Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Risk factors for severe bronchopulmonary dysplasia in a Chinese cohort of very preterm infants.

OBJECTIVES: To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. METHODS: In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. RESULTS: A significant inverse correlation was revealed between BPD severity and both GA and BW (p<0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (≥7d), multiple blood transfusion (≥3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110 kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. CONCLUSION: Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.Clinical Trial Reg. No.: ChiCTR1900023418.

Hyperglycemia in pregnancy did not worsen the short-term outcomes of very preterm infants: a propensity score matching study.

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear. Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups. Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P < 0.05). Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

Real-world evidence regarding the growth of very premature infants with small for gestational age after birth: a multicenter survey in China.

BACKGROUND: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge. METHODS: The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < -1.28. RESULTS: This study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors. CONCLUSION: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR. TRIAL REGISTRATION: CHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn .

Association of duration of skin-to-skin contact after cesarean delivery in China: a superiority, multicentric randomized controlled trial.

BACKGROUND: In China, the rates of early initiation and exclusive breastfeeding are low. The high cesarean delivery rates further contribute to low breastfeeding outcomes. Skin-to-skin contact, a key component of early essential newborn care, is known to be associated with improved breastfeeding initiation and exclusivity; however, the necessary duration has not been subjected to a randomized control trial. OBJECTIVE: This study aimed to determine the association of the duration of skin-to-skin contact after cesarean delivery with breastfeeding outcomes and maternal and neonatal health outcomes in China. STUDY DESIGN: This was a multicentric randomized controlled trial that was conducted at 4 hospitals in China. A total of 720 participants at ≥37 gestational weeks with a singleton pregnancy and who received an elective cesarean delivery with epidural anesthesia or spinal anesthesia or combined spinal-epidural anesthesia were randomly divided into 4 groups at a ratio of 1:1:1:1. The control group received routine care. Intervention group 1 (G1), 2 (G2), and 3 (G3) received 30, 60, and 90 minutes of skin-to-skin contact immediately after the cesarean delivery, respectively. RESULTS: Between January 3 and October 14, 2021, 659 participants were recruited, including 173 in the control group, 176 in G1, 146 in G2, and 164 in G3. Among G1, G2, and G3, the rate of early initiation of breastfeeding within 60 minutes of birth was 56%, 71%, and 72%, respectively, compared with 22% in the control group (P<.001). The exclusive breastfeeding rate at discharge was 69%, 62%, and 71%, respectively, compared with 57% in the control group (P=.003). Early essential newborn care practices were associated with a reduction in postpartum blood loss and neonatal intensive care unit or neonatal ward admission (P<.001; P=.022) . CONCLUSION: Our findings highlight that prolonged skin-to-skin contact after a cesarean delivery was associated with higher initiation and exclusive breastfeeding at discharge rates. It also found associations with reduced postpartum blood loss and neonatal intensive care unit or neonatal ward admission.

The impact of early empirical antibiotics treatment on clinical outcome of very preterm infants: a nationwide multicentre study in China.

BACKGROUND: Infants with rule-out infections are responsible for the majority of empirical antibiotics treatment (EAT) in neonatal intensive care units (NICUs), particularly very preterm infants (VPIs). Antibiotic overuse has been linked to adverse outcomes. There is a paucity of data on the association between EAT and clinical outcomes (containing the nutritional outcomes) of VPIs without infection-related morbidities. METHODS: Clinical data of VPIs admitted in 28 hospitals in 20 provinces of China from September 2019 to December 2020 were collected. EAT of VPIs was calculated as the number of days with initial usage in the first week after birth, and then categorized into 3 groups (antibiotic exposure: none, 1-4 days, and > 4 days). Clinical characteristics, nutritional status , and the short-term clinical outcomes among 3 groups were compared and analyzed. RESULTS: In total, 1834 VPIs without infection-related morbidities in the first postnatal week were enrolled, including 152 cases (8.3%) without antibiotics, 374 cases (20.4%) with EAT ≤4 days and 1308 cases (71.3%) with EAT > 4 days. After adjusting for the confounding variables, longer duration of EAT was associated with decreased weight growth velocity and increased duration of reach of full enteral feeding in EAT > 4 days group (aß: -4.83, 95% CI: - 6.12 ~ - 3.53; aß: 2.77, 95% CI: 0.25 ~ 5.87, respectively) than those receiving no antibiotics. In addition, the risk of feeding intolerance (FI) in EAT > 4 days group was 4 times higher than that in non-antibiotic group (aOR: 4.14, 95%CI: 1.49 ~ 13.56) and 1.8 times higher than that in EAT ≤4 days group (aOR: 1.82, 95%CI: 1.08 ~ 3.17). EAT > 4 days was also a risk factor for greater than or equal to stage 2 necrotizing enterocolitis (NEC) than those who did not receive antibiotics (aOR: 7.68, 95%CI: 1.14 ~ 54.75) and those who received EAT ≤4 days antibiotics (aOR: 5.42, 95%CI: 1.94 ~ 14.80). CONCLUSIONS: The EAT rate among uninfected VPIs was high in Chinese NICUs. Prolonged antibiotic exposure was associated with decreased weight growth velocity, longer duration of reach of full enteral feeding, increased risk of feeding intolerance and NEC ≥ stage 2. Future stewardship interventions to reduce EAT use should be designed and implemented.

Effect of early initiation of enteral nutrition on short-term clinical outcomes of very premature infants: A national multicenter cohort study in China.

OBJECTIVES: The management of enteral nutrition in very preterm infants (VPIs) is still controversial, and there is no consensus on the optimal time point after birth at which enteral nutrition can be started. The aim of this study was to investigate the effect of early initiation of enteral nutrition on the short-term clinical outcomes of VPIs. METHODS: Data of infants (n = 2514) born before 32 wk of gestation were collected from 28 hospitals located in seven different regions of China. Based on whether enteral feeding was initiated within or after 24 h since birth, the infants were divided into an early initiation of enteral feeding (EIEF) group and a delayed initiation of enteral feeding (DIEF) group. RESULTS: Compared with the DIEF group, the EIEF group was more likely to tolerate enteral nutrition and had less need for parenteral nutrition (all P < 0.05). The EIEF group was associated with lower incidence rates of feeding intolerance, extrauterine growth restriction (EUGR), and late-onset sepsis (LOS) (all P < 0.05). There was no significant difference in the incidence of necrotizing enterocolitis (NEC) (Bell stage ≥2) between the two groups (P = 0.118). The multivariate logistic regression analysis revealed that EIEF was a protective factor against EUGR (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.544-0.735; P < 0.001), feeding intolerance (OR, 0.658; 95% CI, 0.554-0.782; P < 0.001), and LOS (OR, 0.706; 95% CI, 0.550-0.906; P = 0.006). CONCLUSIONS: Early initiation of enteral feeding was associated with less frequency of feeding intolerance, EUGR, and LOS, and it may shorten the time to reach total enteral feeding without increasing the risk of NEC.

Association between Skin-to-Skin Contact Duration after Caesarean Section and Breastfeeding Outcomes.

We aimed to explore the association between skin-to-skin contact (SSC) duration after caesarean sections (CSs) and breastfeeding outcomes. A prospective study was conducted in four hospitals in China during January and August 2021. A total of 679 participants with singleton pregnancy who delivered by elective CS after 37 gestational weeks using epidural or spinal anesthesia were included. Logistic regression was applied to assess the association between SSC duration and early initiation of breastfeeding (EIBF), as well as the promoting factors for exclusive breastfeeding (EBF) at hospital discharge. Immediate SSC after CSs was strongly associated with higher rates of EIBF (p < 0.001) and EBF at hospital discharge (p = 0.002). The EIBF rates increased with longer duration of SSC, with the at least 90 min SSC group having the highest EIBF rate (74.5%). Skin-to-skin contact durations of at least 90 min, 60−89 min and 30−59 min were significantly associated with 8.53 times (OR = 8.53, 95%CI: 4.94−14.72, Padj < 0.001), 8.04 times (95%CI: 4.68−13.80, Padj < 0.001) and 6.28 times (95%CI: 3.75−10.51, Padj < 0.001), respectively, higher EIBF rates compared to those without immediate SSC. After multiple-testing correction, the rates of EBF at hospital discharge were found to be independent of the duration of SSC (Padj = 0.12). Early initiation of breastfeeding was not a significant predictor of EBF. Our results suggested that SSC is important for EIBF in Chinese baby-friendly hospitals. Skin-to-skin contact should be practiced after CS to promote breastfeeding and providing SSC with longer duration is encouraged to obtain the full benefit; if it is not feasible, a minimum of 30 min SSC could achieve improved EIBF and EBF at discharge.

Analysis of "true extrauterine growth retardation" and related factors in very preterm infants-A multicenter prospective study in China.

Objective: To investigate the incidence and related factors of extrauterine growth retardation (EUGR) and "true EUGR" in very preterm infants (VPI) from different regions of China. Materials and methods: Clinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as "true EUGR." The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups. Results: Among the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and "true EUGR" evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for "true EUGR," while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for "true EUGR." Conclusion: More attention should be paid to the nutritional management of VPI to prevent "true EUGR." Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of "true EUGR" in VPI.

Factors influencing extrauterine growth retardation in singleton-non-small for gestational age infants in China: A prospective multicenter study.

BACKGROUND: The incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of "EUGR" in SGA infants is not "true EUGR". The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR. OBJECTIVES: To analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China. METHODS: A prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912). RESULTS: Compared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks and 31-31+6 weeks) and distinct BW groups (classifications of BW<1000 g, 1000-1249 g, 1250-1499 g, 1500-1999g and 2000-2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR.

Risk factors of extrauterine growth restriction in very preterm infants with bronchopulmonary dysplasia: a multi-center study in China.

OBJECTIVE: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD. METHOD: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied. RESULTS: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000-1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA). CONCLUSION: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies.

Human Milk Fortification in Very Preterm Infants in China: A Multicenter Survey.

Aim: To investigate the use of human milk fortifier (HMF) for very preterm infants (VPIs) and complications and nutritional status of VPIs due to various breast milk enhancement strategies among the Chinese population. Methods: VPIs with birth weight < 1,800 g and wholly or predominantly breastfed were assigned to the following fortification groups: no HMF, early HMF (adding HMF at an enteral volume of ≤ 80 ml·kg-1·day-1), middle HMF (adding HMF at an enteral volume of 80-100 ml·kg-1·day-1), and late HMF (adding HMF at an enteral volume of ≥100 ml·kg-1·day-1). The growth status and complications for various groups were evaluated. Results: We enrolled 985 VPIs, of which 847 VPIs (86.0%) received HMF, whereas 138 VPIs (14.0%) did not. The number of VPIs in the early, middle, and late fortification groups were 89 (9.0%), 252 (25.6%), and 506 (51.4%), respectively. The complete fortification of the early, middle, and late fortification groups was achieved in 13.2 ± 11.0, 13.8 ± 11.7, and 12.3 ± 13.0 days, respectively, without significant differences (p > 0.05). The groups did not exhibit significant differences in the incidence of feeding intolerance, necrotizing enterocolitis (Bell stage ≥ 2), late-onset sepsis, and metabolic bone diseases (p > 0.05). The middle fortification groups exhibited the fastest growth velocity and the least dramatic decrease in the Z-score of weight and length, and the lowest incidence of EUGR (35.7%), whereas the "no HMF" groups exhibited the slowest growth velocity and the largest decline in the Z-score, and the highest incidence of EUGR (61.6%). Conclusions: The usage rate of HMF was relatively low among Chinese VPIs, fortification often occurred in the late feeding stage, and the time to reach complete fortification was long. Adding HMF and different breast milk enhancement strategies did not increase the incidence of feeding intolerance and necrotizing enterocolitis. The enteral volume of 80-100 ml·kg-1·day-1 with HMF addition led to increased growth in the weight and length and lower EUGR incidence, indicating that the addition of HMF at the specific feeding volume might be the best practice for promoting growth.

Hsa_circ_0009057 can be a novel potential diagnostic biomarker and a therapeutic target for premature brain injury.

Circular RNAs (CircRNAs) represent a novel class of noncoding RNAs, and are widely expressed in brain tissues, indicating their great potential as novel biomarkers for the diagnosis of neuropsychiatric disorders. However, the expression profiles of circRNAs for infants with premature brain injury (PBI) have not been fully explored. This study assessed the differentially expressed circRNAs in plasma of infants with and without PBI using the human circRNA microarray analysis. Hsa_circ_0009057, a significantly up-regulated circRNA in infants with PBI, was selected for further study. The microRNA (miRNA)-recognition element prediction analysis and construction of the circRNA-miRNA-mRNA network showed that hsa_circ_0009057 was associated with several miRNAs and mRNAs, which played important roles in the regulation of neuropsychiatric disorders. The results of the receiver operating characteristic curve analysis showed that hsa_circ_0009057 had high degrees of specificity and sensitivity. The results also indicated that hsa_circ_0009057 could be served as a novel potential diagnostic biomarker and a therapeutic target for PBI.

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OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Antenatal corticosteroids is associated with better postnatal growth outcomes of very preterm infants: A national multicenter cohort study in China.

Introduction: Antenatal corticosteroids (ACS) administration is a standardized prenatal care for accelerating fetal maturation before anticipated preterm delivery, however, its effect on nutrition and growth is yet uncertain. This study aimed to examine if ACS application is associated with improvement in postnatal growth and nutrition in very preterm infants (VPIs). Methods: This was a secondary analysis of a multicenter prospective survey included infants born before 32 weeks gestation and admitted to 28 tertiary neonatal intensive care units throughout China from September 2019 to December 2020. Infants were divided into no ACS, partial ACS and complete ACS groups according to the steroids exposure. For infants exposed to antenatal corticosteroids, complete ACS was defined as receiving all doses of steroids 24 h-7 days before delivery, otherwise it was referred to partial ACS. The primary outcomes of postnatal growth were compared among the 3 groups. The multivariable regression analyses were applied to evaluate the association of different steroids coverage with postnatal growth and nutritional outcomes while adjusting for potential confounders. For each outcome, no ACS coverage was defined as the reference group. Data were presented as unstandardized coefficients or adjusted odds ratios with 95% confidence intervals, P < 0.05 (2-sided) indicated statistical significance. Results: Among 2,514 infants included, complete ACS, partial ACS and no ACS group accounted for 48.7% (1,224/2,514), 29.2% (735/2,514) and 22.1% (555/2,514), respectively. The median weight growth velocity was 14.6 g/kg/d, 14.1 g/kg/d and 13.5 g/kg/d in complete, partial and no ACS group respectively with significant difference (P < 0.001). In multivariable analyses, both complete and partial ACS coverage were associated with shorter cumulative fasting time, faster weight growth velocity, less dramatic decline in Z-score of weight, and lower incidence of extrauterine growth restriction [aOR (95%CI): 0.603 (0.460, 0.789) and 0.636 (0.476,0.851), respectively] when compared with no ACS. Moreover, the faster length growth velocity and earlier enteral feeding start time were observed only in infants with complete ACS coverage. Conclusions: Both complete and partial ACS are associated with better postnatal growth outcomes in very preterm infants. This efficacy appeared to be more obvious in infants exposed to complete ACS.

Necrotizing enterocolitis in low birth weight infants in China: Mortality risk factors expressed by birth weight categories.

BACKGROUND: We retrospectively investigated incidence, morbidity, and mortality of neonatal necrotizing enterocolitis in China, with special emphasis on determining the predictors of necrotizing enterocolitis associated mortality. METHODS: We identified neonates as having necrotizing enterocolitis if they met the accepted diagnostic criterion. Data pertaining to antenatal period, labor and birth, and the postnatal course of illness were collected. Multivariate analysis and logistic regression were used to analyze the risk factors. RESULTS: There were 1167 cases of necrotizing enterocolitis identified from the 95 participating NICUs in mainland China in 2011, with the incidence of 2.50% and 4.53% in LBW (birth weight <2500 g) and VLBW (birth weight <1500 g) infants, respectively. Stage 1, 2 and 3 diseases were noted in 51.1%, 30.3% and 18.6% of cases respectively. The mortality from stage 2 and 3 necrotizing enterocolitis in this cohort was 41.7%. In VLBW infants, the important risk factors for mortality were small for gestation age (OR: 5.02, 95% CI 1.73-14.6; P = 0.003) and stage 3 NEC (OR: 8.09, 95% CI 2.80-23.3, P < 0.001). In moderate LBW infants (birth weight 1500-2499 g), the risk factors identified for mortality were sepsis during hospitalization (OR: 2.59, 95% CI 1.57-4.28, P < 0.001) and stage 3 NEC (OR: 5.37, 95% CI 3.24-8.90; P < 0.001). CONCLUSIONS: Necrotizing enterocolitis remains an important cause of morbidity and mortality in prematurely born neonates in Chinese neonatal units. Awareness of the associated risk factors and appropriate interventions may improve the outcome of necrotizing enterocolitis in different birth weight subgroup.

Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study.

BACKGROUND: Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China. METHODS: All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed. RESULTS: A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal. CONCLUSIONS: Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

BACKGROUND: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. METHODS: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. RESULTS: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. CONCLUSIONS: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.