Infant Distress and Development of Functional Gastrointestinal Disorders in Childhood: Is There a Connection?

One infant in 4 manifests with abundant crying, fussing, or colic cry and is brought for medical evaluation during the first months of life.¹ Concomitantly, excessive antigen uptake and bacterial translocation ensue across the immature gut barrier.² Not surprisingly, infant crying has been related to food allergy³ and aberrant gut microbiota composition⁴ and these have, in turn, been linked to functional gastrointestinal disorders (FGIDs).⁵ We hypothesized that colic crying is associated with FGIDs later in childhood.

The study was approved by the committees on ethical practice at Turku University Hospital and the Health Office of Turku. Written informed consent was obtained from the children and their parents.

The study population comprised children participating in an ongoing, randomized, double-blind, prospective follow-up study of probiotic intervention in the perinatal period and risk of allergic and inflammatory diseases later in life (clinicaltrials.gov/ct/gui/show/NCT00167700), described in detail elsewhere.⁴ In brief, mothers (n = 159) of these children were randomly assigned to receive placebo or Lactobacillus rhamnosus GG (ATCC 53103; Valio Ltd) daily for 4 weeks before expected delivery. After the delivery, the preparation was given either to the child, or continuously to the mother, if breast-feeding, for 6 months. During the seventh and 12th weeks of life, parents recorded their infants’ behavior patterns, vomit, stools, and skin condition, using a modified 24-hour Barr chart on 7 consecutive days as previously described.⁴ During the study visit at age 13 years, a clinical examination was carried out by A.P., who was not involved in the original study and was blinded for the randomization and the behavioral diaries.

The diagnosis of FGID was based on the modified Rome III Diagnostic Questionnaire for pediatric FGID.⁶ The questionnaire was translated from English into Finnish and it was completed by the children with parental help at home before the follow-up visit.

Comparisons between 2 continuous and categorical variables were made by unpaired t test and χ² test or Fisher exact test, as appropriate, respectively. Univariate associations between FGID and continuous variables were studied by logistic regression analysis. Statistical analyses were made by SAS for Windows (version 9.2; SAS Institute Inc).

The 13-year follow-up was completed by 75 of the 132 invited children (56.8%) and the questionnaire by 74 (56.1%). Clinical characteristics are shown in the Table. Functional gastrointestinal disorder was diagnosed in 15 children (20.3%). Abdominal migraine and irritable bowel syndrome, being the most common diagnoses, were found in 7 (9.5%) and 4 children (5.4%), respectively.

By the age of 13 years, 28% and 5.6% of the children with and without colic-type crying during the seventh week of life, respectively, developed FGID (P = .05). Likewise, children manifesting with FGID had had more colic-type crying than healthy children during the seventh week of life (mean [SD], 31 [26] and 10 [13] min/d, respectively [P = .005]). The same tendency was still observed during the 12th week of life (mean [SD], 14 [22] and 4 [8] min/d, respectively [P = .08]). Other modes of infant distress were comparable between the groups (Table). The early probiotic supplementation had no effect on the development of FGID (Table).

Our findings herein invite an intriguing theory that early bouts of unsoothable crying could actually represent an early manifestation of abdominal pain–related FGIDs. Thus, our results extend those of a previous study lacking rigorous crying diaries.⁷L rhamnosus GG did not affect the emergence of FGID later in childhood in our study, suggesting that different probiotics or probiotic combinations may be required. Alternatively, they may be more operative in the treatment of pediatric FGID.⁸ Limitations of our study include a rather small study population and a considerable rate of dropouts, while the prospective nature and 13 years of follow-up emphasize its strength. Thus, further search of long-term sequelae of infant distress behavior is warranted, not only to add understanding about their origins but also to find new remedial options.

Corresponding Author: Anna Partty, MD, Department of Pediatrics, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland (aklein@utu.fi).

Published Online: August 19, 2013. doi:10.1001/jamapediatrics.2013.99.

Author Contributions: The authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition of data: Partty, Salminen, Isolauri.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: Partty, Salminen, Isolauri.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Partty, Isolauri.

Obtained funding: Salminen, Isolauri.

Administrative, technical, or material support: Salminen, Isolauri.

Study supervision: Kalliomaki, Isolauri.

Conflict of Interest Disclosures: None reported.

Funding/Support: The study has been funded by the Foundation for Pediatric Research and an EVO grant from Turku University Hospital.

Trial Registration: clinicaltrials.gov Identifier: NCT00167700.

Additional Contributions: We thank the families participating in our study, Jaakko Matomaki, MSc, for statistical consultation, Robert MacGilleon, MA, for language review of the manuscript, and Johanna Hvitfelt-Koskelainen for help with the follow-up of participants.