1 Service de Gynécologie-Obstétrique, CHI Créteil, 40 avenue de Verdun, 94010 Créteil and 2 Clinique Universitaire Baudelocque, Hôpital Cochin, 123 BD de Port-Royal, 75014 Paris, France
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Abstract |
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Key words: fetal growth retardation/human chorionic gonadotrophin
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Introduction |
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Elevated concentrations in second trimester of human chorionic gonadotrophin (HCG) have been associated with Down's syndrome, triploidy or multiple gestation. In several reports studying the relationship between Down's syndrome and second trimester HCG concentrations, high rates of FGR were observed in women with abnormal concentrations of HCG and normally structured fetuses (Gonen et al., 1992; Lieppman et al., 1993
; Wenstrom et al., 1994
; Morssink et al., 1995
; Muller et al., 1996
).
This study was designed to investigate the possible relationship between maternal serum HCG profiles obtained early in the first trimester and FGR in women whose pregnancies were obtained after in-vitro fertilization (IVF). IVF pregnancies were chosen because gestational age is clearly defined and serial blood samples are routinely performed to evaluate early gestation.
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Materials and methods |
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All women had serial analysis (two or more) of serum HCG (4.14 ± 1.39, range: 29) at 48 h intervals at least. They were evaluated for the risks of the following adverse pregnancy outcomes: FGR without any malformation (birthweight below the 10th percentile of local standard curves), preterm delivery, pre-eclampsia (defined as a diastolic blood pressure >90 mmHg at 4 h apart and 24 h proteinuria 300 mg or ++ dipstick albuminuria at 4 h apart).
Hormone assays
Serum HCG was assayed by using a commercial reagent kit (Amerlite HCG 60®; Johnson and Johnson Clinical Diagnostics, Chatenay Malabry, France) between the 13th and 35th day after conception (i.e. the day of IVF); 85.9% of all the samples (n = 977) were obtained before the 28th day (Figure 1). The values were plotted against the 10th and 90th percentile values determined over the same gestation period in our laboratory for a control series of 333 IVF singleton pregnancies followed during 7 weeks gestation (unpublished data, Figure 2
). The profile of serum HCG values was considered abnormal when <10th or >90th percentile.
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Results |
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Sensitivity, specificity, positive predictive value and negative predictive value of low serum HCG profile early in the first trimester for FGR were 26, 96, 45 and 92%, respectively (Table V).
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Discussion |
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The proportions of elevated and low profiles of early first trimester serum HCG in the study population were at 12.3% and 19.5% respectively. The high frequency of low profiles is partially explained by the significant rate of spontaneous abortion and this association has already been described (Stabile et al., 1989; Henderson et al., 1992
). The high rate of early miscarriage in this population is in accordance with that observed after IVF in North America (Assisted Reproductive Technology in the United States and Canada, 1998
).
High serum HCG profiles (>90th percentile) obtained early in pregnancy in our series were not significantly associated with FGR, in agreement with the prior observation (Morssink et al., 1998) later in the first trimester. We have observed a RR of 2.1, which is in accordance with RR values obtained in the second trimester (Gonen et al., 1992
; Lieppman et al., 1993
; Benn et al., 1996
; Muller et al., 1996
) but it was not significant. It may be that our series was too short to allow a sufficient statistical power (0.23).
Low serum HCG profiles (<10th percentile) obtained early in the first trimester were strongly associated with FGR (RR 6.5). This association remained significant after controlling for pre-eclampsia (RR 5.6). In the second trimester, low HCG concentrations were also described as having a weak relationship with FGR (RR 1.2) (Morssink et al., 1995). However, in another study (Santolaya-Forgas et al., 1994
), a low second trimester maternal serum HCG had no influence on pregnancy outcome. Recently, no relationship was demonstrated between serum free ßHCG concentrations, obtained at 73 ± 4 days of gestation, just before chorionic villus sampling, and FGR (Morssink et al., 1998
). Our findings, which do not agree with those of Morssink et al. (1998), could be explained by the fact that gestational age in our study population was precisely known by the conception date whereas in Morssink et al. (1998) it was defined by last menstrual period and ultrasound examination, with a possible discrepancy of 7 days.
The association between early low serum HCG profile and subsequent FGR may reflect an impaired trophoblast function which might later lead to placental insufficiency. Recently, a relationship between FGR and hepatocyte growth factor (HGF), which is mainly synthesized and released in pregnant women by the placenta and trophoblast (Wolf et al., 1991), has been analysed (Aoki et al., 1998
). Decreased maternal HGF concentrations were found in those women having a small for gestational age infant (Aoki et al., 1998
). This may indicate a decreased release of HGF from the placenta as a result of decreased production reflecting placental insufficiency.
To our knowledge, this study is the first time the association between FGR and early low serum HCG has been described so early during gestation. The low sensitivity of low serum HCG profiles for prediction of FGR (26%, Table V) does not support the systematic use of such a marker as a screening test. In contrast, in women undergoing IVF, the good positive predictive value of early HCG profiles performed to monitor early gestation could be used to predict women at risk of FGR.
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Notes |
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References |
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Assisted reproductive technology in the United states and Canada: 1995 results generated from the American Society for Reproductive Medecine/Society for Assisted Reproductive Technology Registry (1998) Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine, Birmingham, Alabama. Fertil. Steril., 69, 389398.[ISI][Medline]
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Submitted on March 12, 1999; accepted on August 4, 1999.