Prospective evaluation of maternal serum human chorionic gonadotropin levels in 3428 pregnancies.

As part of a multicenter prospective study, second-trimester human chorionic gonadotropin and alpha-fetoprotein concentrations were evaluated. Data included maternal age, human chorionic gonadotropin level, alpha-fetoprotein level, weight, race, and pregnancy outcome of 3428 pregnancies at between 15 and 20 weeks' gestation. The results of the study indicate that human chorionic gonadotropin levels decrease as maternal weight increases, that weight-adjusted human chorionic gonadotropin levels for Oriental and black women are higher than for white or Hispanic women, and that twin pregnancies have higher human chorionic gonadotropin levels than singleton pregnancies. Of 255 pregnancies that did not have normal outcomes, 54 (21.2%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median and 26 (10.2%) had alpha-fetoprotein levels greater than 2.5 multiples of the median. Of 11 pregnancies with fetal aneuploidy, 6 (54.5%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median. It is concluded that in human chorionic gonadotropin screening programs for fetal Down syndrome, weight and race adjustments are necessary for accurate risk assessment.     

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

OBJECTIVE: We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. STUDY DESIGN: A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. RESULTS: In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. CONCLUSION: Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.     

Elevated maternal midtrimester serum free beta-human chorionic gonadotropin levels in vegetarian pregnancies that cause increased false-positive Down syndrome screening results

OBJECTIVE: The aim of this study was to examine whether midtrimester maternal serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels for Down syndrome screening differed in vegetarian pregnancies and omnivore pregnancies and to evaluate whether maternal serum vitamin B(12) concentration affected these maker levels. STUDY DESIGN: Ninety-eight vegetarian and 122 omnivore singleton pregnancies were studied. Reference levels of free beta-human chorionic gonadotropin and alpha-fetoprotein were based on a population of 6312 singleton euploid pregnancies that had been surveyed previously. Serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels were measured by enzyme immunoassay or radioimmunoassay. Multiples of the median values were calculated to determine whether different diet habits affected serum biomarker levels. Maternal serum vitamin B(12) levels were determined with radioimmunoassay. RESULTS: The free beta-human chorionic gonadotropin multiples of the median values were elevated significantly in the vegetarian pregnancies group (1.28 multiples of the median) compared with that of the reference population (1.00 multiples of the median) (P<.001). A negative association between the serum free beta-human chorionic gonadotropin multiples of the median values and the concentration of maternal serum vitamin B(12) was observed in the vegetarian pregnancies. No correlation was found between the alpha-fetoprotein multiples of the median values and the maternal serum vitamin B(12) concentration. CONCLUSION: The current data showed that the midtrimester maternal serum free beta-human chorionic gonadotropin levels increased in vegetarian pregnancies and led to an elevated false-positive rate in screening for Down syndrome compared with pregnant women with regular diet and resulted in unnecessary invasive procedures. It is necessary to establish vegetarian pregnancy alpha-fetoprotein and beta-human chorionic gonadotropin reference levels to correct increased false-positive screening results.     

Maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol levels in midtrimester trisomy 18 pregnancies.

OBJECTIVE: The purpose was to evaluate the levels of maternal serum human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol in trisomy 18 pregnancies compared with normal singleton pregnancies. STUDY DESIGN: Sera from 14 trisomy 18 pregnancies (13 retrospectively and one prospectively ascertained) were analyzed for human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol. RESULTS: The alpha-fetoprotein levels in the 10 trisomy 18 pregnancies without open neural tube or ventral wall defect had a median of 0.65 multiple of the median, although two had alpha-fetoprotein levels above 2.5 multiples of the median. The human chorionic gonadotropin levels had a median of 0.32 multiple of the median and the unconjugated estriol levels had a median of 0.56 multiple of the median. Although most women with trisomy 18 pregnancies had serum human chorionic gonadotropin levels that were less than 1.0 multiple of the median, three had markedly elevated human chorionic gonadotropin levels (greater than 5.0 multiples of the median). CONCLUSION: Our data are partially consistent with those previously published but suggest the possibility of a bimodal distribution of alpha-fetoprotein and human chorionic gonadotropin levels in trisomy 18-affected pregnancies, unrelated to a neural tube or abdominal wall defect. The efficiency of screening for trisomy 18 prospectively, using the three serum markers, requires further evaluation.     

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome.

OBJECTIVE--To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in twin pregnancies and to consider the implications of the results for antenatal screening for Down's syndrome. DESIGN--Measurement of maternal serum uE3 and hCG levels from 15-22 weeks of gestation in twin and singleton pregnancies. Previously available maternal serum alpha-fetoprotein (AFP) levels were also presented. SETTING--Stored serum samples collected from women receiving routine antenatal care in Oxford were used. SUBJECTS--200 women with a twin pregnancy and, for each, three singleton control pregnancies matched for gestational age (same completed week of pregnancy) and duration of storage of the serum sample (same calendar quarter). RESULTS--The median uE3, hCG and AFP levels in the twin pregnancies were respectively, 1.67 (95% CI 1.56-1.79), 1.84 (95% CI 1.64-2.07) and 2.13 (95% CI 1.97-2.31) multiples of the median (MoM) for singleton pregnancies at the same gestational age. The variance of values for the three serum markers (expressed in logarithms), and the correlation coefficients between any two, were similar in the twin and singleton pregnancies. CONCLUSION--In maternal serum screening programmes for Down's syndrome dividing uE3, hCG and AFP MoM values in twin pregnancies by the corresponding medians for twin pregnancies will, in expectation, yield a similar false-positive rate in twin pregnancies as in singleton pregnancies.     

A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies

OBJECTIVES: To determine the levels of first-trimester free beta-human chorionic gonadotrophin (free betahCG), pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency (NT) in twin pregnancies. METHODS: The study included 93 patients with twin pregnancy and 4,977 with singletons who underwent first-trimester testing using free betahCG, PAPP-A and NT at 10-13 weeks of gestational age. RESULTS: In twin pregnancies, the maternal serum free betahCG level was 2.18 higher and the PAPP-A level was 2.38 higher than in singleton pregnancies. These marker levels were significantly higher than the expected 2.0 multiples of the median (MoM). In contrast, NT values did not differ between twins and singletons. CONCLUSION: These data may be used to establish first-trimester combined screening for twin pregnancies.     

First-trimester maternal serum alpha-fetoprotein and chorionic gonadotropin in aneuploid pregnancies.

First-trimester maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels were measured in samples from 29 women with cytogenetically abnormal pregnancies and 145 women with cytogenetically normal pregnancies matched for gestational age, race, and sample storage time. All patients had a risk of fetal aneuploidy greater than or equal to that of a mother 35 years of age. AFP was significantly lower in samples from pregnancies affected with trisomy 21 (0.67 MoM; p less than 0.05), while HCG values were no different from those of matched controls. Trisomies 13 and 18 could not be distinguished from matched controls by AFP. However, levels of HCG were significantly lower in such pregnancy samples, with median values of 0.65 MoM in trisomy 13 and 0.32 MoM in trisomy 18 (p less than 0.05). Variations in AFP and HCG levels suggest that expressed differences between autosomal aneuploidies include differences in fetal and placental protein production in the first trimester.     

The impact of protease inhibitors on maternal serum screening analyte levels in pregnant women who are HIV positive

OBJECTIVE: The purpose of this study was to compare alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol levels in women who take protease inhibitors and those women who do not. STUDY DESIGN: This retrospective review from August 2000 to May 2003 was performed for maternal serum screen results, medication use, pregnancy, and perinatal outcomes. RESULTS: Thirty-nine women met study criteria. Sixteen women were treated with protease inhibitors, and 23 women were not treated with protease inhibitors. There was no difference in initial viral load or initial CD4 count between the groups. No difference was found for human chorionic gonadotropin and estriol levels; significantly lower alpha-fetoprotein multiples of the median were found for the women who were treated with protease inhibitors compared with the women who were not (0.97 +/- 0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%) had positive maternal serum screens. All the babies were normal at birth, and there were no cases of perinatal transmission of human immunodeficiency virus. CONCLUSION: Protease inhibitors are associated with lower alpha-fetoprotein levels in women who are infected with human immunodeficiency virus.     

Gender impact on first trimester markers in Down syndrome screening

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses.     

Elevated maternal mid-trimester chorionic gonadotropin > or =4 MoM is associated with fetal cerebral blood flow redistribution

BACKGROUND: Elevated mid-trimester human chorionic gonadotropin (hCG) is associated with adverse maternal and perinatal outcome. The aims of the study were to evaluate the association between elevated hCG, fetal pathological arterial waveforms and maternal and perinatal complications. METHODS: Pulsatility indices (PI) of middle cerebral artery (MCA) and umbilical artery (UA) were determined prospectively in 121 consecutive patients with abnormal maternal serum hCG (> 2.5 MoM). Each patient had four US scans during pregnancy. Patients with known structural or chromosomal anomalies were excluded. RESULTS: Of 121 women with hCG > 2.5 MoM, 36/121(29.6%) had hCG between 2.5 and 3.0 MoM, 35/121(28.9%) had hCG between 3.0 and 3.5 MoM, 21/121(17.3%) had hCG of 3.5-4.0 MoM, 17/121(14.1%) had hCG levels between 4.0 and 4.5 MoM, and 12/121(9.9%) had hCG > 4.5 MoM. Middle cerebral artery PI was significantly lower in women with hCG > 4.0 MoM between 28 and 36 weeks' gestation, but not between 18 and 27 weeks' gestation. No differences of MCA PI were found when the cut-off point of hCG was 3.5. Women with hCG levels > 4.0 MoM had a significantly higher rate of preterm deliveries, cesarean sections, higher rate of Apgar scores < 7 and a significantly lower mean birth weight in comparison with women with hCG < 4.0 MoM. The prevalence of PIH and preeclampsia and perinatal death were found to be higher among patients with hCG levels > 4.0 MoM, although not significantly. No differences were found at hCG levels less than 4.0 MoM. CONCLUSIONS: In pregnancies with mid-trimester hCG > 4.0 MoM, redistribution of cerebral blood flow is expressed after 28 weeks' gestation. These pregnancies have higher rates of maternal and neonatal complications as compared to pregnancies with lower hCG levels.     

Maternal serum alpha-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus

OBJECTIVE: The purpose of this study was to establish whether there is a correlation between maternal serum genetic screen analyte results in pregnant women with human immunodeficiency virus and corresponding human immunodeficiency virus index values. STUDY DESIGN: Medical records of all pregnant women with human immunodeficiency virus who were delivered at Bronx Lebanon Hospital Center from January 2000 through December 2001 were reviewed for maternal serum screen results, viral load, CD4 counts and percent, antiretroviral therapy, opportunistic infections, substance abuse, and other demographic data. Statistical analysis was accomplished with the chi(2) test, Mann-Whitney U test, and Spearman rank correlation test, with a probability value of <.05 considered significant. RESULTS: Of the 98 women with human immunodeficiency virus who were delivered, 49 women (50%) had a maternal serum genetic screen available. Screened and unscreened women had similar severity of human immunodeficiency virus disease, CD4 count and percentage, and viral loads. Serum screen results showed elevations in maternal serum human chorionic gonadotropin (1.43 +/- 1.04 multiples of the median [MoM]; range, 0.2-5.2 MoM) and maternal serum alpha-fetoprotein (1.29 +/- 0.9 MoM; range, 0.5-3.3 MoM) compared with expected values in the general obstetric population. Maternal serum human chorionic gonadotropin was correlated inversely with CD4 count (P =.002) and CD4 percent (P <.0001). Maternal serum alpha-fetoprotein varied directly with viral load (P <.0001). CONCLUSION: Increasing maternal serum human chorionic gonadotropin and maternal serum alpha-fetoprotein levels in patients with human immunodeficiency virus are correlated with increasing viral load and decreasing CD4 counts.     

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.     

Triploidy identified through second-trimester serum screening

OBJECTIVES: To describe the maternal serum marker patterns of triploid pregnancies and estimate the second-trimester prevalence of triploidy. METHODS: Forty-two cases of triploidy were identified in six serum screening programmes, five in the United Kingdom, one in Canada. This study describes the serum marker patterns, serum screening results for Down syndrome, trisomy 18 and open neural tube defects, and maternal age of these triploidy cases. The risk cut-off levels were > or = 1 in 250 for Down syndrome, > or =2.5 MoMs alpha-fetoprotein for open neural tube defects and > or =1:100 for trisomy 18 screening. The estimated second-trimester prevalence of triploidy was based on 22 triploidy cases ascertained in 599 934 pregnancies from three routine screening programmes, which attempted complete ascertainment of aneuploidy cases. RESULTS: The observed second-trimester rate of triploidy was 0.37 per 10 000 fetuses. Two different serum marker patterns were seen in triploid pregnancies, distinguished from each other by typically very high or very low levels of total hCG or free beta-hCG. The median maternal ages were respectively 33 years for triploidy with human chorionic gonadotrophin levels < 1.0 MoM, and 26 years for those with hCG levels > or =1.0 MoM. Fifty-seven percent of the pregnancies with a triploid fetus had a risk estimate > or =1:100 for trisomy 18 alone, 10% had an alpha-fetoprotein > or =2.5 MoM, 5% were screen positive for Down syndrome alone, and 19% had an increased risk or positive results for more than one anomaly. CONCLUSION: The simultaneous use of maternal serum tests designed to screen prenatally for Down syndrome, neural tube defects, and an increased risk of trisomy 18 resulted in a screen-positive result for 90% of pregnancies with triploidy.     

Co-variables in first trimester maternal serum screening

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)-A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centre's own medians. Information on maternal weight was available in 2259 pregnancies, on self-reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP-A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free beta-hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP-A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free beta-hCG. Results of a similar magnitude and direction were found for parity. The median level of free beta-hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP-A, maternal smoking are important first trimester screening co-variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers.     

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was -0.21 which was statistically significant (p=0.02, 95% confidence interval -0.38 to -0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester.     

Second-trimester maternal serum free-beta-human chorionic gonadotropin and alpha-fetoprotein levels in normal twin and singleton pregnancies: a report of local Chinese population

OBJECTIVES: The study evaluated the differences between Chinese normal twin and singleton pregnancies in the levels of maternal serum free-beta-human chorionic gonadotropin (free beta-hCG) and alpha-fetoprotein (AFP) used in second-trimester Down syndrome (DS) screening. METHODS: The concentrations of maternal serum markers of 456 twin pregnancies and 12 067 singleton controls in gestational 15 to 20 weeks were measured by time-resolved fluoroimmunoassay, and the levels of markers were compared between the twins and singletons. RESULTS: Significant differences were found between the levels of free beta-hCG in twins and twice of those in singletons in 16, 17 and 19 gestational weeks (p < 0.05 for all); while considering AFP, significant differences were found in 16 and 19 gestational weeks (p < 0.05 for both). No correlations were found in twins between the levels of markers and maternal weights in most gestational weeks (Free beta-hCG: p > 0.05 for 15 to 18 and 20 gestational weeks; AFP: p > 0.05 for 16 to 20 gestational weeks). CONCLUSIONS: The Chinese gestational age-specific levels of maternal serum markers in normal twins are not twice as those in singletons. The current weight-correction model for DS screening may be not feasible for twins.     

Second trimester maternal serum hCG level in an Asian population: normal reference values by ultrasound dating

OBJECTIVE: To establish normative data of maternal serum chorionic gonadotropin (hCG) during the second trimester in an Asian population. METHODS: We measured the maternal serum hCG levels in 17,955 normal singleton pregnancies between 15 and 21 weeks of gestation. The gestation age was estimated by measurement of fetal biparietal distance (BPD) in all cases. Median values of hCG at various gestational weeks were calculated and the values of hCG were converted to multiple of median (MoM). The incidences of low MoM value and high MoM value were also calculated. RESULTS: The mean and median values of hCG were 57,153 mIU/ml and 50,120 mIU/ml, respectively, at 15 weeks of gestation and then decreased to 30,898 mIU/ml and 26,226 mIU/ml, respectively, at 21 weeks. We found 8.6% and 9.4% of normal singleton pregnancies have hCG MoM values >2.0 MoM and <0.5 MoM, respectively. CONCLUSIONS: Our report provides a normal reference data of second trimester maternal hCG levels by ultrasound dating in an Asian population.     

Prenatal screening for Down syndrome with maternal serum human chorionic gonadotropin levels

Human chorionic gonadotropin levels in midtrimester pregnancies may be predictive of Down syndrome. A commercially available enzyme immunoassay kit was used to measure the beta-subunit of human chorionic gonadotropin in maternal sera from 38 Down syndrome pregnancies and 114 gestational age matched controls. The human chorionic gonadotropin levels were also assayed in 236 normal sera and plasma samples to determine normative values and appropriate individual corrections. Serum and plasma human chorionic gonadotropin levels are closely correlated and are stable at room temperature, during refrigeration, and throughout freeze-thaw cycles. There is no correlation between the human chorionic gonadotropin level and maternal age, weight, or race. However, the human chorionic gonadotropin level decreases with each week of gestation from 15 to 19 weeks. Medians for each week of gestation were established to account for this variable. Up to 63% of the Down syndrome pregnancies were detected with a cutoff of 2.0 multiples of the normal median. A computational combination of human chorionic gonadotropin and maternal serum alpha-fetoprotein testing will detect additional Down syndrome pregnancies and decrease the false-positive rate. The measurement of human chorionic gonadotropin appears to be a valuable addition to maternal serum alpha-fetoprotein screening programs that can significantly increase the proportion of Down syndrome cases diagnosed.     

Unexplained elevated maternal serum beta-HCG concentration and adverse pregnancy outcome

OBJECTIVE: To investigate the association between unexplained elevated maternal serum beta-Human chorionic gonadotrophin (HCG) in the second trimester of pregnancy and adverse pregnancy outcome. METHODS: In a case-controlled study of 3463 women who opted for second-trimester serum screening for Down syndrome, 142 were found to have a serum beta-HCG of > or =3.5 multiples of the median (MoM), 56 of whom had a serum beta-HCG of > or =5.0 MoM. These women were compared with a control group of women with serum beta-HCG within the 95% confidence interval around the median. RESULTS: In the elevated beta-HCG group (> or =5 MoM) significantly more babies required admission to the special care baby unit (p = 0.02) and were small for gestational age (SGA) (p = 0.03). The mean birth weight was also significantly lower in the group with elevated beta-HCG. Women with a serum beta-HCG of > or =5, > or =6, > or =7 or > or =8 MoM were associated with SGA babies in 40, 44, 64 and 86% respectively. All babies born to the six women with beta-HCG of 8.75-24.1 MoM were SGA. CONCLUSION: Increased surveillance is necessary in pregnancies where the maternal serum beta-HCG in the second trimester is inexplicably elevated to > or =5 MoM.     

The influence of smoking and parity on serum markers for Down's syndrome screening.

OBJECTIVE: To evaluate the impact of smoking and number of previous births on maternal serum levels of alpha-fetoprotein and free beta-subunit of human chorionic gonadotropin (free beta-hCG). METHODS: The study included 3,252 completed unaffected singleton pregnancies that proceeded beyond 37 weeks' gestation and resulted with a birth of healthy child. Smoking status of mothers and data concerning gravidity and parity were collected at the sampling date. Serum markers were measured between 13 and 22 gestational weeks, corrected for maternal weight, and converted to multiples of median (MoM) for unaffected pregnancy of the corresponding gestational age. Median MoM values for both markers were examined in relation to both: smoking habits and number of previous births. RESULTS: Smokers had significantly decreased free beta-hCG MoM values compared to nonsmokers (p < 0.001). The median levels showed a negative relationship with the number of previous births. The significance of a decreasing trend was proved, both in smokers (p < 0.001) and nonsmokers (p < 0.001). The median maternal serum alpha-fetoprotein MoM values did not show any significant dependence, neither with regard to smoking (p = 0.65) nor with regard to parity (p = 0.07). CONCLUSIONS: The recommendable adjustment of serum markers to smoking habits, especially concerning the free beta-hCG levels, would be worthwhile. The evidence of the coexisting influence of parity on serum levels of free beta-hCG, both in smokers and nonsmokers, should perhaps be a stimulus for reconsideration of which corrections the screening performance is dependent on.