{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:17:25Z","timestamp":1782929845934,"version":"3.54.5"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15731.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000}}],"reference-count":66,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203905"],"award-info":[{"award-number":["203905"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Introduction:<\/ns3:bold>\n                    Climate change predictions indicate that global temperatures are likely to exceed those seen in the last 200,000 years, rising by around 4\u00b0C above pre-industrial levels by 2100 (without effective mitigation of current emission rates). In regions of the world set to experience extreme temperatures, women often work outside in agriculture even during pregnancy. The implications of heat strain in pregnancy on maternal health and pregnancy outcome are not well understood. This protocol describes a study to assess the physiological response of pregnant women to environmental heat stress and the immediate effect this has on fetal wellbeing.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods and analysis:<\/ns3:bold>\n                    The study will be performed in West Kiang district, The Gambia; a semi-arid zone in West Africa with daily maximum temperatures ranging from approximately 32 to 40\u00b0C. We will recruit 125 pregnant women of all ages who perform agricultural work during their pregnancy. Participants will be followed every two months until delivery. At each study visit fetal growth will be measured by ultrasound scan. During the course of their working day we will take the following measurements: continuous maternal physiological measurements (heart rate, respiratory rate, chest skin temperature and tri-axis accelerometer data); intermittent maternal tympanic core temperature, four point skin temperature, blood pressure; intermittent fetal heart rate and, if eligible, umbilical artery doppler; intermittent environmental measurements of air temperature, humidity, solar radiation and wind speed. Venous blood and urine will be collected at beginning and end of day for biomarkers of heat strain or fetal distress and hydration status.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15731.2","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T10:55:07Z","timestamp":1585652107000},"page":"32","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["A protocol for an observational cohort study of heat strain and its effect on fetal wellbeing in pregnant farmers in The Gambia"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-762X","authenticated-orcid":false,"given":"Ana","family":"Bonell","sequence":"first","affiliation":[{"name":"Fajara Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0176-2651","authenticated-orcid":false,"given":"Jane","family":"E Hirst","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health and the George Institute for Global Health Oxford University of Oxford"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Vicedo-Cabrera","sequence":"additional","affiliation":[{"name":"Oeschger Center for Climate Change Research Bern University of Bern"},{"name":"Institute of Social and Preventive Medicine Bern University of Bern"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8053-4605","authenticated-orcid":false,"given":"Andy","family":"Haines","sequence":"additional","affiliation":[{"name":"Department of Public Health, Environment and Society; Department of Population health London London School of Hygiene and Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Prentice","sequence":"additional","affiliation":[{"name":"Fajara Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil S.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Environmental Extremes Laboratory Brighton University of Brighton"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1841-56","DOI":"10.1175\/bams-d-16-0007.1","article-title":"Estimating Changes in Global Temperature since the Preindustrial Period.","volume":"98","author":"E Hawkins","year":"2017","journal-title":"Bull Am Meteorol Soc."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"45-50","DOI":"10.1038\/nature24672","article-title":"Greater future global warming inferred from Earth\u2019s recent energy budget.","volume":"552","author":"P Brown","year":"2017","journal-title":"Nature."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"994-7","DOI":"10.1126\/science.1098704","article-title":"More intense, more frequent, and longer lasting heatwaves in the 21st century.","volume":"305","author":"G Meehl","year":"2004","journal-title":"Science."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"5030-3","DOI":"10.1029\/2018GL078430","article-title":"The Inequality of Climate Change From 1.5 to 2\u00b0C of Global Warming.","volume":"45","author":"A King","year":"2018","journal-title":"Geophys Res Lett."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"6672-80","DOI":"10.1029\/2018GL078888","article-title":"How Uneven Are Changes to Impact-Relevant Climate Hazards in a 1.5 \u00b0C World and Beyond?","volume":"45","author":"L Harrington","year":"2018","journal-title":"Geophys Res Lett."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"563-82","DOI":"10.1002\/tcm.1770060610","article-title":"Hyperthermia as a teratogen: a review of experimental studies and their clinical significance.","volume":"6","author":"M Edwards","year":"1986","journal-title":"Teratog Carcinog Mutagen."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"251-7","DOI":"10.1002\/(SICI)1096-9926(199812)58:6<251::AID-TERA6>3.0.CO;2-L","article-title":"Maternal fever and birth outcome: a prospective study.","volume":"58","author":"C Chambers","year":"1998","journal-title":"Teratology."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"146-58","DOI":"10.2165\/00007256-199010030-00002","article-title":"Thermoregulation in pregnancy. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17244.r37958, Matthew F. Chersich, Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 02 Mar 2020, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-32\/v1#referee-response-37958","order":0,"name":"referee-response-37958","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ana Bonell<\/b>; \n<i>Posted: 18 Mar 2020<\/i>; Thank you for your time and effort in providing the feedback on the paper. We are very grateful for the scientific review and hope that the changes we have made in response to the suggestions make the article stronger scientifically. 1. I think more is needed to distinguish between subsistence farming and farming done done for income.  In the Gambia there is a clear gender divide in farming. Men work on the cash crops and women grow what they use themselves with the potential to sell at the village markets.This has been added into the background context to aid understanding of the local situation.  &nbsp;2. It is also not clear if there will be a set of questions asked about heat behaviours, for example, changes in work hours as gestation progresses, changes in kinds of activities done depending on temperature, changes in behaviours, like starting earlier in the day. Changes in gender roles with gestation or temperature? Do men do more when&nbsp;it is hot? Is drinking water accessible?  These questions will not be asked as part of this study, however additional qualitative work is planned to explore these questions to complement this work.We specifically ask about heat illness symptoms, thermal comfort and sensation, thirst and perceived exertion. &nbsp; 3. There is a line which is problematic 'almost no data and no field studies concerning impact of heat stress on maternal physiology...; there is a lot written about thermoregulation in pregnancy, and it is fascinating.  I completely agree, there is a lot of data on thermoregulation in pregnancy, but field-based physiology studies in heat stressed human pregnancies are lacking. I have rephrased the sentence to more accurately reflect this. &nbsp; 4. The claim about hyperthermia being a teratogen in humans is perhaps over-stated. As I understand there is still a controversy about this in terms of saunas etc.  Hyperthermia is a teratogen in the first trimester, as shown from fever studies and studies with documented prolonged rises in core temperature. I have clarified that it is a teratogen in the first trimester in the manuscript. &nbsp; 5. I wonder if it might be better to target the physiological measurements to days above a certain temperature threshold, based on forecasting. That is the key question I think, It depends what your question is: impact of total heat burden during pregnancy, or impact of 'extreme heat'. If it is the later then measures on days with Tmax &gt;90th percentile might make more sense.  This would give us a detailed idea of extreme heat. However without the ability to compare to physiological changes at cooler times it would be difficult to differentiate the heat from the exercise effects. This was the rational to recruit throughout the year. &nbsp; 6. The ability of women to thermoregulate in pregnancy is remarkable I think, their relative 'hypothermia' and shifting of blood away from the fetus means that you may not detect any major impact, a major missed opportunity  The ability to thermoregulate is impressive, however the conditions here in The Gambia are extreme in terms of what we as humans can adapt to. In particular if occupational guidelines were followed the max WBGT is often above the level at which outdoor work is advised. Therefore even with a starting relative hypothermia we expect to see some changes. Additionally, the shifting of the blood away from the fetus is a very important physiological change to document as a starting point to understand the impact of heat in pregnancy. I have added detail on the max WBGT we expect the women to be exposed to and how this puts them at risk of heat illness according to the ACGIH &nbsp; 7. I wonder if you need a limitations section, the one limitation under participants did not make sense to me. How much will behaviours change with the presence of a field worker? The hourly tympanic membrane measure seems excessive intrusion that may alter the behaviour you are trying to asess. I really dount the core temp will rise, certainly not by the hour! She may have heat stress and discomfort but for that to raise her temperature is unlikely I imagine.  A limitations section has been added. The taking of hourly tympanic membrane measurements was a compromise as we were unable to measure continuous core temperature as would have been the gold standard in heat strain studies. Rectal temperature was impossible and core telemetry pills have yet to be proved safe in pregnancy. In heat chamber studies, volunteers will put their core temperature up within 20 mins of exercise in a hot\/humid environment and this will return to baseline relatively quickly which is the rational for the hourly measurements. &nbsp; 8. The sample size refers to the 30% increases incidence in the primary outcome? &nbsp;  Yes, this is for the primary outcome I have clarified this in the manuscript","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-32\/v2#referee-comment-4101","order":1,"name":"referee-comment-4101","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17328.r38292, Beth Holder, Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, 07 Apr 2020, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-32\/v2#referee-response-38292","order":2,"name":"referee-response-38292","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The project is supported by the Wellcome Trust. AB is supported by a Wellcome Clinical PhD Fellowship (203905). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}