Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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

Important Notice

Original article / research
Year : 2012 | Month : August | Volume : 6 | Issue : 6 | Page : 929 - 932

Urinary Placental Growth Factor in Pregnancies Complicated by Preeclampsia

Betsy Varughese, Kalpana Luthra, Rani Kumar, Neerja Bhatla, Sada Nand Dwivedi, Renu Dhingra

1. PhD Student, Department of Anatomy, 2. Additional Professor, Department of Biochemistry 3. Professor&Head(Superannuated), Department of Anatomy 4. Professor, Department of Obstetrics and Gynaecology 5. Professor, Department of Biostatistics 6. Additional Professor, Department of Anatomy All India Institute of Medical Science, New Delhi, India.

Correspondence Address :
Betsy Varughese
PhD Student, Department of Anatomy,
AIIMS, Ansari Nagar, New Delhi-29
Phone: 91-9868156347
E-mail: Varghese.betsy@gmail.com

Abstract

Introduction: Preeclampsia is associated with alterations in the maternal serum levels of the vascular endothelial growth factor (VEGF), the placental growth factor (PlGF) and the soluble fms-like tyrosine kinase-1 (sFlt-1). The serial measurement of these angiogenic factors in the serum may be used to pre-empt the diagnosis of preeclampsia, but obtaining such measurements during the routine antenatal care needs a cost-effective analysis. A promising tool is a non-invasive, alternative screening method for measuring the urinary placental growth factor (PlGF).

Objective: To estimate the levels of urinary PlGF in preeclamptic and normotensive, non proteinuric pregnant women in the Indian population and also to analyze the association of this factor with the onset of the disease.

Methods: A case control-study was planned in 80 patients, among which 40 were preeclamptic patients and 40 were normotensive, non proteinuric pregnant women who served as the controls. Urine samples were obtained both from the preeclamptic women and the control women and they were analyzed for the levels of urinary PlGF by using ELISA.

Results: The levels of urinary PlGF were significantly reduced in the preeclamptic patients as compared to those in the normotensive, non-proteinuric pregnant women (30.08 ± 9.42 pg/ml Vs 77.70 ± 24.70 pg/ml, p< 0.0001). Further, the levels were also significantly reduced in early-onset preeclampsia compared to those in late-onset preeclampsia (25.44±6.35 pg/ml Vs 40.92 ±5.71 pg/ml, p<0.0001).

Conclusion: A significant reduction in the levels of urinary PlGF was found in the preeclamptic patients and this reduced level of urinary PlGF may be used to pre-empt the onset of preeclampsia and to institute the appropriate therapeutic measures.

Keywords

Preeclampsia, Placental growth factor, Vascular endothelial growth factor, Vascular endothelial growth factor receptor-1, Soluble fms like tyrosine kinase-1.

How to cite this article :

Betsy Varughese, Kalpana Luthra, Rani Kumar, Neerja Bhatla, Sada Nand Dwivedi, Renu Dhingra. URINARY PLACENTAL GROWTH FACTOR IN PREGNANCIES COMPLICATED BY PREECLAMPSIA. Journal of Clinical and Diagnostic Research [serial online] 2012 August [cited: 2018 Oct 18 ]; 6:929-932. Available from
http://jcdr.net/back_issues.asp?issn=0973-709x&year=2012&month=August&volume=6&issue=6&page=929-932&id=2295

Introduction
Preeclampsia (PE) is a life threatening, pregnancy-specific syndrome which affects 5-10% of the pregnancies and it is characterized by hypertension and proteinuria after twenty weeks of gestation (1),(2). It is a two-stage disorder in which the initial (placental) asymptomatic stage is marked by abnormal placentation (3), followed by the placental elaboration of certain soluble factors which enter into the maternal circulation and cause subsequent widespread endothelial dysfunction, leading to the maternal symptoms of preeclampsia (4). The placental factors which enter into the maternal circulation include angiogenic factors like the vascular endothelial growth factor (VEGF), the placental growth factor (PlGF) and the soluble vascular endothelial growth factor receptor-1(sVEGFR-1)/soluble fms like tyrosine kinase-1 (sFlt-1).

The serial measurement of the angiogenic factors in the serum might be ideal for ascertaining the risk of preeclampsia (5), but obtaining various serum samples during the routine antenatal care is more labour intensive and invasive as compared to the non-invasive urine samples. Therefore, the estimation of the angiogenic factors by a non-invasive test would be easier and useful in the early assessment of the women who are at a high risk of preeclampsia. One such plausible test may be the estimation of PlGF in urine. Though the levels of VEGF, PlGF and sFlt-1 can be estimated in serum (5), only PlGF acts as a better marker in urine. sFlt1 is a large molecule of 100 kDa and it is usually not filtered into the urine unless there is renal damage (6), whereas urinary VEGF is a small molecule of ~45 kDa and it is present in the cellsSectionof the kidney itself ( glomerular podocytes and tubular cells). These factors are unlikely to reflect the circulating angiogenic state in the preeclamptic mother (7). The urinary PlGF is a small molecule of ~30 kDa which is derived from the circulating blood and is filtered by the kidney in the early stages of preeclampsia. Therefore, the estimation of urinary PlGF acts a better and a plausible alternative. Moreover, the incidence of preeclampsia also varies across the world and this variation may influence the levels of the angiogenic factors. Thus, it is important to analyze the baseline value of urinary PlGF in a given population, so as to determine the threshold value for predicting the disease. Hence, the present study was aimed at measuring the levels of PlGF in the urine of preeclamptic and normotensive pregnant women in the Indian population and also in analyzing whether the urinary PlGF was associated with early- and late- onset preeclampsia.

Material and Methods

Study Design
A case-control study was planned with 80 patients, among which 40 women had preeclampsia and 40 women had normal pregnancies. The patients (cases and controls) were selected from the antenatal clinic and the inpatient ward of the Department of Obstetrics and Gynecology, All India Institute of Medical Science, New Delhi, India. The cases and the controls were matched for the maternal age and the gestational age at the time of the urine collection. The preeclamptic women were selected according to the criteria of the International Society for the Study of Hypertension inPregnancy (ISSHP) (7): pregnant women who had systolic and diastolic blood pressures above 140 and 90 mm Hg respectively, in at least two consecutive measurements, at least 4 hours apart, which occurred after the twentieth week of gestation and were accompanied by proteinuria (>300 mg per liter in a 24 h urine collection/>1+ on a urine dipstick). The preeclamptic women were included immediately after the clinical diagnosis, whereas the cases with chorioamnionitis, chronic hypertension, pre-gestational hypertension, renal disease, cardiac disease, active asthma, thyroid disease and epilepsia were excluded from the study. The normotensive, non-proteinuric, pregnant women without any other medical as well as obstetrics complications were enrolled as the control group. The patients with preeclampsia were also sub-classified as either early-onset (< 34 weeks of gestation) or late-onset (>34 weeks of gestation) preeclampsia, according to the gestational age when the preeclampsia had developed. This study was approved by the institutional ethics committee and a written informed consent was obtained from all the women who were enrolled in the study. All the enrolled women were included in the final analysis.

The immuno assay procedure
Urine samples were obtained both from women with preeclampsia (soon after the clinical manifestation of the disease) and age matched (gestational and maternal) normotensive, non-proteinuric, pregnant women who were in 23 to 39 weeks of gestation. The urine samples were collected by the “clean catch” technique. The collected urine samples were then centrifuged at 3000 rpm for 20 minutes, aliquoted and immediately stored at -20ºC. The urinary placental growth factor (PlGF) was measured by a sandwich-type enzyme linked immunosorbent assay (ELISA; Quantikine ® human PlGF, R&D Systems Inc., Minneapolis, MN, U.S.A). According to the kit, the minimum detectable level for PlGF was 9.0 ρpg/ml and the intra assay variation and inter assay variation were 3.6% and 11.0% respectively.

Statistical Analysis
Between the two matched groups, the quantitative variables like systolic blood pressure, diastolic blood pressure, body mass index, urinary protein, uric acid and urinary placental growth factor (PlGF) of the preeclamptic and the control women were compared by using the Wilcoxon sign rank test/paired t- test. The independent t-test was used to compare the urinary PlGF levels between the early-onset and the late-onset preeclampsia cases. The correlation of the urinary PlGF levels with the systolic and the diastolic blood pressure was analyzed by using Pearson’s/Spearman’s correlation. The result was considered to be statistically significant at a 5% level of significance (i.e., p<0.05). The statistical analysis was performed by using the statistical package, SPSS, version 13.

Results

The clinical characteristics of the study population are shown in (Table/Fig 1). The systolic blood pressure, diastolic blood pressure, body mass index, urinary protein and the uric acid levels were significantly higher in the preeclamptic pregnant women than in the normotensive, non-proteinuric, pregnant women (Table/Fig 1). The preeclamptic patients had lower levels of the urinary placental growth factor (PlGF) as compared to the women with normal pregnancies (30.08±9.42 pg/ml Vs 77.70±24.70 pg/ml, p< 0.0001) (Table/Fig 2). When the urinary levels of PlGF in the early-onset preeclamptic group (< 34 weeks of gestation) were compared to those in their matched control group, a significant reduction was observed (25.44 ± 6.35 pg/ml Vs 85.78± 25.87 pg/930ml, p<0.0001). A similar pattern was also found in the late-onset preeclamptic group (> 34 weeks of gestation), when the values of the urinary placental growth factor were compared with those in their matched control group (40.92 ± 5.71 pg/ml Vs 48.87 ± 6.14 pg/ml, p<0.05). The urinary levels of PlGF were significantly reduced in the early-onset preeclamptic group (< 34 weeks of gestation) as compared to those in the late-onset preeclamptic group (> 34 weeks of gestation) (25.44± 6.35 pg/ml Vs 40.92 ± 5.71 pg/ml, p<0.0001) (Table/Fig 3). In contrast, the urinary levels of PlGF were significantly higher in the control women who were at < 34 weeks of gestation than in the control women who were atpreeclamp> 34 weeks of gestation (85.78± 25.87 pg/ml Vs 48.87 ± 6.14 pg/ml, p<0.0001). The correlation of the urinary placental growth factor with the maternal blood pressure was also analyzed in the preeclamptic and the control groups. There was a significant negative correlation between the urinary PlGF and the blood pressure (systolic blood pressure, r = -0.694, p< 0.001 and diastolic blood pressure, r = -0.649, p<0.001) in the preeclamptic patients (Table/Fig 4). A similar pattern was also found in the control group (systolic blood pressure, r = -0.584, p<0.001 and diastolic blood pressure, r = -0.514, p<0.001).

Discussion

This study found that preeclampsia was associated with the alterations in the levels of the angiogenic factors (8),(9) and that these alterations were more pronounced in the early- than in the late-onset preeclampsia cases. In the present study, a significant decrease in the levels of the urinary placental growth factor (PlGF) was found in the preeclamptic women as compared to those in the normotensive, non-proteinuric pregnant women. The reduced levels of urinary PlGF may be due to the reduced circulating PlGF, which in turn was attributed to the increased binding of the free PlGF to the increased circulating soluble fms like tyrosine kinase-1 (sFlt-1) in the circulation (8),(10). sFlt-1 acts as a decoy receptor and binds to the free PlGF in the circulation (11),(12), thereby inducing an anti-angiogenic state that may play a causal role in the pathogenesis of the maternal syndrome in preeclampsia. Our previous study also reported higher levels of serum sFlt-1 and lower levels of free PlGF in the sera of preeclamptic women (8).

Although the serum analysis of the angiogenic factors, especially the analysis of serum sFlt-1 could be a better screening method for preeclampsia, obtaining such measurements during the routine antenatal care need a cost-effective analysis. An alternative method is to measure one of these proteins in urine. sFlt-1 is a large molecule of 100 Kda (6) which can’t be filtered by the healthy kidney into the urine in the absence of renal damage and VEGF is expressed in podocytes during embryogenesis and in the mature glomerulus. Also, the mRNA for the vascular endothelial growth factor and its receptors, the vascular endothelial growth factor receptor-1 (Flt-1) and the vascular endothelial growth factor receptor-2 (Flk-1) are expressed on the glomerular podocytes, the distal tubules, and the collecting ducts (13),(14),(15),(16). It is therefore unlikely to estimate these factors in the urine of preeclamptic mothers (6). Urinary VEGF and sFlt-1 acts as poor indicators in reflecting the circulating angiogenic state and thus, urinary931PlGF acts as plausible alternative. PlGF is considerably a smaller protein of ~30 KDa and it is not produced by the kidneys. The urinary levels of this angiogenic factor in turn, reflect its circulating levels (17). Previous studies had reported that the low serum levels of PlGF had antedated the development of preeclampsia (18),(19). Therefore, it is reasonable to expect that the low levels of urinary PlGF would also be a good predictor of preeclampsia. As the variations in the levels of the serum angiogenic factors are reported across the world to be due to geographical, social, economic and racial differences (20),(21),(22),(23), we presumed that even the levels of urinary PlGF had variations among the population. Hence, a reference value for the patients of Indian origin would be very beneficial. Thus, in the present study, we estimated the levels of urinary PlGF in the preeclamptic patients of the Indian population.

In order to analyze whether urinary PlGF was associated with the onset of the disease, we estimated the levels of urinary PlGF in the early- and late onset preeclampsia cases. A significant reduction in the levels of urinary PlGF was found in the early-onset (< 34 weeks of gestation) as compared to the late-onset preeclampsia (>34 weeks of gestation) cases. In contrast, the level of urinary PlGF was much higher in the control women at < 34 weeks of gestation as compared to that in the control women at >34 weeks of gestation. This was consistent with the findings of previous longitudinal studies, where increasing levels of PIGF had been found during the normal pregnancy upto the end of the second trimester, followed by a decrease during the third trimester (6). We also analyzed the association of urinary PlGF with the maternal syndrome. A significant negative correlation was found between the urinary PlGF and the systolic and the diastolic blood pressure in preeclamptic women. This indicated that low levels of urinary PlGF were also associated with the severity of the disease.

Since preeclampsia contributes to significant maternal morbidity and mortality in India, a prompt diagnosis and intervention are of vital importance in its management. The burden of preeclampsia on the health care resources may be improved by reducing the delay in the patient’s decision to seek care, the delay in the patients’ arrival at the hospital or the tertiary care centre and the delay in the provision of adequate care, especially the delay in the diagnosis of the disease. The delay in the diagnosis can be considerably mitigated by a reliable, valid and an economical test that could predict pre-eclampsia. One such test may be the urinary test for PlGF. A noninvasive, urine test would be superior to one that requires a blood draw. A urinary test for PlGF could probably be performed less expensively than could a blood test for sFlt-1, because it wouldn’t require the services of a medical professional to draw blood. Moreover, a urine sample could conceivably be collected at home, and then brought into a medical lab for testing. This would be an advantage over a blood test, especially in the countries which lacked trained medical staff to draw the blood. Once the preeclamptic women were identified through this urine PlGF test, studies could be targeted to find effective ways to prevent its progression or to keep the most dangerous complications from occurring.

Conclusion

Our study suggested that preeclampsia could be associated with low levels of urinary PlGF at the time of the clinical manifestation. Further analysis will be required to clarify the regulation and the secretion of these angiogenic factors in women with preeclampsia. A rapid, non-invasive screening of the preeclamptic women, based on the angiogenic factors, may be used to define the severity of the disease and this appeared to be superior to the routine urinary protein measurements. A prospective study on the levels of urinary PlGF before and after the onset of preeclampsia is progressing in our lab. A cost effective analysis which is done by the serial measurement of urinary PlGF during the routine antenatal care can not only pre-empt the diagnosis of preeclampsia, but it can also bring about an improvised therapeutic management and decrease the stagnating MMR (maternal mortality ratio); thereby improving the maternal health in India.

Key Message

We thank Indian Council of Medical Research for giving the Senior Research Fellowship and All India Institute of Medical Science for providing the infra structure for the study. We also thank Mr. Ashish Datt Upadhyay for doing the statistical analysis of the data.

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Date of Submission: May 31, 2012
Date of Peer Review: Jun 28, 2012
Date of Acceptance: Jul 19, 2012
Date of Publishing: Aug 10, 2012

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