Fetal Growth Restriction and Repeat Antenatal Corticosteroid Therapy

Abstract

Background: Fetal growth restriction (FGR) occurs when the fetus fails to achieve its intrauterine growth potential. FGR is commonly associated with preterm birth, and both increase the risk of short and long-term health and neurological sequelae. Antenatal corticosteroids are an important therapy for preterm birth, and administration of repeat doses reduces neonatal morbidity. However, there is concern that increased fetal exposure to corticosteroids may have long-term adverse effects in FGR. Aims: 1) To determine the influence of FGR on the effects of repeat dose(s) of antenatal betamethasone at mid-childhood; and 2) to compare rates of small- and large-for-gestational age (SGA, LGA) infants in a multi-ethnic obstetric population using four different weight centiles, and to relate this classification to neonatal morbidity. Methods: Aim 1) secondary analysis of data from the Australasian Collaborative Trial of Repeat Doses of Corticosteroids Mid-Childhood Outcome Studies. At 6-8 years’ corrected age, children were assessed for neurosensory and cardiometabolic function. FGR was defined as severe FGR at entry, caesarean delivery for FGR, or customised centile <3. Aim 2) in a multi-ethnic obstetric cohort, infants were classified as SGA or LGA by population reference, population standard, fetal growth curves, and customised centiles. Neonatal morbidity risk was determined with comparison to a common referent group. Results: At mid-childhood, there was a significant interaction between FGR and repeat betamethasone treatment for the effect on height. FGR did not influence the effect of repeat betamethasone on risk factors for cardiometabolic disease, survival free of disability, or neurocognitive function, which were similar between treatment groups for both FGR and non- FGR subgroups. SGA and LGA rates varied up to three-fold by different centiles. Those at highest neonatal morbidity risk were SGA or LGA on both the population reference and an alternative centile. Conclusions: Repeat antenatal betamethasone did not have adverse effects on cardiometabolic or neurocognitive function at mid-childhood, even in the presence of FGR. Clinicians should use repeat antenatal corticosteroids when indicated, regardless of FGR, in view of the associated neonatal benefits. Combined, rather than single, use of a population reference and customised centiles provides a more comprehensive assessment of infants at risk of neonatal morbidity due to abnormal intrauterine growth.