Planned early delivery versus expectant management to reduce adverse pregnancy outcomes in pre-eclampsia in a low- and middle-income setting: study protocol for a randomised controlled trial (CRADLE-4 Trial).
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SUBMITTER: Beardmore-Gray A
PROVIDER: S-EPMC7684962 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Planned early delivery versus expectant management to reduce adverse pregnancy outcomes in pre-eclampsia in a low- and middle-income setting: study protocol for a randomised controlled trial (CRADLE-4 Trial).
Beardmore-Gray Alice A Vousden Nicola N Charantimath Umesh U Katageri Geetanjali G Bellad Mrutyunjaya M Kapembwa Kunda K Chinkoyo Sebastian S Vwalika Bellington B Clark Matthew M Hunter Rachael R Seed Paul P Goudar Shivaprasad S Chappell Lucy C LC Shennan Andrew A
Trials 20201123 1
<h4>Background</h4>Pre-eclampsia is a pregnancy complication characterised by high blood pressure and multi-organ dysfunction in the mother. It is a leading contributor to maternal and perinatal mortality, with 99% of these deaths occurring in low- and middle-income countries (LMIC). Whilst clear guidelines exist for management of early-onset (< 34 weeks) and term (≥ 37 weeks) disease, the optimal timing of delivery in pre-eclampsia between 34<sup>+ 0</sup> and 36<sup>+ 6</sup> weeks is less cle ...[more]
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Project description:BackgroundPre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity globally. Planned delivery between 34+0 and 36+6 weeks may reduce adverse pregnancy outcomes but is yet to be evaluated in a low and middle-income setting. Prior to designing a randomised controlled trial to evaluate this in India and Zambia, we carried out a 6-month feasibility study in order to better understand the proposed trial environment and guide development of our intervention.MethodsWe used mixed methods to understand the disease burden and current management of pre-eclampsia at our proposed trial sites and explore the acceptability of the intervention. We undertook a case notes review of women with pre-eclampsia who delivered at the proposed trial sites over a 3-month period, alongside facilitating focus group discussions with women and partners and conducting semi-structured interviews with healthcare providers. Descriptive statistics were used to analyse audit data. A thematic framework analysis was used for qualitative data.ResultsCase notes data (n = 326) showed that in our settings, 19.5% (n = 44) of women with pre-eclampsia delivering beyond 34 weeks experienced an adverse outcome. In women delivering between 34+0 and 36+6 weeks, there were similar numbers of antenatal stillbirths [n = 3 (3.3%)] and neonatal deaths [n = 3 (3.4%)]; median infant birthweight was 2.2 kg and 1.9 kg in Zambia and India respectively. Lived experience of women and healthcare providers was an important facilitator to the proposed intervention, highlighting the serious consequences of pre-eclampsia. A preference for spontaneous labour and limited neonatal resources were identified as potential barriers.ConclusionsThis study demonstrated a clear need to evaluate the intervention and highlighted several challenges relating to trial context that enabled us to adapt our protocol and design an acceptable intervention. Our study demonstrates the importance of assessing feasibility when developing complex interventions, particularly in a low-resource setting. Additionally, it provides a unique insight into the management of pre-eclampsia at our trial settings and an understanding of the knowledge, attitudes and beliefs underpinning the acceptability of planned early delivery.
| S-EPMC8173959 | biostudies-literature
Project description:BackgroundIn women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia.MethodsIn this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing.FindingsBetween Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79-0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08-1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group.InterpretationThere is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery.FundingNational Institute for Health Research Health Technology Assessment Programme.
| S-EPMC6892281 | biostudies-literature
Project description:BackgroundPre-eclampsia is a pregnancy disorder, characterised by hypertension and multisystem complications in the mother. The adverse outcomes of pre-eclampsia include severe hypertension, stroke, renal and hepatic injury, haemorrhage, fetal growth restriction and even death. The optimal time to instigate delivery to prevent morbidity when pre-eclampsia occurs between 34 and 37?weeks' gestation, without increasing problems related to infant immaturity or complications, remains unclear.Methods/designThe PHOENIX trial is a non-masked, randomised controlled trial, comparing planned early delivery (with initiation of delivery within 48?h of randomisation) with usual care (expectant management) in women with pre-eclampsia between 34+?0 and 36+?6 weeks' gestation. The primary objectives of the trial are to determine if planned delivery reduces adverse maternal outcomes, without increasing the short-term harm to infants (composite of perinatal deaths or neonatal unit admissions up to infant hospital discharge) or impacting long-term infant neurodevelopmental status at 2 years corrected age (Parent Report of Cognitive Abilities-Revised).DiscussionCurrent practice in the UK at the time of trial commencement for management of pre-eclampsia varies by gestation. Previous trials have shown that in women with pre-eclampsia after 37?weeks of gestion, delivery is initiated, as maternal complications are reduced without increasing fetal risks. Prior to 34?weeks of gestation, usual management aims to prolong pregnancy for fetal benefit, unless severe complications occur, necessitating preterm delivery. This trial aims to address the uncertainty for women where the balance of benefits and risks of delivery compared to expectant management are uncertain. Previous trials in this area have been undertaken, but have not provided a definitive answer, and the research question remains active. The results of this trial are expected to influence clinical practice internationally, through direct adoption and by incorporation into guidelines in countries with similar settings.Trial registrationISRCTN01879376 . Registered on 25 November 2013.
| S-EPMC6350286 | biostudies-literature
Project description:BACKGROUND:Hypertensive disorders in pregnancy, specifically pre-eclampsia and eclampsia (PE/E), are the second biggest killer of pregnant women globally and remains the least understood and most challenging maternal morbidity to manage. Although great strides were made in reducing maternal and newborn mortality between 1990 and 2015, this was clearly not enough to achieve the global health goals. To reduce maternal deaths: 1) early detection of PE needs to be improved; 2) effective management of PE/E needs to occur at lower health system levels and should encourage timely care-seeking; and 3) prioritizing the scale up of a comprehensive package of services near to where women live. FINDINGS:This commentary describes a pragmatic approach to test scalable and sustainable strategies for expanding access to quality under-utilized maternal health commodities, interventions and services. We present a primary health care (PHC) PE/E Model based on implementation research on identified gaps in care in several countries, accepted global best practice and built on the basic premise that PHC providers can take on additional skills with adequate capacity building, coaching and supervision, and community members desire control over their own health. The PHC PE/E model displays the linkages and opportunities to prevent and treat PE/E in a simplified way; however, there are numerous interlinking factors, angles, and critical points to consider including leadership, policies and protocols; relevant medicines and commodities, ongoing capacity building strategies at lower levels and understanding what women and their communities want for safe pregnancies. CONCLUSION:The PHC model described here uses PE/E as an entry to improve the quality of ANC and by extension the pregnancy continuum. Bringing preventive and treatment services nearer to where pregnant women live makes sense.
| S-EPMC7132984 | biostudies-literature
Project description:OBJECTIVE:This study describes the availability of core parameters for Early Warning Scores (EWS), evaluates the ability of selected EWS to identify patients at risk of death or other adverse outcome and describes the burden of triggering that front-line staff would experience if implemented. DESIGN:Longitudinal observational cohort study. SETTING:District General Hospital Monaragala. PARTICIPANTS:All adult (age >17 years) admitted patients. MAIN OUTCOME MEASURES:Existing physiological parameters, adverse outcomes and survival status at hospital discharge were extracted daily from existing paper records for all patients over an 8-month period. STATISTICAL ANALYSIS:Discrimination for selected aggregate weighted track and trigger systems (AWTTS) was assessed by the area under the receiver operating characteristic (AUROC) curve.Performance of EWS are further evaluated at time points during admission and across diagnostic groups. The burden of trigger to correctly identify patients who died was evaluated using positive predictive value (PPV). RESULTS:Of the 16?386 patients included, 502 (3.06%) had one or more adverse outcomes (cardiac arrests, unplanned intensive care unit admissions and transfers). Availability of physiological parameters on admission ranged from 90.97% (95% CI 90.52% to 91.40%) for heart rate to 23.94% (95% CI 23.29% to 24.60%) for oxygen saturation. Ability to discriminate death on admission was less than 0.81 (AUROC) for all selected EWS. Performance of the best performing of the EWS varied depending on admission diagnosis, and was diminished at 24?hours prior to event. PPV was low (10.44%). CONCLUSION:There is limited observation reporting in this setting. Indiscriminate application of EWS to all patients admitted to wards in this setting may result in an unnecessary burden of monitoring and may detract from clinician care of sicker patients. Physiological parameters in combination with diagnosis may have a place when applied on admission to help identify patients for whom increased vital sign monitoring may not be beneficial. Further research is required to understand the priorities and cues that influence monitoring of ward patients. TRIAL REGISTRATION NUMBER:NCT02523456.
| S-EPMC5922475 | biostudies-literature
Project description: Not available
| S-EPMC6465052 | biostudies-literature
Project description:BackgroundLow socioeconomic status (SES) is associated with more adverse perinatal health outcomes, risk factors and lower access to and use of maternal health care services. However, evidence for the association between SES and maternal health outcomes is limited, particularly for middle-income countries like sub-Saharan Ghana. We assessed the association between parental SES and adverse maternal and perinatal outcomes of Ghanaian women during pregnancy, delivery and the postpartum period.MethodsA prospective cohort study of 1010 women of two public hospitals in Accra, Ghana (2012-2014). SES was proxied by maternal and paternal education, wealth and employment status. The association of SES with maternal and perinatal outcomes was analyzed with multivariable logistic and linear regression.ResultsThe analysis included 790 women with information on pregnancy outcomes. Average age was 28.2?years (standard deviation, SD 5.0). Over a third (n?=?292, 37.0%) had low SES, 176 (22.3%) were classified to have high SES using the assets index. Nearly half (n?=?374, 47.3%) of women had lower secondary school or vocational training as highest education level. Compared to women with middle assets SES, women with low assets SES were at higher risk for miscarriage (odds ratio, OR 1.61, 95% CI 1.06 to 2.45) and instrumental delivery (OR 1.74, 95% CI 1.03 to 2.94), but this association was not observed for the other SES proxies. For any of the maternal or perinatal outcomes and SES proxies, no other statistically significant differences were found.ConclusionWomen attending public maternal health care services in urban Ghana had overall equitable maternal and perinatal health outcomes, with the exception of a higher risk of miscarriage and instrumental delivery associated with low assets SES. This suggests known associations between SES, risk factors and outcomes could be mitigated with universal and accessible maternal health services.
| S-EPMC6580627 | biostudies-literature
Project description:ObjectiveTo assess the effect of short message service (SMS) communication on facility delivery, exclusive breastfeeding (EBF), and contraceptive use.DesignMobile WACh was a three-arm unblinded individually randomised controlled trial.SettingA public sector maternal child health (MCH) clinic in Nairobi, Kenya.PopulationThree hundred women attending antenatal care were randomised, 100 to each arm, and followed for 24 weeks postpartum. Pregnant women, at least 14 years old with access to a mobile phone and able to read SMS were eligible for participation.MethodsWomen were randomised (1:1:1) to receive one-way SMS versus two-way SMS with a nurse versus control. Weekly SMS content was tailored for maternal characteristics and pregnancy or postpartum timing.Main outcome measuresFacility delivery, EBF, and contraceptive use were compared separately between each intervention arm and the control arm by Kaplan-Meier analysis and chi-square tests using intent-to-treat analyses.ResultsThe overall facility delivery rate was high (98%) and did not differ by arm. Compared with controls, probability of EBF was higher in the one-way SMS arm at 10 and 16 weeks, and in the two-way SMS arm at 10, 16, and 24 weeks (P < 0.005 for all). Contraceptive use was significantly higher in both intervention arms by 16 weeks (one-way SMS: 72% and two-way SMS: 73%; P = 0.03 and P = 0.02 versus 57% control, respectively); however, this difference was not significant when correcting for multiple comparisons.ConclusionOne-way and two-way SMS improved EBF practices and early contraceptive use. Two-way SMS had an added benefit on sustained EBF, providing evidence that SMS messaging influences uptake of interventions that improve maternal and neonatal health.Source of fundingFunding was provided by the National Institutes of Health (K12HD001264 to JAU, R01HD080460, K24HD054314 to GJS, and K01AI116298 to ALD), the National Science Foundation (Graduate Research Fellowship to TP and BD), as well as the University of Washington Global Center for Integrated Health of Women Adolescents and Children (Global WACh).Tweetable abstractThe Mobile WACh RCT demonstrates that SMS improved practice of exclusive breastfeeding and early postpartum contraception.
| S-EPMC6179930 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is a leading cause of childhood mortality in infants below 6 months of age. In low-income and middle-income countries (LMICs), the public health burden is substantial and resources are limited. It is critical to inform decision makers about effectiveness of new interventions.MethodsWe developed a mathematical model where individual RSV subtype A (RSV-A) and B (RSV-B) maternally derived neutralizing titers were predicted at time of birth after maternal vaccination with the RSV prefusion F protein-based vaccine. We estimated the subsequent duration of vaccine-induced immunity and compared this to the age at time of death distribution in the RSV GOLD Mortality Database to predict the potential impact of maternal vaccination on RSV-related childhood mortality. We used country-specific timing of antenatal care visits distributions and mortality estimates to make country-specific predictions for number of cases averted.FindingsThe model predicts that on average a neonate born at 40 weeks gestational age will be protected between 6 and 7 months from RSV-A and approximately 5 months from RSV-B related mortality. We estimated the potential impact of RSV-related mortality for in-hospital and out-of-hospital cases in LMICs and predicted that in 51 GAVI-eligible countries maternal vaccination could avert between 55% and 63% of the RSV-related in-hospital mortality cases below 6 months of age.InterpretationWe show that maternal vaccination could substantially decrease RSV-A and RSV-B related in-hospital and out-of-hospital mortality in LMICs in the first 6 months of life.
| S-EPMC10498305 | biostudies-literature
Project description:ObjectivesThis systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC).DesignWe searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020.SettingObservational or interventional studies from LMICs.ParticipantsSingleton pregnancies of any risk profile.InterventionsUmbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava.Primary and secondary outcome measuresPerinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO).ResultsWe identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations.ConclusionLocal evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative.Prospero registration numberCRD42019128546.
| S-EPMC8640672 | biostudies-literature