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

Users Online : 103622

AbstractMaterial and MethodsResultsDiscussionConclusionAcknowledgementReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

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 Dermatolgy,
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
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

Important Notice

Original article / research
Year : 2023 | Month : June | Volume : 17 | Issue : 6 | Page : CC19 - CC22 Full Version

Heart Rate Variability and Cold Pressor Test before Onset of Pre-eclampsia in Pregnant Women-A Longitudinal Study


Published: June 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/60716.18094
Tazyeen Fatima, Shobitha Muthukrishnan, Neha Gupta, Ashish Kumar Maurya

1. Tutor, Department of Physiology, SGT Medical College, Hospital and Research Institute, Gurugram, Haryana, India. 2. Professor, Department of Physiology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India. 3. Associate Professor, Department of Obstetrics and Gynaecology, Hamdard Institute of Medical Sciences, HAHC Hospital, Jamia Hamdard, New Delhi, India. 4. Assistant Professor, Department of Computer Science and Engineering, Greater Noida Institute of Technology, Greater Noida, Uttar Pradesh, India.

Correspondence Address :
Dr. Shobitha Muthukrishnan,
Professor, Department of Physiology, School of Medical Sciences and Research, Sharda University, Greater Noida-201306, Uttar Pradesh, India.
E-mail: drshobitha@gmail.com

Abstract

Introduction: A major obstetric complication, that leads to severe maternal and foetal morbidity is Preeclampsia (PE). Studies evaluating the autonomic nervous activity in pregnant women with PE shows conflicting results. Previous studies are inadequate for the identification of the most useful tools to detect and monitor autonomic dysfunction prior to PE. The cold pressor test is a simple and validated test, in which the afferent sensory pathways are stimulated by the cold stimulus, resulting in an increase in Blood Pressure (BP).

Aim: To evaluate the response to cold pressor test and Heart Rate Variability (HRV) to detect increased vascular reactivity and sympathetic activity prior to the clinical manifestation of PE in pregnant women.

Materials and Methods: A longitudinal study was conducted in in the Department of Physiology at Hamdard Institute of Medical Sciences, HAHC Hospital, Jamia Hamdard, New Delhi, India. The duration of the study was 11 months, from December 2018 to November 2019. Subjects were 50 pregnant women, between age 18-40 years and of 12-14 weeks of gestation. Cold pressor test and HRV were parameters measured for the assessment of the autonomic functions during 12 and 21 weeks of gestational period. The Statistical Package for Social Sciences (SPSS) version 26.0 was used for analysis of the quantitative data. Paired t-test was done for comparison of all values.

Results: The mean age of the study participants was 29±2.7 years. There was no hyper-reaction to cold pressor test at 12 weeks of gestation, nor the subjects showed any signs of PE. At 14 weeks of gestation, 2 (4%) showed hyper-reaction to cold pressor test. At 21 weeks of gestation, 3 (6%) subjects showed hyper-reactions to cold pressor test and out of them, two developed PE. Root Mean Square Standard Deviation (RMSSD) and difference between adjacent Standard Deviation of N-N intervals (SDNN) of HRV analysis were significantly higher in the first trimester as compared to 21 weeks of pregnancy.

Conclusion: Response to cold pressor test showed increased vascular reactivity, as a sign before the development of PE. HRV analysis could not detect any significant features of increased sympathetic activity prior to the clinical manifestation of PE in pregnant women.

Keywords

Autonomic nervous system, Gestational disorders, Maternal morbidity, Non invasive assessments, Pregnancy induced hypertension

The PE is an obstetric complication, that increases the risk of unfavourable consequences for both the mother and the foetus (1). The severity of complications can be curtailed by early detection of PE, which can also improve clinical outcomes. PE is a complex gestational disorder, with a worldwide prevalence of 5%-8% (1),(2). Among mothers, PE increases the risk of premature death, Type 2 Diabetes Mellitus (T2DM), cardiovascular diseases, and hypothyroidism (3). Moreover, the offspring also has an increased risk of cardiovascular and metabolic disorders later in life (4). Previous study suggests that, there is over activity of the sympathetic nervous system in women with PE which leads to increased vascular reactivity (5). Studies evaluating the autonomic nervous activity in pregnant women with PE show conflicting results (5),(6),(7). These studies compared the values in pregnancy with postpartum values. Very few studies were conducted before the onset of PE in pregnant women and were inadequate for the identification of the most useful tools to detect and monitor autonomic dysfunction in pre-eclamptic women (6),(7). Majority of the previous studies, used one Autonomic Nervous System (ANS) assessment test and very few studies used two assessment tests (8),(9),(10).

The PE is defined according to the clinical criteria established by the American College of Obstetricians and Gynecologist (ACOG) as the “occurrence of Hypertension (HTN) defined as Systolic Blood Pressure (SBP) ≥140 mmHg or Diastolic Blood Pressure (DBP) ≥90 mmHg after 20 weeks of gestation in woman, who is normotensive before, and proteinuria defined as presence of 300 mg or more of protein in 24 hour urine sample or >2+on dipstick” (11). A new onset HTN (>140/90 mmHg) after 20 weeks of pregnancy in women, who were normally normotensive was recently revised and updated by the ACOG to include other complications in case of absence of proteinuria (2). It was found that, there is a paucity of studies, to detect the increased vascular reactivity prior to the clinical manifestation of PE. Previous studies (6),(7),(8),(9),(10) have not compared autonomic functions utilising both, HRV and response to cold pressor test together in pregnant women prior to the clinical manifestations of the disease. The present study therefore, evaluated the measurements of HRV and response to cold pressor test, to detect the increased sympathetic activity and vascular reactivity prior to the clinical manifestation of PE in pregnant women.

The present study hypothesised that, non invasive assessment of autonomic cardiovascular control using analysis of HRV and response to cold pressor test can be a predictive tool to identify early the women who were at increased risk of developing PE. Hence, present study was conducted, to evaluate the measurements of response to cold pressor test and HRV to detect any increased vascular reactivity and sympathetic activity, prior to the clinical manifestation of PE in pregnant women.

Material and Methods

A longitudinal study was conducted in the Department of Physiology at Hamdard Institute of Medical Sciences, HAHC Hospital, Jamia Hamdard, New Delhi, India. The duration of the study was 11 months, from December 2018 to November 2019. The study was approved by Institutional Ethics Committee on 26/11/18. Informed consent was obtained from volunteered subjects. The procedure followed were in accordance with the ethical standards of the responsible committee on human experimentation.

Inclusion criteria: Pregnant women aged between 18-40 years and of 12-14 weeks of gestation were included in the study.

Exclusion criteria: Pregnant women with diabetes, chronic renal disease, neurological disorders, smokers, multiple pregnancies and cardiorespiratory illnesses were excluded from the study.

Sample size calculation: A total of 50 pregnant women were enrolled for the study by convenient sampling. Total 50 subjects were considered for both, cold pressor test and HRV analysis.

Study Procedure

Parameteric assessment of the autonomic functions was done during 12, 14 and 21 weeks of gestational period for BP response to cold pressor test and HRV was assessed at 12 and 21 weeks of gestation.

Cold pressor test: After 10 minutes of rest, the cold pressor test for the assessment of sympathetic vascular reactivity was done in sitting position by the method as described by Hines EA and Brown GE (12). The subjects were seated comfortably and baseline BP was recorded by auscultatory method using Omron 8712 automatic BP monitor (13). Then the subject was asked to immerse one hand up to the wrist in ice cold water (4-5°C) for one minute. The BP from the other arm, was recorded after every 30 seconds intervals for one minute. The maximum increase in SBP and DBP were noted and compared with the pretest readings. The change in the ?SBP and DBP was calculated by subtracting pretest reading from the reading obtained after hand immersion. The subjects having ?SBP <20 mmHg and ?DBP <10 mmHg were labelled as normal reactors and ?SBP ≥20 mmHg and ?DBP ≥10 mmHg were labelled as hyper-reactors. The results were expressed as the percentages.

Heart Rate Variability (HRV): Laboratory chart data analysis software, Analog Digital (AD) instrument was used for the assessment of the autonomic functions in the subjects. The time domain and frequency domain analysis of HRV was done in uniform settings (14). Time domain measures, included SDNN and square root of mean of the sum of the squares of differences between adjacent NN interval (RMSSD), both expressed in milliseconds (ms). Frequency domain HRV indices included Very Low Frequency (VLF) power, Low Frequency (LF) power (0.04-0.15 Hz), High Frequency (HF) power (0.15-0.4 Hz), and Total Power (TP). LF and HF were also measured in normalised units (nu). The ratio of LF to HF power, was also calculated as a measure of sympathovagal balance. The findings of HRV were interpreted as LF/HF ratio >1 as unhealthy. SDNN values below 50 ms are classified as unhealthy, 50-100 ms have compromised health, and above 100 ms are healthy (14). The reference range for RMSSD was 13-107 ms, which reflects the integrity of vagus nerve-mediated autonomic control of the heart. Proportion of NN50 (pNN50) lower than 3% is considered indicative of high risk.

Statistical Analysis

The quantitative statistical data was analysed using SPSS version 26.0. Paired sample t-test was done for comparison of all values with significant p-value ≤0.05.

Results

Study was conducted on 50 pregnant female subjects with average age of 29±2.7 years.

Frequency domain and time domain of Heart Rate Variability (HRV): The observed mean values of LF normal units (nu), HF (nu) and LF/HF ratio during 21 weeks of gestation, were significantly higher as compared to 12 weeks of gestation. There was significant decrease in SDNN values, RMSSD and pNN50 values during 21 weeks of gestation as compared to 12 weeks (Table/Fig 1).

Cold pressor test: There was no hyper-reaction to cold pressor test at 12 weeks of gestation, nor the subjects showed signs of PE or Pregnancy Induced Hypertension (PIH). At 14 weeks of gestation, two subjects showed hyper-reaction to cold pressor test. At 21 weeks of gestation, three subjects showed hyper-reactions to cold pressor test and out of these, two developed PE or PIH (Table/Fig 2).

There was significant increase in SBP during the cold pressor test. When compared with healthy pregnant women, the change in BP was more evident in women developing PE. (SBP: 20.8±3.4 vs 14.15±5.84 mmHg) (Table/Fig 3).

Discussion

The present study compared the response to cold pressor test between 12,14 and 21 weeks of gestation and found that, there was no hyper-reaction to cold pressor test at 12 weeks of gestation, nor the subjects showed signs of PE or PIH. At 14 and 21 weeks of gestation, 4% and 6% of the total subjects showed hyper-reaction to cold pressor test respectively. A total of 2 (4%) out of 50 pregnant women developed PE. Previous study has found that, the central sympathetic output was significantly increased in women with PIH, as compared to normal pregnant women (15). Studies have also reported decreased vagal tone, along with increased sympathetic activity to be associated with PIH/PE [16-18]. Previous attempts for early prediction of PIH/PE in clinical practice by using a variety of biological, biochemical and biophysical markers have been inadequate [19,20]. However, in the present study, there was significant increase in BP during the cold pressor test in women developing PE between 14 to 21 weeks of gestation. Study by Woisetschlager C et al., found significant increase in SBP and DBP during the cold pressor test (19). The change was significant in women, who developed PE between 16 to 20 weeks of gestation. It was interpreted as increased vascular activity detected prior to clinical manifestation of PE.

The present study has found that, the pregnant women, who developed PE or PIH showed, increased BP reactivity to cold pressor test as early as 14 weeks of gestation. Therefore, in the present study, increased vascular activity prior to clinical manifestation of PE was detected during the early 14 weeks of gestation. Cold pressor test was done to assess the percentage of hyper-reactors, who develop PE in later pregnancy. The present study found 4% of the total pregnant women subjects developed PE. The finding is in concordance with the finding of previous study that, PE affected 2%-8% of the total pregnancy (19),(20).

The present study, compared the time and frequency domain analysis of HRV between 12 weeks and 21 weeks of gestation. The ACOG states that, heart rate fluctuation is very much varied throughout the gestation (21). Therefore, HRV was analysed during end of first trimester and during 21 weeks of second trimester, when PE changes are expected to begin. It has been recommended that, short term recordings of five minutes performed in the present study under uniform and stable conditions would be processed by frequency domain methods (14). Frequency domain analysis of HRV showed significant increase of LF waves during 21 weeks of pregnancy compared to first trimester. The LF/HF ratio during 21 weeks of gestation was found to be less than one, which is considered as good cardiovascular health (14). LF modulation (0.04-0.15Hz) of R-R Interval changes corresponds to the sympathetic and parasympathetic activities together. HF modulation (0.15-0.4 Hz) of R-R interval changes is primarily regulated through innervation of the heart through the parasympathetic (vagal) nerve (14). The time domain parameters i.e., RMSSD and SDNN were significantly higher in the first trimester, as compared to 21 weeks of pregnancy. The time-domain Standard Deviation (SD) of all N-N intervals (SDNN) reflect the total variability and along with the RMSSD between adjacent N-N intervals reflects parasympathetic activity (14).

In the present study, there was a significant decrease in SDNN, RMSSD values during 21 weeks of gestation, as compared to 12 weeks suggesting reduced parasympathetic activity. It is known that, SDNN is a measure of combined sympathetic and parasympathetic activity, and RMSSD represents parasympathetic activity, which reflects the integrity of vagus nerve mediated autonomic control of the heart (14). Previous study has observed that, increased sympathetic activity and may already be present before the clinical presentation of PE, eventhough, the signs and symptoms of PE appear late in pregnancy (21). The results of the present study are similar to the prospective cohort study, which evaluated the predictive value of spectral analysis of heart rate and BP for hypertensive diseases of pregnancy at 28 weeks of pregnancy. The study by Flood P et al., concluded that, although, useful for PIH, it was not able to detect women who developed PE afterward in pregnancy (22).

The HRV analysis in the present study, could not detect features of increased sympathetic activity during 12 weeks of gestation. Women, who developed increased sympathetic activity leading to PE after 12 weeks of pregnancy could not be detected by analysis of HRV. This could be attributed to the fact that, BP regulation by ANS is disturbed at several levels between the hypothalamus and the periphery. Therefore, the results are limited (23). Previous reports of HRV in PE patients are conflicting. Some studies have found elevated sympathetic activity as a manifestation of ANS dysfunction and reduced parasympathetic activity (21),(23) while other have showed, no significant difference between the PE group and the control group (24). Comparison of previous studies with the present study on HRV during pregnancy has been shown in (Table/Fig 4) (25),(26),(27),(28).

Limitation(s)

Long term follow-up of subjects could not be done. Delivery outcomes and foetal status of the detected PE subjects could not be assessed. Future studies can include appropriate comparison groups with longer follow-ups.

Conclusion

Response to cold pressor test showed increased vascular reactivity, as a sign before the development of PE. HRV analysis could not detect features of significantly increased sympathetic activity prior to the clinical manifestation of PE in pregnant women. HRV analysis could not detect women, who developed increased sympathetic activity and PE after 12 weeks of pregnancy. Therefore, cold pressor test in early pregnancy may be a useful indicator for development of PIH or PE later in pregnancy.

Acknowledgement

The authors would like to thank the staff of Physiology Department of HIMSR, Jamia Hamdard, New Delhi.

References

1.
Duley L. The global impact of pre-eclampsia and eclampsia. In Seminars in perinatology. 2009;33(3):130-37. WB Saunders. [crossref][PubMed]
2.
Mohan M, Ramawat J, La Monica G, Jayaram P, Fattah SA, Learmont J, et al. Electronic intrapartum fetal monitoring: A systematic review of International clinical practice guidelines. AJOG Global Reports. 2021;1(2):100008. [crossref][PubMed]
3.
Tranquilli AL, Landi B, Giannubilo SR, Sibai BM. Preeclampsia: No longer solely a pregnancy disease. Pregnancy Hypertension: Int J Women’s Cardiovascular Health. 2012;2(4):350-57. [crossref][PubMed]
4.
O’Tierney-Ginn PF, Lash GE. Beyond pregnancy: Modulation of trophoblast invasion and its consequences for fetal growth and long-term children’s health. J Reproductive Immunol. 2014;104-105:37-42. [crossref][PubMed]
5.
Swansburg ML, Brown CA, Hains SM, Smith GN, Kisilevsky BS. Maternal cardiac autonomic function and fetal heart rate in preeclamptic compared to normotensive pregnancies. Canadian J Cardiol Nurs. 2005;15(3):42-52.
6.
Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiolo. 2010;141(2):122-31. [crossref][PubMed]
7.
Robbe HW, Mulder LJ, Rüddel H, Langewitz WA, Veldman JB, Mulder G. Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension. 1987;10(5):538-43. [crossref][PubMed]
8.
Rang S, Wolf H, Montfrans GA, Karemaker JM. Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia. J Hypertens. 2004;22(2):369-76. [crossref][PubMed]
9.
Weber TM, Lackner HK, Roessler A, Papousek I, Kolovetsiou-Kreiner V, Lucovnik M, et al. Heart rate variability and baroreceptor reflex sensitivity in early-versus late-onset preeclampsia. PLoS One. 2017;12(10):e0186521. [crossref][PubMed]
10.
Faber R, Baumert M, Stepan H, Wessel N, Voss A, Walther T. Baroreflex sensitivity, heart rate, and blood pressure variability in hypertensive pregnancy disorders. J Hum Hypertens. 2004;18(10):707-12.[crossref][PubMed]
11.
Kattah AG, Garovic VD. The management of hypertension in pregnancy. Advances in Chronic Kidney Disease. 2013;20(3):229-39. [crossref][PubMed]
12.
Hines Jr EA, Brown GE. The cold pressor test for measuring the reactibility of the blood pressure: Data concerning 571 normal and hypertensive subjects. Am Heart J. 1936;11(1):01-09. [crossref]
13.
Myers MG, Godwin M. Automated measurement of blood pressure in routine clinical practice. J Clin Hypertens. 2007;9(4):267-70. [crossref][PubMed]
14.
Heart Rate Variability. Standards of measurement, physiological interpretation, and clinical use. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996;17(3):354-81.
15.
Airaksinen KE, Kirkinen P, Takkunen JT. Autonomic nervous dysfunction in severe pre-eclampsia. Eur J Obstet Gynecol. 1985;19(5):269-76. [crossref][PubMed]
16.
Cnossen JS, Van der Post JA, Mol BW, Khan KS, Meads CA, Riet G. Prediction of pre-eclampsia: A protocol for systematic reviews of test accuracy. BMC Pregnancy and Childbirth. 2006;6(1):01-08. [crossref][PubMed]
17.
Greenwood JP, Stoker JB, Walker JJ, Mary DA. Sympathetic nerve discharge in normal pregnancy and pregnancy-induced hypertension. J Hypertens. 1998;16(5):617-24. [crossref][PubMed]
18.
Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: Current concepts. Am J Obstet Gynecol. 1998;179(5):1359-75. [crossref][PubMed]
19.
Woisetschläger C, Waldenhofer U, Bur A, Herkner H, Kiss H, Binder M, et al. Increased blood pressure response to the cold pressor test in pregnant women developing pre-eclampsia. J Hypertens. 2000;18(4):399-403. [crossref][PubMed]
20.
Jeyabalan A. Epidemiology of preeclampsia: Impact of obesity. Nutr Rev. 2013;71(Suppl 1):S18-25. [crossref][PubMed]
21.
Andreas M, Kuessel L, Kastl SP, Wirth S, Gruber K, Rhomberg F, et al. Bioimpedance cardiography in pregnancy: A longitudinal cohort study on hemodynamic pattern and outcome. BMC Pregnancy and Childbirth. 2016;16(1):01-09. [crossref][PubMed]
22.
Flood P, McKinley P, Monk C, Muntner P, Colantonio LD, Goetzl L, et al. Beat- to-beat heart rate and blood pressure variability and hypertensive disease in pregnancy. Am J Perinatol. 2015;32(11):1050-58. [crossref][PubMed]
23.
Fu Q, Levine BD. Autonomic circulatory control during pregnancy in humans. In Seminars in Reproductive Medicine. 2009;27(04):330-37. [crossref][PubMed]
24.
Faber R, Baumert M, Stepan H, Wessel N, Voss A, Walther T. Baroreflex sensitivity, heart rate, and blood pressure variability in hypertensive pregnancy disorders. J Hum Hypertens. 2004;18(10):707-12. [crossref][PubMed]
25.
Kimmel MC, Fransson E, Cunningham JL, Brann E, Grewen K, Boschiero D, et al. Heart rate variability in late pregnancy: Exploration of distinctive patterns in relation to maternal mental health. Translational Psychiatry. 2021;11(1):01-01. [crossref][PubMed]
26.
Solanki JD, Desai FH, Desai KH. Heart rate variability is reduced in normal pregnancy irrespective of trimester: A cross-sectional study from Gujarat, India. Fam Med Prim Care Rev. 2020;9(2):626-27. [crossref][PubMed]
27.
Moors S, Staaks KJ, Westerhuis ME, Dekker LR, Verdurmen KM, Oei SG, et al. Heart rate variability in hypertensive pregnancy disorders: A systematic review. Pregnancy Hypertension. 2020;20:56-68. [crossref][PubMed]
28.
Gandhi PH, Mehta HB, Gokhale AV, Desai CB, Gokhale PA, Shah CJ. A study on cardiac autonomic modulation during pregnancy by non-invasive heart rate variability measurement. Int J Med and Public Health. 2014;4(4):441-45.[crossref]

DOI and Others

DOI: 10.7860/JCDR/2023/60716.18094

Date of Submission: Oct 11, 2022
Date of Peer Review: Dec 05, 2022
Date of Acceptance: Apr 05, 2023
Date of Publishing: Jun 01, 2023

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? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 12, 2022
• Manual Googling: Feb 23, 2023
• iThenticate Software: Mar 25, 2023 (21%)

ETYMOLOGY: Author Origin

EMENDATIONS: 7

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com