Characterization of the vitamin A transport in preterm infants after repeated high-dose vitamin A injections.

BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status. SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life. RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P<0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P<0.01) but not in controls. In the vitamin A group, the retinol-to-RBP4 ratio was >1 in 15% of all infants on D3 and in 45% of infants on D28, but was ⩽1 in all, but one, controls on D28. CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i.m. vitamin A, serum retinol concentrations increased by 55%, with molar concentrations of retinol exceeding those of RBP4 in 45% of the infants suggesting transport mechanisms other than RBP4.

[Harlequin ichthyosis--medical and psychosocial challenges]. / Ichthyosis congenita gravis--eine medizinische und psychosoziale Herausforderung.

Harlequin ichthyosis is the most severe congenital keratinizing disorder. It is caused by mutations in the ABCA12 gene leading to defective lipid transport. The infants are born with ectropion, eclabium and fissured plate-like skin. Today these infants can survive with neonatal intensive care and retinoid therapy and need long-term interdisciplinary treatment in order to improve quality of life. However, the outcome in our case is impaired by severe psychomotor developmental delay, which has not yet been associated with Harlequin Ichthyosis.

Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus.

AIM: To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA). METHODS: We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen. RESULTS: Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2wksd) in early (median CRIB 6 and 5, respiratory distress >2 degrees in 36 and 34 infants) and late morbidities (intraventricular hemorrhage >2 degrees in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0wksd) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24months corrected age. CONCLUSION: Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.

Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants.

AIM: To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. METHODS: We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiographic criteria for the indication of PDA invention have remained unchanged. RESULTS: Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. CONCLUSION: In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin.

Growth in high risk infants <1500 g birthweight during the first 5 weeks.

BACKGROUND: Growth of very low birthweight (VLBW) infants is used to monitor nutrition and intrauterine velocity is taken as the desired goal. AIM: We hypothesised that beside nutrition growth failure is caused by disease severity. METHODS: Prospective longitudinal study of 45 VLBW infants undergoing intensive care, mechanical ventilation was used as proxy to disease severity. Nutritional intake, body weight, length, head circumference, and lower leg length (LLL) were measured during the first 5 weeks of life. RESULTS: Birthweight and gestational age were lower in 22 ventilated than in 23 unventilated infants (p<0.01). Median daily intake was 3.2 and 2.8 g/kg for protein (n.s.), 108 and 112 kcal/kg for energy (n.s.), 175 and 160 ml/kg for volume (p<0.01) up to day 35, respectively. Chronic lung disease occurred in 12 infants, five of whom were treated with dexamethasone. Artificial ventilation (p<0.01) and dexamethasone treatment (p<0.05) were independent predictors of weight gain. Median weight gain (8.2 and 9.7 g/kg/d), head growth (0.45 and 0.60 cm/week), and LLL growth (0.28 and 0.35 mm/d) were lower (p<0.05) in ventilated than in non-ventilated infants, respectively. The correlation of LLL growth with body length (r=0.31, p<0.05) and head growth (r=0.42, p<0.01) was weak. Dexamethasone arrested growth; median LLL gain was 0.21 and 0.31 mm/d in ventilated infants with and without dexamethasone (p<0.05). CONCLUSION: In VLBW infants, fetal growth rates are not reached with current feeding practice. In addition to inadequate nutrition, factors directly related to disease and treatment contribute to postnatal growth failure.

Selenium status in term and preterm infants during the first months of life.

OBJECTIVE: We hypothesized that very low birth weight (VLBW) infants have reduced serum and red blood cell (RBC) selenium (Se) at birth, which decrease further with current nutrition and are associated with chronic lung disease and septicaemia. DESIGN: We studied Se intake, concentration in serum and RBCs and glutathione peroxidase (GSH-Px) activity in preterm and term infants from birth until 16 weeks. Data are mean+/-standard deviation (s.d.). SETTING: Seventy-two preterm infants in two groups, born in Berlin, gestational age 26+0/30+0 weeks, birth weight 845/1270 g, with low Se intake (2.2+/-0.8/2.5+/-1.2 microg/kg/day), and 55 term infants, gestational age 39+1 weeks, birth weight 3160 g, born in Venezuela (high Se intake: 29+/-8 microg/day). RESULTS: A balance study in 10 preterm infants showed that Se is well absorbed from human milk (77+/-9%). Serum concentration was higher in term (142.0+/-40.0 microg/l) than in preterm infants (17.8+/-8.1/19.9+/-2.2 microg/l) at 4/7 weeks. Serum and RBC concentration of Se declined in all infants, low values in preterm infants did not correlate with chronic lung disease and septicaemia. GSH-Px activity in RBCs remained stable until 6 weeks of age in all infants and was not correlated with Se in RBCs. CONCLUSIONS: Se concentration in serum decreases during the first weeks of life and depends on intake. GSH-Px activity is not useful as a marker for Se status in infants up to 16 weeks after birth.

[Minimum patient volume in care for very low birthweight infants: a review of the literature]. / Mindestmengen in der Versorgung sehr untergewichtiger Frühgeborener: Eine Literaturübersicht.

BACKGROUND: Following the introduction of the DRG system and the definition of structural requirements for neonatal intensive care units (NICUs) in Germany, the number of perinatal centres has increased dramatically. The question arises if the formation of a great number of small NICUs compromises the outcome of infants with less than 1 500 g birthweight (VLBW). MATERIAL AND METHODS: A systematic medline search was performed for publications on patient volume in relation to outcome of VLBW infants. Mortality and intraventricular hemorrhage were used as outcome criteria. 9 publications from North America, 7 from non-German Europe and 5 from Germany were found. In 18 studies odds ratios and 95 % confidence intervals were reported for volume-outcome relations. RESULTS: For VLBW infants, mortality and intraventricular hemorrhage rates varied greatly between hospitals. In 20 of 21 publications, results were significantly less favourable in smaller hospitals. The threshold for obstetrics was 500-1000 deliveries per year and for neonatology 35-50 VLBW admissions per year. No significant relation of volume and outcome was found above 50 VLBW infants per year. DISCUSSION: The requirement of a minimum patient volume is a necessary, but not the only condition for good results in VLBW infants. CONCLUSIONS: In addition to fulfilling formal structural requirements, perinatal centres should be established in large delivery hospitals with at least 35 to 50 VLBW admissions per year.

Neonatal end-of-life practice in a German perinatal centre.

AIM: To investigate the end-of-life practice in a large perinatal centre in Germany. METHODS: Retrospective chart review was performed in all neonates deceased in the delivery room (n = 31) and the neonatal intensive care unit (n = 47) between 2002 and 2004. RESULTS: Neonatal death was preceded by an end-of-life decision (EOLD) in 81% of cases in the delivery room and 83% in the neonatal intensive care unit. The majority of deceased neonates were born prematurely or with congenital malformation. Life-sustaining treatment was not initiated in 74% of the infants deceased in the delivery room. In the unit, 52% died after withdrawal of therapy. Mechanical ventilation was withdrawn most frequently (79% of cases). Futility and immediate death were common considerations in EOLD, but the infant's suffering and future quality of life also played a role. Parents were involved in EOLD-making in all but emergency cases. No active termination of life was performed. CONCLUSION: In our perinatal centre, the majority of neonatal deaths occurred after limitation of therapy. Treatment was actively withdrawn in half of the infants in the neonatal intensive care unit. Actual end-of-life practice in a large perinatal centre differs from the restrictive attitude towards EOLD reported for German neonatologists in previous surveys.

Bilateral agenesis of the superior vena cava associated with congenital hydrothorax.

Agenesis of the superior vena cava is a rare anomaly that is generally asymptomatic in the neonate. We report a male neonate with bilateral (total) agenesis of the superior vena cava with obstructed thoracic duct and subsequent congenital hydrothorax, anomalies that were detected by prenatal ultrasound at 25 weeks' gestation. The cardiac anomaly was confirmed by postnatal magnetic resonance angiography. The chylothorax disappeared with conservative therapy.

Low soluble Fas (sFas) and sFas ligand (sFasL) content in breast milk after preterm as opposed to term delivery.

AIM: Various mechanisms of innate immunity and gastrointestinal integrity are potentially affected by soluble Fas (sFas) and sFas ligand (sFasL). Assuming that sFas and sFasL in milk reflect cellular events during lactogenesis, we aimed to assess the impact of premature parturition and duration of lactation on the concentrations of sFas and sFasL in human milk. PATIENTS AND METHODS: The content of the soluble form of the cell surface receptor Fas (sFas) and its natural ligand (sFasL) was measured in human breast milk of 44 healthy mothers after preterm (<35 wk, n=21) and term (>37 wk, n=23) delivery. Milk was furthermore classified as immature breast milk (days 4-7 of lactation) or mature breast milk (days 35-45 of lactation). Breast milk (2-3 ml) was sampled 5 min after the start of breastfeeding by manual expression or milk pump, and stored at -20 degrees C until analysis by an ELISA. RESULTS: sFas and sFasL concentrations were lower in immature milk after preterm compared to term delivery (sFas: 1.71; 1.38-2.47 ng/ml vs 3.03; 2.02-4.30 ng/ml, p < 0.001; sFasL: 0.13; 0.07-0.21 ng/ml vs 0.29; 0.15-0.60 ng/ml, p < 0.001 [median +/- interquartile range]). Mature milk samples, taken 1 mo later from both gestational groups, did not differ in sFas/sFasL content. Soluble Fas was positively correlated with sFasL in the same sample of immature (p < 0.001) and mature human milk (p < 0.05). A positive correlation was found between sFas and sFasL in immature and mature milk samples of the same mother (p < 0.01). The body mass index of the mothers and duration of pregnancy were positively correlated with the sFas and sFasL content in immature milk (p < 0.05 and p < 0.01, respectively) but not in mature milk. CONCLUSION: Preterm newborn infants fed with breast milk have a lower intake of sFas and sFasL compared to term neonates. Our results demonstrate that preterm delivery affects breast milk composition.

Development of a surveillance system for nosocomial infections: the component for neonatal intensive care units in Germany.

Neonates are at high risk of nosocomial infections and surveillance has been shown to be valuable for the reduction of nosocomial infections. The National Nosocomial Infections Surveillance (NNIS) system established in the US has a special surveillance component for neonatal intensive care units (NICUs) with some fairly specific methods. However, there are no specific definitions of nosocomial infections in this patient group. When creating a surveillance component for NICUs in Germany we therefore decided not to adopt merely all Centers for Disease Control and Prevention definitions and NNIS methods, but also to develop our own surveillance methods for this patient group. For this process four steps became necessary: (1)development of modified definitions for nosocomial infections and their evaluation; (2)testing the NNIS method in three NICUs with infection control nurses; (3)a pilot project for a surveillance component within the national surveillance system in Germany; and (4)establishment of a surveillance component within our national surveillance system. The system is now established in 33 hospital departments and 66 NICUs participate in the surveillance system. We have an overview of 3357 neonates in three birthweight groups. This article explains the reasons for the various steps, and the advantages and disadvantages of modification of the original NNIS methods and definitions.

[The clinical relevance of subcutaneous-thoracic ratio in preterm newborns as a possibility for quantification of capillary leak syndrome]. / Die klinische Bedeutung der Weichteildicke in Röntgen-Thoraxaufnahmen bei Frühgeborenen mit einem Geburtsgewicht unter 1500 Gramm - eine Quantifizierungsmöglichkeit des Kapillarlecksyndroms.

BACKGROUND: Capillary leak syndrome (CLS) is associated with increased morbidity and mortality in preterm newborns (PN) with sepsis or necrotizing enterocolitis. PATIENTS AND METHODS: In order to provide improved standards for measuring edema and for the definition of CLS, subcutaneous-thoracic ratios (S/T) were calculated from 821 anteroposterior supine chest radiographs of 119 PN with a birth weight below 1500 g. The S/T was computed by 100 % minus ratio of dividing the outer margins of the eighth rib by the total diameter of the thorax at the same position. Birth weight, gestational age, need for assisted ventilation and the position of the diaphragm did not significantly affect S/T. The S/T drifted downwards slightly with postnatal age. RESULTS: To provide normal standards of S/T in PN, the ratio was calculated in percentiles and the higher percentiles correlated with diseases. 771 S/T were lower than 10.1 % (95th percentile), 21 were 10.1 - 12.6 % (97.5th percentile) and 20 were even higher. 3 of the 100 PN (84 %) with an S/T < 10.1 % died because of extreme immaturity. Eight patients (6.7 %) had an S/T between the 95th and the 97.5th percentile in at least one of their radiographs. Four of them had a respiratory distress syndrome and one died. Eleven PN had an S/T > 12.6 %. All of them showed a multiple organ failure and four died. When the SIT was > 15 % the edema became visible. A CLS was diagnosed in two PN with an S/T > 20 %. CONCLUSIONS: The threshold for the capillary leak syndrome was found to be 12.6 % also in reference to the course of diseases. The S/T is a useful tool because it is simple to measure and calculate, and is available from a single frontal film. The ratio can measure objectively the edema and the CLS in PN.

Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn infants of 23-26 weeks gestation.

In preterm newborn infants, topical iodine-containing antiseptics disturb thyroid hormone regulation while alcohol-based disinfectants may cause local burns. We therefore investigated the use of an aqueous solution containing 0.1% octenidine and 2% 2-phenoxyethanol for skin disinfection during the first seven days of life in premature newborns with a gestational age <27 weeks who were consecutively admitted to our level III neonatal intensive care unit between November 1, 2000 and December 31, 2001 (N=24). In boys. (N=13) the renal excretion of absorbed 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid was quantitated by high-pressure liquid chromatography. In the most immature newborn (gestational age 23 6/7 weeks), a transient erythematous reaction was observed following application of the octenidine/phenoxyethanol solution prior to umbilical vessel catheterization. No other local reactions were observed. The urinary concentration of 2-phenoxyethanol was <2 ppm in all samples, while urinary 2-phenoxyacetic acid concentrations reached 5-95 ppm (median 24 ppm). One infant had a culture-proven septicaemia (Bacillus species) during the first seven days of life. We conclude that, in contrast to alcohol-based antiseptics, an aqueous solution of 0.1% octenidine and 2-phenoxyethanol does not cause major skin damage in premature newborn infants <27 weeks' gestation. 2-Phenoxyethanol is readily absorbed by the newborn's skin but apparently undergoes extensive oxidative metabolization to 2-phenoxyacetic acid.

Calcium, phosphorus and magnesium balance: FM 85 fortification of human milk does not meet mineral needs of extremely low birthweight infants.

OBJECTIVE: Extremely low birthweight (<1000 g) infants are growing rapidly and their nutritional requirements for calcium, phosphorus, magnesium are high. DESIGN: Prospective, mineral balance. SETTING: The study was carried out at the Department of Neonatology, Virchow-Hospital, Charité Berlin and the Department of Molecular Trace Element Research, Hahn-Meitner-Institute Berlin. SUBJECTS: Nineteen infants <1000 g birthweight were admitted, nine infants dropped out and 10 infants (birthweight 730-995 g), fed fortified human milk were included. INTERVENTION: We collected infant's urine and feces for 72 h, a sample of human milk and infant's blood at 7 and 12 weeks of age. Elements were measured by inductively coupled plasma atomic emission spectrophotometry. RESULTS: Mean (s.d.) mineral concentration in milk was low especially at 12 weeks: calcium 9.88 (+/-3.58) mmol/l, phosphorus 7.02 (+/-3.81) mmol/l, magnesium 1.59 (+/-0.54) mmol/l. Calcium retention was minimal or negative during the study, whereas phosphorus and magnesium balances were positive. Caffeine and diuretics increased mineral excretion. Serum alkaline phosphatase was mostly <800 U/l, and 162 U/l in one infant with zinc deficiency at 12 weeks. Alkaline phosphatase correlated with absorption and retention of phosphorus, and with longitudinal growth. CONCLUSIONS: Infants <1000 g have high nutritional needs for calcium, phosphorus and magnesium, which are not met by a human milk fortifier widely used in Europe. Controlled trials are needed to assess requirements, duration and risks of mineral supplementation.

Hyperoxia- and hypoxia-mediated activation of polymorphonuclear leukocytes: a comparison of cord and adult venous blood.

BACKGROUND: Among the most prominent changes occurring in newborn infants is the exposure of tissues and blood cells to increased oxygen tension. This increase is even more pronounced in neonatal resuscitation using 100% oxygen, currently recommended in the published guidelines. OBJECTIVE: To analyse the response of neonatal and adult polymorphonuclear neutrophils (PMN) to high or low oxygen tension in vitro. MATERIALS: Neonatal cord blood and adult venous blood without previous contact to ambient air was exposed to 0, 21, or 100% oxygen for 30 min followed by incubation for up to 24 h. METHODS: Flow cytometry was used to assess PMN activation as indicated by downregulation of L-selectin expression. Cell viability was quantified by the amount of propidium iodide uptake. RESULTS: In adult PMN, L-selectin downregulation was greatly accelerated by hypoxia (PO2=27.2+/-3.4 mmHg) compared with both normoxia (PO2=71.0+/-11.0 mmHg) or hyperoxia (PO2=653.2+/-9.4) (P<0.05). In contrast, hyperoxia was the most potent stimulus for cord blood PMN, compared with both normoxia and hypoxia (P<0.05). Evidence of necrosis as indicated by positive staining for propidium iodide was similar in cord blood (10 h: 5.83% in oxygen) and in adult blood (10 h: 6.45% in oxygen). No differences were found between exposure to hypoxia, normoxia, or hyperoxia. CONCLUSION: Oxygen exposure of neonatal PMN leads to a more pronounced activation as compared with adult cells. Exposure towards high concentrations of oxygen may contribute to inflammatory processes during early neonatal life.

Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus.

BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2-51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP.

Patent ductus arteriosus in very low birthweight infants: complications of pharmacological and surgical treatment.

AIMS: To evaluate complications of surgical and pharmacological treatment of symptomatic patent ductus arteriosus (PDA) in very low birthweight (VLBW) infants. PATIENTS AND METHODS: Of 931 VLBW infants consecutively admitted 1987-1998, a significant PDA prompted first-choice treatment by indomethacin in 101 infants, and surgery in 55 infants. PDA closed or became asymptomatic after indomethacin in 64 patients (63%), while 34 went on to surgery. PDA closure was achieved in all 61 infants after ligation and in 26 of 28 infants after clipping. RESULTS: Transient renal impairment after indomethacin treatment was recorded in 40 of 101 infants (40%), compared to renal impairment in 9 of 55 infants (16%) undergoing surgery without prior indomethacin. No differences in necrotizing enterocolitis and intracranial hemorrhage rates were seen. Air leak occurred in 6 of 89 infants after surgery, two of which had fatal tension pneumothorax. Intraoperative hemorrhage requiring emergency transfusion occurred in 2 infants, wound infection occurred in 2 infants and phrenic palsy in one infant. Based on an intention-to-treat analysis, the overall fatality rates were 16 of 101 (16%) for indomethacin and 14 of 55 (25%) for surgery. CONCLUSIONS: Despite the short-comings inherent to retrospective analyses, we propose that surgery should be reserved for infants not responding to pharmacological PDA closure.

Neonate with spinal hypoplasia on T12 and a localized vertebral malformation on L4.

We report a case of a neonate with sectional narrowing of the spinal cord on the level of T12 to L2 and a deformed vertebral body on a different level, L4. In previously described cases of sectional spinal dysgenesis, the vertebral and spinal cord malformations are usually found on the same level. Our case may represent a new variant of spinal dysgenesis.

Breast milk from mothers of very low birthweight infants: variability in fat and protein content.

UNLABELLED: While breast milk appears to be superior to formula for the development of very low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands of the rapidly growing premature infant. To estimate the nutritional variability of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method) and fat content (creamatocrit) were measured in breast-milk spot samples from mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of lactation. Protein content (median 1.9 g dl(-1), range 1.1-3.5 g dl(-1)) and fat content (3.8/1.0-14.6 g dl(-1)) were highly variable and lacked a normal distribution over all samples and in individual women's milk. There was only a weak correlation between fat and protein (rs=0.416, p < 0.001). Fat but not protein was lower in morning samples than in samples collected later in the day (p < 0.001). Protein but not fat content decreased during the weeks of lactation (rs =-0.446, p < 0.001). No impact of the baby's gestational age was observed. CONCLUSION: The fat and protein content of breast milk from mothers of VLBW infants is highly variable, calling into question the clinical feasibility of individualized supplementation of breast milk for VLBW infants based on spot sample measurements.