Salivary Sex Steroid Levels in Infants and the Relation with Infantile Colic

Objective: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic.

Effects of probiotics on gastrointestinal symptoms, anthropometric measurements, and breastfeeding duration in infants with colic: a randomized control trial

ABSTRACT BACKGROUND: Infantile colic has a multifactorial etiology. Recent studies have suggested that probiotics may be effective in its management. OBJECTIVE: This study was carried out to evaluate the effect of the Actiregularis strain (5×106 cfu/ml) included in maternal nutrition on gastrointestinal problems, growth development, and breastfeeding outcomes in infantile colic. DESIGN AND SETTING: The study was a randomized controlled trial conducted in the neonatal outpatient clinic of a training and research hospital in Turkey. METHODS: A probiotic drink containing the Actiregularis (5×106 cfu/ml) strain was added to the diet of mothers in the probiotics group once daily for 15 consecutive days. Data were collected for each infant's 0th (birth), 1st, 4th, and 6th months. RESULTS: Infants whose mothers were administered Actiregularis for 15 days had decreased crying intensity (P = 0.000). When the difference in breastfeeding rates between the groups was significant at the 4th and 6th months (P = 0.044; P = 0.035). There was no difference in anthropometric values except the babies' weights at the 6th month. (P < 0.001). CONCLUSION: Infants treated with Actiregularis, which was added to their mothers' diet for 15 days, showed a decrease in the frequency of crying, and the difference in breastfeeding rates between the groups was significant at the 4th and 6th months. There was no difference in anthropometric values except the babies' weights at the 6th month. CLINICAL TRIALS REGISTRATION: NCT04374955 (https://clinicaltrials.gov/ct2/show/).

Recognition and management of infantile colic / 中国小儿急救医学

Infantile colic(IC)is a common process that occurs in the infants within five months of age.The main characteristic of IC is paroxysm of inconsolable crying.Although IC is a benign self-limiting process, it is a common source of concern for family, and usually bring challenge to doctors.The diagnostic criteria is Roma Ⅳ criteria, which is mainly based on the typical feature and duration of crying.The etiology is unknown.The proposed causes can be classified into gastrointestinal and non-gastrointestinal factors.There is still no standard treatment for IC.The current management includes dietary modification, behavioral modification, pharmacological intervention, manual therapy, and so on.More clinical studies are needed to confirm the effect of these treatment strategies.Pediatricians should be familiar with the main causes and management of IC, and should also be adept at recognizing the individual reasons, managing the infants, and improving the prognosis.

Efficacy of Bifidobacterium animalis subsp. lactis, BB-12® on infant colic - a randomised, double-blinded, placebo-controlled study.

To evaluate the administration of Bifidobacterium animalis subsp. lactis, BB-12® (BB-12) on infant colic in breastfed infants, a double-blind, placebo-controlled randomised study was conducted in Chengdu, China from April 2016 to October 2017 with 192 full-term infants less than 3 months of age and meeting the ROME III criteria for infant colic. After a 1-week run-in the infants were randomly assigned to receive daily BB-12 (1×109 cfu/day) or placebo for 3 weeks. Crying/fussing time were recorded using a 24 h structured diary. The primary endpoint was the proportion of infants achieving a reduction in crying and fussing time of ≥50% from baseline. Parent's/caregiver's health related quality of life was measured using a modified PedsQL™ 2.0 Family Impact Module and immunological biomarkers were evaluated from faecal samples at baseline and after the 21-day intervention. The percentage of infants achieving a reduction in the daily crying/fussing time ≥50% after the 21-day intervention was significantly higher in the infants supplemented with BB-12 (P<0.001). The mean number of crying episodes was significantly reduced in the BB-12 group compared to the placebo group (10.0±3.0 to 5.0±1.87 vs 10.5±2.6 to 7.5±2.8, respectively) (P<0.001) and the mean daily sleep duration was markedly increased from baseline to end of intervention in the BB-12 group compared to the infants in the placebo group (60.7±104.0 vs 31.9±102.7 min/day, respectively) (P<0.001). The faecal levels of human beta defensin 2, cathelicidin, slgA, calprotectin and butyrate were statistically higher in the BB-12 group compared to the placebo group after the 21-day intervention. At the end of the intervention the parent's/caregiver's physical, emotional and social functioning scores were significantly higher for the BB-12 group compared to the placebo group (all P<0.05). Supplementation of BB-12 is effective in reducing crying and fussing in infants diagnosed with infant colic.

Reducing the maternal dietary intake of indigestible and slowly absorbed short-chain carbohydrates is associated with improved infantile colic: a proof-of-concept study.

BACKGROUND: To investigate if a low fermentable oligo-, di- and mono-saccharides and polyols (FODMAP) diet consumed by breastfeeding mothers may be associated with reduced symptoms of infantile colic. METHODS: Exclusively breastfeeding mothers and their typically-developing healthy infants who met the Wessel Criteria for infantile colic were recruited from the community, to this single-blind, open-label, interventional study. After a 3-day qualifying period, mothers were provided a low FODMAP 7-day diet. On days 5, 6 and 7 mothers completed a Baby Day Diary. At baseline and at the end of the 7-day dietary intervention, breast milk was analysed for FODMAP content and infant faecal samples for pH. RESULTS: Eighteen breastfeeding mothers (aged 27-40 years) adhered (100%) to the low FODMAP diet. Infants were of gestational age 37-40.3 weeks and aged 2-17 weeks. At entry, crying durations were a mean [95% CI] of 142 [106-61] min and fell by 52 [178-120] min (P = 0.005; ancova). Combined crying-fussing durations fell by 73 [301-223] min (n = 13; P = 0.007), as did crying episodes (P = 0.01) and fussing durations (P = 0.011). Infant sleeping, feeding, or awake-and-content durations did not change. Infant faecal pH did not change. Breast milk lactose content was stable and other known FODMAPs were not detected. At end of study, mothers reported their baby 'is much more content' and 'can be put down without crying'. CONCLUSIONS: Maternal low FODMAP diet may be associated with a reduction in infant colic symptoms. A randomized controlled study is warranted to determine if a maternal low FODMAP diet is effective in reducing symptoms.

Knowledge, attitudes, and practices of pediatricians on infantile colic in the Middle East and North Africa region.

BACKGROUND: Regional evidence-based guidelines for the prophylaxis and management of infantile colic are not available for the Middle East and North Africa (MENA) region. The Allied Against Infantile Functional GI Disorders (ACT) Working Group was created in January, 2015 to determine the knowledge gaps and the current management practices of infantile colic by physicians in the MENA region. The ACT group determined the need for a survey to address these questions. The objectives of the survey were to highlight current clinical practices on the management of infantile colic and to raise awareness on colic severity in the MENA region. METHODS: The ACT working group developed the survey which included respondent characteristics and closed questions on practice in colic prevention. The survey was subject to validation and ethics committee approval in all countries. RESULTS: A total of 1628 physicians (mostly pediatricians (75.4%), neonatologists (2.4%) and general practitioners (19.8%)) responded to the survey. The 5 most represented countries were KSA (27.9%), Kuwait (22.1%), Morocco (13.8%), Lebanon (10.6%), and Iraq (7.4%). Most of the respondents (77.8%) practiced in governmental settings. A majority of respondents (91.7%) reported that colic is diagnosed predominantly by clinical examination. Above 63%, of pediatricians surveyed, believed that the colic prevalence rate was >40%, which is greater than the 20% rate reported in worldwide surveys. Yet, most of the responding physicians (73%) prefer to simply reassure parents rather than prescribe a therapeutic agent. Most physicians were either neutral (58%) or did not endorse (18.4%) colic prophylaxis. Of those who prescribed formulae for non-breastfed children, a majority (64.3%) chose "Comfort" formulae over hydrolyzed or lactose-free formulae or formulae with probiotics. CONCLUSIONS: The results of this survey suggest that a substantial proportion of responding physicians from the selected MENA countries do not advocate for prophylaxis of colic. The findings of this survey suggest that more educational efforts are required to increase awareness of the strong body of evidence supporting the efficacy of probiotics in the prevention and management of infantile colic.

Hypoallergenic formula with Lactobacillus rhamnosus GG for babies with colic: A pilot study of recruitment, retention, and fecal biomarkers.

AIM: To investigate recruitment, retention, and estimates for effects of formula supplementation with Lactobacillus rhamnosus GG (LGG) on inflammatory biomarkers and fecal microbial community in infants with colic. METHODS: A prospective, double-blind, placebo-controlled trial was conducted in otherwise healthy infants with colic. We screened 74 infants and randomized and analyzed results in 20 infants [9 receiving LGG (LGG+) and 11 not receiving LGG (LGG-)]. LGG was incorporated in the formula (Nutramigen(®)) (minimum of 3 × 10(7) CFU/d) in the LGG+ group. Fecal microbiota and inflammatory biomarkers, including fecal calprotectin (FC), plasma cytokines, circulating regulatory T cells (Tregs), and crying + fussing time were analyzed to determine optimal time points and effect sizes for a larger trial. RESULTS: Recruitment in this population was slow, with about 66% of eligible infants willing to enroll; subject retention was better (75%). These rates were influenced by parents' reluctance to volunteer their infant for a clinical trial and by their tendency to change formulas. The maximal difference of crying + fussing time was observed at day 14, comparing the 2 groups, with a mean difference of -91 (95%CI: -76, 259) min (P = NS). FC showed no significant difference, but the optimal time to determine a potential effect was at day 90 [with a mean difference of 121 (95%CI: -48, 291) µg/g stool], observing a lower level of FC in the LGG+ group. The fecal microbial communities were chaotic, as determined by Shannon's diversity index and not apparently influenced by the probiotic. No significant change was observed in plasma inflammatory cytokines or Tregs, comparing LGG+ to LGG- groups. CONCLUSION: Designing future colic trials involving a probiotic-supplemented formula for infants in the United States will require consideration for difficult enrollment. Infants with colic have major variations in feal microbiota and calprotectin, both of which improve with time, with optimal time points for measurement at days 14 and 90 after treatment.