METHODS
This is an observational cohort study of singleton term (≥ 37 weeks)
neonates born in a single tertiary centre between October 2016 and
September 2019. STROBE guidelines were followed. Exclusion criteria were
diagnosis of neonatal sepsis 17, multiple pregnancies,
those with uncertain dates, and those complicated by major structural
fetal abnormalities, aneuploidy, or genetic syndromes.
Outcome measures were 1) severe neonatal hypoglycaemia, defined as
capillary blood glucose < 2.0 mmol/l in the first 24 hours of
life and requiring admission to NNU and 2) the need for mechanical
ventilation or CPAP, (selected due to inconsistency in diagnosis of
respiratory distress syndrome (RDS)). Where measured, the lowest blood
glucose in the first 24 hours was also recorded.
Blood glucose level was measured in neonates considered at risk (BAPM)
using an Abbott ‘i-STAT handheld’ glucometer 2-4 hours after birth,
(usually before the second feed) and immediately if there were clinical
signs suggestive of hypoglycaemia (lethargy, abnormal feeding behaviour,
high pitched cry, altered level of consciousness, hypotonia, seizures,
hypothermia (<36.5°C), apnoea).
Criteria for admission to the
Neonatal Unit (NNU) due to neonatal hypoglycaemia were single glucose
measurement < 1 mmol/l; two or more consecutive measurements
between 1.0-1.9 mmol/l despite ongoing feeding support; or clinical
signs consistent with hypoglycaemia.
One complete corticosteroid course of two doses Betamethasone 12 mg 24
hours apart was administered where the risk of preterm birth
(< 34+0 weeks) in the following 7 days was
perceived to be high. Betamethasone was also used at the discretion of
the clinician from 34+0 weeks, prior to planned
elective late preterm or early term birth. If a course of betamethasone
was previously administered for any indication, a second course was not
given. Breastfeeding was supported within the first hour and for those
declining, formula feed 10-15ml/kg was offered, with 3-hrly subsequent
feeds.
Pregnancies were dated using crown-rump length (CRL) between
9+0 and 13+6 weeks. Birthweight (BW)
was converted into centiles according to Intergrowth-21st standards18: small for gestational age (SGA) was defined as
< 10th centile. Gestational diabetes and
hypertensive disorders were defined according to NICE criteria19, 20.
Prospectively collected data were merged from electronic maternity
record (Cerner Millennium) and neonatal records (Badgernet, Clevermed,
Edinburgh, UK). Statistical analysis was performed using Statistical
Package for Social Sciences (SPSS) v26.0 (IBM Inc., Chicago, IL, USA).
The study cohort was divided into three groups according to
corticosteroid exposure: the non-exposed (comparison) group; the exposed
group 1 where ACS were given before 34+0 weeks; and
the exposed group 2 where ACS were given at or after
34+0 weeks. A subset of the latter group, where ACS
were administered within 7 days before planned caesarean birth was
further analysed (exposed group 2a).
As neonates born from diabetic mothers represent the group with the
highest risk of developing neonatal hypoglycaemia, a secondary subgroup
analysis was carried out to assess relationship between ACS exposure and
neonatal outcomes in pregnancies affected by pre-existing or gestational
diabetes.
Continuous variables were presented as median and interquartile range
(IQR), while categorical variables were presented as absolute numbers
and percentages. Demographic and pregnancy variables were calculated for
each group of neonates. Demographic characteristics, pregnancy
characteristics and corticosteroid exposure, including timing, were then
compared between hypoglycaemic and normoglycaemic neonates. Group
comparisons of variables were performed with Mann–Whitney U test,
χ2 test or Fisher’s exact tests where appropriate.
Differences were considered significant when p value was
<0.05.
The association between ACS exposure and neonatal outcomes was assessed
for each group. Demographic and pregnancy characteristics significantly
associated with neonatal outcomes on univariate analysis were then
included into a multivariate backward-stepwise regression model to
adjust for potential confounders. Adjusted odds ratios (aOR) and 95%
confidential intervals (CI) were calculated.
Finally, among neonates exposed to ACS who had a glucose measured within
24 hours of birth, the correlation between time interval between
corticosteroid exposure and birth, and minimum neonatal glucose value,
was assessed using scatter plots. Pearson’s correlation was performed to
assess the relationship between variables.
NHS Health Research Authority ethical approval for this analysis was
granted on 27/07/2017 (IRAS project ID 222260; REC reference
17/SC/0374).