to knowledge and 269 to no knowledge of FFN. No trials were identified on asymptomatic women or multiple gestations.The risk of bias of included studies was mixed. For selected important outcomes, preterm birth before 37, 34, and 32 weeks, and maternal hospitalization, we graded the quality of the evidence and created a \u27Summary of findings\u27 table. For these outcomes, the evidence was graded as mainly low quality due to the imprecision of effect estimates.Management based on knowledge of FFN results may reduce preterm birth before 37 weeks (21.6%) versus controls without such knowledge (29.2%) (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.52 to 1.01; 4 trials; 357 women; low-quality evidence). However, management based on knowledge of FFN results may make little or no difference to preterm birth before 34 (RR 1.09, 95% CI 0.54 to 2.18; 4 trials; 357 women; low-quality evidence) or maternal hospitalization (RR 1.06, 95% CI 0.79 to 1.43; 5 trials; 441 women; low-quality evidence). The evidence for preterm birth before 32 weeks is uncertain because the quality was found to be very low (average RR 0.79, 95% CI 0.16 to 3.96; 4 trials; 357 women; very low-quality evidence).For all other outcomes, for which there were available data (preterm birth less than 28 weeks; gestational age at delivery (weeks); birthweight less than 2500 g; perinatal death; tocolysis; steroids for fetal lung maturity; time to evaluate; respiratory distress syndrome; neonatal intensive care unit (NICU) admission; and NICU days), knowledge of FFN results may make little or no difference to the outcomes. AUTHORS\u27 CONCLUSIONS: The evidence from this review suggests that management based on knowledge of FFN results may reduce preterm birth before 37 weeks. However, our confidence in this result is limited as the evidence was found to be of low quality. Effects on other substantive outcomes are uncertain due to serious concerns in study design, inconsistency, and imprecision of effect estimates. No trials were identified on asymptomatic women, or multiple gestations.Future studies are needed that include specific populations (e.g. singleton gestations with symptoms of preterm labor), a study group managed with a protocol based on the FFN results, and that report not only maternal but also important perinatal outcomes. Cost-effectiveness analyses are also needed

Cervical assessment by ultrasound for preventing preterm delivery.

BACKGROUND: Measurement of cervical length by ultrasound is predictive of preterm birth (PTB). There are three methods of ultrasound cervical assessment: transvaginal (TVU), transabdominal (TAU), and transperineal (TPU, also called translabial). Cervical length measured by TVU is a relatively new screening test, and has been associated with better prediction of PTB than previously available tests. It is unclear if cervical length measured by ultrasound is effective for preventing PTB. This is an update of a review last published in 2013. OBJECTIVES: To assess the effectiveness of antenatal management based on transvaginal, transabdominal, and transperineal (also called translabial) ultrasound screening of cervical length for preventing preterm birth. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth\u27s Trials Register, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to 30 August 2018; reviewed the reference lists of all articles, and contacted experts in the field for additional and ongoing trials. SELECTION CRITERIA: We included published and unpublished randomised controlled trials (RCT) including pregnant women between the gestational ages of 14 to 32 weeks, for whom the cervical length was screened for risk of PTB with TVU, TAU, or TPU. This review focused on studies based on knowledge versus no knowledge of cervical length results, or ultrasound versus no ultrasound for cervical length. We excluded studies based on interventions (e.g. progesterone, cerclage) for short cervical length. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: We included seven RCTs (N = 923): one examined asymptomatic women with twin pregnancies; four included women with singleton pregnancies and symptoms of preterm labour (PTL); one included women with singleton pregnancies and symptoms of preterm premature rupture of membranes (PPROM); and one included asymptomatic singletons. All trials used TVU for screening.We assessed the risk of bias of the included studies as mixed, and the quality of the evidence for primary outcomes as very low for all populations.For asymptomatic women with twin pregnancies, it is uncertain whether knowledge of TVU-measured cervical length compared to no knowledge reduces PTB at less than 34 weeks (risk ratio (RR) 0.62, 95% confidence intervals (CI) 0.30 to 1.25; 1 study, 125 participants) because the quality of the evidence is very low. The results were also inconclusive for preterm birth at 36, 32, or 30 weeks; gestational age at birth, and other maternal and perinatal outcomes.Four trials examined knowledge of TVU-measured cervical length of singletons with symptoms of PTL versus no knowledge. We are uncertain of the effects because of inconclusive results and very low-quality evidence for: preterm births at less than 37 weeks (average RR 0.59, 95% CI 0.26 to 1.32; 2 studies, 242 participants; I² = 66%; Tau² = 0.23). Birth occurred about four days later in the knowledge groups (mean difference (MD) 0.64 weeks, 95% CI 0.03 to 1.25; 3 trials, 290 women). The results were inconclusive for the other outcomes for which there were available data: PTB at less than 34 or 28 weeks; birthweight less than 2500 g; perinatal death; maternal hospitalisation; tocolysis; and steroids for fetal lung maturity.The trial of singletons with PPROM (N = 92) evaluated safety of using TVU to measure cervical length in this population as its primary outcome, not its effect on management. The results were inconclusive for incidence of maternal and neonatal infections between the TVU and no ultrasound groups.In the trial of asymptomatic singletons (N = 296), in which women either received TVU or not, the results were inconclusive for preterm birth at less than 37 weeks (RR 1.27, 95% CI 0.61 to 2.61; I² = 0%), gestational age at birth, and other perinatal and maternal outcomes.We downgraded evidence for limitations in study design, inconsistency between the trials, and imprecision, due to small sample size and wide confidence intervals crossing the line of no effect.No trial compared the effect of knowledge of the CL with no knowledge of CL in other populations, such as asymptomatic women with singleton pregnancies, or symptomatic women with twin pregnancies. AUTHORS\u27 CONCLUSIONS: There are limited data on the effects of knowing the cervical length, measured by ultrasound, for preventing preterm births, which preclude us from drawing any conclusions for women with asymptomatic twin or singleton pregnancies, singleton pregnancies with PPROM, or other populations and clinical scenarios.Limited evidence suggests that knowledge of transvaginal ultrasound-measured cervical length, used to inform the management of women with singleton pregnancies and symptoms of preterm labour, appears to prolong pregnancy by about four days over women in the no knowledge groups.Future studies could look at specific populations separately (e.g. singleton versus twins; symptoms versus no symptoms of PTL), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU-measured cervical length

MFM Guidance for COVID-19

The World Health Organization (WHO) has declared COVID-19 a global pandemic. Healthcare providers should prepare internal guidelines covering all aspect of the organization in order to have their unit ready as soon as possible. This document addresses the current COVID-19 pandemic for maternal-fetal medicine (MFM) practitioners. The goals the guidelines put forth here are two fold- first to reduce patient risk through healthcare exposure, understanding that asymptomatic health systems/healthcare providers may become the most common vector for transmission, and second to reduce the public health burden of COVID-19 transmission throughout the general population. Box 1 outlines general guidance to prevent spread of COVID-19 and protect our obstetric patients. Section 1 outlines suggested modifications of outpatient obstetrical (prenatal) visits. Section 2 details suggested scheduling of obstetrical ultrasound. Section 3 reviews suggested modification of nonstress tests (NST) and biophysical profiles (BPP). Section 4 reviews suggested visitor policy for obstetric outpatient office. Section 5 discusses the role of trainees and medical education in the setting of a pandemic. These are suggestions, which can be adapted to local needs and capabilities. Guidance is changing rapidly, so please continue to watch for updates

Pregnancy after liver transplantation: a case series and review of the literature

Objective: To evaluate maternal and perinatal outcomes in pregnant women after liver transplantation with a case series and literature systematic review. Methods: This was a single-center case-series study performed at University of Naples Federico II. All consecutive women with liver transplantation who reported pregnancy at our institution were included in a dedicated database. In addition, a systematic literature review was performed, including case series, population-based studies, and national registries, including maternal and perinatal outcomes of pregnant women with liver transplant. Studies with fewer than 10 cases and surveys were excluded. The primary outcome was perinatal death, defined as either stillbirth (defined as intrauterine fetal death after 20 weeks of gestation) or neonatal death (death of a live-born infant within the first 28 d of life). Results: During the study period, two women who underwent liver transplantation had a pregnancy in our Institution. Both of them underwent liver transplantation for biliary atresia at 1 year of age. One of them received cyclosporin as immunosuppressive regime during pregnancy, while the other one received tacrolimus. Both of them had a pregnancy with no major complications and delivered by cesarean section at term a baby with normal weight. One of them developed thrombocytopenia. Seventeen articles were included in this systematic review. Preterm birth at less than 37 weeks of gestations occurred in 279 women (33.6%). One-hundred women (14.9%) experienced preeclampsia, and 206 women (49.2%) delivered by cesarean delivery. Graft rejection related to pregnancy occurred in 73 women (8.3%). 117 women (12.9%) experienced miscarriage, and 22 (2.3%) IUFD. Fifty-two women (9.52%) underwent elective I-TOP. 195 fetuses (33.4%) were LBW. Eight neonatal deaths were recorded (1.3%). Conclusion: The maternal and perinatal outcome is usually favorable, but with an increased risk of preeclampsia, preterm birth, and perinatal morbidity and mortality. However, appropriate counseling about risks and complications is essential but women shouldn't be advised against pregnancy

Effects of progestogens in women with preterm premature rupture of membranes

Different strategies have been adopted for prevention of spontaneous preterm birth, including use of progestogens. So far, five randomized trials have been published evaluating the efficacy of progestogens in women with PPROM, including a total of 425 participants. All the five trials enrolled pregnant women with singleton pregnancies randomized between 20 and 34 weeks of gestation. In four trials women were randomized to either weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate or placebo, while Mirzaei et al. was a three arms trials in which women received weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate, or rectal progesterone 400 mg daily, or no treatment. In all the trials, latency antibiotics were used, and tocolysis was used permitted for first 48 hours at discretion of attending physician. Recently a meta-analysis including the five trials has been published. They found that when compared to placebo weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate did not alter the latency period to delivery in singleton gestations with PPROM. Additionally, there was no difference in gestational age at delivery between groups or in mode of delivery. No significant differences were reported in maternal or neonatal outcomes, with latency not significantly altered in sensitivity analyses. So far, no trials have been published evaluating natural vaginal progesterone in women with PPROM

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

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