Second trimester maternal serum β human chorionic gonadotrophin and pregnancy outome

The aim of this prospective, controlled study was to examine the relation between second trimester maternal serum β human chorionic gonadotrophin (HCG) and birthweight. The study population con sisted of 192 women with maternal serum βHCG ≥ 3.5 multiple of the median and a control group with the same number of women with maternal serum βHCG ≥ 2.0 multiple of the median. There was no difference in birthweight and other pregnancy outcomes between the two groups. When used prospectively, elevated βHCG in the mid-trimester is not a predictor for intrauterine growth restriction or other pregnancy complications.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome

OBJECTIVE: The purpose of this study was to evaluate whether abnormal levels of first trimester maternal serum free human chorionic gonadotropin (beta-hCG) are predictive of adverse pregnancy outcomes. METHODS: The study included 1,622 consecutive patients with singleton pregnancies who underwent first trimester Down syndrome screening using nuchal translucency, and maternal serum free beta-hCG and pregnancy-associated plasma protein-A. Patients with fetal anomalies or chromosome aberrations were excluded from the study. The incidences of various adverse pregnancy outcomes were evaluated according to maternal serum free beta-hCG levels. Outcome variables included spontaneous miscarriage, proteinuric and non-proteinuric pregnancy-induced hypertension, fetal growth restriction, intrauterine fetal demise, spontaneous preterm delivery, oligohydramnios and placental abruption. RESULTS: No significant differences were noted between groups for any of the demographic variables. The only statistically significant result was an increase in the relative risk for spontaneous miscarriage (RR = 6.33) at free beta-hCG <0.2 multiples of the medians. No other statistically significant result was noted for the other adverse outcomes or for the overall complication rate. CONCLUSION: Low free beta-hCG is associated with a higher incidence of spontaneous miscarriage but is a poor predictor of other pregnancy complications.     

Correlation between second trimester maternal serum inhibin-A and human chorionic gonadotrophin for the prediction of pre-eclampsia

We aimed to investigate the relationship between inhibin-A and human chorionic gonadotrophin (hCG) concentrations in the second trimester in the same cohort of women and compare their screening efficiency for the subsequent development of pre-eclampsia. The main outcome measures were pre-eclampsia and pre-eclampsia requiring delivery before 37 weeks.We carried out a retrospective examination of inhibin-A and free beta-hCG levels taken between 15 and 19 weeks of gestation, from 685 women. The values were corrected for weight and gestation and presented as multiples of the median (MoM). Receiver operator characteristic (ROC) curves for the prediction of pre-eclampsia and pre-eclampsia requiring delivery before 37 weeks were created for both analytes alone and in combination. Based on this data the sensitivities for the prediction of pre-eclampsia using inhibin-A and hCG, alone and in combination were examined for a specificity of 90 per cent.Thirty-five (5.5 per cent) women developed pre-eclampsia, of whom 15 (2.7 per cent) required delivery before term as a result of pre-eclampsia. There was no correlation between inhibin-A and hCG for the whole population (r=0.08) but there was a significant correlation for women who subsequently developed pre-eclampsia (r=0.648) or preterm pre-eclampsia (r=0.84). For a specificity of 90 per cent the sensitivity using inhibin-A was significantly better than for hCG (48.6 per cent versus 31.4 per cent, P< 0.05). The results were similar for preterm pre-eclampsia (P< 0.05). The addition of hCG data to inhibin-A data did not improve the sensitivity for pre-eclampsia compared to inhibin-A alone (42.9 per cent versus 48.6 per cent, P< 0.20).Inhibin-A is a more sensitive marker for the subsequent development of pre-eclampsia than hCG. Addition of hCG data to inhibin-A did not improve the screening efficacy for pre-eclampsia suggesting that inhibin-A and hCG are markers of the same underlying pathological process.     

Confined placental mosaicism for trisomy 14 and maternal uniparental disomy in association with elevated second trimester maternal serum human chorionic gonadotrophin and third trimester fetal growth restriction

A case of confined placental mosaicism (CPM) and maternal uniparental isodisomy 14 identified after placental karyotype revealed trisomy 14 in a newborn with intrauterine growth restriction (IUGR) and minor dysmorphic features is reported. During the second trimester of the pregnancy, multiple marker screening revealed an increased risk for Down syndrome of > 1 in 10. The maternal serum human chorionic gonadotrophin (MShCG) was markedly elevated at 4.19 MoM. Amniocentesis revealed a normal 46,XX karyotype. Fetal growth restriction has been associated with elevated MShCG and placental aneuploidy with CPM for chromosomes 2, 7, 9 and 16. The present case of CPM for chromosome 14 was also associated with fetal growth restriction and elevated second trimester MShCG, suggesting a common link. Further studies need to be done to determine if indeed elevation of second trimester MShCG is associated with increased risk of CPM. The present case again demonstrates the need to perform placental karyotype in unexplained fetal growth restriction.     

Collaborative study of maternal urine beta -core human chorionic gonadotrophin screening for Down syndrome.

Several studies have shown that second-trimester maternal urine beta-core human chorionic gonadotrophin (hCG) levels are raised on average in Down syndrome pregnancies. However, in all but one, testing was retrospective after extended sample storage and so we carried out a large international multicentre prospective study. 16 centres provided 6730 samples from 14-19 week pregnancies: 39 with Down syndrome, 12 with Edwards' syndrome, 42 with other aneuploidies, 52 unaffected twins and 6585 singleton unaffected pregnancies. Samples were from those having routine maternal serum screening in 6 centres and invasive prenatal diagnosis for reasons unrelated to maternal serum screening in 10 centres. Normalized levels of beta-core hCG (nmom/mmol creatinine) were expressed as multiples of the gestation-specific normal median (MoMs). The median beta-core hCG level in Down syndrome was 1.70 MoM (95 per cent confidence interval, 1.26-2.30); 14 (36 per cent) exceeded the normal 90th centile and 9 (23 per cent) the 95th centile. The median level in Edwards' syndrome was 0.23 MoM. On the basis of our results alone it is unlikely that urinary beta-core hCG will be a useful marker in Down syndrome screening practice. But the considerable variability in results between studies means that further research is needed before a reliable conclusion can be drawn.     

Second trimester amniotic fluid oestriol, dehydroepiandrosterone sulphate, and human chorionic gonadotrophin levels in Down's syndrome.

OBJECTIVE--To investigate the reason for low maternal serum unconjugated oestriol (uE3) and raised human chorionic gonadotrophin (hCG) levels in Down's syndrome pregnancies. DESIGN--Measurement of uE3, total oestriol (tE3), dehydroepiandrosterone sulphate (DHEAS), a precursor of oestriol, and hCG in 15-20 week amniotic fluid samples from pregnancies with and without Down's syndrome. SETTING--The retrieval and use of stored amniotic fluid samples collected from women who had had an amniocentesis for antenatal diagnosis. SUBJECTS--45 women with a Down's syndrome pregnancy and 224 unaffected controls of the same gestational age. RESULTS--The median level of amniotic fluid in affected pregnancies was low for uE3, tE3 and DHEAS but high for hCG: 0.50, 0.46, 0.35 and 1.58 multiples of the normal median, respectively. CONCLUSION--These results suggest that the abnormal maternal serum levels of uE3 and hCG in affected pregnancies are due mainly to abnormal feto-placental synthesis, rather than feto-maternal transfer.     

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.     

孕中期孕妇母血清hCG测定对于妊娠高血压综合征的预测性研究

目的 为明确孕中期血清绒毛膜促性腺激素(hCG)的异常升高是否增加妊高征发生的危险及其能否作为预测妊高征的有效指标。方法 在孕中期(13-27周)对432例单胎妊妇进行血清hCG的测定,并将测得值转换成中位数的倍数(mom),随访妊娠情况至产后,利用群组研究的方法,将hCG异常升高组作为研究组,而低于相应阈值的组作为对照组,探讨hCG的异常升高和妊高征的关系。结果 孕中期血清hCG的异常升高增加了重度妊高征(先兆子痫)发生的危险,而与轻中度妊高征的发生无明显关系。当hCG≥2.0 mom、≥2.5 mom或≥3.0 mom时,发生先兆子痫的危险分别是对照组的7.88倍,31.2倍或34.5倍,95％CI分别为1.55-40.12,2.56-68.03,6.31-188.67;95％CI的下限均大于1;筛查的敏感度均为50％,特异度分别为88.7％,93％,97％。结论孕中期血清hCG的异常升高增加了先兆子痫发生的危险,孕中期hCG的异常升高值可作为预报妊高征及监测病情程度的指标。     

Human chorionic gonadotrophin and alpha-fetoprotein levels in matched samples of amniotic fluid, extraembryonic coelomic fluid, and maternal serum in the first trimester of pregnancy.

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound-guided amniocentesis from 32 women between 7 and 12 weeks of pregnancy were analysed for human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). There was a highly significant difference between the hCG levels in amniotic fluid (median level 6.3 U/ml; range 1.6-310.0 U/ml) and those in extraembryonic coelomic fluid (median level 400.0 U/ml; range 135.0-2250.0 U/ml) (p less than 0.001; Mann-Whitney U-test). The levels of AFP were very similar in amniotic fluid (median 26.0 kU/ml; range 10.0-116.5 kU/ml) and extraembryonic coelomic fluid (median level 24.1 kU/ml; range 12.4-94.4 kU/ml).     

Maternal serum activin,inhibin, human chorionic gonadotrophin and alpha-fetoprotein as second trimester predictors of pre-eclampsia

Objective To compare the serum levels of human chorionic gonadotrophin (hCG), α-fetoprotein, activin A, inhibin A and inhibin isoforms containing pro and αC in the second trimester serum of women who subsequently developed hypertensive disorders of pregnancy with those who remained normotensive throughout pregnancy.
Design Retrospective case–control study of 15–20 week serum samples matched for duration of storage at −20°C.
Setting Antenatal clinics at a teaching hospital in Scotland.
Sample Second trimester serum samples of 39 women who subsequently developed pre-eclampsia, 31 who subsequently developed pregnancy-induced hypertension and 155 women who remained normotensive throughout pregnancy.
Main outcome measures hCG, α-fetoprotein, activin A, inhibin A and inhibin pro–αC serum levels.
Results Activin A levels in serum were significantly elevated in women who later developed pregnancy-induced hypertension (26% increase compared with controls) and hCG levels were significantly elevated in women who later developed pre-eclampsia (24% increase compared with controls). α-Fetoprotein, inhibin A and inhibin pro–αC levels were not significantly elevated in the patient groups compared with their controls.
Conclusions A combination of analyses including second trimester serum activin A and hCG may yet prove to be helpful predictors of women at risk of hypertensive disorders of pregnancy. While the results proved significant, the effects reported in this study are too modest compared with natural variability to be useful as screening tools on their own.     

Correlation of abnormal second trimester maternal serum alpha-fetoprotein (MSAFP) levels and adverse pregnancy outcome.

This study investigated the relationship between abnormal second trimester MSAFP levels and adverse pregnancy outcome. The findings revealed an association between low birth weight, prematurity and antepartum haemorrhage with abnormal unexplained high levels of second trimester MSAFP levels. However, macrosomia and increased gestational age at delivery were reported in relation to unexplained low levels of MSAFP in the second trimester. The positive predictive values for this test were poor (9-12%), that would question the use of this test to formulate a treatment plan. As the negative predictive values were high (96%), this test might be used to reassure women about their pregnancy.     

体外受精-胚胎移植周期中注射人绒毛膜促性腺激素日患者血清孕酮水平与妊娠结局的相关性

目的 探讨体外受精-胚胎移植(IVF-ET)周期中注射人绒毛膜促性腺激素(hCG)日患者血清孕酮水平与临床妊娠结局的相关性.方法 对2002年3月-2007年4月在南京医科大学第一附属医院生殖医学科注射hCG日有血清孕酮水平检测结果的786个IVF周期进行回顾性分析.每个周期均采用促性腺激素释放激素激动剂(GnRH-a)降调节,采用促性腺激素(Gn)促排卵.将孕酮水平为5.5、6.0、6.5、7.0、7.5、8.0、8.5和9.0 nmol/L设定为不同界值,孕酮水平<相应界值者为低孕酮水平,≥相应界值者为高孕酮水平,分别比较采用不同界值时高、低孕酮水平患者的各项实验室及临床检测指标.结果 786个周期中,采用不同的孕酮水平界值时,注射hCG日高孕酮水平与低孕酮水平患者的正常受精率、优质胚胎率、种植率、生化妊娠率、临床妊娠率、活产率比较,差异均无统计学意义(P>0.05);以8.5及9.0 nmol/L为孕酮水平界值时,高孕酮水平患者的早期流产率分别为27.3%(3/11)和3/7,均高于低孕酮水平者[分别为8.8%(26/297)和8.6%(26/301)],差异均有统计学意义(P<0.05);以9.0 nmol/L为孕酮水平界值时,高孕酮水平患者的总流产率为3/7,高于低孕酮水平者[11.0%(34/301)],差异也有统计学意义(P<0.05).结论 注射hCG日血清孕酮水平与临床妊娠率及活产率无关,当以8.5或9.0 nmol/L为孕酮水平界值时,早期流产率或总流产率与高孕酮水平相关.     

Clinical follow-up of high mid-trimester maternal serum intact human chorionic gonadotrophin concentrations in singleton pregnancies

Mid-trimester biochemical screening of 38 143 pregnancies in south-east Scotland revealed 127 cases (0.34 per cent) in which the maternal serum (MS) intact human chorionic gonadotrophin (hCG) concentration was > or = 4 multiples of the median in singleton pregnancies (MOM). Three were lost to follow-up but in 72 (58 per cent) complications developed or there were associated fetal abnormalities. This percentage was greatest at very high hCG concentrations, 92 per cent with hCG > or = 10 MOM (n = 12) compared with 48 per cent with hCG concentrations of 4-4.99 MOM (n=69). 22 cases had an MS alpha-fetoprotein > or = 2 MOM in addition to an MS hCG > or = 4 MOM, and in only 3 of these was the pregnancy uneventful; 86 per cent were associated with abnormalities or pregnancy complications.     

Prenatal diagnosis of 5p deletion syndrome following abnormally low maternal serum human chorionic gonadotrophin

Prenatal diagnosis of 5p deletion syndrome, or cri du chat, following an abnormally low measurement of a screening of serum human chorionic gonadotrophin (hCG), is reported. Karyotyping following amniocentesis revealed a terminal deletion in the short arm of one chromosome 5. The pregnancy was electively terminated. 5p deletion syndrome has been described with abnormally high hCG levels and normal hCG levels. This is the first report of its association with abnormally low levels. The association between chromosomal abnormalities and hCG is discussed.