Data
The dataset was derived from pregnancies managed in the UK national GAP
programme which was running during the study period in a total of 132
NHS Trusts, Health Boards or Health and Social Care Trusts in England,
Wales, Scotland and Northern Ireland. Information was entered into the
GROW App software (version 1.2.6.1, www.gestation.net) which produces
customised growth charts and birthweight centiles adjusted for each
pregnancy according to early pregnancy maternal weight, height, parity
and ethnic origin 12. Also recorded was whether the
pregnancy was considered at increased risk of growth restriction on the
basis of obstetric or medical history and risk factors such as smoking
or high body mass index, and whether serial third trimester ultrasound
biometry was instituted according to protocol. The number of growth
scans was not collected in the database but, according to routine audits
within the programme, usually consisted of 3 to 4 third trimester scans
from 28 weeks to delivery. Pregnancies were dated according to the
routine 1st trimester ultrasound scan. Outcomes
recorded after delivery included birthweight, sex and gestational age at
delivery, and whether live birth or stillbirth. Stillbirth was defined
as a baby born with no signs of life from 24.0 weeks gestation.
Gestational age for stillbirths was based on the age at delivery minus 2
days to adjust for the average delay in third trimester between
intrauterine demise and delivery 19.
There were 1,641,897 singleton pregnancies delivered> 24.0 weeks gestation between January 2015 and
January 2020. After excluding late fetal losses (725) and cases with
missing or incomplete data (68,355), the final study cohort consisted of
1,572,817 pregnancies. All data were fully anonymised including
institution of origin, date of birth and all other maternal, new-born
and pregnancy-related identifiers, and hence ethics approval was not
required.
Statistical Methods To assess the association between customised GROW centiles and
stillbirth, we developed receiver operator curves (ROCs) according to
standard methodology20 on the overall cohort as well
as the low and high risk subgroups. Risk status was recorded in
1,308,967 (83%) of the cases, with the remainder missing mostly because
the detailed data items were not contained in the version of the local
electronic system in use during the study period.
Analyses were carried out using SAS software (version 9.4, SAS
Institute, NC, USA). Optimal centile cut-offs were determined by
balancing sensitivity and specificity using Youden’s
index21, and model performance was assessed according
to area under the curve (AUC) analysis. Differences between pregnancy
characteristics were determined using the Kruskal Wallis test for
continuous variables and a Z Test between proportions. Outcome between
groups was compared using relative risk (RR) with 95% confidence
interval (CI).