AFP is an oncofetal protein with molecular weight of 68,000 Da
2. AFP is produced in the developing fetus in equal amounts by the yolk sac and the fetal liver
7. Because the human yolk sac involutes at the 9
th week, the fetal liver and to lesser extent, the gastrointestinal tract is responsible for most of the AFP production during fetal development
12. During early pregnancy AFP is the predominant serum protein, showing maximum fetal serum levels of 3-4g/L in the 12
th week of pregnancy. As AFP crosses the placenta it can be measured in the serum of the pregnant women
2. The synthesis of AFP does not cease entirely at term, but a small amount of AFP is continuously synthesized until 8 months of age. The infant plasma concentration falls exponentially from a mean of 50.000 U/ml to a typical adult concentration of less than 10 U/ml at 6 to 8 months of age
1,7. The explanation for the observation of AFP synthesis not ceaseing entirely at term may be the presence of fetal hepatocytes, that sustain transient production of AFP during the early postnatal period, although they decrease in number
7.
The value of serum AFP for detection and/or differentiation of a great number of infantile diseases is well established, especially for germ cell tumor with yolk sac component and hepatoblastoma, and benign liver disorders 2,12. But serum AFP levels are high in normal fetuses and children in early infancy, making the interpretation of AFP levels very difficult at this age group 1. Abnormal concentrations of AFP in biologic fluids during embryonic and fetal development have been found to be associated with congenital malformations and hereditary disorders 12-18.
Reference values for AFP in healthy full-term newborns at birth are not well-defined 4. The postnatal serum AFP levels are age-dependent and gradually decline as the infant matures 1,3,5,6. Low birth weight infants have a clearly greater mean concentration of AFP than other newborns 5. When the low birth weight group was partitioned into two subgroups to distinguish small for gestastional age from premature infants, a distinctively high mean was found for both groups 5. On the other hand, birth weight itself has been correlated with gestational age 6. Since the estimation of gestational age without sonography can be highly subjective, Mizejewski GJ, et al. 5 suggested that birth weight is the parameter of choice upon which to measure postnatal AFP blood concentrations. In the present study, we excluded infants with birth weight inappropriate for gestationel age to eliminate any factor that may cause a change in serum AFP concentration. In our study fetal sonography is a routine examination for the determination of gestational age and it is also confirmed by the mother’s estimated date of her last menstrual period and physical examination of the neonatologyst by the new Ballard scoring system.
Bellini C, et al. 4 examined AFP levels in 150 healthy newborns and preterms within the postnatal 24 hours. All babies included in their study were of appropriate birth weight. They found a significant correlation between AFP values and both birth weight and gestational age. In their study mean AFP values in male and female newborns were 151±61mg/L and 150±59 mg/L, respectively. These were higher than our AFP values as a result of presence of premature babies in their study group. Blohm ME, et al. 19, found that, at birth mean serum AFP levels were 41,687 ng/ml in 256 term babies. We found higher mean AFP values (67,246 + 52,137 ng/ml) in a similar group with a wide range (105-226,000). Our mean values in newborns and infants are similar to Wu JT, et al. 20 but show wider AFP ranges in all postnatal age groups.
In most infants, serum AFP levels decrease to normal adult levels within the first 8-10 months, but in a significant proportion of children AFP levels do not normalize until the end of the 2nd year of life 19,21. Our study group was limited to 12 month-old infants. Some babies had normal adult values even in the 7th month but this study is inefficient to make a conclusion about the age for AFP decrease to normal adult values.
Findings of sex-related differences in serum AFP levels, especially in early postnatal life, have been conflicting, and the cause of these controversies remain obscure 3,7. The levels of fetal AFP at parturition are found to be significantly higher in the male infants 8,22. In a study fetal AFP serum concentration was found higher in boys than girls and this sex related difference remained during the first week of life 22. Lee PI, et al 3 investigated the normal developmental pattern of serum AFP level. Their results support the presence of a sex-related difference in AFP levels during early postnatal life. Higher AFP levels are noted for newborn boys during the first 2 postnatal weeks. In newborn girls, the mean serum AFP level decreased rapidly from postnatal day 1 to 2 and remained relatively constant thereafter until 7 days of age. It is hard to explain the different developmental patterns of AFP in male and female neonates. It may also be that the biodynamics of AFP is influenced by such sex-determined factors as hormones. Sex related difference diminish with increasing age 3. However, Bellini C, et al. 4 found that there was no significant difference between AFP values in males vs. females in 150 healthy newborns and preterms 4. In the present study AFP values were not statisticaly different in males and females except values of the 7th month which were higher in females. We showed with exponential and linear regression analyses that a significant sex dependency does not exist in AFP values of 0-12 month-old infants. But we can not make a final conclusion with this small group of infants and such a wide variation of AFP levels.
Observation on the relationship between race and AFP levels has been inconsistent. In fact, maternal serum AFP values have been shown to be higher in blacks and Orientals than in Caucasians 3. Maternal serum AFP concentrations are affected by a number of variables including ethnicity 23,24. However, there is no evidence about ethnical differences in infant serum AFP levels 3. More studies are necessary to explain wide variations in ethnicity.
In conclusion, we showed that the normal range of AFP in healthy infants who were followed-up in our center is very wide and pediatric oncologists must consider moderately high values carefully and if the decrease in the follow-up measurement is slower than the expected half-life for that age, the probability of an AFP-producing tumor could be high. This approach would prevent unnecessary interventions depending on false positive AFP results.
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