Pediatric Allergy and Immunology
ORIGINAL ARTICLE
Skin and eye disease
Perinatal factors and the risk of atopic dermatitis: A cohort study Fabio Parazzini1, Sonia Cipriani2, Cornelia Zinetti1, Liliane Chatenoud3, Luigi Frigerio4, Giuseppe Amuso5, Massimo Ciammella6, Anna Di Landro1,7 & Luigi Naldi1,8 1
Centro Studi GISED, Bergamo, Italy; 2Dipartimento Materno-Infantile, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Universit a degli Studi di Milano, Milano, Italy; 3IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; 4Department of Gynecology and Obstetrics, Ospedali Riuniti di Bergamo, Bergamo, Italy; 5Department of Gynecology and Obstetrics, Ospedale Pesenti Fenaroli, Alzano Lombardo, Italy; 6Department of Gynecology and Obstetrics, Azienda Ospedaliera Bolognini, Seriate, Italy; 7Department of Gynecology and Obstetrics, Azienda Ospedaliera Ospedale Treviglio Caravaggio, Treviglio Caravaggio, Italy; 8Department of Dermatology, Ospedali Riuniti di Bergamo, Bergamo, Italy
To cite this article: Parazzini F, Cipriani S, Zinetti C, Chatenoud L, Frigerio L, Amuso G, Ciammella M, Landro AD, Naldi L. Perinatal factors and the risk of atopic dermatitis: A cohort study. Pediatr Allergy Immunol 2014: 25: 43–50.
Keywords risk factors; birth weight; atopic dermatitis; breast feeding Correspondence Luigi Naldi, Centro Studi GISED, Via Garibaldi 13 24100 Bergamo, Italy Tel.: +39 0352278 719, -720 Fax: +39 0352278673 E-mail: [email protected] Accepted for publication 7 October 2013 DOI:10.1111/pai.12165
Abstract Objective: To analyze the effects of pregnancy and early events in the newborn on the risk of subsequent atopic dermatitis (AD) during the first year of life. Patients and Methods: This is a prospective multicenter cohort study of newborns during the first year of life. Newborns identified on random days in three obstetrics departments in the area of Bergamo, Lombardy, Northern Italy, were eligible. At baseline, the mothers were interviewed by medical staff during their stay in hospital after delivery. At 6 and 12 months after delivery, a postal questionnaire was sent to the parents. Relative risks were calculated with and without adjustment by multiple regression analysis. Results: A total of 1081 newborns entered the study: 796 (74%) parents answered the 12-month questionnaire. Hundred and thirty-eight (17%) reported a diagnosis of AD at 6 months and 222 (28%) at 12 months. Parental history of AD and/or asthma was associated with an increased risk of AD (RR 1.5, 95%CI 1.1–2.0). Birth weight was slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001–1.08 (continuous variable, increment of 100 grams). No association emerged between breast feeding, smoking, and risk of AD. Conclusions: This study in an Italian offspring cohort points to family history of atopic diseases and body weight at birth as relevant risk factors. The study was unable to document associations with other perinatal factors particularly breast feeding and parental smoking in the perinatal period.
Atopic dermatitis (AD) is the first step in the progression of atopic disorders in infants, the so-called atopic march, from AD to allergic rhinitis and asthma. Recent studies support the role of skin barrier defects (i.e., loss of function of filaggrin, an epidermal barrier protein) as facilitating entry for pathogens, allergens, and other environmental insults (toxins, irritants, pollutants). Therefore, genetic predisposition together with skin barrier defects and environmental exposure are now considered the main mechanisms of development of AD (1, 2). The prevalence of AD has risen steeply in the last five decades, reaching about 20% in the first 2 yr of life in many industrialized countries, and becoming the most common inflammatory skin disease in childhood (3). Thus, exposure during pregnancy or during the first weeks of life may greatly influence the risk of AD. Breast feeding and
antibiotic use in pregnancy have all been considered in relation to the risk of AD, with variable results (4). To analyze the effects of pregnancy and early events in newborns on the risk of AD during the first year of life, we conducted a prospective cohort study. Most published studies on the epidemiology of AD have been conducted in North European and American countries, and few data are available from southern European populations for very young children. This study was conducted in the Bergamo area, Lombardy, Italy. Methods This was a prospective multicenter cohort study of newborns during the first year of life. Newborns identified on random
Pediatric Allergy and Immunology 25 (2014) 43–50 ª 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
43
Perinatal factors and risk of atopic dermatitis
days in the three obstetric departments in the area of Bergamo, Lombardy, Northern Italy, were eligible. Subjects from families not speaking Italian or not resident in the Bergamo area were not included. The mothers were identified and interviewed by medical interviewers during their stay in hospital after delivery. The investigator enrolled all the consecutive newborns observed from the start of the study who met the inclusion criteria on selected random days. Enrollment started in February 2007 and was concluded in May 2009 when the number of patients established by the protocol (see below) was reached. Three questionnaires were planned: a face-to-face questionnaire with trained interviewers and two postal questionnaires sent to the parents 6 and 12 months after delivery. The baseline questionnaire collected information about the main demographic characteristics and personal habits of the parents (smoking, alcohol consumption), parents’ history of allergic diseases, number of brothers and sisters of the newborn, course of pregnancy and mode of delivery, antibiotic treatment, and streptococcus prophylaxis during pregnancy, gestational age at delivery, birth weight, details of the child’s home. The follow-up questionnaires collected information about breast feeding, the home, baby’s diet, selected diseases and the signs and symptoms associated with them, any hospital admission, discharge diagnosis, other health problems of the baby, parents’ smoking habits during the baby’s first year of life. Diagnosis of AD Diagnosis of AD was established when there was a history of itching skin rash (5), and a diagnosis of ‘atopic dermatitis’ or ‘atopic eczema’ made by a pediatrician or a dermatologist. Statistical analysis The main objective of the study was to analyze the 12-month incidence of AD in the study population and the risk factors for the development of AD. Adjusted and unadjusted relative risks (RR) and 95% confidence interval were calculated with the classical Mantel–Haenszel analysis of case–control data modified for the analysis of cohort studies (6). In the model with adjustment, we included gender, mother’s and father’s age and education, family history of AD (or mother’s history of AD and father’s history of AD or mother’s history of asthma and father’s history of asthma, alternatively included in the model because of the correlation), cats, or dogs in the house at birth (or cats or dogs in the house after birth), disease in pregnancy, gestational age at delivery, mode of delivery, birth weight, use of antibiotic during pregnancy, streptococcus treatment during pregnancy, antibiotic use in the newborn, breast feeding (or duration of breast feeding or duration of breast feeding/other milk).
Parazzini et al.
was approved by the ethics committees of the participating centers. Written informed consent was obtained from the mothers before the study. Results A total of 1081 newborns entered the study: 285 parents (26%, 95% CI 24–29%) did not respond to the postal questionnaire or phone interview at 12 months (Fig. 1). Thus, these analyses are based on 796 (74%, 95% CI 71–76%) newborns followed up for 12 months. The characteristics of the newborns lost to follow-up were largely similar to those for which follow-up data were available (Table 1). A total of 222 newborns reported a diagnosis of AD, 138 (62%, 95% CI 56–69%) within 6 months, and an additional 84 (29%, 95% CI 31–44%) between 6 and 12 months. Therefore, incidence estimates were, respectively, 17% (95% CI 15–20%) and 28% (95% CI 25–31%) at 6 and 12 months. Table 2 shows the distribution of study subjects according to the diagnosis of AD at 12 months and selected factors. A family history of AD and/or asthma was associated with an increased risk of AD in the newborns (RR 1.5, 95% CI 1.1–2.0). Maternal history of AD (RR 1.8, 95% CI 1.1–2.9) and paternal history of asthma (RR 1.9, 95% CI 1.2–2.8) were significantly associated with an increased risk of AD in the newborns. No association emerged between maternal and paternal age and education, parents’ smoking habits, presence of cats and dogs in the child’s house, gestational age at delivery, and the risk of AD. Table 3 shows the relation between the risk of AD and pregnancy, delivery factors, and breast feeding. Birth weight was slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001–1.08 (continuous variable, increment of 100 grams). The risk of AD was slightly increased with gestational age at delivery: RR 1.1, 95%CI 1.03–1.3 (continuous variable, increment of 1 wk), but with loss of significance after adjustment (RR 1.1, 95%CI 0.98–1.3). No association emerged between a history of gestational diseases (diabetes, hypertension, liver diseases) in pregnancy, mode of delivery, and maternal use of antibiotics during pregnancy, and risk of AD. No relationship emerged between breast feeding and risk of AD. A sample size of 796 subjects with a proportion of AD diagnosis of 27.9% (222 cases) achieve at least 80% power to detect an RR = 1.5 if the proportion of exposure in the control
Ethics The study was conducted in accordance with the Declaration of Helsinki and the ICH-GCP guidelines. The study protocol
44
Figure 1 Flow of subjects in the study population.
Pediatric Allergy and Immunology 25 (2014) 43–50 ª 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Parazzini et al.
Perinatal factors and risk of atopic dermatitis
Table 1 Comparison of characteristics between subjects lost to follow-up and those included in the analysis Lost to follow-up (12 months) Yes (n = 285)
Gender Male Female Mother’s and father’s age (years) Mother
ORIGINAL ARTICLE
Skin and eye disease
Perinatal factors and the risk of atopic dermatitis: A cohort study Fabio Parazzini1, Sonia Cipriani2, Cornelia Zinetti1, Liliane Chatenoud3, Luigi Frigerio4, Giuseppe Amuso5, Massimo Ciammella6, Anna Di Landro1,7 & Luigi Naldi1,8 1
Centro Studi GISED, Bergamo, Italy; 2Dipartimento Materno-Infantile, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Universit a degli Studi di Milano, Milano, Italy; 3IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; 4Department of Gynecology and Obstetrics, Ospedali Riuniti di Bergamo, Bergamo, Italy; 5Department of Gynecology and Obstetrics, Ospedale Pesenti Fenaroli, Alzano Lombardo, Italy; 6Department of Gynecology and Obstetrics, Azienda Ospedaliera Bolognini, Seriate, Italy; 7Department of Gynecology and Obstetrics, Azienda Ospedaliera Ospedale Treviglio Caravaggio, Treviglio Caravaggio, Italy; 8Department of Dermatology, Ospedali Riuniti di Bergamo, Bergamo, Italy
To cite this article: Parazzini F, Cipriani S, Zinetti C, Chatenoud L, Frigerio L, Amuso G, Ciammella M, Landro AD, Naldi L. Perinatal factors and the risk of atopic dermatitis: A cohort study. Pediatr Allergy Immunol 2014: 25: 43–50.
Keywords risk factors; birth weight; atopic dermatitis; breast feeding Correspondence Luigi Naldi, Centro Studi GISED, Via Garibaldi 13 24100 Bergamo, Italy Tel.: +39 0352278 719, -720 Fax: +39 0352278673 E-mail: [email protected] Accepted for publication 7 October 2013 DOI:10.1111/pai.12165
Abstract Objective: To analyze the effects of pregnancy and early events in the newborn on the risk of subsequent atopic dermatitis (AD) during the first year of life. Patients and Methods: This is a prospective multicenter cohort study of newborns during the first year of life. Newborns identified on random days in three obstetrics departments in the area of Bergamo, Lombardy, Northern Italy, were eligible. At baseline, the mothers were interviewed by medical staff during their stay in hospital after delivery. At 6 and 12 months after delivery, a postal questionnaire was sent to the parents. Relative risks were calculated with and without adjustment by multiple regression analysis. Results: A total of 1081 newborns entered the study: 796 (74%) parents answered the 12-month questionnaire. Hundred and thirty-eight (17%) reported a diagnosis of AD at 6 months and 222 (28%) at 12 months. Parental history of AD and/or asthma was associated with an increased risk of AD (RR 1.5, 95%CI 1.1–2.0). Birth weight was slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001–1.08 (continuous variable, increment of 100 grams). No association emerged between breast feeding, smoking, and risk of AD. Conclusions: This study in an Italian offspring cohort points to family history of atopic diseases and body weight at birth as relevant risk factors. The study was unable to document associations with other perinatal factors particularly breast feeding and parental smoking in the perinatal period.
Atopic dermatitis (AD) is the first step in the progression of atopic disorders in infants, the so-called atopic march, from AD to allergic rhinitis and asthma. Recent studies support the role of skin barrier defects (i.e., loss of function of filaggrin, an epidermal barrier protein) as facilitating entry for pathogens, allergens, and other environmental insults (toxins, irritants, pollutants). Therefore, genetic predisposition together with skin barrier defects and environmental exposure are now considered the main mechanisms of development of AD (1, 2). The prevalence of AD has risen steeply in the last five decades, reaching about 20% in the first 2 yr of life in many industrialized countries, and becoming the most common inflammatory skin disease in childhood (3). Thus, exposure during pregnancy or during the first weeks of life may greatly influence the risk of AD. Breast feeding and
antibiotic use in pregnancy have all been considered in relation to the risk of AD, with variable results (4). To analyze the effects of pregnancy and early events in newborns on the risk of AD during the first year of life, we conducted a prospective cohort study. Most published studies on the epidemiology of AD have been conducted in North European and American countries, and few data are available from southern European populations for very young children. This study was conducted in the Bergamo area, Lombardy, Italy. Methods This was a prospective multicenter cohort study of newborns during the first year of life. Newborns identified on random
Pediatric Allergy and Immunology 25 (2014) 43–50 ª 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
43
Perinatal factors and risk of atopic dermatitis
days in the three obstetric departments in the area of Bergamo, Lombardy, Northern Italy, were eligible. Subjects from families not speaking Italian or not resident in the Bergamo area were not included. The mothers were identified and interviewed by medical interviewers during their stay in hospital after delivery. The investigator enrolled all the consecutive newborns observed from the start of the study who met the inclusion criteria on selected random days. Enrollment started in February 2007 and was concluded in May 2009 when the number of patients established by the protocol (see below) was reached. Three questionnaires were planned: a face-to-face questionnaire with trained interviewers and two postal questionnaires sent to the parents 6 and 12 months after delivery. The baseline questionnaire collected information about the main demographic characteristics and personal habits of the parents (smoking, alcohol consumption), parents’ history of allergic diseases, number of brothers and sisters of the newborn, course of pregnancy and mode of delivery, antibiotic treatment, and streptococcus prophylaxis during pregnancy, gestational age at delivery, birth weight, details of the child’s home. The follow-up questionnaires collected information about breast feeding, the home, baby’s diet, selected diseases and the signs and symptoms associated with them, any hospital admission, discharge diagnosis, other health problems of the baby, parents’ smoking habits during the baby’s first year of life. Diagnosis of AD Diagnosis of AD was established when there was a history of itching skin rash (5), and a diagnosis of ‘atopic dermatitis’ or ‘atopic eczema’ made by a pediatrician or a dermatologist. Statistical analysis The main objective of the study was to analyze the 12-month incidence of AD in the study population and the risk factors for the development of AD. Adjusted and unadjusted relative risks (RR) and 95% confidence interval were calculated with the classical Mantel–Haenszel analysis of case–control data modified for the analysis of cohort studies (6). In the model with adjustment, we included gender, mother’s and father’s age and education, family history of AD (or mother’s history of AD and father’s history of AD or mother’s history of asthma and father’s history of asthma, alternatively included in the model because of the correlation), cats, or dogs in the house at birth (or cats or dogs in the house after birth), disease in pregnancy, gestational age at delivery, mode of delivery, birth weight, use of antibiotic during pregnancy, streptococcus treatment during pregnancy, antibiotic use in the newborn, breast feeding (or duration of breast feeding or duration of breast feeding/other milk).
Parazzini et al.
was approved by the ethics committees of the participating centers. Written informed consent was obtained from the mothers before the study. Results A total of 1081 newborns entered the study: 285 parents (26%, 95% CI 24–29%) did not respond to the postal questionnaire or phone interview at 12 months (Fig. 1). Thus, these analyses are based on 796 (74%, 95% CI 71–76%) newborns followed up for 12 months. The characteristics of the newborns lost to follow-up were largely similar to those for which follow-up data were available (Table 1). A total of 222 newborns reported a diagnosis of AD, 138 (62%, 95% CI 56–69%) within 6 months, and an additional 84 (29%, 95% CI 31–44%) between 6 and 12 months. Therefore, incidence estimates were, respectively, 17% (95% CI 15–20%) and 28% (95% CI 25–31%) at 6 and 12 months. Table 2 shows the distribution of study subjects according to the diagnosis of AD at 12 months and selected factors. A family history of AD and/or asthma was associated with an increased risk of AD in the newborns (RR 1.5, 95% CI 1.1–2.0). Maternal history of AD (RR 1.8, 95% CI 1.1–2.9) and paternal history of asthma (RR 1.9, 95% CI 1.2–2.8) were significantly associated with an increased risk of AD in the newborns. No association emerged between maternal and paternal age and education, parents’ smoking habits, presence of cats and dogs in the child’s house, gestational age at delivery, and the risk of AD. Table 3 shows the relation between the risk of AD and pregnancy, delivery factors, and breast feeding. Birth weight was slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001–1.08 (continuous variable, increment of 100 grams). The risk of AD was slightly increased with gestational age at delivery: RR 1.1, 95%CI 1.03–1.3 (continuous variable, increment of 1 wk), but with loss of significance after adjustment (RR 1.1, 95%CI 0.98–1.3). No association emerged between a history of gestational diseases (diabetes, hypertension, liver diseases) in pregnancy, mode of delivery, and maternal use of antibiotics during pregnancy, and risk of AD. No relationship emerged between breast feeding and risk of AD. A sample size of 796 subjects with a proportion of AD diagnosis of 27.9% (222 cases) achieve at least 80% power to detect an RR = 1.5 if the proportion of exposure in the control
Ethics The study was conducted in accordance with the Declaration of Helsinki and the ICH-GCP guidelines. The study protocol
44
Figure 1 Flow of subjects in the study population.
Pediatric Allergy and Immunology 25 (2014) 43–50 ª 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Parazzini et al.
Perinatal factors and risk of atopic dermatitis
Table 1 Comparison of characteristics between subjects lost to follow-up and those included in the analysis Lost to follow-up (12 months) Yes (n = 285)
Gender Male Female Mother’s and father’s age (years) Mother
