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

Table 1 Comparison of baseline characteristics of randomized patients in the two study groups

	LGG+ group		LGG- group
Continuous variables	n	mean ±SD	n	mean ± SD	P
Age at the time randomized (d)	9	57 ± 30	11	68 ± 28	0.341
Gestational age (wk)	9	38 ± 2	11	37 ± 2	0.201
Birth weight (kg)	9	3.1 ± 0.8	11	2.9 ± 1.1	0.471
Birth height (cm)	7	51.6 ± 1.8	9	47.2 ± 5.3	0.041
Discrete variables	n	mean ± SD	n	mean ± SD
Gender	9		11
Female		4 (44.4)		4 (36.4)	1.0
Male		5 (55.6)		7 (63.6)
Race	9		11		1.0
African-american		3 (33.3)		4 (36.4)
Caucasian		6 (66.7)		7 (63.6)
Ethnicity	9		11		1.0
Hispanic or latino		2 (22.2)		2 (18.2)
Not hispanic or latino		7 (77.8)		9 (81.8)
Partial breast feed	9		11		1.0
Yes		3 (33.3)		3 (27.3)
No		6 (66.7)		8 (72.7)
Formula type	9		11
Earth’s best		1 (11.1)		0 (0)
Enfamil		1 (11.1)		0 (0)
Enfamil gentleease		1 (11.1)		0 (0)
Gerber good start		0 (0)		1 (9.1)
Isomil		1 (11.1)		1 (9.1)
Neocate		0 (0)		1 (9.1)
Nutramigen ready mix		0 (0)		1 (9.1)
Similac		2 (22.2)		0 (0)
Similac advance		1 (11.1)		0 (0)
Similac senstive		0 (0)		5 (45.5)
Breast milk		2 (22.2)		2 (18.2)

¹Denotes P values obtained by non-parametric Wilcoxon rank sum test. All other P values are obtained by Fisher’s exact test. The values in parentheses indicate percentage.

Table 2 Longitudinal analysis of clinical variables by study group (LGG+ vs LGG-) at baseline and follow up visits

	Adjusted means (95%CI)			P value
	LGG+ group	LGG- group	Mean differences(95%CI)
Crying + fussing time (min)
Visit 1 (Baseline)	296 (210, 381)	337 (251, 422)	41 (-80, 161)	0.51
Visit 2	197 (117, 278)	289 (142, 436)	91 (-76, 259)	0.29
Visit 3	144 (54, 234)	199 (69, 328)	55 (-104, 213)	0.50
Visit 4	111 (65, 157)	133 (60, 205)	22 (-64, 107)	0.62
Fecal calprotectin (μg/g)
Visit 1 (Baseline)	285 (199, 371)	294 (184, 404)	9 (-131, 149)	0.90
Visit 2	226 (182, 270)	305 (186, 423)	79 (-48, 205)	0.22
Visit 3	229 (113, 345)	250 (154, 347)	21 (-130, 172)	0.78
Visit 4	211 (80, 342)	332 (225, 440)	121 (-48, 291)	0.16

Longitudinal model: Barr Diary data = β₀ + β₁× visit2 + β₂× visit3 + β₃× visit4 + β₄ group + β₅× visit2 group + β₆× visit3 group + β₇× visit4 group. Here, visit2, visit3, visit4 are dummy variables; visit2 = 1 if at visit 2, 0 otherwise; visit3 = 1 if at visit 3, 0 otherwise; visit4 = 1 if at visit 4, 0 otherwise; group = 1 if in LGG group, 0 otherwise.

Table 3 Longitudinal analysis of cytokins by study group (LGG+ vs LGG-) at baseline and follow up visits

	Adjusted geometric means (95%CI)		P
	LGG+ group	LGG- group
Cytokines
IFN-γ (pg/mL)
Visit 1 (Baseline)	0.7 (0.4, 1.3)	0.6 (0.3, 1.2)	0.84
Visit 2	1.2 (0.7, 2.0)	0.5 (0.3, 0.9)	0.04
Visit 4	0.4 (0.3, 0.6)	0.2 (0.1, 0.4)	0.07
IL-10 (pg/mL)
Visit 1 (Baseline)	3.7 (2.3, 6.0)	4.2 (2.2, 8.1)	0.78
Visit 2	4.3 (3.2, 5.7)	3.8 (2.3, 6.4)	0.72
Visit 4	2.7 (1.7, 4.2)	2.0 (1.1, 3.7)	0.47
IL-12p70 (pg/mL)
Visit 1 (Baseline)	0.2 (0.1, 0.4)	0.2 (0.1, 0.4)	0.85
Visit 2	0.3 (0.2, 0.4)	0.4 (0.3, 0.6)	0.29
Visit 4	0.2 (0.1, 0.5)	0.3 (0.2, 0.4)	0.57
IL-1β (pg/mL)
Visit 1 (Baseline)	0.08 (0.05, 0.13)	0.19 (0.08, 0.43)	0.09
Visit 2	0.27 (0.08, 0.88)	0.15 (0.06, 0.40)	0.45
Visit 4	0.11 (0.05, 0.21)	0.16 (0.05, 0.49)	0.52
IL-6 (pg/mL)
Visit 1 (Baseline)	0.3 (0.2, 0.5)	0.4 (0.3, 0.6)	0.36
Visit 2	0.3 (0.2, 0.6)	0.3 (0.2, 0.4)	0.66
Visit 4	0.2 (0.1, 0.4)	0.2 (0.1, 0.3)	0.63
IL-8 (pg/mL)
Visit 1 (Baseline)	6.5 (4.8, 8.7)	7.0 (5.3, 9.4)	0.69
Visit 2	5.4 (4.1, 7.3)	9.5 (6.6, 13.7)	0.02
Visit 4	4.9 (3.2, 7.5)	4.6 (2.8, 7.8)	0.88
TNF-α (pg/mL)
Visit 1 (Baseline)	4.5 (3.8, 5.3)	4.8 (3.7, 6.2)	0.69
Visit 2	5.4 (4.4, 6.5)	4.2 (3.2, 5.5)	0.15
Visit 4	4.4 (3.3, 5.9)	5.7 (4.7, 6.9)	0.14
Treg (%)
Visit 1 (Baseline)	7.2 (6.5, 8.0)	6.7 (5.9, 7.5)	0.37
Visit 2	7.5 (6.8, 8.2)	8.5 (7.0, 10.3)	0.23
Visit 4	7.5 (6.1, 9.3)	9.2 (8.1, 10.5)	0.10

Longitudinal model: ln(cytokines) = β₀ + β₁× visit2 + β₂× visit4 + β₃× group + β₄× visit2 group + β₅× visit4 group; Here, visit2, visit4 are dummy variables; visit2 = 1 if at visit 2, 0 otherwise; visit4 = 1 if at visit 4, 0 otherwise; group = 1 if in LGG group, 0 otherwise. The geometric mean is the anti-log of arithmetic mean of log-transformed value. P values are obtained using wald test to test whether the differences of cytokines between study groups are significant at each visit.