Differential RNA expression in late onset fetal growth restriction

1. Women who developed late onset fetal growth restriction had upregulation of certain placental genes at 26-30 weeks gestation.

2. A combination of biomarkers was predictive of severe late onset fetal growth restriction.

Evidence Rating Level: 3 (Average)

Study Rundown: Fetal growth restriction (FGR), a term used to describe a fetus that has not reached its full growth potential due to fetal, placental or maternal factors, affects approximately 10% of pregnancies in developed countries. Infants with FGR are at increased risk for premature delivery, asphyxia, impaired thermoregulation, hypoglycemia, impaired immune function, neurocognitive deficits, and neonatal death. As such, efforts have been made to identify FGR early. Fetal Dopplers can be useful in distinguishing between fetuses that are growth-restricted and those who are constitutionally small prior to 36 weeks but are less useful beyond 36 weeks. Overall, existing techniques to evaluate FGR have limited diagnostic abilities and have not been shown to improve perinatal outcomes. Based on previous work showing that placental RNA is differentially expressed in pregnancies with early FGR, in the present work the authors assessed whether this would also be the case in late onset FGR. They found that 7 placental genes were significantly upregulated in women who had an infant with late onset FGR.

Strengths of the study included collection of a wide range of biomarkers and PCR validation of biomarker expression. The study was limited by small sample size and case-control design. Further prospective studies evaluating the predictive ability of these biomarkers in detecting late onset FGR, as well as longer term outcomes, are needed to determine the utility of these biomarkers as a screening test.

Click to read the study in AJOG

Relevant Reading: Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction

In-Depth [case-control study]: This nested case-control study within a larger prospective cohort study compared the expression of placental genes in women delivering infants with late onset FGR (n = 40) and normal growth (n = 80). Late onset FGR was defined as weight <5th percentile at >36 weeks gestation. Placental RNA in maternal blood at 26-30 weeks gestation was measured to determine whether there was differential expression in women who experienced late onset FGR.

Among women with FGR, there was increased expression of Activating Transcription Factor 3 (ATF3) (p = 0.03), Adrenomedullin (p = 0.02), Insulin-like Growth Factor 1 (p = 0.01), Tachykinin 3 (p = 0.02), Kisspeptin 1 (p = 0.01) and Syncytian (p = 0.04). Expression of ATF3 was positively correlated with the degree of FGR. A combined biomarker expression score had a sensitivity of 79% and specificity of 88% for detecting an infant weighing <3rd percentile.

Image: CC/Wiki/Difference_DNA_RNA-DE.svg: Sponk (talk)

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