·         Factors influencing MOM calculations- The multiples of median value of MSAFP that define normal and abnormal usually lies between 2 MOM and 3 MOM. Values are adjusted for gestational age, obesity (lower MSAFP), black women (MSAFP levels 10—15% higher than non-blacks) and maternal insulin dependent diabetes (lower MSAFP).

·         Misdated pregnancy- MSAFP values vary with gestational age. They rise, reaching a peak at approximately 30 weeks gestation. The amniotic fluid AFP peaks around 12 weeks gestation. Approximately 20% of raised MSAFP levels are related to inaccurate dating, usually relating to LMP.

·         Multiple gestation- Twin pregnancy gives rise to approximately twice the concentration of MSAFP as singleton pregnancy. Twin pregnancy does not usually affect amniotic AFP. One should remember that the twin may be concordant or discordant for the presence of congenital anomaly associated with an elevated AFP.

·         Dying/recently dead fetus- Both MSAFP and amniotic fluid AFP are elevated. The cause of the elevation is unclear but may be related to loss of skin and membrane integrity.

·         Normal pregnancy- In many cases it is impossible to find a cause for a raised MSAFP; however, it should be noted that there is an increased prevalence of prenatal mortality and morbidity among mothers with elevated MSAFP reflecting placental insufficiency.

·         IUGR- Placental insufficiency in the third trimester is often associated with a raised MSAFP screening test.

·         Open fetal defects- These include: (1) anencephaly; (2) exancephaly; (3) encephalocele; (4) spina bifida; (5) omphalocele; (6) gastoschisis; (7) bladder extrophy; (8) cloacal extrophy; (9) ectopia cordis; and (10) limb—body wall complex. These lesions may either be covered by a membrane or fully exposed to AF. There is an increased diffusion of AFP from the open surface into AF. This high level of AFP is reflected in MSAFP. Sacrococcygeal teratoma, skin defects, epignathus, pilonidal sinus and ABS can be added to the list of open defects. MSAFP levels are usually normal in the presence of a cystic hygroma. Occasionally the hygroma may rupture, with leak of AFP-rich lymphatic fluid into the AF.

·         Fetomaternal hemorrhage- The increase in MSAFP depends upon the size of the fetomaternal hemorrhage. After amniocentesis there may be transient elevation of MSAFP, probably related to fetomaternal hemorrhage.

·         Renal anomalies- These include: (1) renal agenesis; (2) congenital nephrosis; (3)cystic kidney; (4) urinary tract obstruction. Congenital nephrosis is rare except in Finland. Antenatal US diagnosis of congenital nephrosis is difficult due to lack of specific features. In mothers with very elevated MSAFP in whom an open fetal defect has been excluded on ultrasound, congenital nephrosis should be considered and an amniocentesis performed.

·         Placental and AF abnormalities- These include: (1) chorioangioma; (2) placental hematoma; (3)umbilical cord hematoma or hemangioma; (4) OH.

·         Fetal liver abnormalities- These include: (1) liver necrosis: (2) liver tumor.

·         Maternal liver disease- Hepatomas and hepatitis.