Perioperative Medicine  |   March 2011
Latex Sensitization: A Special Risk for the Obstetric Population?
Author Affiliations & Notes
  • Gaetano Draisci, M.D.
  • Bruno A. Zanfini, M.D.
  • Eleonora Nucera, M.D.
  • Stefano Catarci, M.D.
  • Raffaella Sangregorio, M.D.
  • Domenico Schiavino, M.D.
  • Alice Mannocci, M.S., Ph.D.
  • Giampiero Patriarca, M.D.
  • * Staff Anesthesiologist, Department of Anesthesiology and Intensive Care, † Staff Allergologist, Department of Allergology, ‡ Resident in Anesthesiology, Department of Anesthesiology and Intensive Care, Catholic University of Sacred Heart, Rome, Italy; § Staff Biostatistic, Unit of Hygiene, Department of Public Health and Infectious Diseases, Sapienza University of Roma, Rome, Italy.
Article Information
Perioperative Medicine / Obstetric Anesthesia
Perioperative Medicine   |   March 2011
Latex Sensitization: A Special Risk for the Obstetric Population?
Anesthesiology 3 2011, Vol.114, 565-569. doi:10.1097/ALN.0b013e318206ff50
Anesthesiology 3 2011, Vol.114, 565-569. doi:10.1097/ALN.0b013e318206ff50
What We Already Know about This Topic
  • Latex sensitization is more common in women, but whether there is a special risk during pregnancy is not known

What This Article Tells Us That Is New
  • In nearly 600 women undergoing cesarean delivery or gynecologic surgery, the prevalence of latex sensitization was three times greater in the pregnant women (5.4% versus  1.7%)

ANAPHYLAXIS is a severe and potentially fatal systemic allergic reaction that occurs suddenly and is triggered by the binding of allergen to specific immunoglobulin E. It implies previous exposure and sensitization to the triggering substance or a cross-reactive allergen.1 
In the general population, the incidence of anaphylaxis during general anesthesia has been estimated to be 1:10,000–1:20,000.2,3 Muscle relaxants are the anesthetic agents most frequently associated with intraoperative anaphylactic reactions (60–70%),4 followed by natural rubber latex and antibiotics.5 
The incidence of latex sensitization is approximately 1:100 in the general population. Patients with spina bifida and urogenital abnormalities, those undergoing multiple surgical procedures, healthcare workers, and subjects with allergy to fruits carry a higher risk of this event.6–9 Moreover, latex sensitization is more common in women; therefore, latex anaphylaxis could occur frequently during obstetric and gynecologic surgery.10 
We previously reported a higher incidence (1:310) of anaphylactic reactions to latex in the obstetric population than that observed in other reports.11 Such events may be life threatening for both the woman and the fetus because an instability in maternal hemodynamic can impair placental perfusion. Therefore, anaphylactic reactions represent a serious concern for obstetricians, anesthesiologists, and neonatologists.
This study evaluates the prevalence of latex sensitization in the obstetric population in comparison with nulliparous patients undergoing gynecologic surgery.
Materials and Methods
Study Setting and Design
Between July 2003 and September 2008, 588 consecutive patients were enrolled in this study, which was conducted at the Department of Anesthesiology and Intensive Care, Catholic University of Sacred Heart, Rome, Italy. Patients were assigned to one of the following groups. Group A had 294 American Society of Anesthesiologists physical status classification system I patients with singleton term pregnancy scheduled for elective cesarean section under spinal anesthesia. Group B had 294 American Society of Anesthesiologists physical status classification system I nulliparous patients, with childbirth potential, scheduled for benign gynecologic surgery under general anesthesia (diagnostic laparoscopy, myomectomy, hysteroscopy). The local Ethical Committee (Rome, Italy) approved the study design, and every patient signed a written and educated informed consent.
Study Procedures
After overnight fasting, all patients preoperatively received 100 mg intravenous ranitidine and 10 mg intravenous metoclopramide. In group A, spinal anesthesia was performed at L3-L4 interspace using hyperbaric solution of 8–10 mg bupivacaine, 0.5%, plus 5 μg sufentanil to improve the block and minimize the risk for maternal and fetal side effects. After discharge, 20 IU oxytocin was administered in a 500-ml glucose solution (5%). In group B, general anesthesia was induced with 4–5 μg/kg fentanyl, 2 mg/kg propofol, and 1 mg/kg vecuronium bromide. After intubation, anesthesia was maintained with sevoflurane and 50% air in oxygen. In both groups, postoperative analgesia was maintained by the administration of intravenous paracetamol and intravenous morphine.
The protocol included a questionnaire regarding age, weight, previous history of allergy (atopy and/or food, drug, latex allergy), and number of previous surgical procedures (see 1).
Perioperative allergic reactions were recorded and graded according to Rüggeberg's criteria.12 Immediately before surgery, venous blood samples were collected to measure serum concentrations of specific antinatural rubber latex immunoglobulin E by a fluorescent enzyme immunoassay test (UniCAP System; Pharmacia, Uppsala, Sweden). A specific immunoglobulin E concentration less than 0.35 kilounits/l was considered normal.13 Patients experiencing allergic reactions during surgery underwent a skin-prick test with a standard latex extract (500 μg/ml; ALK Abellò, Madrid, Spain). Because glove powder may include cornstarch, the presence of allergy to corn extract was also tested. Skin-prick tests and intradermal tests with oxytocin or other drugs administered in the study were performed to exclude drug allergy in patients who experienced adverse reactions. Skin-prick tests were performed with a Morrow-Brown needle (ALK Abellò) on the volar surface of the forearm. Glycerine solution and histamine (10 mg/ml) were used as negative and positive controls, respectively. Skin-prick tests were assessed after 20 min and results considered positive when wheal diameters were more than 4 mm; if results were judged negative, a minimal amount (0.02 ml) of the testing material was injected intradermally. Natural rubber latex allergy was diagnosed on the basis of specific immunoglobulin E results and/or positive skin-prick test.
Statistical Analysis
Sample size estimation was performed with a significance level of 5% and a power of 80%, by Epi Info Version 3.3 software (Centers for Disease Control and Prevention, Atlanta, GA). We expected a disease frequency of 5% in this obstetric population,14 whereas the prevalence of disease in the general population was set at 0.05% according to the prevalence recently reported by Monitto et al  .,15 Turjanmaa and Makinen-Kiljunen,16 and Brehler.17 To limit the potential bias to the statistical analysis caused by the possible presence of patients with no response, the sample size was increased by 15%, so the sample size included 588 patients.
Data were analyzed by descriptive statistics; categorical variables were described by frequency and percentage. The continuous variables with normal distribution were represented by mean ± SD, whereas those with nonparametric distribution were described by reporting the median and interquartile range.
The univariate analysis was performed by chi-square test and Fisher exact test for dichotomous and categorical variables, as appropriate; Student t  test (variables with normal distribution) and Mann-Whitney U test (variables without normal distribution) were used for continuous variables (age and immunoglobulin E serum concentration).
The Kolmogorov-Smirnov test was performed to examine the normality distribution. Only the age appeared to present a Gaussian distribution (age: P  = 0.083 group A, P  = 0.414 group B; immunoglobulin E concentration level: P  < 0.001 for both groups). A two-tailed P  value < 0.05 was considered statistically significant. Data were analyzed by SPSS 12.0 software package (SPSS Inc., Chicago, IL).
We recruited a total of 588 patients; all subjects completed the study. The demographic and clinical variables for the two groups are represented in table 1. Overall, a significantly higher proportion of patients in group A tested positive for latex-specific immunoglobulin E than did those in group B (15/294, 5.1% vs.  5/294, 1.7%; P  = 0.023). Moreover, the median serum concentration of immunoglobulin E in patients with specific immunoglobulin E greater than 0.35 kilounits/l was higher in pregnant subjects than in nonpregnant ones (1.93 kilounits/l; interquartile range = 2.28 vs.  0.78 kilounits/l; interquartile range = 1.07; P  = 0.044) (table 2).
Table 1.  Demographic and Clinical Variables in Group A (Obstetric Patients) and Group B (Nonpregnant Patients)
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Table 1.  Demographic and Clinical Variables in Group A (Obstetric Patients) and Group B (Nonpregnant Patients)
Table 2.  Latex Immunoglobulin E Serum Concentration in Patients with Specific Immunoglobulin E Greater than 0.35 kilounits/l
Image not available
Table 2.  Latex Immunoglobulin E Serum Concentration in Patients with Specific Immunoglobulin E Greater than 0.35 kilounits/l
Two patients in group A experienced anaphylactic reaction approximately 30–50 min after the starting of procedures and oxytocin infusion. The first patient experienced facial edema, itching, generalized erythematous rash, and sensation of throat closure. The second patient experienced facial edema, itching, urticaria, profuse sweating, and a decreased level of consciousness. Both reactions were judged as anaphylaxis with level 2 of diagnostic certainty. Neither hypotension nor bronchospasm was observed. Symptoms resolved completely after the administration of intravenous antihistamine, intravenous steroid, and oxygen therapy. In group B, no anaphylactic reactions were observed.
No significant differences between groups were seen in terms of risk factors associated with latex allergy (multiple surgical procedures, high-risk work, atopy, or previous history of allergy).
In this observational study, we assessed the prevalence of latex sensitization in the obstetric population and found a higher prevalence and higher specific immunoglobulin E serum concentration in obstetric patients than in nulliparous women.
Our data seem to confirm the previous findings of Brown et al.  18 : in obstetric patients, the prevalence of latex sensitization is higher than that of allergy with clinical symptoms. Therefore, in patients at an early stage of sensitization, a reduction or avoidance of latex exposure can minimize the progression to symptomatic disease.
However, it must be acknowledged that our observations are related to a very specific population (all of the subjects studied were women) and a very specific setting (obstetric surgery).
A significantly higher incidence of latex-related reactions has been observed in women.4,19,20 This finding may be related to the higher predisposition to allergic diseases observed in women, a more frequent exposure to latex objects during everyday life, and a greater mucosal contact with latex through contraceptives.21,22 
The obstetric population may present additional risk factors. For instance, changes in progesterone levels23 or in immunomodulation (cytokine signaling, depressed T-cell response, impaired cell-mediated immunity)24 may contribute to hypersensitivity events, including latex reactions, reported in pregnant women. Many episodes of anaphylactic reactions induced by latex gloves have been reported after normal vaginal delivery or vaginal exploration, likely because of the extensive contact of surgical gloves with highly absorptive membranes.25–28 Therefore, obstetric and gynecologic procedures appear the most common setting for latex anaphylaxis during surgery and account for approximately 50% of all reactions caused by natural rubber latex.10 In our study, the higher immunoglobulin E serum concentrations in pregnant women with positive results on fluorescent enzyme immunoassay tests could indicate a greater sensitivity of obstetric patients; it may also be related to the high number of vaginal explorations performed during pregnancy and, possibly, to the physiologic hormonal modifications occurring during pregnancy.
The two adverse reactions reported in our study occurred 30–50 min after the start of the surgical procedure and oxytocin infusion. The delay between the exposure to allergen and the anaphylactic reaction could be related to the injection of oxytocin, which may be a reaction trigger. In fact, oxytocin can induce uterine contraction, which may provoke the release of latex particles from the uterus into the bloodstream.10 Another possible mechanism could be a cross-reaction between synthetic oxytocin and latex. In fact, oxytocin may be a part of the epitope of latex antigen: in a patient sensitized to latex, the subsequent administration of oxytocin could facilitate the antigen recognition, thus causing an anaphylactic response to latex.29 
No adverse reactions to latex during surgery were reported in nonpregnant patients. However, all of these patients underwent general anesthesia, so it is not possible to exclude clinical manifestations of anaphylaxis occurring during general anesthesia and not being observed. The sample sizes we observed are too small to estimate whether spinal anesthesia is less safe than general anesthesia.
Our findings have immediate clinical significance. In fact, because our data show that the prevalence of latex sensitization is higher in the obstetric population, identification of high-risk patients during the preanesthetic visit is advisable. Patient history appears to be the most important prognostic tool: in our study, patients who experienced anaphylactic reaction had previously experienced allergic disease and hand itching after the use of rubber gloves. Unfortunately, we found no significant correlations between accepted risk factors (multiple surgical procedure, high-risk work, atopy, cross-reacting fruits/vegetables, or previous history of allergy) and latex allergy, in contrast to the data reported by Chen et al  .30 
In conclusion, our data indicate that the obstetric population has a higher prevalence of latex sensitization than do nonpregnant subjects undergoing gynecologic surgery. Additional investigations, carried out in a larger group of patients, are needed to establish the possible causes of this greater sensitization and assess a potential greater risk of adverse reactions to latex in the obstetric population.
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW: Second symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. Ann Emerg Med 2006; 47:373–80Sampson, HA Muñoz-Furlong, A Campbell, RL Adkinson, NF Bock, SA Branum, A Brown, SG Camargo, CA Cydulka, R Galli, SJ Gidudu, J Gruchalla, RS Harlor, AD Hepner, DL Lewis, LM Lieberman, PL Metcalfe, DD O'Connor, R Muraro, A Rudman, A Schmitt, C Scherrer, D Simons, FE Thomas, S Wood, JP Decker, WW
Mertes PM: Anaphylactic reactions during anaesthesia—let us treat the problem rather than debating its existence. Acta Anaesthesiol Scand 2005; 49:431–3Mertes, PM
Laxenaire MC: Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994–December 1996). Ann Fr Anesth Reanim 1999; 18:796–809Laxenaire, MC
Mertes PM, Laxenaire MC, GERAP: Anaphylactic and anaphylactoid reactions occurring during anaesthesia in France. Seventh epidemiologic survey (January 2001–December 2002). Ann Fr Anesth Reanim 2004; 23:1133–43Mertes, PM Laxenaire, MC GERAP,
Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G: Epidemiology of life-threatening and lethal anaphylaxis: A review. Allergy 2005; 60:443–51Moneret-Vautrin, DA Morisset, M Flabbee, J Beaudouin, E Kanny, G
Rendeli C, Nucera E, Ausili E, Tabacco F, Roncallo C, Pollastrini E, Scorzoni M, Schiavino D, Caldarelli M, Pietrini D, Patriarca G: Latex sensitisation and allergy in children with myelomeningocele. Childs Nerv Syst 2006; 22:28–32Rendeli, C Nucera, E Ausili, E Tabacco, F Roncallo, C Pollastrini, E Scorzoni, M Schiavino, D Caldarelli, M Pietrini, D Patriarca, G
Suli C, Parziale M, Lorini M, De Silva E, Miadonna A, Tedeschi A: Prevalence and risk factors for latex allergy: A cross sectional study on health-care workers of an Italian hospital. J Investig Allergol Clin Immunol 2004; 14:64–9Suli, C Parziale, M Lorini, M De Silva, E Miadonna, A Tedeschi, A
Gentili A, Ricci G, Di Lorenzo F, Pigna A, Tonini C, Baroncini S: Latex allergy in pediatric age: An interdisciplinary perioperative management and case reports. Minerva Anestesiol 2001; 67:29–40Gentili, A Ricci, G Di Lorenzo, F Pigna, A Tonini, C Baroncini, S
Lavaud F: Cross-sensitization between latex and fruits. J Allergy Clin Immunol 1996; 98:473–4Lavaud, F
Lieberman P: Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol 2002; 110:S64–9Lieberman, P
Draisci G, Nucera E, Pollastrini E, Forte E, Zanfini B, Pinto R, Patriarca G, Schiavino D, Pietrini D: Anaphylactic reactions during cesarean section. Int J Obstet Anesth 2007; 16:63–7Draisci, G Nucera, E Pollastrini, E Forte, E Zanfini, B Pinto, R Patriarca, G Schiavino, D Pietrini, D
Rüggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, de Souza Brito G, Heininger U, Imoukhuede B, Khamesipour A, Erlewyn-Lajeunesse M, Martin S, Mäkelä M, Nell P, Pool V, Simpson N, Brighton Collaboration Anaphylaxis Working Group: Anaphylaxis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2007; 25:5675–84Rüggeberg, JU Gold, MS Bayas, JM Blum, MD Bonhoeffer, J Friedlander, S de Souza Brito, G Heininger, U Imoukhuede, B Khamesipour, A Erlewyn-Lajeunesse, M Martin, S Mäkelä, M Nell, P Pool, V Simpson, N Brighton Collaboration Anaphylaxis Working Group,
Wood RA, Segall N, Ahlstedt S, Williams PB: Accuracy of IgE antibody laboratory results. Ann Allergy Asthma Immunol 2007; 99:34–41Wood, RA Segall, N Ahlstedt, S Williams, PB
Ownby DR, Ownby HE, McCullough J, Shafer AW: The prevalence of anti-latex IgE antibodies in 1000 volunteer blood donors. J Allergy Clin Immunol 1996; 97:1188–92Ownby, DR Ownby, HE McCullough, J Shafer, AW
Monitto CL, Hamilton RG, Levey E, Jedlicka AE, Dziedzic A, Gearhart JP, Boyadjiev SA, Brown RH: Genetic predisposition to natural rubber latex allergy differs between health care workers and high-risk patients. Anesth Analg 2010; 110:1310–7Monitto, CL Hamilton, RG Levey, E Jedlicka, AE Dziedzic, A Gearhart, JP Boyadjiev, SA Brown, RH
Turjanmaa K, Mäkinen-Kiljunen S: Latex allergy: Prevalence, risk factors, and cross-reactivity. Methods 2002; 27:10–4Turjanmaa, K Mäkinen-Kiljunen, S
Brehler R. Latex allergy. Compr Ther 2002; 28:244–9Brehler, R
Brown RH, Schauble JF, Hamilton RG: Prevalence of latex allergy among anesthesiologists: Identification of sensitized but asymptomatic individuals. Anesthesiology 1998; 89:292–9Brown, RH Schauble, JF Hamilton, RG
Mertes PM, Laxenaire MC, Alla F, Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques: Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999–2000. Anesthesiology 2003; 99:536–45Mertes, PM Laxenaire, MC Alla, F Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques,
Laxenaire MC, Mertes PM, Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques: Anaphylaxis during anaesthesia. Results of a two-year survey in France. Br J Anaesth 2001; 87:549–58Laxenaire, MC Mertes, PM Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques,
Kam PC, Lee MS, Thompson JF: Latex allergy: An emerging clinical and occupational health problem. Anaesthesia 1997; 52:570–5Kam, PC Lee, MS Thompson, JF
Dakin MJ, Yentis SM: Latex allergy: A strategy for management. Anaesthesia 1998; 53:774–81Dakin, MJ Yentis, SM
Meggs WJ, Pescovitz OH, Metcalfe D, Loriaux DL, Cutler G Jr, Kaliner M: Progesterone sensitivity as a cause of recurrent anaphylaxis. N Engl J Med 1984; 311:1236–8Meggs, WJ Pescovitz, OH Metcalfe, D Loriaux, DL Cutler, G Kaliner, M
Heinly TL, Lieberman P: Anaphylaxis in pregnancy. Immunol Allergy Clin North Am 2000; 20:831–8Heinly, TL Lieberman, P
Turjanmaa K, Reunala T, Tuimala R, Kärkkäinen T. Allergy to latex gloves: Unusual complication during delivery. BMJ 1988; 297:1029Turjanmaa, K Reunala, T Tuimala, R Kärkkäinen, T
Laurent J, Malet R, Smiejan JM, Madelenat P, Herman D: Latex hypersensitivity after natural delivery. J Allergy Clin Immunol 1992; 89:779–80Laurent, J Malet, R Smiejan, JM Madelenat, P Herman, D
Deusch E, Reider N, Marth C: Anaphylactic reaction to latex during cesarean delivery. Obstet Gynecol 1996; 88:727Deusch, E Reider, N Marth, C
Santos R, Hernández-Ayup S, Galache P, Morales FG, Batiza VA, Montoya D: Severe latex allergy after a vaginal examination during labor: A case report. Am J Obstet Gynecol 1997; 177:1543–4Santos, R Hernández-Ayup, S Galache, P Morales, FG Batiza, VA Montoya, D
Ogata J, Minami K: Synthetic oxytocin and latex allergy. Br J Anaesth 2007; 98:845–6Ogata, J Minami, K
Chen FC, von Dehn D, Büscher U, Dudenhausen JW, Niggemann B: Atopy, the use of condoms, and a history of cesarean delivery: Potential predisposing factors for latex sensitization in pregnant women. Am J Obstet Gynecol 1999; 181:1461–4Chen, FC von Dehn, D Büscher, U Dudenhausen, JW Niggemann, B
Appendix 1: Questionnaire Used to Collect Data
Questionnaire n°………Date……….Patient ……………………….
Age …….years Weight………kg
Procedure □ Gynecologic surgery □ Obstetric surgery
Referred Allergy to:
Drugs □ No □ Yes
Foods □ No □ Yes
Pollens □ No □ Yes
Metals □ No □ Yes
Fruits □ No □ Yes
Vegetables □ No □ Yes
Plants □ No □ Yes
Latex □ No □ Yes
Others □ No □ Yes
Previous reaction to natural rubber latex (NRL)?
□ No □ Yes
Dyspnea: □ No □ Yes; Rhinitis □ No □ Yes; Conjunctivitis □ No □ Yes Urticarial reaction □ No □ Yes; Angioedema □ No □ Yes; Erythema □ No □ Yes; Local symptoms □ No □ Yes
Suspected reaction during dental surgery? □ No □ Yes
Neurologic pathology, spina bifida, tracheoesophageal fistula, bladder dysfunction, myelomeningocele, urogenital dysfunction?
□ No □ Yes
Healthcare worker?
□ No □ Yes
Use of latex gloves in work?
□ No □ Yes
More than two surgical procedures?
□ No □ Yes
Suspected reaction during or after surgical procedure?
□ No □ Yes
Family history of atopy?
□ No □ Yes
Table 1.  Demographic and Clinical Variables in Group A (Obstetric Patients) and Group B (Nonpregnant Patients)
Image not available
Table 1.  Demographic and Clinical Variables in Group A (Obstetric Patients) and Group B (Nonpregnant Patients)
Table 2.  Latex Immunoglobulin E Serum Concentration in Patients with Specific Immunoglobulin E Greater than 0.35 kilounits/l
Image not available
Table 2.  Latex Immunoglobulin E Serum Concentration in Patients with Specific Immunoglobulin E Greater than 0.35 kilounits/l