Theoretical models currently used to explain infant crying in the first months of life

Theoretical model	Key management strategies	Summary of evidence
Medical condition - reflux/GORD, allergy, restricted oral connective tissues, lactose intolerance, migraine	Anti-secretory medications, maternal elimination diet, frenotomy & bodywork, lactose-free formula	Not supported by evidence (1-5)
Normal developmental phase (6)	Support carer coping. Reassure crying will pass. Entrain infant biology with first wave behavioural (FWB) strategies.	Ignores evidence that crying durations are modifiable by infant care practices (7,8). High level evidence shows that FWB strategies don't decrease frequency of night waking (9-11)
'A mysterious disorder of the microbiota-gut-brain axis' or gut inflammation secondary to gut dysbiosis	Probiotics	Probiotics may decrease crying in breastfed infants (placebo response 66%) but studies don't control for the breastfeeding problem of functional lactose overload; don't take into account complex and bidirectional nature of gut-brain axis (multiple confounders). Gut dysbiosis is confounder, not a cause (15,16)
Biorhythm disorder	Proposed in a single 2023 cohort study. Claimed to be of idiopathic aetiology; the proposed model doesn't inquire into multiple related factors which shape biorhythms from birth, such as parent approach to infant sleep (18). No translation into clinical intervention proposed	Melatonin has been demonstrated to follow - not cause - circadian rhythm disruption. Melatonin and H3f3b mRNA are markers of, not causative or, circadian disruption. You can find out about melatonin here, here, and here.
Neurobiological model of infant cry-fuss problems (Possums or NDC)	5 domain (multi-lateral) approach: multiple interventions in each domain or breastfeeding/feeds; sleep (including circadian intervention as required); sensory motor nourishment; baby's gut & health; parent mental health	Preliminary studies positive (19,20). Requires further evaluation

References

1. Douglas P. Diagnosing gastro-oesophageal reflux disease or lactose intolerance in babies who cry alot in the first few months overlooks feeding problems. J Paediatr Child Health. 2013;49(4):e252-e256.

2. Gieruszczak-Bialek D, Konarska Z, Skorka A, Vandenplas Y, Szajewska H. No effect of proton pump inhibitors on crying and irritability in infants: systematic review of randomized controlled trials. Journal of Pediatrics. 2015;166:767-770.

3. O'Shea JE, Foster JP, O'Donnell CPF, Breathnach D, Jacobs SE, Todd DA, et al. Frenotomy for tongue-tie in newborn infants (Review). Cochrane Database of Systematic Reviews. 2017(3):Art. No.:CD011065.

4. Bergmann MM, Caubet J-C, McLin V, Belli D, Schappi M, Eigenmann P. Common colic, gastroesophageal reflux and constipation in infants under 6 months do not necessitate an allergy work-up. Pediatric Allergy and Immunology. 2014:doi: 10.1111/pai.12199.

5. Gordon M, Biagioli E, Sorrenti M, Lingua C, Moja L, Banks SS, et al. Dietary modifications for infantile colic. Cochrane Database of Systematic Reviews. 2018:doi:10.1002/14651858.CD14601129.pub14651852.

6. Zeifman DM, St James-Roberts I. Parenting the crying infant. Current Opinion in Psychology. 2017;15:149-154.

7. Wolke D, Bilgin A, Samara M. Systematic review and meta-analysis: fussing and crying durations and prevalence of colic in infants. Journal of Pedatrics. 2017;185:55-61.

8. Vermillet A-Q, Tolboll K, Mizan SL, Skewes JC, Parsons CE. Crying in the first 12 months of life: a systematic review and meta-analysis of cross-country parent-reported data and modeling of the "cry curve". Child Development. 2022.

9. NHMRC. Report on the evidence: promoting social and emotional development and wellbeing of infants in pregnancy and the first year of life. http://www.nhmrc.gov.au: Australian Government, 2017.

10. Kempler L, Sharpe L, Miller CB, Bartlett DJ. Do psychosocial sleep interventions improve infant sleep or maternal mood in the postnatal period? A systematic review and meta-analysis of randomised controlled trials. Sleep Medicine Reviews. 2016;29:15-22.

11. Douglas P, Hill PS. Behavioural sleep interventions in the first six months of life do not improve outcomes for mothers or infants: a systematic review. J Dev Behav Pediatr. 2013;34:497–507.

12. Partty A, Kalliomaki M. Infant colic is still a mysterious disorder of the microbiota-gut-brain axis. Acta Paediatrica. 2017;106:528-529.

13. Rhoads JM, Collins J, Fatheree NY, Hashmi SS, Taylor CMea, Luo M, et al. Infant colic represents gut inflammation and dysbiosis. Journal of Pedatrics. 2018;203:55-61.

14. Zeevenhooven J, Browne PD, L/Hoir MP, De Weerth C, Benninga MA. Infant colic: mechanisms and management. Nature Reviews: Gastroenterology and Hepatology. 2018;15:479-496.

15. Sung V, D'Amico F, Cabana MD, Chau K, Koren G, Savino F, et al. Lactobacillus reuteri to treat infant colic: a meta-analysis. Pediatrics. 2017;141(1):e20171811.

16. Fatheree NY, Liu Y, Taylor CMea. Lactobacillus reuteri for infants with colic: a double-blind, placebo-controlled, randomized clinical trial. Journal of Pediatrics. 2017;191:170-178.

17. Douglas PS, Hill PS. A neurobiological model for cry-fuss problems in the first three to four months of life. Med Hypotheses. 2013;81:816-822.

18. Egeli TU, Tufekci KU, Ural C. A new perspective on the pathogenesis of infantile colic: is infantile colic a biorhythm disorder? Journal of Pediatric Gastroenterology and Nutrition. 2023;77(2):171-177.

19. Ball H, Douglas PS, Whittingham K, Kulasinghe K, Hill PS. The Possums Infant Sleep Program: parents' perspectives on a novel parent-infant sleep intervention in Australia. Sleep Health. 2018;4(6):519-526.

20. Douglas P, Miller Y, Bucetti A, Hill PS, Creedy D. Preliminary evaluation of a primary care intervention for cry-fuss behaviours in the first three to four months of life ("The Possums Approach"): effects on cry-fuss behaviours and maternal mood. Australian Journal of Primary Health. 2013;21:38-45.