Altered Fetal Head Growth in Preeclampsia: A Retrospective Cohort Proof-Of-Concept Study

Abstract

BackgroundPreeclampsia is associated with fetal growth restriction and low birth weights. Neurotrophins, which mediate neuronal growth and development, are also increased in the placenta and cord blood in preeclampsia. Hence, the aim of this study was to determine whether fetal head growth is altered in preeclampsia, adjusting for growth restriction and other confounding variables.MethodsThis research included a retrospective cohort study, looking at fetal head circumference at birth, plus a case–control study examining fetal head circumference at mid-gestation. The head circumference at birth analysis consisted of 14,607 pregnancies (preeclampsia = 382, control = 14,225), delivered between July 2006 and June 2012 at Nepean Hospital, Australia. Head circumference at birth, in addition to other maternal and fetal variables, was sourced from the Nepean Obstetric Database. The head circumference at mid-gestation study consisted of 756 pregnancies (preeclampsia = 248, control = 508), delivered within the same data collection period at Nepean Hospital. Head circumference at mid-gestation was retrieved from an earlier ultrasound scan. Exclusion criteria included >1 fetus, illegal drug use, alcohol consumption, and chronic or gestational hypertension. Generalized linear models were used to analyze fetal head circumference in preeclampsia versus controls, adjusting for confounding variables.ResultsHead circumference increased at a greater rate in preeclampsia versus controls, adjusted for gestation, fetal gender, birth weight and length, smoking, maternal BMI, and growth restriction. At mid-gestation, there was no difference in head circumference between preeclampsia and controls.ConclusionFor the first time, this research has suggested increased fetal head growth in preeclampsia, adjusted for confounders. This finding may be explained by altered fetal exposure to neurotrophins in preeclampsia. The long-term neurodevelopmental consequences of preeclampsia remain unclear.

Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia

“…For Nepean cohort 1 , an initial power calculation revealed a sample of 100 subjects (50 cases with preeclampsia and 50 controls) to provide over 80% power to detect an effect size of 0.6 on thymus volume at the 5% level of significance. An effect of this magnitude represented a conservative interpretation of the results of our previous study 30 , which found a difference in thymus diameter corresponding to an effect size of 0.8 and obtained similar results using an approximated thymus volume based on the diameter measures. Intra-observer and inter-rater reliability were assessed used a Bland-Altman plot and a paired t -test for each assessment.…”

“…The estimated prevalence of preeclampsia at Nepean Hospital was based on our earlier retrospective study. The estimates of the standard deviation in thymus diameter measurements and the plausible odds ratio are also informed by the results of our previous retrospective study 30 . The effect of fetal thymus diameter on the odds of preeclampsia was evaluated in both univariate and multivariate logistic regression analyses (Model 1 and Model 2).…”

“…Together with gestational age and maternal BMI, AUC increased to 0.78. Since our group had previously found that increased fetal head growth was also associated with preeclampsia after adjusting cofounders 30 , we then included the fetal head circumference in the model. When fetal thymus diameter at mid-gestation, fetal head circumference at mid-gestation, gestational age, and maternal BMI were included, we could reach an AUC of 0.81 (Supplementary Fig.…”

Proposing a new approach to measuring birth size asymmetry

“…Neonates with a preeclamptic mother were at twice the risk of having a large BBR, while the asymmetry measures indicated that this association was driven by neonates being at more than twice the risk of low birthweight asymmetry, with no association noted for HC asymmetry. Importantly, the latter findings are in line with earlier research indicating that preeclampsia associates with disproportionate reductions in fetal weight and length, while brain growth is preserved 23,24 …”

Placental Neuropeptide Y (NPY) and NPY receptors expressions and serum NPY levels in preeclampsia

“…There were no statistically significant differences in gestational age or neonatal head circumference between the PE and NP groups indicative of preservation of fetal brain blood flow and development of fetal head growth. 50 Placental weight of the PE group had positive correlations with gestational age, neonatal weight, neonatal length, and neonatal head circumference. These results indicate that placenta plays a crucial role in fetal growth and inadequate placentation is assumed to be important for the fetal development.…”