Background
Methods
Eligibility criteria
Type of studies
Type of participants
Type of intervention
Type of outcomes
Search strategy
Study selection and data extraction
Quality assessment
Data analysis
Results
Description of studies
Study characteristics
Study ID | Sample size | Age | Sex M/F | Comparisons | Outcome | Follow up |
---|---|---|---|---|---|---|
CAM vs usual care, 3 studies | ||||||
Liu CH 2009 [20] | T:150 C:148 | T:1-6 m, 80 cases; 6-12 m, 50 cases; 1-2 y, 20 cases C:1-6 m, 83 cases; 6-12 m, 44 cases; 1-2 y, 21 cases | T:88/62 C:86/44 | Swimming therapy + Baibu (Stemona japonica) lotion (bath) + Tuina vs Cyproheptadine (oral) + Boric lotion (external application with cold lotion)/Hydrocortisone butyrate cream (external use)/Zinc oxide cream (external use) (7-15d) | Improvement of symptoms and signs and signs; IgG; Relapse (T:26/150, 3 m; 37/150, 6 m C:80/148, 3 m; 96/148, 6 m) | 3 m, 6 m |
Liu WQ 2016 [21] | T:60 C:60 | T:(4.5 ± 3.8) y C:(5.3 ± 4.5) y | T:37/23 C:33/27 | Fasting and rotation diet vs Pevisone paste (external use) (3 m) | Improvement of symptoms and signs; IgG; Relapse (T:4/60 C:11/60) | 3 m |
Wu YQ 2014 [22] | T:74 C:74 | T:(6.35 ± 1.36) m C:(5.98 ± 1.23) m | T:41/33 C:31/43 | Velvetfeeling lotion (external application) + Moisturizing cream (external use) + Saline water (dipping) vs Boric lotion (external application) + Vitamin E (external use) + Saline water (dipping) (7d) | Improvement of symptoms and signs; CGI-EI | NR |
CAM + usual care vs usual care, 10 studies | ||||||
Chen DX 2015 [23] | T:20 C:20 | T:(3.82 ± 0.7) m C:(2.35 ± 1.3) m | NR | Bifid triple viable capsules (oral) + Hydrocortisone butyrate cream (external use) vs Hydrocortisone butyrate cream (external use) (180d) | Improvement of symptoms and signs | 6 m |
Chen YL 2015 [24] | T:58 C:58 | T:(11 ± 5) m C:(12 ± 5) m | T:31/27 C:30/28 | Probiotics (oral) + Chlorphenamine maleate tablets (oral) + Vitamin B6 + Fluocinonide cream (external use) + Calcium supplement (oral) vs Chlorphenamine maleate tablets (oral) + Vitamin B6 + Fluocinonide Cream (external use) + Calcium supplement (oral) (28d) | Improvement of symptoms and signs; CGI-EI; Interleukin; Interferon; Relapse (T:9/58 C:29/58) | NR |
Guo YH 2015 [25] | T:90 C:90 | T:2 m-3 y C:2 m-3 y | total: 98/82 | Tetralogy of viable bifidobacterium tablets (oral) + Usual care (Calamine lotion/ Zinc oxide cream/ Loratadine syrup/ Mometasone furoate cream) vs Usual care (Calamine lotion/Zinc oxide cream/Loratadine syrup/Mometasone furoate cream) (30d) | Improvement of symptoms and signs; IL-4, IL-10, IFN-γ, IgE, Th1/Th2; Relapse (T:24/90 C:62/90) | 3 m |
Jiang YX 2013 [26] | T:65 C:60 | T:2 y C:2 y | total: 72/53 | Velvetfeeling lotion (external application) + Usual care (eg. Chlorphenamine maleate tablets) vs Usual care (eg. Chlorphenamine maleate tablets) + Boric lotion (external application) (28d) | Improvement of symptoms and signs | NR |
Li DY 2012 [27] | T:32 C:30 | T:(7.15 ± 2.06) m C:(6.89 ± 2.54) m | T:17/15 C:16/14 | Bifid triple viable capsules (oral) + Zinc oxide cream (external use) + Boric lotion (external application) vs Zinc oxide cream (external use) + Boric lotion (external application) (14d drugs for external use/28d Oral bifid-triple viable capsule) | Improvement of symptoms and signs; Relapse (T:6/32 C:20/30) | NR |
Mao HX 2013 [28] | T:50 C:50 | T:2 m-5 y C:2 m-5 y | T:24/26 C:28/22 | Probiotics (oral) + Antihistamines (oral) + Calcium supplement (oral) + Skincare cream (external use) vs Antihistamines (oral) + Calcium supplement (oral) + Skincare cream (external use) | Improvement of symptoms and signs; Relapse (T:2/50 C:12/50) | NR |
Wei MX 2010 [29] | T:38 C:36 | T:(6.78 ± 2.62) m C:(7.14 ± 2.10) m | T:22/16 C:19/17 | Viable Bacillus coagulans tablets (oral) + Boric lotion (wash-out) + Zinc oxide cream (external use) vs Boric lotion (wash-out) + Zinc oxide cream (external use) (28d) | Improvement of symptoms and signs; Relapse (T:7/38 C:24/36) | 6 m |
Ye CQ 2017 [30] | T:48 C:48 | T:(6.9 ± 2.4) m C:(6.8 ± 2.6) m | T:27/21 C:28/20 | Condensation living bacterium bacillus (oral) + Boric lotion (wash-out) + Zinc oxide cream (external use) vs Boric lotion (wash-out) + Zinc oxide cream (external use) (28d) | Improvement of symptoms and signs; Relapse (T:6/48 C:28/48) | 6 m |
Zhang MH 2013 [31] | T:35 C:35 | T:(5 ± 3) m C:(6 ± 3) m | T:27/8 C:25/10 | Bifico lriple viable (oral) + Boric lotion (wash-out) + Zinc oxide cream (external use) + Cetirizine hydrochloride drops (oral) vs Boric lotion (wash-out) + Zinc oxide cream (external use) + Cetirizine hydrochloride drops (oral) (30d) | IFN-γ; Interleukin; T-Cell; Relapse (T:6/35 C:16/58) | 6 m |
Zhang XN 2013 [32] | T:36 C:34 | total:(7.06 ± 3.48) y | total:32/38 | Velvetfeeling lotion (external application) + Butyl flufenamate ointment (external use) + Antihistamine (oral) vs Saline water (external application) + Butyl flufenamate ointment (external use) + Antihistamine (oral) (14d) | Improvement of symptoms and signs; CGI-EI | NR |
CAM vs placebo, 9 studies | ||||||
D. Sistek 2006 [33] | T:30 C:29 | T:3.8 y C:4.4 y | T:15/14 C:17/13 | Probiotics (oral) vs Placebo (oral) (12w) | Improvement of symptoms and signs | 4w |
Hyeon-Jong Yang 2014 [34] | T:50 C:50 | T:(58.7 ± 29.9) m C:(47.4 ± 28.1) m | T:29/21 C:24/26 | Probiotics (oral) vs Placebo (oral) (6w) | Improvement of symptoms and signs; Fecal cell counts; IL-4; TNF-α | NR |
Reza 2011 [35] | T:19 C:21 | T:(28.68 ± 40.86) m C:(22.76 ± 34.03) m | T:11/8 C:14/7 | Synbiotic (oral) vs Placebo (oral) (8w) | Improvement of symptoms and signs Mononuclear cells | NR |
S Weston 2017 [36] | T:28 C:28 | T:(11.5 ± 4.2) m C:(10.3 ± 3.2) m | T:14/14 C:16/12 | VRI-003 PCC freeze dried powder probiotics (oral) vs Placebo (oral) (8w) | Improvement of symptoms and signs; total IgE levels; radioallergosorbent test | 8w |
Sergei V. Gerasimov 2010 [37] | T:48 C:48 | T:(25.6 ± 7.7) m C:(24.1 ± 6.3) m | T:28/15 after withdrew C:28/19 after withdrew | Probiotics (oral) vs Placebo (oral) (8w) | Improvement of symptoms and signs; Quality of life; Total IgE; Eosinophil count | NR |
Shoko 2007 [38] | T:16 C:16 | T:4.44 y C:5.56 y | T:9/7 C:12/4 | Borage oil (undershirts coated with oil) vs Placebo (non-coated undershirts) (2w) | Improvement of symptoms and signs; Changes of transepidermal water loss | NR |
Wu YJ 2017 [39] | T:33 C:33 | T:(1.5 ± 1.1) m C:(7.14 ± 2.10) m | T:25/8 C:19/14 | Probiotics (Lactobacillus rhamnosus) (oral) vs Placebo (oral) (8w) | Improvement of symptoms and signs; Quality of Life (Infant Dermatitis Quality of Life Questionnaires and Dermatitis Family Impact Questionnaires); | NR |
Yavuz 2012 [40] | T:20 C:20 | total:1-13 y | total: 23/17 | Probiotic bacteria (oral) vs Placebo (oral) (8w) | Improvement of symptoms and signs; cytokine analyse/IgE/Eosinophil cationic protein | 10w |
Youngshin 2012 [41] | T:58 C:60 | T:(4.6 ± 3.3) y C:(5.1 ± 3.3) y | T:34/24 C:35/25 | Probiotics (L. plantarum CJLP133) (oral) vs Placebo (oral) (12w) | Improvement of symptoms and signs; total IgE levels/specific IgE | 2w |
Multi-armed trials, 2 studies | ||||||
Pasi E. Kankaanpa 2002 [42] | T1:5 T2:5 C1:5 | T1:(4.5 ± 2) m T2:(5.7 ± 2.2) m C1:(5.6 ± 2.1) m | T1:2/3 T2:3/2 C1:2/3 | Probiotics (Lactobacillus GG) (oral) vs Probiotics (Bifidobacterium Bb12) (oral) vs placebo (oral) (①4.4 ± 1.7 m ②7.3 ± 0.7 m ③5.7 ± 2.0 m) | Fatty acid analysis | ≥36 m follow until panticipants at the age of 3 years |
C. Gore 2011 [43] | T1:45 T2:45 C1:47 C2:22 C3:49 | T1:19 [16-23] w T2:20.5 [17-23] w C1:20 [16-23] w C2:15 [13-19.5] w C3:19 [15-21.5] w | T1:28/17 T2:24/21 C1:28/19 C2:16/6 C3:25/24 | Probiotics (Lactobacillus paracasei) (oral) vs Probiotics (Bifidobacterium) (oral) vs Placebo (oral) vs Exclusively breastfed vs Standard formula-fed (12w) | Improvement of symptoms and signs; Quality of life; Stool; GI-Permeability; Specific serum IgE; Urinary EPX | NR |
Therapy | Administration | Dosage | Frequency | Detail | Formula | Trials numbers | %(/22) |
---|---|---|---|---|---|---|---|
Probiotics | oral | depend on formula | 2–3/d | Oral probiotics preparation | The probiotic formulation was a mixture of Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABLA-12 with fructo-oligosaccharide in a rice maltodextrin powder. | 18 | 72% |
Diet | oral | None | 3 m | To avoid to severe and moderate intolerant food, and take mild intolerant food per 6 days | None | 2 | 8% |
Biofilm | external application | appropriate amount | 2–3/d | The main ingredient is chitosan with low polymer (OPC). External application help form a protective film on the skin. | Velvetfeeling | 3 | 12% |
Borage oil | undershirts coated withoil | 498 mg of GLA per 100 g of cotton) | 2 w | Borage oil was chemically bonded to the cotton fibers of the undershirts that made of pure organic cotton. The borage oil was gradually released from the cotton fibers and absorbed into the skin. The undershirts were designed such that the sutures did not touch and stimulate the skin directly. | Borage oil | 1 | 4% |
Swimming | Passively by nurse; Autonomous swimming | None | 1/d | Trained nurse helps baby to stretch the limb as passively swimming or baby swim autonomously. | None | 1 | 4% |
Risk of bias of included trials
Effects of interventions
Study ID | Sample size | Main intervention | Estimate effect [95% CI] | Outcome |
P
|
---|---|---|---|---|---|
CAM vs usual care | |||||
Liu CH 2009 [20] | T:150 C:148 | Swimming therapy | RR 1.01 [0.92, 1.11] RR 1.01 [0.96, 1.07] RR 0.38 [0.28, 0.52] | Clinical effectiveness rate 50% Improvement of symptoms and signs Relapse rate | P = 0.8318 P = 0.5671 P < 0.00001 |
Liu WQ 2016 [21] | T:60 C:60 | Fasting and Rotation diet | RR 1.57 [1.04, 2.38] RR 1.32 [1.09, 1.60] RR 0.36 [0.12, 1.08] | Clinical effectiveness 50% Improvement of symptoms and signs; Relapse rate | P = 0.0323 P = 0.0049 P = 0.0681 |
Wu YQ 2014 [22] | T:74 C:74 | Velvetfeeling lotion (external application) | RR 1.92 [1.36, 2.72] RR 1.33 [1.10, 1.61] | Clinical effectiveness rate 50% Improvement of symptoms and signs | P = 0.0002 P = 0.0031 |
CAM + usual care vs usual care | |||||
Chen DX 2015 [23] | T:20 C:20 | Bifid Triple Viable capsules (oral) | RR 1.63 [0.87, 3.04] RR 1.73 [1.15, 2.60] | Clinical effectiveness rate 50% Improvement of symptoms and signs | P = 0.1283 P = 0.0088 |
Chen YL 2015 [24] | T:58 C:58 | Probiotics (oral) | RR 1.21 [0.87, 1.68] RR 1.19 [0.99, 1.42] RR 0.31 [0.16, 0.60] | Clinical effectiveness rate 50% Improvement of symptoms and signs Relapse rate | P = 0.2659 P = 0.0624 P = 0.0004 |
Guo YH 2015 [25] | T:90 C:90 | Tetralogy of viable bifidobacterium tablets (oral) | RR 1.37 [1.01, 1.85] RR 1.27 [1.04, 1.55] RR 0.39 [0.27, 0.56] | Clinical effectiveness rate 50% Improvement of symptoms and signs Relapse rate | P = 0.0400 P = 0.0172 P < 0.00001 |
Jiang YX 2013 [26] | T:65 C:60 | Velvetfeeling lotion (external application) | RR 1.85 [0.90, 3.79] RR 1.91 [1.46, 2.50] | Clinical effectiveness rate 50% Improvement of symptoms and signs | P = 0.0947 P < 0.00001 |
Li DY 2012 [27] | T:32 C:30 | Bifid Triple Viable capsules (oral) | RR 1.36 [1.03, 1.79] RR 1.32 [1.06, 1.65] RR 0.28 [0.13, 0.60] | Clinical effectiveness rate 50% Improvement of symptoms and signs; Relapse rate | P = 0.0295 P = 0.0151 P = 0.0011 |
Mao HX 2013 [28] | T:50 C:50 | Probiotics (oral) | RR 0.17 [0.04, 0.71] | Relapse rate | P = 0.0151 |
Wei MX 2010 [29] | T:38 C:36 | Viable Bacillus Coagulans tablets (oral) | RR 1.33 [1.05, 1.68] RR 1.30 [1.07, 1.58] RR 0.28 [0.14, 0.56] | Clinical effectiveness rate 50% Improvement of symptoms and signs; Relapse rate | P = 0.0189 P = 0.0089 P = 0.0004 |
Ye CQ 2017 [30] | T:48 C:48 | Condensation living bacterium bacillus (oral) | RR 1.57 [1.21, 2.02] RR 1.31 [1.10, 1.55] RR 0.21 [0.10, 0.47] | Clinical effectiveness rate 50% Improvement of symptoms and signs; Relapse rate | P = 0.0005 P = 0.0019 P = 0.0001 |
Zhang MH 2013 [31] | T:35 C:35 | Bifico Lriple Viable (oral) | RR 1.15 [0.91, 1.46] RR 0.38 [0.17, 0.85] | 50% Improvement of symptoms and signs; Relapse rate | P = 0.2371 P = 0.0180 |
Zhang XN 2013 [32] | T:36 C:34 | Velvetfeeling lotion (external application) | RR 6.61 [1.62, 26.96] RR 1.25 [1.00, 1.56] | Clinical effectiveness rate 50% Improvement of symptoms and signs | P = 0.0084 P = 0.0542 |
CAM vs placebo | |||||
Reza 2011 [35] | T:19 C:21 | Synbiotic (oral) | MD 19.10 [7.60, 30.60] | Clinical effectiveness scores | P = 0.0017 |
Sergei V. Gerasimov 2010 [37] | T:48 C:48 | Probiotics (oral) | MD 6.40 [2.71, 10.09] | Clinical effectiveness scores | P = 0.0009 |
Wu YJ 2017 [39] | T:33 C:33 | Probiotics (Lactobacillus rhamnosus) (oral) | MD 10.85 [3.82, 17.88] | Clinical effectiveness scores | P = 0.0035 |
Yavuz 2012 [40] | T:20 C:20 | Probiotic (oral) | MD 10.20 [7.45, 12.95] | Clinical effectiveness scores | P < 0.00001 |
Youngshin 2012 [41] | T:58 C:60 | Probiotics (L. plantarum CJLP133) (oral) | MD 7.30 [2.63, 11.97] | Clinical effectiveness scores | P = 0.0029 |
Global improvement (symptoms and signs improvement ≥95%, such as itching, skin lesions, swelling, and papula)
Relapse rate
≥50% improvement of symptoms and signs (such as itching, skin lesions, swelling, and papula)
Adverse events
Study ID | Total sample num | Sample num in intervention group | Sample num in control group | Adverse events cases | Intervention group | Control group | Treatment for adverse event |
---|---|---|---|---|---|---|---|
C. Gore 2011 [43] | 208 | 137 | 71 | T: 42/137 C: NR | green loose stools; increased vomiting; feed-refusal; colic | NR | 24/137 (17.5%) participants stopped the study formula. |
Chen YL 2015 [24] | 116 | 58 | 58 | T: 1/58 C: 2/58 | 1 for dizzy. | 1 for dizzy; 1 for drowsy. | NR |
Liu CH 2009 [20] | 298 | 150 | 148 | T: 0/150 C: 57/148 | None | 21 for facial flushing; 18 for dry skin; 8 for partial facial skin thinning; 10 for facial skin with mild pigmentation; Unclear for other hormonal dermatitis symptoms. | NR |
Sergei V. Gerasimov 2010 [37] | 96 | 48 | 48 | T: 26/48 C: 24/48 | 11 for upper respiratory tract infections; 4 for lower respiratory tract infections; 7 for herpetic stomatitis; 3 for diarrhea; 6 for constipation; 5 for abdominal colic; 2 for burn and croup with severe adverse events. | 10 for upper respiratory tract infections; 5 for lower respiratory tract infections; 5 for herpetic stomatitis; 2 for diarrhea; 6 for constipation; 4 for abdominal colic; 3for head injury, food poisoning with severe adverse events. | None was related to the medications under investigation. |
Wu YQ 2014 [22] | 148 | 74 | 74 | T: 2/74 C: 5/74 | 2 for crying and mildly red skin lesions on the 2nd day. | 5 for crying, irritability, and red skin lesions. | Without any treatment, to ease soon and symptoms disappearance. |
Ye CQ 2017 [30] | 96 | 48 | 48 | T:3/48 C:14/48 | 1 for diarrhea; 2 for constipation. | 6 for diarrhea; 8 for constipation. | NR |
Zhang XN 2013 [32] | 70 | 36 | 34 | T: 1/36 C: 2/34 | 1 for mild skin irritation after using Velvetfeeling Lotion | 2 forskin lesions reddening after using Butyl Flufenamate Ointment. | Without any treatment, to ease soon and symptoms disappearance. |