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First-Trimester Pregnancy: Considerations for Wilderness and Remote Travel

Open AccessPublished:February 24, 2023DOI:https://doi.org/10.1016/j.wem.2022.12.001
      Women increasingly participate in outdoor activities in wilderness and remote environments. We performed a literature review to address diagnostic and therapeutic considerations during first-trimester pregnancy for remote multiday travel. Pretrip planning for pregnant patients traveling outside access to advanced medical care should include performing a transvaginal ultrasound to confirm pregnancy location and checking D rhesus status. We discuss the risk of potential travel-related infections and recommended vaccinations prior to departure based on destination. Immediate evacuation to definitive medical care is required for patients with a pregnancy of unknown location and vaginal bleeding. We propose algorithms for determining the need for evacuation and present therapeutic options for nausea and vomiting, urinary tract infections, and candidiasis in the field.

      Keywords

      Introduction

      Women participate in extreme activities in remote and wilderness locations. They comprised 41% of trekkers in the Everest region in 2014
      • Keyes L.E.
      • Mather L.
      • Duke C.
      • Regmi N.
      • Phelan B.
      • Pant S.
      • et al.
      Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in Nepal: an epidemiologic survey and case series.
      and, according to a US outdoor industry survey, made up 46% of outdoor activity participants in 2019. Between 2014 and 2017, 41% of rescues by Seattle Mountain Rescue were for women.
      • McDonough M.J.
      • Feinstein B.A.
      • Webster G.E.
      • Condino A.E.
      Medical care during mountain rescue in King County, Washington, from 2004 to 2017.
      Pregnant individuals partake in many outdoor activities, including hiking, mountain biking, rock climbing, skiing, snowboarding, sailing, diving, kayaking, surfing, stand-up paddling, and others, but may receive little advice from their healthcare advisers regarding these activities.
      • Keyes L.E.
      • Hackett P.H.
      • Luks A.M.
      Outdoor activity and high altitude exposure during pregnancy: a survey of 459 pregnancies.
      It has been reported that 45% of pregnancies in the United States are unintended
      • Finer L.B.
      • Zolna M.R.
      Declines in unintended pregnancy in the United States, 2008-2011.
      ; consequently, a person may not be aware of a current pregnancy when embarking on a wilderness trip. Wilderness providers and trip leaders need to be prepared to address medical concerns in travelers with a known or newly discovered early pregnancy. This literature review addresses common potential emergencies for pregnant travelers on multiday trips in the wilderness and other remote environments prior to 14 wk of gestation. Although women constitute most individuals who become pregnant and give birth, our aim is to provide helpful information pertaining to all pregnant persons.

      Methods

      We identified medical considerations in the first trimester of pregnancy and performed a literature review using PubMed and Cochrane Library, along with a targeted search for wilderness and travel-specific references. We identified original research where the evidence was directly applicable or could be extrapolated to practice in remote settings. Abstracts and non-English manuscripts were excluded.

      Pretrip Recommendations

      Pretravel planning for expeditions, specifically extended travel into remote areas, must consider the needs of individual travelers, including issues around pregnancy. If a sexually active premenopausal traveler is embarking on a multiday wilderness trip, they should consider performing a pregnancy test before departure. A negative test, however, does not eliminate the risk of first-trimester pregnancy during travel. Early during pregnancy, urine human chorionic gonadotropin (hCG) testing may be negative before hormone levels rise adequately. A previous study reported a urine hCG test maximum sensitivity rate of 90% on the first day vs 97% 1 wk after a missed period.
      • Wilcox A.J.
      • Baird D.D.
      • Dunson D.
      • McChesney R.
      • Weinberg C.R.
      Natural limits of pregnancy testing in relation to the expected menstrual period.
      For those taking oral contraceptives, travel disruptions, including illness, lost or missing medication in luggage, and changes in time zones, may impair adherence, increasing the risk of unintended pregnancy. Rapid urine hCG tests are essential in medical travel kits. If an individual is unable to provide a urine sample, several drops of blood can serve as a substitute for these tests.
      • Fromm C.
      • Likourezos A.
      • Haines L.
      • Khan A.N.
      • Williams J.
      • Berezow J.
      Substituting whole blood for urine in a bedside pregnancy test.

      Pretrip Planning in Pregnant Travelers

      Pretrip travel planning is important for pregnant patients, especially for those engaging in remote and more physically demanding travel. We recommend that travelers with a known pregnancy seek medical care prior to departure for any extended travel or travel to remote locations. Participants should investigate local resources at their destination and have an evacuation plan to reach definitive medical care. We recommend evacuation insurance for all pregnant travelers. The safety of remote travel during pregnancy may vary with individual risk factors such as age, medical history, conception method (in vitro fertilization or intrauterine insemination), and individual risk tolerance.
      We recommend a first-trimester transvaginal ultrasound to determine the location of the pregnancy prior to departure for any remote or multiday travel. If an intrauterine pregnancy (IUP) is confirmed, the risk of complications occurring during travel decreases. Individuals with early pregnancy of unknown location with bleeding or pain should not travel and should be referred immediately for definitive medical care. Low risk, asymptomatic pregnant participants may consider delaying travel to remote locations with poor access to medical care until an IUP can be confirmed at approximately 6 wk of estimated gestational age. We recommend that those at high risk of ectopic pregnancy (Table 1) do not travel to remote locales until an IUP is confirmed. Practitioners should advise against travel and address ectopic pregnancies immediately when suspected.
      Table 1Risk factors for ectopic pregnancy
      Previous ectopic pregnancyAssisted reproductive technology pregnancy
      Previous fallopian tube surgeryEndometriosis
      Previous pelvic or abdominal surgerySmoking
      History of pelvic inflammatory diseaseAge > 35 y
      History of infertilityIntrauterine device
      All patients, especially those at high risk of fetal genetic disorders, such as advanced maternal age or a personal or family history of genetic diseases, may want to arrange the travel timing to accommodate fetal genetic testing, typically performed between 10 and 14 wk.
      Blood type and D rhesus (RhD) status should be determined if not already documented. RhD-negative pregnant individuals should be counseled on the increased risk of RhD alloimmunization if they do not receive RhD immune globulin within 72 h of vaginal bleeding during pregnancy. During alloimmunization, anti-RhD antibodies develop, which may cause severe fetal anemia or death in subsequent pregnancies.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 181: prevention of Rh D alloimmunization.
      If RhD-negative pregnant travelers have vaginal bleeding, they should seek care at a facility with RhD immune globulin within 72 h.

      Nongenitourinary Infections During Travel

      Travelers early in pregnancy should be counseled about the risks of mosquito-borne diseases. Zika is a teratogenic infection initially reported in a large epidemic throughout French Polynesia in 2013 and spread extensively during 2015. Zika infection during pregnancy can result in developmental abnormalities in the fetus, including microcephaly and central nervous system lesions.
      • Roth N.M.
      • Reynolds M.R.
      • Lewis E.L.
      • Woodworth K.R.
      • Godfred-Cato S.
      • Delaney A.
      • et al.
      Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection—US Zika pregnancy and infant registry, December 1, 2015-March 31, 2018.
      This risk decreases as pregnancy progresses, with the reported highest risk (8%) in the first trimester, which gradually decreases to 4% in the third trimester.
      • Roth N.M.
      • Reynolds M.R.
      • Lewis E.L.
      • Woodworth K.R.
      • Godfred-Cato S.
      • Delaney A.
      • et al.
      Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection—US Zika pregnancy and infant registry, December 1, 2015-March 31, 2018.
      Although most pregnant patients infected with Zika will have a mild or asymptomatic clinical course, the developing fetus can still be affected.
      • Pacheco O.
      • Beltrán M.
      • Nelson C.A.
      • Valencia D.
      • Tolosa N.
      • Farr S.L.
      • et al.
      Zika virus disease in Colombia—preliminary report.
      The risk of contracting Zika depends on multiple factors, including the local prevalence of Zika and the patient’s exposure risk. Prevention primarily involves mosquito control measures,
      • Faria N.R.
      • Azevedo R.D.
      • Kraemer M.U.
      • Souza R.
      • Cunha M.S.
      • Hill S.C.
      • et al.
      Zika virus in the Americas: early epidemiological and genetic findings.
      which include wearing protective clothing, using mosquito repellants, staying indoors during heavy biting times, and sleeping under bed netting. The US Centers for Disease Control and Prevention (CDC) recommends Environmental Protection Agency‒registered insect repellents (N,N-diethyl-meta-toluamide (DEET), picaridin, insect repellent 3535, oil of lemon eucalyptus, or paramenthanediol) that are safe during pregnancy. Permethrin-treated clothing is also recommended. No adverse effects have been noted with topical permethrin use in pregnant patients.
      • Kennedy D.
      • Hurst V.
      • Konradsdottir E.
      • Einarson A.
      Pregnancy outcome following exposure to permethrin and use of teratogen information.
      Pregnant individuals or those desiring pregnancy should avoid travel to areas where Zika is prevalent.
      • Vouga M.
      • Chiu Y.C.
      • Pomar L.
      • de Meyer S.V.
      • Masmejan S.
      • Genton B.
      • et al.
      Dengue, Zika and chikungunya during pregnancy: pre- and post-travel advice and clinical management.
      Malaria is a parasitic infection transmitted by the Anopheles mosquito, infecting millions of people worldwide annually. Pregnant individuals infected with malaria have increased morbidity and mortality and experience high risks of intrauterine demise, miscarriage, low-birth-weight neonates, premature delivery, and neonatal death.
      • Schantz-Dunn J.
      • Nour N.M.
      Malaria and pregnancy: a global health perspective.
      Malaria is the leading infectious cause of fetal growth restriction worldwide.
      • Chua C.L.
      • Khoo S.K.
      • Ong J.L.
      • Ramireddi G.K.
      • Yeo T.W.
      • Teo A.
      Malaria in pregnancy: from placental infection to its abnormal development and damage.
      Patients should be counseled about the risks of malaria during pregnancy and encouraged to take appropriate protection measures, including deferring travel if possible. If they are unable to defer travel, chemoprophylaxis and mosquito avoidance are recommended. The optimal antimalarial agent for prevention depends on regional transmission, drug resistance patterns, and patients’ characteristics. For travel to chloroquine-sensitive areas, the agent of choice during pregnancy is chloroquine, and for travel to areas with chloroquine-resistant malaria, mefloquine is commonly used.
      • Irvine M.H.
      • Einarson A.
      • Bozzo P.
      Prophylactic use of antimalarials during pregnancy.
      Doxycycline carries a risk of skeletal or dental malformation, and primaquine has a risk of severe hemolysis in glucose-6-phosphate dehydrogenase‒deficient individuals, so both drugs should be avoided during pregnancy.
      • Nosten F.
      • McGready R.
      • d'Alessandro U.
      • Bonell A.
      • Verhoeff F.
      • Menendez C.
      • et al.
      Antimalarial drugs in pregnancy: a review.
      The mosquito avoidance measures previously mentioned should be taken.
      Travelers’ diarrhea is common during international travel, with the most common bacterial agents being Escherichia coli, Campylobacter, Salmonella, and Shigella. Norovirus and rotavirus dominate the viral landscape, whereas exposure to contaminated water can result in Giardia intestinalis and Cryptosporidium infections.
      • Kanhutu K.
      • Torda A.
      Travel and pregnancy: an infectious diseases perspective.
      We recommend prompt oral hydration and use of azithromycin over fluoroquinolones during pregnancy because of an improved safety profile.
      • Sarkar M.
      • Woodland C.
      • Koren G.
      • Einarson A.R.
      Pregnancy outcome following gestational exposure to azithromycin.
      ,
      • Yefet E.
      • Schwartz N.
      • Chazan B.
      • Salim R.
      • Romano S.
      • Nachum Z.
      The safety of quinolones and fluoroquinolones in pregnancy: a meta-analysis.
      Rifamycin is used as an alternative treatment for noninvasive travelers’ diarrhea. There is evidence demonstrating a decrease in systemic exposure of oral contraceptives with rifamycin use, but its safety in pregnancy is unknown,
      • Simmons K.B.
      • Haddad L.B.
      • Nanda K.
      • Curtis K.M.
      Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review.
      and therefore, it is not recommended. The US Food and Drug Administration recommends avoiding bismuth subsalicylate during pregnancy but considers loperamide safe.
      Nausea during pregnancy, combined with gastrointestinal losses due to travelers’ diarrhea, places pregnant patients at a high risk of dehydration. Hydration status should be closely monitored. Management of nausea and vomiting is discussed below. Travelers and expedition leaders should ensure that they carry appropriate antimicrobials that are safe during pregnancy in their medical kit (Table 2).
      Table 2Antimicrobials for pregnant adventurers
      InfectionMedicationDose (mg)FrequencyAvoid
      Malaria prophylaxisChloroquine

      Mefloquine
      In chloroquine-resistant areas.
      300 base (500 salt)

      228 base (250 salt)
      Weekly

      Weekly
      Doxycycline

      Primaquine
      Travelers’ diarrheaAzithromycin1000OnceFluoroquinolones
      Urinary tract infectionAmoxicillin



      Cephalexin

      Nitrofurantoin
      In patients with anaphylaxis to penicillin.
      500 or

      875

      250 to 500

      100
      8 h

      12 h

      6 h

      12 h
      Fluoroquinolones



      Sulfamethoxazole

      Trimethoprim
      CandidiasisClotrimazole

      Miconazole (Vag supp)
      100

      200
      Daily

      Daily
      Fluconazole
      Vag supp, vaginal suppository.
      a In chloroquine-resistant areas.
      b In patients with anaphylaxis to penicillin.

      Vaccinations During Pregnancy

      Many pregnant patients worry about the safety of vaccinations during pregnancy. Individuals who are planning a pregnancy should complete all age-based CDC-recommended vaccinations before becoming pregnant. Vaccinations during pregnancy should be considered when there is a high possibility of exposure to an infection that could harm the traveler or fetus and the vaccine is unlikely to cause adverse effects.
      • Kroger A.T.
      • Atkinson W.L.
      • Sumaya C.V.
      • Pickering L.K.
      General recommendations on immunization; recommendations of the Advisory Committee on Immunization Practices (ACIP).
      Regardless of destination, pregnant people should be encouraged to get an annual influenza vaccine and complete their coronavirus disease 2019 vaccine series and boosters based on current CDC guidance. Live attenuated virus vaccines, such as typhoid (oral) and yellow fever, are traditionally contraindicated during pregnancy because of a theoretical risk of crossing the placenta and causing a viral infection in the fetus.
      • Sur D.K.
      • Wallis D.H.
      • O'Connell T.X.
      Vaccinations in pregnancy.
      Pregnant people can receive a typhoid (injectable) polysaccharide vaccine when needed, but safety and efficacy studies have not been performed in pregnant individuals.
      • Kroger A.T.
      • Atkinson W.L.
      • Sumaya C.V.
      • Pickering L.K.
      General recommendations on immunization; recommendations of the Advisory Committee on Immunization Practices (ACIP).
      There are no large, prospective trials evaluating the risks of yellow fever vaccination in pregnancy; however, retrospective
      • Hall C.
      • Khodr Z.G.
      • Chang R.N.
      • Bukowinski A.T.
      • Gumbs G.R.
      • Conlin A.M.
      Safety of yellow fever vaccination in pregnancy: findings from a cohort of active duty US military women.
      and observational
      • Suzano C.E.
      • Amaral E.
      • Sato H.K.
      • Papaiordanou P.M.
      Campinas group on yellow fever immunization during pregnancy. The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil.
      studies support no association between vaccination during pregnancy and adverse outcomes. The World Health Organization recommends yellow fever vaccination when the risks of yellow fever infection outweigh the risks of vaccination, including unavoidable travel to an endemic area.
      World Health Organization
      Safety of immunization during pregnancy: a review of the evidence: Global Advisory Committee on Vaccine Safety.
      We recommend that patients seek counsel from a travel medicine specialist to discuss the need for other vaccines during pregnancy (Table 3).
      Table 3Travel vaccinations during pregnancy
      VaccineTypeRecommendation
      COVID-19Messenger RNA Viral vectorMessenger RNA preferred over viral vector vaccines
      Hepatitis AKilledIf traveling to highly endemic areas
      Influenza (injection)KilledRecommended annually
      Influenza (nasal)Live attenuatedContraindicated
      Japanese encephalitisKilledConsider when traveling to highly endemic areas. Discuss with travel physician
      Meningococcal (MenACWY) (MenB)

      Conjugated

      Recombinant


      Recommended

      Postponed until after pregnancy unless outbreak reported
      RabiesKilledIf high risk of rabies exposure

      Pre-exposure and postexposure prophylaxis safe
      Typhoid (injection)



      Typhoid (oral)
      Killed



      Live
      Avoid unless high risk of exposure

      Contraindicated
      Yellow feverLive attenuatedConsider if benefits outweigh risks
      COVID-19, coronavirus disease 2019; MenACWY, Meningococcal serogroups A, C, W, and Y; MenB, Meningococcal serogroup B; RNA, ribonucleic acid.

      First-Trimester Bleeding

      Early pregnancy bleeding has been reported to affect approximately 27% of pregnancies.
      • Hasan R.
      • Baird D.D.
      • Herring A.H.
      • Olshan A.F.
      • Funk M.L.
      • Hartmann K.E.
      Association between first-trimester vaginal bleeding and miscarriage.
      There are many causes of vaginal bleeding and pelvic discomfort during the first trimester, including normal gestation, early pregnancy loss, ectopic pregnancy, threatened miscarriage, and molar pregnancy.
      American College of Obstetricians and Gynecologists
      Practice bulletin no. 200: early pregnancy loss.
      Evacuation may not be required for all pregnant individuals who develop bleeding in the wilderness, but assessing risk is mandatory (Figure 1). A pretrip ultrasound that confirms an IUP provides reassurance against ectopic pregnancy. Assessment is more challenging for those without a prior confirmatory ultrasound or who are unaware that they are pregnant. Bleeding in these cases may represent an emergency requiring evacuation. Anyone with the potential to be pregnant who develops abdominal pain in the wilderness should have a urine hCG test performed and confirm the last menstrual period (LMP), defined as the first day of bleeding from the most recent period.
      Figure thumbnail gr1
      Figure 1Evaluation of pregnant patients with abdominal pain or vaginal bleeding during the first trimester in a remote setting. RhD, D rhesus.
      The severity of bleeding should be determined. Heavy bleeding is often defined as soaking through 1 to 2 large pad(s) or tampon(s) every hour for 2 h in a row.
      American College of Obstetricians and Gynecologists
      Practice bulletin no. 200: early pregnancy loss.
      A full menstrual cup is approximately equivalent to 2 saturated tampons. Menstrual cups often have measurements allowing for quantification of volume. Individuals with significant bleeding should be evacuated to mitigate risk of hemorrhage, which could lead to anemia, hypovolemia, shock, or death.
      Early pregnancy ultrasound helps rule out ectopic pregnancy and should be performed in the field when available. Transabdominal ultrasound has lower sensitivity during early pregnancy than transvaginal ultrasound, which is often not available in remote settings. Identification of an intrauterine gestational sac with either a yolk sac or an embryo is required to diagnose an IUP. Fetal heart activity (FHA) confirms viability, but if assessed using transabdominal ultrasound, failure to detect FHA does not necessarily indicate a nonviable pregnancy.
      Although mild cramping in the first trimester can be normal, ectopic pregnancy must be excluded for anyone with abdominal pain or pelvic pain and a positive pregnancy test result without confirmed IUP. If ultrasound is not available at the time of early pregnancy diagnosis in the field, any vaginal bleeding or pain should prompt evacuation to a medical facility with these capabilities as soon as possible. Quantitative β-hCG and other laboratory diagnostic tools used in clinical settings are unlikely to be available in most remote environments.

      Ectopic Pregnancy

      An ectopic pregnancy is at risk of rupture within the abdomen, which can lead to severe occult bleeding that may not be recognized in the field until the patient has already experienced substantial, life-threatening blood loss. An ectopic pregnancy occurs when a fertilized egg implants in a structure outside of the uterine cavity. Patients with an ectopic pregnancy may report pelvic or abdominal pain, missed menses, or vaginal bleeding. Syncope, lightheadedness, referred shoulder pain, urinary symptoms, rectal pressure, or other gastrointestinal symptoms may be present. On examination, abdominal, pelvic, adnexal, or cervical motion tenderness may be present. Peritoneal signs, tachycardia, hypotension, pallor, or abdominal distention are also concerning findings.
      National Guideline Alliance (UK)
      Ectopic pregnancy and miscarriage: diagnosis and initial management.
      ,
      American College of Obstetricians and Gynecologists
      Practice bulletin no. 193: tubal ectopic pregnancy.
      Ultrasound findings that may indicate an ectopic pregnancy include empty uterus, fluid collection within the uterine cavity (pseudosac), or free fluid. The absence of a mass does not rule out ectopic pregnancy.
      • Barnhart K.T.
      Clinical practice. Ectopic pregnancy.
      Although heterotopic pregnancy is rare, the adnexa should also be evaluated, even when an IUP is identified. Given the limitation of diagnostics in the wilderness environment, one should err on the side of caution and evacuate any pregnant person with a suspected ectopic pregnancy. Patients with an intrauterine device who discover that they are pregnant should be evacuated immediately regardless of symptoms because there is a high likelihood of an ectopic pregnancy.
      • Li C.
      • Zhao W.H.
      • Meng C.X.
      • Ping H.
      • Qin G.J.
      • Cao S.J.
      • et al.
      Contraceptive use and the risk of ectopic pregnancy: a multi-center case-control study.
      ,
      American College of Obstetricians and Gynecologists
      Practice bulletin no. 121: long-acting reversible contraception: implants and intrauterine devices.

      Early Pregnancy Loss

      Early pregnancy loss (EPL), also referred to as miscarriage or spontaneous abortion, is defined as a nonviable IUP with either an empty gestational sac or a gestational sac containing an embryo or fetus without FHA prior to 13 completed weeks of gestation.
      National Guideline Alliance (UK)
      Ectopic pregnancy and miscarriage: diagnosis and initial management.
      Pregnancy loss is most common during the first trimester.
      • Wang X.
      • Chen C.
      • Wang L.
      • Chen D.
      • Guang W.
      • French J.
      Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study.
      Prior EPL and advanced maternal age are risk factors for EPL, and rates of EPL rise with increasing maternal age.
      Practice Committee of the American Society for Reproductive Medicine
      Evaluation and treatment of recurrent pregnancy loss: a committee opinion.
      Diagnosing EPL in remote environments may be appropriate if there was a previously confirmed viable IUP on ultrasound, followed by vaginal bleeding, and subsequent ultrasound imaging revealing an empty uterus (complete miscarriage) or an IUP without FHA (missed or incomplete miscarriage) (Figure 2). Transvaginal ultrasound confirmation is the most reliable imaging method but is unlikely to be available in the wilderness setting. The LMP may not accurately represent gestational age because of variation in menstrual cycle length; therefore, LMP alone should not be used to determine whether FHA is expected.
      National Guideline Alliance (UK)
      Ectopic pregnancy and miscarriage: diagnosis and initial management.
      Wilderness providers should be cautious to diagnose EPL based on an initial field transabdominal ultrasound without a prior confirmed viable IUP, because they could misdiagnose an ectopic pregnancy or an early viable pregnancy that does not yet meet radiographic criteria. This is particularly relevant when the equipment quality or sonographer’s experience are limited. When available, remote telemedicine consultation should be considered to review images. If ultrasound is not available to confirm EPL, the patient should be evacuated.
      Figure thumbnail gr2
      Figure 2Evaluation of pregnant patients with a previously confirmed intrauterine pregnancy and bleeding during the first trimester in a remote setting. IUP, intrauterine pregnancy; FHA, fetal heart activity; RhD, D rhesus.
      A patient who has passed products of conception, has an empty uterus on subsequent ultrasound (complete miscarriage), and has minimal to no bleeding does not require medical evacuation and may desire to remain in the wilderness environment. Providers should recognize the need for grief management and the potential desire to be evacuated even if a physical complication is unlikely following a complete miscarriage. A person with a complete miscarriage, with significant bleeding, should be evacuated.
      In the clinical environment, missed or incomplete miscarriages can be treated with expectant, medical, or surgical management. It is difficult to predict when and if significant bleeding and pain will occur in these cases. Expectant management has the potential to pose risks to the patient and group in remote environments, and other options are unlikely to be available. We recommend evacuation for all missed or incomplete miscarriages.

      Threatened Miscarriage

      A threatened miscarriage is diagnosed in a patient with a confirmed IUP with FHA and vaginal bleeding. It has been reported that over 90% of threatened miscarriages result in viable pregnancies.
      • Tannirandorn Y.
      • Sangsawang S.
      • Manotaya S.
      • Uerpairojkit B.
      • Samritpradit P.
      • Charoenvidhya D.
      Fetal loss in threatened abortion after embryonic/fetal heart activity.
      Light bleeding is not a significant marker of risk of miscarriage, although heavy bleeding is concerning.
      American College of Obstetricians and Gynecologists
      Practice bulletin no. 200: early pregnancy loss.
      If bleeding stops, it may be appropriate to continue the current wilderness activity based on the patient’s level of comfort and ability to access healthcare facilities if needed. The patient should be evacuated promptly if bleeding worsens. Bed rest does not prevent miscarriages.
      • Aleman A.
      • Althabe F.
      • Belizán J.
      • Bergel E.
      Bed rest during pregnancy for preventing miscarriage.
      Proposed strategies for preventing or reducing risk of miscarriage, such as progestogen supplementation, have little supporting data
      • Haas D.M.
      • Hathaway T.J.
      • Ramsey P.S.
      Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology.
      and are not applicable to remote settings.

      Medications

      Ideally, RhD status is known before travel to identify those at risk of alloimmunization. Pregnant patients with vaginal bleeding who are not confident that they are RhD positive should consider evacuation for confirmation of RhD status and potential need for Rho(D) immunoglobulin.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 181: prevention of Rh D alloimmunization.
      Tranexamic acid is indicated for many severe bleeding scenarios and is often included in expedition medical kits. There are limited case reports on its successful use for hemorrhage in ectopic pregnancies.
      • Grassetto A.
      • Fullin G.
      • Cerri G.
      • Simioni P.
      • Spiezia L.
      • Maggiolo C.
      Management of severe bleeding in a ruptured extrauterine pregnancy: a theragnostic approach.
      ,
      • Murphy N.C.
      • Hayes N.E.
      • Ainle F.B.
      • Flood K.M.
      Jehovah’s Witness patients presenting with ruptured ectopic pregnancies: two case reports.
      The safety of tranexamic acid regarding birth defects and obstetric complications, including venous thromboembolism, is unclear. Therefore, tranexamic acid should only be used to mitigate severe, life-threatening hemorrhage during early pregnancy when immediate evacuation is not possible or in unstable patients during evacuation. Dosing options include 1 g of tranexamic acid intravenously once (may repeat in 30 min to 1 h if severe bleeding persists) or 1300 mg orally 3 times daily up to 5 d.

      Nausea and Vomiting during Pregnancy

      When travelers of reproductive age present with nausea and vomiting in a remote environment, pregnancy should be considered. A careful history, including LMP (if known) and use of contraception, should be taken and a pregnancy test performed. Nausea and vomiting may occur in 50% of pregnancies, and typical onset is prior to 9 wk gestational age.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Persistent vomiting may represent a condition known as hyperemesis gravidarum, which can present with ≥ 5% body weight loss, abnormalities of electrolytes, liver function tests, and thyroid function tests.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Other causes of nausea and vomiting should still be ruled out (Figure 3). Associated fever, headache, and moderate-to-severe abdominal pain raise concerns for an alternative etiology.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Abdominal pain could suggest appendicitis, ectopic pregnancy, ovarian torsion, renal calculi, urinary tract infection, or intestinal obstruction.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Diarrhea does not usually accompany nausea and vomiting of pregnancy (NVP) and suggests an alternative diagnosis. In individuals who have recently ascended to altitudes >2500 m, nausea and vomiting, accompanied by headache, suggest acute mountain sickness; or if severe and associated with altered mental status or gait abnormalities, suggest high altitude cerebral edema.
      • Luks A.M.
      • Auerbach P.S.
      • Freer L.
      • Grissom C.K.
      • Keyes L.E.
      • McIntosh S.E.
      • et al.
      Wilderness Medical Society clinical practice guidelines for prevention and treatment of acute altitude illness: 2019 update.
      An abnormal neurological exam does not occur with NVP.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Fever may accompany gastroenteritis, appendicitis, hepatitis, or pyelonephritis.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Exercise-associated hyponatremia should be considered in those aggressively hydrating with water who develop nausea and vomiting.
      • Bennett B.L.
      • Hew-Butler T.
      • Hoffman M.D.
      • Rogers I.R.
      • Rosner M.H.
      Wilderness Medical Society guidelines for treatment of exercise-associated hyponatremia: 2014 update.
      Activity in high ambient temperatures may lead to heat exhaustion or heat stroke, accompanied by nausea and vomiting.
      • Lipman G.S.
      • Gaudio F.G.
      • Eifling K.P.
      • Ellis M.A.
      • Otten E.M.
      • Grissom C.K.
      Wilderness Medical Society clinical practice guidelines for the prevention and treatment of heat illness.
      Evaluation of NVP in a remote environment includes assessment of the differential diagnosis, available treatments, and ability of the patient to continue with the trip vs evacuation. Adequate hydration is critical in pregnant patients with nausea and vomiting, regardless of the underlying cause.
      Figure thumbnail gr3
      Figure 3Differential diagnosis of nausea and vomiting during pregnancy.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      • Luks A.M.
      • Auerbach P.S.
      • Freer L.
      • Grissom C.K.
      • Keyes L.E.
      • McIntosh S.E.
      • et al.
      Wilderness Medical Society clinical practice guidelines for prevention and treatment of acute altitude illness: 2019 update.
      • Bennett B.L.
      • Hew-Butler T.
      • Hoffman M.D.
      • Rogers I.R.
      • Rosner M.H.
      Wilderness Medical Society guidelines for treatment of exercise-associated hyponatremia: 2014 update.
      • Lipman G.S.
      • Gaudio F.G.
      • Eifling K.P.
      • Ellis M.A.
      • Otten E.M.
      • Grissom C.K.
      Wilderness Medical Society clinical practice guidelines for the prevention and treatment of heat illness.
      If evaluation is consistent with NVP, dietary changes may help, including eating frequent, small meals, avoiding fatty and spicy foods, and eating bland or dry foods (Table 4).
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Ginger may help with nausea (tea or capsules) but not with vomiting.
      • Viljoen E.
      • Visser J.
      • Koen N.
      • Musekiwa A.
      A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting.
      Acupressure on the inside of the wrist (wrist bands) may be beneficial.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Various medications are used, although evidence of their effectiveness is limited.
      • Matthews A.
      • Haas D.M.
      • O'Mathúna D.P.
      • Dowswell T.
      • Doyle M.
      Interventions for nausea and vomiting in early pregnancy.
      Vitamin B6 with doxylamine is safe and considered first-line therapy for NVP.
      • Koren G.
      • Clark S.
      • Hankins G.D.
      • Caritis S.N.
      • Miodovnik M.
      • Umans J.G.
      • et al.
      Effectiveness of delayed release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial.
      Diphenhydramine has also been shown to be effective in controlling NVP.
      • Magee L.A.
      • Mazzota P.
      • Koren G.
      Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP).
      Metoclopramide and phenothiazines (promethazine and prochlorperazine) are effective and, in most studies, have not been associated with increased congenital malformations.
      • Magee L.A.
      • Mazzota P.
      • Koren G.
      Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP).
      ,
      • Tan P.C.
      • Khine P.P.
      • Vallikkannu N.
      • Omar S.Z.
      Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial.
      Ondansetron has been used successfully to treat NVP, with insufficient data on fetal safety; however, the absolute risk is believed to be low.
      • Abas M.N.
      • Tan P.C.
      • Azmi N.
      • Omar S.Z.
      Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial.
      • Kashifard M.
      • Basirat Z.
      • Golsorkhtabar-Amiri M.
      • Moghaddamnia A.
      Ondansetron or metoclopramide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study.
      • Carstairs S.D.
      Ondansetron use in pregnancy and birth defects: a systematic review.
      Ondansetron should not be combined with phenothiazine because of cardiac risk of QT interval prolongation.
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Table 4Therapeutic options for management of nausea and vomiting during pregnancy
      • American College of Obstetricians and Gynecologists
      Practice bulletin no. 189: nausea and vomiting of pregnancy.
      Dietary changes:
      Frequent, small meals
      Eat bland and dry foods (toast, dry cereal, crackers)
      Avoid fatty or spicy foods
      Over-the-counter options:
      MedicationDosage (mg)FrequencyRouteSpecial notes
      Folic acid alone rather than full prenatal vitamin0.6DailyOralStandard 600-microgram dose
      Ginger capsules250Every 6 hOral
      Vitamin B6 (pyridoxine) and/or

      Doxylamine
      10 to 25

      12.5
      Every 6 to 8 h

      Every 6 to 8 h
      Oral

      Oral
      Dimenhydrinate or

      Diphenhydramine
      25 to 50

      25 to 50
      Every 4 to 6 h

      Every 4 to 6 h
      Oral

      Oral
      WARNING: Do not exceed 200 mg daily if patient also taking doxylamine
      Wrist bands for nausea-As neededWristEx: Sea-Band, ReliefBand
      Prescription medications:
      MedicationDosage (mg)FrequencyRouteSpecial notes
      Doxylamine or Pyridoxine10/10 DR (2 tablets) or 20/20 ERAt bedtime



      At bedtime
      Oral



      Oral
      More frequent dosing per pharmaceutical guideline
      Prochlorperazine or Promethazine25

      12.5 to 25
      Every 12 h

      Every 4 to 6 h
      Rectal

      Oral or rectal
      Long-term or excess use may cause dystonic reactions
      If symptoms persist:
      Metoclopramide or Ondansetron5 to 10

      4
      Every 6 to 8 h

      Every 8 h
      Oral

      Oral
      WARNING: Do not combine ondansetron with use of prochlorperazine or promethazine
      DR, delayed release (Diclegis); ER, extended release (Bonjesta).
      Patients with isolated nausea and vomiting may respond to conservative measures or treatment. Mild NVP does not have an adverse effect on the fetus, and some data support an association with a lower risk of miscarriage compared with controls.
      • Hinkle S.N.
      • Mumford S.L.
      • Grantz K.L.
      • Silver R.M.
      • Mitchell E.M.
      • Sjaarda L.A.
      • et al.
      Association of nausea and vomiting during pregnancy with pregnancy loss: a secondary analysis of a randomized clinical trial.
      We recommend evacuation if the patient is unable to tolerate fluids for 24 h or has coffee ground or bloody emesis.

      Genitourinary Infections

      Urinary Tract Infections

      Urinary tract infections (UTIs) in pregnant people risk progressing to pyelonephritis because of multiple different physiologic changes during pregnancy and may be associated with preterm birth, low birth weight, and perinatal mortality,
      • Hill J.B.
      • Sheffield J.S.
      • McIntire D.D.
      • Wendel Jr., G.D.
      Acute pyelonephritis in pregnancy.
      as well as a risk of sepsis and maternal death if left untreated. The most common pathogens are Klebsiella, E coli, and group B streptococcus.
      • Hill J.B.
      • Sheffield J.S.
      • McIntire D.D.
      • Wendel Jr., G.D.
      Acute pyelonephritis in pregnancy.
      UTI symptoms may include burning or pain with urination, urinary frequency, and change in urine smell or color. Urine dipsticks can easily be carried in medication kits to test for infection. If a pregnant individual has symptoms consistent with a UTI, oral antibiotics should be initiated, such as penicillins or first- and second-generation cephalosporins. Amoxicillin and cephalexin are safe during pregnancy.
      • Bookstaver P.B.
      • Bland C.M.
      • Griffin B.
      • Stover K.R.
      • Eiland L.S.
      • McLaughlin M.
      A review of antibiotic use in pregnancy.
      In the case of severe anaphylaxis to penicillins, nitrofurantoin can be used. Patients with symptoms that include fever, flank pain, vomiting, and/or costovertebral angle tenderness
      • Jolley J.A.
      • Wing D.A.
      Pyelonephritis in pregnancy: an update on treatment options for optimal outcomes.
      require evacuation to a medical center that can evaluate and manage pyelonephritis and sepsis. Pregnant patients with symptoms of a UTI that do not improve in 48 h should be reevaluated and evacuation considered.
      • Schimelpfenig T.
      National Outdoor Leadership School Wilderness Medicine.

      Candidal Infections

      Candida vulvovaginitis is a vaginal yeast infection caused by Candida. Normally, Candida is not pathogenic, but loss of chemical balance, especially hormonal changes during pregnancy, can cause Candida to multiply.
      • Ramos-E-Silva M.
      • Martins N.R.
      • Kroumpouzos G.
      Oral and vulvovaginal changes in pregnancy.
      ,
      • Sobel J.D.
      Vulvovaginal candidosis.
      Common symptoms include thick, white vaginal discharge; vaginal itching or soreness; swelling; painful urination; and painful intercourse.
      • Eckert L.O.
      • Hawes S.E.
      • Stevens C.E.
      • Koutsky L.A.
      • Eschenbach D.A.
      • Holmes K.K.
      Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm.
      Pregnant patients with symptoms of vulvovaginal candidiasis can use clotrimazole or miconazole creams or suppositories. Common medication side effects include burning, redness, and irritation. While oral azole treatment is commonly used for uncomplicated infections outside of pregnancy, oral treatment during the first trimester is not recommended because of a potential increased risk of miscarriage or birth defects, although data are conflicting.
      • Mølgaard-Nielsen D.
      • Svanström H.
      • Melbye M.
      • Hviid A.
      • Pasternak B.
      Association between use of oral fluconazole during pregnancy and risk of spontaneous abortion and stillbirth.
      ,
      • Bérard A.
      • Sheehy O.
      • Zhao J.P.
      • Gorgui J.
      • Bernatsky S.
      • de Moura C.S.
      • et al.
      Associations between low- and high-dose oral fluconazole and pregnancy outcomes: 3 nested case-control studies.
      Vulvovaginal candidiasis does not require evacuation.

      Conclusions

      With proper preparation and precaution, remote travel can be safe and appropriate during early pregnancy. We offer considerations for pretrip planning and a practical approach to vaginal bleeding, nausea and vomiting, and genitourinary infections for pregnant individuals participating in wilderness and remote travel. Research is lacking on pregnancy outcomes and first-trimester exposure to remote and extreme environments. Future investigations are needed to address this important health issue.

      Acknowledgments

      The authors acknowledge the Wilderness Medical Society Women in Wilderness Medicine Research Committee for creating the space for collaboration on women’s health in wilderness environments. The authors thank Hillary E. Davis, MD, PhD, and Jonathan Steller, MD, for their critical revision of the manuscript.
      Author Contributions: All authors participated in the concept and design, drafting, critical revision, and final approval of the manuscript.
      Financial/Material Support: None
      Disclosures: None.

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