Coexistence of neuropathic corneal pain, corneal nerve abnormalities, depression, and low quality of life.

PURPOSE: To evaluate the quality of life (QoL), mental health conditions and corneal morphology in neuropathic corneal pain (NCP) subjects without a significant ocular surface disease. METHODS: A composite questionnaire was administered to 228 consecutive subjects, assessing the pain intensity, duration, and quality using a modified version of the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Pain Detect (PD) questionnaires. Subjects diagnosed with possible central NCP and two sub-groups of patients diagnosed with peripheral ocular pain completed an additional battery of mental health questionnaires and were examined by In Vivo Confocal Microscopy (IVCM). RESULTS: Of the 76 subjects that reported chronic ocular pain (duration >1 month), 53 were classified with probable NCP. Nine subjects without signs that justify the pain and non-responding to topical anaesthesia, were considered affected by central NCP. In these patients, a significant negative correlation was found between the presence pain and the mental component of the QoL (R2 = 0.733), and a positive correlation between the severity of pain the presence post-traumatic stress disorder (R2 = 0.83) and depression (R2 = 0.93). Although neuromas and sprouting had higher frequency in the central NCP group compared the control groups, these differences was not statistically different. CONCLUSIONS: The assessment of ocular pain characteristics using multiple questionnaires and IVCM may help to recognize differences between nociceptive and neuropathic pain. An association between pain intensity and mental health condition may guide the therapeutical choices.

Corneal Microstructural Changes by Confocal Microscopy in Vernal Keratoconjunctivitis Patients Treated with Topical Cyclosporine.

Purpose: To compare corneal morphologic changes in vernal keratoconjunctivitis (VKC) patients before and after treatment with topical cyclosporin (CsA).Methods: 23 VKC patients and 40 healthy subjects as controls were considered. All patients were treated with 1%CsA during their active phase. The impact of treatment on quality of life was evaluated administering the QUICK questionnaire. Both eyes were evaluated using the in vivo confocal microscopy (IVCM) before treatment (T0), at the end of treatment in Autumn (T1) and at the recurrence of symptoms in the next season (T2).Results: All VKC patients improved their QUICK scores after CsA treatment. IVCM highlighted corneal microstructural changes at the level of epithelium, sub-basal nerve plexus and stroma in patients affected by VKC and allowed to follow their evolution after topical treatment with CsA.Conclusions: IVCM is a valuable tool to evaluate the dynamic corneal changes in VKC before and after treatment with CsA.

Cornea verticillata in Fabry disease: a comparative study between slit-lamp examination and in vivo corneal confocal microscopy.

PURPOSE: To compare the diagnostic power of slit-lamp examination with the in vivo corneal confocal microscopy (IVCM) as the gold standard in assessing the presence of corneal epithelial deposits in patients with Fabry disease (FD). METHODS: Fourteen patients with FD (4 males, 10 females; mean age, 46.8 years) and eight healthy controls (4 males, 4 females; mean age, 36.75 years) were included. All subjects underwent slit-lamp examination and IVCM of both central and peripheral corneal quadrants with the Heidelberg Retina Tomograph-III in combination with the Rostock Cornea Module. RESULTS: In patients with FD, 9 of 28 eyes (32%) showed the presence of cornea verticillata at the slit-lamp examination and 25 eyes (89%) showed the presence of epithelial hyper-reflective deposits at the IVCM. Of the 19 eyes negative at the slit-lamp examination, 16 eyes showed the presence of epithelial deposits at the IVCM. Compared with controls, patients with FD had a significantly reduced number, density and length of nerve fibres at the level of corneal sub-basal nerve plexus, but a significantly higher grade of fibres tortuosity. CONCLUSIONS: The slit-lamp examination has a limited diagnostic power in the detection of epithelial deposits in patients with FD when compared with the IVCM. In fact, the slit-lamp examination suffers from a high number of false negative results and, consequently, from a low negative predictive value (16%). IVCM allows the detection of corneal microstructural changes in patients with FD and may represent a reliable tool for the early diagnosis and follow-up of the disease.

Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK scoring scale.

AIM: To propose a new scoring system in the assessment of ocular surface epithelial damage in vernal keratoconjunctivitis (VKC). METHODS: 25 consecutive patients with VKC (50 eyes) were evaluated using the Quality of Life in children with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and lissamine green staining and cornea confocal microscopy (Heidelberg Retina Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used to evaluate the epithelial damage after staining. RESULTS: Mean Oxford and VKC-CLEK scores were significantly different after fluorescein staining (P<0.001), but significantly correlated (P<0.001; r=0.649). The same data were obtained comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001; r=0.760). In patient with limbal VKC, a statistically significant difference was found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores (P<0.001), but not in tarsal VKC. A statistically superior concordance was found between QUICK and VKC-CLEK scores compared with standard staining scores values (P<0.001). CONCLUSIONS: Oxford and Van Bijsterveld scores are not adequate for the evaluation of the epithelial damage in patients with limbal VKC because the staining patterns considered for these tests do not correspond to the staining patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to better evaluate both limbal and tarsal epithelial damage in patients with VKC.

Rapid Decrease in Rates of Hospitalization Resulting From Invasive Pneumococcal Disease and Community-Acquired Pneumonia in Children Aged <60 Months After 13-Valent Pneumococcal Conjugate Vaccine Introduction in Argentina.

BACKGROUND: In January 2012, Argentina included universal pneumococcal vaccination in the routine childhood vaccination program using a 13-valent pneumococcal conjugate vaccine (PCV13). A 2 + 1 schedule (2 doses in the first year of life and a booster dose at 12 months of age) in children aged <2 years and 2-dose catch-up immunization in children aged 13 to 24 months was administered during the first year of vaccine introduction. The purpose of this study was to assess the burdens of invasive pneumococcal disease (IPD) and/or community-acquired pneumonia (CAP) in hospitalized children younger than 5 years during the first 2 years of the program compared to those in the prevaccination period in our setting. METHODS: This was a multicenter, prospective, and descriptive study. Rates of hospitalization resulting from IPD and/or CAP in 5 pediatric reference centers across the country were analyzed (every 10 000 admissions). Clinical, epidemiologic, and microbiological data were recorded. Statistical analysis using Stata 8.0 was performed. RESULTS: A comparison of rates of hospitalization resulting from global IPD and/or CAP in the prevaccine (2009-2011) and postvaccine (2012-2013) periods revealed significant decreases of 50% (P = .003) and 51% (P < .0001), respectively. Significant decreases were also observed in number of hospitalizations resulting from empyema (39%; P = .03) and pneumococcal empyema (67.8%; P = .007); the reduction was not statistically significant for pneumococcal CAP (58%; P = .18). Hospital stays for IPD and/or CAP decreased by 56%. CONCLUSION: Rapid and significant decreases in the rates of hospitalization resulting from IPD and/or CAP during the first 2 years after PCV13 introduction were observed. A longer surveillance period is required to confirm these results and the effectiveness of the vaccination program.

Epidemiology of allergic conjunctivitis: clinical appearance and treatment patterns in a population-based study.

PURPOSE OF REVIEW: To analyse the most recently published studies on the prevalence of allergic conjunctivitis alone or in association with allergic rhinitis, and the clinical and demographic aspects of the disease. RECENT FINDINGS: Allergic conjunctivitis or conjunctival symptoms are present in 30-71% of patients with allergic rhinitis. Allergic conjunctivitis alone has been estimated in 6-30% of the general population and in up to 30% in children alone or in association with allergic rhinitis. Seasonal allergic conjunctivitis is the most frequent form; however, studies from tertiary, ophthalmology referral centers report that the chronic forms, such as vernal and atopic keratoconjunctivitis, are the most frequently seen by ophthalmologists. A recent large survey performed at a national level involving 304 ophthalmologists showed that the majority of patients with allergic conjunctivitis suffer annually of few episodes of mild ,intermittent conjunctivitis. However, 30% of patients are affected by frequent episodes with intense and persistent symptoms. Treatment is frequently not appropriate. SUMMARY: Even though allergic conjunctivitis is often associated to allergic rhinitis, epidemiology studies frequently do not include specific ophthalmological evaluations. An understanding of allergic conjunctivitis disease, its prevalence, demographics and treatment paradigms will provide important information towards understanding its pharmacoeconomics and burden on the national health systems.

Small fiber peripheral neuropathy in Wilson disease: an in vivo documentation by corneal confocal microscopy.

PURPOSE: Wilson disease (WD) is a disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs, as the brain and cornea. The aim of this study was to investigate central corneal changes and in particular to assess the parameters of corneal subbasal nerve plexus (SBNP) in patients affected by WD, using corneal confocal microscopy (CCM). METHODS: A total of 24 patients affected by WD and 24 healthy control subjects were included in this cross-sectional comparative study. One eye of each subject was examined to quantify different corneal parameters. Mean cell diameter and mean cell density of the epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of branchings (NBr), number of beadings (NBe), and fiber tortuosity (FT) of the SBNP; mean cell density of keratocytes of the anterior, medium, and posterior stroma; and mean cell density, polimegatism, and pleomorphism of the endothelium, and central corneal sensitivity were analyzed. RESULTS: Wilson disease induced significant alterations in SBNP, and corneal epithelium. The NFLD (P < 0.0001), NF (P = 0.001), NBe (P = 0.025), and NBr (P < 0.0001) were significantly lower, whereas FT (P < 0.0001) was significantly higher in WD subjects compared to controls. Moreover mean epithelial cell diameter (P < 0.0001) and mean epithelial cell density (P < 0.0001) were significantly higher and lower compared to controls, respectively. CONCLUSIONS: The CCM showed significant corneal changes in SBNP, with concomitant corneal epithelium changes in WD, demonstrating the presence of small fiber peripheral neuropathy in these patients. The CCM may contribute to diagnosis and monitoring of the peripheral nervous system involvement in WD.

Aging and corneal layers: an in vivo corneal confocal microscopy study.

PURPOSE: To describe age-related changes of different corneal layers using a quantitative analysis of in vivo corneal confocal microscopy. DESIGN: Descriptive observational cross-sectional study. METHODS: A total of 108 healthy corneas of 108 subjects, distributed in four age categories, underwent in vivo corneal confocal microscopy. The effect of aging on the main features of corneal epithelium, sub-basal nerve plexus, stroma, and endothelium was investigated. RESULTS: Mean diameter of superficial epithelial cells increases with age (0.05 µm per year; p < 0.0001). Mean cell density of basal epithelium does not change with age (p = 0.37). The sub-basal nerve plexus fiber number, density, and the number of beadings do not statistically change with age (p = 0.14, p = 0.10 and p = 0.17, respectively). Keratocyte density significantly reduces with age in each stromal layer (p < 0.0001). Endothelial cell count decreases by 10.92 cells/mm(2) per year (p < 0.0001). Endothelial polymegathism index and pleomorphism index do not change with age (p = 0.79 and p = 0.39, respectively). CONCLUSIONS: Corneal confocal microscopy allows a non-invasive examination of the living cornea, analyzing the microstructure of each corneal layer. Aging significantly influences the corneal confocal microscopy parameters of individual corneal layers, except sub-basal nerve plexus and basal epithelium.

Pandemic influenza A/H1N1 2009 antibodies in the metropolitan area of Buenos Aires in Argentina.

OBJECTIVE: To estimate the infection prevalence in Buenos Aires during the outbreak of pandemic influenza A/H1N1 2009 virus (A(H1N1)pdm09). METHODS: A(H1N1)pdm09-specific antibodies were measured by hemagglutination inhibition assay in human serum samples collected 6 months after the outbreak and before the introduction of the A(H1N1)pdm09 vaccine in Argentina. Baseline levels of cross-reactive antibodies to A(H1N1)pdm09 were determined by testing 162 serum samples collected before 2009. RESULTS: The overall seroprevalence of A(H1N1)pdm09 in 150 children and 427 adults was 28.9% (95% confidence interval (CI) 25-33%), with a 58.0% prevalence in children <19 years of age and an 18.7% prevalence in adults ≥19 years of age (p<0.001). The prevalence was 43.5% in children <5 years old and 60.6% among children aged 5-18 years. The prevalence in adults declined with increasing age: 24.9% in 19-39-year-olds, 9.7% in 40-59-year-olds, and 8.1% in those ≥60 years old. The prevalence of specific A(H1N1)pdm09 antibodies was higher compared with the baseline in children (p=0.014), adolescents (p<0.001), and adults <40 years old (p=0.017). Seroprevalence in health care workers was not different from the rest of the population (13.6% vs. 19.3%, respectively; p=0.421). CONCLUSIONS: The prevalence of specific A(H1N1)pdm09 antibodies was high at 28.9%. The highest prevalence was observed in children, adolescents, and young adults.

Vernal keratoconjunctivitis-like disease in adults.

PURPOSE: To identify clinical, demographic, immunologic, and health-related quality-of-life data from a cohort of vernal keratoconjunctivitis (VKC) patients with the onset of the disease after puberty (VKC-like disease). DESIGN: Retrospective, observational case series. METHODS: Forty-nine patients with late-onset VKC-like disease from among 600 consecutive VKC patients. History of disease, test results for allergen sensitivity, signs and symptoms, impact of disease on work productivity, health-related quality of life, and treatment satisfaction were assessed. In addition, multiplex bead analysis for Th1/Th2 cytokines were carried out in tear samples from 20 VKC patients (10 adults and 10 children) and from 10 normal subjects. RESULTS: A family history of allergy was positive in only 28% and positive prick test results were present in 55% of the 49 VKC-like adult patients. Based on typical signs and symptoms, 48% were affected by the limbal form, 33% were affected by the tarsal form, and 19% were affected by the mixed form. Corneal ulcer complicated the disease in only 2 adult patients. Although the disease was not considered a limiting factor for work, productivity was reduced by 26% and social activities were reduced by 31% during active flare-ups. No significant differences were found in tear cytokine pattern production between VKC in children and VKC in adults. CONCLUSIONS: A late onset VKC-like disease can appear in young adults with signs and symptoms similar to those in pediatric disease, but with less corneal involvement.

Cytostatic and cytotoxic effects of 5-fluorouracil on human corneal epithelial cells and keratocytes.

PURPOSE: To investigate the effects of various 5-fluorouracil (5-FU) concentrations, exposure times, and application techniques on in vitro-cultured human corneal cells. METHODS: Human corneal epithelial cell (HCEC) and human corneal keratocyte (HCK) cultures were exposed to different 5-FU concentrations (0.025%-1%) and incubation durations (5 minutes to 2 hours). The cytostatic effect was evaluated as the percentage of inhibition of migration relative to the control. The evaluation of cytotoxic effect included both phase contrast microscopic observations and viability measures performed using an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] colorimetric assay. The results are expressed as ratio of optical density (OD) reduction 24 hours after exposure. RESULTS: The cytostatic effect was time and dose dependent. The 50% inhibiting dose was 0.55% after 1 hour of incubation for HCECs and was 0.5% after 2 hours of incubation for HCKs. A 100% inhibitory effect was never observed at any concentration or incubation duration. No cytotoxic changes were observed using an 5-FU concentration of <1%; 1% 5-FU showed time-dependent cytotoxic changes in HCEC cultures only. MTT analysis showed no OD reduction at 5-FU concentrations of <1%, whereas 1% 5-FU showed OD reduction <50% at any tested exposure time. HCECs showed higher reduction in OD than HCKs. CONCLUSIONS: 5-FU formulations topically used in clinical practice showed limited toxicity in normal cultured corneal epithelial cells and keratocytes.

Corneal confocal microscopy in patients with vernal keratoconjunctivitis.

PURPOSE: To compare corneal morphologic features using in vivo confocal microscopy in vernal keratoconjunctivitis (VKC) patients compared with normal subjects. DESIGN: Prospective, comparative study. PARTICIPANTS: Thirty-two VKC patients (26 males, 6 females; mean age, 17.1 years) and 40 normal subjects (20 males, 20 females; mean age, 19.3 years) were included. METHODS: All subjects underwent a full ophthalmologic examination. Confoscan CS4 (Nidek, Gamagori, Japan) images of the central cornea were obtained with a ×40 noncontact lens and Z-ring device. MAIN OUTCOME MEASURES: The superficial and basal epithelium, subbasal nerve plexus, anterior stroma, stromal nerves, and endothelium of the central cornea were studied. RESULTS: The VKC patients had increased diameter, reflectivity, and presence of nuclear activation of superficial epithelial cells; reduced density of the basal membrane; lower density of keratocytes, increased presence of activated keratocytes, and inflammatory cells in the anterior stroma; and lower density and number of fibers, lower number of beadings, and higher grade of tortuosity of fibers in the subbasal nerve plexus. Increased alterations in thickness, deflections, and tortuosity were observed in stromal corneal nerves. An increased number of inflammatory cells in close proximity to the subbasal and stromal nerve fibers also was observed in VKC subjects. CONCLUSIONS: Corneal involvement in VKC is associated with alterations of the epithelium and subbasal and stromal corneal nerves. These changes may relate to the tear dysfunction and nonspecific hyperreactivity typical of these patients. Corneal confocal microscopy is a useful tool for studying in vivo pathologic corneal changes in VKC.

Mitomycin C-assisted photorefractive keratectomy in high myopia: a long-term safety study.

PURPOSE: To evaluate the long-term corneal safety of topical mitomycin C (MMC) used during photorefractive keratectomy to prevent haze formation in highly myopic eyes. METHODS: Twenty-eight patients with bilateral high myopia underwent photorefractive keratectomy. One eye was randomly assigned to intraoperative 0.02% MMC and the fellow eye to conventional treatment. Each eye was checked at baseline and at 5 years after surgery using in vivo corneal confocal microscopy. RESULTS: At baseline, the endothelial cell density was 2970 ± 295 cells per square millimeter in the MMC-treated eyes and 2839 ± 323 cells per square millimeter in the control eyes. At 5 years, it was 2803 ± 307 and 2780 ± 264 cells per square millimeter, respectively (P = 0.27). The number of corneal nerve fibers was 3.9 ± 1.6 in the MMC-treated eyes and 4.4 ± 1.3 in the control eyes. At 5 years, it was 3.0 ± 1.6 and 2.7 ± 1.3, respectively (P = 0.15). The density of corneal nerves was 9600 ± 2915 µm/mm(2) in the MMC-treated eyes and 11,352 ± 3898 µm/mm(2) in the control eyes. At 5 years, the density was higher in the MMC-treated eyes (6790 ± 2447 µm/mm(2)) than in the control eyes (6024 ± 2977 µm/mm(2)) (P = 0.003). The number of nerve beadings at baseline was 12.9 ± 1.7/100 µm in the MMC-treated eyes and 12.3 ± 2.0/100 µm in the control eyes. At 5 years, it was 9.9 ± 2.6/100 and 9.4 ± 2.9/100 µm, respectively (P = 1.00). At 5 years, corneal nerve branching and tortuosity were similar in the 2 groups (P = 0.88 and 0.54, respectively). Epithelium thickness remained statistically unchanged (P = 0.69). CONCLUSIONS: Intraoperative use of topical 0.02% MMC compared with standard treatment does not induce significant long-term corneal changes, as assessed by in vivo corneal confocal microscopy.

Topical 1% 5-fluorouracil in ocular surface squamous neoplasia: a long-term safety study.

BACKGROUND/AIMS: The aim of this study was to evaluate the long-term corneal toxicity of topical chemotherapy with 1% 5-fluorouracil (5-FU) as a sole or adjuvant treatment of ocular surface squamous neoplasia (OSSN). METHODS: Forty-one consecutive cases of OSSN were included in this prospective study. Patients underwent topical chemotherapy with 1% 5-FU four times/day for 4 weeks (one course). Adjunctive courses were repeated until clinical and cytological tumour regression. Clinical confocal microscopy was used to check for 5-FU long-term corneal toxicity. RESULTS: Mean follow-up was 89.7±14.4 months (range 63-122 months). Twenty-two patients (53.7%) underwent topical 5-FU as a sole treatment, and 19 patients (46.3%) as adjuvant and/or debulking therapy. The mean number of 5-FU cycles was 1.9 (range 1-5 cycles). Three tumours (7.3%) treated with 5-FU alone recurred during follow-up. Recurrences were successfully treated with additional 5-FU courses. Clinical confocal microscopy showed no long-term difference between the treated eye and fellow (control) eye in: endothelial cells count, pleomorphism and polymegatism, anterior stromal keratocyte density, sub-basal nerve plexus fibre number, density, and beadings and central cornea epithelium thickness (p=NS). CONCLUSION: Topical 5-FU, as a sole or combined therapy, must be considered a long-term safe and effective treatment for patients affected by OSSN.

Comparación de la morbimortalidad entre recién nacidos prematuros pequeños y adecuados para la edad gestacional de acuerdo a estándares de crecimiento neonatales y fraccionales / Comparison of the morbimortality between small premature newborns and adequate for gestational age in agreement to standards of neonatal and fractional growth

Objetivo: Evaluar eventos neonatales adversos en recién nacidos prematuros ≤ 34 semanas pequeños y adecuados para su edad gestacional de acuerdo a estándares de crecimiento neonatales y fraccionales. Material y métodos: Estudio de una cohorte hospitalaria de recién nacidos prematuros con una edad gestacional ≤ 34 semanas, admitidos a la unidad de cuidados intensivos neonatales, desde el 1/1/98 hasta el 31/12/08. Las variables estudiadas fueron: mortalidad, enfermedad de membrana hialina, displasia broncopulmonar, hemorragia intraventricular (todos los grados), enterocolitis necrotizante y retinopatía del prematuro (todos los estadios). Las mismas se analizaron en un modelo de riesgo estimado mediante el cálculo del OR con IC95 por ciento. Resultados: La prevalencia de recién nacidos pequeños para la edad gestacional de acuerdo a los estándares de crecimiento neonatales fue de 56/218 (25,7 por ciento IC95 por ciento 19,6 a 31,7), mientras que de acuerdo a los estándares fraccionales fue de 78/218 (35,8 por ciento IC95 por ciento 29,2 - 42,4, p = 0,029). Cuando los recién nacidos prematuros pequeños para la edad gestacional fueron comparados a los adecuados para la edad gestacional de acuerdo a los estándares fraccionales presentaron un riesgo significativamente aumentado para mortalidad (OR 3 IC95 por ciento 1,2-7,7); enfermedad de membrana hialina (OR 2,7 IC95 por ciento 1,1-6,9), displasia broncopulmonar (OR 1,9 IC95 por ciento 1,1-3,7) y hemorragia intraventricular (OR 3,8 IC95 por ciento 2-6,9), mientras que el cotejo con estándares neonatales no arrojó diferencias. Conclusión: Las curvas fraccionales identificaron un aumento significativo en el riesgo de eventos adversos en prematuros pequeños para la edad gestacional, en comparación con las curvas neonatales.

Objective: To evaluate neonatal and fractional growth standards in determining charges of mortality and morbidity between premature small for gestational age infants. Material and methods: Hospital-based cohort study of singleton newborns of ≤ 34 weeks gestational age admitted to neonatal intensive care unit between January 1, 1998 and December 31, 2008. Outcome variables include: mortality, hyaline membrane disease, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and retinopathy of prematurity. For each variable bivariate analysis were performed (OR CI95 per cent). Results: The prevalence of small for gestational age according to neonatal growth standards was 56/218 (25.7 per cent, CI95 per cent 19.6-31.7) and according to fractional standards was 78/218 (35.8 per cent CI95 per cent 29.2-42.4, p= 0.029). According to fractional growth standards, when small for gestational age was compared with adequate for gestational age, it was associated with an increased risk of mortality (OR 3 CI95 per cent 1.2-7.7), hyaline membrane disease (OR 2, 7, CI95 per cent 1.1-6.9), bronchopulmonary dysplasia (OR 1.9 CI 95 per cent 1.1-3.7) and intraventricular hemorrhage (OR 3.8 CI95 per cent 2-6.9). Neonatal growth standard was not associated with an increased risk of mortality or morbidity. Conclusions: Fractional growth standards identifying an increased risk of adverse neonatal outcomes between preterm SGA infants, than neonatal standards.