PAPP-A is a substance produced by the placenta, the temporary organ responsible for nourishing the developing fetus. This protein is released into the maternal bloodstream and serves as a measurable marker during the first trimester of pregnancy. A blood test for PAPP-A is routinely performed as part of early screening to assess both fetal and placental health. When the level is lower than expected, it suggests a need for closer monitoring. This finding is not a diagnosis but an indicator of an increased statistical risk for certain outcomes.
PAPP-A’s Role in First Trimester Screening
PAPP-A is a large zinc-binding glycoprotein created by the syncytiotrophoblast layer of the placenta. Its primary function is to support fetal development by regulating the availability of insulin-like growth factors (IGFs). PAPP-A cleaves specific IGF-binding proteins, freeing up IGFs necessary for cell growth and proliferation in the developing fetus and placenta.
Measurement of PAPP-A occurs as part of the combined first-trimester screening, usually conducted between 10 and 14 weeks of gestation. This screening combines the PAPP-A blood test with free beta-human chorionic gonadotropin (hCG) measurement and ultrasound assessment of nuchal translucency (NT). These three factors are analyzed together to calculate a personalized risk estimate for specific chromosomal conditions.
The result is expressed as a Multiple of the Median (MoM), which compares the individual’s PAPP-A level to the average level for all pregnancies at the same gestational age. A MoM value of 1.0 is considered the median for that stage of pregnancy. A result is considered low when it falls below a threshold, often set at 0.4 or 0.5 MoM, indicating a concentration significantly less than the mean. A low MoM suggests that the placenta’s ability to produce the protein is reduced.
Underlying Conditions Associated with Low Levels
Low PAPP-A in the first trimester is interpreted as a marker for underlying issues related to placental function or fetal development. The most well-known association is with certain chromosomal abnormalities in the fetus. Pregnancies affected by Trisomy 21 (Down syndrome) and Trisomy 18 (Edwards syndrome) often exhibit reduced levels of PAPP-A in the maternal blood.
The low protein level may reflect that the genetic condition has affected the early formation and function of the placenta. While low PAPP-A contributes to the calculated risk for these conditions, it is not the cause of the genetic change. Further testing is needed to determine if a chromosomal anomaly is present.
Beyond chromosomal concerns, a low PAPP-A result indicates potential placental insufficiency later in gestation. The reduced protein production suggests the placenta may not have implanted or developed optimally in early pregnancy. This suboptimal development can lead to complications, particularly as fetal growth demands increase in the second and third trimesters.
One major concern is an increased risk for Fetal Growth Restriction (FGR), where the baby is smaller than expected due to insufficient nutrient and oxygen supply from the placenta. When PAPP-A is low, the mechanism that releases growth factors may be compromised, contributing to restricted fetal size. This association is often stronger with extremely low PAPP-A levels, such as those below 0.2 MoM.
A low PAPP-A level also increases the risk for certain maternal complications, specifically preeclampsia and preterm birth. Preeclampsia is characterized by high blood pressure and signs of organ damage, fundamentally linked to problems with the placenta’s blood supply. The protein’s low concentration serves as an early signal that the mother may be at higher risk for developing this condition.
Clinical Follow-Up and Pregnancy Monitoring
Once a low PAPP-A result is identified, the first step in clinical management involves clarifying the risk for chromosomal conditions. Non-Invasive Prenatal Testing (NIPT) is often offered, as it provides a highly accurate screening of fetal DNA found in the mother’s blood. For a definitive diagnosis, invasive procedures like Chorionic Villus Sampling (CVS) or amniocentesis may be discussed, though these carry a small risk of miscarriage.
If chromosomal abnormalities are ruled out, the focus shifts to managing the risk of placental complications. The patient is often managed with increased surveillance throughout the remainder of the pregnancy. This typically involves serial growth ultrasounds, usually starting in the third trimester, to track the baby’s development and ensure proper weight gain.
These specialized ultrasounds may also include Doppler studies, which measure blood flow through the umbilical cord and uterine arteries, assessing placental efficiency. In some cases, low-dose aspirin may be recommended, often started early in the second trimester, as a preventative measure to improve blood flow and potentially reduce the risk of preeclampsia or growth restriction. Ultimately, a low PAPP-A result necessitates close monitoring, but the majority of babies with this finding are born healthy.