Miscarriage - Ectopic Pregnancy - Hyperemesis Gravidarum - Nausea - Vomiting
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First Trimester Pregnancy Emergencies: Recognition and Management

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First Trimester Pregnancy Emergencies: Recognition and Management

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  About This Issue

When a first-trimester-pregnant patient presents to the ED, emergency clinicians must consider the life and health of both the mother and the fetus in diagnosis and management. Abdominal pain, bleeding, urinary tract infection, and nausea and vomiting are common conditions in the differential for pregnant patients – as well as for patients who don’t yet know they’re pregnant. This issue provides the latest evidence on managing the most common emergencies in the first trimester.

• Confirming an intrauterine pregnancy is key: how are hCG levels correlated with ultrasound results? What are the best imaging studies if it’s unclear?
• What are the key features of the physical examination that will tell you whether a miscarriage has occurred or may occur?
• What can you say when a patient asks, “will I lose my baby?” What can say when the answer is “yes”?
• Should you screen routinely for UTI? Asymptomatic bacteriuria? When is admission required?
• What are the immediate actions to take when ectopic pregnancy is on the differential?
• Is there any good treatment for nausea and vomiting in pregnancy? What’s the best stepwise approach to managing this common condition?
• What are the cautions when imaging pregnant patients?

  Issue Information

Author: Ryan Pedigo, MD

Peer Reviewers: Jennifer Beck-Esmay, MD; Taku Taira, MD, FACEP

Publication Date: January 1, 2019

CME Expiration Date: January 1, 2022

CME Credits: 4 AMA PRA Category 1 CreditsTM, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2A or 2B CreditsIncluded as part of the 4 credits, this CME activity is eligible for 2 Pharmacology CME credits.

PubMed ID: 30570248

  Issue Features
  Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Etiology and Pathophysiology
    1. Miscarriage
    2. Ectopic Pregnancy
    3. Nausea and Vomiting of Pregnancy (and Hyperemesis Gravidarum)
    4. Asymptomatic Bacteriuria and Urinary Tract Infections
    5. Acute Appendicitis in Pregnancy
  6. Differential Diagnosis
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. History
    2. Physical Examination
  9. Diagnostic Studies
    1. Urine Pregnancy Testing
    2. Diagnostic Studies in Miscarriage and Ectopic Pregnancy
      1. Imaging Studies
      2. Rh Status
    3. Diagnostic Studies in Nausea and Vomiting of Pregnancy
    4. Diagnostic Studies in Asymptomatic Bacteriuria and Urinary Tract Infections
    5. Diagnostic Studies in Acute Appendicitis in Pregnancy
  10. Treatment
    1. Prevention of Rh Alloimmunization
    2. Miscarriage
      1. Managing Communication Around Pregnancy Loss
    3. Pregnancy of Unknown Location and Ectopic Pregnancy
    4. Nausea and Vomiting of Pregnancy
    5. Asymptomatic Bacteriuria and Urinary Tract Infections
    6. Acute Appendicitis in Pregnancy
  11. Special Circumstances
    1. Ionizing Radiation in Pregnancy
  12. Controversies and Cutting Edge
    1. Pregnancy Testing Using Whole Blood With Point-of-Care Testing Devices
    2. Expectant Management of Ectopic Pregnancy
  13. Disposition
  14. Summary
  15. Risk Management Pitfalls for Emergency Department Management of First-Trimester Pregnant Patients
  16. Time- and Cost-Effective Strategies
  17. Case Conclusions
  18. Clinical Pathway for Emergency Department Management of Nausea and Vomiting of Pregnancy
  19. Tables and Images
    1. Table 1. Differential Diagnosis for Abdominal Pain in Pregnancy
    2. Table 2. Types of Miscarriage and Associated Physical Examination and Ultrasound Findings
    3. Table 3. Fetal Radiation Doses Associated With Common Radiologic Examinations
    4. Figure 1. Sites of Ectopic Pregnancy Implantation
    5. Figure 2. Changes in hCG Levels Over 48 Hours in Patients With Intrauterine Pregnancies, Ectopic Pregnancies, and Spontaneous Abortion / Miscarriage
    6. Figure 3. Definitive Intrauterine Pregnancy on Ultrasound
    7. Figure 4. Definitive Ectopic Pregnancy on Ultrasound
  20. References

 

Abstract

Timely management of patients presenting to the ED while in their first trimester of pregnancy can improve outcomes for both the patient and the fetus. Common obstetric problems encountered include vaginal bleeding and miscarriage, ectopic pregnancy and pregnancy of undetermined location, and nausea and vomiting of pregnancy, including hyperemesis gravidarum. Optimal diagnostic approaches and management strategies are covered, including which antiemetics are safe to give in pregnancy. Common nonobstetric problems include asymptomatic bacteriuria, urinary tract infections including pyelonephritis, and acute appendicitis. This article also reviews the various imaging modalities available for pregnant patients and reviews the risks of ionizing radiation as well as various contrast media.

 

Case Presentations

Your first patient of the shift is a 23-year-old woman whom the nurse has rushed into the resuscitation bay due to hypotension and altered mental status. The patient's blood pressure is 70/40 mm Hg, with a heart rate of 70 beats/min, and she states that she has had abdominal pain and vaginal bleeding since this morning. You wonder what would be the fastest way to get this patient diagnosed and treated…

The patient in the room next door is a 19-year-old woman who presents due to light vaginal spotting for the past few hours. She says she came in because she has been trying to get pregnant for months, and finally had a positive pregnancy test yesterday. This is her first visit to a doctor since learning of her pregnancy. She is tearful, and asks, “Does this mean I am going to lose my baby?” You are not quite sure how to answer her question, and you ask yourself what tests need to be done today in the ED...

Later that shift, you evaluate a 26-year-old woman who has a confirmed intrauterine pregnancy at 11 weeks’ gestation and presents for fever, dysuria, and right flank pain. An ultrasound was performed in triage that showed bilateral mild hydronephrosis. You are not sure what to make of that finding, which antibiotics would be safe for treatment, and whether she can be managed as an outpatient…

 

Introduction

Patients in their first trimester of pregnancy frequently present to the emergency department (ED) with both obstetric and nonobstetric complaints that range from benign to life-threatening for both mother and fetus. Managing these patients is an important skill, but a recent survey demonstrated that only 56% of emergency medicine residents felt they had adequate exposure to obstetric emergencies. On a multiple-choice test covering knowledge of obstetric emergencies, a mean of 58% of items were answered correctly.1 This identifies an important area for further education and training, as timely diagnosis and appropriate management can improve outcomes.

Common obstetric problems in the first trimester of pregnancy include vaginal bleeding and the spectrum of miscarriage (experienced by 7%-27% of pregnant patients)2, nausea and vomiting (85%)3, hyperemesis gravidarum (3%), and ectopic pregnancy (2%)4. Common nonobstetric problems include appendicitis and urinary tract infections (UTIs). The most recent report on pregnancy-related mortality, published in 2017 and encompassing 2011-2013 data for pregnancies in the United States, showed a stable rate of 17 deaths per 100,000 pregnancies, but with significant racial-ethnic disparities.5

This issue of Emergency Medicine Practice reviews important issues that affect patients in their first trimester, management pearls and pitfalls, and a review of the literature surrounding current recommendations.

 

Critical Appraisal of the Literature

Medical Subject Headings (MeSH) via PubMed were searched for pregnancy trimester, first (14,929 articles), hyperemesis gravidarum (1379 articles), ectopic pregnancy (13,953 articles), and abortion, spontaneous (34,256 articles). These articles were further limited to English language only, human subjects, and then divided into reviews and clinical trials.

Guidelines from the American College of Obstetricians and Gynecologists (ACOG) were reviewed, including evidence-based Practice Bulletins on critical care in pregnancy (2016)6, medical management of first-trimester abortion (2014)7, tubal ectopic pregnancy (2018)8, nausea and vomiting of pregnancy (2018)9, and prevention of RhD alloimmunization (2017)10. ACOG Committee Opinions on the risk of birth defects with antibiotics for UTI (2017)11 and guidelines for imaging in pregnancy (2017)12 were also reviewed. The American College of Radiology Practice Parameter for imaging of pregnant women (2013)13, a consensus-based guideline based on the review of the available evidence, was reviewed, along with the 2005 guidelines from the Infectious Diseases Society of America (IDSA) on asymptomatic bacteriuria.14

The Cochrane Database of Systematic Reviews has reviews on interventions for nausea and vomiting in pregnancy (2015)15, hyperemesis gravidarum (2016)16, antibiotic regimens for asymptomatic bacteriuria (2010)17, UTIs (2011)18, expectant versus surgical management of miscarriage (2012)19, and medical treatments for incomplete miscarriage (2017)20. Most of these reviews include multiple randomized controlled trials, and the data are generally good for these topics. The American College of Emergency Physicians (ACEP) released a 2017 update on their Clinical Policy, “Critical Issues in the Initial Evaluation and Management of Patients Presenting to the ED in Early Pregnancy,” although no new significant updates were added since their previous 2012 recommendations.21,22

The relevant literature that guides ED management of first trimester emergencies is, overall, very good, and many of the recommendations in this issue of Emergency Medicine Practice can be made based on robust data. Some data, such as the utility of a pelvic examination when an ultrasound is performed, are underpowered to detect potential small, but true, differences in outcomes and are areas for further study.

 

Risk Management Pitfalls for Emergency Department Management of First-Trimester Pregnant Patients

3. “The patient was 11 weeks’ pregnant and had pyelonephritis; she had a fever and was vomiting, but looked okay, so I sent her home with antibiotics.”

Until further data support initial outpatient management of pyelonephritis, it is best to admit all pregnant patients with pyelonephritis for an initial course of IV antibiotics.

5. “My patient was 10 weeks’ pregnant and had nausea, so I sent her home with 60 tablets of ondansetron.”

Although the risk of birth defects with maternal ondansetron exposure is low, there are safer alternatives for treatment of nausea and vomiting in pregnancy. Pyridoxine or pyridoxine with doxylamine should be considered first-line therapy.

9. “My patient was hypotensive and had a positive pregnancy test. I could not see an IUP, but she had free intraperitoneal fluid. I figured I would rule out other diagnoses with a CT scan, but she coded in the scanner!”

An unstable pregnant patient without an identified IUP with abdominal pain and/or vaginal bleeding has an ectopic pregnancy until proven otherwise. Unstable patients should proceed immediately to surgical management with an obstetrician.

 

Tables and Images

 

Table 2. Types of Miscarriage and Associated Physical Examination and Ultrasound Findings

 

 

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

  1. Janicki AJ, MacKuen C, Hauspurg A, et al. Obstetric training in emergency medicine: a needs assessment. Med Educ Online. 2016;21(1):28930. (Survey; 212 residents)
  2. Hasan R, Baird DD, Herring AH, et al. Association between first-trimester vaginal bleeding and miscarriage. Obstet Gynecol. 2009;114(4):860-867. (Cohort study; 4510 patients)
  3. McParlin C, O’Donnell A, Robson SC, et al. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review. JAMA. 2016;316(13):1392-1401. (Systematic review; 78 studies, 8930 participants)
  4. Ectopic pregnancy--United States, 1990-1992. MMWR Morb Mortal Wkly Rep. 1995;44(3):46-48. (CDC statistical report)
  5. Creanga AA, Syverson C, Seed K, et al. Pregnancy-related mortality in the United States, 2011-2013. Obstet Gynecol. 2017;130(2):366-373. (Observational study)
  6. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins-Obstetrics. Practice Bulletin no. 170: critical care in pregnancy. Obstet Gynecol. 2016;128(4):e147-e154. (ACOG Practice Bulletin)
  7. American College of Obstetricians and Gynecologists. Practice Bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014;123(3):676-692. (ACOG Practice Bulletin)
  8. American College of Obstetricians and Gynecologists Practice Bulletin no. 193; summary: tubal ectopic pregnancy. Obstet Gynecol. 2018;131(3):613-615. (ACOG Practice Bulletin)
  9. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin no. 189: nausea and vomiting of pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. (ACOG Practice Bulletin)
  10. Committee on Practice Bulletins-Obstetrics. Practice Bulletin no. 181: prevention of Rh D alloimmunization. Obstet Gynecol. 2017;130(2):e57-e70. (ACOG Practice Bulletin)
  11. Committee on Obstetric Practice. Committee opinion no. 717: sulfonamides, nitrofurantoin, and risk of birth defects. Obstet Gynecol. 2017;130(3):e150-e152. (ACOG Committee Opinion)
  12. Committee on Obstetric Practice. Committee Opinion no. 723: guidelines for diagnostic imaging during pregnancy and lactation. Obstet Gynecol. 2017;130(4):e210-e216. (ACOG Committee Opinion)
  13. American College of Radiology. ACR-SPR practice parameter for imaging pregnant or potentially pregnant adolescents and women with ionizing radiation. American College of Radiology. Available at: https://www.acr.org/-/media/ACR/Files/Practice-Parameters/Pregnant-Pts.pdf. Accessed December 10, 2018. (Committee Opinion)
  14. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40(5):643-654. (IDSA guideline)
  15. Matthews A, Haas DM, O’Mathuna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015(9):CD007575. (Cochrane review; 41 randomized controlled trials, 5449 pregnant women)
  16. Boelig RC, Barton SJ, Saccone G, et al. Interventions for treating hyperemesis gravidarum. Cochrane Database Syst Rev. 2016(5):CD010607. (Cochrane review; 25 trials, 2052 women)
  17. Guinto VT, De Guia B, Festin MR, et al. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2010(9):CD007855. (Cochrane review; 5 randomized controlled trials, 1140 women)
  18. Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev. 2011(1):CD002256. (Cochrane review; 10 trials, 1125 women)
  19. Nanda K, Lopez LM, Grimes DA, et al. Expectant care (waiting) versus surgical treatment for miscarriage. Cochrane Database Syst Rev. 2012(3):CD003518. (Cochrane review; 7 randomized controlled trials, 1521 women)
  20. Kim C, Barnard S, Neilson JP, et al. Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev. 2017;1:CD007223. (Cochrane review; 24 studies, 5577 women)
  21. Hahn SA, Lavonas EJ, Mace SE, et al. Clinical Policy: critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy. Ann Emerg Med. 2012;60(3):381-390. (ACEP Clinical Policy)
  22. American College of Emergency Physicians Clinical Policies Subcommittee on Early Pregnancy, Hahn SA, Promes SB, et al. Clinical Policy: critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy. Ann Emerg Med. 2017;69(2):241-250. (ACEP Clinical Policy)
  23. Committee on Practice Bulletins-Gynecology. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015;125(5):1258-1267. (ACOG Practice Bulletin)
  24. Hasan R, Baird DD, Herring AH, et al. Patterns and predictors of vaginal bleeding in the first trimester of pregnancy. Ann Epidemiol. 2010;20(7):524-531. (Retrospective study; 2539 patients)
  25. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod. 2002;17(2):446-451. (Analysis of fetal tissue from patients with recurrent miscarriage; 420 specimens)
  26. Saraswat L, Bhattacharya S, Maheshwari A, et al. Maternal and perinatal outcome in women with threatened miscarriage in the first trimester: a systematic review. BJOG. 2010;117(3):245-257. (Systematic review; 14 studies)
  27. Handler A, Davis F, Ferre C, et al. The relationship of smoking and ectopic pregnancy. Am J Public Health. 1989;79(9):1239-1242. (Case-control study; 634 patients with ectopic pregnancy)
  28. Backman T, Rauramo I, Huhtala S, et al. Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol. 2004;190(1):50-54. (Survey; 17,360 patients with an intrauterine device)
  29. Kohn MA, Kerr K, Malkevich D, et al. Beta-human chorionic gonadotropin levels and the likelihood of ectopic pregnancy in emergency department patients with abdominal pain or vaginal bleeding. Acad Emerg Med. 2003;10(2):119-126. (Retrospective review; 730 patients)
  30. Tal J, Haddad S, Gordon N, et al. Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993. Fertil Steril. 1996;66(1):1-12. (Literature review)
  31. Hinkle SN, Mumford SL, Grantz KL, et al. Association of nausea and vomiting during pregnancy with pregnancy loss: a secondary analysis of a randomized clinical trial. JAMA Intern Med. 2016;176(11):1621-1627. (Analysis of randomized controlled trial data; 797 patients)
  32. Heitmann K, Nordeng H, Havnen GC, et al. The burden of nausea and vomiting during pregnancy: severe impacts on quality of life, daily life functioning and willingness to become pregnant again - results from a cross-sectional study. BMC Pregnancy Childbirth. 2017;17(1):75. (Cross-sectional study; 712 patients)
  33. Kazemier BM, Koningstein FN, Schneeberger C, et al. Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial. Lancet Infect Dis. 2015;15(11):1324-1333. (Multicenter prospective cohort study; 248 patients with asymptomatic bacteriuria)
  34. Andersson RE, Lambe M. Incidence of appendicitis during pregnancy. Int J Epidemiol. 2001;30(6):1281-1285. (Case-control study; 53,058 women)
  35. Mourad J, Elliott JP, Erickson L, et al. Appendicitis in pregnancy: new information that contradicts long-held clinical beliefs. Am J Obstet Gynecol. 2000;182(5):1027-1029. (Retrospective consecutive chart review; 66,993 deliveries with 67 patients with appendicitis)
  36. Abbasi N, Patenaude V, Abenhaim HA. Management and outcomes of acute appendicitis in pregnancy-population-based study of over 7000 cases. BJOG. 2014;121(12):1509-1514. (Population-based matched cohort study; 7114 women with appendicitis)
  37. Hasson J, Tsafrir Z, Azem F, et al. Comparison of adnexal torsion between pregnant and nonpregnant women. Am J Obstet Gynecol. 2010;202(6):531-536. (Retrospective case-control study; 118 patients with torsion)
  38. Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med. 1999;33(3):283-290. (Prospective observational study; 441 patients)
  39. Linden JA, Grimmnitz B, Hagopian L, et al. Is the pelvic examination still crucial in patients presenting to the emergency department with vaginal bleeding or abdominal pain when an intrauterine pregnancy is identified on ultrasonography? A randomized controlled trial. Ann Emerg Med. 2017;70(6):825-834. (Prospective randomized trial; 202 patients)
  40. Ikomi A, Matthews M, Kuan AM, et al. The effect of physiological urine dilution on pregnancy test results in complicated early pregnancies. Br J Obstet Gynaecol. 1998;105(4):462-465. (Prospective study; 40 patients)
  41. Connolly A, Ryan DH, Stuebe AM, et al. Reevaluation of discriminatory and threshold levels for serum beta-hCG in early pregnancy. Obstet Gynecol. 2013;121(1):65-70. (Retrospective review; 651 patients)
  42. Barnhart KT, Sammel MD, Rinaudo PF, et al. Symptomatic patients with an early viable intrauterine pregnancy: hCG curves redefined. Obstet Gynecol. 2004;104(1):50-55. (Observational study; 287 patients)
  43. Silva C, Sammel MD, Zhou L, et al. Human chorionic gonadotropin profile for women with ectopic pregnancy. Obstet Gynecol. 2006;107(3):605-610. (Retrospective review; 200 patients)
  44. Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis. Ann Emerg Med. 2010;56(6):674-683. (Meta-analysis; 2057 patients in 10 studies)
  45. Angelescu K, Nussbaumer-Streit B, Sieben W, et al. Benefits and harms of screening for and treatment of asymptomatic bacteriuria in pregnancy: a systematic review. BMC Pregnancy Childbirth. 2016;16(1):336. (Systematic review; 4 randomized controlled trials, 454 patients)
  46. Konrad J, Grand D, Lourenco A. MRI: first-line imaging modality for pregnant patients with suspected appendicitis. Abdom Imaging. 2015;40(8):3359-3364. (Retrospective study; 140 patients)
  47. Duke E, Kalb B, Arif-Tiwari H, et al. A systematic review and meta-analysis of diagnostic performance of MRI for evaluation of acute appendicitis. AJR Am J Roentgenol. 2016;206(3):508-517. (Meta-analysis)
  48. Ray JG, Vermeulen MJ, Bharatha A, et al. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA. 2016;316(9):952-961. (Retrospective cohort study; over 1.4 million patients)
  49. Abbasi N, Patenaude V, Abenhaim HA. Evaluation of obstetrical and fetal outcomes in pregnancies complicated by acute appendicitis. Arch Gynecol Obstet. 2014;290(4):661-667. (Population-based cohort study; 1203 pregnant women with appendicitis)
  50. Hannafin B, Lovecchio F, Blackburn P. Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin? Am J Emerg Med. 2006;24(4):487-489. (Literature review)
  51. Bique C, Usta M, Debora B, et al. Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion. Int J Gynaecol Obstet. 2007;98(3):222-226. (Randomized trial; 270 patients)
  52. Weeks A, Alia G, Blum J, et al. A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion. Obstet Gynecol. 2005;106(3):540-547. (Randomized trial; 317 patients)
  53. Trinder J, Brocklehurst P, Porter R, et al. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial. BMJ. 2006;332(7552):1235-1240. (Randomized trial; 1200 patients)
  54. Baird S, Gagnon MD, deFiebre G, et al. Women’s experiences with early pregnancy loss in the emergency room: a qualitative study. Sex Reprod Healthc. 2018;16:113-117. (Qualitative study with telephone survey; 10 patients)
  55. Catlin A. Interdisciplinary guidelines for care of women presenting to the emergency department with pregnancy loss. MCN Am J Matern Child Nurs. 2018;43(1):13-18. (Practice guidelines)
  56. Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril. 2007;87(3):481-484. (Systematic review; 5 observational studies, 503 women)
  57. Barnhart KT, Gosman G, Ashby R, et al. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol. 2003;101(4):778-784. (Meta-analysis of studies 1966-2001; 1327 women)
  58. Adlan AS, Chooi KY, Mat Adenan NA. Acupressure as adjuvant treatment for the inpatient management of nausea and vomiting in early pregnancy: a double-blind randomized controlled trial. J Obstet Gynaecol Res. 2017;43(4):662-668. (Double-blind randomized controlled trial; 120 patients)
  59. Sharifzadeh F, Kashanian M, Koohpayehzadeh J, et al. A comparison between the effects of ginger, pyridoxine (vitamin B6) and placebo for the treatment of the first trimester nausea and vomiting of pregnancy (NVP). J Matern Fetal Neonatal Med. 2017:1-6. (Randomized controlled trial; 77 patients)
  60. Pope E, Maltepe C, Koren G. Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: a matched, controlled cohort study. J Clin Pharmacol. 2015;55(7):809-814. (Comparative study; 160 patients)
  61. Koren G, Clark S, Hankins GD, et al. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy Childbirth. 2016;16(1):371. (Randomized trial; 256 patients)
  62. Carstairs SD. Ondansetron use in pregnancy and birth defects: a systematic review. Obstet Gynecol. 2016;127(5):878-883. (Systematic review; 8 records reviewed)
  63. Tan PC, Norazilah MJ, Omar SZ. Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2013;121(2 Pt 1):291-298. (Randomized trial; 202 patients)
  64. Glaser AP, Schaeffer AJ. Urinary tract infection and bacteriuria in pregnancy. Urol Clin North Am. 2015;42(4):547-560. (Review)
  65. Widmer M, Lopez I, Gulmezoglu AM, et al. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev. 2015(11):CD000491. (Cochrane review; 13 studies, 1622 women)
  66. Millar LK, Wing DA, Paul RH, et al. Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial. Obstet Gynecol. 1995;86(4 Pt 1):560-564. (Randomized controlled trial; 120 patients)
  67. Pernia S, DeMaagd G. The new pregnancy and lactation labeling rule. P T. 2016;41(11):713-715. (FDA rule change description)
  68. Joo JI, Park HC, Kim MJ, et al. Outcomes of antibiotic therapy for uncomplicated appendicitis in pregnancy. Am J Med. 2017. (Prospective observational study; 20 patients)
  69. Hurwitz LM, Yoshizumi T, Reiman RE, et al. Radiation dose to the fetus from body MDCT during early gestation. AJR Am J Roentgenol. 2006;186(3):871-876. (Pregnant manikin radiation study)
  70. McCollough CH, Schueler BA, Atwell TD, et al. Radiation exposure and pregnancy: when should we be concerned? Radiographics. 2007;27(4):909-917. (Review)
  71. Fromm C, Likourezos A, Haines L, et al. Substituting whole blood for urine in a bedside pregnancy test. J Emerg Med. 2012;43(3):478-482. (Prospective blinded study; 633 patients)
  72. Gottlieb M, Wnek K, Moskoff J, et al. Comparison of result times between urine and whole blood point-of-care pregnancy testing. West J Emerg Med. 2016;17(4):449-453. (Prospective observational study; 265 patients)
  73. Silva PM, Araujo Junior E, Cecchino GN, et al. Effectiveness of expectant management versus methotrexate in tubal ectopic pregnancy: a double-blind randomized trial. Arch Gynecol Obstet. 2015;291(4):939-943. (Randomized trial; 23 patients)
  74. Jurkovic D, Memtsa M, Sawyer E, et al. Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial. Ultrasound Obstet Gynecol. 2017;49(2):171-176. (Multicenter randomized trial; 80 patients)
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Last Modified: 01/16/2019
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