The establishment and development of the intestinal microbiota in early life is critical to the development of intestinal immune system, digestive function, metabolic function, and central nervous system function in infants.The first 1000 days of life is a critical period for the establishment of intestinal microbiota, which is susceptible to many factors.The disorder of intestinal microbiota in this period will increase the risk of some diseases in the long-term life.In this review, we will describe the main physiological functions of the early-life microbiota and its role in programming future health of infants.We also will describe the establishment and development of the intestinal microbiota in early life and its main drivers.

Objective To investigate the characteristics of intestinal microbiota in neonates on the first and third day after birth.Methods A total of 50 healthy singleton neonates who were born between June 15,2016 and August 3,2016 in Shanghai First Maternity and Infant Hospital were enrolled.Their stool samples were collected on the first and third day after birth and the samples were labeled according to the time of collection (D1 and D3 groups,n=50 each).Illumina NexSeq high-throughput sequencing platform was used to sequence the variable region 4 and 5 of all bacterial 16S rRNA genes in the samples.The composition of intestinal microbial communities was determined and the differences between the two groups were compared by Metastats analysis.Results (1) A total of 100 stool samples were sequenced and the retrieved sequences were from 25 bacterial phyla,119 families,227 genera and 159 species.(2) Major phyla in the two groups were the same,namely,Proteobacteria,Frimicutes,Bacteroidetes and Actinobacteria.The relative abundances of Frimicutes (0.27 ± 0.03 vs 0.41 ± 0.05) and Bacteroidetes (0.07 ± 0.01 vs 0.09 ± 0.03) increased over time,while that of Actinobacteria (0.10±0.01 vs 0.01 ±0.00) decreased on day 3.No significant difference in the relative abundance of Proteobacteria (0.51 ±0.03 vs 0.49± 0.05) was observed between D1 and D3 groups.There were significant difference in relative abundances of Frimicutes and Actinobacteria between the two groups (both q=-0.01,both P＜0.05).(3) Among the top ten most abundant families,Enterobacteriaceae,Staphylococcaceae,Enterococcaceae,Streptococcaceae and Lachnospiraceae were detected in both of the two groups.The relative abundances of Enterobacteriaceae (0.25 ± 0.02 vs 0.46 ± 0.06),Staphylococcaceae (0.07 ± 0.02 vs 0.12 ± 0.03),Enterococcaceae (0.04±0.02 vs 0.10±0.04),Streptococcaceae (0.03 ±0.02 vs 0.06±0.01) increased over time,while that of Lachnospiraceae (0.03 ± 0.01 vs 0.02 ± 0.02) decreased on day 3.Only the relative abundance of Enterobacteriaceae had statistical difference between the two groups (q=0.00,P＜0.05).(4) Among the top ten most abundant genera,Staphylococcus,Enterococcus,Streptococcus,Bacteroides and Pseudomonas were detected in both groups.The relative abundances of aerobic and facultative anaerobic bacteria which belonged to genera of Stenotrophomonas,Propionibacterium,Acinetobacter,Bacillus,Sphingomonas and so on decreased on day 3 as compared with those on day 1 (0.00±0.00 vs 0.07±0.02,0.00±0.00 vs 0.06±0.01,0.00±0.00 vs 0.03±0.01,0.00±0.00 vs 0.02±0.01,0.00±0.00 vs 0.02±0.00,all q=0.00,all P＜0.05).However,the relative abundances of anaerobic bacteria which belonged to Bacteroides,Veillonella,Parabacteroides and so on increased on day 3 (0.01 ±0.00 vs 0.08±0.03,0.00±0.00 vs 0.03±0.02,0.00±0.00 vs 0.01 ±0.00,q=0.01,0.01 and 0.00,all P＜0.05).(5) The most abundant species in intestinal microbiota was escherichia coli in both groups.Three less abundant species including lactobacillus gasseri,lactobacillus animalis and bifidobacterium bifidum were detected in both groups.(6) Regardless of the mode of delivery,Staphylococcus,was the highest predominant genera in meconium samples,followed by stenotrophomonas.Stool samples collected on the third day after birth were divided into four groups based on deliver modes and feeding patterns.Neonates who were born abdominally with exclusive breastfed thereafter were different from those of the other three groups in predominant intestinal bacteria,but the difference was not statistically significant.Bifidobacterium and Subdoligranulum were only detected in the vaginally born neonates.Conclusions Meconium is not sterile.Although the intestinal microbiota on the first day of life is different from that on the third day of life,the dominant bacteria are common.During the first three days of life,the relative abundances of aerobic and facultative anaerobic bacteria decreased significantly over time,while the relative abundance of anaerobic bacteria increased.

ObjectiveTo investigate the effects of care bundles on the lactation of mothers of preterm infants.MethodsFrom January to June 2015, postpartum women who had preterm deliveries in First Maternity and Infant Hospital Affiliated to Tongji University with the neonates hospitalized in neonatal intensive care unit were enrolled in this study. They were randomly divided into intervention group (n=25) receiving bundle care (assist the mothers to determine lactation target; pump/express breastmilk within six hours after birth and keep a lactation diary to record the times and volume of pumped/expressed milk) and control group (n=22) given normal mammary guidance only. The time of the first pumped/expressed milk, the times for pumping/expressing milk a day, the total milk volume per day and rate of breastfeeding were compared between the two groups. Statistical analyses were conducted using two independent samplest-test,Chi-square test and nonparametric test.ResultsThe initial time of pumped/expressed milk of the intervention group was (6.1±3.4) h after delivery, significantly earlier than the control group [(10.7±9.3) h](t=-2.301,P=0.026). The times for pumping/expressing milk per day were significantly more in the intervention group than in the controlgroup on the 1st, 2nd and 3rd day after delivery [(4.2±2.2) vs (3.0±1.6); (6.2±1.1) vs (4.7±1.9); and (7.1±1.9) vs (5.9±1.9) times, respectively](t=2.083, 2.564 and 2.194, allP<0.05). From the second postpartum day, the milk volume of the intervention group was more than the control group [M(range) were 10.0(25.0) vs 2.0(5.0) ml] (Z=-2.879,P=0.005); and on the 21st day, the milk volume of the intervention mothers reached 800.0(295.0) ml, still higher than the control group [300.0(155.0) ml](Z=-3.179,P=0.001). The primarily breastfeeding (adding formula milk≤2 times a day) rate in the intervention group was significantly higher than in the control group on the 42nd postpartum day [68% (17/25) vs 41% (9/22),χ2=5.874,P=0.045].ConclusionThe care bundles on lactation can improve the lactation of the mothers of preterm infants.

After birth,the premature infants usually need a proper way for intestinal nutrition.The composition and configuration of nutrition admixture must meet the special requirements of the premature infants.In the first few days,because of invisible water lose,they should maintain a stable internal environment,and 1 week later,they need to gradually achieve a stable growth rate.Parenteral nutrition may lead to various complications,such as infection,metabolic complications,etc.monitoring the index,then adjusting the dosage,and achieving full enteral nutrition as soon as possible,may be effective prevention measures.

As survival of premature infants has increased,nutritional support has become a more prominent component of patient care.Aggressive nutritional strategies can reduce the incidence of extrauterine growth retardation (EUGR),speed up the physical growth and promote the development of intelligence.But excessive weight gain may also increase the risk of obesity and cardiovascular diseases in the future.This review mainly introduces and interprets the enteral nutrient supply for preterm infants:commentary from the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN),2010,to provide an evidence-based medicine nutritional guideline for preterm infants.

Objective To evaluate the predictive value of cord blood bilirubin levels for subsequent neonatal hyperbilirubinemia in term infants with ABO hemolytic disease.Methods A total of 292 term newborns with ABO hemolytic disease admitted from August 1,2011 to July 31,2012 were enrolled.Cord blood bilirubin levels were analyzed and the clinical characteristics of the neonatal hyperbilirubinemia group (n=34) and non-hyperbilirubinemia group (n=258) were compared.A receiver operating characteristic (ROC) curve analysis was performed to identify the predictive value of the occurrence and cut-off point of hyperbilirubinemia in term infants with ABO hemolytic disease.Paired-t-test,Chi-square test and Spearman correlation were used for statistical analysis.Results Of the 292 term infants with ABO hemolytic disease,34 cases had hyperbilirubinemia,with an incidence of 11.6％.Cord blood bilirubin levels were significantly associated with the presence of hyperbilirubinemia.The mean cord blood bilirubin level in infants who developed hyperbilirubinemia was (52.4± 13.2) μ mol/L,and was (35.0±8.0) μ mol/L for those who did not develop hyperbilirubinemia (t=7.540,P=-0.001).When cord blood bilirubin concentration increased,the incidence of hyperbilirubinemia gradually increased (x2=113.715,P＜0.001; rs=7.19,P＜0.001).The ROC area under the curve of 0.882 (standard error 0.005,95％CI:0.873-0.891,P＜0.001) was significant in predicting neonatal hyperbilirubinemia by cord blood bilirubin,and the occurrence of hyperbilirubinemia increased with increasing cord blood bilirubin level.Neonatal cord blood total bilirubin ≥ 50 μ mol/L predicted hyperbilirubinemia,and the positive predictive value was 0.683,negative predictive value was 0.959,sensitivity was 0.690 and specificity was 0.958.Conclusions Cord blood bilirubin level is useful in predicting subsequent neonatal hyperbilirubinemia in term infants with ABO hemolytic disease.

After birth,premature infants have greater nutritional needs,because of decreased intrauterine nutrient deposition,immaturity of the gastrointestinal tract (GI),and medical conditions such as hypoxia,acidosis and surgery.In order to reach the optimal growth rate,continual reassessment and delivery of adequate energy and nutritional support are imperative.We suggest initiating enteral feeding in the first few days after birth to prime the GI in the premature infant,and then gradually achieve full enteral feedings when clinical condition is stable.Many signs may suggest feeding intolerance.Clinicians should composite these factors to determine.The use of drugs such as erythromycin to treat feeding intolerance in premature infants needs to be clarified.

Preterm infants are often significantly growth retarded at the time of hospital discharge.They often in the nutritional crisis after hospital discharge,and should be carefully follow up evaluated.Preterm formula and fortified breast milk may improve the growth of preterm infants and is a reasonable option for preterm infants.Preterm formula and fortified breast milk are recommended for preterm infants with weights below the 10th percentile for age at the time of hospital discharge and those birth weights below 1 500 g.After hospital discharge,exclusively human milk-fed preterm infants are at increased risk for suboptimal growth compared to formula-fed infants.Infants with BPD are at increased risk of growth retardation after hospital discharge.Protein and mineral enriched formula may provide short-term growth catch-up.

To assess the effects of resuscitation with oxygen or room air on the cardiac circulation and the activity of superoxide dismutase (SOD) in a hypoxic newborn piglet model. Methods Newborn piglets(1.6-2.5 kg) were randomly assigned into three groups:control group (n=8) with no hypoxic insult;room air group (n=12) resuscitated with room air for 240 min after 120 min hypoxia;and oxygen group (n=12) resuscitated with 100% oxygen for 30 min followed by 210 min with room air after 120 min hypoxia. Blood gas analysis, blood pressure and hemodynamic parameters were recorded at 0, 10, 30, 60, 120, 180 and 240 min of resuscitation. The activity of superoxide dismutase (SOD) in the left ventricle was measured at 240 min of resuscitation using enzyme method . One-way analysis of variance, two-way analysis of variance measured repeatedly and Student-Newman-Keuls test were applied as statistical methods. Results Severe metabolic acidosis, hypotension and hypoxemia were caused by hypoxia.(1)Arterial oxygen partial pressure(PaO2):At 10 min of resuscitation, PaO2 of control group, room air group and oxygen group was (67±4), (78±12) and (409±42)mmHg(1 mmHg=0.133 kPa) (F=580.19, P<0.01). At 30 min of resuscitation, PaO2 of the three group was (68±3), (79±15) and (342±62)mmHg(F=173.67;P<0.01). PaO2 of oxygen group was higher than room air group and control group (10 min:q=42.51 and 39.28, 30 min: q=23.17 and 21.67, all P<0.05). There was no statistical significance between the room air group and control group. (2)Cardiac output(CO):At 240 min of resuscitation,CO of control group, room air group and oxygen group was(181.6±33.8), (150.9±70.1) and (103.6±53.6) dl/(min·kg) (F=4.82, P<0.05). CO of oxygen group was lower than control group (q=4.25,P<0.05). There was no statistical significance between oxygen group and room air group, neither was between room air group and control group (all P>0.05). (3)Arterial oxygen content (CaO2):At 10 min of resuscitation, CaO2 of control group, room air group and oxygen group was(87.0±16.1), (76.9±13.2) and (102.2±15.9) ml O2/dl (F=8.64, P<0.01). At 30 min of resuscitation, CaO2 of the three group was(87.5±14.9), (79.9±11.3) and (100.1±16.7) ml O2/dl (F=5.98, P<0.01). At 10 min of resuscitation, CaO2 of oxygen group was higher than control group and room air group (q=3.14 and 5.85, all P<0.05). At 30 min of resuscitation, CaO2 of oxygen group was higher than room air group (q=4.85, P<0.01), but there was no statistical significance between oxygen group and control group (q=2.71, P>0.05). (4)Oxygen delivery (DO2): At 10, 30, 60, 120, 180 and 240 min of resuscitation, there were no statistical significance among DO2 of control group, room air group and oxygen group [10 min:(16.5±3.3), (15.7±9.9) and (16.9±4.2)L O2/(kg·min), F=0.10;30 min:(16.2±4.1), (15.1±5.5) and (14.5±3.3) L O2/(kg·min), F=0.38;60 min:(16.1±4.2), (14.9±4.0)and(13.3±3.8)L O2/(kg·min), F=1.28;120 min:(15.5±3.7),(15.6±6.1)and(13.4± 4.6) L O2/(kg·min), F=0.66;180 min:(15.4±3.1), (15.3±9.3) and (11.9±5.0) L O2/(kg·min), F=0.97;240 min:(14.7±3.4), (13.4±6.7) and (9.3±5.2) L O2/(kg·min), F=2.84;all P>0.05]. (5) SOD activity in the left ventricle:At 240 min of resuscitation, SOD activity of control group (n=6), room air group (n=8) and oxygen group (n=8) was (289±107), (210±75) and (142±61)U/mg protein, F=5.75, P<0.05]. SOD activity of oxygen group was lower than control group (q=4.79, P<0.01). There was no statistical significance between oxygen group and room air group, neither was between room air group and control group(q=2.58 and 2.39, all P>0.05). Conclusions Despite higher oxygen content in the blood, resuscitation with oxygen is not beneficial to recovery from metabolic acidosis in newborn hypoxic piglets. Oxygen supplementation does not increase oxygen delivery but reduces SV compared to resuscitation with room air. Resuscitation with oxygen may impair the oxidative stress defense.

Objective To investigate the hemodynamic changes and their association with the expression of β 1 and β 2 adrenoceptors after hypoxia-reoxygenation injury in a neonatal swine model of asphyxia.Methods One to four day-old piglets were randomly assigned to control group (n=6),acute hypoxia group (n=8) and subacute hypoxia group (n=8).The piglets in the control group were observed for 50 h under normoxic mechanical ventilation; while the acute and subacute hypoxia groups were subject to two hours of hypoxic injury induced by ventilation with 0.10-0.15 oxygen followed by 4 or 48 h of observation under normoxic mechanical ventilation,respectively.Blood gases were analyzed and the mean arterial blood pressure,heart rate,and cardiac output were recorded at different time points during the experiment.Tissues from the left ventricle were also harvested to assay lactate,glutathione and β adrenoceptors at the end of the experiment.Analysis of variance,the Tukey test and Pearson correlation analysis were used for statistical analysis of the data.Results Two hours after hypoxia,pH,HCO3-and partial pressure of oxygens (PO2) in the acute hypoxia group and subacute hypoxia group were lower than in the control group,however,pH and HCO3-in animals in the subacute hypoxia group recovered to 7.38 ± 0.05 and (23.04± 2.40)mmol/L,respectively,after reoxygenation,which was similar to those in the control group,and higher than in the acute hypoxia group [7.25±0.07 and (16.88±2.40) mmol/L,respectively,q=6.76 and 7.81,both P＜0.01].Mean arterial pressure,cardiac output and stroke volume in the acute group and subacute group were lower than those in the control animals following two hours of hypoxic injury (all P＜0.01).After reoxygenation,the mean arterial pressure in the acute hypoxia group and subacute group recovered to (42.17±6.14) and (43.19± 5.55) mmHg (1 mmHg=0.133 kPa),cardiac output recovered to (150.04± 56.17) and (169.75 ± 37.85) dl/min,respectively,and there were no differences compared with the control group (all P＞0.05).Expressions of β 1 and β 2 adrenoceptors in the left ventricle in the subacute hypoxia group (1.51 ±0.51 and 2.14±0.66,respectively),were higher than those in the control group (0.56±0.24 and 0.38±0.21,q=7.02 and 10.97,both P＜0.01) and the acute hypoxia group (0.65±0.20 and 0.45±0.11,q=6.86 and 11.38,both P＜0.01).The lactate level in the acute hypoxia group and subacute hypoxia group was higher than that in the control group [(6.95±0.32) and (6.92±0.40) vs (5.03±0.19) μ mol/mg protein,respectively,q=15.43 and 15.19,both P＜0.01].The level of glutathione in the subacute hypoxia group was lower than the control group and acute hypoxia group [(352.00± 16.51) vs (438.35±33.66) and (464.66±52.65) nmol/mg protein,respectively,q=6.00 and 8.46,both P＜0.01).In the subacute hypoxia group,the expressions of β 1 and β 2 adrenoceptors were negatively correlated with the changes in cardiac output (r=-0.60 and-0.59,respectively,both P＜0.05).Conclusions Severe metabolic acidosis and cardiac dysfunction resulting from perinatal asphyxia may recover after reoxygenation,which may be associated with the enhanced expression of β adrenoceptors in the left ventricle during the subacute phase.