Costing the impact of interventions during pregnancy in the UK: a systematic review of economic evaluations.

OBJECTIVE: The aim of this review was to summarise the current evidence on the costing of resource use within UK maternity care, in order to facilitate the estimation of incremental resource and cost impacts potentially attributable to maternity care interventions. METHODS: A systematic review of economic evaluations was conducted by searching Medline, the Health Management Information Consortium, the National Health Service (NHS) Economic Evaluations Database, CINAHL and National Institute for Health and Care Excellence (NICE) guidelines for economic evaluations within UK maternity care, published between January 2010 and August 2019 in the English language. Unit costs for healthcare activities provided to women within the antenatal, intrapartum and postnatal period were inflated to 2018-2019 prices. Assessment of study quality was performed using the Quality of Health Economic Analyses checklist. RESULTS: Of 5084 titles or full texts screened, 37 papers were included in the final review (27 primary research articles, 7 review articles and 3 economic evaluations from NICE guidelines). Of the 27 primary research articles, 21 were scored as high quality, 3 as medium quality and 3 were low quality. Variation was noted in cost estimates for healthcare activities throughout the maternity care pathway: for midwife-led outpatient appointment, the range was £27.34-£146.25 (mean £81.78), emergency caesarean section, range was £1056.44-£4982.21 (mean £3508.93) and postnatal admission, range was £103.00-£870.10 per day (mean £469.55). CONCLUSIONS: Wide variation exists in costs applied to maternity healthcare activities, resulting in challenges in attributing cost to maternity activities. The level of variation in cost calculations is likely to reflect the uncertainty within the system and must be dealt with by conducting sensitivity analyses. Nationally agreed prices for granular unit costs are needed to standardise cost-effectiveness evaluations of new interventions within maternity care, to be used either for research purposes or decisions regarding national intervention uptake. PROSPERO REGISTRATION NUMBER: CRD42019145309

Using electronic patient records to assess the effect of a complex antenatal intervention in a cluster randomised controlled trial-data management experience from the DESiGN Trial team.

BACKGROUND: The use of electronic patient records for assessing outcomes in clinical trials is a methodological strategy intended to drive faster and more cost-efficient acquisition of results. The aim of this manuscript was to outline the data collection and management considerations of a maternity and perinatal clinical trial using data from electronic patient records, exemplifying the DESiGN Trial as a case study. METHODS: The DESiGN Trial is a cluster randomised control trial assessing the effect of a complex intervention versus standard care for identifying small for gestational age foetuses. Data on maternal/perinatal characteristics and outcomes including infants admitted to neonatal care, parameters from foetal ultrasound and details of hospital activity for health-economic evaluation were collected at two time points from four types of electronic patient records held in 22 different electronic record systems at the 13 research clusters. Data were pseudonymised on site using a bespoke Microsoft Excel macro and securely transferred to the central data store. Data quality checks were undertaken. Rules for data harmonisation of the raw data were developed and a data dictionary produced, along with rules and assumptions for data linkage of the datasets. The dictionary included descriptions of the rationale and assumptions for data harmonisation and quality checks. RESULTS: Data were collected on 182,052 babies from 178,350 pregnancies in 165,397 unique women. Data availability and completeness varied across research sites; each of eight variables which were key to calculation of the primary outcome were completely missing in median 3 (range 1-4) clusters at the time of the first data download. This improved by the second data download following clarification of instructions to the research sites (each of the eight key variables were completely missing in median 1 (range 0-1) cluster at the second time point). Common data management challenges were harmonising a single variable from multiple sources and categorising free-text data, solutions were developed for this trial. CONCLUSIONS: Conduct of clinical trials which use electronic patient records for the assessment of outcomes can be time and cost-effective but still requires appropriate time and resources to maximise data quality. A difficulty for pregnancy and perinatal research in the UK is the wide variety of different systems used to collect patient data across maternity units. In this manuscript, we describe how we managed this and provide a detailed data dictionary covering the harmonisation of variable names and values that will be helpful for other researchers working with these data. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 02/11/16

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care

Differences in Factors Associated With Preterm and Term Stillbirth: A Secondary Cohort Analysis of the DESiGN Trial.

OBJECTIVE: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth. DESIGN: Secondary cohort analysis of the DESiGN RCT. SETTING: Thirteen UK maternity units. POPULATION: Singleton pregnant women and their babies. METHODS: Multiple logistic regression was used to assess whether the 12 factors explored were associated with stillbirth. Interaction tests assessed for a difference in these associations between the preterm and term periods. MAIN OUTCOME MEASURE: Stillbirth stratified by preterm (<37+0 weeks') and term (37+0-42+6 weeks') births. RESULTS: A total of 195 344 pregnancies were included. Six hundred and sixty-seven were stillborn (3.4 per 1000 births), of which 431 (65%) were preterm. Significant interactions were observed for maternal age, ethnicity, IMD, BMI, parity, smoking, PAPP-A, gestational hypertension, pre-eclampsia and gestational diabetes but not for chronic hypertension and pre-existing diabetes. Stronger associations with term stillbirth were observed in women with obesity compared to BMI 18.5-24.9 kg/m2 (BMI 30.0-34.9 kg/m2 term adjusted OR 2.1 [95% CI 1.4-3.0] vs. preterm aOR 1.1 [0.8-1.7]; BMI ≥ 35.0 kg/m2 term aOR 2.2 [1.4-3.4] vs. preterm aOR 1.5 [1.2-1.8]; p-interaction < 0.01), nulliparity compared to parity 1 (term aOR 1.7 [1.1-2.7] vs. preterm aOR 1.2 [0.9-1.6]; p-interaction < 0.01) and Asian ethnicity compared with White (p-interaction < 0.01). A weaker or lack of association with term, compared to preterm, stillbirth was observed for older maternal age, smoking and pre-eclampsia. CONCLUSION: Differences in association exist between mothers experiencing preterm and term stillbirth. These differences could contribute to design of timely surveillance and interventions to further mitigate the risk of stillbirth

Characteristics associated with antenatally unidentified small-for-gestational-age fetuses: prospective cohort study nested within the DESiGN randomized control trial.

OBJECTIVE: To identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with antenatally unidentified SGA, compared to those in which it is identified, to understand how to better design interventions that improve antenatal SGA identification. METHODS: A prospective cohort study of singleton, non-anomalous, small for gestational age (SGA, birthweight<10th centile) babies born after 24+0 gestational weeks, from 13 UK sites, collected for the baseline period and control arm of the DESiGN trial. We define pregnancies with antenatally unidentified SGA where there was no scan or a final scan with estimated fetal weight, EFW, at 10th centile or above; and as identified SGA if EFW was below 10th centile at last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, ultrasound frequency, duration between the last scan and the birth, absolute centile difference between the last scan and the birth) were described and associations with missed SGA were also studied by unadjusted and adjusted logistic regression but stratified by presence of indications for serial ultrasound. RESULTS: Of the 15,784 SGA babies included, SGA was not identified antenatally in 78.7%. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9,410 pregnancies with complete data on key maternal co-morbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (aOR 0.56, 95% CI: 0.49-0.64), Asian ethnicity (aOR 0.80 compared to white, 95% CI: 0.69-0.93) and non-cephalic presentation (aOR 0.58, 95% CI: 0.46-0.73). The risk of unidentified SGA was highest among women with BMI 25.0-29.9 kg/m2 (aOR 1.15 compared to 18.5-24.9 kg/m2 , 95% CI: 1.01-1.32) and lowest in those with underweight BMI (aOR 0.61, 95% CI: 0.48-0.76). Compared to women with identified SGA, those with unidentified SGA had fetuses of higher SGA birthweight centile (adjusted mean difference 1.21, 95% CI: 1.18-1.23). Duration between the last scan and birth increased with advancing gestation in pregnancies with unidentified SGA. SGA babies born within a week of the last growth scan had a mean EFW: birthweight centile difference of +19.5 (SD: 13.8) for unidentified SGA babies and +0.2 (SD: 3.3) for identified SGA babies (adjusted difference 19.0, CI: 17.8-20.1). CONCLUSIONS: Unidentified SGA was more common amongst women without indications for serial ultrasound, cephalic presentation, BMI 25.0-29.9 kg/m2 and less severe SGA. Ultrasound EFW was overestimated in women with unidentified SGA. This demonstrates the importance of improving the accuracy of SGA screening strategies in low-risk populations, and continuing ultrasound scans for term pregnancies. This article is protected by copyright. All rights reserved

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVES: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESIGN trial, is cost-effective in terms of antenatal detection of small for gestational age (SGA) neonates, when compared to standard care. METHODS: Design: An incremental cost-effectiveness analysis undertaken from a UK National Health Service hospital provider perspective. SETTING: Thirteen maternity units from England, UK, were recruited to the DESiGN trial, a randomised cluster control trial. POPULATION: Singleton, non-anomalous pregnancies in which the baby was born after 24+0 gestational weeks between 05 November 2015 and 28 February 2019. ANALYSIS: Probabilistic decision modelling using clinical trial data. MAIN OUTCOME MEASURES: The expected incremental cost of GAP and additional number of SGA neonates identified antenatally, the incremental cost-effectiveness ratio (ICER) of GAP (cost per additional SGA neonate identified). Secondary analysis: the ICER estimated as the incremental cost per infant quality adjusted life year (QALY) gained. RESULTS: The expected incremental cost of GAP over standard care was an additional £34,559 per 1000 pregnancies with a 68% probability that GAP would increase costs (including hospital care and implementation costs) to sustain programme delivery. GAP identified an additional 1.77 SGA neonates per 1000 pregnancies (55% probability of being more clinically effective). The ICER for GAP was £19,525 per additional SGA neonate identified (44% probability that GAP would jointly increase cost and identify more SGA neonates than standard care). The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental additional cost per infant QALY gained ranged from £68,242 to £545,940 depending on assumptions regarding the QALY value of SGA detection. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported here. This conclusion should be viewed in the context that cost-effectiveness analyses are always limited by the assumptions made, and our study is no different. This article is protected by copyright. All rights reserved

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol

Objective: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. Methods: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. Results: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. Conclusion: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology