Obstetric outcomes in women with elevated maternal serum human chorionic gonadotropin

doi:10.1016/j.ajog.2006.03.011

American Journal of Obstetrics and Gynecology

Volume 194, Issue 6, June 2006, Pages 1676-1681

https://doi.org/10.1016/j.ajog.2006.03.011 Get rights and content

Objective

This study was undertaken to assess outcomes in unselected women with maternal serum human chorionic gonadotropin (MShCG) 2.0 MoM or greater.

Study design

This is an observational cohort study of 309 women with MShCG 2 MoM or greater and 309 women of the same age and ethnicity with MShCG less than 2.0 MoM who were evaluated for preterm delivery (PTD), preeclampsia, stillbirth, birth weight 10% or less, and birth weight 90% or greater (larger for gestational age [LGA]). Confounding variables evaluated were nulliparity, prior PTD, chronic hypertension, diabetes, and maternal serum alpha-fetoprotein and estriol.

Results

There was no overall increase in adverse outcomes despite associations found with PTD for preeclampsia with MShCG 3.0 MoM or greater (odds ratio [OR] 5.9, CI 1.5-23.2) and PTD for fetal indications with MShCG 4.0 MoM or greater (OR 45.5, CI 4.1-509). There was an increase of LGA infants with MShCG 3.0-3.9 MoM (OR 2.5, CI 1.0-5.8).

Conclusion

Adverse pregnancy outcome is associated with MShCG 3.0 MoM or greater, thus increased surveillance is not warranted with lower values.

Section snippets

Material and methods

This is an observational cohort study approved by the University of California-Davis Office of Human Subjects Protection. Women who had MShCG 2.0 MoM or greater on the expanded AFP (x-AFP) screening test performed through the California Department of Health Services, Genetic Disease Branch comprise the study group. For each woman with MShCG 2.0 MoM or greater, a woman of the same age and ethnicity with MShCG less than 2.0 MoM was identified. Multiple gestations and losses before 20 weeks of

Results

There were 344 women identified with MShCG 2.0 MoM or greater. Twelve losses (7 terminations for aneuploidy or anomalies and 5 demises found on evaluation of abnormal x-AFP) before 20 weeks were excluded. Another 23 women were excluded as they transferred care during their pregnancy. This left 309 women with MShCG 2.0 MoM or greater, of whom 75.7% had values between 2.0 and 2.99 MoM, 17.5% were between 3.0 and 3.99 MoM, and 6.8% had values 4 MoM or greater.

Table I reveals the obstetric and

Comment

Similar to other studies on elevated MShCG, we identified an association with PTD and preeclampsia. We found that preterm preeclampsia was the primary factor leading to the increase in PTDs; however, it was associated only with MShCG 3.0 MoM or greater. In many studies, term and preterm preeclampsia were not evaluated separately.7, 8, 12 Our data found only a correlation between elevated MShCG and preterm preeclampsia, and not term preeclampsia. We also found an association between MShCG 4.0

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Cited by (34)

Association between human chorionic gonadotropin (hCG) levels and adverse pregnancy outcomes: A systematic review and meta-analysis
2023, Pregnancy Hypertension
Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and adverse pregnancy outcomes. We conducted a systematic review including studies measuring hCG blood levels in the first or second trimester, reporting on any of the 12 predefined adverse pregnancy outcomes with logistic regression-adjusted association estimates. The primary outcomes were placenta-associated complications, such as miscarriage, preeclampsia, intrauterine growth restriction, and preterm delivery. We searched PubMed, Embase and CINAHL Complete. The hCG levels were analysed as multiple of the median (MoM). Odds ratio (OR) and 95% confidence interval (CI) were used. Risk of bias and the certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Meta-analysis also showed that hCG levels, reported as MoM ≥2/2.31/2.5, might be associated with an increased risk of preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), but the evidence is very uncertain. High second trimester hCG levels may be associated with preeclampsia and preterm delivery but confidence in evidence is low.
Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case–control study in China
2020, Clinica Chimica Acta
Citation Excerpt :
Our multivariate regression analysis also pointed out that a low hCG concentration is a risk factor for low birth weight, and a high hCG concentration is a risk factor for macrosomia. Although it has been reported that an increase in hCG concentration in the second trimester of pregnancy is associated with an increase in the incidence of adverse pregnancy outcomes, such as preeclampsia, SGA, premature delivery, intrauterine death, and placental abruption [17], our results do not show such a relationship. Our results only suggest that a high hCG concentration is an independent risk factor for GDM.
We assessed whether the results of quadruple screening during pregnancy are associated with an increased risk of adverse pregnancy outcomes.
We measured serum marker concentrations using quadruple screening in the second trimester of pregnancy and analyzed the relationship between adverse perinatal outcomes and serum markers in 12,124 pregnant women. A multivariate logistic regression analysis was used to evaluate the relative risk of quadruple screening and adverse pregnancy outcomes.
Compared with the control group, increased concentrations of alpha-fetoprotein (AFP) and inhibin A were risk factors for preeclampsia and preterm delivery; low concentrations of unconjugated estriol and high inhibin A were risk factors for pregnancy hypertension; an increased concentration of human chorionic gonadotropin (hCG) was a risk factor for gestational diabetes mellitus; high AFP, low hCG, and high inhibin A were risk factors for low birth weight; and low AFP and high hCG were risk factors for macrosomia.
Quadruple screening in the second trimester of pregnancy can provide early warning signs for maternal and fetal adverse pregnancy outcomes.
Mid-Trimester Maternal Serum AFP and hCG as Markers of Preterm and Term Adverse Pregnancy Outcomes
2015, Journal of Obstetrics and Gynaecology Canada
Citation Excerpt :
Mid-trimester maternal serum markers have been used for prenatal aneuploidy screening for more than 20 years.1 In the absence of aneuploidy or neural tube defect, these serum markers have also been associated with several placenta-mediated adverse pregnancy outcomes, including preeclampsia, intrauterine growth restriction, and stillbirth.2–4 The Society of Obstetricians and Gynaecologists of Canada suggests that an unexplained elevation of maternal serum alpha-fetoprotein (> 2.5 MoM) and/or human chorionic gonadotropin (> 3.0 MoM) is associated with an increased frequency of PMAPOs.2
To evaluate the predictive values of mid-trimester serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for preterm and term placenta-mediated adverse pregnancy outcomes (PMAPOs).
We extracted data for nulliparous women with a singleton pregnancy without aneuploidy or lethal fetal anomalies from a prospective cohort study. Maternal serum AFP and hCG measured between 13 and 17 weeks of gestation and expressed as multiples of the median (MoM) for gestational age were compared between women who developed a PMAPO (preeclampsia, intrauterine growth restriction, fetal death) before term or at term and women who did not develop any of these complications.
Among 3466 nulliparous women, maternal serum AFP and hCG levels were available in 2110 and 2125 cases, respectively. Women who developed a PMAPO before term had a higher median level of serum AFP (1.4 vs. 1.1 MoM; P < 0.01) and hCG (1.3 vs. 1.1 MoM; P < 0.01) than controls. A serum hCG > 2.0 MoM was associated with a higher risk of PMAPO before term (RR 4.6; CI 95% 2.3 to 9.1) but had no impact on the risk of PMAPO at term (RR 1.1; CI 95% 0.7 to 1.7). Maternal serum AFP > 2.0 MoM was also associated with a significant increase in the risk of preterm PMAPO (RR 3.9; CI 95% 1.6 to 9.8) but not term PMAPO (RR 1.2; CI 95% 0.6 to 2.3).
Maternal serum AFP or hCG > 2.0 MoM increases the risk of preterm PMAPO but not term PMAPO in our population. We suggest that women with elevated serum AFP or hCG should receive standard pregnancy care once they have reached 37 weeks of gestation if fetal growth is in the normal range.
Évaluer les coefficients de prévision propres aux taux sériques d’alphafœtoprotéine (AFP) et de gonadotrophine chorionique (hCG) constatés au deuxième trimestre pour ce qui est des issues de grossesse indésirables à médiation placentaire (IGIMP) obtenues avant le terme et à terme.
Nous avons tiré, d’une étude de cohorte prospective, des données concernant des femmes nullipares ayant connu une grossesse monofœtale exempte d’aneuploïdie ou d’anomalies fœtales mortelles. Nous avons comparé les taux sériques maternels d’AFP et de hCG (mesurés entre 13 et 17 semaines de gestation et exprimés sous forme de multiples de la médiane [MoM] en fonction de l’âge gestationnel) des femmes ayant connu une IGIMP (prééclampsie, retard de croissance intra-utérin, décès fœtal) avant le terme ou à terme à ceux des femmes qui n’en sont pas venues à connaître de telles complications.
Au sein d’un groupe de 3 466 femmes nullipares, les taux sériques maternels d’AFP et de hCG étaient connus dans 2 110 cas et 2 125 cas, respectivement. Les femmes qui ont connu une IGIMP avant le terme présentaient des valeurs de MoM pour ce qui est des taux sériques d’AFP (1,4 vs 1,1 MoM; P < 0,01) et de hCG (1,3 vs 1,1 MoM; P < 0,01) plus élevées que celles des femmes du groupe témoin. Bien que la constatation d’un taux sérique de hCG > 2,0 MoM ait été associée à un risque accru d’IGIMP avant le terme (RR, 4,6; IC à 95 %, 2,3 - 9,1), elle n’exerçait aucun effet sur le risque d’IGIMP à terme (RR, 1,1; IC à 95 %, 0,7 - 1,7). La constatation d’un taux sérique maternel d’AFP > 2,0 MoM a également été associée à une hausse considérable du risque d’IGIMP avant le terme (RR, 3,9; IC à 95 %, 1,6 - 9,8); le risque d’IGIMP à terme (RR, 1,2; IC à 95 %, 0,6 - 2,3) n’en était toutefois pas affecté.
Au sein de la population à l’étude, les taux sériques maternels d’AFP ou de hCG > 2,0 MoM ont entraîné une hausse du risque d’IGIMP avant le terme, mais n’ont pas exercé une influence sur le risque d’IGIMP à terme. Lorsque la croissance fœtale se situe dans la plage normale, les femmes qui présentent des taux sériques élevés d’AFP ou de hCG devraient recevoir des soins de grossesse standard, une fois qu’elles ont atteint 37 semaines de gestation.
Population-based biomarker screening and the development of severe preeclampsia in California
2014, American Journal of Obstetrics and Gynecology
The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies.
Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia.
Approximately 0.9% of all women (n = 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers.
The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.
Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy
2014, Pregnancy Hypertension
Citation Excerpt :
Two platforms measuring placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1), either singly (i.e., PlGF) or as a ratio (e.g., sFlt-1/PlGF ratio) [134,135] are being licenced in North America. Of the many risk markers for preeclampsia (Table 5) [99,111,136–164], many are known at booking and increase the risk of preeclampsia two- to fourfold [165]. The strongest of these are previous preeclampsia, antiphospholipid antibody syndrome, pre-existing medical conditions, and multiple pregnancy (all bolded in Table 5).
This guideline summarizes the quality of the evidence to date and provides a reasonable approach to the diagnosis, evaluation and treatment of the hypertensive disorders of pregnancy (HDP).
The literature reviewed included the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines from 2008 and their reference lists, and an update from 2006. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT) and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2006 and March 2012. Articles were restricted to those published in French or English. Recommendations were evaluated using the criteria of the Canadian Task Force on Preventive Health Care and GRADE.
Toxicity assessment on trophoblast cells for some environment polluting chemicals and 17β-estradiol
2013, Toxicology in Vitro
Citation Excerpt :
In most of the studies low β-hCG levels in early gestation have been associated to early fetal loss (Braunstein et al., 1978; Goetzl et al., 2004 and Goetzl, 2010; van Ravenswaaij et al., 2011). In contrast to the low levels of hCG in the first trimester, high levels in the second trimester have been linked to pregnancy complications such as preeclampsia, intrauterine growth restriction and preterm birth (Tuuli and Odibo, 2011; Towner et al., 2006). Even though it is difficult to translate the data obtained in vitro with the pathophysiological conditions, any effect on the concentration of β-hCG by external substances might result in problems during pregnancy.
The identification of reproductive toxicants is a major scientific challenge for human health. We investigated the effects of a selected group of environmental polluting chemicals mostly provided with estrogenic activity on the human trophoblast cell lines BeWo and HTR-8/SVneo. Cells were exposed for 24 h to various concentrations (from 0.1 pM to 1 mM) of atrazine (ATR), diethylstilbestrol (DES), para-nonylphenol (p-NP), resveratrol (RES) and 17 β-estradiol (E2) and assayed for cell viability and human beta-Chorionic Gonadotropin (β-hCG) secretion.
Decrease of cell viability as respect to control, vehicle-treated, cultures was obtained for all chemicals in the concentration range of 1 μM–1 mM in both cell types.
A parallel decrease of β-hCG secretion was observed in BeWo cells, at 1 μM–1 mM concentrations, with the only exception of ATR which caused an increase at concentrations up to 1 mM. β-hCG release was also unexpectedly inhibited by ATR, DES, p-NP and RES at non-toxic (pM–nM) concentrations.
These findings raise concern about the negative, potential effects of various environmental polluting chemicals on pregnancy success and fetal health.

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: Support was provided by the Department of Obstetrics and Gynecology, University of California at Davis, Sacramento, CA.

: Presented at the 72nd Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, September 28-October 2, 2005, Kauai, HI.

: Editor's Note: This manuscript was revised after presentation at the Annual Meeting.

: Reprints not available from the authors.

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Transactions of the 72nd Annual Meeting of the Pacific Coast Obstetrical and Gynecological SocietyObstetric outcomes in women with elevated maternal serum human chorionic gonadotropin

Objective

Study design

Results

Conclusion

Section snippets

Material and methods

Results

Comment

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

Placenta

Pregnancy outcomes after increasing maternal serum alpha-fetoprotein levels

Obstet Gynecol

Data from an alpha-fetoprotein pilot screening program in Maine

Obstet Gynecol

An association between elevated levels of human chorionic gonadotropin in the midtrimester and adverse pregnancy outcome

Am J Obstet Gynecol

Transactions of the 72nd Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society
Obstetric outcomes in women with elevated maternal serum human chorionic gonadotropin