Maternal serum human chorionic gonadotropin level at fifteen weeks is a predictor for preeclampsia

doi:10.1016/S0002-9378(96)70247-8

American Journal of Obstetrics and Gynecology

Volume 175, Issue 1, July 1996, Pages 37-40

https://doi.org/10.1016/S0002-9378(96)70247-8 Get rights and content

Abstract

OBJECTIVE: Our purpose was to study the correlation between maternal serum human chorionic gonadotropin levels measured at 15 to 18 weeks of amenorrhea and pregnancy-induced hypertension, preeclampsia, and small-for-gestational-age neonates. STUDY DESIGN: Prospective trisomy 21 human chorionic gonadotropin screening data from 5776 patients were examined in a retrospective investigation of the relationship between human chorionic gonadotropin and pregnancy-induced hypertension (234 cases), preeclampsia (34 cases), and small-for-gestational-age neonates (238 cases). RESULTS: Maternal serum human chorionic gonadotropin (multiples of the median) was higher in the three populations with pathologic disorders. This difference was statistically significant in patients with small-for-gestational-age neonates (p < 0.0163) and preeclampsia (p < 0.0001) but not in those with pregnancy-induced hypertension. In the preeclampsia subgroup, with a cutoff value of 2 multiples of the median, specificity was 32% and sensitivity was 10%; with a cutoff value of 1 multiples of the median, specificity was 100% and sensitivity was 50%. CONCLUSION: High maternal serum human chorionic gonadotropin levels at 15 weeks are related to a risk for preeclampsia. Depending on the human chorionic gonadotropin cutoff value, 32% or 100% of preeclampsia patients would be selected. The usefulness of preventive aspirin treatment from the fifteenth week needs more investigation in a larger multicenter study of preeclampsia. (Am J Obstet Gynecol 1996;175:37-40.)

Section snippets

MATERIAL AND METHODS

A multicenter retrospective study was carried out on patients who gave birth in the CMC Foch maternity unit between Jan. 1, 1989, and Dec. 1, 1992, or at the Hôpital de Saint-Brieuc between Jan. 1, 1990, and Dec. 31, 1991. Maternal serum hCG screening for trisomy 21 was performed in all patients between 15 and 18 weeks of amenorrhea. hCG was measured with an immunoenzymatic assay (SFRI, Paris). All samples were assayed in the same laboratory. hCG values were expressed as multiples of the

RESULTS

Of the 5776 patients who underwent maternal hCG screening for trisomy 21, 234 were affected by pregnancy-induced hypertension and 34 by preeclampsia. In 238 cases SGA neonates were observed.

The results are shown in Table I. For these three populations of patients, hCG values expressed in multiples of the median were higher than in the control population: 1.15 in pregnancy-induced hypertension, 1.67 in preeclampsia, and 1.21 in SGA neonates. These hCG values were not statistically different

COMMENT

A link between elevated maternal hCG levels and pregnancy-induced hypertension has been long suspected. As early as 1950 the placental hormone hCG was reported to be elevated in toxemia-affected pregnancies.⁸ In 1968, Teoh and Sivasamboo⁹ observed a third-trimester rise in hCG levels in hypertensive patients. More recently, the predictive value of maternal hCG for pregnancy-associated vascular disease was investigated by Vaillant et al.¹⁰ These authors presented a series of 252 cases, of which

Acknowledgements

We thank midwives Marie Caron and Brigitte Neveu of the Hôpital Foch who delivered our patients and recorded clinical information.

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Several other biomarkers, apart from the ones reviewed above, have been tested, but have in general not proven useful in the prediction of preeclampsia (reviewed in [33]). AFP and hCG are elevated in clinical preeclampsia [127], and have also been found elevated in second trimester in women later developing preeclampsia [128–130]. However, this association was only found for multiparous, but not nulliparous women in another study, with very low sensitivity and low positive predictive values [131].
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Le diagnostic anténatal d’anomalies fœtales est basé sur la recherche de signes d’appels échographiques ou biologiques à l’aide des marqueurs sériques maternels. En France, les premières études ont commencé en 1990, conduisant à un dépistage de la trisomie 21 au 2^e trimestre de grossesse mis en place en 1997 au niveau national. La législation de 1997 basée sur l’âge maternel et les marqueurs sériques maternels vient d’être modifiée en 2009 pour inclure la mesure de la clarté nucale au calcul de risque de trisomie 21 fœtale, et élargir la période de dépistage au 1^er trimestre de grossesse afin de diminuer le nombre d’amniocentèses. Le risque final classe ou non les patientes dans un groupe à risque accru de trisomie 21. Mais à côté de ce risque, on doit regarder de façon attentive le profil des marqueurs qui peut orienter le médecin vers une autre pathologie fœtale ou maternelle. Ce nouveau dépistage basé sur la législation de 2009 permet non seulement de dépister la trisomie 21 mais d’autres anomalies chromosomiques telles que la trisomie 13, la trisomie 18 ou la triploïdie, et des anomalies non-chromosomiques telles que la mort fœtale in utero, les défauts de fermeture du tube neural ou de la paroi abdominale. Des pathologies maternelles peuvent également être détectées et traitées en conséquence (mole, pré-éclampsie, toxémie gravidique, HELLP syndrome).
Antenatal diagnosis of fetal abnormalities is based on ultrasound scan and biochemical markers. In France, first studies began in 1990 leading to a national screening of Down syndrome in 1997 combining maternal age and biochemical markers in second-trimester (at 14-18 weeks gestation) This legislation has just been modified in 2009 to allow first-trimester screening (at 11- 13 weeks gestation) by adding fetal nuchal translucency to risk calculation in order to reduce amniocentesis. Final risk select pregnant women at increased risk of Down syndrome. Nevertheless, the profile of markers must be looked in an attentive way to detect other fetal or maternal pathology. This new screening of 2009 allows to detect Down syndrome but also other chromosomic abnormalities (as trisomy 13, trisomy 18 or triploidy), or non-chromosomic abnormalities as In Utero Fetal Death, neural tube defects or congenital abdominal wall defects. Maternal pathologies can also be detected and treated accordingly (mole, pre eclampsia, gravidic toxaemia, HELLP syndrome).
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Predicting PE would enable a better understanding of the physiological mechanisms responsible for this disease. It would also permit the identification of an at-risk population and consequently ease the set up of clinical trials.
Over 12,000 articles have been published on this subject. Critical review of the literature reveals that none of the investigations, performed individually, bears sufficient predictive value.
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Prediction refers to the application of a test to asymptomatic people for the purpose of classifying them in respect to their likelihood of developing a particular disease at a later date. In this respect preeclampsia is an ideal disorder in which to establish and evaluate predictive tests, some of the reasons being the following. Preeclampsia is a treacherous disease responsible for increases in maternal and perinatal morbidity and mortality. There are prophylactic interventions such as low dose aspirin and calcium that produce small–moderate benefits in terms of prevention, that a practitioner might wish to restrict to women at higher risk to develop the disease. The ability to predict the appearance of preeclampsia later in pregnancy would be of great value. It would identify those women who require more intensive monitoring, result in earlier recognition of the preeclamptic syndrome, and permit intercession before life-threatening complications develop. In addition, early identification of women at risk might help select the patients most likely to benefit from any therapeutic measures. It could further help clarify pathogenic mechanisms and might ultimately lead to more specific, mechanistically based strategies for prevention and treatment.
Elevated Serum Levels of Interleukin-15, Interleukin-16, and Human Chorionic Gonadotropin in Women With Preeclampsia
2009, Journal of Obstetrics and Gynaecology Canada
We sought to investigate the relationship between serum levels of interleukin 15 (IL-15), interleukin 16 (IL-16), and human chorionic gonadotropin (β-hCG) in women with a normal pregnancy and with preeclampsia, and their association with disease severity. We also wished to calculate the accuracy of these markers in diagnosing the disease and predicting its severity.
The study was conducted at Al Fayoum University in Cairo between December 2006 and September 2007. Thirty-two primigravid women with preeclampsia (preeclamptic group) scheduled for Caesarean Section were recruited and matched for age and duration of pregnancy with 35 normotensive primigravid women (control group). Of the preeclamptic women, 18 had severe preeclampsia, and 14 had mild preeclampsia. Blood sampling was performed for assays of serum IL-15, IL-16, and β-hCG.
Serum concentrations of IL-15, IL-16, and β-hCG were significantly greater in preeclamptic women than in normotensive pregnant women (P < 0.001). Moreover, they were significantly higher in women with severe preeclampsia than in mild cases (P < 0.001). There was a positive correlation between serum IL-15, IL-16, and β-hCG among all groups. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of serum β-hCG in predicting preeclampsia were 56.25%, 91.43%, 85.71%, 69.57%, and 74.63%, respectively. These values for IL-15 were 94.44%, 89.8%, 77.27%, 97.78%, and 91.04%, respectively, and for IL-16, the values were 88.89%, 95.92%, 88.89%, 95.92%, and 94.03%, respectively.
Serum levels of IL-15, IL-16, and β-hCG were significantly increased in preeclamptic women compared with normotensive women, and these levels correlated with disease severity. However, serum IL-15 and 16 had a greater overall accuracy than β-hCG in diagnosing severe preeclampsia.
Nous avons cherché à explorer la relation entre les taux sériques d’interleukine 15 (IL-15), d’interleukine 16 (IL-16) et de gonadotrophine chorionique (β-hCG) chez les femmes présentant une grossesse normale et une prééclampsie, ainsi que leur association avec la gravité de la maladie. Nous souhaitions également calculer la précision de ces marqueurs dans le diagnostic de la maladie et la prévision de sa gravité.
L’étude a été menée à l’Université Al Fayoum au Caire entre décembre 2006 et septembre 2007. Trente-deux primigravides présentant une prééclampsie (groupe « prééclampsie ») qui devaient subir une césarienne ont été recrutées et appariées en fonction de l’âge et de la durée de la grossesse avec 35 primigravides normotendues (groupe témoin). Au sein du groupe « prééclampsie », 18 femmes présentaient une prééclampsie grave et 14, une prééclampsie bénigne. Du sang a été prélevé aux fins du dosage des taux sériques d’IL-15, d’IL-16 et de β-hCG.
Les concentrations sériques d’IL-15, d’IL-16 et de β-hCG se sont avérées significativement plus élevées chez les femmes prééclamptiques que chez les femmes enceintes normotendues (P < 0,001). De surcroît, ces concentrations étaient considérablement plus élevées chez les femmes qui présentaient une prééclampsie grave que chez celles qui présentaient une prééclampsie bénigne (P < 0,001). Une corrélation positive a été constatée entre les taux sériques d’IL-15, d’IL-16 et de β-hCG parmi tous les groupes. La sensibilité, la spécificité, le coefficient de prévision d’un test positif, le coefficient de prévision d’un test négatif et la précision globale du taux sérique de β-hCG dans la prévision de la prééclampsie étaient de 56,25 %, de 91,43 %, de 85,71 %, de 69,57 % et de 74,63 %, respectivement. Pour ce qui est de l’IL-15, ces valeurs étaient de 94,44 %, de 89,8 %, de 77,27 %, de 97,78 % et de 91,04 %, respectivement, tandis que pour l’IL-16, elles étaient de 88,89 %, de 95,92 %, de 88,89 %, de 95,92 % et de 94,03 %, respectivement.
Les taux sériques d’IL-15, d’IL-16 et de β-hCG étaient considérablement accrus chez les femmes prééclamptiques, par comparaison avec les femmes normotendues, et étaient en corrélation avec la gravité de la maladie. Cependant, les taux sériques d’IL-15 et d’IL-16 présentaient une plus grande précision globale que la β-hCG dans le diagnostic de la prééclampsie grave.

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^☆: From the Service de Biochimie, Hôpital Ambroise Paré,^a the Service de Gynécologie-Obstétrique, Hôpital Foch,^b and the Service de Gynécologie-Obstétrique, Hôpital Saint-Brieuc.^c

^☆☆: Reprint requests: Françoise Muller, Biochimie, Hôpital Ambroise Paré, 92104 Boulogne, France.

^★: 0002-9378/96 $5.00 + 0 6/1/71427

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Maternal serum human chorionic gonadotropin level at fifteen weeks is a predictor for preeclampsia☆,☆☆,★

Abstract

Section snippets

MATERIAL AND METHODS

RESULTS

COMMENT

Acknowledgements

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Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Placenta

Am J Obstet Gynecol

Am J Obstet Gynecol

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