Maternal Alpha-fetoprotein Levels Research Articles

472 G6PD deficiency is associated with decreased maternal serum Alpha-fetoprotein levels

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited X-linked recessive disorder, being the most common enzymatic defect of erythrocytes in humans. Since G6PD deficiency has been associated with metabolic comorbidities and placental dysfunction, we aimed to examine whether this disorder can affect the levels of maternal serum biochemical screening markers. For this retrospective study, we collected data of all pregnant women delivering in our medical center between January 2015 to December 2019. The inclusion criteria were any documentation of maternal serum biochemical screening markers: free beta-human chorionic gonadotropin (HCG), pregnancy-associated plasma protein A (PAPP-A), maternal serum alpha-fetoprotein (AFP), HCG and unconjugated estriol. Overall, 6,186 women with documented maternal serum biochemical screening markers were detected, 63 of these (1.0%) with G6PD deficiency. No difference in demographic or obstetrical characteristics was noted between G6PD-deficient women to the remaining cohort (including maternal age, body mass index, gestational age and birth weight). In G6PD-deficient women, significantly lower levels of maternal AFP were found compared to the remaining cohort (0.87±0.28 vs. 1.05±0.28 multiples of median, respectively, p<0.001, Table 1). In addition, marginally lower second trimester HCG levels were found in G6PD deficiency (1.0±0.58 vs. 1.15±0.69 multiples of median in the remaining cohort, p=0.07). Since the placenta plays a major role in HCG synthesis, as well as in transferring the fetal AFP to maternal circulation, the placental effects of G6PD deficiency may explain lower levels of these markers. As maternal serum AFP measurement serves as a screening tool for neural tube defects, as well as a component of biochemical screening for Down syndrome, G6PD status may affect the screening results. Thus, the findings of our study may be of great importance in prenatal surveillance, and should be further explored.

Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk?: A systematic review and meta-analysis

Objective We have carried out a systematic review of the association between elevated second trimester maternal serum alpha-fetoprotein (AFP) and singleton preterm birth in order to determine its accuracy and the best AFP cut-off level in clinical tests in the general population. Study design 24 studies published between January 1991 and October 2007 were included, comprising 207,135 women. Results An elevated AFP test (expressed as multiple of the median, MoM) had high specificity but low sensitivity to predict preterm birth: using a 2.5 MoM as the cut-off in the AFP test improved the accuracy compared with 2.0 MoM. However, the overall likelihood ratios for positive and negative tests were not improved. The likelihood ratios for positive tests were: 2.99 (95% CI: 2.45–3.66) and 3.18 (95% CI: 2.07–4.88) for 2.0 MoM and 2.5 MoM, respectively; and for negative tests were: 0.94 (95% CI: 0.91–0.97) and 0.97 (95% CI: 0.95–0.98) for 2.0 MoM and 2.5 MoM, respectively. The available data do not allow us to distinguish whether the association between elevated AFP and preterm birth occurs in spontaneous preterm labour, in elective preterm delivery, or in both. Moreover, in these studies AFP was measured together with other biomarkers (e.g. human chorionic gonadotrophin, oestriol) which often were also elevated. When we included only women in whom AFP was elevated in isolation, there was no association with preterm birth (OR = 1.80, 95%CI: 0.92–2.68). Conclusion Our findings suggest that maternal AFP levels are strongly related to preterm birth, but only in the context of other abnormal pregnancy markers. The results question the potential usefulness of AFP screening as a primary preterm birth marker and highlight the need for further studies on the functional role of AFP in pregnancy.

Levels and correlates of alpha-fetoprotein in normal pregnancies among Caucasian and Chinese women

Alpha-fetoprotein has been suggested to have anti breast cancer properties both in adult life and in utero. We studied correlates of maternal serum alpha-fetoprotein levels in normal singleton pregnancies. This was a prospective study relying on women attending maternal units in major teaching hospitals in Boston, USA and Shanghai, China. Specifically, 212 Caucasian women in Boston, and 196 Asian women in Shanghai provided blood samples at the 16th and 27th gestational week. Maternal serum alpha-fetoprotein levels were measured and correlated with maternal and newborn parameters through multiple regression procedures, controlling for a set of potential confounders, including maternal levels of measured hormones. Alpha-fetoprotein was strongly inversely associated with maternal prepregnancy body mass index (-4.73 ng/l at the 27th week per 1 kg/m of body mass index, with 95% confidence intervals -7.09 to -2.36), whereas it was not related to parity, gender of offspring or birth weight. Duration of gestation was inversely associated with maternal alpha-fetoprotein levels, particularly among Caucasian women (-0.22 weeks per 60 ng/l of alpha-fetoprotein at the 27th week, with 95% confidence intervals -0.39 to -0.05). In normal pregnancies, maternal alpha-fetoprotein is inversely related to prepregnancy body mass index and appears to have a physiologic role on duration of gestation rather than on birth weight.

Second-Trimester Maternal Serum Levels of Alpha-Fetoprotein and the Subsequent Risk of Sudden Infant Death Syndrome

Because an elevated maternal serum level of alpha-fetoprotein (AFP) in the second trimester of pregnancy is evidence of placental function and strongly predicts unexplained stillbirth, a study was planned to determine whether second-trimester maternal AFP levels are associated with the future risk of sudden infant death syndrome (SIDS). Unexplained stillbirth and SIDS are known to have some characteristics in common. A prenatal screening database for women in western Scotland totalled 214,532 women having singleton births in the years 1991–2001. Deaths designated as being SIDS deaths occurred within the first year of life. The 114 deaths designated as SIDS made the incidence of such deaths 5.3 per 10,000 live births (95% confidence interval, 4.4–6.4). Women whose infants died of SIDS were younger and shorter than the others and had lower body mass indices. Their parity was higher and they were likelier to be socioeconomically deprived. The same mothers were more likely to smoke, more often delivered male infants, and had offspring of lower birth weight. Second-trimester AFP levels were higher in the SIDS mothers, and the risk of SIDS increased with increasing maternal serum AFP levels. The risk of SIDS correlated inversely with both birth weight and gestational age at birth. Although the association between AFP and SIDS was less marked after adjusting for these factors, it remained significant. Adjusting for maternal age, infant gender, parity, and smoking status by multivariate analysis did not substantially influence the association between AFP and the risk of SIDS. No significant interactions were found between maternal serum AFP and any maternal or obstetric characteristics. The risk of SIDS did not relate to maternal serum levels of human chorionic gonadotropin. These findings support a direct association between maternal serum AFP levels in midpregnancy and the subsequent risk of SIDS. An adverse intrauterine environment in early pregnancy, impairing fetal growth and disposing to preterm birth, may be a major determinant of the risk of SIDS.

Reproductive factors and extreme levels of maternal serum alpha‐fetoprotein: a population‐based study

Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring. Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14-21 and whose present and previous pregnancies resulted in live-born singletons. Many previous births and an interval of less than 2 years since last birth were significantly associated with extremely low levels of AFP in the mother. However, age at first birth and age at present pregnancy did not influence the AFP level. Women who gave birth to a girl had AFP levels that were 5%[95% confidence interval (CI) 4-6%] lower than those of women who had a boy. Adjustment for birthweight did not significantly affect the estimate. Low serum AFP levels in pregnancy are significantly correlated with high parity and with a short interval between births. The significantly lower levels of AFP in women who gave birth to girls could indicate a possible gender-specific regulatory mechanism.

Reproductive factors and extreme levels of maternal serum alpha-fetoprotein: a population-based study

Background. Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring. Methods. Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14–21 and whose present and previous pregnancies resulted in live-born singletons. Results. Many previous births and an interval of less than 2 years since last birth were significantly associated with extremely low levels of AFP in the mother. However, age at first birth and age at present pregnancy did not influence the AFP level. Women who gave birth to a girl had AFP levels that were 5%[95% confidence interval (CI) 4–6%] lower than those of women who had a boy. Adjustment for birthweight did not significantly affect the estimate. Conclusions. Low serum AFP levels in pregnancy are significantly correlated with high parity and with a short interval between births. The significantly lower levels of AFP in women who gave birth to girls could indicate a possible gender-specific regulatory mechanism.

Feto-maternal transfusion after chorionic villus sampling: clinical implications

Feto-maternal transfusion following chorionic villus sampling (CVS) in the first trimester of pregnancy was evaluated by alpha-fetoprotein (AFP) level determination in maternal serum before and after sampling. Some fetal haemorrhage was suggested in 72% of 283 continuing pregnancies by a significant increase of maternal AFP level. Fetal bleeding appeared to stop a short time after CVS, and did not complicate detection of neural tube defects (NTDs) in the second trimester. The change in the maternal serum AFP level was correlated with the size of the chorionic tissue specimen, but no association was observed between fetal and neonatal outcome. The risk of maternal rhesus (Rh) iso-immunization must be taken into account, and anti-D immunoglobulin administrated after CVS. Maternal Rh immunization should be considered as a contraindication to CVS.

Maternal serum alpha-fetoprotein levels in a triplet pregnancy with 2 papyraceous fetuses

Serum Alpha-Fetoprotein (AFP) was found to rise to exceedingly high levels in a case of triplet pregnancy after two fetuses died in the 21st week of gestation. The surviving infant was born in the 36th week accompanied by the two fetus papyracei. By the time the process of mummification of the two dead fetuses appeared to be complete on ultrasound, the maternal AFP level had returned to the normal range for singleton pregnancies. HCG, hPL, and estriol and the coagulation profile remained within the normal range throughout the pregnancy.

Alpha-fetoprotein levels in placenta, maternal, and cord blood in normal and pathologic pregnancy.

The level of placental alpha-fetoprotein (AFP) in normal pregnancy at term was found to be 5050 +/- ng/g fresh tissue. A significant increase was noted in the toxemic placenta associated with a rise in circulating maternal AFP level and a nonsignificant increase in cord blood. The increase in maternal AFP level in cases of premature delivery before 33 weeks' gestation and postmature delivery after 40 weeks' gestation predicted that maternal AFP measurement throughout the second and third trimester of pregnancy could be clinically established as an index of placental function.

Evolution of alpha-fetoprotein serum levels throughout life in humans and rats, and during pregnancy in the rat.

A radioimmunoassay method (RIA) with specific antisera for human and rat alpha fetoprotein (AFP) was used to study the evolution of AFP levels in humans and rats, respectively, throughout the life span. Sera of 66 rats, aged 3-70 weeks, as well as sera of 201 clinically well children, 192 healthy blood donors, and 16 persons aged 70-98 were assayed. In humans, AFP levels decreased steeply during the 1st year of life, reaching a low basal range by the end of the 2nd year which is maintained throughout adulthood. Rats showed a similar pattern, but concentrations were higher at every stage of life. Puberty occurs in rats while AFP is still decreasing, whereas in humans the adult basal level is stabilized long before puberty. Maternal serum AFP was studied in 29 rats, and the levels were found to begin a sharp increase on the 10th-13th day of gestation. From Day 13-19, a deceleration of AFP increase was observed which led to a decrease between Day 17 and 19. From Day 19-21, AFP levels increased sharply again. A significant correlation was observed on Day 21 of pregnancy between the number of rat fetuses and the maternal AFP level. Hemihysterectomy led to a reduction of AFP level that was grossly proportional to the number of remaining fetuses. The stable level of AFP that persists throughout adult life is attributed to the stability of this protein's synthesis. Conversely, in pregnancy the evolution of serum AFP curve is dependent on the fetal synthesis, maternal and fetal catabolism, and permeability of the placental barrier.

Alpha fetoprotein in maternal serum: A new marker for detection of fetal distress and intrauterine death

Increase in circulating maternal alpha fetoprotein (AFP) is associated with intrauterine fetal death. The AFP levels in 13 women whose fetuses died in utero were from 280 to 9,000 ng. per milliliter. Nine of them (70 per cent) were above 530 ng. per milliliter, which was the upper normal level in 65 uncomplicated pregnancies. In high-risk pregnancies, the AFP test correctly predicted 60 per cent of the cases with fetal distress and 92 per cent of the cases with normal fetoplacental function. If maternal AFP levels were above 800 ng. per milliliter, fetal distress or intrauterine fetal death occurred in 85 per cent of the cases, and intrauterine fetal death occurred in all 6 cases where the maternal AFP concentration was higher than 1,075 ng. per milliliter. The increase in maternal AFP took place before the fetal death. Clinically established fetal distress was correctly predicted by the AFP test in 2 women whose estriol excretion was normal. The results suggest that the AFP test contributes to the biochemical detection of fetal distress and intrauterine death.

Alpha-fetoprotein in Abortion

The clinical value of maternal serum alpha-fetoprotein (AFP) as a guide to the outcome of threatened abortion was assessed. After the thirteenth week of gestation, abortion occurred more frequently (10/12) in women with abnormal serum AFP levels than in those (2/12) whose AFP concentrations were within the normal range. Low levels were present in women with blighted ovum and high concentrations were associated with intrauterine fetal death. In legal first and second trimester abortions, the circulating maternal AFP levels in postabortion samples were often higher than before abortion, irrespective of whether abortion was performed instrumentally or induced with prostaglandins. Maternal serum AFP levels provide a new means for prediction of the outcome of threatened abortion.