RESEARCH ARTICLE

https://doi.org/10.5005/jp-journals-10006-1840
Journal of South Asian Federation of Obstetrics and Gynaecology
Volume 12 | Issue 6 | Year 2020

TORCH Infection and Its Influence on High-risk Pregnancy

Smriti Baghel1, Saunitra A Inamdar2, 3

1,3Department of Obstetrics and Gynaecology, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India

2Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India

Corresponding Author: Smriti Baghel, Department of Obstetrics and Gynaecology, Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India, Phone: +91 9589498924, e-mail: drsaurabhvermabyt@gmail.com

How to cite this article: Baghel S, Inamdar SA. TORCH Infection and Its Influence on High-risk Pregnancy. J South Asian Feder Obst Gynae 2020;12(6):376–382.

Source of support: Nil

Conflict of interest: None

ABSTRACT

Introduction: Toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex virus (TORCH) infections are important groups of organisms which are initially inapparent, asymptomatic, and difficult to diagnose on the clinical ground during pregnancy but have the potential to cause bad obstetrical outcomes. The aim was to study the association of TORCH infection with the perinatal outcome in cases of high-risk pregnancies.

Materials and methods: A total of 200 high-risk pregnant patients of age group <35 years attending Antenatal Care Outpatient Department or admitted in Inpatient Department of Obstetrics and Gynaecology Department at Acharya Vinoba Bhave Rural Hospital, Sawangi, were included in the present study. The study group includes high-risk pregnant women with fetal congenital anomalies, recurrent pregnancy loss, oligohydramnios, intrauterine fetal death, fetal growth restriction, hypertensive disorders, bad obstetric history, preterm labor, polyhydramnios, and other medical disorders. Patient’s serum was analyzed for IgG (immunoglobulin G) and IgM (immunoglobulin M) antibodies against TORCH agents using ELISA kit and followed till delivery for the perinatal outcome. Perinatal outcome in high-risk pregnant women with seropositivity and seronegativity was compared.

Results: In 200 cases of high-risk pregnancy, the majority of women with seropositivity for TORCH infection were of younger age group with low parity, residing over rural areas and of low socioeconomic status. One hundred sixty-two cases (81%) were seropositive and 38 cases (19%) were seronegative for TORCH antibodies. The seropositivity in high-risk pregnant women for toxoplasma, rubella, cytomegalovirus, and herpes was 5.5, 75.5, 56, and 14.5%, respectively for IgG, while it was 0, 6, 4, and 0% for IgM, respectively. Our study showed that pregnant patients with high-risk factors for TORCH infection with seropositivity showed a significant association with adverse perinatal outcomes.

Conclusion: Association of seropositivity with high-risk factors for TORCH infection was found to be associated with adverse perinatal outcome as compared to seronegativity in same high-risk groups.

Keywords: High-risk pregnancy, Perinatal outcome, Seronegativity, Seropositivity, TORCH.

INTRODUCTION

For thousands of couples, the joyous event of birth of a child in their family may become the beginning of a long tortuous and tumultuous life. Human reproduction is a relatively insufficient process.1 Pregnancy loss is a challenging and frustrating problem for couples and clinicians alike. Miscarriage is often associated with guilt, embarrassment, and depressive states.2

"High-risk pregnancy (HRP) is a condition where the mother or the developing fetus or both are at an increased risk for complications during or after pregnancy and at birth."3 Bad obstetric outcome is a multifactorial condition, in which one of the major causes is maternal infection. One of the maternal infections caused by toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex virus (TORCH) group of organisms usually goes unnoticed and undiagnosed, which is transmitted in utero at several stages of pregnancy and causes adverse perinatal outcomes.

The TORCH infections are important groups of organisms which are initially inapparent, asymptomatic, and difficult to diagnose on the clinical ground during pregnancy but have the potential to cause bad obstetrical outcome in the form of congenital anomalies, oligohydramnios, FGR (fetal growth restriction), IUFD (Intrauterine fetal death), recurrent pregnancy loss (RPL), and stillbirth. The acronym TORCH was coined by immunologist Andre Nahmias.1 TORCH is an acronym which stands for toxoplasmosis, other agents, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV) infection. The majority of TORCH infections cause mild maternal illness, but the fetal consequences are serious. Treatment of maternal infection frequently has no impact on fetal outcomes. Early recognition of maternal disease and fetal monitoring once the disease is recognized are vital. Knowledge of these diseases can help the clinician appropriately counsel mothers on preventive measures to avoid these infections and aid in counseling parents on the potential for adverse fetal outcomes when these infections are present.4

Toxoplasmosis in human beings is caused by Toxoplasma gondii, an intracellular protozoan parasite, that is transmitted through contaminated food or water and undercooked meat. The incubation period is 5–23 days after ingesting the cysts. The infected women are usually asymptomatic, and during pregnancy, they may undergo pregnancy loss, stillbirth, and intrauterine malformations in the fetus.5,6

Rubella infection is transmitted from person to person by tiny droplets in air and mother to child through placental transfer. This disease lasts for 1–5 days and the incubation period is 2–3 weeks.7 It usually presents as a mild or asymptomatic infection in children and adults. However, the virus may cross the placenta and could result in miscarriage, fetal death, or an infant with serious birth defects including hearing impairment, cataracts, and cardiac defects, collectively known as congenital rubella syndrome.8

CMV is ubiquitous and species specific. Human beings are the reservoir hosts for this virus and the viruses are transmitted by direct contact with saliva, urine, and genital secretions. In pregnant women, the transmission is by direct contact with infected urine or saliva from young children or through sexual activity.9 The incubation period of CMV infection ranges between 4 and 12 weeks. In neonates, the symptoms include intrauterine growth retardation, microcephaly with intracranial calcification, hepatosplenomegaly, jaundice, chorioretinitis, thrombocytopenic purpura, and anemia.10 The major childhood disabilities like loss of vision, hearing, and cognitive impairment are also due to CMV infection.11

HSV is the most common sexually transmitted viral disease worldwide. HSV1 is transmitted during childhood by nonsexual contacts, while HSV2 is always transmitted sexually and is the major cause of genital herpes.12,13 Incubation period of herpes ranges between 4 and 21 days. In more than 75% of cases, primary genital HSV infection remains asymptomatic.14 In newborns, this infection remains a major cause of morbidity and mortality.15–17 Genital herpes infection during pregnancy may lead to spontaneous abortion, prematurity, or congenital and neonatal herpes.17,18

Most of the maternal infections are initially asymptomatic. Diagnosis based on the clinical presentation is difficult. Thus, the diagnosis of these infections largely depends on serological evidence.1 Utilizing TORCH panel for screening may help prevent many of these potential birth defects, as some of the TORCH infections can be effectively treated if the mother is diagnosed early in her pregnancy. Detection of IgM antibody against toxoplasma, rubella, HSV, and CMV is the best diagnostic modality for these infections. A national screening program for TORCH infections is lacking in INDIA. There are some controversial studies about the association between TORCH infection and adverse perinatal outcomes. Hence, we have decided to study the association between various HRPs and the relationship with perinatal outcome.

MATERIALS AND METHODS

Institute’s ethical committee approval was taken and, after explaining in detail the methodology of the study, an informed valid written consent was obtained from all the eligible subjects.

SAMPLE SIZE

At 95% confidence level,

Expected proportion taken as 50%

Absolute error or precision 7.5%

n = Z1-α/Z2 P(I − P)/δ2

n = sample size, Z1-α = 1.96, value of standard normal variable corresponding to the level of significance alpha 5%, P = expected proportion, q = I − P, δ = absolute error or precision, n = 1.962 × 50 (100 − 50)/7.52

Minimum sample size = 171 (rounded up to 200, which is adequate for the study)

In the present observational study, a total of about 200 pregnant patients of age group <35 years attending Antenatal Outpatient Department or admitted in Inpatient Department of Obstetrics and Gynaecology, Department at Acharya Vinoba Bhave Rural Hospital, Sawangi, during 2 years (2017–2019) were selected and included in the present study. The pregnant women with fetal congenital anomalies, oligohydramnios, IUFD, FGR, hypertensive disorders, preterm labor, polyhydramnios, and other medical disorders (like thyroid dysfunction, diabetes mellitus, heart diseases, sickle cell hemoglobinopathy, and anemia) in present pregnancy and pregnant patients with RPL and BOH (bad obstetric history) were included, while pregnant patients of age >35 years with consanguineous marriage and fetal congenital malformations caused due to exposure to teratogenic drugs, noxious gases, etc., were excluded.

Patients were evaluated on the basis of predesigned pro forma with respect to history, clinical examination, and investigation. Two milliliters of blood obtained aseptically from each woman in a duly labeled plain test tube was kept at room temperature for 20 minutes. The sample was then centrifuged and sera were separated and stored at -20°C until tested. Serum was analyzed for IgG (immunoglobulin G) and IgM (immunoglobulin M) antibodies against TORCH agents using a commercially available ELISA kit (Calbiotech, El Cajon, CA, USA] following the manufacturer’s instruction. The optical density (OD) at 450 nm with a filter of 600 to 650 nm dual-wavelength mode was measured by microwell ELISA reader (Robonik Elisa Plate Analyzer). The intensity of color generated was proportional to the amount of specific antibody in the sample. Negative and positive controls were used provided in the kit. The results were interpreted by immune status ratio index, calculated by dividing the specimen OD value by the cutoff calibrator ratio (calibrator OD × calibrator factor) in the central research laboratory of Jawaharlal Nehru Medical College of Datta Meghe Institute of Medical Sciences, Sawangi. ELISA kits used were having sensitivity >98% and specificity >98%. Results of seropositivity and seronegativity for TORCH infections were recorded by levels of IgG and IgM in antenatal patients. These readings were standardized and followed by Federation of Obstetric & Gynecological Societies of India guidelines.19 The statistical analysis was drawn on the basis of results obtained using Chi-square test and calculating odds ratio (OR) at 95% confidence interval for risk analysis. Software used is SPSS version 21.0. P-value < 0.05 and OR >2 were considered significant.

Antibody index interpretation: [As per criteria given in ELISA kits from Calbiotech, El Cajon, CA, USA] <0.9-no detectable antibody, 0.9–1.1-borderline positive, >1.1-detectable antibody. Patients showing seropositivity and seronegativity were followed till delivery for the perinatal outcome. Thereafter, the outcome of seropositivity and seronegativity in high-risk pregnant women was compared.

RESULTS

A total of 200 high-risk pregnant women were studied for a period of 2 years. As displayed in Table 1, it was observed that the majority of high-risk pregnant women with seropositivity for TORCH infection were of younger age group with low parity, residing over rural areas and of low socioeconomic status. In 200 cases of HRP, 162 cases (81%) were seropositive and 38 cases (19%) were seronegative for TORCH antibodies, as shown in Figure 1.

Fig. 1: Percentage of cases according to seropositivity and seronegativity for TORCH infection in the study group

Table 1: Distribution of demographic characteristics in high-risk pregnant women [200]
Variable No. of cases Percentage (%)
Maternal age
<25 years 103 51.5
26–29 years 77 38.5
>30 years 20 10
Gravida
1 77 38.5
2 56 28
3 or more 67 33.5
Religion
Hindu 193 96.5
Muslim 7 3.5
Others 0 0
Residence
Rural 186 93
Urban 14 7
Maternal education
Middle school or less 132 66
High and higher secondary 56 28
Graduate and more 12 6
Maternal occupation
Housewife 79 39.5
Laborer 65 32.5
Skilled workers 45 22.5
Professionals 11 5.5
Family income
<5,000 48 24.0
5,000–10,000 125 62.5
>10,000 27 13.5
*Socioeconomic status
Upper (I) 1 0.5
Upper middle (II) 1 0.5
Middle (III) 10 5
Lower middle (IV) 20 10
Lower (V) 168 84
*According to modified B.G. Prasad scale 2017, socioeconomic status is divided into five groups

Figure 2 depicts that seropositivity for toxoplasma IgG antibody was 5.5%, while no patients in the study group had IgM positive for toxoplasma. For rubella IgG, 75.5% of pregnant women showed seropositivity, while 6% were positive for IgM anti-rubella antibody. The seropositivity of pregnant women for CMV IgG and IgM was 56 and 4%, respectively. With respect to HSV, 14.5% of pregnant women were positive for IgG and none of them were positive for IgM antibodies.

Fig. 2: Seropositivity for TORCH infection in high-risk cases (162 cases)

*p-value <0.05 **p-value <0.001

In our study of 200 high-risk pregnant women, maximum risk factors were hypertensive disorder in 41 patients (20.5%), then oligohydramnios in 38 (19%) patients, and 24 patients (12%) with congenital anomaly while preterm labor in 19 patients (9.5%), eighteen cases of FGR (9%), fifteen cases of RPL (7.5%) present, twelve cases of polyhydramnios (6%), eleven cases of previous BOH (5.5%), and eight cases of IUFD (4%).

Table 2 depicts the correlation of high-risk factors in present pregnancy with seropositivity for TORCH agents.

Table 2: Correlation of high-risk factors in present pregnancy with seropositivity for TORCH agents
Risk factors >Toxoplasma Rubella Cytomegalovirus Herpes
IgG (%) IgM (%) IgG (%) IgM (%) IgG (%) IgM (%) IgG (%) IgM (%)
Preterm labor (19) 0 0 17 0 9 0 4 0
0 0 11.3 0 8.0 0 14.3 0
Intrauterine fetal death (8) 1 0 5 3* 5 0 2 0
9.1 0 3.3 25 4.5 0 7.2 0
Fetal growth restriction (18) 0 0 16 0 13 0 4 0
0 0 10.6 0 11.6 0 14.3 0
Oligohydramnios (38) 0 0 25 0 19 0 2 0
0 0 16.6 0 17.0 0 7.1 0
Previous bad obstetric history (11) 0 0 11 1 8 1* 0 0
0 0 7.3 8.3 7.1 12.5 0 0
Congenital anomaly (24) 4* 0 21 6** 15 6** 3 0
36.4 0 13.9 50.0 13.4 75.0 10.7 0
Hypertensive disorder (41) 2 0 32 1 24 0 9 0
18.2 0 21.2 8.3 21.4 0 32.2 0
Polyhydramnios (12) 1 0 10 0 10 0 5 0
9.1 0 6.6 0 8.9 0 17.9 0
Recurrent pregnancy loss (15) 0 0 13 0 12 0 0 0
0 0 8.6 0 10.7 0 0 0
Other medical disorders (18) 2 0 11 1 10 1 3 0
18.2 0 7.3 8.3 8.9 12.5 10.7 0
Total (200)
*p-value <0.05,
**p-value <0

Eight different perinatal outcomes were found in different high-risk factors in pregnant patients as shown in Table 3.

Table 3: Association of perinatal outcome with TORCH infection in high-risk pregnancy
S. No. Perinatal outcome (total) Toxoplasma Rubella Cytomegalovirus Herpes Seronegative cases
IgG IgM IgG IgM IgG IgM IgG IgM
1 Dead baby (8) Cases 2 0 5 3 5 0 2 0 1
P-value 0.014 – 0.383 0.589 0.758 0.556 0.360 – 0.966
OR 6.778 – 0.525 1.495 0.795 1.43 2.128 – 0.954
2 Neonatal intensive care unit admission (18) Cases 0 0 14 1 11 0 3 0 0
P-value 0.314 – 0.245 0.008 0.911 0.395 0.568 – 0.107
OR 1.064 – 2.401 1.460 1.065 – 1.468 – 1.165
3 Anomalous baby (24) Cases 4 0 21 6 15 6 3 0 2
P-value 0.011 – 0.145 0.645 0.577 0.000 0.821 – 0.469
OR 4.829 – 2.477 0.795 0.778 29.000 0.863 – 0.576
4 Abortus (3) Cases 0 0 2 1 2 1 0 0 0
P-value 0.674 – 0.720 0.868 0.975 0.009 0.481 – 0.500
OR – – 0.644 1.228 0.962 13.571 – – 1.152
5 Early neonatal death (6) Cases 0 0 6 1 4 1 1 0 0
P-value 0.549 – 0.157 0.499 0.965 0.108 0.848 – 0.336
OR – – 1.338 0.481 0.962 5.343 1.237 – 1.155
6 Stillbirth (3) Cases 0 0 2 2 2 0 1 0 0
P-value 0.674 – 0.720 0.147 0.975 0.722 0.331 – 0.500
OR 1.059 – 0.644 5.036 0.962 1.042 3.148 – 1.152
7 Premature baby (25) Cases 0 0 22 6 16 0 3 0 2
P-value 0.197 – 0.120 0.556 0.690 0.275 0.758 – 0.427
OR 1.067 – 2.615 0.747 0.837 – 0.818 – 0.547
8 Normal baby (113) Cases 5 0 81 0 81 0 15 0 32
P-value 0.366 – 0.014 0.109 0.535 11.747 0.326 – 0.013
OR 0.573 – 0.418 1.684 1.208 – 0.792 – 3.413
Total (200)

DISCUSSION

In our study, the maximum number of patients were in the age group of less than 25 years (51.5%) as shown in Table 1. This may be because maximum patients were of rural areas in our study. Rubella shows maximum seropositivity among all age groups followed by CMV. This is comparable with the study done by Rebekah et al.20 In our study, the maximum of our study population was from rural areas (83%) and studied till middle school (34.5%). The maximum number of patients was housewives and laborers in our study (72%). Maximum seropositive cases were from the lower class (168 cases, 84%). In the lower class, the number of cases was maximum for anti-rubella IgG antibody (84.8%) followed by CMV IgG (83.9%). Study done by Turbadkar et al.21 and Rajani4 is comparable with our study. In our study, we observed high-risk patients were more common in primigravida patients (38.5%), which was comparable to a study done by Rebekah et al.20

SEROPOSITIVITY FOR TORCH INFECTION

In our study of 200 cases, 162 cases (81%) were seropositive and 38 cases (19%) were seronegative for TORCH antibodies.

The seropositivity for toxoplasma IgG antibody was 5.5%, while no patients had IgM positivity for toxoplasma. Pregnant women of 75.5% showed seropositivity for rubella IgG antibody, while 6% were positive for IgM anti-rubella antibody. The seropositivity of pregnant women for CMV IgG and IgM was 56 and 4%, respectively. With respect to HSV, 14.5% were positive for IgG and nil for IgM antibodies.

The studies done by Kumar et al.,1 Pradhan,22 Padmavathy et al.,23 and Tatjana et al.24 were comparable with our study for seropositivity for TORCH infections.

PERINATAL OUTCOME

  1. Perinatal outcome with seropositivity for TORCH infection:
    In our study of total 200 cases, 8 different perinatal outcomes were found. There were dead baby (4%), NICU admission (8%), anomalous baby (12%), abortion (1.5%), early neonatal death (3%), stillbirth (1.5%), prematurity (12.5%), and normal baby (57.5%).
    • Dead baby has significant association with toxoplasma IgG (p-value <0.05). Also, toxoplasma IgG is a risk factor for IUFD (OR 6.778).
    • NICU admission has significant association with rubella IgM (p-value <0.05).
    • Rubella IgG is a risk factor for NICU admission (OR 2.477).
    • There is a strong association between CMV IgM antibody and anomalous baby (p-value <0.001). CMV IgM is a very high risk factor for anomalous baby as perinatal outcome (OR 29.00).
    • Significant association is also present between anomalous baby and toxoplasma IgG (p-value <0.05), with toxoplasma IgG also as a risk factor for anomalous baby (OR 4.829).
    • Significant association is also present between abortion and CMV IgM (p-value <0.05). CMV IgM is a risk factor for abortion (OR 13.571).
    • In our study, CMV IgM is also a strong risk factor for early neonatal death (OR 5.343).
    • Rubella IgM and herpes IgG are risks associated with stillbirth as perinatal outcome (OR >2).
    • Rubella IgG is a risk associated with prematurity as perinatal outcome (OR >2).
    The above-mentioned points show the significance of seropositivity for TORCH agents with a poor perinatal outcome.
    In our study, we have only studied the association of seropositivity and perinatal outcome in HRP.
    In the study done by Kumar et al.,1 of 75 women with HRP, 40 (53.33%) had RPL, 16 (21.33%) had IUFDs, 6 (8%) had early neonatal deaths, and 4 (5.33%) had congenital malformations. Another study done by Sarkar et al.25 reported that 38, 9, 5, and 20% of cases of abortions, IUFDs, stillbirth, congenital malformations, and early neonatal deaths, respectively.
    In study by Mohammad and Salman,26 perinatal outcome showed a high frequency of stillbirths (94.11%), IUFD (80%), abortion (70%), and congenital malformation (63%).
  2. Perinatal outcome with seropositivity for TORCH infection in different high-risk pregnant patients (Table 2).
    • Preterm labor (19 patients)
      Maximum seropositivity in preterm patients was found as rubella IgG (84.21).
      Perinatal outcome among them was maximum as a premature baby (13 cases, 68.4%).
      There was a highly significant association of preterm labor as a risk factor with a premature baby (p-value <0.001) with very high OR (30.514). Significant association was seen between early neonatal death and preterm labor as a risk factor (p-value 0.043, OR 5.206).
    In study done by Rebekah et al.,20 preterm labor showed the highest seropositivity for toxoplasma (55%).
    • IUFD (8 patients)
      Serologically, five patients were positive for rubella IgG and CMV IgG, three for rubella IgM, two for herpes IgG, and one for toxoplasma IgG. Significant association was found between toxoplasma IgG and dead baby as a perinatal outcome (p-value <0.05).
      Perinatal outcome associated with this was dead baby (eight cases, 100%). A very high significant association was present (p-value 0.000).
    In study done by Rebekah et al.,20 IUFD showed high seropositivity for toxoplasma (45%) and CMV (96%). This was comparable with our study.
    • Congenital anomaly (24 patients)
      Serologically, 21 patients were positive for rubella IgG and 15 for CMV IgG. Six patients were seropositive for rubella IgM and CMV IgM, four for toxoplasma IgG, and three for herpes IgG. A very high significant association was found between CMV antibody IgM and rubella IgM with anomalous baby (p-value <0.001). Significant association was seen in toxoplasma IgG and anomalous baby as a perinatal outcome (p-value <0.05). There is also a higher risk of abortion associated with congenital anomaly (OR 3.783).
      Perinatal outcome associated with this was anomalous baby (24 cases, 100%). A very high significant association was present (p-value 0.000).
    In study done by Rebekah et al.,20 anomalous malformation showed high seropositivity for rubella (97%) and CMV (97%). This is comparable to our study.
    In our study, congenital anomaly includes anencephaly, tetralogy of Fallot, ventricular septal defects, encephalocele, meningomyelocele, hydranencephaly, musculoskeletal dysplasia, congenital diaphragmatic hernia, and mesenteric cyst.
    Consanguinity and history of exposure to teratogenic agents were excluded from our study. However, chromosomal studies could not be done as many of the patients could not come for follow-up.
    • Hypertensive disorders (41 patients)
      In patients with hypertensive disorders, the presence of rubella IgM antibody has significant association with stillbirth in our study (p-value <0.05).
      Significant association was seen between hypertensive disorders as a risk factor and normal baby delivered (p-value 0.013).
      Perinatal outcome among them was maximum for normal baby (31 cases, 75.60%). Four cases (9.75%) were NICU admissions. There were three premature babies delivered (7.31%). Early neonatal death (two cases, 4.8%) and stillbirth (two cases, 4.8%) were perinatal outcomes associated.
    • Previous BOH (11 patients)
      In our study, there is a significant association between CMV IgM antibody with early neonatal death and rubella IgM with premature baby as a perinatal outcome (p-value <0.05).
      Perinatal outcome among them was maximum for normal baby (six cases, 54.54%). Two cases (18.18%) were premature babies. There was one case each of abortion, NICU admission, and early neonatal death as a perinatal outcome (9.09%).
      There is a high risk of abortion with previous BOH (OR 9.350). There is a significant association of previous BOH with abortion (p-value <0.05) in our study.
    However, study done by Surpam et al.27 in 225 patients, 150 previous BOH cases consisted of abortion in 44 (29.33%), IUGR in 32 (21.33%) cases, IUFD in 17 (11.33%) cases, premature in 11 (7.33%), early neonatal death in 25 (16.66%), and congenital malformation in 21 (14%).
    • Oligohydramnios (38 patients)
      Serologically, 25 cases were positive for rubella IgG and 19 cases were positive for CMV IgG.
    Perinatal outcome with oligohydramnios was maximum for normal baby (33 cases, 86.84%). Two cases had NICU admissions (5.26%). There was one case each of stillbirth, premature baby, and early neonatal death as perinatal outcome (2.63%).
    Significant association was seen between oligohydramnios and premature baby as a perinatal outcome (p-value <0.05). Highly significant association was noted between oligohydramnios and normal baby (p-value <0.001).
    • FGR (18 patients)
      Maximum seropositivity in FGR was seen for rubella IgG (16 cases) and CMV IgG (13 cases).
      Perinatal outcome among them was maximum for normal baby (10 cases, 55.55%). Four cases (22.22%) were NICU admissions. There were three cases of premature baby (16.66%) and one case of stillbirth (5.55%).
      FGR as a risk factor is significantly associated with NICU admission of the newborn (p-value <0.05). FGR is also a high-risk factor for stillbirth and NICU admissions (OR >2).
    • Polyhydramnios (12 patients).
      Serologically, 10, 10, and 5 cases were positive for rubella IgG, CMV IgG, and herpes IgG, respectively.
      However, perinatal outcome associated with this was normal baby (12 cases, 100%). Significant association was seen between polyhydramnios and normal baby (p-value <0.05).
    • RPL (15 patients)
      In our study, maximum seropositivity for RPL is seen in rubella IgG and CMV IgG.
      Perinatal outcome among them was maximum for normal baby (10 cases, 66.66%). Three cases (20%) were premature baby and two cases were NICU admissions (13.33%).
    However, there is an increased risk of NICU admissions with RPL (OR 3.308).
    In study done by Rebekah et al.,20 RPL had high seropositivity for rubella (87%). This is comparable with our study.
    However, other causes like uterine anomaly, incompetent os, etc.. are not elicited in our study.
    • Other medical disorders (18 patients)
      Other medical disorders included thyroid dysfunction, diabetes mellitus, heart diseases, sickle cell hemoglobinopathy, and anemia.
      In our study, maximum seropositivity for other medical disorders is seen in rubella IgG followed by CMV IgG.
      Also, there is increased risk of abortion with other medical disorders (OR 5.294).
      There was a significant association between other medical disorders and normal baby (p-value <0.05).
      Perinatal outcome among them was maximum for normal baby (16 cases, 88.88%). There was one case each of abortion and NICU admissions (5.55%).
  3. Perinatal outcome with seronegativity for TORCH infection in different high-risk pregnant patients.
    Of 38 seronegative cases, 32 (84.2%) had normal baby as outcome, which is significantly associated (p-value <0.05).
    Maximum seronegative cases were seen with oligohydramnios as a risk factor.

CONCLUSION

From our study, we conclude that association of seropositivity for TORCH infection with high-risk factors was found to be associated with adverse perinatal outcome as compared to seronegativity in same high-risk groups. As it is not made a protocol for screening of high-risk cases for TORCH, it should be considered for high-risk cases for diagnosis and management to get better perinatal outcome. Screening and early diagnosis of TORCH infection in high-risk patients have a definite role in early detection and appropriate management to prevent perinatal morbidity and mortality. Neonatal screening of congenital TORCH infection could not be carried out due to the nonavailability of facilities. Follow-up after 1 month was found difficult in IgM-positive cases due to noncompliance of patients from rural areas. Chromosomal study could not be carried out in patients with congenital anomalies as there were many defaulters in this group for further follow-up.

REFERENCES

1. Kumar R, Binnani A and Shyoran S. Seroprevalence of TORCH infections in pregnant women with bad obstetric history in and around Bikaner, Northern Western Rajasthan. J Appl Med Sci 2018;6(5):2018-2023. DOI: 10.21276/sjams.2018.6.5.30.

2. Singh G, Sidhu K. Bad obstetric history: a prospective study. Med J Armed Forces India 2010;66(2):117-120. DOI: 10.1016/s0377-1237(10)80121-2.

3. Pradeep MK, Gnanadeep NV, Umesh RD, et al. Prevalence of high risk pregnancy in rural Dharwad. IOSR J Dent Med Sci 2015;10:29-32.

4. Rajani M. Serological profile of TORCH infection among antenatal women at a Tertiary Care Center in North India. J Pure Appl Microbiol 2018;12(4): 2305-2311.

5. Montoya JG, Remington JS. Toxoplasma gondii. In: Mandel GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennetts' principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000, pp. 2858-2888.

6. Jones J, Lopez A, Wilson M. Congenital toxoplasmosis. Am Fam Physician 2003;67:2131-2138.

7. Ramesh V, Pardeep K, Suraj C. Rubella vaccine: new horizon in prevention of congenital rubella syndrome in the India. Hum Vaccines Immuno Ther 2012;8(6):831-833. DOI: 10.4161/hv.19584.

8. Lee JY, Bowden DS. Rubella virus replication and links to teratogenicity. Clin Microbiol Rev 2000;13:571-587. DOI: 10.1128/CMR.13.4.571.

9. Fowler KB, Pass RF. Risk factors for congenital cytomegalovirus infection in the offspring of young women: exposure to young children and recent onset of sexual activity. Pediatrics 2006;118:e286-e292. DOI: 10.1542/peds.2005-1142.

10. Al-Hareth Z, Monem F, Abdel Megiud N. Is low birth weight a risk indicator for congenital cytomegalovirus infection? J Infect Dev Countries 2010;4:44-47. DOI: 10.3855/jidc.539.

11. Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 2007;17:355-363. DOI: 10.1002/rmv.544.

12. Elena A, Daniela F, Monica M, et al. Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention. Virol J 2009;6:40. DOI: 10.1186/1743-422X-6-40.

13. Marco C, Massimo G. The importance of diagnosing genital herpes. J Antimicrob Chemother 2001;47:9-16.

14. Serdar U. Genital herpes in pregnancy. http://emedicine.medscape.com/article/274874-overview. Accessed 18 November 2011.

15. O'Riordan DP, Golden WC, Aucott SW. Herpes simplex virus infections in preterm infants. Pediatrics 2006;118(6):e1612-e1620. DOI: 10.1542/peds.2005-1228.

16. Brown ZA, Benedetti J, Ashley R, et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. New Engl J Med 1991;324(18):1247-1252. DOI: 10.1056/NEJM199105023241804.

17. Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. New Engl J Med 1997;337(8):509-515. DOI: 10.1056/NEJM199708213370801.

18. Biswas D, Borkakoty B, Mahanta J, et al. Seroprevalence and risk factors of herpes simplex virus type-2 infection among pregnant women in Northeast India. BMC Infect Dis 2011;11:325. DOI: 10.1186/1471-2334-11-325.

19. Pundit S, Gupte S, Sheriar N, et al. Screening and management of TORCH in pregnancy. Consensus Group meeting, 2014, pp. 1-6.

20. Prasoona KR, Srinadh B, Sunitha T, et al. Seroprevalence and influence of torch infections in high risk pregnant women: a large study from South India. J Obstet Gynaecol India 2015;65(5):301-309. DOI: 10.1007/s13224-014-0615-3.

21. Turbadkar D, Mathur M, Rele M. Seroprevalence of torch infection in bad obstetric history. Indian J Med Microbiol 2003;21:108-110.

22. Pradhan SV. Epidemiological and serological profiles of TORCH infection in pregnancy. J Pathol Nepal 2015;5:705-708. DOI: 10.3126/jpn.v5i9.13690.

23. Padmavathy M, Gowri M, Malini J, et al. Seroprevalence of TORCH infections and adverse reproductive outcome in current pregnancy with bad obstetric history. J Clin Biomed Sci 2013;3(2):62-71.

24. Vilibie-Cavlek T, Ljubin-Sternak S, Ban M, et al. Seroprevalence of TORCH infection in women of child bearing age in Croatia. J Matern Fetal Neonatal Med 2010;24(2):280-283. DOI: 10.3109/14767058.2010.485233.

25. Sarkar MD, Anuradha B, Sharma N, et al. Seropositivity of toxoplasmosis in antenatal women with bad obstetric history in a Tertiary-care Hospital of Andhra Pradesh, India. J Health Popul Nutr 2012; 30(1):87-92. DOI: 10.3329/jhpn.v30i1.11287.

26. Mohammad EAK, Salman YJ. Study of TORCH infections in women with Bad Obstetric History (BOH) in Kirkuk city. Int J Curr Microbiol Appl Sci 2014;3(10):700-709.

27. Surpam RB, Kamlakar UP, Khadse RK, et al. Serological study for TORCH infections in women with bad obstetric history. J Obstet Gynecol India 2006;56(1):41-43.

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