A Randomized Controlled Trial of Osteopathic Manipulative Therapy to Reduce Cranial Asymmetries in Young Infants with Nonsynostotic Plagiocephaly.

OBJECTIVE: This study aimed to compare the efficacy of osteopathic manipulative therapy (OMTh) versus light touch therapy (LTT) in reducing cranial asymmetries in infants with nonsynostotic plagiocephaly (NSP). STUDY DESIGN: A prospective, parallel-group, single-center, LTT-controlled randomized clinical trial was conducted in the Department of Neonatology of Sant'Anna Hospital in Turin, Italy, from September 6, 2016 to February 20, 2020. We enrolled infants of 1 to 6 months of age with NSP, who were then randomly assigned to the study group (repositioning therapy plus six sessions of OMTh) or the control group (repositioning therapy plus six sessions of LTT). The outcome was the reduction of the oblique diameter difference index (ODDI) score <104%, which was assessed at the end of the intervention protocol (at 3 months) and at 1 year of age. RESULTS: A total of 96 infants were randomized, 48 in the OMTh group and 48 in the LTT group, with mean ages of 3.1 versus 3.2 months, and baseline ODDI score of 110.2 versus 108.7%. In the OMTh group, a significant reduction of the ODDI score <104%, compared with the LTT group, was observed in the intension-to-treat (ITT) and per-protocol (PP) analyses. The ITT analysis revealed an ODDI score <104% in the OMTh group at 3 months (risk difference: 0.41; 95% confidence interval [CI]: 0.25-0.53; p < 0.001) and at the follow-up at 1 year of age (risk difference: 0.47; 95% CI: 0.31-0.64; p < 0.001). The PP analysis at 3 months reported a risk difference of 0.44 (95% CI: 0.27-0.60; p < 0.001), and at 1 year of age, a risk difference of 0.54 (95% CI: 0.36-0.72; p < 0.001). CONCLUSION: In infants with NSP, a course of six OMTh sessions significantly reduced cranial asymmetries at both the 3-month and 1-year follow-up assessments, compared with LTT. This study is registered with ClinicalTrial.gov (identifier: NCT03970395; www. CLINICALTRIALS: gov ). KEY POINTS: · OMTh plus repositioning therapy significantly decreased the risk and severity of NSP compared with LTT.. · OMTh reduced mild and moderate cranial asymmetries.. · The role of OMTh in severe cranial asymmetries should be investigated in a multicenter trial..

Osteopathic Manipulative Treatment in Pediatric and Neonatal Patients and Disorders: Clinical Considerations and Updated Review of the Existing Literature.

Osteopathic medicine is a form of complementary and alternative medicine. Osteopathic practitioners treat patients of all ages: according to the Osteopathic International Alliance's 2012 survey, about one-third of all treated patients are aged between 31 and 50 years and nearly a quarter (23.4%) are pediatric patients, with 8.7% of them being younger than 2 years. In 2013 a systematic review evaluated the effectiveness of osteopathic manipulative treatment (OMT) in pediatric patients with different underlying disorders, but due to the paucity and low methodological quality of the primary studies the results were inconclusive. The aim of this review is therefore to update the evidence concerning OMT in perinatal and pediatric disorders and to assess its clinical impact. Most published studies favor OMT, but the generally small sample sizes in these studies cannot support ultimate conclusions about the efficacy of osteopathic therapy in pediatric age. In turn, clinical trials of OMT in premature infants might represent an important step in the osteopathic research because they can address both cost-effectiveness issues, and an innovative, multidisciplinary approach to the management of specific pediatric diseases cared for by the same, common health care system. The available studies in neonatal settings provide evidence that OMT is effective in reducing the hospital length of stay of the treated infants, therefore, suggesting that robust cost-effectiveness analyses should be included in the future clinical trials' design to establish new possible OMT-shared strategies within the health care services provided to newborns.

Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: a multicenter randomized controlled trial.

BACKGROUND: Human milk feeding protects against oxidative stress-induced damage in preterm neonates, including severe multifactorial diseases such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). The carotenoids, which are not found in formula milk, might play a key role in these actions. METHODS: A multicenter, double-blind, randomized controlled trial was conducted in three tertiary Italian neonatal intensive care units. All preterm infants < 32(+6) weeks' gestational age were eligible and were randomized to a single, oral, daily 0.5-mL dose of carotenoid supplementation (0.14 mg lutein + 0.0006 mg zeaxanthin) or placebo (5% glucose solution) from birth till 36 weeks' corrected gestational age. Primary outcomes were threshold ROP, NEC > second stage, and BPD. Surveillance for detection of these diseases and for intolerance/adverse effects was performed. RESULTS: No treatment-related adverse effect was documented in the 229 analyzed infants, whose clinical/demographical characteristics were similar in the two groups. Threshold ROP incidence did not significantly differ in treated (6.2%) versus not treated infants (10.3%; p = 0.18). The same occurred for NEC (1.7% versus 5.1%; p = 0.15) and BPD (4.5% versus 10.3%; p = 0.07). Noteworthy, the progression rate from early ROP stages to threshold ROP was decreased by 50% (0.30 versus 0.44; p = 0.23). CONCLUSION: Lutein/zeaxanthin supplementation in preterm infants is well tolerated. No significant effect was seen on threshold ROP, NEC, or BPD. The decreasing trends of these outcomes in the treatment group need to be assessed and confirmed on larger sample-sizes.

Early-onset neutropenia is a risk factor for Candida colonization in very low-birth-weight neonates.

Neutropenia is a major risk factor for bacterial colonization and sepsis in preterm neonates in the neonatal intensive care unit (NICU), but little is known about its relationships with candidal colonization (CC) in these settings. We performed a case-control study on neonates with birth weight of <1500 g admitted to our NICU during a 7-year period (1996-2003, N = 585). Through database search, infants with early-onset neutropenia (EON) (n = 68, group A) were identified and 1:1 matched with controls without EON (n = 68, group B). Microbiologic data from weekly surveillance cultures were examined to determine the presence and intensity of CC. Groups A and B were similar clinically and demographically. All group A neonates recovered from EON before the 8th day of life. Incidence of CC in the 1st month of life (at least 1 site) was significantly higher in group A (61.8% versus 35.3%, P = 0.002) and was not modified by treatment with recombinant granulocyte colony-stimulating factor. The same was true of CC intensity, expressed as the number of sites affected (P = 0.002). Incidence of candidal sepsis, mortality rates, and relative frequencies of the various subspecies of Candida among the isolates did not significantly differ between the 2 groups. In conclusion, EON in preterm neonates is a significant, independent risk factor for CC. Larger, prospective, adequately powered studies should verify whether increased CC related to neutropenia may translate into a similar increased occurrence of candidal sepsis in these settings.

CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN) in two preterm twin neonates.

The diagnosis of congenital CMV is usually guided by a number of specific symptoms and findings. Unusual presentations may occur and diagnosis is challenging due to uncommon or rare features. Here we report the case of two preterm, extremely low birthweight, 28-week gestational age old twin neonates with CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN). They were born to a HIV-positive mother, hence they underwent treatment with zidovudine since birth. Both infants featured severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support, with full recovery after 2 months. Treatment with ganciclovir was not feasible due the concomitant treatment with zidovudine and the risk of severe, fatal toxicity. Therefore administration of intravenous hyperimmune anti-CMV immunoglobulin therapy was initiated. Severe lung involvement at birth and subsequent pulmonary hypertension are rarely described in preterm infants as early manifestations of CMV congenital disease. In the two twin siblings here described, the extreme prematurity and the treatment with zidovudine likely worsened immunosuppression and ultimately required a complex management of the CMV-associated lung involvement.

Human milk feeding prevents retinopathy of prematurity (ROP) in preterm VLBW neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationships with neonatal nutritional policies. Human, maternal milk is the best possible nutritional option for all premature infants, including those at high risk for severe complications of prematurity, such as ROP. OBJECTIVE: This is a secondary analysis of data collected during two multicenter RCTs performed consecutively (years 2004 through 2008) by a network of eleven tertiary NICUs in Italy. The two trials aimed at assessing effectiveness of fluconazole prophylaxis (Manzoni et al., N Engl J Med 2007 Jun 14;356(24):2483-95), and of bovine lactoferrin supplementation (Manzoni et al., JAMA 2009 Oct 7;302(13):1421-8), in prevention of invasive fungal infection, and of late-onset sepsis in VLBW infants, respectively. We tested the hypothesis that exclusive feeding with fresh maternal milk may prevent ROP of any stage - as defined by the ETROP study - in VLBW neonates, compared to formula feeding. METHODS: We analyzed the database from both trials. Systematic screening for detection of ROP was part of the protocol of both studies. The definition of threshold ROP was as defined by the ETROP study. Univariate analysis was performed to look for significant associations between ROP and several possible associated factors, and among them, the type of milk feeding (maternal milk or formula for preterms). When an association was indicated by p < 0.05, multiple logistic regression was used to determine the factors significantly associated with ROP. RESULTS: In both trials combined, 314 infants received exclusively human maternal milk (group A), and 184 a preterm formula because their mothers were not expected to breastfeed. The clinical, demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12-0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05-0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. CONCLUSIONS: Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.

Routine Lactobacillus rhamnosus GG administration in VLBW infants: a retrospective, 6-year cohort study.

BACKGROUND: In preterm neonates, use of probiotic mixtures is increasingly popular and is effective in preventing NEC, fungal colonization, and improving feeding tolerance. However, concerns exist about safety and tolerability of long-lasting administration of living microrganisms to not-immunocompetent hosts. We report a 6-year, two-NICUs experience of routinary Lactobacillus rhamnosus GG (LGG) use in VLBW infants. METHODS: Clinical charts review, retrospective study of VLBW infants admitted to two Italian NICUs in the years 2003-2008. Standard protocol of LGG administration consisted of 3 x 109 CFU/day, in single oral dose, since 4th day-of-life, for 4-to-6-week courses. Nutritional policy relied on administration of fresh, expressed mother's milk, supplementation with preterm formula if needed. Data about LGG safety and tolerability, infections, feeding tolerance, microbiological clinical and surveillance cultures were retrieved and analysed. RESULTS: Complete data were obtained for 743 of 811 VLBW infants. Mean birth-weight was 1056 g; mean gestational age 29.5 weeks. A total of 17,108 LGG doses were administered (mean 23.1/infant). No adverse effects or intolerances putatively attributable to LGG occurred. Overall, 5350 clinical and surveillance cultures from 13 different sites/devices were performed (mean: 7.2 cultures from 6.5 different sites/infant). None ever grew LGG, or other Lactobacilli. No clinical sepsis episode was attributable to LGG. Full enteral feeding was achieved at 19.2 mean days-of-life; 73% of infants were exclusively/partially breastfed. Fourteen NEC cases occurred (=1.9%), with 5 (=0.7%) being>2b stage. CONCLUSIONS: Routinary supplementation of probiotic LGG in a large, 6-year VLBW infants Italian cohort proved microbiologically safe and clinically well tolerated.

Type and number of sites colonized by fungi and risk of progression to invasive fungal infection in preterm neonates in neonatal intensive care unit.

AIMS: Retrospective cohort study to assess if different patterns of Candida colonization determine different risks of progression to invasive fungal infection (IFI) in preterm neonates in NICU. METHODS: Weekly surveillance cultures from all neonates weighing at birth <1500 g admitted over a 6-year period were reviewed. Infants with available results from at least 3 cultures/week and from at least 4 different sites were enrolled and identified by the number of sites involved [1-2 (low-grade), 3 or more (high-grade)] and type (low-risk, if colonization was recovered from skin, stool, ear canal swab, gastric aspirate, nasopharynx secretions, endotracheal tube; high-risk, from urine, catheter tip, drains, surgical devices). Progression rates from colonization to IFI were calculated for each subgroup. Univariate analysis was performed looking for significant associations between IFI and a number of risk factors, including the different subgroups of colonization. Multiple logistic regression assessed all significantly (P<0.05) associated risk factors. MAIN RESULTS: In the 405 eligible infants, overall colonization rate was 42.9%, IFI rate 9.9%, overall progression rate to IFI 0.23, the latter being significantly higher in high-grade or high-risk than in low-grade or low-risk colonized infants (0.59 vs. 0.18, P=0.001; 0.44 vs. 0.11, P<0.001, respectively). Infants with concomitant high-grade + high-risk colonization had 4-fold higher risk of progression than any other colonized infant, and 7-fold higher risk than infants concomitantly low-grade + low-risk colonized (P<0.001). At multivariate analysis, high-grade and high-risk colonization (P=0.001 for both), birth weight (P=0.02) and presence of central venous line (P=0.04) remained independent predictors of IFI. CONCLUSIONS: Density and severity of fungal colonization condition the progression to IFI in preterm infants in NICU, and certain patterns of colonization are independent predictors of IFI. Increased culture surveillance and prophylactic measures should be addressed to preterm colonized infants in NICU featuring the most risky colonization patterns.