Rises in maternal levels of alpha-fetoprotein during pregnancy are considered unexplained if they occur in the absence of fetal chromosomal abnormalities, fetal structural anomalies (for example, open neural tube defects, abdominal wall defects), placental anomalies (e.g. chorioangioma), multiple pregnancy, fetal demise, or maternal conditions such as an ovarian tumour or choriocarcinoma.

The exact cause of the unexplained AFP elevation isn’t completely understood, but placental pathology studies suggest that it’s associated with chorionic villitis and placental vascular lesions that allow leakage of the AFP from the high-concentration fetal circulation to the low-concentration maternal circulation, thus elevating maternal AFP. Elevated AFP has been associated with an increased frequency of maternal uterine malformation (possibly related to abnormal placentation).

Obstetrical complications that have been associated with an unexplained elevated maternal serum AFP include intrauterine growth restriction (IUGR), antepartum hemorrhage, placental abruption, preterm labour and preterm delivery, spontaneous abortion, fetal death > 24 weeks, gestational hypertension +/- proteinura, oligohydramnios, infant death, and perinatal morbidity (low Apgars, asphyxia, neonatal ICU admissions). The current SOGC Guidelines (October 2008) recommend that in the presence of an unexplained maternal serum AFP and a placenta previa in the second or third trimester, the index of suspicion for a placenta accreta, increta, or percreta should increase and that an assessment (ultrasound, MRI) of the placental-uterine interface should be performed.

Hence, women with unexplained AFP elevations warrant close observation and follow-up throughout their pregnancy. This includes ongoing assessments of fetal growth and well-being, placental localization, signs or symptoms of preterm labour, and maternal blood pressure monitoring.

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