Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04764461 |
| Other study ID # |
FMH01 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 14, 2021 |
| Est. completion date |
July 15, 2022 |
Study information
| Verified date |
February 2021 |
| Source |
Fatima Memorial Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A prospective randomised control trial to evaluate the effectiveness of customised growth
charts for detection of small for gestational age fetus in low risk women, in comparison to
conventional standard of care.
Description:
The most sensitive quality index of women and child health is perinatal mortality rate. The
annual toll of losses includes about 3 million stillbirths and 3.8 million neonatal deaths:
half die on the first day of life.1,2 The top ten countries with highest neonatal death rate
are India, Nigeria, Pakistan, China, DR Congo, Ethopia, Bangladesh, Indonesia, Afghanistan
and Sudan. These countries encompass 67% and 63% of the global total with 1.5 million
neonatal deaths and 1.77 million stillbirths.3 Pakistan is the country with the highest
stillbirth rate of 43.1 stillbirths per 1000 total births when compared to a global estimate
of 18.4 in 2015.4 The most common condition associated with stillbirth is SGA, conventionally
defined as a fetus with birth weight below 10th centile of its gestational age.5,6 SGA
accounts for 30% of total stillbirths, perinatal mortality being highest if remain undetected
before birth or when the birth weight is below the 3rd centile.7,8 One of the key strategy to
prevent stillbirth is prediction and recognition of growth restricted fetuses. Experts have
reached to consensus to use 32 weeks as a cutoff to define early and late onset growth
restriction.9 Early onset growth restricted fetuses have highl association with pre-eclampsia
and angiogenic disbalance and can be predicted in about 90% of cases by incorporating
maternal risk factors, uterine artery dopplers and angiogenic factors. Whereas late onset
FGR, using SGA as a proxy, remains unpredicted even after combining maternal characteristics,
risk factors, blood pressure records, second trimester biometry and uterine artery dopplers
(43.3% DR for 10% false positive rate).10 Late onset SGA with high prevalence around 10% are
associated with non-evident placental disease, resulting in clinical challenge in its
detection and diagnosis. Late onset SGA if remains undetected are at increased risk of
perinatal mortality (25-48% of non-anomalous stillbirths)5 and morbidity including fetal
distress, acidosis and admissions in neonatal intensive unit.11,12 Adverse long-term health
outcomes including type 2 diabetes, obesity and coronary heart disease are also associated
with late onset SGA.13,14,15 Unfortunately, the burden of small for gestational age births is
concentrated in South Asia, with prevalence of about 41.5%.16 To date, the research done in
Pakistan on small for gestational age fetus is sparse. The limited data quotes the incidence
of small for gestational age babies between 3-10% and accounts for 18% of stillbirths.17,18
One of the key objectives of antenatal care aiming at improving neonatal outcomes includes
recognition of risk factors, detection of growth restricted babies, longitudinal surveillance
and deciding the best time to deliver them. Six national guidelines on SGA by authorized
bodies of United Kingdom (RCOG)7, United States of America (ACOG)19, Ireland (Health service
Executive)20, Canada (Society of Obstetrician and gynecologist of Canada)21, New Zealand (New
Zealand Maternal Fetal medicine Network)22 and France (French College of Obstetrician and
Gynecologist)23 have a general consensus on first trimester booking screening for risk
factors of SGA and classifying woman into either high risk or low risk group. Risk factors
for SGA, requiring increased surveillance include maternal age > 40 years, cocaine abuse,
maternal or paternal SGA, previous history of SGA or still birth, chronic hypertension,
diabetes with vascular disease, renal impairment, PAPPA < 0.4 mom, echogenic bowel and
heaving bleeding similar to menses.24 All bodies except US recommends use of Aspirin from 16
weeks onward in all woman categorized as High risk. There is unanimous agreement on
surveillance with serial growth scans and umbilical artery dopplers. However, 4 national
bodies (RCOG, Health service Executive of Ireland, French College of Obstetrician and
Gynecologist & New Zealand Maternal Fetal medicine Network) recommends use of plotting EFW on
customized charts whereas, ACOG & SOGC does not specify EFW charts.24 For low risk woman the
antenatal screening practice comprises of fundal height measurements. All international
guidelines recommend a tape measure for fundal height measurement. Three guidelines (RCOG,
Health service Executive of Ireland and New Zealand Maternal Fetal medicine Network)7,20,22
advocates serial plotting of fundal height measurements on customized charts whereas, two
guidelines (ACOG & SOGC)19,21 recommends use of McDonalds rule and suspects suboptimal growth
when the fundal height measurement is > 3cm less than the gestational age in weeks. A single
RCT did not show any significant difference between palpation and fundal height measurements
in detection of SGA.25 A meta-analysis published in 2013 concluded symphysiofundal height
unsuitable as a primary screening method for detection of SGA and LBW, with 60% DR for SGA
for a false positive rate of 15%. The meta analysis comprised of 46 mostly hospital-based
studies, which may be a source of bias in concluding results. For prediction of LBW there was
no statistical difference between the pooled sensitivity and specificity (p=0.15 and 0.96,
respectively) of cohort verses case control studies and between prospective and retrospective
studies for prediction of SGA. Whereas, for prediction of SGA there was also no statistical
difference between the pooled sensitivity and specificity (p=0.26 and 0.65, respectively) of
cohort verses case control studies and on the contrary the prospective studies decreased the
pooled sensitivity (0.85 verses 0.89; p=0.00) in comparison to retrospective studies.26 A
prospective cohort study concluded that by Incorporating a third trimester scan to fundal
height measurements in low risk woman the detection rate for SGA can increase to 57%, whereas
selective use detected only 20% of SGA.27 On the contrary, all national guidelines do not
recommend routine third trimester scan for detection of SGA.7,19,20,21,22,23 The concept of
customized or GROW charts by Gardosi et al is based on the principles: 1. physiological
variables that impact fetal growth (maternal ethnicity, height, weight and parity) 2.
Excluding pathological conditions like diabetes, hypertension and smoking.28 Use of GROW
charts derived from uncomplicated pregnancies delineating estimated weight for a given
gestation. Gardosi et al reported the likelihood of detecting SGA by using standardized
fundal height measurement alone when plotted on a customized chart to 47.9% in contrary to
29.2% with conventional symphysis-fundal height measurement without increasing the
utilization of ultrasound scans.29 In 2013, the Perinatal institute of UK introduced Growth
assessment Protocol (GAP). GAP training encompasses of (1) staff training supported by
theoretical and practical e-learning modules, (2) clinical application of evidence based
guidelines including risk assessment, investigation and surveillance of fetal growth (3)
training and bringing accuracy in measuring and plotting fundal height on customized growth
charts (4) serial auditing to record process and outcome indicators and (5) audit of missed
cases to explore the reason of not being detected antenatally.30 This program has been
associated with increased detection rate of SGA and reduction in perinatal mortality.31 Based
on this evidence and Royal College of Obstetrician & Gynecologist recommendation, the GAP
program has been implemented in 80% of hospital trusts across UK. Recently a 10-year
population-based cohort study was conducted to evaluate effect of implementation of GAP
program and reduction in stillbirths in UK. Data of 6,561,560 births from 133 units in
England was analyzed and still birth rates were calculated and compared between non-GAP (39
units or 29.3%), partial GAP (29 units or 21.8%) and Complete GAP (65 units or 48.9%)
implementation units. There was an overall reduction in the stillbirth rate from 5.11/1000 to
4.18/1000, with reduction in still birth rate among all the three groups. However, the cross
sectional comparison between the two group showed a 9% lower still birth rate among GAP units
along with greater fall in stillbirth rate (24%) when compared to the than the non-GAP
units.32 GAP program when adopted outside UK, in The Royal women's Hospital, Melbourne,
resulted in doubled detection rate of SGA from 21% to 41% without increase in false positive
rate.33 Similarly, results of another non-randomized, quasi controlled, pre and posttest
designed study found doubling (24.8% to 50.6%) in detection rate of SGA after plotting serial
FH on customized charts as an intervention.34 A prospective observational study to determine
the diagnostic effectiveness of customized charts for identification of fetal growth patterns
concluded that serial SFH measurements has a positive likelihood ratio of 4.7 for the
detection of SGA.35 To date, all the published research demonstrating the effectiveness of
GAP program are non-randomized, prospective cohorts, pre and post implementation designed.
Therefore, making it impossible to determine whether it's the diagnostic effectiveness of the
customized chart alone or it's the GAP bundle comprising of staff education, training and
change in protocol resulting in increased detection rate of SGA. It is comprehensively
established that the best evidence is derived by RCT and so is highlighted in the Cochrane
review36. To the best of investigators knowledge no randomized controlled trial has been
published to compare the diagnostic effectiveness of serial standardized fundal height
measurements on a customized chart with the conventional method. This study would also help
us to establish the role customized charts as a screening tool for detection of SGA
especially in low resourced countries. It can play a pivotal role, being in expensive,
noninvasive for detection of SGA in developing countries with high perinatal morbidity and
mortality.
