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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
First Trimester Combined Aneuploidy Screening for Trisomy 21: A Three Years Retrospective Study
Correspondence Address :
Varsha Birla,
Kohinoor City, Commercial Building-A, 4th Floor, Off-L.B.S. Marg, Vidyavihar (West), Mumbai-400070, Maharashtra, India.
E-mail: Varsha.birla@metropolisindia.com
Introduction: Prenatal testing also known as maternal screening is primarily performed to screen out most common chromosomal anomalies in the foetus using maternal blood. It provides an accurate and sensitive assessment of a patient’s risk of carrying a foetus with chromosomal anomalies.
Aim: To study the first trimester prenatal screening using a Foetal Medicine Foundation (FMF) certified platform to estimate the risk of foetal trisomy 21.
Materials and Methods: This retrospective study was conducted at Global Reference Laboratory, Mumbai, Maharashtra, India, from January 2018 to March 2021 on samples of 86118 pregnant Asian women with respect to age, the risk cut-off was set at 1:250 for trisomy 21. The study included determination of free β-human Chorionic Gonadotropin (β-hCG) and Pregnancy Associated Plasma Protein-A (PAPP-A) in maternal serum, ultrasound studies of Crown Rump Length (CRL), Nuchal Translucency (NT) and nasal bone and maternal characteristics. Concentration of biochemical parameters was expressed in Multiple of Medians (MoM) respective to gestation age. Risk assessment of trisomy 21 was analysed using lifecycle software cut-off being 1:250 at sampling.
Results: The overall positive risk (high risk) for trisomy 21 obtained was 2.58%, association with advanced maternal age, history of Insulin dependent diabetes mellitus and absent nasal bone status. Biochemically, the MOM of β-hCG was high with mean MoM of 2.40 (>1.5) and MoM of PAPP-A was low with mean MoM of 0.64 (≤0.6).
Conclusion: This study enabled us to understand the importance of prenatal testing, a non invasive screening of chromosomal disorders like trisomy 21 which gives the advantages of early counseling and diagnosis quite as early as in the first trimester of pregnancy. It helps in drastically reducing the use of invasive procedures associated with risk of miscarriages. It is suggested that screening for chromosomal abnormalities be offered in all antenatal women irrespective of age and parity.
Crown rump length, Human chorionic gonadotropin, Nasal bone, Nuchal translucency, Multiple of medians, Pregnancy associated plasma protein A
Prenatal testing also known as maternal screening is primarily performed to screen out most common chromosomal anomalies in the foetus using maternal blood. It provides an accurate and sensitive assessment of a patient’s risk of carrying a foetus with chromosomal anomalies (1). Earlier the screening was offered to only elderly pregnancies however there are several studies and statistics proving the risk of trisomy in young age group as well. Thus, all pregnant females should be offered both screening and diagnostics tests irrespective of maternal age, all should undergo counselling and have the right to accept or reject the test. Screening inturn also helps in reducing the risk of miscarriage involved in undergoing invasive procedure (2).
First trimester combined screening involves Nuchal Translucency (NT) screening along with “dual marker” or double marker test. NT is the sonographic appearance of a collection of fluid under the skin behind the foetal neck in the first trimester of pregnancy. The term translucency is used, irrespective of whether it is septated or not and whether it is confined to the neck or envelopes the whole foetus. Because slight misinterpretations in evaluating NT values will cause wide variation in accuracy of the calculations, it is essential to combine NT with maternal serum screening and is the recognised first trimester screen performed between 10 and 13.6 weeks of gestation (1),(3),(4).
Screening tests are associated with identifying Patau, Edwards and Downs syndromes (trisomy 13, 18 and 21, respectively), and the less severe Turner (monosomy X) and Klinefelter (XXY) syndromes. First trimester screening means screening for trisomy’s (13,18,21) and trisomy 21 being the most common cause of mental retardation is included in this screening programme (5). Downs syndrome, with an incidence rate of 1 in 800 pregnancies, is the predominant reason for women seeking prenatal diagnosis (6),(7).
The invasive diagnostics test like amniocentesis and chorionic villous sampling required for karyotyping and confirmation of trisomy’s carries risk of miscarriage and currently these procedures are offered to only a small group of pregnant women who are at high risk of having an offspring with a chromosomal defect as compared to the general population (8). The aim of the currently available screening tests is actually to identify, with the highest possible sensitivity and specificity, those women who should be offered the invasive procedure. The risk for many of the chromosomal defects increases with maternal age. Additionally, because foetuses with chromosomal defects are more likely to die in-utero than normal foetuses, the risk decreases with gestational age.
Objective of this study was to understand positivity amongst different age groups with the variables such as clinical history, type of pregnancy and Ultrasound (USG) markers. This would help to target the high-risk population at an early stage.
This retrospective study was conducted at Global Reference Laboratory, Mumbai, Maharashtra, India, from January 2018 to March 2021, included samples of 86118 pregnant Asian women with respect to age, the risk cut-off was set at 1:250 for trisomy 21 (4). The maternal age ranging from 18 years to 50 years of age was considered. Biochemical markers like free β-human Chorionic Gonadotropin (β-hCG) and Pregnancy Associated Plasma Protein-A (PAPP-A) was performed using maternal blood from 11 to 13.6 weeks of gestation on PerkinElmer® platform by Time Resolved Fluroimmunoassay (TRF). Information about the patient’s age, clinical history details were collected and taken from the maternal Test Requisition Form (TRF) and Ultrasonography report. First trimester combined screening was performed by calculating risk using software with ultrasound findings, serum biochemical markers and maternal characteristics (9). The study was conducted retrospectively from the data available in information system of the laboratory. The approval was obtained to use this data for publication from Conscience Independent Ethics Committee (wide letter dated 2nd June 2021).
Assay
Maternal serum concentrations of Pregnancy Associated Plasma Protein-A (PAPP-A) and free β-hCG biomarkers have been read with PerkinElmer® kits {Foetal Medicine Foundation (FMF) certified} on AutoDELPHIA platform operates on the principle of time resolved fluroimmunoassay. Maternal characteristics like age, weight, ethnicity, history of smoking, diabetes, previous history of trisomy, gestation of foetus, number of foetus, mode of conception was taken into consideration. Ultrasonography details like date of USG, Crown Rump Length (CRL), Nuchal Translucency (NT) and nasal bone status was incorporated. The processing of data and determination of the risk of trisomy 21 has been done with LifeCycle 7.0 software (Perkin Elmer Prenatal software).
The measured concentration of free β-hCG and PAPP-A is converted into MoM appropriate to the gestation age of pregnancy (2). The Multiples of the Median (MoM) value is obtained by dividing an individual’s marker concentration by the median level of that marker for the entire population at the same gestational age in that laboratory (10).
Statistical Analysis
Data was analysed using R software version 3.5.2. Result of quantitative variable like β-hCG MoM, PAPP-AMoM, NT MoM, trisomy 21 age risk are expressed as mean+Standard Deviation (SD), median {Interquartile Range (IQR)} and range. Result of qualitative variable like age at Expected Date of Delivery (EDD) (in years), weight (in kg), gestational age (in weeks), number of foetuses, smoking history, ethnicity, assistance method, diabetic, nasal bone, trisomy 21 is expressed in number and percentage. Shapiro-Wilks Test was used to determine whether data sets differed from a normal distribution. For categorised variables like age group, gestational age, weight, smoking, ethnicity, nasal bone compared to trisomy 21 Pearson’s Chi-square test or Fisher’s-exact test has been used. For continuous variable between two groups was compared using Mann-Whitney U test and for three or more groups Kruskal-Wallis test was used based on normality testing. To determine the independent effects of variables associated with the positive trisomy 21, a multiple binary logistic regression analysis was then performed including variables with a p-value <0.1 from bivariate analysis. Result was considered significant at p-value <0.05.
Dual marker maternal screening was performed on FMF certified platform and a total of 86118 cases were studied from January 2018 to March 2021.
Total 72.2% of pregnant females were in the age group of 26-35 years. A significant number of pregnant females lies in elderly age group of ≥36 years (12.45%) (Table/Fig 1). The overall positive risk (high risk) for trisomy 21 obtained was 2.58% (Table/Fig 2). Cases mentioned under the category of unknown were excluded from statistical calculation (unknown are those cases which failed to provide specific demographic data).
There was significant association of risk for Downs syndrome with increased maternal age (Table/Fig 3). Risk of trisomy 21 was found to be as high as 6.11% in maternal age group of 36 years to 40 years. Association was seen with presence of maternal history of insulin dependent diabetes (Table/Fig 3).
The risk of T21 was high in cases with absent (unossified/hypomineralised) nasal bone (Table/Fig 4). Although 69.67% of foetus with absent nasal bones were normal foetuses, still it is one of the soft markers in the risk assessment of aneuploidy.
Biochemically, the MOM of β-hCG was high with mean MoM of 2.40 (>1.5) and MoM of PAPP-A was low with mean MoM of 0.64 (≤0.6) (Table/Fig 5).
The age-related risk for Trisomy 21 increases with increase in maternal age (Table/Fig 6).
Multivariate analysis identified patient with age group >40 years (p-value=0.0001, OR=7.5533), 36-40 year (p-value=0.0007, OR=2.8636), gestational age 13-13.6 weeks (p-value=0.0416, OR=1.1783), NB (p-value=0.0001, OR=1.6295), Ethnicity Caucasian (p-value=0.0001, OR=3.623), β-hCG MoM (p-value=0.0001, OR=2.7094, NT MOM (p-value=0.0001, OR=9.6457) where independently associated with positive T21 (Table/Fig 7).
A screening programme should be efficient enough to identify an anomaly at right time and should be able to offer a solution at the same time. Now-a-days, prenatal screening and diagnosis between 10 to 14 weeks of gestation is becoming more and more available and efficient worldwide. Recent studies by Malone FD et al., also concluded that the sensitivity of first trimester screening (87%) is much more than second trimester tests (81%) (3),(11). So apart from the fact of higher sensitivity in comparison to other tests the first trimester screening method is also cost-effective since the indication of number of invasive procedures will be clearly defined.
One of the biggest advantages of the first trimester screening test is that counselling and invasive diagnosis of chromosomal defects can be accomplished early in pregnancy thus significantly reducing the anxiety. By providing the option of early termination of pregnancy the situation becomes less complicated for both the patient and the obstetrician (12). According to Carlson LM and Vora NL, one should remember that the double marker test is only a screening test which provides a risk for the genetic disorder, but not the diagnosis (13).
The outcome of prenatal screening is in the form of screen positive or screen negative for Trisomy 21 and these results are based on the laboratory specific cut-offs (14). The sensitivity of the estimated risk significantly depends on the accuracy of the information provided. The necessary adjustments are made in the measured maternal serum concentration of free β-hCG and PAPP-A in accordance with the gestational age, maternal age, weight, ethnicity, smoking status, history of insulin dependent diabetes mellitus, method of conception, parity (15).
Hence, it is essential to submit accurate information along with maternal sample to laboratory for risk assessment failing which may lead to significant alterations. In the present retrospective study, the risk evaluation was calculated at sampling and there was statistically significant increase in risk for Downs syndrome in pregnant females with history of insulin dependent diabetes mellitus, twin gestation and absent/unossified nasal bone status. Although there was no statistically significant increase in risk with respect to history of smoking and assisted reproduction, but the risk was high in cases with history of smoking and cases of In-Vitro Fertilisation (IVF) pregnancies in accordance with Hook EB and Cross PK book- Cigarette Smoking and Downs Syndrome (16),(17). Previous studies were compared with the present study (Table/Fig 8) (2),(12),(14),(16),(18).
In the present study, it was demonstrated that the age-related risk for Trisomy 21 increases significantly with maternal age. Mean estimated Risk of 1:1200 for age group less than 20 years to 1:66 in maternal age greater than 40 years. This can be used as an independent marker in interpreting trisomy 21 age related risk. This was in accordance with review article published by Shiefa S et al., in 2013 (14). A molecular biology study has demonstrated that in trisomy 21 there is marked increase in free β-hCG concentration. Decreased levels of PAPP-A are found in association with abnormal placental function which has formed the basis for the first trimester screening of foetal Downs syndrome (19).
In the current study, the biochemical marker behaved in the similar fashion strengthening the above association. Using MoM values, rather than absolute levels, also allows results from different laboratories to be interpreted in a consistent way. In euploid pregnancies, the average adjusted value for both free β-hCG and PAPP-A is 1.0 MoM at all gestations (14). In the present study, the MoM of Trisomy 21 high risk cases free β-hCG was high with mean MoM of 2 (>1.5) and MoM of PAPP-A was low with mean MoM of 0.6 (≤0.6) (Table/Fig 5).
The strength of the present study includes the huge sample size with varied demographic findings, evaluation using a FMF certified platform.
Limitation(s)
The limitation of this study was that the data of outcome analysis with respect to confirmatory testing was not available to understand the true positive rate. An insignificant number of cases (9%) failed to provide accurate demographic data like previous history of trisomy, history of smoking, diabetes mellitus and nasal bone status. The present study was based on large number of data points in Indian population which gives a better scenario of Indian Subcontinental clinical picture.
The risk of foetal chromosomal anomaly like trisomy 21 is not limited to elderly women and thus, the prenatal first trimester screening should be offered to all pregnant females irrespective of maternal age. The dual marker screening performed in first trimester have high sensitivity, so abnormalities can be screened in early gestation and provides enough time to perform confirmatory testing and for decision making. It should be kept in mind that screening tests are not diagnostic but they can indeed alter the odds.
DOI: 10.7860/JCDR/2022/52357.16000
Date of Submission: Sep 14, 2021
Date of Peer Review: Oct 26, 2021
Date of Acceptance: Dec 11, 2021
Date of Publishing: Feb 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA
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