Primary and secondary prevention of preterm birth: a review of systematic reviews and ongoing randomized controlled trials

BACKGROUND: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention. OBJECTIVE: To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions. SEARCH STRATEGY: A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016. SELECTION CRITERIA: We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible. DATA COLLECTION AND ANALYSIS: The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks. MAIN RESULTS: In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease. CONCLUSION: The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not

Cost-effectiveness of uterine tamponade devices for the treatment of postpartum hemorrhage: A systematic review

Background: Uterine tamponade is widely promoted for treating refractory postpartum hemorrhage (PPH); however, its cost‐effectiveness may vary depending on unit costs and setting. Objective: To review available data on cost‐effectiveness of uterine tamponade devices when used for PPH treatment. Search strategy: PubMed and EMBASE were searched (1980 to January 2020), as well as the National Health Services Economic Evaluation database from inception (1995) to March 2015. Selection criteria: Eligible studies were any type of economic evaluation, or effective‐ ness studies that provided cost or economic data. Data collection and analysis: Two reviewers independently screened studies, extracted data, and assessed quality. Main results: Eleven studies using a range of devices (condom catheter, uterine suc‐ tion devices, Bakri, Inpress, Ellavi) were identified. Cost of condom catheter devices or kits ranged from US$0.64 to US$6, whereas purpose‐designed device costs were up to US$400. Two studies that took a health system perspective assessed the cost‐ effectiveness of using uterine balloon tamponade and suggested that it was highly cost‐ effective because of the low cost per disability‐adjusted life‐year averted, although both used effect estimates from case series. Conclusions: Evidence on the cost‐effectiveness of uterine tamponade devices was limited and not generalizable. Rigorous economic evaluations based on updated effect estimates are needed.Fil: Vogel, Joshua P.. Monash University; AustraliaFil: Wilson, Alyce N.. Burnet Institute; AustraliaFil: Scott, Nick. Monash University; Australia. Burnet Institute; AustraliaFil: Widmer, Mariana. Organizacion Mundial de la Salud; ArgentinaFil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Oladapo, Olufemi T.. Organizacion Mundial de la Salud; Argentin

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background: Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.Methods: We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.Results: 279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60-2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40-4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95-6.62) and stillbirth (AOR 1.22, 95% CI 0.58-2.57) did not reach significance. Amongst twins alone, maternal age 15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.Conclusions: Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low- resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.Australian Postgraduate AwardA & A Saw ScholarshipUniv Western Australia, Sch Populat Hlth, Fac Med Dent & Hlth Sci, Perth, WA 6009, AustraliaUNDP UNFPA UNICEF WHO World Bank Special Programm, Dept Reprod Hlth & Res, World Hlth Org, Geneva, SwitzerlandUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilBrazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWeb of Scienc

What matters to women and healthcare providers in relation to interventions for the prevention of postpartum haemorrhage: A qualitative systematic review

Abstract Background Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity. Reducing deaths from PPH is a global challenge. The voices of women and healthcare providers have been missing from the debate around best practices for PPH prevention. The aim of this review was to identify, appraise and synthesize available evidence about the views and experiences of women and healthcare providers on interventions to prevent PPH. Methods We searched eight electronic databases and reference lists of eligible studies published between 1996 and 2018, reporting qualitative data on views and experiences of PPH in general, and of any specific preventative intervention(s). Authors’ findings were extracted and synthesised using meta-ethnographic techniques. Confidence in the quality, coherence, relevance and adequacy of data underpinning the resulting themes was assessed using GRADE-CERQual. A line of argument synthesis was developed. Results Thirty-five studies from 29 countries met our inclusion criteria. Our results indicate that women and healthcare providers recognise the dangers of severe blood loss in the perinatal and postpartum period, but don’t always share the same beliefs about the causes and consequences of PPH. Skilled birth attendants and traditional birth attendants (TBA’s) want to prevent PPH but may lack the required resources and training. Women generally appreciate PPH prevention strategies, especially where their individual needs, beliefs and values are taken into account. Women and healthcare providers also recognize the value of using uterotonics (medications that contract the uterus) to prevent PPH but highlight safety concerns and potential misuse of the drugs as acceptability and implementation issues. Conclusions Based on stakeholder views and experiences, PPH prevention strategies are more likely to be successful where all stakeholders agree on the causes and consequences of severe postpartum blood loss, especially in the context of sufficient resources and effective implementation by competent, suitably trained providers

Fundal pressure during the second stage of labour

Background Fundal pressure during the second stage of labour (also known as the 'Kristeller manoeuvre') involves application of manual pressure to the uppermost part of the uterus directed towards the birth canal, in an attempt to assist spontaneous vaginal birth and avoid prolonged second stage orthe need for operative birth. Fundal pressure has also been applied using an inflatable belt. Fundal pressure is widely used, however methods of its use vary widely. Despite strongly held opinions in favour of and against the use of fundal pressure, there is limited evidence regarding its maternal and neonatal benefits and harms. There is a need for objective evaluation of the eGectiveness and safety of fundal pressure in the second stage of labour. Objectives To determine if fundal pressure is eGective in achieving spontaneous vaginal birth, and preventing prolonged second stage or the need for operative birth, and to explore maternal and neonatal adverse eGects related to fundal pressure. Search methods We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies. Selection criteria Randomised and quasi-randomised controlled trials of fundal pressure (manual or by inflatable belt) versus no fundal pressure in women in the second stage of labour with singleton cephalic presentation. Data collection and analysis Two or more review authors independently assessed potential studies for inclusion and quality. We extracted data using a pre-designed form. We entered data into Review Manager 5 soAware and checked for accuracy. Main results Nine trials are included in this updated review. Five trials (3057 women) compared manual fundal pressure versus no fundal pressure. Four trials (891 women) compared fundal pressure by means of an inflatable belt versus no fundal pressure. It was not possible to blind women and staG to this intervention. We assessed two trials as being at high risk of attrition bias and another at high risk of reporting bias. All other trials were low or unclear for other risk of bias domains. Most of the trials had design limitations. Heterogeneity was high for the majority of outcomes. Manual fundal pressure versus no fundal pressure Manual fundal pressure was not associated with changes in: spontaneous vaginal birth within a specified time (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.71 to 1.28; 120 women; 1 trial; very low-quality evidence), instrumental births (RR 3.28, 95% CI 0.14 to 79.65; 197 women; 1 trial), caesarean births (RR 1.10, 95% CI 0.07 to 17.27; 197 women; 1 trial), operative birth (average RR 0.66, 95% CI 0.12 to 3.55; 317 women; 2 studies; I2 = 43%; Tau2 = 0.71; very low-quality evidence), duration of second stage (mean diGerence (MD) -0.80 minutes, 95% CI -3.66 to 2.06 minutes; 194 women; 1 study; very low-quality evidence), low arterial cord pH in newborn babies (RR 1.07, 95% CI 0.72 to 1.58; 297 women; 2 trials; very low-quality evidence), or Apgar scores less than seven at five minutes (average RR 4.48, 95% CI 0.28 to 71.45; 2759 infants; 4 trials; I2 = 89%; Tau2 = 3.55; very low-quality evidence). More women who received manual fundal pressure had cervical tears than in the control group (RR 4.90, 95% CI 1.09 to 21.98; 295 women; 1 trial). No neonatal deaths occurred in either of the two studies reporting this outcome (very low-quality evidence). No trial reported the outcome severe maternal morbidity or death. Fundal pressure by inflatable belt versus no fundal pressure Fundal pressure by inflatable belt did not reduce the number of women havinginstrumental births (average RR 0.73, 95% CI 0.52 to 1.02; 891 women; 4 trials; I2 = 52%; Tau2 = 0.05) or operative births (average RR 0.62, 95% CI 0.38 to 1.01; 891 women; 4 trials; I2 = 78%; Tau2 = 0.14; very low-quality evidence). Heterogeneity was high for both outcomes. Duration of second stage was reported in two trials, which both showed that inflatable belts shortened duration of labour in nulliparous women (average MD -50.80 minutes, 95% CI -94.85 to -6.74 minutes; 253 women; 2 trials; I2 = 97%; Tau2 = 975.94; very low-quality evidence). No data on this outcome were available for multiparous women. The inflatable belt did not make any diGerence to rates of caesarean births (average RR 0.56, 95% CI 0.14 to 2.26; 891 women; 4 trials; I2 = 70%; Tau2 = 0.98), low arterial cord pHin newborn babies (RR 0.47, 95% CI 0.09 to 2.55; 461 infants; 1 trial; low-quality evidence), or Apgar scores less than seven atfive minutes (RR 4.62, 95% CI 0.22 to 95.68; 500 infants; 1 trial; very low-quality evidence). Third degree perinealtears were increased in the inflatable belt group (RR 15.69, 95% CI 2.10 to 117.02; 500 women; 1 trial). Spontaneous vaginal birth within a specified time, neonatal death, andsevere maternal morbidity or death were not reported in any trial. Authors' conclusions There is insuGicient evidence to draw conclusions on the beneficial or harmful eGects of fundal pressure, either manually or by inflatable belt. Fundal pressure by an inflatable belt during the second stage of labour may shorten duration of second stage for nulliparous women, and lower rates of operative birth. However, existing studies are small and their generalizability is uncertain. There is insuGicient evidence regarding safety for the baby. There is no evidence on the use of fundal pressure in specific clinical settings such as inability of the mother to bear down due to exhaustion or unconsciousness. There is currently insuGicient evidence for the routine use of fundal pressure by any method on women in the second stage of labour. Because of current widespread use of the procedure and the potential for use in settings where other methods of assisted birth are not available, further good quality trials are needed. Further evaluation in other groups of women (such as multiparous women) will also be required. Future research should describe in detail how fundal pressure was applied and consider safety of the unborn baby, perineal outcomes, longer-term maternal and infant outcomes and maternal satisfaction

Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Background: Despite the global burden of morbidity and mortality associated with preterm birth, little evidence is available for use of antenatal corticosteroids and tocolytic drugs in preterm births in low-income and middle-income countries. We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) to assess coverage for these interventions in preterm deliveries. Methods: WHOMCS is a facility-based, cross-sectional survey database of birth outcomes in 359 facilities in 29 countries, with data collected prospectively from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries after 22 weeks’ gestation and we excluded births that occurred outside a facility or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids in women who gave birth between 26 and 34 weeks’ gestation, when antenatal corticosteroids are known to be most beneficial. We also calculated use in women at 22–25 weeks’ and 34–36 weeks’ gestation. We assessed tocolytic drug use, with and without antenatal corticosteroids, in spontaneous, uncomplicated preterm deliveries at 26–34 weeks’ gestation. Findings: Of 303 842 recorded deliveries after 22 weeks’ gestation, 17 705 (6%) were preterm. 3900 (52%) of 7547 women who gave birth at 26–34 weeks’ gestation, 94 (19%) of 497 women who gave birth at 22–25 weeks’ gestation, and 2276 (24%) of 9661 women who gave birth at 35–36 weeks’ gestation received antenatal corticosteroids. Rates of antenatal corticosteroid use varied between countries (median 54%, range 16–91%; IQR 30–68%). Of 4677 women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated with bed rest or hydration and 2248 (48%) received no treatment. β-agonists alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of potentially eligible women received both a tocolytic drug and antenatal corticosteroids. Interpretation: Use of interventions was generally poor, despite evidence for their benefit for newborn babies. A substantial proportion of antenatal corticosteroid use occurred at gestational ages at which benefit is controversial, and use of less effective or potentially harmful tocolytic drugs was common. Implementation research and contextualised health policies are needed to improve drug availability and increase compliance with best obstetric practice

Healthcare providers experiences of using uterine balloon tamponade (UBT) devices for the treatment of post-partum haemorrhage: A meta-synthesis of qualitative studies

Background: Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and severe morbidity globally. When PPH cannot be controlled using standard medical treatments, uterine balloon tamponade (UBT) may be used to arrest bleeding. While UBT is used by healthcare providers in hospital settings internationally, their views and experiences have not been systematically explored. The aim of this review is to identify, appraise and synthesize available evidence about the views and experiences of healthcare providers using UBT to treat PPH. Methods: Using a pre-determined search strategy, we searched MEDLINE, CINAHL, PsycINFO, EMBASE, LILACS, AJOL, and reference lists of eligible studies published 1996–2019, reporting qualitative data on the views and experiences of health professionals using UBT to treat PPH. Author findings were extracted and synthesised using techniques derived from thematic synthesis and confidence in the findings was assessed using GRADE-CERQual. Results: Out of 89 studies we identified 5 that met our inclusion criteria. The studies were conducted in five low- and middle-income countries (LMICs) in Africa and reported on the use of simple UBT devices for the treatment of PPH. A variety of cadres (including midwives, medical officers and clinical officers) had experience with using UBTs and found them to be effective, convenient, easy to assemble and relatively inexpensive. Providers also suggested regular, hands-on training was necessary to maintain skills and highlighted the importance of community engagement in successful implementation. Conclusions: Providers felt that administration of a simple UBT device offered a practical and cost-effective approach to the treatment of uncontrolled PPH, especially in contexts where uterotonics were ineffective or unavailable or where access to surgery was not possible. The findings are limited by the relatively small number of studies contributing to the review and further research in other contexts is required to address wider acceptability and feasibility issues