Biochemical Markers in Adverse Pregnancy Outcomes

Biochemical markers measured in maternal blood offer a non-invasive window on placental function and foetal health. Key analytes such as free β-human chorionic gonadotrophin (βHCG), pregnancy-associated plasma protein A (PAPP-A), inhibin-A, alpha-foetoprotein and placental growth factor reflect trophoblast viability, angiogenesis and nutrient transfer. Aberrant concentrations of these proteins in the first and second trimesters correlate with a spectrum of complications including pre-eclampsia, intrauterine growth restriction, small-for-gestational-age infants, preterm delivery and stillbirth. Multiples of the median (MoM) standardise measurements across populations and gestational ages, improving risk stratification. Recent advances in high-throughput proteomics have expanded the repertoire of candidate markers and enabled multi-parameter screening algorithms that combine biochemical, biophysical and clinical variables. Such integrated approaches aim to identify at-risk pregnancies early, allowing targeted surveillance and prophylactic interventions. Global studies have underlined the need for population-specific reference ranges and the importance of adjusting for maternal characteristics such as ethnicity, body mass index and smoking. As the field moves towards precision medicine, novel markers and machine-learning models promise better predictive accuracy and the prospect of tailored antenatal care.

Research from Nature Portfolio

Recent studies have demonstrated that extreme first-trimester free βHCG MoM values, either below 0.2 or above 5.0, significantly increase the risk of chromosomal anomalies, placental insufficiency and adverse maternal outcomes such as pre-eclampsia, gestational diabetes and preterm labour. These findings underscore the dual risk associated with both low and high βHCG levels in routine aneuploidy screening programmes and support incorporation of these thresholds into early risk assessment protocols. Separate work has explored the long-term implications of low first-trimester PAPP-A. Women with PAPP-A in the lowest quartile not only face an elevated risk of small-for-gestational-age infants and obstetric complications but also show a higher incidence of de-novo diabetes and cardiovascular events several years after pregnancy. Offspring of these pregnancies tend to exhibit reduced stature, hinting at persistent effects of early placental insufficiency on postnatal growth trajectories.

Biochemical Markers in Adverse Pregnancy Outcomes publication trend

The graph below shows the total number of articles in biochemical markers in adverse pregnancy outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Multiple of the median (MoM): A normalisation metric expressing an individual marker level relative to the median value for a given gestational age.

Free β-HCG: The unbound subunit of human chorionic gonadotrophin produced by the syncytiotrophoblast, indicative of early placental activity.

PAPP-A: Pregnancy-associated plasma protein A, a metalloproteinase that regulates availability of insulin-like growth factors and reflects placental development.

Inhibin-A: A glycoprotein hormone secreted by the placenta; elevated levels in mid-trimester signal potential placental dysfunction.

References

1. Extreme βHCG levels in first trimester screening are risk factors for adverse maternal and fetal outcomes. Scientific Reports (2023).
2. First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring. Scientific Reports (2020).
3. Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers. PLOS ONE (2017).
4. A cohort study of the association between maternal serum Inhibin-A and adverse pregnancy outcomes: a population-based study. BMC Pregnancy and Childbirth (2019).
5. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study. European Journal of Epidemiology (2015).