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Do allergy shots help seasonal allergies more than antihistamines and nasal steroids?
Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis (strength of recommendation [SOR]: A). No RCTs directly compare immunotherapy with conservative management. Treatment decisions are driven by the clinical presentation, patient and physician preferences, practice guidelines, and expert opinion1 (SOR: C, based on expert opinion). In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis.
Usually there’s an acceptable treatment alternative with better symptom control or fewer side effects
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
When patients ask me about allergy shots, I ask them to tell me about their concerns about their allergies and experiences with previous treatments. Often I find that they do not really want shots, but just want to feel better! Usually you can find an acceptable treatment alternative, one with better symptom control or fewer side effects.
When patients are referred for immunotherapy, it’s important for them to have realistic expectations. The initial process involves weekly visits, and it may take years to gain adequate symptom control. For patients with the commitment, time, and insurance coverage, however, the outcomes can be very positive.
Evidence summary
A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.2 Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.3 The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.6
For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.2,7
The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.8 In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.9 Studies indicate that immunotherapy is effective for several years after treatment is discontinued.10
A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.11 However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.12
Recommendations from others
The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.10
1. Rachelefsky GS. National guidelines needed to manage rhinitis and prevent complications. Ann Allergy Asthma Immunol 1999;82:296-305.
2. Long A, et al. Management of allergic and nonallergic rhinitis. Evid Rep Technol Assess (Summ) 2002;54:1-6.
3. Juniper EF, et al. Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 1990;85:606-611.
4. Rak S, et al. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol 2001;108:921-928.
5. Rak S, Heinrich C, Scheynius A. Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy. Allergy 2005;60:643-649.
6. Giovannini M, et al. Comparison of allergen immunotherapy and drug treatment in seasonal rhinoconjunctivitis: a 3-years study. Allerg Immunol (Paris) 2005;37:69-71.
7. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-1629.
8. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-562.
9. Naclerio R, Solomon W. Rhinitis and inhalant allergens. JAMA 1997;278:1842-1848.
10. American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter. Ann Allergy Asthma Immunol 2003;90(1 Suppl 1):1-40.
11. Dinakar C, Portnoy JM. Allergen immunotherapy in the prevention of asthma. Curr Opin Allergy Clin Immunol 2004;4:131-136.
12. Matloff SM, et al. Systemic reactions to immunotherapy. Allergy Proc 1993;14:347-350.
Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis (strength of recommendation [SOR]: A). No RCTs directly compare immunotherapy with conservative management. Treatment decisions are driven by the clinical presentation, patient and physician preferences, practice guidelines, and expert opinion1 (SOR: C, based on expert opinion). In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis.
Usually there’s an acceptable treatment alternative with better symptom control or fewer side effects
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
When patients ask me about allergy shots, I ask them to tell me about their concerns about their allergies and experiences with previous treatments. Often I find that they do not really want shots, but just want to feel better! Usually you can find an acceptable treatment alternative, one with better symptom control or fewer side effects.
When patients are referred for immunotherapy, it’s important for them to have realistic expectations. The initial process involves weekly visits, and it may take years to gain adequate symptom control. For patients with the commitment, time, and insurance coverage, however, the outcomes can be very positive.
Evidence summary
A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.2 Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.3 The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.6
For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.2,7
The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.8 In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.9 Studies indicate that immunotherapy is effective for several years after treatment is discontinued.10
A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.11 However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.12
Recommendations from others
The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.10
Multiple randomized controlled trials (RCTs) demonstrate the effectiveness of both allergen immunotherapy and antihistamines, with or without nasal steroids, in the treatment of seasonal allergic rhinitis (strength of recommendation [SOR]: A). No RCTs directly compare immunotherapy with conservative management. Treatment decisions are driven by the clinical presentation, patient and physician preferences, practice guidelines, and expert opinion1 (SOR: C, based on expert opinion). In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis.
Usually there’s an acceptable treatment alternative with better symptom control or fewer side effects
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
When patients ask me about allergy shots, I ask them to tell me about their concerns about their allergies and experiences with previous treatments. Often I find that they do not really want shots, but just want to feel better! Usually you can find an acceptable treatment alternative, one with better symptom control or fewer side effects.
When patients are referred for immunotherapy, it’s important for them to have realistic expectations. The initial process involves weekly visits, and it may take years to gain adequate symptom control. For patients with the commitment, time, and insurance coverage, however, the outcomes can be very positive.
Evidence summary
A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.2 Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.3 The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.6
For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.2,7
The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.8 In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.9 Studies indicate that immunotherapy is effective for several years after treatment is discontinued.10
A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.11 However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.12
Recommendations from others
The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.10
1. Rachelefsky GS. National guidelines needed to manage rhinitis and prevent complications. Ann Allergy Asthma Immunol 1999;82:296-305.
2. Long A, et al. Management of allergic and nonallergic rhinitis. Evid Rep Technol Assess (Summ) 2002;54:1-6.
3. Juniper EF, et al. Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 1990;85:606-611.
4. Rak S, et al. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol 2001;108:921-928.
5. Rak S, Heinrich C, Scheynius A. Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy. Allergy 2005;60:643-649.
6. Giovannini M, et al. Comparison of allergen immunotherapy and drug treatment in seasonal rhinoconjunctivitis: a 3-years study. Allerg Immunol (Paris) 2005;37:69-71.
7. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-1629.
8. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-562.
9. Naclerio R, Solomon W. Rhinitis and inhalant allergens. JAMA 1997;278:1842-1848.
10. American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter. Ann Allergy Asthma Immunol 2003;90(1 Suppl 1):1-40.
11. Dinakar C, Portnoy JM. Allergen immunotherapy in the prevention of asthma. Curr Opin Allergy Clin Immunol 2004;4:131-136.
12. Matloff SM, et al. Systemic reactions to immunotherapy. Allergy Proc 1993;14:347-350.
1. Rachelefsky GS. National guidelines needed to manage rhinitis and prevent complications. Ann Allergy Asthma Immunol 1999;82:296-305.
2. Long A, et al. Management of allergic and nonallergic rhinitis. Evid Rep Technol Assess (Summ) 2002;54:1-6.
3. Juniper EF, et al. Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 1990;85:606-611.
4. Rak S, et al. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol 2001;108:921-928.
5. Rak S, Heinrich C, Scheynius A. Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy. Allergy 2005;60:643-649.
6. Giovannini M, et al. Comparison of allergen immunotherapy and drug treatment in seasonal rhinoconjunctivitis: a 3-years study. Allerg Immunol (Paris) 2005;37:69-71.
7. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-1629.
8. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-562.
9. Naclerio R, Solomon W. Rhinitis and inhalant allergens. JAMA 1997;278:1842-1848.
10. American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter. Ann Allergy Asthma Immunol 2003;90(1 Suppl 1):1-40.
11. Dinakar C, Portnoy JM. Allergen immunotherapy in the prevention of asthma. Curr Opin Allergy Clin Immunol 2004;4:131-136.
12. Matloff SM, et al. Systemic reactions to immunotherapy. Allergy Proc 1993;14:347-350.
Evidence-based answers from the Family Physicians Inquiries Network
What are the risks to the fetus associated with diagnostic radiation exposure during pregnancy?
There is no evidence of significant risk to the developing fetus from any single diagnostic x-ray exposure (strength of recommendation: C, based on non-homogenous case-control studies). No studies were found on fetal exposure risks from other forms of diagnostic radiation such as computed tomography (CT) scans, fluoroscopy, or mammography. Prudent clinicians should order only those studies that result in clinically important information and efforts should be made to minimize fetal exposure.
Communication with the patient can go a long way to alleviate concerns regarding effects of radiation
Timothy Huber, MD
Oroville, Calif
The lack of high-quality research coupled with a general societal fear of radiation during pregnancy can create tension between the physician and the patient who needs diagnostic studies during pregnancy. This review reassures the conscientious practitioner that there is little to fear from the prudent use of routine studies. There is less clarity when a woman needs multiple or higher-dose radiation studies, especially in the first trimester.
Patients need our best estimates regarding the medical necessity, diagnostic benefit, and overall risk in these situations. Open communication with the patient can go a long way to alleviate concerns regarding the possible teratogenic or carcinogenic effects of radiation. Working more closely with our radiology colleagues to determine the best set of studies for a particular situation can help reduce the overall total radiation exposure. I refer patients who are Internet-savvy to www.familydoctor.org for more information about diagnostic radiation exposure in pregnancy.
Evidence summary
Clinicians have been concerned about x-ray exposure during pregnancy since the 1950s. Much of this concern was based on the Oxford Survey of Childhood Leukemia, as well as other early case-control studies.1-3 These studies reported an approximate 40% increase in the risk of childhood leukemia among offspring of women who received diagnostic x-rays in pregnancy. However, by modern standards, these studies are of poor quality as they are limited by reliance on maternal recall of prenatal x-ray exposure, lack of consideration for multiple confounding factors, lack of blinding in determination of exposure and outcome status, limitations in selection of both cases and controls, and other significant methodological flaws.
Modern, well-designed studies have failed to replicate the association between in utero radiation and childhood malignancies found in the early studies. We found 1 good-quality and 5 fair-quality case-control studies examining the association between in utero x-ray exposure and childhood leukemia, as well as 6 fair-quality case-control studies examining the association with other childhood malignancies. These studies found no significant association between in utero exposure to any x-ray in general, or to abdominal or pelvic x-rays and development of subsequent childhood leukemia, central nervous system tumors or other malignancies (TABLE).
No meta-analyses, randomized controlled trials, cohort studies or good- or fair-quality case-control studies were found examining in utero x-rays and decreased head circumference, congenital malformations, spontaneous abortion, low birth weight, or developmental problems. One recent, fair-quality case-control study found an association between prenatal dental x-rays and low birth weight (odds ratio [OR]=1.8 [95% confidence interval, 1.09–1.36]) for radiation exposures above 0.4 Gy.4 However, this study has been criticized for several reasons, including lack of biological plausibility and failure to control for dental disease.5
There does not appear to be an increased risk of adverse pregnancy outcomes with prenatal endoscopic retrograde cholangiopancreaticogram (ERCP), though this conclusion is based on 2 incomplete case series reports with no follow-up of the infants after delivery.6,7 No good- or fair-quality studies were found examining the association between other diagnostic radiation exposures (CT scan, mammography, positron emission tomography scan, dual-energy x-ray absorptiometry [DEXA]) with adverse pregnancy outcomes.
TABLE
Risk of childhood malignancy after in utero diagnostic X-ray studies1
| OUTCOME | TYPE OF STUDY | ODDS RATIO [95% CI] |
|---|---|---|
| Leukemia9-14 | Any x-ray | 0.8–1.8 [0.5–3.6] |
| Pelvic x-ray | 0.7–3.4 [0.4–12.9] | |
| CNS tumor12,15 | Any x-ray | 0.78 [0.44–1.36] |
| Abdominal x-ray | 1.5 [0.5–4.2] | |
| Any cancer12,13,16,17 | Any x-ray | 0.92–1.2 [0.47–2.4] |
| Abdominal x-ray | 1.4 [0.8–2.5] |
Recommendations from others
The American College of Obstetricians and Gynecologists recommends that women be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Concern about possible effects of ionizing radiation exposure should not prevent medically indicated diagnostic x-ray procedures from being performed on a pregnant woman.8
1. Fattibene P, Mazzei F, Nuccetelli C, Risica S. Prenatal exposure to ionizing radiation: sources, effects and regulatory aspects. Acta Paediatr 1999;88:693-702.
2. Bross ID, Natarajan N. Risk of leukemia in susceptible children exposed to preconception, in utero and postnatal radiation. Prev Med 1974;3:361-369.
3. Stewart A, Webb J, Hewitt D. A survey of childhood malignancies. BMJ 1958;1:1495-1508.
4. Hujoel PP, Bollen AM, Noonan CJ, del Aguila MA. Antepartum dental radiography and infant low birth weight. JAMA 2004;291:1987-1993.
5. Brent RL. Commentary on JAMA article by Hujoel et al. Health Phys 2005;88:379-381.
6. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc 2004;60:287-292.
7. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy [see comment]. Am J Gastroenterol 2003;98:308-311.
8. ACOG Bulletins. ACOG Committee Opinion No. 299: Guidelines for diagnostic imaging during pregnancy. Obstet Gynecol 2004;104:647-651.
9. Roman E, Ansell G, Bull D. Leukaemia and non-Hodgkin’s lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease? Br J Cancer 1997;76:406-415.
10. Shu XO, Potter JD, Linet MS, et al. Diagnostic X-rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia by immunophenotype. Cancer Epidemiol Biomarkers Prev 2002;11:177-185.
11. McKinney PA, Cartwright RA, Saiu JM, et al. The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma. Arch Dis Child 1987;62:279-287.
12. Rodvall Y, Pershagen G, Hrubec Z, Ahlbom A, Pedersen NL, Boice JD. Prenatal X-ray exposure and childhood cancer in Swedish twins. Int J Cancer 1990;46:362-365.
13. Shu XO, Jin F, Linet MS, et al. Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Br J Cancer 1994;70:531-536.
14. Naumburg E, Bellocco R, Cnattingius S, Hall P, Boice JD, Ekbom A. Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes. Radiat Res 2001;156:718-723.
15. Schuz J, Kaletsch U, Kaatsch P, Meinert R, Michaelis J. Risk factors for pediatric tumors of the central nervous system: results from a German population-based case-control study. Med Pediatr Oncol 2001;36:274-282.
16. Shiono PH, Chung CS, Myrianthopoulos NC. Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia. J Natl Cancer Inst 1980;65:681-686.
17. Meinert R, Kaletsch U, Kaatsch P, Schuz J, Michaelis J. Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany. Cancer Epidemiol Biomarkers Prev 1999;8:793-799.
There is no evidence of significant risk to the developing fetus from any single diagnostic x-ray exposure (strength of recommendation: C, based on non-homogenous case-control studies). No studies were found on fetal exposure risks from other forms of diagnostic radiation such as computed tomography (CT) scans, fluoroscopy, or mammography. Prudent clinicians should order only those studies that result in clinically important information and efforts should be made to minimize fetal exposure.
Communication with the patient can go a long way to alleviate concerns regarding effects of radiation
Timothy Huber, MD
Oroville, Calif
The lack of high-quality research coupled with a general societal fear of radiation during pregnancy can create tension between the physician and the patient who needs diagnostic studies during pregnancy. This review reassures the conscientious practitioner that there is little to fear from the prudent use of routine studies. There is less clarity when a woman needs multiple or higher-dose radiation studies, especially in the first trimester.
Patients need our best estimates regarding the medical necessity, diagnostic benefit, and overall risk in these situations. Open communication with the patient can go a long way to alleviate concerns regarding the possible teratogenic or carcinogenic effects of radiation. Working more closely with our radiology colleagues to determine the best set of studies for a particular situation can help reduce the overall total radiation exposure. I refer patients who are Internet-savvy to www.familydoctor.org for more information about diagnostic radiation exposure in pregnancy.
Evidence summary
Clinicians have been concerned about x-ray exposure during pregnancy since the 1950s. Much of this concern was based on the Oxford Survey of Childhood Leukemia, as well as other early case-control studies.1-3 These studies reported an approximate 40% increase in the risk of childhood leukemia among offspring of women who received diagnostic x-rays in pregnancy. However, by modern standards, these studies are of poor quality as they are limited by reliance on maternal recall of prenatal x-ray exposure, lack of consideration for multiple confounding factors, lack of blinding in determination of exposure and outcome status, limitations in selection of both cases and controls, and other significant methodological flaws.
Modern, well-designed studies have failed to replicate the association between in utero radiation and childhood malignancies found in the early studies. We found 1 good-quality and 5 fair-quality case-control studies examining the association between in utero x-ray exposure and childhood leukemia, as well as 6 fair-quality case-control studies examining the association with other childhood malignancies. These studies found no significant association between in utero exposure to any x-ray in general, or to abdominal or pelvic x-rays and development of subsequent childhood leukemia, central nervous system tumors or other malignancies (TABLE).
No meta-analyses, randomized controlled trials, cohort studies or good- or fair-quality case-control studies were found examining in utero x-rays and decreased head circumference, congenital malformations, spontaneous abortion, low birth weight, or developmental problems. One recent, fair-quality case-control study found an association between prenatal dental x-rays and low birth weight (odds ratio [OR]=1.8 [95% confidence interval, 1.09–1.36]) for radiation exposures above 0.4 Gy.4 However, this study has been criticized for several reasons, including lack of biological plausibility and failure to control for dental disease.5
There does not appear to be an increased risk of adverse pregnancy outcomes with prenatal endoscopic retrograde cholangiopancreaticogram (ERCP), though this conclusion is based on 2 incomplete case series reports with no follow-up of the infants after delivery.6,7 No good- or fair-quality studies were found examining the association between other diagnostic radiation exposures (CT scan, mammography, positron emission tomography scan, dual-energy x-ray absorptiometry [DEXA]) with adverse pregnancy outcomes.
TABLE
Risk of childhood malignancy after in utero diagnostic X-ray studies1
| OUTCOME | TYPE OF STUDY | ODDS RATIO [95% CI] |
|---|---|---|
| Leukemia9-14 | Any x-ray | 0.8–1.8 [0.5–3.6] |
| Pelvic x-ray | 0.7–3.4 [0.4–12.9] | |
| CNS tumor12,15 | Any x-ray | 0.78 [0.44–1.36] |
| Abdominal x-ray | 1.5 [0.5–4.2] | |
| Any cancer12,13,16,17 | Any x-ray | 0.92–1.2 [0.47–2.4] |
| Abdominal x-ray | 1.4 [0.8–2.5] |
Recommendations from others
The American College of Obstetricians and Gynecologists recommends that women be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Concern about possible effects of ionizing radiation exposure should not prevent medically indicated diagnostic x-ray procedures from being performed on a pregnant woman.8
There is no evidence of significant risk to the developing fetus from any single diagnostic x-ray exposure (strength of recommendation: C, based on non-homogenous case-control studies). No studies were found on fetal exposure risks from other forms of diagnostic radiation such as computed tomography (CT) scans, fluoroscopy, or mammography. Prudent clinicians should order only those studies that result in clinically important information and efforts should be made to minimize fetal exposure.
Communication with the patient can go a long way to alleviate concerns regarding effects of radiation
Timothy Huber, MD
Oroville, Calif
The lack of high-quality research coupled with a general societal fear of radiation during pregnancy can create tension between the physician and the patient who needs diagnostic studies during pregnancy. This review reassures the conscientious practitioner that there is little to fear from the prudent use of routine studies. There is less clarity when a woman needs multiple or higher-dose radiation studies, especially in the first trimester.
Patients need our best estimates regarding the medical necessity, diagnostic benefit, and overall risk in these situations. Open communication with the patient can go a long way to alleviate concerns regarding the possible teratogenic or carcinogenic effects of radiation. Working more closely with our radiology colleagues to determine the best set of studies for a particular situation can help reduce the overall total radiation exposure. I refer patients who are Internet-savvy to www.familydoctor.org for more information about diagnostic radiation exposure in pregnancy.
Evidence summary
Clinicians have been concerned about x-ray exposure during pregnancy since the 1950s. Much of this concern was based on the Oxford Survey of Childhood Leukemia, as well as other early case-control studies.1-3 These studies reported an approximate 40% increase in the risk of childhood leukemia among offspring of women who received diagnostic x-rays in pregnancy. However, by modern standards, these studies are of poor quality as they are limited by reliance on maternal recall of prenatal x-ray exposure, lack of consideration for multiple confounding factors, lack of blinding in determination of exposure and outcome status, limitations in selection of both cases and controls, and other significant methodological flaws.
Modern, well-designed studies have failed to replicate the association between in utero radiation and childhood malignancies found in the early studies. We found 1 good-quality and 5 fair-quality case-control studies examining the association between in utero x-ray exposure and childhood leukemia, as well as 6 fair-quality case-control studies examining the association with other childhood malignancies. These studies found no significant association between in utero exposure to any x-ray in general, or to abdominal or pelvic x-rays and development of subsequent childhood leukemia, central nervous system tumors or other malignancies (TABLE).
No meta-analyses, randomized controlled trials, cohort studies or good- or fair-quality case-control studies were found examining in utero x-rays and decreased head circumference, congenital malformations, spontaneous abortion, low birth weight, or developmental problems. One recent, fair-quality case-control study found an association between prenatal dental x-rays and low birth weight (odds ratio [OR]=1.8 [95% confidence interval, 1.09–1.36]) for radiation exposures above 0.4 Gy.4 However, this study has been criticized for several reasons, including lack of biological plausibility and failure to control for dental disease.5
There does not appear to be an increased risk of adverse pregnancy outcomes with prenatal endoscopic retrograde cholangiopancreaticogram (ERCP), though this conclusion is based on 2 incomplete case series reports with no follow-up of the infants after delivery.6,7 No good- or fair-quality studies were found examining the association between other diagnostic radiation exposures (CT scan, mammography, positron emission tomography scan, dual-energy x-ray absorptiometry [DEXA]) with adverse pregnancy outcomes.
TABLE
Risk of childhood malignancy after in utero diagnostic X-ray studies1
| OUTCOME | TYPE OF STUDY | ODDS RATIO [95% CI] |
|---|---|---|
| Leukemia9-14 | Any x-ray | 0.8–1.8 [0.5–3.6] |
| Pelvic x-ray | 0.7–3.4 [0.4–12.9] | |
| CNS tumor12,15 | Any x-ray | 0.78 [0.44–1.36] |
| Abdominal x-ray | 1.5 [0.5–4.2] | |
| Any cancer12,13,16,17 | Any x-ray | 0.92–1.2 [0.47–2.4] |
| Abdominal x-ray | 1.4 [0.8–2.5] |
Recommendations from others
The American College of Obstetricians and Gynecologists recommends that women be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Concern about possible effects of ionizing radiation exposure should not prevent medically indicated diagnostic x-ray procedures from being performed on a pregnant woman.8
1. Fattibene P, Mazzei F, Nuccetelli C, Risica S. Prenatal exposure to ionizing radiation: sources, effects and regulatory aspects. Acta Paediatr 1999;88:693-702.
2. Bross ID, Natarajan N. Risk of leukemia in susceptible children exposed to preconception, in utero and postnatal radiation. Prev Med 1974;3:361-369.
3. Stewart A, Webb J, Hewitt D. A survey of childhood malignancies. BMJ 1958;1:1495-1508.
4. Hujoel PP, Bollen AM, Noonan CJ, del Aguila MA. Antepartum dental radiography and infant low birth weight. JAMA 2004;291:1987-1993.
5. Brent RL. Commentary on JAMA article by Hujoel et al. Health Phys 2005;88:379-381.
6. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc 2004;60:287-292.
7. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy [see comment]. Am J Gastroenterol 2003;98:308-311.
8. ACOG Bulletins. ACOG Committee Opinion No. 299: Guidelines for diagnostic imaging during pregnancy. Obstet Gynecol 2004;104:647-651.
9. Roman E, Ansell G, Bull D. Leukaemia and non-Hodgkin’s lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease? Br J Cancer 1997;76:406-415.
10. Shu XO, Potter JD, Linet MS, et al. Diagnostic X-rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia by immunophenotype. Cancer Epidemiol Biomarkers Prev 2002;11:177-185.
11. McKinney PA, Cartwright RA, Saiu JM, et al. The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma. Arch Dis Child 1987;62:279-287.
12. Rodvall Y, Pershagen G, Hrubec Z, Ahlbom A, Pedersen NL, Boice JD. Prenatal X-ray exposure and childhood cancer in Swedish twins. Int J Cancer 1990;46:362-365.
13. Shu XO, Jin F, Linet MS, et al. Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Br J Cancer 1994;70:531-536.
14. Naumburg E, Bellocco R, Cnattingius S, Hall P, Boice JD, Ekbom A. Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes. Radiat Res 2001;156:718-723.
15. Schuz J, Kaletsch U, Kaatsch P, Meinert R, Michaelis J. Risk factors for pediatric tumors of the central nervous system: results from a German population-based case-control study. Med Pediatr Oncol 2001;36:274-282.
16. Shiono PH, Chung CS, Myrianthopoulos NC. Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia. J Natl Cancer Inst 1980;65:681-686.
17. Meinert R, Kaletsch U, Kaatsch P, Schuz J, Michaelis J. Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany. Cancer Epidemiol Biomarkers Prev 1999;8:793-799.
1. Fattibene P, Mazzei F, Nuccetelli C, Risica S. Prenatal exposure to ionizing radiation: sources, effects and regulatory aspects. Acta Paediatr 1999;88:693-702.
2. Bross ID, Natarajan N. Risk of leukemia in susceptible children exposed to preconception, in utero and postnatal radiation. Prev Med 1974;3:361-369.
3. Stewart A, Webb J, Hewitt D. A survey of childhood malignancies. BMJ 1958;1:1495-1508.
4. Hujoel PP, Bollen AM, Noonan CJ, del Aguila MA. Antepartum dental radiography and infant low birth weight. JAMA 2004;291:1987-1993.
5. Brent RL. Commentary on JAMA article by Hujoel et al. Health Phys 2005;88:379-381.
6. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc 2004;60:287-292.
7. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy [see comment]. Am J Gastroenterol 2003;98:308-311.
8. ACOG Bulletins. ACOG Committee Opinion No. 299: Guidelines for diagnostic imaging during pregnancy. Obstet Gynecol 2004;104:647-651.
9. Roman E, Ansell G, Bull D. Leukaemia and non-Hodgkin’s lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease? Br J Cancer 1997;76:406-415.
10. Shu XO, Potter JD, Linet MS, et al. Diagnostic X-rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia by immunophenotype. Cancer Epidemiol Biomarkers Prev 2002;11:177-185.
11. McKinney PA, Cartwright RA, Saiu JM, et al. The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma. Arch Dis Child 1987;62:279-287.
12. Rodvall Y, Pershagen G, Hrubec Z, Ahlbom A, Pedersen NL, Boice JD. Prenatal X-ray exposure and childhood cancer in Swedish twins. Int J Cancer 1990;46:362-365.
13. Shu XO, Jin F, Linet MS, et al. Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Br J Cancer 1994;70:531-536.
14. Naumburg E, Bellocco R, Cnattingius S, Hall P, Boice JD, Ekbom A. Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes. Radiat Res 2001;156:718-723.
15. Schuz J, Kaletsch U, Kaatsch P, Meinert R, Michaelis J. Risk factors for pediatric tumors of the central nervous system: results from a German population-based case-control study. Med Pediatr Oncol 2001;36:274-282.
16. Shiono PH, Chung CS, Myrianthopoulos NC. Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia. J Natl Cancer Inst 1980;65:681-686.
17. Meinert R, Kaletsch U, Kaatsch P, Schuz J, Michaelis J. Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany. Cancer Epidemiol Biomarkers Prev 1999;8:793-799.
Evidence-based answers from the Family Physicians Inquiries Network