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Gastrointestinal symptoms in infancy: A population-based prospective study
Digestive and Liver Disease 37 (2005) 432–438
Alimentary Tract
Gastrointestinal symptoms in infancy: A population-based prospective study G. Iacono a , R. Merolla b , D. D’Amico a , E. Bonci c , F. Cavataio a , L. Di Prima d , C. Scalici a , L. Indinnimeo c , M.R. Averna d , A. Carroccio d,∗ the Paediatric Study Group on Gastrointestinal Symptoms in Infancy1 a
d
Paediatric Gastroenterology, ‘Di Cristina’ Hospital of Palermo, Italy b Medical Department, ABBOTT, Italy c Paediatric Department, University of Rome ‘La Sapienza’, Italy Internal Medicine, University Hospital of Palermo, via Coffaro 25, Palermo 90124, Italy Received 23 August 2004; accepted 17 January 2005 Available online 2 March 2005
Abstract Background. During the first months of life, infants can suffer from many ‘minor’ gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. Aims. (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. Study design and patients. Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. Results. 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breastfeeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. Conclusions. Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a ‘dietary’ milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms. © 2005 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. Keywords: Colic; Constipation; Diarrhoea; Epidemiology; Failure to thrive; Feeding; Infancy; Regurgitation; Vomiting
1. Introduction
∗ 1
Corresponding author. Tel.: +39 091 6552860; fax: +39 091 6552936. E-mail address: [email protected] (A. Carroccio). See Appendix A.
During the first months after birth our gastrointestinal system strives to adapt itself to the various nutrients in order to perfect its digestive, absorptive and immunological functions. Obviously, during this ‘stressful’ period infants can suf-
1590-8658/$30 © 2005 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. doi:10.1016/j.dld.2005.01.009
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fer from many gastroenterological disturbances, which in the majority of cases are dealt with by paediatricians without the need for hospitalisation and/or laboratory/instrumental investigations. However, little is known about the real frequency of these ‘minor’ gastrointestinal disturbances, the factors which predispose or facilitate their onset and the relationship between these disturbances and the type of feeding the infants receive. The aims of the present prospective, population-based study were: (a) to ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence that some variables have on the onset of these symptoms; (c) to clarify the causes for hospitalisation due to gastrointestinal disturbances.
2. Patients and methods 2.1. Study design The study was carried out between January and December 1999 with the collaboration of 150 paediatricians distributed throughout Italy (40 in the north of Italy, 35 in the centre, 40 in the south and 25 in the islands). In accordance with the Italian Health Organisation regulations for the assistance of infants, parents are required to choose a paediatrician immediately after the childbirth to be able to receive adequate primary assistance in case of illness or, simply, to monitor the regular development of infants. The paediatricians involved in the present study were asked to record the presence of gastrointestinal symptoms in the first 20 infants to be registered with them during the study period. The data were recorded from the moment the infant was registered up to the age of 6 months. Inclusion criteria were: (a) age at entry to the study of less than 2 weeks; (b) absence of any disease diagnosed before entry to the study. Consequently, infants older than 2 weeks and those with a definite diagnosis of gastroenterological, respiratory, urinary, neurological or metabolic disease were excluded. Data were collected using a standard clinical chart which included: date of birth, sex, weight and height at birth, gestational age, mother’s age and father’s level of education, type of feeding (bottle, breast or mixed). Furthermore, following the medical visits, the paediatricians reported the presence of the following symptoms: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or, in any case, during a set monthly visit. Hospitalisation or feeding changes following the onset of any of the above symptoms were recorded. Constipation was defined as chronic faecal retention characterised by one bowel movement every 3 days or more, often associated with crying fits. Diarrhoea was defined as the
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number of daily bowel movements higher than the 97th percentile for bowel frequency recorded in healthy age-matched infants [1], with very liquid stools. Consequently, the upper limit was six evacuations/day within the first month of life, and 4.5 evacuations/day between the second and sixth months [1]. Vomiting was defined as the loss of a consistent part (about 50% or more) of the previous meal, after retching. Regurgitation was defined as the loss of a small part of the meal, without retching. Failure to thrive was defined as the weight growth of less than 400 g/month, or a decrease in the weight/height curve compared with the previous medical examination. Colic was defined as prolonged fits of crying, without apparent reason, with a mean daily duration of over 3 h, for more than 3 days/week during the previous 2 weeks [2], accompanied by swelling of the abdomen due to intestinal gas and sleep disturbances. Twenty-five clinical monitors visited the paediatricians involved in the study each month to help them compile the clinical charts and to ensure that the data were correctly recorded according to the study protocol definitions. Furthermore, close telephone contact between the paediatricians and the monitors was ensured during the whole period of the study. 2.2. Patients According to the study design, a total of 3000 infants were initially included in the study; however, only 2879 concluded the 6-month period of the study. In fact, the remaining 121 infants were lost from the study as they moved out of the original geographical area (72 cases) or decided to change paediatricians (49 cases). At the time of entry to the study, mean age (±S.D.) of the 2879 infants who concluded the study (1422 f, 1457 m) was 10.1 ± 2.2 days (range 7–13 days). Mean birth weight was 3263 ± 455 g (range 2100–5000 g). Mean gestational age was 39.1 ± 1.4 weeks (range 32–43 weeks). Mean mother’s age was 29.7 ± 4.7 years (range 14–50 years). The father’s level of education was: 4% primary school, 38% lower secondary school, 43% upper secondary school and 15% had a university degree. As regards the type of feeding at entry to the study, 2332 infants (81%) were breast-fed, 230 (8%) were mixed-fed and 317 (11%) were bottle-fed. However, during the study period many infants changed their feeding habits, with a progressive reduction in exclusively breast-fed and an increase in mixed- or bottle-fed subjects. Infants who changed feeding habits during the study period, before the onset of a symptom, were included in the analysis only if the symptom appeared at least 2 weeks after the beginning of the new regimen. Consequently, in evaluating the relationship between the type of feeding and symptoms, we considered ‘breast-fed’ those infants exclusively breast-fed until the onset of a symptom, ‘mixed-fed’ those mixed-fed from at least 2 weeks to the onset of a symptom and ‘bottle-fed’ those exclusively fed with an adapted milk formula from at least 2 weeks.
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No standard guidelines were drawn up to establish the reasons or the time for changes in milk formulas. The paediatricians decided on and suggested a change in formula milk whenever they considered it necessary, both in the presence of gastrointestinal or extra-gastrointestinal symptoms and also for different reasons. The parents of all the infants gave their informed consent to the study and it was approved by the Ethics Committee of the University Hospital of Palermo.
3. Statistical analysis The frequency of each symptom was calculated and expressed as a percentage of the total number of infants included in the study. For each symptom Student’s t-test was used to compare mean values of birth weight, gestational age and mother’s age in the patients with a specific symptom versus all the others without that symptom. Furthermore, the relevance of the low birth weight and the gestational age was evaluated using the χ2 -test; in fact, we compared the frequency of infants with birth weight <2500 g or with gestational age <36 weeks in the patients with a specific symptom versus all the others without that symptom. The same test was used to compare the frequency of the different levels of education of the father and the type of milk feeding in the infants with a specific symptom and in those without that symptom. The χ2 -test was also used to compare the frequency of hospitalisation in the infants with a symptom versus those without that symptom. P-values <0.05 were considered significant.
4. Results During the study period 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms which we scheduled. Regurgitation was the most common disturbance (present in 664/2879 infants, 23.1%), followed by colic (589 cases, 20.5%), constipation (507 cases, 17.6%), failure to thrive (439 cases, 15.2%), vomiting (174 cases, 6%), diarrhoea (117 cases, 4.1%). A single symptom was present in 966 subjects (61.1% of the patients with gastrointestinal symptoms), two symptoms were present in 417 (26.3%), three in 140 (8.8%), four in 50 (3%) and five in 14 (0.8%). 4.1. Factors associated with each symptom Regurgitation was present in 334 males and 330 females. It was diagnosed at a mean age (±S.D.) of 32 ± 25 days. Infants with regurgitation had a lower birth weight and gestational age than those without this symptom (3213 ± 461 g versus 3279 ± 453 g; t = 3.24; P < 0.001 for birth weight; 38.98 ± 1.36 weeks versus 39.17 ± 1.48 weeks; t = 2.79; P < 0.005 for gestational age). Furthermore, in the infants with birth weight lower than 2500 g, the frequency of regurgitation was higher than in all the other infants (30.6% ver-
sus 22.9%; χ2 = 3.8; P < 0.05). No difference was observed as regards mother’s age, father’s level of education and type of feeding. Colic was present in 589/2879 infants (279 males and 310 females). It was diagnosed at a mean age (±S.D.) of 31 ± 21 days. There was no difference in the parameters considered in this study between infants with colic and those without this symptom. Constipation was present in 507/2879 infants (252 males and 255 females). It was diagnosed at a mean age (±S.D.) of 33 ± 27 days. Infants with constipation did not differ from those without this symptom in terms of birth weight, gestational age, mother’s age and father’s level of education; however, there was a significantly lower frequency of breast feeding than in infants without constipation (76.3% versus 84.9%; χ2 = 9.9; P = 0.007). Failure to thrive was recorded in 439/2879 infants (182 males and 257 females). It was observed at a mean age (±S.D.) of 59 ± 42 days. The infants with low growth had a lower birth weight than all the other study subjects (3174 ± 449 g versus 3280 ± 455 g; t = 4.502; P < 0.001). There was no difference in any of the other parameters evaluated between the subjects with failure to thrive and those with normal growth. Vomiting was present in 174/2879 infants (84 males and 90 females). This symptom was diagnosed at a mean age (±S.D.) of 43 ± 30 days. The infants with vomiting had a significantly lower birth weight than all the others included in the study (3200 ± 451 g versus 3270 ± 445 g; t = 1.95; P < 0.05). Furthermore, the frequency of vomiting in infants with birth weight lower than 2500 g was higher than in all the other infants (10.2% versus 6%; χ2 = 3.5; P < 0.05). There was no difference between them and all the other infants for any of the other parameters evaluated. Diarrhoea was present in 117/2879 infants (55 males and 62 females). This symptom was diagnosed at a mean age (±S.D.) of 60 ± 41 days. The infants with diarrhoea had a lower gestational age than all the other infants (38.71 ± 1.71 weeks versus 39.15 ± 1.44 weeks; P < 0.002), and the frequency of diarrhoea in infants with gestational age below 36 weeks was higher than in all the other infants (14.6% versus 3.9%; χ2 = 12.1; P < 0.01). In all the other parameters considered (birth weight, mother’s age, father’s level of education and type of feeding) there were no differences between infants with diarrhoea and those without. Table 1 summarises the association between each symptom observed during the study and the variables considered as possible causal factors. Low birth weight appeared to be the most common influencing factor in determining the onset of gastrointestinal symptoms. 4.2. Frequency and causes of hospitalisation During the study period, 93 infants (3.2% of the infants included in the study: 50 males, 43 females) were hospitalised for one or more of the gastrointestinal symptoms we consid-
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Table 1 Association between the presence of symptoms and the variables considered in the study
Sex Low birth weight Low gestational age Mother’s age Father’s level of education Type of feeding
Regurgitation (N = 664)
Colic (N = 589)
Constipation (N = 507)
Failure to thrive (N = 439)
Vomiting (N = 174)
Diarrhoea (N = 117)
N.S. P < 0.001 P < 0.005 N.S. N.S. N.S.
N.S. N.S. N.S. N.S. N.S. N.S.
N.S. N.S. N.S. N.S. N.S. P < 0.007a
N.S. P < 0.001 N.S. N.S. N.S. N.S.
N.S. P < 0.05 N.S. N.S. N.S. N.S.
N.S. N.S. P < 0.002 N.S. N.S. N.S.
For each symptom the patients suffering from that symptom were compared with all the other subjects included in the study. A total of 2879 infants were studied. a Infants with constipation showed a lower frequency of breast-feeding than the infants without constipation: 76.3% versus 84.9% (χ2 = 9.9; P = 0.007).
ered. Mean age at hospitalisation was 50 ± 27 days. A single symptom caused hospitalisation in 35/93 cases, two associated symptoms in 49/93 infants, three symptoms in 5/93 cases, four in 2/93 cases and five in 2/93 cases. Fig. 1 shows the frequency of each symptom as the cause of hospitalisation. In view of its high frequency in our study population, regurgitation was the most frequent symptom in the hospitalised patients. However, only 6.2% of the infants with regurgitation were hospitalised (frequency of hospitalisation in patients with regurgitation versus all the other infants included in the study: P = 0.026). Furthermore, hospitalisation was necessary in 5.8% of the infants with colic (P < .0001 versus all the other infants), 7.5% of the infants with failure to thrive (P < 0.001 versus all the other infants), 12.1% of the infants with vomiting (P < 0.0001 versus all the other infants), 14.5% of the infants with diarrhoea (P < 0.0001 versus all the other infants) and 3.9% of the infants with constipation (difference not significant versus all the other infants). Finally, as regards the influence of the gastrointestinal symptoms in determining a change in feeding, we recorded that during the whole study period the type of milk feeding was changed in 1152/2879 (40%) on the advice of the paediatrician. In detail, a change of feeding was suggested in 949/1582 (60%) infants with one or more of the gastrointestinal symptoms we recorded, and in 203/1297 (15.5%) of the infants who did not suffer from any gastrointestinal problems (in 192 out of these 203 due to the presence of
Fig. 1. Frequency (number and percentage of the total number of cases of hospitalisation) of regurgitation, colic, constipation, failure to thrive, vomiting and diarrhoea as the cause of hospitalisation in the 93 infants who were hospitalised for gastrointestinal symptoms during the first 6 months after birth. More than one symptom in the same subject may have led to hospitalisation.
dermatological or respiratory symptoms, in 11 patients for reasons not recorded). As regards each symptom, a change in feeding was suggested in 414/664 (62.3%) infants with regurgitation (P < 0.0001 versus all the other infants included in the study), 303/589 (51.4%) infants with colic (P < 0.0001 versus all the other infants included in the study), 253/507 (49.9%) infants with constipation (P < 0.0001 versus all the other infants included in the study), 278/439 (63.4%) infants with failure to thrive (P < 0.0001 versus all the other infants included in the study), 113/174 (65%) infants with vomiting (P < 0.0001 versus all the other infants included in the study), and 76/117 (64.6%) infants with diarrhoea (P < 0.0001 versus all the other infants in the study). In none of the infants who were breast-fed at the onset of their symptoms a change in feeding habit was suggested. A feeding change was suggested in mixed- or bottle-fed infants who were receiving various cow-milk-derived, adapted formulas.
5. Discussion The presence of gastrointestinal symptoms is a frequent problem in paediatric patients and often determines numerous visits to the paediatrician, changes in feeding, parental anxiety and loss of parents’ working days. Despite these relevant sanitary and social aspects, very little is known about the frequency of the ‘minor’ gastrointestinal disturbances in infancy and the possible determining factors associated with their onset. In fact, to our knowledge, no epidemiological studies have evaluated these aspects in the general population. Consequently, we performed the present prospective population-based study to evaluate the frequency, from birth to 6 months, of the six disturbances which we considered the most common in infants: regurgitation, vomiting, diarrhoea, constipation, colic and failure to thrive. To do so, we requested the collaboration of 150 paediatricians distributed throughout Italy, who monitored approximately 3000 healthy infants. A printed clinical chart allowed us to obtain detailed information about the onset of gastrointestinal disturbances and the presence of possible associated causal factors. Our results showed that the ‘minor’ gastrointestinal disturbances are frequent in infants: in fact, we observed a symp-
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tom in over half of the infants studied (1582/2879; 54.9%). Regurgitation was the most common disturbance, as it was present in 664/2879 infants (23.1%). This result was not at all surprising, as regurgitation can be considered a physiological phenomenon in infants in the first year of life [3] and it has been reported that 50% of all infants 0–3 months regurgitate at least once a day [4]. It is due to gastro-oesophageal reflux (GER), whose frequency in children has been estimated between 1% and 22% [5,6], but most infants with regurgitation and GER are not brought to medical attention [7]. Vomiting, another symptom which could indicate GER, was found in our study in a much lower percentage of infants than regurgitation: 6%. However, it must be remembered that this symptom can be due to a number of different pathological conditions, such as central nervous system diseases, pyloric stenosis, etc., and it cannot automatically be associated with GER [8,9]. The second most frequent symptom we recorded was infantile colic. Frequency in our study was 20.5%, thus in the range (16–48%) of the incidence estimated in other studies [2,10]. It is known that the pathogenesis of infantile colic is considered to be either based on psycho-social factors and disturbances in the mother-child relationship [11], or linked to cow’s milk protein intolerance [12,13], or to GER [14]. These latter two diseases can be treated with a dietary approach. Constipation was the third most frequent symptom we observed, as it was present in 17.6% of the infants. Our definition of constipation (‘one bowel movement every 3 days or more’) is lower than the third percentile of bowel movement frequency in healthy age-matched infants [1]. To our knowledge, there are no other studies reporting the frequency of constipation in neonates or infants younger than 6 months. It is noteworthy that in the present study constipation was linked to a lower frequency of breast-feeding; this result is in agreement with previous evidence that breast-fed healthy infants pass stools almost 50% more often than formula-fed infants [1]. In general, low birth weight was the factor most frequently associated with the presence of gastrointestinal symptoms. This is in agreement with previous studies which reported impaired digestive function not only in pre-term infants but also in full-term infants small for their gestational age [15]. Despite the very high frequency of gastrointestinal symptoms, only 3.2% of the infants (93/2879) were hospitalised for one or more of these symptoms. Hospitalisation was probably determined by the presence of more than one single symptom; in fact 58/93 hospitalised infants had two or more gastroenterological symptoms as has been reported in the cases of vomiting and constipation [16]. Finally, it is interesting to recall the relationship between the type of feeding given to the studied infants and their gastroenterological disturbances. In general, our study population was characterised by a high frequency of breast-feeding (81%) and a correspondingly low frequency of bottle-feeding (11%), at the beginning of the study. In contrast with the
more obvious expectations, we did not find a higher frequency of gastrointestinal symptoms in bottle-fed than in breast-fed infants. The only influence of the type of feeding was recorded in constipated infants with a lower frequency of breast-feeding than infants without constipation. As several studies have underlined the great and numerous advantages of breast-feeding [17,18], the observation of a low relation between bottle-feeding and gastrointestinal symptoms in the first 6 months after birth must not determine any change in the paediatric policy of encouraging the diffusion of breastfeeding. Furthermore, it must be considered that during the study period many infants changed their feeding, suspending breast-feeding and beginning mixed- or exclusively bottlefeeding. Another aspect to comment on is the influence that the onset of a gastrointestinal symptom had on feeding. In patients with one or more gastrointestinal symptoms a change was observed in about 60%, whereas it was recorded in only 15.5% of the infants without gastrointestinal troubles (in these cases mainly due to the appearance of respiratory or dermatological symptoms). This result seems to indicate that gastrointestinal symptoms are the main reason for change feeding in infants. Although we have no data as to the type of new milk formula prescribed at the onset of the gastrointestinal symptoms, it appears obvious to hypothesise that a number of ‘thickened’, lactose-free, partially hydrolysed, and/or other ‘curing’ formulas were prescribed. The cost of these ‘dietary’ formulas is generally much higher than that of the common adapted formulas; consequently the economic impact of the ‘minor’ gastrointestinal troubles of the infants merits a more detailed investigation and the real usefulness of the change in milk formula should be evaluated in future studies, although there is evidence that both regurgitation, GER and colic can improve with dietary treatment [4,6,19,20]. In conclusion, we found that gastrointestinal symptoms are very common in infants during the first 6 months after birth; these symptoms caused hospitalisation in a small percentage of cases (3%), but determined the prescription of a ‘dietary’ milk formula in about 60% of cases. Conflict of interest statement None declared. Acknowledgement We would like to thank Mrs. Carole Greenall for her precious revision of the English. Appendix A. Paediatric Study Group on Gastrointestinal Symptoms in Infancy Paediatricians involved in the study to record the presence of gastro-intestinal symptoms in the first 20 infants registered with them during the study period:
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Di Palma Salvatore, Bartolucci Giuliana, Palumbo Marina, Collacciani Giuseppe, Cappellini Cristina, Santilli Antonella, Righetti Maria, Santirocco Maria Rita, Petitta Marco, Massimino Stefania, Ferraro Gabriella, Crua Giorgio, Zicari Francesco, Mietta Adriano, Baldassar Ferraro AnnaMaria, Martino Filomena, Imperiale Claudio, Barrile Luciano, Sanni Letteria, Gatto Silvana, D’urso Giovanna, Fiamingo Mario, Gattarello Annunziata, Martelli Dafne, Cinconze Salvatore, Moroni Emiliano, Caronariti Valeria, Bravetti Emanuela, Martines Maristella, Pellegrini Lucia, Serra Margherita, De Felicis Arcangeli Carla, Cesarini A.Rita, Paolini Fabrizia, Candio Francesco, Orr`u Gennaro, Bellaveglia M.Luisa, Gramenzi Rita, Bianchini Fabrizio, Bonsi Simonetta, Gozzo Matilda, Franchini Maddalena, Miglioranzi Paola, Previdi Mauro, Melotti Giancarlo, Monicelli Ugo, Martone Gabriella, Reali Laura, Manetta Fiorella, Ferrazzoli Maria Lucia, Diamanti Isabella, Falletta Salvatore, La Cava Giovanna, Paoletti Silvia, Andreini Carla, Bianchera Raffaella, Locatelli M. Elisa, Mannori Carlo, Sabatini Walter, Pasquini Anna, Pasquini Fulvio, Grossi Cristina, Belsito Luisa, Rana Pierangela, Scadavecchia Laura, Balducci Ottavio, Peccarisi Lucia, Bonvino Angelica, De Laurentis Lelio, Zarella Mariolina, Farinelli Claudio, Pasquantonio Antonella, Antogiovanni Assunta, Antogiovanni Luigi, Favi Valeria, De Vino Annette, Totaro Lucia, Becattini Laura, Casaregola Matilde, Barone Patrizia, Dau Giovanna, Argellati Sandra, Testori Franco, Maggiani Giuliano, Antonini Emanuela, Bawa Paola, Pandolfi Maria Eva, Borsellino Giuseppe, Mognaschi Claudia, De Martino Flavia, Perfetti Miriam, Longoni Rosa Maria, Marchione Laura, Invernizzi Lorella, Salvioni Francesca, Mariani Daniela, Gelpi Bruna, Carchesio Isidora, De Angelis Monica, Thiebat Elena, Romeo Lucia, Bollani Tiziana, Colombo Mania, Florioli Alessandro, De Poli Daniela, Bonori Massimo, Barbera Caterina, Denis Franca, Calore AnnaMaria, Criconia Carla, Giaretta Letizia, Menegus Elena, Passuello Giovanna, Turio Chiara, Ranieri Luigi, Grotteria Salvatore, Lentidoro Irene, Pelaggi Paola, Gullo Paola, Marino Filippo, Giancotti Laura, Licata Caruso Donatella, Esposito Andreina, Chianese Anna Maria, Masini Luigi, Greco Palmira, Lamanna Sergio, Maida Walter, Iovine Alfredo, Vitiello Giuseppe, Mariani Laura, Botto Anna, Cuocco Anna, Rampini Luigina, Pioggio Cinzia, Bellati Rosanna, Fontana Carla, Ettore Silvia, Gatto Fulvia, Caneva Egidio, Bianchi Gianpiero, Calcante Sara, Perrone Maria Sara, Saggese Teresa, Fallarino Stefania, Boffelli Elena, Aramini Lucio, Cornalba Ludovico, D’amato Vincenza, La Macchia Nicola, Mineo Santa, Paternostro Daniela, Piric`o Laura,Scillieri Maria Adriana, Costagliola Rosalba, Spataro Maria, Frezzetti Andrea, Fattore Stanislao, Coronella Angelo, Brunese Francesco Paolo, Minichino Anna Maria, De Vita Sergio, Mandia Francesco, Falcone Anna Maria, Mastrominico Augusto, Cavazzuti Donatella, Boschini Cesare, Baroni Isabella, Mazzini Franco, Ponti Roberto, Lucchi Elide, Faedi Clara, Trebbi Miro, Mele Roberto, Cera Melania, Rosas Paolo, Pala Antonio, Urru Luciano, Piras Stella, Zichera Tiziana, Cartone Franca, Centamore Maria,
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Ferro Sebastiana, Duminuco Calogera, Caltabiano Loredana, Scaringi Carmelo, Spedace Antonella and Francario Elisabetta. Clinical monitors who visited the paediatricians involved in the study to help them compile the clinical charts and to verify that the data were recorded correctly according to the study protocol definitions: Cinque Massimo, Coppo Elena, De Leo Silvana, Del Giudice, Di Bitetto Rosa Rina, Ferraro Luigi, Ganzarolli Stefania, Gibaldi Giovanni, Landini Luca, Losurdo Luigi, Maraglino Vita Maria, Merusi Ilaria, Moscatelli Daniela, Otelli Valeria, Panisi Cristina, Panizzolo Cristina, Pensabene Lucia, Porzio Salvatore, Ravera Brunella, Ricci Antonio, Russo Delia, Stabile Donatella, Viola Laura, Putzu Sandro and Montes Sebastiana.
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[16] Borowitz SM, Sutphen JL. Recurrent vomiting and persistent gastroesophageal reflux caused by unrecognized constipation. Clin Pediatr (Phila) 2004;43:461–6. [17] Lawrence RA. Promotion of Breast-feeding Intervention Trial (PROBIT) a randomized trial in the Republic of Belarus. J Pediatr 2001;139:164–5. [18] Castro-Rodriguez JA, Stern DA, Halonen M, Wright AL, Holberg CJ, Tussig LM, et al. Relation between infantile colic and
asthma/atopy: a prospective study in an unselected population. Pediatrics 2001;108:878–82. [19] Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, Husby S. Severe gastro-esophageal reflux disease and cow’s milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure. J Pediatr Gastroenterol Nutr 2004;39:383–91. [20] Miller-Loncar C, Bigsby R, High P, Wallach M, Lester B. Infant colic and feeding difficulties. Arch Dis Child 2004;89:908–12.
Alimentary Tract
Gastrointestinal symptoms in infancy: A population-based prospective study G. Iacono a , R. Merolla b , D. D’Amico a , E. Bonci c , F. Cavataio a , L. Di Prima d , C. Scalici a , L. Indinnimeo c , M.R. Averna d , A. Carroccio d,∗ the Paediatric Study Group on Gastrointestinal Symptoms in Infancy1 a
d
Paediatric Gastroenterology, ‘Di Cristina’ Hospital of Palermo, Italy b Medical Department, ABBOTT, Italy c Paediatric Department, University of Rome ‘La Sapienza’, Italy Internal Medicine, University Hospital of Palermo, via Coffaro 25, Palermo 90124, Italy Received 23 August 2004; accepted 17 January 2005 Available online 2 March 2005
Abstract Background. During the first months of life, infants can suffer from many ‘minor’ gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. Aims. (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. Study design and patients. Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. Results. 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breastfeeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. Conclusions. Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a ‘dietary’ milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms. © 2005 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. Keywords: Colic; Constipation; Diarrhoea; Epidemiology; Failure to thrive; Feeding; Infancy; Regurgitation; Vomiting
1. Introduction
∗ 1
Corresponding author. Tel.: +39 091 6552860; fax: +39 091 6552936. E-mail address: [email protected] (A. Carroccio). See Appendix A.
During the first months after birth our gastrointestinal system strives to adapt itself to the various nutrients in order to perfect its digestive, absorptive and immunological functions. Obviously, during this ‘stressful’ period infants can suf-
1590-8658/$30 © 2005 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. doi:10.1016/j.dld.2005.01.009
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fer from many gastroenterological disturbances, which in the majority of cases are dealt with by paediatricians without the need for hospitalisation and/or laboratory/instrumental investigations. However, little is known about the real frequency of these ‘minor’ gastrointestinal disturbances, the factors which predispose or facilitate their onset and the relationship between these disturbances and the type of feeding the infants receive. The aims of the present prospective, population-based study were: (a) to ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence that some variables have on the onset of these symptoms; (c) to clarify the causes for hospitalisation due to gastrointestinal disturbances.
2. Patients and methods 2.1. Study design The study was carried out between January and December 1999 with the collaboration of 150 paediatricians distributed throughout Italy (40 in the north of Italy, 35 in the centre, 40 in the south and 25 in the islands). In accordance with the Italian Health Organisation regulations for the assistance of infants, parents are required to choose a paediatrician immediately after the childbirth to be able to receive adequate primary assistance in case of illness or, simply, to monitor the regular development of infants. The paediatricians involved in the present study were asked to record the presence of gastrointestinal symptoms in the first 20 infants to be registered with them during the study period. The data were recorded from the moment the infant was registered up to the age of 6 months. Inclusion criteria were: (a) age at entry to the study of less than 2 weeks; (b) absence of any disease diagnosed before entry to the study. Consequently, infants older than 2 weeks and those with a definite diagnosis of gastroenterological, respiratory, urinary, neurological or metabolic disease were excluded. Data were collected using a standard clinical chart which included: date of birth, sex, weight and height at birth, gestational age, mother’s age and father’s level of education, type of feeding (bottle, breast or mixed). Furthermore, following the medical visits, the paediatricians reported the presence of the following symptoms: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or, in any case, during a set monthly visit. Hospitalisation or feeding changes following the onset of any of the above symptoms were recorded. Constipation was defined as chronic faecal retention characterised by one bowel movement every 3 days or more, often associated with crying fits. Diarrhoea was defined as the
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number of daily bowel movements higher than the 97th percentile for bowel frequency recorded in healthy age-matched infants [1], with very liquid stools. Consequently, the upper limit was six evacuations/day within the first month of life, and 4.5 evacuations/day between the second and sixth months [1]. Vomiting was defined as the loss of a consistent part (about 50% or more) of the previous meal, after retching. Regurgitation was defined as the loss of a small part of the meal, without retching. Failure to thrive was defined as the weight growth of less than 400 g/month, or a decrease in the weight/height curve compared with the previous medical examination. Colic was defined as prolonged fits of crying, without apparent reason, with a mean daily duration of over 3 h, for more than 3 days/week during the previous 2 weeks [2], accompanied by swelling of the abdomen due to intestinal gas and sleep disturbances. Twenty-five clinical monitors visited the paediatricians involved in the study each month to help them compile the clinical charts and to ensure that the data were correctly recorded according to the study protocol definitions. Furthermore, close telephone contact between the paediatricians and the monitors was ensured during the whole period of the study. 2.2. Patients According to the study design, a total of 3000 infants were initially included in the study; however, only 2879 concluded the 6-month period of the study. In fact, the remaining 121 infants were lost from the study as they moved out of the original geographical area (72 cases) or decided to change paediatricians (49 cases). At the time of entry to the study, mean age (±S.D.) of the 2879 infants who concluded the study (1422 f, 1457 m) was 10.1 ± 2.2 days (range 7–13 days). Mean birth weight was 3263 ± 455 g (range 2100–5000 g). Mean gestational age was 39.1 ± 1.4 weeks (range 32–43 weeks). Mean mother’s age was 29.7 ± 4.7 years (range 14–50 years). The father’s level of education was: 4% primary school, 38% lower secondary school, 43% upper secondary school and 15% had a university degree. As regards the type of feeding at entry to the study, 2332 infants (81%) were breast-fed, 230 (8%) were mixed-fed and 317 (11%) were bottle-fed. However, during the study period many infants changed their feeding habits, with a progressive reduction in exclusively breast-fed and an increase in mixed- or bottle-fed subjects. Infants who changed feeding habits during the study period, before the onset of a symptom, were included in the analysis only if the symptom appeared at least 2 weeks after the beginning of the new regimen. Consequently, in evaluating the relationship between the type of feeding and symptoms, we considered ‘breast-fed’ those infants exclusively breast-fed until the onset of a symptom, ‘mixed-fed’ those mixed-fed from at least 2 weeks to the onset of a symptom and ‘bottle-fed’ those exclusively fed with an adapted milk formula from at least 2 weeks.
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No standard guidelines were drawn up to establish the reasons or the time for changes in milk formulas. The paediatricians decided on and suggested a change in formula milk whenever they considered it necessary, both in the presence of gastrointestinal or extra-gastrointestinal symptoms and also for different reasons. The parents of all the infants gave their informed consent to the study and it was approved by the Ethics Committee of the University Hospital of Palermo.
3. Statistical analysis The frequency of each symptom was calculated and expressed as a percentage of the total number of infants included in the study. For each symptom Student’s t-test was used to compare mean values of birth weight, gestational age and mother’s age in the patients with a specific symptom versus all the others without that symptom. Furthermore, the relevance of the low birth weight and the gestational age was evaluated using the χ2 -test; in fact, we compared the frequency of infants with birth weight <2500 g or with gestational age <36 weeks in the patients with a specific symptom versus all the others without that symptom. The same test was used to compare the frequency of the different levels of education of the father and the type of milk feeding in the infants with a specific symptom and in those without that symptom. The χ2 -test was also used to compare the frequency of hospitalisation in the infants with a symptom versus those without that symptom. P-values <0.05 were considered significant.
4. Results During the study period 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms which we scheduled. Regurgitation was the most common disturbance (present in 664/2879 infants, 23.1%), followed by colic (589 cases, 20.5%), constipation (507 cases, 17.6%), failure to thrive (439 cases, 15.2%), vomiting (174 cases, 6%), diarrhoea (117 cases, 4.1%). A single symptom was present in 966 subjects (61.1% of the patients with gastrointestinal symptoms), two symptoms were present in 417 (26.3%), three in 140 (8.8%), four in 50 (3%) and five in 14 (0.8%). 4.1. Factors associated with each symptom Regurgitation was present in 334 males and 330 females. It was diagnosed at a mean age (±S.D.) of 32 ± 25 days. Infants with regurgitation had a lower birth weight and gestational age than those without this symptom (3213 ± 461 g versus 3279 ± 453 g; t = 3.24; P < 0.001 for birth weight; 38.98 ± 1.36 weeks versus 39.17 ± 1.48 weeks; t = 2.79; P < 0.005 for gestational age). Furthermore, in the infants with birth weight lower than 2500 g, the frequency of regurgitation was higher than in all the other infants (30.6% ver-
sus 22.9%; χ2 = 3.8; P < 0.05). No difference was observed as regards mother’s age, father’s level of education and type of feeding. Colic was present in 589/2879 infants (279 males and 310 females). It was diagnosed at a mean age (±S.D.) of 31 ± 21 days. There was no difference in the parameters considered in this study between infants with colic and those without this symptom. Constipation was present in 507/2879 infants (252 males and 255 females). It was diagnosed at a mean age (±S.D.) of 33 ± 27 days. Infants with constipation did not differ from those without this symptom in terms of birth weight, gestational age, mother’s age and father’s level of education; however, there was a significantly lower frequency of breast feeding than in infants without constipation (76.3% versus 84.9%; χ2 = 9.9; P = 0.007). Failure to thrive was recorded in 439/2879 infants (182 males and 257 females). It was observed at a mean age (±S.D.) of 59 ± 42 days. The infants with low growth had a lower birth weight than all the other study subjects (3174 ± 449 g versus 3280 ± 455 g; t = 4.502; P < 0.001). There was no difference in any of the other parameters evaluated between the subjects with failure to thrive and those with normal growth. Vomiting was present in 174/2879 infants (84 males and 90 females). This symptom was diagnosed at a mean age (±S.D.) of 43 ± 30 days. The infants with vomiting had a significantly lower birth weight than all the others included in the study (3200 ± 451 g versus 3270 ± 445 g; t = 1.95; P < 0.05). Furthermore, the frequency of vomiting in infants with birth weight lower than 2500 g was higher than in all the other infants (10.2% versus 6%; χ2 = 3.5; P < 0.05). There was no difference between them and all the other infants for any of the other parameters evaluated. Diarrhoea was present in 117/2879 infants (55 males and 62 females). This symptom was diagnosed at a mean age (±S.D.) of 60 ± 41 days. The infants with diarrhoea had a lower gestational age than all the other infants (38.71 ± 1.71 weeks versus 39.15 ± 1.44 weeks; P < 0.002), and the frequency of diarrhoea in infants with gestational age below 36 weeks was higher than in all the other infants (14.6% versus 3.9%; χ2 = 12.1; P < 0.01). In all the other parameters considered (birth weight, mother’s age, father’s level of education and type of feeding) there were no differences between infants with diarrhoea and those without. Table 1 summarises the association between each symptom observed during the study and the variables considered as possible causal factors. Low birth weight appeared to be the most common influencing factor in determining the onset of gastrointestinal symptoms. 4.2. Frequency and causes of hospitalisation During the study period, 93 infants (3.2% of the infants included in the study: 50 males, 43 females) were hospitalised for one or more of the gastrointestinal symptoms we consid-
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Table 1 Association between the presence of symptoms and the variables considered in the study
Sex Low birth weight Low gestational age Mother’s age Father’s level of education Type of feeding
Regurgitation (N = 664)
Colic (N = 589)
Constipation (N = 507)
Failure to thrive (N = 439)
Vomiting (N = 174)
Diarrhoea (N = 117)
N.S. P < 0.001 P < 0.005 N.S. N.S. N.S.
N.S. N.S. N.S. N.S. N.S. N.S.
N.S. N.S. N.S. N.S. N.S. P < 0.007a
N.S. P < 0.001 N.S. N.S. N.S. N.S.
N.S. P < 0.05 N.S. N.S. N.S. N.S.
N.S. N.S. P < 0.002 N.S. N.S. N.S.
For each symptom the patients suffering from that symptom were compared with all the other subjects included in the study. A total of 2879 infants were studied. a Infants with constipation showed a lower frequency of breast-feeding than the infants without constipation: 76.3% versus 84.9% (χ2 = 9.9; P = 0.007).
ered. Mean age at hospitalisation was 50 ± 27 days. A single symptom caused hospitalisation in 35/93 cases, two associated symptoms in 49/93 infants, three symptoms in 5/93 cases, four in 2/93 cases and five in 2/93 cases. Fig. 1 shows the frequency of each symptom as the cause of hospitalisation. In view of its high frequency in our study population, regurgitation was the most frequent symptom in the hospitalised patients. However, only 6.2% of the infants with regurgitation were hospitalised (frequency of hospitalisation in patients with regurgitation versus all the other infants included in the study: P = 0.026). Furthermore, hospitalisation was necessary in 5.8% of the infants with colic (P < .0001 versus all the other infants), 7.5% of the infants with failure to thrive (P < 0.001 versus all the other infants), 12.1% of the infants with vomiting (P < 0.0001 versus all the other infants), 14.5% of the infants with diarrhoea (P < 0.0001 versus all the other infants) and 3.9% of the infants with constipation (difference not significant versus all the other infants). Finally, as regards the influence of the gastrointestinal symptoms in determining a change in feeding, we recorded that during the whole study period the type of milk feeding was changed in 1152/2879 (40%) on the advice of the paediatrician. In detail, a change of feeding was suggested in 949/1582 (60%) infants with one or more of the gastrointestinal symptoms we recorded, and in 203/1297 (15.5%) of the infants who did not suffer from any gastrointestinal problems (in 192 out of these 203 due to the presence of
Fig. 1. Frequency (number and percentage of the total number of cases of hospitalisation) of regurgitation, colic, constipation, failure to thrive, vomiting and diarrhoea as the cause of hospitalisation in the 93 infants who were hospitalised for gastrointestinal symptoms during the first 6 months after birth. More than one symptom in the same subject may have led to hospitalisation.
dermatological or respiratory symptoms, in 11 patients for reasons not recorded). As regards each symptom, a change in feeding was suggested in 414/664 (62.3%) infants with regurgitation (P < 0.0001 versus all the other infants included in the study), 303/589 (51.4%) infants with colic (P < 0.0001 versus all the other infants included in the study), 253/507 (49.9%) infants with constipation (P < 0.0001 versus all the other infants included in the study), 278/439 (63.4%) infants with failure to thrive (P < 0.0001 versus all the other infants included in the study), 113/174 (65%) infants with vomiting (P < 0.0001 versus all the other infants included in the study), and 76/117 (64.6%) infants with diarrhoea (P < 0.0001 versus all the other infants in the study). In none of the infants who were breast-fed at the onset of their symptoms a change in feeding habit was suggested. A feeding change was suggested in mixed- or bottle-fed infants who were receiving various cow-milk-derived, adapted formulas.
5. Discussion The presence of gastrointestinal symptoms is a frequent problem in paediatric patients and often determines numerous visits to the paediatrician, changes in feeding, parental anxiety and loss of parents’ working days. Despite these relevant sanitary and social aspects, very little is known about the frequency of the ‘minor’ gastrointestinal disturbances in infancy and the possible determining factors associated with their onset. In fact, to our knowledge, no epidemiological studies have evaluated these aspects in the general population. Consequently, we performed the present prospective population-based study to evaluate the frequency, from birth to 6 months, of the six disturbances which we considered the most common in infants: regurgitation, vomiting, diarrhoea, constipation, colic and failure to thrive. To do so, we requested the collaboration of 150 paediatricians distributed throughout Italy, who monitored approximately 3000 healthy infants. A printed clinical chart allowed us to obtain detailed information about the onset of gastrointestinal disturbances and the presence of possible associated causal factors. Our results showed that the ‘minor’ gastrointestinal disturbances are frequent in infants: in fact, we observed a symp-
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tom in over half of the infants studied (1582/2879; 54.9%). Regurgitation was the most common disturbance, as it was present in 664/2879 infants (23.1%). This result was not at all surprising, as regurgitation can be considered a physiological phenomenon in infants in the first year of life [3] and it has been reported that 50% of all infants 0–3 months regurgitate at least once a day [4]. It is due to gastro-oesophageal reflux (GER), whose frequency in children has been estimated between 1% and 22% [5,6], but most infants with regurgitation and GER are not brought to medical attention [7]. Vomiting, another symptom which could indicate GER, was found in our study in a much lower percentage of infants than regurgitation: 6%. However, it must be remembered that this symptom can be due to a number of different pathological conditions, such as central nervous system diseases, pyloric stenosis, etc., and it cannot automatically be associated with GER [8,9]. The second most frequent symptom we recorded was infantile colic. Frequency in our study was 20.5%, thus in the range (16–48%) of the incidence estimated in other studies [2,10]. It is known that the pathogenesis of infantile colic is considered to be either based on psycho-social factors and disturbances in the mother-child relationship [11], or linked to cow’s milk protein intolerance [12,13], or to GER [14]. These latter two diseases can be treated with a dietary approach. Constipation was the third most frequent symptom we observed, as it was present in 17.6% of the infants. Our definition of constipation (‘one bowel movement every 3 days or more’) is lower than the third percentile of bowel movement frequency in healthy age-matched infants [1]. To our knowledge, there are no other studies reporting the frequency of constipation in neonates or infants younger than 6 months. It is noteworthy that in the present study constipation was linked to a lower frequency of breast-feeding; this result is in agreement with previous evidence that breast-fed healthy infants pass stools almost 50% more often than formula-fed infants [1]. In general, low birth weight was the factor most frequently associated with the presence of gastrointestinal symptoms. This is in agreement with previous studies which reported impaired digestive function not only in pre-term infants but also in full-term infants small for their gestational age [15]. Despite the very high frequency of gastrointestinal symptoms, only 3.2% of the infants (93/2879) were hospitalised for one or more of these symptoms. Hospitalisation was probably determined by the presence of more than one single symptom; in fact 58/93 hospitalised infants had two or more gastroenterological symptoms as has been reported in the cases of vomiting and constipation [16]. Finally, it is interesting to recall the relationship between the type of feeding given to the studied infants and their gastroenterological disturbances. In general, our study population was characterised by a high frequency of breast-feeding (81%) and a correspondingly low frequency of bottle-feeding (11%), at the beginning of the study. In contrast with the
more obvious expectations, we did not find a higher frequency of gastrointestinal symptoms in bottle-fed than in breast-fed infants. The only influence of the type of feeding was recorded in constipated infants with a lower frequency of breast-feeding than infants without constipation. As several studies have underlined the great and numerous advantages of breast-feeding [17,18], the observation of a low relation between bottle-feeding and gastrointestinal symptoms in the first 6 months after birth must not determine any change in the paediatric policy of encouraging the diffusion of breastfeeding. Furthermore, it must be considered that during the study period many infants changed their feeding, suspending breast-feeding and beginning mixed- or exclusively bottlefeeding. Another aspect to comment on is the influence that the onset of a gastrointestinal symptom had on feeding. In patients with one or more gastrointestinal symptoms a change was observed in about 60%, whereas it was recorded in only 15.5% of the infants without gastrointestinal troubles (in these cases mainly due to the appearance of respiratory or dermatological symptoms). This result seems to indicate that gastrointestinal symptoms are the main reason for change feeding in infants. Although we have no data as to the type of new milk formula prescribed at the onset of the gastrointestinal symptoms, it appears obvious to hypothesise that a number of ‘thickened’, lactose-free, partially hydrolysed, and/or other ‘curing’ formulas were prescribed. The cost of these ‘dietary’ formulas is generally much higher than that of the common adapted formulas; consequently the economic impact of the ‘minor’ gastrointestinal troubles of the infants merits a more detailed investigation and the real usefulness of the change in milk formula should be evaluated in future studies, although there is evidence that both regurgitation, GER and colic can improve with dietary treatment [4,6,19,20]. In conclusion, we found that gastrointestinal symptoms are very common in infants during the first 6 months after birth; these symptoms caused hospitalisation in a small percentage of cases (3%), but determined the prescription of a ‘dietary’ milk formula in about 60% of cases. Conflict of interest statement None declared. Acknowledgement We would like to thank Mrs. Carole Greenall for her precious revision of the English. Appendix A. Paediatric Study Group on Gastrointestinal Symptoms in Infancy Paediatricians involved in the study to record the presence of gastro-intestinal symptoms in the first 20 infants registered with them during the study period:
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Di Palma Salvatore, Bartolucci Giuliana, Palumbo Marina, Collacciani Giuseppe, Cappellini Cristina, Santilli Antonella, Righetti Maria, Santirocco Maria Rita, Petitta Marco, Massimino Stefania, Ferraro Gabriella, Crua Giorgio, Zicari Francesco, Mietta Adriano, Baldassar Ferraro AnnaMaria, Martino Filomena, Imperiale Claudio, Barrile Luciano, Sanni Letteria, Gatto Silvana, D’urso Giovanna, Fiamingo Mario, Gattarello Annunziata, Martelli Dafne, Cinconze Salvatore, Moroni Emiliano, Caronariti Valeria, Bravetti Emanuela, Martines Maristella, Pellegrini Lucia, Serra Margherita, De Felicis Arcangeli Carla, Cesarini A.Rita, Paolini Fabrizia, Candio Francesco, Orr`u Gennaro, Bellaveglia M.Luisa, Gramenzi Rita, Bianchini Fabrizio, Bonsi Simonetta, Gozzo Matilda, Franchini Maddalena, Miglioranzi Paola, Previdi Mauro, Melotti Giancarlo, Monicelli Ugo, Martone Gabriella, Reali Laura, Manetta Fiorella, Ferrazzoli Maria Lucia, Diamanti Isabella, Falletta Salvatore, La Cava Giovanna, Paoletti Silvia, Andreini Carla, Bianchera Raffaella, Locatelli M. Elisa, Mannori Carlo, Sabatini Walter, Pasquini Anna, Pasquini Fulvio, Grossi Cristina, Belsito Luisa, Rana Pierangela, Scadavecchia Laura, Balducci Ottavio, Peccarisi Lucia, Bonvino Angelica, De Laurentis Lelio, Zarella Mariolina, Farinelli Claudio, Pasquantonio Antonella, Antogiovanni Assunta, Antogiovanni Luigi, Favi Valeria, De Vino Annette, Totaro Lucia, Becattini Laura, Casaregola Matilde, Barone Patrizia, Dau Giovanna, Argellati Sandra, Testori Franco, Maggiani Giuliano, Antonini Emanuela, Bawa Paola, Pandolfi Maria Eva, Borsellino Giuseppe, Mognaschi Claudia, De Martino Flavia, Perfetti Miriam, Longoni Rosa Maria, Marchione Laura, Invernizzi Lorella, Salvioni Francesca, Mariani Daniela, Gelpi Bruna, Carchesio Isidora, De Angelis Monica, Thiebat Elena, Romeo Lucia, Bollani Tiziana, Colombo Mania, Florioli Alessandro, De Poli Daniela, Bonori Massimo, Barbera Caterina, Denis Franca, Calore AnnaMaria, Criconia Carla, Giaretta Letizia, Menegus Elena, Passuello Giovanna, Turio Chiara, Ranieri Luigi, Grotteria Salvatore, Lentidoro Irene, Pelaggi Paola, Gullo Paola, Marino Filippo, Giancotti Laura, Licata Caruso Donatella, Esposito Andreina, Chianese Anna Maria, Masini Luigi, Greco Palmira, Lamanna Sergio, Maida Walter, Iovine Alfredo, Vitiello Giuseppe, Mariani Laura, Botto Anna, Cuocco Anna, Rampini Luigina, Pioggio Cinzia, Bellati Rosanna, Fontana Carla, Ettore Silvia, Gatto Fulvia, Caneva Egidio, Bianchi Gianpiero, Calcante Sara, Perrone Maria Sara, Saggese Teresa, Fallarino Stefania, Boffelli Elena, Aramini Lucio, Cornalba Ludovico, D’amato Vincenza, La Macchia Nicola, Mineo Santa, Paternostro Daniela, Piric`o Laura,Scillieri Maria Adriana, Costagliola Rosalba, Spataro Maria, Frezzetti Andrea, Fattore Stanislao, Coronella Angelo, Brunese Francesco Paolo, Minichino Anna Maria, De Vita Sergio, Mandia Francesco, Falcone Anna Maria, Mastrominico Augusto, Cavazzuti Donatella, Boschini Cesare, Baroni Isabella, Mazzini Franco, Ponti Roberto, Lucchi Elide, Faedi Clara, Trebbi Miro, Mele Roberto, Cera Melania, Rosas Paolo, Pala Antonio, Urru Luciano, Piras Stella, Zichera Tiziana, Cartone Franca, Centamore Maria,
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Ferro Sebastiana, Duminuco Calogera, Caltabiano Loredana, Scaringi Carmelo, Spedace Antonella and Francario Elisabetta. Clinical monitors who visited the paediatricians involved in the study to help them compile the clinical charts and to verify that the data were recorded correctly according to the study protocol definitions: Cinque Massimo, Coppo Elena, De Leo Silvana, Del Giudice, Di Bitetto Rosa Rina, Ferraro Luigi, Ganzarolli Stefania, Gibaldi Giovanni, Landini Luca, Losurdo Luigi, Maraglino Vita Maria, Merusi Ilaria, Moscatelli Daniela, Otelli Valeria, Panisi Cristina, Panizzolo Cristina, Pensabene Lucia, Porzio Salvatore, Ravera Brunella, Ricci Antonio, Russo Delia, Stabile Donatella, Viola Laura, Putzu Sandro and Montes Sebastiana.
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