4.2. Viabilidad de mercado
4.2.5. Resultados y análisis de las encuestas aplicadas
Chapter 6: Conclusion
6.1.SUMMARY OF RESULTS
This study has shown that combined screening by maternal factors and EFW Z-score at 35-37 weeks, predicted 90%, 92% and 94% of SGA neonates with birth weight <10th, <5th and <3rd percentiles delivering at <2 weeks of assessment, at 10% false positive rate; the respective values for SGA delivering at >37 weeks were 66%, 73% and 80%.
Addition of UtA PI and MAP to combined testing using maternal factors and fetal biometry at 35-37 weeks has not improved the performance of screening.
When PlGF and sFlt-1 were both added to a model that combines maternal factors and EFW Z-score, sFlt-1 did not remain as a significant independent predictor of SGA <5th. Combined screening by maternal factors, EFW Z-score and serum PlGF, predicted 88%, 96% and 94% of SGA neonates with birth weight <10th, <5th and <3rd percentiles delivering at <2 weeks of assessment and the respective values for SGA delivering at >37 weeks were 64%, 75% and 80%. Hence, addition of serum PlGF only marginally improves the performance of screening.
Such performance of screening is superior to that achieved by the current method in the UK, which is based on maternal characteristics and measurement of SFH21.
6.2.STRENGTHS AND LIMITATIONS
This study has several strengths. Firstly, this was the largest routine screening study carried out at 35-37 weeks, a gestational age when there was few literature regarding assessing fetal growth and wellbeing. Secondly, the study ensured that only appropriately trained doctors, certified by the Fetal Medicine Foundation, using specific methodology undertook the measurements of HC, AC FL, MAP and uterine artery PI. Thirdly, it assessed two biochemical markers (PlGF and sFlt-1), which have been associated with impaired placentation at late third trimester. Fourthly, the study used Bayes theorem to combine the prior risk from maternal characteristics and medical history with biomarkers, to estimate patient-specific risks and the performance of screening for SGA of different
severities delivering at selected intervals from the time of assessment, which is an essential step for establishing patient management protocols.
The main limitation of the study is that the patient's obstetricians were made aware of the screening results. This would have led to further monitoring of identified SGA fetuses and possible delivery. Such intervention would positively bias the performance of screening, particularly those delivering within 2 weeks of assessment.
6.3.IMPLICATIONS FOR CLINICAL PRACTICE
This study has the potential to influence clinical practice. Since completion of the studies in this thesis, colleagues from the same department have examined the potential value of screening for SGA neonates at 30-34 weeks’ gestation. They compared screening at 30- 34 weeks, also with biophysical and biochemical markers, namely, maternal factors, EFW, UtA PI, MAP and the PlGF (sFlt-1 was not included, as the use of PlGF alone was better predictor than PlGF and sFlt-1). The DRs, at a FPR of 10%, of SGA neonates with BW
<10th, <5th and<3rd percentiles delivering ≥37 weeks were 57%, 65%, 71%192 compared with our study's results of 64%, 75%, and 80%. Thus, the 35-37 weeks scan performed better for detection of SGA ≥ 37 weeks.
In the proposed new pyramid of pregnancy care193, an integrated clinic at 11-13 weeks’ gestation, in which biophysical and biochemical markers are combined with maternal characteristics and medical history, aims to identify pregnancies at high-risk of developing PE and/or SGA137, 194 and through pharmacological intervention (eg, aspirin) to reduce the prevalence of these complications195-198.
The objective of subsequent visits, at around 22 and 32 or 36 weeks’ gestation, are to identify the high-risk group and through close monitoring of such pregnancies to minimize adverse perinatal events by determining the appropriate time and place for iatrogenic delivery. It was proposed that all women should be offered a third-trimester scan for assessment of fetal growth and wellbeing and that the timing of such scan, at 32 and/or 36 weeks, should be contingent on the results of assessment at around 22 weeks187-188,199.
The 19-24 gestational weeks' model, simultaneously proposed by colleagues of the same Department199, uses maternal factors, fetal biometry, UtA-PI and serum PlGF and AFP as
significant independent contributions to the prediction of SGA (< 5th percentile). The detection rate (DR) of such combined screening at 19-24 weeks was 100%, 78% and 42% for SGA (< 5th percentile) delivering < 32, at 32-36 and ≥ 37 weeks' gestation, respectively, at a false-positive rate (FPR) of 10%. In a hypothetical model, it was estimated that if the desired objective of prenatal screening is to predict about 80% of the cases of SGA < 5th, at a FPR of 10%, it would be necessary to select 11% of the population at the 19-24-week assessment to be reassessed at 32 weeks and 44% to be reassessed at 36 weeks; 57% would not require a third-trimester scan.
Following a 35-37 weeks scan, on the basis of results from this thesis study, if the assessment includes a combination of maternal factors, fetal biometry and serum PlGF, potentially 80%, 90% and 100% of cases of SGA <5th without PE could be detected at respective FPRs of 14%, 21% and 75%. The subsequent management of the screen positive group with the objective of reducing perinatal death and handicap remains to be determined.
Regarding the timing of the 35-37 weeks routine appointment, which up until the publication of the studies of this thesis there was very scarce information on, it can also be useful, not only to predict SGA without PE, but also to predict term pre-eclampsia. Colleagues from the same department200 developed a model for prediction of term pre- eclampsia (PE) based on a combination of maternal factors and late third-trimester biomarkers. Screening for term PE by a combination of maternal factors, MAP, PlGF and
sFlt‐1 at 35–37 weeks' gestation predicted about 85% of affected pregnancies, at a FPR
of 10%. Hence, the screening performance at 35-37 weeks for late PE is also superior to that achieved by screening at 11–13, 19–24 or 30–34 weeks, with respective DRs of 47%, 46% and 66%.
Since the publication and presentation of the data in this thesis, late third trimester routine growth scans have been progressively implemented and further studies have been being pursued in this field.
6.4.FUTURE STUDIES
The proposed model from this thesis for prediction of SGA neonates requires prospective intervention studies that would firstly, evaluate the predicted performance of such
screening and secondly, examine the extent to which such assessment and appropriate management of the high-risk pregnancies can reduce the high perinatal mortality and morbidity associated with SGA fetuses.