The safety of immunotherapy during pregnancy W. James Metzger, Chicago,
M.D., Elaine Turner,
M.D., and Roy Patterson,
M.D.
Ill.
A group of 121 pregnancies from 90 atopic mothers who had received immunotherapy during pregnancy were studied retrospectively with the use of physician or maternal questionnaires and obstetric records. The inciaknce of prematurity, toxemia, abortion, neonatal death, and congenital malformation was no greater than that for the general population. The offspring of the treated mothers developed allergic disease as frequently as children born into allergic families. A group of I47 untreated pregnancies of atopic mothers were similarly studied, and the incidence of those parameters were similar except for a greater incidence of abortion. The implications of these findings are discussed.
Since its introduction by Noon’ and Freeman,2 immunotherapy (IT) for allergic disease has been shown to be effective for certain inhalant allergies and presumptively effective for others.3 During therapy, young atopic females may become pregnant. The question of the relative safety of IT for the mother and the fetus may then be raised by the mother or her obstetrician. It has heretofore been our standard practice to cautiously continue perennial IT throughout pregnancy as an important adjunct in the treatment of selected cases of allergic rhinitis or extrinsic asthma. Intermpting perennial therapy would mean beginning anew as well as a loss of effectiveness and a financial loss for the patient. Standard textbooks of allergic diseases43 5 have also recommended its continued use throughout pregnancy. Although many case reports and several small compilations of patients supported this concept, definitive information regarding the risk to the mother or fetus was not available. This kind of information appeared desirable in order to recommend the continuation of IT to women who become pregnant while receiving IT for allergic disease. This has become especially important since the
recent concern over the use of any medication during pregnancy. It would also be important to know if IT had any effect on the developing child and if it either protected him from atopy or predisposed him to earlier manifestations of allergic disease. These questions were addressed with the use of a retrospective review of 121 pregnancies of 90 atopic mothers who had received IT during gestation.
From the Department of Internal Medicine, Section of Allergy and Immunology, Northwestern University Medical School. Supportedby the Ernest S. Bazley Grant and United StatesPublic Health Service Grant AI 11403. Received for publication Aug. 31, 1977. Accepted for publication Nov. 28, 1977. Reprint requeststo: Roy Patterson,M.D., Section of Allergy/ Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Ill. 60611.
retrospective nature of the study. The questionnaires requested information regarding maternal age and diagnosis, treatment program, dosage,
Vol. 61, No. 4, pp. 266-272
MATERIALS AND METHODS The recordsof atopic women who had received IT during one or more pregnancies were reviewed retrospectively. The patients were derived from the Northwestern University Allergy Service population and the practices of several al-
lergists who were closely associatedwith the Northwestern University Allergy teaching program. The diversified patient population was derived from an innercity clinic, the city’s upper socioeconomiclevels, and private allergy practices in the midwest and the west coast. All races and socioeconomic levels were represented. The data were obtained through several means: (1) the physician reviewed the patients’ allergic records and completed a physician data questionnaire, (2) the patient completed a maternal questionnaire, (3) obstetric records, when available, were reviewed by the physician to supplement the previous two. All data were not available in every case because of the
local or systemic reactions, maternal medications, alcohol and cigarette consumption, birth weight, previous pregnancies and results, and atopic status of the infants and children. For the purpose of this study, toxemia was defined as hypertension and proteinuria during the last half of preg0091-6749178/0461-0268$00.50/O
@ 1978 The C. V. Mosby
Co.
VOLUME NUMBER
Immunotherapy during pregnancy 209
61 4
nancyti and prematurity as a birth weight less than 2,500 grams.’ In one instance, the child of a diabetic mother weighed more than 2500 grams, but the pregnancy lasted only 7 mo. This child was consideredpremature.The atopic statusof the infants was determinedby the attending physician and derived from history and/or physical examination. In somecases,skin testing had been done, and in one case an elevated serum IgE level was found. The mothers had been determined to have IgE-mediated rhinitis or asthmaby the usual criteria of history, physical examination, and multiple positive and correlative skin tests to common inhalant allergens. Each patient was receiving aqueousextracts of the common inhalant allergens basedon a w/v concentration. In nearly all cases,pregnancyresulted after IT had been begun. The recordsof a secondgroup of atopic pregnant women were reviewed who had not received IT during pregnancy. This group of patients was composed,in part (60%) by the sameatopic women as in the “treated” group. The remaining 40% were atopic women categorized in tbe samemanner as the “treated” patients but who had never received IT during any pregnancies. All these were patients of the Northwestern University Allergy Service. This combined group of untreated pregnancieswas considered the control group. They were matched in 60% of the casesexcept for age and parity, and the remaining patients were derived from the same clinic population and treated by the same physician. RESULTS
From these sources, 121 pregnancies from 90 atopic women who had received IT durinq the preg-
nancy were analyzed. Table I depicts the charatceristics of this group of women. Their agesrange-dfrom 18 to 45 yr (mean, 27), and they were being treated for allergic rhinitis (82.4%), extrinsic asthma (17.6%), or both (41.8%). These patients were receiving aqueousextracts of tree, grass, ragweed pollens, molds, or house dust. During their pregnancies, 64% were receiving approximately a 1: 50 w/v dilution of extract, while 82% were receiving at least the first dilution. Thus, most patients were treated with high- or moderate-dosetherapy* during pregnancy. Table II is a comparison between the incidence of complications experienced by the atopic treated mothers and the incidence expected for the general population. The expected incidence for the general population was derived from the literature with the use of generally acceptedvalues (Table II). There were 6 abortions (5.0%) in the study population but no stillbirths or neonatal deaths. There were also 4 premature births (3.3%), 3 toxemic pregnancies (2.5%) and 3 congenital malformations (2.5%). These were all less than the greatest incidence expected for the general population. Thosecongenital malformations recognized at birth
I. Characteristics of treated and untreated populations
TABLE
Pop&tin
Treated
lhemaed
Number pregnancies
121
147
Number mothers Mean age Range
90 39 I x-45
03 i/,I h-45
Diagnosis Allergic rhinitis (o/c) Asthma (%) Rhinitis and asthma(96)
x2.4 17.6 41 x
70.3 29.7 44.7
Immunotherapy Approximately 1:50 w/v (%)
64.0
Not applicable
First dilution, I:500 w/v (%) Other
I8 IX
II. Comparison of complications during pregnancy
TABLE
Abortion Stiilbirth Neonatal death Prematurity (
M.D., Elaine Turner,
M.D., and Roy Patterson,
M.D.
Ill.
A group of 121 pregnancies from 90 atopic mothers who had received immunotherapy during pregnancy were studied retrospectively with the use of physician or maternal questionnaires and obstetric records. The inciaknce of prematurity, toxemia, abortion, neonatal death, and congenital malformation was no greater than that for the general population. The offspring of the treated mothers developed allergic disease as frequently as children born into allergic families. A group of I47 untreated pregnancies of atopic mothers were similarly studied, and the incidence of those parameters were similar except for a greater incidence of abortion. The implications of these findings are discussed.
Since its introduction by Noon’ and Freeman,2 immunotherapy (IT) for allergic disease has been shown to be effective for certain inhalant allergies and presumptively effective for others.3 During therapy, young atopic females may become pregnant. The question of the relative safety of IT for the mother and the fetus may then be raised by the mother or her obstetrician. It has heretofore been our standard practice to cautiously continue perennial IT throughout pregnancy as an important adjunct in the treatment of selected cases of allergic rhinitis or extrinsic asthma. Intermpting perennial therapy would mean beginning anew as well as a loss of effectiveness and a financial loss for the patient. Standard textbooks of allergic diseases43 5 have also recommended its continued use throughout pregnancy. Although many case reports and several small compilations of patients supported this concept, definitive information regarding the risk to the mother or fetus was not available. This kind of information appeared desirable in order to recommend the continuation of IT to women who become pregnant while receiving IT for allergic disease. This has become especially important since the
recent concern over the use of any medication during pregnancy. It would also be important to know if IT had any effect on the developing child and if it either protected him from atopy or predisposed him to earlier manifestations of allergic disease. These questions were addressed with the use of a retrospective review of 121 pregnancies of 90 atopic mothers who had received IT during gestation.
From the Department of Internal Medicine, Section of Allergy and Immunology, Northwestern University Medical School. Supportedby the Ernest S. Bazley Grant and United StatesPublic Health Service Grant AI 11403. Received for publication Aug. 31, 1977. Accepted for publication Nov. 28, 1977. Reprint requeststo: Roy Patterson,M.D., Section of Allergy/ Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, Ill. 60611.
retrospective nature of the study. The questionnaires requested information regarding maternal age and diagnosis, treatment program, dosage,
Vol. 61, No. 4, pp. 266-272
MATERIALS AND METHODS The recordsof atopic women who had received IT during one or more pregnancies were reviewed retrospectively. The patients were derived from the Northwestern University Allergy Service population and the practices of several al-
lergists who were closely associatedwith the Northwestern University Allergy teaching program. The diversified patient population was derived from an innercity clinic, the city’s upper socioeconomiclevels, and private allergy practices in the midwest and the west coast. All races and socioeconomic levels were represented. The data were obtained through several means: (1) the physician reviewed the patients’ allergic records and completed a physician data questionnaire, (2) the patient completed a maternal questionnaire, (3) obstetric records, when available, were reviewed by the physician to supplement the previous two. All data were not available in every case because of the
local or systemic reactions, maternal medications, alcohol and cigarette consumption, birth weight, previous pregnancies and results, and atopic status of the infants and children. For the purpose of this study, toxemia was defined as hypertension and proteinuria during the last half of preg0091-6749178/0461-0268$00.50/O
@ 1978 The C. V. Mosby
Co.
VOLUME NUMBER
Immunotherapy during pregnancy 209
61 4
nancyti and prematurity as a birth weight less than 2,500 grams.’ In one instance, the child of a diabetic mother weighed more than 2500 grams, but the pregnancy lasted only 7 mo. This child was consideredpremature.The atopic statusof the infants was determinedby the attending physician and derived from history and/or physical examination. In somecases,skin testing had been done, and in one case an elevated serum IgE level was found. The mothers had been determined to have IgE-mediated rhinitis or asthmaby the usual criteria of history, physical examination, and multiple positive and correlative skin tests to common inhalant allergens. Each patient was receiving aqueousextracts of the common inhalant allergens basedon a w/v concentration. In nearly all cases,pregnancyresulted after IT had been begun. The recordsof a secondgroup of atopic pregnant women were reviewed who had not received IT during pregnancy. This group of patients was composed,in part (60%) by the sameatopic women as in the “treated” group. The remaining 40% were atopic women categorized in tbe samemanner as the “treated” patients but who had never received IT during any pregnancies. All these were patients of the Northwestern University Allergy Service. This combined group of untreated pregnancieswas considered the control group. They were matched in 60% of the casesexcept for age and parity, and the remaining patients were derived from the same clinic population and treated by the same physician. RESULTS
From these sources, 121 pregnancies from 90 atopic women who had received IT durinq the preg-
nancy were analyzed. Table I depicts the charatceristics of this group of women. Their agesrange-dfrom 18 to 45 yr (mean, 27), and they were being treated for allergic rhinitis (82.4%), extrinsic asthma (17.6%), or both (41.8%). These patients were receiving aqueousextracts of tree, grass, ragweed pollens, molds, or house dust. During their pregnancies, 64% were receiving approximately a 1: 50 w/v dilution of extract, while 82% were receiving at least the first dilution. Thus, most patients were treated with high- or moderate-dosetherapy* during pregnancy. Table II is a comparison between the incidence of complications experienced by the atopic treated mothers and the incidence expected for the general population. The expected incidence for the general population was derived from the literature with the use of generally acceptedvalues (Table II). There were 6 abortions (5.0%) in the study population but no stillbirths or neonatal deaths. There were also 4 premature births (3.3%), 3 toxemic pregnancies (2.5%) and 3 congenital malformations (2.5%). These were all less than the greatest incidence expected for the general population. Thosecongenital malformations recognized at birth
I. Characteristics of treated and untreated populations
TABLE
Pop&tin
Treated
lhemaed
Number pregnancies
121
147
Number mothers Mean age Range
90 39 I x-45
03 i/,I h-45
Diagnosis Allergic rhinitis (o/c) Asthma (%) Rhinitis and asthma(96)
x2.4 17.6 41 x
70.3 29.7 44.7
Immunotherapy Approximately 1:50 w/v (%)
64.0
Not applicable
First dilution, I:500 w/v (%) Other
I8 IX
II. Comparison of complications during pregnancy
TABLE
Abortion Stiilbirth Neonatal death Prematurity (
