Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants

AIMS—To improve energy intake in sick very low birthweight (VLBW) infants; to decrease growth problems, lessen pulmonary morbidity, shorten hospital stay, and avoid possible feeding related morbidity. Morbidity in VLBW infants thought to be associated with parenteral and enteral feeding includes bronchopulmonary dysplasia, necrotising enterocolitis, septicaemia, cholestasis and osteopenia of prematurity.METHODS—A prospective randomised controlled trial (RCT) comparing two types of nutritional intervention was performed involving 125 sick VLBW infants in the setting of a regional neonatal intensive care unit. Babies were randomly allocated to either an aggressive nutritional regimen (group A) or a control group (group B). Babies in group B received a conservative nutritional regimen while group A received a package of more aggressive parenteral and enteral nutrition. Statistical analysis was done using Student''s t test, the Mann-Whitney U test, the χ² test and logistic regression.RESULTS—There was an excess of sicker babies in group A, as measured by initial disease severity (P <0.01), but mean total energy intakes were significantly higher (P <0.001) in group A at days 3 to 42 while receiving total or partial parenteral nutrition. Survival and the incidences of bronchopulmonary dysplasia, septicaemia, cholestasis, osteopenia and necrotising enterocolitis were similar in both groups. Growth in early life and at discharge from hospital was significantly better in babies in group A. There were no decreases in pulmonary morbidity or hospital stay.CONCLUSION—Nutritional intake in sick VLBW infants can be improved without increasing the risk of adverse clinical or metabolic sequelae. Improved nutritional intake resulted in better growth, both in the early neonatal period and at hospital discharge, but did not decrease pulmonary morbidity or shorten hospital stay.     

Association of late-onset neonatal sepsis with late neurodevelopment in the first two years of life of preterm infants with very low birth weight

Objectiveto establish the influence of late-onset sepsis on neurodevelopment of preterm infants with very low birth weight (VLBW), according to the etiologic agent.Methodthis was a cohort of newborns with birth weight < 1,500 g and gestational age less than 32 weeks, admitted to the institutional intensive care unit (ICU) with up to 48 hours of life, and followed-up at the outpatient follow-up clinic for preterm infants with VLBW until 2 years of corrected age. Exclusion criteria: death within the first 72 hours of life, congenital malformations and genetic syndromes, children with congenital infection by the human immunodeficiency virus (HIV), congenital infection (STORCH), presence of early-onset sepsis and cases with more than one pathogen growth in blood cultures. Septic and non-septic infants were compared regarding neonatal outcomes and mortality. Neurodevelopment was assessed using the Bayley Scale (BSDI-II) at 18 to 24 months of corrected age.Results411 preterm infants with VLBW were eligible; the mean gestational age was 29 ± 2.2 weeks and mean birth weight was 1,041 ± 281grams. Late-onset sepsis occurred in 94 preterm infants with VLBW (22.8%). VLBW infants with Gram-positive infection showed motor deficit when compared to the non-septic group, 68.8% vs. 29.3%, respectively (OR 6; 1.6-21.8, p = 0.006); the cognitive development was similar between the groups. The overall mortality rate from infection was 26.7%; considering the pathogens, the rates were 18.7% for coagulase-negative Staphylococcus, 21.8% for Gram-positive bacteria, and 50% for Gram-negative bacteria and fungi.Conclusionneonatal sepsis has a significant influence on late neurodevelopment at 2 years of corrected age in preterm infants with VLBW, and Gram-positive infections are associated with motor deficit.     

Light reduction and the electroretinogram of preterm infants

AIMS—To examine the effects of light on retinal development and function in preterm infants as measured by the electroretinogram (ERG). Secondary outcomes included visual acuity testing, the incidence of retinopathy of prematurity, and general wellbeing, reflected in feeding tolerance, rate of weight gain, and length of hospital stay.METHODS—Eligibility criteria for enrolment were birthweight ? 1250 g and gestational age ? 31 weeks. Sixty one infants were randomly allocated by 6 hours after birth to a control or treatment group which wore 97% light filtering goggles for a minimum of four weeks or until the infant reached 31 weeks postmenstrual age.RESULTS—There were no significant differences between the two groups in the numbers of electroretinograms performed at 36 weeks of postmenstrual age. Although the sample size was not large enough to exclude clinically important differences in secondary outcomes, no significant differences were observed between the groups in visual acuity testing at 4-6 months corrected age, incidence of retinopathy of prematurity, weight gain, or length of stay.CONCLUSION—These data support the safety and feasibility of this intervention. A much larger study will be needed to determine whether light reduction to the eyes of very low birthweight infants will reduce the incidence of retinopathy of prematurity or enhance general wellbeing.     

Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants

AIM—To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants.METHODS—Forty infants were randomly allocated to receive either hydrocortisone (n=21) or dopamine (n=19).RESULTS—All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group.CONCLUSION—Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.     

Role of epidermal growth factor and transforming growth factor α in the developing stomach

AIMS—To determine whether epidermal growth factor (EGF) or the related transforming growth factor α (TGFα) may have a role in the developing human stomach; to substantiate the presence of EGF in human liquor in the non-stressed infant and whether EGF in amniotic fluid is maternally or fetally derived.METHODS—The temporal expression and localisation of EGF, TGFα, and their receptors during fetal and neonatal life were examined in 20 fetal and five infant stomachs. Simultaneously, samples of amniotic fluid and fetal urine from 10 newborn infants were collected and assayed for EGF by radioimmunoassay.RESULTS—EGF immunoreactivity was not noted in any of the specimens examined. In contrast, TGFα immunoreactivity was shown in mucous cells from 18 weeks of gestation onwards. EGF receptor immunoreactivity was seen on superficial mucous cells in gastric mucosa from 18 weeks of gestation onwards. The median concentration of EGF was 30 and 8.5 pg/ml in amniotic fluid and fetal urine, respectively, suggesting that EGF is not produced by the fetus.CONCLUSIONS—This study adds weight to the hypothesis that swallowed EGF, probably produced by the amniotic membranes, and locally produced TGFα, may have a role in the growth and maturation of the human stomach.     

Hepatitis B vaccination in preterm infants

AIM—To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants.METHODS—Recombinant hepatitis B vaccine (H-B-VAX II, 5 µg per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of ?2000 g received three doses at 0, 1, and 6 months of age.RESULTS—After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study.CONCLUSIONS—Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.     

Hypothyroxinemia and effectiveness of thyroxin supplementation in very low birth weight infants with abdominal distension and poor weight gain

Background

Very low birth weight (VLBW) infants sometimes develop abdominal distension and poor weight gain. The influence of thyroid function on these symptoms in VLBW infants has not been reported.

Methods

In a retrospective study, 18 VLBW infants whose abdominal distension and poor weight gain did not improve with standard treatment were enrolled as subjects. Serum levels of free thyroxin (fT₄) and thyroid stimulating hormone (TSH) were measured. Subjects with serum fT₄ levels less than 1.3 ng/dl received thyroxin supplementation. Another 18 VLBW infants were recruited as age- and weight-matched controls. We compared degree of intestinal dilation on X-ray, weight gain, and quantity of milk tolerated before and after starting thyroxin supplementation in the subjects and the controls.

Results

All subjects had serum fT₄ levels less than 1.3 ng/dl (mean, 0.72 ng/dl). TSH values varied widely and were less than 8 µU/ml in 12 subjects. Therefore, all subjects received thyroxin supplementation; after starting this, mean serum fT₄ level increased significantly to 1.31 ng/dl. In parallel with fT₄ increase, intestinal dilation improved in 16 of 18 subjects (mean grade of dilation decreased from 2.8 to 1.6). Weight gain and quantity of tolerated milk were significantly increased with thyroxin supplementation in all and 17 of the 18 subjects, respectively.

Conclusions

Thyroxin supplementation was effective in improving abdominal symptoms in VLBW infants whose serum fT₄ level was less than 1.3 ng/dl.     

Bacteremia induced by Bifidobacterium breve in a newborn with cloacal exstrophy

Bifidobacterium breve is an effective probiotic agent used in the field of neonatology. Although B. breve has been considered safe, a case of B. breve bacteremia has been reported. The pathogenic mechanism underlying the bacteremia is unknown. Herein, we report a second case of B. breve bacteremia that developed in a neonate with multiple abdominal organ anomalies. Following surgical repair immediately after birth, B. breve treatment was started. After 1 week, the infant developed B. breve bacteremia following the onset of adhesive ileus. The bacteremia was thought to have been associated with an intestinal obstruction. A pediatric culture bottle is theoretically unsuitable for incubating B. breve because B. breve is an obligate anaerobic bacterium. It was, however, cultured from pediatric culture bottles in the present case, suggesting that pediatric culture bottles may be useful for procuring B. breve and for determining antimicrobial susceptibility for screening purposes in neonatal patients.     

Intestinal flora in very low-birth weight infants

Aim:  To study the early faecal microbiota in very low-birth weight infants (VLBW, <1500 g), possible associations between faecal microbiota and faecal calprotectin (f-calprotectin) and to describe the faecal microbiota in cases with necrotizing enterocolitis (NEC) before diagnosis.
Methods:  Stool samples from the first weeks of life were analysed in 48 VLBW infants. Bacterial cultures were performed and f-calprotectin concentrations were measured. In three NEC cases, cultures were performed on stool samples obtained before diagnosis.
Results:  Bifidobacteria and lactobacilli were often identified in the first stool sample, 55% and 71% of cases, respectively within the first week of life. A positive correlation between lactic acid bacteria (LAB) and volume of enteral feed was found. Other bacteria often identified were Escherichia coli , Enterococcus and Staphyloccus sp. F-calprotectin was not associated with any bacterial species. All NEC cases had an early colonization of LAB. Prior to onset of disease, all cases had a high colonization of non- E. coli Gram-negative species.
Conclusion:  In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.     

Early increase of TNFα and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants

AIM—To investigate if early changes in concentrations of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF) from preterm infants could be used to detect infants at risk of chronic lung disease (CLD) and help in the selection of patients for early steroid treatment.METHODS—Twenty eight preterm infants less than 34 weeks of gestation (median 26 weeks) were intubated and daily measurements of TAF concentrations of tumour necrosis factor α (TNFα) and the interleukins IL-1β, IL-6, and IL-8 were made, using enzyme immunoassay techniques.RESULTS—Seventeen of the infants developed CLD. The infants who developed CLD had significantly increased concentrations of TNFα, IL-1ß, IL-6 on days 2 and 3. TNFα, IL-6, and IL-8 concentrations were significantly related to gestational age and duration of supplemental oxygen; TNFα, IL-6, and IL-8 concentrations also correlated with length of time on the ventilator.CONCLUSION—These data indicate that tracheobronchial aspirate fluid cytokine concentrations may be used as a predictor of subsequent CLD and may help select a group of preterm infants at high risk of developing CLD for early treatment.     

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease

AIM—To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease.METHODS—A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required.RESULTS—Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months ?0.50, 95% confidence interval ?1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians ?2, 95% CI ?4, 0). The study was stopped early because of failure to recruit babies at the expected rate.CONCLUSIONS—R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.     

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure

AIMS—To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated.METHODS—Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied.RESULTS—The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO₂. As a group, the mean (SD) PaO₂/FIO₂ improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO₂ from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P= 0.028). These improvements were sustained throughout the next 48 hours.CONCLUSION—High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.     

Influence of obstetric management on outcome of extremely preterm growth retarded infants

AIM—To describe the long term outcome of extremely preterm growth retarded infants in relation to obstetric management and various perinatal events.METHODS—A cohort study was undertaken in two tertiary care centres with different obstetric management. All infants with fetal growth retardation due to placental insufficiency and resulting in fetal distress at 26 to 32 weeks of gestation, were included for the years 1984-89. Main outcome measures were impairment, disability, or handicap at 2 years corrected age and at school age (4 1/2 to 10 1/2 years).RESULTS—One hundred and twenty five (98%) were followed up until 2 years corrected age in the outpatient department; 114 (90%) were assessed at school age. Impairments were found in 37% and disabilities or handicaps in 9% of the assessed infants, with no difference between centres. All disabled or handicapped children had already been identified by 2 years corrected age.CONCLUSIONS—Disability or handicap were related to neonatal complications (intracerebral haemorrhage or bronchopulmonary dysplasia) and not to obstetric variables, thus making antenatal prediction impossible. The incidence of disability or handicap in these growth retarded infants was comparable with that of other preterm infants.     

Effects of hydrotherapy and tactile-kinesthetic stimulation on weight gain of preterm infants admitted in the Neonatal Intensive Care Unit

ObjectiveThe present study aimed to evaluate the effects of hydrotherapy and tactile-kinesthetic stimulation on the birth weight of preterm infants admitted in the Neonatal Intensive Care Unit.MethodIt was a randomized controlled trial, without blinding, in which 44 preterm infants of both sexes with gestational age between 32 and 34 weeks were included into two groups: hydrotherapy group (n = = 22) and tactile-kinesthetic stimulation group (n = 22). Weight gain was the parameter assessed daily.ResultsIn the tactile-kinesthetic stimulation group there was a variation in weight gain, but without significant difference (p = 0,43). However, in the hydrotherapy group, it was observed that increased weight gain started from the 2nd day (p < 0,001).ConclusionsHydrotherapy group presented significantly increased weight after the interventions, indicating that this technique can interfere with weight gain in preterm infants.     

Growth and Nutritional Status at Corrected Term Gestational Age in Very Low Birth Weight Infants

Objective  

To evaluate the growth and nutritional status at term (39–41 weeks) corrected gestational age in VLBW infants and to study the predictors of malnutrition.     

Comparison of three different noninvasive ventilation strategies as initial respiratory support in very low birth weight infants with respiratory distress syndrome: A retrospective study

BackgroundThere is inadequate evidence regarding which noninvasive ventilation (NIV) is superior for initial respiratory support of preterm infants with respiratory distress syndrome.ObjectivesTo compare the failure of noninvasive ventilation (NIV) and neonatal outcomes between nasal continuous positive airway pressure (NCPAP), bi-level positive airway pressure (BiPAP), and nasal intermittent positive pressure ventilation (NIPPV) as the initial respiratory support with less invasive surfactant administration (LISA) in very low birth weight (VLBW) infants.MethodsMedical records of 419 VLBW infants born at 26–30 weeks’ gestation who did not require intubation in the delivery room and were initially supported with either NCPAP (n = 221), BiPAP (n = 101), or NIPPV (n = 97) were retrospectively reviewed. The LISA approach was preferred in cases of surfactant requirement. The primary outcome was the failure of NIV within the first 72 h of life. Failure of NIV was defined as the persistence or recurrence of one or more of the following: hypoxemia, respiratory acidosis, more than one episode of apnea requiring bag and mask ventilation or more than six episodes of apnea requiring stimulation over a 6-h period. Data were analyzed using univariate and multivariate logistic regression analysis.ResultsFailure of NIV within the first 72 h of life was significantly higher in the NCPAP group (29.4%) compared with the BiPAP (12.9%) or NIPPV (12.4%) group (P < 0.001). However, the BiPAP and NIPPV groups were not different in terms of NIV failure (P = 0.91). Multivariable logistic regression analysis showed that antenatal steroid administration (OR: 0.49, 95% CI: 0.27–0.90; P = 0.02) and gestational age ˂ 28 weeks (OR: 2.03, 95% CI: 1.18–3.49; P = 0.01) were independent factors that influence failure of NIV within the first 72 h of life.ConclusionCompared with NCPAP, the use of NIPPV/BiPAP strategies for initial respiratory support can reduce the need for invasive ventilation in infants born at 26–30 weeks’ gestation.     

Impact of massage therapy on motor outcomes in very low‐birthweight infants: Randomized controlled pilot study

Background: The purpose of the present study was to determine the effects of massage therapy on motor development, weight gain, and hospital discharge in preterm very low‐birthweight (VLBW) newborns. Methods: Twenty‐four preterm VLBW newborns (<34 weeks and <1500 g) were enrolled in this randomized controlled pilot study. The intervention group (n = 12) received massage therapy starting at 34 weeks post‐conceptional age (15 min daily, 5 days/week for 4 weeks). The infants in the sham treatment group (n = 12) received similar duration of light still touch. Test of Infant Motor Performance (TIMP) score gain, weight gain, and post‐conceptional age at discharge were compared between the two groups after intervention using Mann–Whitney U‐test. Results: No significant between‐group difference in TIMP score gain and weight gain was identified when all subjects were analyzed. In subgroup analysis, among those with below‐average pre‐treatment TIMP score (<35), the intervention group (n = 6) achieved significantly higher TIMP score gain (P = 0.043) and earlier hospital discharge (P = 0.045) than the sham treatment group (n = 5). These same infants, however, also had significantly shorter duration of total parenteral nutrition than their counterparts in the sham treatment group (P = 0.044). Conclusions: Massage therapy might be a viable intervention to promote motor outcomes in a subgroup of VLBW newborns with poor motor performance. A larger randomized controlled trial is required to further explore the effects of massage therapy in this high‐risk group.     

极低/超低出生体重儿甲状腺功能减退的临床分析

目的 分析极低/超低出生体重（VLBW/ELBW）患儿甲状腺功能减退的危险因素和治疗情况。方法 选择2018年9月至2019年12月诊断为甲状腺功能减退的VLBW/ELBW患儿为病例组（n=29）,按照1：3比例匹配甲状腺功能正常的VLBW/ELBW患儿作为对照组（n=87）,比较两组患儿的临床特征,分析甲状腺功能与出生胎龄、出生体重的相关性及甲状腺功能减退的危险因素。结果 符合纳入标准的VLBW/ELBW患儿共162例,其中病例组29例,甲状腺功能减退发生率为17.9%。出生体重越低,甲状腺功能减退发生率越高（P < 0.05）;三碘甲状腺原氨酸（T3）、游离三碘甲状腺原氨酸（FT3）与出生胎龄呈正相关（P < 0.05）,T3、游离甲状腺素（FT4）与出生体重呈正相关（P < 0.05）。小于胎龄儿、多胎、孕母≥35岁、使用多巴胺是发生甲状腺功能减退的独立危险因素（P < 0.05）。病例组中16例患儿给予左旋甲状腺素（每日5~10 μg/kg）治疗,甲状腺功能在治疗2周后恢复正常。结论 VLBW/ELBW患儿甲状腺功能减退的发生率较高,小于胎龄儿、多胎、孕母高龄、应用多巴胺是其发生甲状腺功能减退的危险因素,应用左旋甲状腺素治疗的患儿需定期随访,以保证用药剂量适宜。     

Growth and neurodevelopmental outcome of VLBW infants at 1 year corrected age

Objectives

To evaluate growth and neurodevelopmental outcome of very low birth weight infants (VLBW) and compare with term normal birth weight infants (NBW) till 12 months corrected age.

Design

A prospective cohort study

Setting

Tertiary care neonatal unit in northern India

Subjects

37 VLBW infants and 35 NBW infants born between January 2007 and December 2007.

Interventions

Anthropometric measurements were recorded and Z-scores were computed serially at birth, discharge, 40 weeks post menstrual age (PMA), and at 1, 3, 6 and 12 months of corrected age. Developmental quotient (DQ) at 12 months corrected age was assessed.

Results

Z-scores for weight, length and head circumference (HC) at birth were ?1.21(±0.92), ?0.98(±1.32) and ?0.70(±1.14), respectively for VLBW infants and ?0.37(±0.72), ?0.11(±0.96) and 0.05(±0.73) respectively for NBW infants. VLBW infants had a significant drop in all Z-scores by discharge (P<0.001). There was a catch up to birth scores by 12 month age. VLBW infants had significantly lower Z-scores for weight, length and HC at one year corrected age as compared to NBW infants (P =0.01, 0.04 and 0.001, respectively). DQ at 12 months was significantly lower in VLBW infants (91.5+7.8) than NBW infants (97.5±5.3) (P <0.001). DQ of small for gestational age (SGA) and appropriate for gestational age (AGA) VLBW infants was comparable.

Conclusion

VLBW infants falter in their growth during NICU stay with a catch-up later during infancy. In comparison to NBW infants, they continue to lag in their physical growth and neurodevelopment at 1 year of corrected age.     

Effect of Bifidobacterium administration on very‐low‐birthweight infants

Background: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very‐low‐birthweight (VLBW) infants. Methods: We conducted a single‐center prospective pilot study. Thirty‐six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. Results: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7–13] days and 11 [10–15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real‐time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. Conclusion: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.