Antenatal Markers Related to Fetal Growth Restriction Can Predict Childhood Systolic Blood Pressure

Abstract

Background: Being born small for gestational age (SGA) is linked with higher systolic blood pressure (SBP). Fetuses with growth restriction (FGR) may be either SGA or appropriate size for gestational age at birth. However, it is not known which factors contributing to size at birth influence the relationship with SBP. Aim. To determine whether antenatal markers of FGR can predict the upper quartile of childhood SBP. Methods: Brachial SBP was measured for 75 children aged 3-6 years from the Manchester BabyGRO Study, using a Tensiomed®Arteriograph with a child-sized cuff. SBP quartiles were generated. Participants were born to mothers who had attended a specialised clinic, following identification of higher FGR risk based on abnormal maternal serology (pregnancy associated plasma protein-A, β-human chorionic gonadotrophin, α-fetoprotein, Inhibin-A). Antenatal ultrasound data at 23 weeks gestation were obtained. Uterine artery Doppler (UtAD) notching was assigned a rank (0=absent, 1=unilateral, 2=bilateral). Random forest (RF) is a machine learning approach that generates many independent, uncorrelated decision trees based on multiple variables. This was used to determine the relative importance of antenatal variables in prediction of upper quartile of childhood SBP. Variables included in the model were maternal body mass index (BMI), parity, ethnicity (black/white/asian/mixed), maternal SBP and diastolic BP (DBP), maternal serology relating to FGR risk, UtAD pulsatility index, resistance index and notching rank (all measures of uteroplacental blood flow resistance), placental size measurements, 23 week estimated fetal weight (EFW) centile, ∆23w EFW-birthweight centile and birthweight SDS. A receiver operating characteristic (ROC) curve was generated, providing an area under the curve (AUC). A variable of importance (VIP) score was calculated for each marker that was significant in the model. All analyses were conducted in R (version 3.6). Results: RF analysis demonstrated antenatal markers relating to FGR risk predict the upper quartile of childhood SBP with an AUC 0.97. The top five ranked variables were maternal DBP (VIP score 14.0), birthweight SDS (11.5), parity (9.9), notching rank (9.5) and ∆23w EFW-birthweight centile (9.1). Conclusion: Maternal and antenatal markers, as well as birthweight SDS are linked with the upper quartile of SBP at 3-6 years. Antenatal markers were within the top five ranked and could help identify those babies at risk of higher SBP in childhood.