Low PAPP-A in pregnancy

By trimester

Weeks 1–13

1st trimester

PAPP-A is interpreted as part of a first-trimester screening calculation with gestational age and other markers. A low value can raise screening risk for trisomies, but a screening result is not confirmation and should be discussed with the prenatal testing team.

Weeks 14–27

2nd trimester

The anatomy scan and any clinician-selected growth assessment add information that one PAPP-A value cannot provide. Low PAPP-A has statistical associations with placental outcomes, yet large cohort data show poor positive predictive value when it is used alone.

Weeks 28–birth

3rd trimester

Growth follow-up and antenatal testing depend on the value, ultrasound findings, medical history, and local plan. ACOG states that weekly surveillance may be considered from 36 weeks when first-trimester PAPP-A is at or below the fifth percentile even if growth appears normal.

What does the evidence show for low PAPP-A?

• PAPP-A is one component of first-trimester serum screening, and lower levels can occur with trisomies 21, 18, and 13; the combined screen estimates risk and does not confirm a chromosome condition. 1
• A nested case-control study comparing 248 pregnancies with adverse outcomes and 244 gestational-age-matched controls found an adjusted odds ratio of 2.1 for a composite adverse outcome with PAPP-A at or below 0.4 MoM, but sensitivity was only 38.7%. 2
• In a prospective low-risk cohort of 4,739 first pregnancies, PAPP-A below 0.4 MoM had poor positive predictive values for preeclampsia, a newborn below the third growth percentile, and fetal death, so isolated low PAPP-A could not predict an individual outcome. 3
• ACOG states that serum screening results can inform decisions about serial growth assessment and that weekly antenatal surveillance may be considered from 36 weeks when first-trimester PAPP-A is at or below the fifth percentile, even with normal growth. 4
• Flashes, blind spots, persistent blurry vision, severe unrelenting headache, severe belly pain, trouble breathing, or a clear reduction in fetal movement are urgent pregnancy warning signs regardless of a PAPP-A result. 5

When should I call my provider about low PAPP-A?

Low PAPP-A itself has no emergency symptom. Seek immediate pregnancy care for a severe headache that does not ease, flashes or blind spots, persistent blurry vision, severe abdominal pain, trouble breathing, vaginal bleeding or fluid leakage, or a clear reduction in fetal movement. These warning signs need assessment on their own and should not wait for a scheduled growth scan or surveillance visit. When in doubt, call your obstetric team the same day. Early input almost always beats waiting, and the on-call line exists exactly for this.