Using the LMS method to calculate z-scores for the Fenton preterm infant growth chart.

OBJECTIVES: The use of exact percentiles and z-scores permit optimal assessment of infants' growth. In addition, z-scores allow the precise description of size outside of the 3rd and 97th percentiles of a growth reference. To calculate percentiles and z-scores, health professionals require the LMS parameters (Lambda for the skew, Mu for the median, and Sigma for the generalized coefficient of variation; Cole, 1990). The objective of this study was to calculate the LMS parameters for the Fenton preterm growth chart (2003). DESIGN: Secondary data analysis of the Fenton preterm growth chart data. METHODS: The Cole methods were used to produce the LMS parameters and to smooth the L parameter. New percentiles were generated from the smooth LMS parameters, which were then compared with the original growth chart percentiles. RESULTS: The maximum differences between the original percentile curves and the percentile curves generated from the LMS parameters were: for weight; a difference of 66 g (2.9%) at 32 weeks along the 90th percentile; for head circumference; some differences of 0.3 cm (0.6-1.0%); and for length; a difference of 0.5 cm (1.6%) at 22 weeks on the 97th percentile. CONCLUSION: The percentile curves generated from the smoothed LMS parameters for the Fenton growth chart are similar to the original curves. These LMS parameters for the Fenton preterm growth chart facilitate the calculation of z-scores, which will permit the more precise assessment of growth of infants who are born preterm.

Higher versus lower protein intake in formula-fed low birth weight infants.

BACKGROUND: The ideal quantity of dietary protein for formula-fed low birth weight infants < 2.5 kilograms is still a matter of controversy and debate. In premature infants, the protein intake must be sufficient to achieve normal growth without negative effects such as acidosis, uremia, and elevated levels of circulating amino acids (e.g. phenylalanine levels). This systematic review evaluates the benefits and risks of higher (>= 3.0 g/kg/day) versus lower (< 3.0 g/kg/day) protein intakes during the initial hospital stay of formula-fed preterm infants < 2.5 kilograms. OBJECTIVES: To determine whether higher (>= 3.0 g/kg/day) versus lower (< 3.0 g/kg/day) protein intakes during the initial hospital stay of formula-fed preterm infants < 2.5 kilograms result in improved growth and neurodevelopmental outcomes without evidence of short and long-term morbidity. SEARCH STRATEGY: Two review authors searched MEDLINE (1966 - May 2005), CINAHL (1982 - May 2005), PubMed (1966 - May 2005), EMBASE (1980 - May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2005), abstracts, conferences and symposia proceedings from Society of Pediatric Research, and American Academy of Pediatrics. Cross references were reviewed independently for additional relevant titles and abstracts for articles up to fifty years old. SELECTION CRITERIA: Randomized controlled trials contrasting levels of formula protein intakes as low (< 3.0 g/kg/day), high (=> 3.0 g/kg/day but < 4.0 g/kg/day), or very high protein intake (=> 4.0 g/kg/day) during hospitalization of neonates less than 2.5 kilograms at birth who were formula-fed. Studies were not included if infants received partial parenteral nutrition during the study period or were fed formula as a supplement to human milk. Given the small number of studies that met all inclusion criteria, studies in which nutrients other than protein also varied (> 10% relative difference) were added in a post-facto analysis. DATA COLLECTION AND ANALYSIS: Two review authors used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group to independently assess trial eligibility and quality, and extracted data. In a 3-arm trial where two groups fell within the same predesignated protein intake group, weighted means and pooled standard deviations were calculated. MAIN RESULTS: The literature search identified 37 studies, of which five met all the inclusion criteria. All five studies compared low (< 3.0 g/kg/day) to high protein intakes (=> 3.0 g/kg/day but < 4.0 g/kg/day). The overall analysis revealed an improved weight gain (WMD 2.36 g/kg/day, 95% CI 1.31, 3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/day, 95% CI 128.7, 158.8) in infants receiving formula with higher protein content while other nutrients were kept constant. None of the studies reported IQ or Bayley scores at 18 months or later. No significant differences were seen in rates of necrotizing enterocolitis, sepsis or diarrhea. Of three studies included in the post-facto analysis, only one could be included in the meta-analysis. The post-facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content (weight gain: WMD 2.53 g/kg/day, 95% CI 1.62, 3.45, linear growth: WMD 0.16 cm/week, 95% CI 0.03, 0.30, and head growth: WMD 0.23, 95% CI 0.12, 0.35). There was no significant difference (WMD 0.25, 95% CI -0.20, 0.70) in the concentration of plasma phenylalanine between the high and low protein intake groups. One study (Goldman 1969) in the post-facto analysis documented a significantly increased incidence of low IQ scores, below 90, in infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg/day). AUTHORS' CONCLUSIONS: This systematic review suggests that higher protein intake (=> 3.0 g/kg/day but < 4.0 g/kg/day) from formula accelerates weight gain. Based on increased nitrogen accretion rates, this most likely indicates an increase in lean body mass. Although accelerated weight gain is considered to be a positive effect, increase in other outcome measures examined may represent a negative or ambivalent effect. These include elevated blood urea nitrogen levels and increased metabolic acidosis. Limited information was available regarding the impact of higher formula protein intakes on long term outcomes such as neurodevelopmental abnormalities. As determined in this review, existing research literature on this topic is not adequate to make specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/day) from formula.

GI complications in pediatric patients post-BMT.

This retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (BMT) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. Hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. Acute graft-versus-host disease (GVHD) occurred in 46% of the population, with liver involvement in 39% and intestinal involvement in 60% of those with acute GVHD. Veno-occlusive disease (VOD) occurred in 18% of the population. A greater increase in hepatic transaminases was noted in GVHD and VOD than nonspecific liver injury. Serum bilirubin may help to differentiate between VOD and hepatic GVHD. Biliary sludging occurred in 20% of patients and was associated with increased morbidity. Common post transplant gastrointestinal complications included mucositis in 90%, vomiting in 85% and abdominal pain in 71%. TPN support post transplant was required in 91%. Diarrhea occurred in 67% with the most common identified etiologies reported as GVHD (27%), viral (6%), Clostridium difficile (8%) infections and unknown (28%). Typhilitis developed in 3.5%. Melena or hematochezia occurred in 11 patients (8%). However, gastrointestinal bleeding was disproportionately represented in intensive care unit admissions (5/27) and 100 day mortality (5/21). Gastrointestinal and hepatic complications represent a major cause of morbidity and mortality in pediatric BMT recipients.

Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients.

The incidence, risk factors and mortality of veno-occlusive disease (VOD) were identified for 142 pediatric hematopoietic stem cell (HSC) transplant recipients with hematological malignancies (83), solid tumors (41) and nonmalignant diseases (18). This historical cohort of 142 HSC transplant patients, from January 1993 through June 2000, was assessed by chart review. Risk factors for the development of VOD and mortality were assessed by multiple logistic regression and Kaplan-Meier survival curves respectively. The incidence of VOD was 18.3% (26/142 transplants). Multivariate analysis reconfirmed the known pretransplant risk factors of induction therapy with busulfan and transplantation with matched unrelated donor cells as significant risk factors for the development of VOD. In addition, two new risk factors, positive CMV serology in the recipient and TPN provided in the 30 days prior to transplant, were identified. Mortality in transplant patients at 100 days was greater in the VOD-positive group (10/26 (38.5%)) compared to the VOD-negative group (11/116 (9.5%) (P=0.001)). The risk of death was 4.97 times higher with 95% CIs (2.11, 11.71) for the VOD-positive group. Decreasing the risk factors for VOD may decrease mortality in this patient population.

Scarring resulting from chickenpox.

Nine hundred and eighty-six children (519 boys, 467 girls) who had chickenpox at least 1 year previously were examined for the presence of scars resulting from this disease. Ninety-six (18.5%) boys and 88 (18.8%) girls had chickenpox scars, giving rise to an overall prevalence of 18.7%. The scars were found on the face in 75 (40.8%), neck 2 (1.1%), shoulders 8 (4.3%), upper limbs 15 (8.2%), anterior thorax 50 (27.2%), abdomen 106 (57.6%), back 65 (35.3%), buttocks 9 (4.9%), and lower limbs 12 (6.5%) affected children. The mean number of scars in the 184 children was 2.8 (standard deviation 1.9). The scars were hyperpigmented in 32, hypopigmented in 160, depressed in 38, and hypertrophic in 32 children. Keloids were noted in two children.

Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions.

BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were conducted for a subset of respondents to confirm reported practices. Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease. RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 [82%] and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001). There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period. INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time. These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations. However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

Chiropractic treatment of patients younger than 18 years of age: Frequency, patterns and chiropractors' beliefs.

OBJECTIVES: To explore how and when chiropractors are involved in the care of patients younger than 18 years of age, and to examine chiropractors' beliefs about treating paediatric patients. DESIGN: A cross-sectional survey of a random sample of 140 chiropractors practising in Alberta. Data were collected by means of a mailed questionnaire, which elicited practice information and chiropractors' beliefs, and included closed-and open-ended questions related to six vignettes of paediatric health problems. RESULTS: Fifty-seven per cent of chiropractors responded to the questionnaire. All chiropractors indicated that they treat patients younger than 18 years of age. Nine per cent of respondents do not treat patients younger than age two years, and 4% do not treat patients from ages six to 11 years. On average, 13% of chiropractors' total patient load over the month preceding the completion of the questionnaires consisted of patients younger than the age of 18 years. With increasing age, patients are more likely to present with musculoskeletal problems (23% of patients younger than age two years, 84% of those aged 14 to 17 years). Chiropractors reported that they provided musculoskeletal treatment regardless of the cause of the problem. A high percentage of chiropractors refer to physicians and reported that they would like to provide concomitant care with physicians. CONCLUSION: The present study has shown that chiropractors do treat children and that their opinions about this practice vary by specific condition. In addition, substantial percentages of chiropractors indicated that they would like to work with physicians in treating patients with nonmusculoskeletal conditions.

Scleral melanocytosis and oculodermal melanocytosis (nevus of Ota) in Chinese children.

Two thousand nine hundred fourteen Chinese children (1510 males and 1404 females) were examined for the presence of scleral melanocytosis (SM) and oculodermal melanocytosis in a cross-sectional prevalence survey. SM was found in 4.9% of boys and 4.1% of girls under the age of 1 year. The peak prevalence was at 6 years of age, when 44.6% of boys and 46.6% of girls were affected. At 18 years of age, only 11.1% of boys and 13.2% of girls had SM. The overall prevalence, regardless of age, was 27.6% in boys and 27. 1% in girls. The condition was bilateral in 78% of cases. The medial superior quadrant was the most frequently affected site, and the lateral inferior quadrant was the least frequently affected site. Oculodermal melanocytosis occurred only in one patient; the pigmentation affected the left side of the face and the ipsilateral sclera.

Parents' ratings of everyday cognitive abilities in very low birth weight children.

Parents' ratings of everyday cognitive functioning in very low birth weight (VLBW) children free of sensorineural impairments and normal birth weight (NBW) children were compared with the children's actual performance on psychometric measures of cognitive and motor skills. Subjects included 19 VLBW children identified at age 3 years as "suspect" for developmental problems, 19 VLBW children identified at age 3 years as "developing normally," and 30 NBW full-term peers. Results indicated that parents of the suspect VLBW group rated their children as having significant impairments in memory, language, cognitive, and motor skills, findings which were consistent with the results of concurrent psychometric assessments. When compared with psychometric test results, parents identified more children as displaying difficulties in memory, language, and cognitive skills, but fewer children with coordination difficulties. These findings suggest that the parents' ratings and the psychometric measures may be assessing somewhat different aspects of the children's functioning.

Long-term neuropsychological outcomes in very low birth weight children free of sensorineural impairments.

This study investigated the neuropsychological outcomes at school age of children with very low birth weight (VLBW) free of sensorineural impairments. Subjects included 19 children with VLBW identified at age 3 as 'suspect' for developmental problems, 19 children with VLBW identified at age 3 as developing normally, and 30 children of normal birth weight (NBW). Results indicated that children in the VLBW 'suspect' group performed significantly more poorly on all of the neuropsychological measures compared to children of NBW. These findings suggest that VLBW children identified as 'suspect' for developmental problems because of impairments in cognitive skills at age 3 continued to show deficits at school age on intellectual and neuropsychological measures.

Assessment of postneonatal growth in VLBW infants: selection of growth references and age adjustment for prematurity.

OBJECTIVES: To assess growth outcomes of VLBW infants using different growth references and to validate the practice of age adjustment for prematurity in the growth assessment for VLBW infants. METHODS: Longitudinal growth data of 514 VLBW infants from 4 to 36 months of adjusted age were analyzed separately based on chronological and adjusted age and by comparison with three growth references. RESULTS: More infants were labelled as having "subnormal growth" assessed on chronological age than on adjusted age throughout the first three years of life. The proportions of subnormal growth determined using a Canadian and the WHO reference for breastfed infants were similar; they were different from those obtained using the NCHS/WHO reference. CONCLUSIONS: Our findings suggested that the interpretations of growth in VLBW infants vary substantially depending on which reference is used. The age adjustment for prematurity makes substantial difference in identifying subnormal growth in VLBW infants. The adjustment should be carried out throughout the first three years of life.

Environmental tobacco smoke and middle ear disease in preschool-age children.

OBJECTIVE: To determine the association between environmental tobacco smoke and middle ear disease in pre-school age children. DESIGN: A population-based case-control study with verification of disease history and exposure reporting in a subsample. SETTING AND PARTICIPANTS: Participants were identified through a population-base probability sample of 1320 first-grade students in 36 schools in Calgary, Alberta. The parents of 625 children meeting case (n = 227) or control (n = 398) definitions were interviewed by telephone for their children's exposure history. The adequacy of exposure and disease measures was assessed using hair continue measurements, home visits, and physician medical records for 92 children. MAIN OUTCOME MEASURES AND RESULTS: A history of middle ear disease was found in 23.9% of the sample. Relationships were found between middle ear disease and 2 or more household smokers (crude odds ratio) [OR], 1.85; 95% confidence interval [CI], 1.15-2.97), 10 or more cigarettes smoked by the mother per day (crude OR, 1.68; 95% CI, 1.12-2.52), and 10 or more cigarettes smoked in total in the household per day (crude OR, 1.40; 95% CI, 0.98-2.00) during the first 3 years of life. In logistic regression modeling these effects persisted after adjusting for child care (type, age started, duration, and group size), infant feeding (type and duration), socioeconomic status, maternal education level, number of prenatal ultrasonographic examinations, and health services use. The mean current hair cotinine levels were higher for children living in homes with 1 or more smokers vs no smokers (0.51 vs 0.31 ng/mg, P = .01). There was fair agreement (75.3%) between physician medical records and parental report of disease history, but some misclassification bias toward the null hypothesis likely. CONCLUSION: Environmental tobacco smoke is an important risk factor for middle ear disease in urban preschool-age children, even in a relatively affluent population.

Before viability: a geographically based outcome study of infants weighing 500 grams or less at birth.

OBJECTIVE: The primary objective of this study was to determine the likelihood of long-term survival and avoidance of disabilities in a geographically based population of infants born at 20 weeks gestation or more and weighing 500 g or less at birth. STUDY DESIGN: This was a 12-year historical cohort follow-up study of all infants born in this gestational age and birth weight category in the Province of Alberta, Canada, between 1983 and 1994. Data were collected from certificates of live births or stillbirths, death certificates, hospital records, and longitudinal multidisciplinary follow-up examinations. RESULTS: One thousand one hundred ninety-three infants were of 20 weeks gestation or more, weighed 500 g or less, and were born between 1983 and 1994. Eight hundred eleven (68.0%) were stillborn and 382 (32.0%) were born alive. Among the latter, neonatal intensive care was provided in 113 (29.6%) and withheld in 269 (70.4%). The infants receiving intensive care were of heavier birth weight, later gestational age, higher antenatal risk scores, were more likely to be born in a level III center, to have received antenatal steroids, and to have been delivered by cesarean section. Of the infants receiving intensive care, 95 (84. 1%) died and 18 (15.9%) were discharged alive, but 5 of these died after discharge because of respiratory complications. The infants discharged alive had later gestational age, were more likely to be small for gestational age, singletons, treated with antenatal steroids, and to have been delivered by cesarean section. Maternal indications were described in the majority of cesarean sections done for live-born infants. The 13 infants who were long-term survivors were followed at ages 12 and 36 months adjusted age. Four had no serious disabilities, 4 had one disability (cerebral palsy or mental retardation), and 5 had multiple disabilities (cerebral palsy plus mental retardation with blindness in 2 cases and deafness in 1 case). CONCLUSION: The majority of infants born at gestational age 20 weeks or more weighing <500 g were stillborn. Among live births, neonatal intensive care was withheld in 70% and initiated in 30%. Of the latter, 11% survived to 36 months of age, and of these, 4 infants (31%), most of whom are small for gestational age, female infants, avoided major disabilities but 9 (69%) had one or more major disabilities. Survivors are prone to rehospitalizations early in life, slow growth, feeding problems, and minor visual difficulties; rates of learning-related and behavioral problems at school age are not yet known. Implications. Parents and caregivers faced with the impending delivery of an infant in this gestational age/birth weight category should understand that survival without multiple major disabilities is possible but rare. They should be made aware of local population-based results and not just isolated reports.

Impact of intrauterine growth restriction on neurodevelopmental and growth outcomes in very low birthweight infants.

The impact of intrauterine growth restriction (IUGR) in very low birthweight preterm infants weighing < or = 1250 g was determined by comparing longitudinal growth and neurodevelopmental outcome to an adjusted age of 36 months in 52 intrauterine growth restricted children, with 55 birthweight-matched and 56 gestational age-matched children. None of these children had chromosomal anomalies, congenital infections, or major congenital malformations. Gestational ages of intrauterine growth restricted, birthweight- and gestational age-matched infants were 30 (+/-3), 26 (+/-2), 29 (+/-2) weeks: birthweights were 842 (+/-232), 872 (+/-201) and 1094 (+/-142) g, respectively. Intrauterine growth restricted children had fewer complications during initial hospitalization (p < 0.05), and had lower weights and head circumferences at follow-up (p < 0.05). No significant differences were present in major neurodevelopmental disabilities between the intrauterine growth restricted and two comparison groups. Persistence of microcephaly was associated with adverse neurodevelopmental outcome.

Province-based study of neurologic disability of children weighing 500 through 1249 grams at birth in relation to neonatal cerebral ultrasound findings.

BACKGROUND: Adverse neurodevelopmental outcome in premature infants is more common in the presence of certain ultrasonographically detectable intracranial lesions. Present nomenclature and classifications of parenchymal changes in preterm infants of varying gestations have led to some confusion. Descriptive definitions may be clinically useful. Regionalized perinatal and neonatal care enables population-based studies of these lesions and subsequent outcomes. METHODS: Two- to 3-year outcomes of neonates weighing 500 through 1249 g born in Alberta to Alberta residents during 1987 through 1990 were reviewed in relation to neonatal cerebral ultrasound lesions. Odds ratios and confidence limits for disability were calculated. RESULTS: Of 960 live births in this weight group, 669 (70%) survived to 1 year adjusted age; 646 (96.6%) were assessed at follow-up, and 80 (12.4%) of these were disabled: cerebral palsy, 8.7%; vision loss, 2.9%; hearing loss, 1.3%; epilepsy, 0.6%; mental retardation, 4.8%; more than one disability per child, 3.6%; and projected dependent disability, 1.4%. Lesions considered to be predictive of disability on ultrasound (excluding germinal layer hemorrhage) were found in 79 (11.8%), parenchymal lesions in 63 (9.4%) of 1-year survivors: intraventricular hemorrhage (IVH) (n = 59), persistent or transient cerebral ventriculomegaly (n = 50), persistent or transient intraparenchymal periventricular echodensity (n = 29), and cystic periventricular leukomalacia (n = 7). All lesions except isolated IVH were associated with adverse outcome; 37% of disabled children, 61% of multiply disabled children, and all children projected to become dependently disabled had parenchymal lesions with or without IVH. Triple lesions of IVH, cerebral ventriculomegaly, and intraparenchymal periventricular echodensity gave an odds ratio for disability of 50. Transient lesions had significant risk. CONCLUSIONS: This province-based study provides a descriptive scheme of serial neonatal cerebral ultrasound lesions and outcome considered useful for clinicians caring for newborns of lowest gestational ages. The overall incidence of parenchymal lesions was lower than frequently reported. Combinations of lesions were linked to increased incidence, complexity, and severity of childhood disability.

Neurodevelopmental outcome after neonatal extracorporeal membrane oxygenation.

OBJECTIVE: To determine the neurodevelopmental outcome of neonates who underwent extracorporeal membrane oxygenation (ECMO group) and similarly critically ill newborns with a lower Oxygenation Index who underwent conventional treatment (comparison group), and to determine whether factors such as the underlying diagnosis and the distance transported from outlying areas affect outcome. DESIGN: Multicentre prospective longitudinal comparative outcome study. SETTING: An ECMO centre providing services to all of western Canada and four tertiary care neonatal follow-up clinics. SUBJECTS: All neonates who received treatment between February 1989 and January 1992 at the Western Canadian Regional ECMO Center and who were alive at 2 years of age; 38 (95%) of the 40 surviving ECMO-treated subjects and 26 (87%) of the 30 surviving comparison subjects were available for follow-up. INTERVENTIONS: ECMO or conventional therapy for respiratory failure. OUTCOME MEASURES: Neurodevelopmental disability (one or more of cerebral palsy, visual or hearing loss, seizures, severe cognitive disability), and mental and performance developmental indexes of the Bayley Scales of Infant Development. RESULTS: Six (16%) of the ECMO-treated children had neurodevelopmental disabilities at 2 years of age, as compared with 1 (4%) of the comparison subjects; the difference was not statistically significant. The mean mental developmental index (91.8 [standard deviation (SD) 19.5] v. 100.5 [SD 25.4]) and the mean performance developmental index (87.2 [SD 20.0] v. 96.4 [SD 20.9]) did not differ significantly between the ECMO group and the comparison group respectively. Among the ECMO-treated subjects those whose underlying diagnosis was sepsis had the lowest Bayley indexes, significantly lower than those whose underlying diagnosis was meconium aspiration syndrome. The distance transported did not affect outcome. CONCLUSIONS: Neurodevelopmental disability and delay occurred in both groups. The underlying diagnosis appears to affect outcome, whereas distance transported does not. These findings support early transfer for ECMO of critically ill neonates with respiratory failure who do not respond to conventional treatment. Larger multicentre studies involving long-term follow-up are needed to confirm these findings.