Hyperglycemia in Extremely Preterm Infants-Insulin Treatment, Mortality and Nutrient Intakes.

OBJECTIVE: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants. STUDY DESIGN: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data. RESULTS: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05). CONCLUSIONS: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age.

BACKGROUND: Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children. METHODS: A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels. RESULTS: After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up. CONCLUSION: Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass.

Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study.

AIM: To explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants. METHODS: Retrospective population-based study of all ELGA infants (<27 weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70 days of postnatal age were retrieved from hospital records. RESULTS: Study infants (n = 531) had a mean ± SD gestational age of 25.3 ± 1.1 weeks and a birth weight of 765 ± 170 g. Between 0 and 70 days, average daily energy and protein intakes were 120 ± 11 kcal/kg and 3.2 ± 0.4 g/kg, respectively. During this period, standard deviation scores for weight, length and head circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational age, baseline anthropometrics and severity of illness into account, lower energy intake correlated with lower gain in weight (r = +0.315, p < 0.001), length (r = +0.215, p < 0.001) and head circumference (r = +0.218, p < 0.001). Protein intake predicted growth in all anthropometric outcomes, and fat intake was positively associated with head circumference growth. CONCLUSION: Extremely low gestational age infants received considerably less energy and protein than recommended and showed postnatal growth failure. Nutrient intakes were independent predictors of growth even after adjusting for severity of illness. These findings suggest that optimized energy and macronutrient intakes may prevent early growth failure in these infants.

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD).

AIM: To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants. METHODS: Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD. RESULTS: Postnatal mean IGF-I levels at postnatal day (PND) 3-21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 µg/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (ß)), PNDs 3-21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30-33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 µg/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3-21 were the most predictive risk factors associated with BPD (r(2) = 0.634, p < 0.001). CONCLUSION: Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD.

Fresh-frozen plasma as a source of exogenous insulin-like growth factor-I in the extremely preterm infant.

CONTEXT: Preterm birth is followed by a decrease in circulatory levels of IGF-I and IGF binding protein (IGFBP)-3, proteins with important neurogenic and angiogenic properties. OBJECTIVE: Our objective was to evaluate the effects of iv administration of fresh-frozen plasma (FFP) from adult donors on circulatory levels of IGF-I and IGFBP-3 in extremely preterm infants. DESIGN, SETTING, AND PATIENTS: A prospective cohort study was performed in 20 extremely preterm infants [mean (SD) gestational age 25.3 (1.3) wk] with clinical requirement of FFP during the first postnatal week. Sampling was performed before initiation of transfusion, directly after, and at 6, 12, 24, and 48 h after completed FFP transfusion. MAIN OUTCOME MEASURES: Concentrations of IGF-I and IGFBP-3 before and after transfusion of FFP were determined. RESULTS: FFP with a mean (SD) volume of 11 ml/kg (3.1) was administered at a median postnatal age of 2 d (range 1-7). Mean (SD) IGF-I and IGFBP-3 concentrations in administered FFP were 130 (39) and 2840 microg/liter (615), respectively. Immediately after FFP transfusion, mean (SD) concentrations of IGF-I increased by 133% from 11 (6.4) to 25 microg/liter (9.3) (P < 0.001) and IGFBP-3 by 61% from 815 (451) to 1311 microg/liter (508) (P < 0.001). Concentrations of IGF-I and IGFBP-3 remained higher at 6 (P < 0.001, P = 0.009) and 12 h (P = 0.017, P = 0.018), respectively, as compared with concentrations before FFP transfusion. Typical half-life of administrated IGF-I was 3.4 h for a 1-kg infant. CONCLUSION: Transfusion of FFP to extremely preterm infants during the first postnatal week elevates levels of IGF-I and IGFBP-3.

A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants.

In preterm infants, low levels of insulin like growth factor 1 (IGF-I) have been associated with impaired growth and retinopathy of prematurity. Our objective was to study safety and pharmacokinetics of i.v. administered rhIGF-I with its binding protein 3 (rhIGFBP-3) to preterm infants. At 3 d chronological age, an i.v. 3 h infusion of rhIGF-I/rhIGFBP-3 was administered followed by serial measurements of IGF-I and IGFBP-3. Infants were evaluated for physiologic safety measurements. The individual dose of rhIGF-I ranged from 1 to 12 microg/kg. The study was conducted at Queen Silvia Children's Hospital, Gothenburg, Sweden, between January and November 2007. Five patients (3 F) with mean (range) post menstrual age 27 wk (26-29) and birth weight 1022 g (810-1310) participated. IGF-I and IGFBP-3 levels before infusion were median (range) 18 (12-28) and 771 (651-1047) ng/mL, respectively. Immediately after study drug infusion, serum IGF-I and IGFBP-3 levels were 38 (25-59) and 838 (754-1182) ng/mL, respectively. Median (range) half-life for IGF-I and IGFBP-3 was 0.79 (0.59-1.42) and 0.87 (0.85-0.94) hours, respectively. Blood glucose, insulin, sodium, potassium, and physiologic safety measures were within normal ranges. The rhIGF-I/rhIGFBP-3 equimolar proportion was effective in increasing serum IGF-I levels and administration under these study conditions was safe and well tolerated.

C-Peptide Suppression During Insulin Infusion in the Extremely Preterm Infant Is Associated With Insulin Sensitivity.

CONTEXT: Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants. OBJECTIVE: To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high-frequency sampling regimen in extremely preterm infants treated with insulin because of hyperglycemia. DESIGN: Prospective longitudinal cohort study. SETTING: Two university hospitals in Sweden between December 2015 and September 2016. PATIENTS AND INTERVENTION: Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose >10 mmol/L) at the start of insulin infusion, at 12, 24, and every 24 hours thereafter during ongoing infusion, and 12, 24, and 72 hours after the end of insulin infusion. MAIN OUTCOME MEASURES: Longitudinal serum concentrations of insulin and C-peptide and plasma glucose levels. RESULTS: During insulin infusion, the serum C-peptide concentrations decreased compared with at start of infusion (P = 0.036), and then increased after ending the infusion. Individual insulin sensitivity based on the nonfasting plasma glucose/insulin ratio at the start of insulin infusion correlated with the initial decrease in serum ΔC-peptide[after 12h] (P = 0.007) and the degree of lasting decrease in serum ΔC-peptide[after end of infusion] (P = 0.015). CONCLUSION: Exogenous insulin infusion suppressed the C-peptide concentration to individually different degrees. In addition, the effect of insulin infusion on ß cells may be linked to individual insulin sensitivity, where a low insulin sensitivity resulted in a more pronounced decrease in C-peptide during insulin infusion.

Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs ω-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of ω-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. Objective: To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating ω-3 and ω-6 LC-PUFAs. Design, Setting, and Participants: This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in Göteborg, Sweden. Main Outcomes and Measures: Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. Results: Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20:4 ω-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. Conclusions and Relevance: Low postnatal levels of the ω-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction. Trial Registration: clinicaltrials.gov Identifier: NCT02760472.

Seronegative, complicated hydatid cyst of the lung: A case report.

Cystic echinococcosis (CE) is an important helminthic zoonotic disease that commonly affects the liver and lungs. Imaging methods and serology establish the diagnosis in most cases. Chest x-ray can diagnose uncomplicated pulmonary hydatid cysts, whereas superinfection and/or rupture of the hydatid cyst (complicated cysts) may change the radiographic appearance and lead to delayed diagnosis and treatment. We report the case of a patient with hemoptysis and chest pain, where computer tomography scan of the lung suggested a large, ruptured hydatid cyst. However, serological tests with indirect hemagglutination (IHA)for Echinococcus granulosus antibodies were negative, and there was massive growth of Streptococcus pneumoniae in sputum. Based on this, we concluded that the patient had a bacterial lung abscess. The diagnosis of CE was only made after surgical removal of the cyst followed by microscopy and polymerase chain reaction.

Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial.

BACKGROUND & AIMS: The purpose of the study was to compare the effects of the parenteral emulsion SMOFlipid®, with 15% fish oil, with Clinoleic® on retinopathy of prematurity (ROP) and other morbidities and growth, and to compare their impact on longitudinal serum levels of fatty acids. Retinopathy of prematurity, other morbidity and growth were correlated with each parenteral lipid supplement. METHODS: Ninety infants born at gestational age <28 weeks were randomized to treatment with SMOFlipid® or Clinoleic®. Two thirds (66%) of the infants received parenteral nutrition for up to 14 days birth (median 8, range 2-14 days), and additional 25% of the infants received for up to 28 days after birth (median 21, range 15-28 days). Cord blood samples and then venous blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were analyzed by gas chromatography-mass spectrometry. Treatment groups were compared with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus sepsis and growth between birth and 36 weeks. RESULTS: Infants on SMOFlipid® had higher fractions of omega-3 LCPUFA eicosapentaenoic acid (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32 postmenstrual weeks compared to infants on Clinoleic®. Treatment groups did not differ in morbidities or growth. CONCLUSION: Supplementation with SMOFlipid® containing 15% fish oil during parenteral nutrition increased EPA substantially, DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce morbidity or affect growth. Since extremely preterm infants accumulate a large deficit of DHA and AA, studies on more prolonged or different levels of DHA and AA supplementation are warranted.

Longitudinal postnatal weight and insulin-like growth factor I measurements in the prediction of retinopathy of prematurity.

OBJECTIVE: To investigate whether postnatal growth and development influence retinopathy of prematurity (ROP) and may be included in screening for ROP. DESIGN: We developed an algorithm to predict for individual infants the risk of later ROP development requiring treatment based on the postnatal longitudinal systemic factors of insulin-like growth factor I (IGF-I) level, IGF binding protein 3 level, and postnatal weight gain. We developed the algorithm based on 79 preterm infants considered at risk for ROP by standard criteria (gestational age, 23.6-31.7 weeks) in a longitudinal study measuring weight gain and serum IGF-I and IGF binding protein 3 levels weekly from birth until discharge from the hospital. We monitored deviations from reference models for weight and IGF-I level (preterm children who developed no or minimal ROP) to detect indications for treatable ROP by Early Treatment for Retinopathy of Prematurity study criteria. RESULTS: This monitoring method detected 6 (100%) of 6 infants in this cohort who required treatment for ROP with a warning signal at least 5 weeks before requiring treatment and at least 3 weeks before the onset of stage 3 ROP. The majority of infants (61/73 infants) requiring no treatment were also correctly identified. CONCLUSIONS: Monitoring the postnatal factors of weight, IGF-I level, and IGF binding protein 3 level substantially enhances the clinician's ability to identify patients who will require treatment for ROP.

Effect of Preterm Birth on Postnatal Apolipoprotein and Adipocytokine Profiles.

BACKGROUND: Critical metabolic changes preparing for ex utero life may occur at the fetal age of approximately 28-32 weeks, and preterm birth <28 weeks postmenstrual age (PMA) may affect these pathways. Children born <28 weeks often have poorer outcomes possibly due to a major shift in metabolism, including nutritional supply and a shift in lipid-transporting particles and lipid profile. This shift may occur in apolipoprotein and adipocytokine levels, which may influence metabolism. OBJECTIVE: To determine whether there is a shift in apolipoprotein and adipocytokine levels in neonates born at a gestational age (GA) of 28 and 32 weeks, respectively. METHODS: Blood samples from 47 infants (GA 32 weeks, n = 30 and GA 28 weeks, n = 17) were collected at birth and, in the GA28 group, also at PMA 32 weeks. Apolipoproteins A-1, A-2, B, C-2, C-3, and E were analyzed, as well as adiponectin and leptin levels. RESULTS: Serum levels of apolipoproteins A-1, C-2, C-3, and E were lower at birth in the GA28 group compared to the GA32 group. Adiponectin and leptin levels were low at birth in the GA28 group. In the GA28 group 4 weeks after birth, leptin levels were still low, whereas adiponectin levels had increased to levels similar to those found at birth in the GA32 group. Apolipoprotein A-1, C-2, C-3, and E levels were negatively correlated with days receiving total parenteral nutrition. CONCLUSION: There are significant differences in apolipoprotein and adipocytokine levels, which can be associated with GA and birth weight. The impact of these changes on neonatal and future morbidity remains to be determined.

Proliferative retinopathy is associated with impaired increase in BDNF and RANTES expression levels after preterm birth.

BACKGROUND: Extremely preterm delivery is, amongst other complications, associated with retinopathy of prematurity (ROP). Untreated, ROP can progress to visual impairment and blindness due to an overgrowth of new vessels in the retina and vitreous cavity. OBJECTIVE: The aim of this study was to identify cytokine markers within the first weeks of life that could be used to predict the risk for development of ROP later in life. METHODS: Serum levels of 27 different cytokines in infants born at gestational weeks 23-30 were analyzed using a multiplex immunoassay method and compared between infants who did not develop ROP and infants who later developed proliferative ROP. In addition, mRNA levels of brain-derived neurotrophic factor (BDNF) in retinas from mice exposed to hyperoxia were analyzed using quantitative real-time PCR. RESULTS: At birth, serum levels of IL-5 were higher in infants with no ROP compared to infants with proliferative ROP. 10-14 days after birth, serum levels of BDNF and RANTES were lower in infants who later developed proliferative ROP compared to infants who did not develop ROP. Furthermore, mRNA expression levels of BDNF in retinas from mice exposed to hyperoxia were significantly lower at postnatal day 15 compared to retinas from mice in room air. CONCLUSIONS: These results indicate that BDNF and RANTES may be important factors in the selective vulnerability of ROP development in preterm infants.

Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening.

BACKGROUND: The risk for sight-threatening retinopathy of prematurity is predicted by using gestational age and/or weight at birth. All infants below a threshold undergo serial ophthalmologic examinations for identification of those who would benefit from treatment (approximately 10%). We hypothesized that factoring in postnatal weight gain could identify children at risk for sight-threatening retinopathy of prematurity more specifically and earlier. METHODS: Weekly weights from birth to postmenstrual week 36 were retrospectively entered into a surveillance system that gave an alarm when the rate of weight gain decreased to a certain level. For all children (N = 354) screened and/or treated for retinopathy of prematurity at Sahlgrenska University Hospital in 2004-2007, weekly weights were recorded. One child was excluded because of known nonphysiologic weight gain (hydrocephalus). RESULTS: For 127 (36%) of 353 children, no alarm was given; for 40%, alarm at low risk was given after postmenstrual week 32. None of those children developed retinopathy of prematurity requiring treatment. Of the remaining 24% of children who received alarm at high or low risk before 32 postmenstrual weeks, 41% developed proliferative retinopathy of prematurity and 29% were treated because of sight-threatening disease. The median time from alarm to treatment was 9 weeks. CONCLUSIONS: The weight, insulin-like growth factor, neonatal retinopathy of prematurity algorithm detected early 100% of infants who developed retinopathy of prematurity requiring treatment and correctly predicted the majority who did not require treatment. With this simple postnatal evaluation, costly stressful eye examinations can be markedly reduced (approximately 75% of infants). In addition, early identification of children at risk may lead to the initiation of interventions and possibly prevent sight-threatening retinopathy of prematurity.

Periventricular leukomalacia and retinopathy in a term infant born to a mother with asthma.

A male child, born at 37+5 gestational weeks (GWs) (birthweight 2000g) after intrauterine growth retardation (IUG; -3 SD), to a mother treated during pregnancy for asthma, developed periventricular leukomalacia and retinopathy with total retinal detachment in the left eye and partial detachment in the right eye. Apart from basic asthma treatment with terbutalin, budesonid, and fenoterolhydrobromid throughout the pregnancy, she was treated with intravenous or oral cortisone for 6.5 weeks from 28+5 GWs. In addition she developed deep venous thrombosis at 29 GWs and was treated with heparin until delivery. Psychotic symptoms during the 31st GW were treated with diazepam, haloperidol, and levomepromazin. Functional sequelae for the child were visual impairment (visual acuity 5/60), uneven intellectual profile (Wechsler Pre-school and Primary Scale of Intelligence, Verbal IQ 94 and Performance IQ 32 at 8y of age), and autistic-like behaviour. The possibility that pre- and perinatal risk factors (e.g. severe maternal illness, IUGR, and cortisone treatment) in a term infant may create conditions for developing eye and brain pathologies commonly closely related to preterm birth should be considered.

Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit.

BACKGROUND: We hypothesized that in premature infants, retinal vascular growth retardation between birth and postmenstrual age of approximately 30 to 32 weeks that initiates retinopathy of prematurity is paralleled by brain growth retardation. METHODS: In a prospective longitudinal study, we measured postnatal head growth, retinopathy of prematurity stage, protein and energy intake, severity of illness and serum insulin-like growth factor-1 levels in 58 preterm infants (mean gestational age at birth: 27.6 weeks) from birth until postmenstrual age of approximately 40 weeks. RESULTS: Premature infant head growth decelerates dramatically after birth until postmenstrual age of approximately 30 weeks. Head growth retardation coincides with retinal vascular growth suppression. Accelerated growth follows between post menstrual ages of approximately 30 to 32 weeks and approximately 40 weeks. The degree of head growth retardation up to postmenstrual age of 31 weeks corresponds to the degree of retinopathy of prematurity and to the degree of suppression of serum levels of insulin-like growth factor-1. At postmenstrual age of 31 weeks, if a child's head circumference SD is below -2.5, then the probability of also developing at least stage 3 retinopathy of prematurity increases fivefold compared with head circumference above -2.5 SD (32% vs 6%) suggesting parallel processes in brain and retina. Serum insulin-like growth factor-1 levels correlate positively with head circumference SD score and with the degree of retinopathy of prematurity. CONCLUSIONS: The correlation between head and retinal growth is consistent with insulin growth factor-1 being one of the postnatal growth factors involved in this multifactorial process and also suggests that factors that contribute to retinopathy of prematurity during this critical period may also affect neurological dysfunction. Additional studies are required to establish this connection.