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Revista de la Facultad de Medicina Humana

Print version ISSN 1814-5469On-line version ISSN 2308-0531

Rev. Fac. Med. Hum. vol.20 no.1 Lima Jan./Mar. 2020 

Original article

Factors associated with gestational trofoblastic disease in a Peruvian Reference Hospital

Johana Huanca-Llamo1  , Surgeon

German Aranzabal-Alegria1  , Surgeon

Willer Chanduvi1 

1Faculty of Human Medicine, Ricardo Palma University. Lima, Peru



To determine the risk factors associated with gestational trophoblastic disease in patients treated in an outpatient office of the Gynecobstetrics service of the National Hospital Hipólito Unanue between January 2014 and December 2018.


An observational, retrospective, analytical study of cases and controls was conducted. A total of 60 cases were taken as a sample and 120 stories were reviewed as a control group. The information obtained from the review of medical records was recorded in the data collection form. The odds ratio was determined with their respective confidence intervals (CI = 95%). For the multivariate analysis, a binary logistic regression model was used.


In the bivariate analysis, the factors associated with gestational trophoblastic disease were the history of abortion (OR 6.54; 95% CI 3.12 - 13.74; p <0.001) and multiparity (OR 3.35; 95% CI: 1.47 - 7.65; p <0.001). Age under 20 years was associated with a lower frequency (OR: 0.13; CI: 0.03-0.48 p <0.001). In the multivariate analysis, the only variables that showed significance were the history of abortion (OR 4.85; 95% CI 1.82-12.91; p = 0.002) as a risk factor and age under 20 years as a protective factor (OR 0.08; 95% CI 0.02 -0.32; p <0.001).


The history of abortion and multiparity were associated with the presence of gestational trophoblastic disease while the age under 20 years behaved as a protective factor.

Keywords:  Gestational; Trophoblastic Disease; hydatidiform mole; risk factors; Trophoblasts (Source: MESH).


Gestational trophoblastic disease is an old pathology. About 2500 years ago, Hippocrates in his theory of the 4 humors described hydatidiform mole as hydrops or fluid retention in the uterus which he attributed to unhealthy water1,2.

The incidence and prevalence of this disease depends on the geographical area; The Asian continent has the highest incidence 1 out of every 500 pregnancies; Also with greater capacity for malignancy, in western countries the incidence is 1 in 1500 pregnancies where only 5 to 10% persists the disease or becomes malignant, in Latin America the incidence ranges from 4.6 per 1000 pregnancies, in our country the incidence ranges from approximately 2.33 to 4.77 per 1000 pregnancies3.

The term of gestational trophoblastic disease is used to describe a group of tumors that are characterized by abnormal trophoblast proliferation. Trophoblast produces human chorionic gonadotropin, which is why it is important to quantify this peptide for the diagnosis, treatment and follow-up of this disease4. From a histological point of view, gestational trophoblastic disease is divided into hydatidiform mole, which is recognized by the presence of villi and non-molar trophoblastic neoplasia, which lacks villi.5,7.

Hydatidiform moles are excessively immature placentas and edematous. These comprise partial, complete and malignant invasive hydatidiform moles. Non-molar trophoblastic neoplasia include choriocarcinoma, placental trophoblastic tumor, and epithelioid trophoblastic tumor. Gestational trophoblastic neoplasia include invasive mole, choriocarcinoma, placental trophoblastic tumor, and epithelioid trophoblastic tumor8,9.

In relation to risk factors, the age under 20 years and over 35 are factors associated with the development of the pathology. Multiparity, history of abortion, history of molar pregnancy among others are factors associated with the development of the disease and some find significant association in relation to the occupation of the father10.

In the past, metastatic tumors had a high mortality rate, but thanks to chemotherapy, most tumors are curable11.

Therefore, our study aimed to evaluate the incidence and factors associated with gestational trophoblastic disease in patients treated at Hipolito Unanue National Hospital.


Type of study

We conducted an observational, retrospective and analytical study of types of cases and controls.


The population consisted of pregnant women treated in the Gynecobstetrics Service of the Hipolito Unanue National Hospital during a period of 6 years. Patients with complete and available medical records were included; While those with incomplete data were excluded. After applying the selection criteria, we took 60 cases of trophoblastic disease and 120 controls from patients from the same service without trophoblastic disease.

Study procedures and variables

The necessary permits were requested for access to the clinical records of the Gynecobstetrics Service of Hipolito Unanue National Hospital, extracting the clinical records according to the list of cases and controls previously selected at random. The incidence of trophophastic disease was determined. Data were obtained from the website of the statistics department of the HNHU, considering the population at risk those patients who were discharged from the postpartum period.

Age, socioeconomic level (based on incomes reported by the family), parity, history of abortion, history of molar pregnancy, use of contraceptives, menarche younger than 12 years and blood group were evaluated as variables potentially associated with gestational trophoblastic disease12.

Statistical analysis

The bivariate analysis for the evaluation of factors associated with gestational trophoblastic disease was performed using the chi square test. Likewise, we determined the odds ratio with their respective confidence intervals (95% CI) using binary logistic regression. Subsequently, a multivariate analysis was performed including the variables significantly associated in the bivariate analysis. A p value <0.05 was considered statistically significant. The calculations were performed using the statistical package SPSS v25.

Ethical aspects

The identity of the patients was respected and the entire protocol was executed with the institutional approval of the Ricardo Palma University and the Hipolito Unanue National Hospital.


Incidence results were 0.7 % during 2014; In 2015 were 0.6%; In 2016 were 0.8% and in 2017 were 0.8%.

Of the total number of patients studied, the most frequent age range was 20 to 35 years, with 65%, and also the majority (53%) had a low socioeconomic level. On the other hand, about a third were multiparous (32.2%) while the majority were primiparous (38.9%). The other general characteristics are shown intable 1.

Table 1. General characteristics of the patients treated at Hipolito Unanue National Hospital. 

  Frequency Percentage
Under 20 years 12 6,7%
Between 20 y 35 years 117 65,0%
Over 35 years 51 28,3%
Socioeconomic level
Low 96 53,3%
Medium 84 46,7%
Nulliparous 46 25,6%
Primiparous 70 38,9%
Multiparous 58 32,2%
Grand Multiparous 6 3,3%
History of twin pregnancy
Yes 1 0,6%
No 179 99,4%
History of abortion
Yes 44 24,4%
No 136 75,6%
Use of contraceptives methods
Yes 13 7,2%
No 167 92,8%
Menarche before 12 years
Yes 14 7,8%
No 166 92,2%
Blood Group
O 176 97,8%
A 4 2,2%

As can be seen intable 2, the most frequent histological type was complete hydatidiform mole with 66.6%; Followed by partial hydatidiform mole with 26.7%; The other histological types had smaller proportions.

Table 2. Histological type of cases of trophoblastic disease of patients treated at Hipolito Unanue National Hospital. 

Histological Type Recount Percentage %
Complete Hydatidiform Mole 40 66,6 %
Partial Hydatidiform Mole 16 26,7 %
Invasive Mole 2 3,3 %
Choriocarcinoma 1 1,7 %
Placental Site Tumor 1 1,7 %
TOTAL 60 100 %

When performing the bivariate analysis, we found that gestational trophoblastic disease was associated with being younger than 20 years, being multiparous and having a history of abortion.

Table 3. Bivariate analysis of the factors associated with developing gestational trophoblastic disease in patients treated at Hipolito Unanue National Hospital. 

Risk Factors Cases n (%) Controls n (%) OR 95% CI P Value
Age 20-35 8 (13,3 %) 4 (3,3 %)      
<20 25 (41,7 %) 92 (76,7 %) 0,13 0,03 - 0,48 0,002
>35 27 (45 %) 24 (20 %) 0,56 0,15 - 2,10 0,393
Socioeconomic Level Low 38 (63,3 %) 58 (48,3 %) 1,84 0,97 - 3,48  
Medium 22 (36,7 %) 62 (51,7 %)     0,057
Parity Nulliparous 13 (21,7 %) 33 (27,5 %)      
Primiparous 10 (16,7 %) 60 (50 %) 0,42 0,16 - 1,07 0,069
Multiparous 33 (55 %) 25 (20,8 %) 3,35 1,46 - 7,65 0,004
Grand Multiparous 4 (6,6 %) 2 (1,7 %) 5,07 0,82 - 31,16 0,079
History of Molar Pregnancy Yes 1 (1,7 %) 0 (0 %) 3,034 2,462 - 3,739 0,156
No 59 (98,3 %) 120 (100 %)      
History of Abortion Yes 29 (48,3 %) 15 (12,5 %) 6,548 3,121-13,739 <0,001
No 31 (51,7 %) 105 (87,5 %)      
Use of Contraceptive Methods Yes 7 (11,7 %) 6 (5 %) 2,509 0,804-7,831 0,103
No 53 (88,3 %) 114 (95 %)      
Menarche < 12 years Yes 8 (13,3 %) 6 (5 %) 2,923 0,965-8,853 0,049
No 52 (86,7 %) 114 (95 %)      
Blood Group O 57 (95 %) 119 (99,2 %) 6,263 0,637-61,545 0,074
A 3 (5 %) 1 (0,8 %)      

When performing the multivariate analysis, the only variables that showed significance were history of abortion as a risk factor and age under 20 years as a protective factor..

Table 4. Multivariate analysis to determine the risk of developing gestational trophoblastic disease of patients treated at Hipolito Unanue National Hospital. 

Variables Adjusted OR 95% CI P value
Age 20 - 35 Ref
Age <20 Age <35 0,08 0,22 0,02 0,06 0,32 1,13 <0,001 0,073
Nulliparous Ref
Primiparous Multiparous Grand Multiparous History of Abortion 0,485 1,759 3,873 4,84 0,17 0,60 0,50 1,81 1,37 5,09 29,09 12,91 0,172 0,298 0,193 0,002


Gestational trophoblastic disease constitutes a diverse group of lesions with specific pathogenesis, morphological characteristics and clinical characteristics13. There are few studies whose objectives were to identify possible risk factors associated with the development of gestational trophoblastic disease. Regarding the frequency of gestational trophoblastic disease in our study we found 7 cases per thousand postpartum women, similar to what was described in a study carried out in Mexico in 201613.

Of the factors studied, the most frequent in the study population was history of abortion, which was present in 48.3% of cases and was associated with an increase of more than six times the risk of developing trophoblastic disease compared to women who had no history of abortion. This result is similar to that found by Shamshiri H. et al14where the risk of developing the disease was 3.17 times, postulating that the woman must have a certain predisposition for the formation, in addition, the presence of recurrent abortions associated with molar pregnancy and multiparity are protective against the whole mole.

Regarding multiparity, which is an important risk factor in pregnancy, childbirth and postpartum for various morbidities. Our study found that 55% of cases had multiparity; However, the relationship found in the bivariate analysis was not found in the multivariate analysis. A study carried out by Garcia L. et al15found an OR of 5.41 associated with multiparity in agreement with what was found by Sanchez A.16in his study, associating it to the educational level of the population concerned. In contrast, it is worth mentioning that in a study by Fletcher et al17the nulliparity associated with the development of gestational trophoblastic disease was analyzed, finding that more than 60% of patients reported a molar pregnancy during their first pregnancy, which agrees with what was found in the present study.

The analysis of the age variable showed that 13.3% of the cases were younger than 20 years and 45% were older than 35 years. It was also found that the age younger than 20 years had an OR lower than 1, behaving as a protective factor for gestational trophoblastic disease, a relationship corroborated in the multivariate analysis. It is worth mentioning that Shamshiri H. et al14reported that the younger the greater the risk of developing gestational trophoblastic disease, this explains a relationship between the risk of molar pregnancy and maternal age extremes; With an increased risk of 10 times in women over 40 years and 1.3 times in adolescents. While the highest risk in older women is consistently high, due to declining fertility in this age group. While the effect of aging on eggs can cause abnormal gametogenesis and/or fertilization may be part of the explanation in advanced maternal age, this does not explain the data on adolescents18.

Regarding socioeconomic level, in the present study no significant association was found. No significant association was found with previous molar pregnancy. This is corroborated by Shamshiri et al14, who associated trophoblastic disease with educational level, observing that this pathology was more frequent in patients with low educational level. These findings are reported in countries of Latin America and Asia where there may be some bias given the high poverty of this region, it is reported that this incidence would decrease through better medical control from the beginning of pregnancy and better access to food sources18.

In turn, no association was found with the use of contraceptive methods. This contrasts with the findings of Palmer et al.19; Those who found an association with a history of oral contraceptive use sometime before pregnancy, increasing the risk of trophoblastic disease as the duration of contraceptive use increased. However, Vecchia C. et al20in their study found no association between these variables, which attributed to the use of the intrauterine device that was frequent in their environment; This is in line with the present study. This may be due to the increased use of injectable or depot contraceptive methods.

Likewise, no significant association was found in relation to blood group A and trophoblastic disease, the same was found in other studies, such as that carried out by Sharifi N. et al8who observed that there was a positive relationship of molar disease with blood group and raised the need to know the blood group of the father, an element also recommended by WHO.

The present study had the limitations that other factors such as diet or genetic factors were not measured. However, the relevance of the factors evaluated and found shed light to perform the respective interventions in order to prevent this disease.


The only risk factor associated with gestational trophoblastic disease in the adjusted analysis was history of abortion, while age under 20 years behaved as a protective factor.


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Financing: self-financed

Received: October 25, 2019; Accepted: December 10, 2019

Correspondence: Luis A. Cano Cárdenas Address: Av. Benavides 5440, Santiago de Surco, Lima-Perú Telephone: +51 999 263 196

Authorship contributions: The authors participated in the genesis of the idea, project design, data collection and interpretation, analysis of results and preparation of the manuscript of this research paper.

Conflict of interest: The authors declare no conflict of interest in the publication of this article

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