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 .

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.

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.

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.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹è¾ åŠ©é€šæ°”æ—©äº§å„¿çš„ç–—æ•ˆè¯„ä¼°ï¼šä¸€é¡¹åˆæ­¥å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

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.

A Regression Model to Predict Linezolid Induced Thrombocytopenia in Neonatal Sepsis Patients: A Ten-Year Retrospective Cohort Study.

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

Vancomycin in neonatal sepsis: predictive performance of a Chinese neonatal population pharmacokinetic model and clinical efficacy evaluation.

BACKGROUND: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods. OBJECTIVE: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration. METHODS: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC0-24/MIC) and trough concentration for clinical efficacy. RESULTS: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC0-24/MIC >425.47 and trough concentration >9.45 mg/L. CONCLUSION: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC0-24/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.

High-proportion breast milk feeding is associated with a reduction in the incidence of IVH in very preterm infants.

Objective: To investigate the protective effect of high-proportion breast milk feeding (>50%) on intraventricular hemorrhage (IVH) in very preterm infants (VPIs). Methods: This was a retrospective secondary analysis of a prospective multi-center study, which included 604 VPIs from six hospitals in eastern China between September 2019 and December 2020. The 604 VPIs were divided into two groups according to whether IVH occurred. High-proportion breast milk feeding was defined as breast milk accounting for 51-100% of the total feeding amount both within 7 days and throughout the hospitalization. The IVH grades and the rate of high-proportion breast milk feeding were analyzed. Furthermore, to explore the relationship between high-proportion breast milk feeding and IVH grading, the VPIs' general information, perinatal factors, growth, and nutritional status during hospitalization, and related complications were compared between the two groups. Results: High-proportion breast milk feeding was reported in 63.41% of the VPIs. Furthermore, IVH grades I-II and III-IV were noted in 39.73% (240/604) and 1.66% (10/604) of the VPIs, respectively. Univariate analysis revealed that IVH occurrence in VPIs is influenced by perinatal factors, invasive respiratory therapy, high-proportion breast milk feeding, start feeding with breast milk, the cumulative amount of early parenteral nutrition, postnatal complications, physical growth, and other factors (P < 0.05). After adjustments for gestational age, birth weight, and possible influencing factors through binary logistic regression analysis, the results revealed that high-proportion breast milk feeding and and start feeding with breast milk were associated with a lower total incidence of IVH. Further stratification showed that high-proportion breast milk feeding was associated with a lower incidence of grade I-II IVH. Similarly, after adjusting for the same factors, breast milk feeding >50% in the 1st week was associated with a decreased incidence of total IVH and further stratification showed that it was associated with a lower incidence of grade I-II IVH. Conclusion: High-proportion breast milk feeding and breast milk feeding more than 50% of total intake during the 1st week might be protective factors for IVH grade I-II in VPIs, which further verified the neuroprotective effect of breast milk. In clinical practice, the construction of breast milk banks should be strengthened, breast milk feeding should be encouraged in neonatal intensive care units, and efforts should be made to increase breast milk feeding rates to improve the outcomes of 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.

Development and verification of a risk prediction model for bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND: To analyze the risk factors of bronchopulmonary dysplasia (BPD) of very low birth weight infants (VLBWIs), and to develop and verify a risk prediction model of BPD. METHODS: The data of 611 VLBWIs from the neonatal intensive care unit (NICU) of a tertiary grade A hospital in Suzhou from January 2017 to September 2019 were collected. The data was randomly divided into the modeling set (451 cases) and the validation set (160 cases). Binary logistic regression was used to analyze the data, and the model was examined by a receiver operating characteristic (ROC) curve. The grouped data was used to verify the sensitivity and specificity of the model. RESULTS: The study found that neonatal asphyxia, the positive rate of sputum culture, neonatal sepsis, neonatal respiratory distress syndrome (NRDS), blood transfusions (≥3), patent ductus arteriosus (PDA), the time of invasive mechanical ventilation, the duration of oxygen therapy, and the time of parenteral nutrition were the independent risk factors of BPD, while 1 min Apgar score was a protective factor. The model formula was Z=neonatal asphyxia * 1.229 + the positive rate of sputum culture * 1.265 + neonatal sepsis * 1.677 + NRDS * 1.848 + blood transfusions (≥3) * 1.455 + PDA * 1.835 - 1 min Apgar score * 0.25 + the time of invasive mechanical ventilation * 0.123 + the duration of oxygen therapy * 0.09 + the time of parenteral nutrition * 0.057 - 8.077. The area under the ROC curve of this model was 0.965 (95% CI: 0.946-0.983), with a sensitivity of 93.7% and a specificity of 91.3%. Verification of this prediction model showed a sensitivity of 92.9% and a specificity of 76%, demonstrating that the effects of this model were satisfactory. CONCLUSIONS: The risk prediction model had a good predictive effect for the risk of BPD in VLBWIs, and can provide a reference for preventive treatment and nursing intervention.

The potential value of plasma receptor interacting protein 3 in neonates with culture-positive late-onset sepsis.

BACKGROUND: Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. METHODS: 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%. CONCLUSIONS: RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

Quantitative trait analysis of polymorphisms in two bilirubin metabolism enzymes to physiologic bilirubin levels in Chinese newborns.

OBJECTIVE: To explore the effects of variants in Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) and Heme Oxygenase-1 (HMOX1) on daily physiological bilirubin levels and bilirubin changes during the first week after birth in Chinese newborns. Both UGT1A1 and HMOX1 code rate-limiting enzymes in the bilirubin metabolism pathway. STUDY DESIGN: We conducted a retrospective quantitative trait study to analyze 4154 daily bilirubin values, 3129 bilirubin changes, and 11 polymorphisms of 988 newborns during the natural course of physiological hyperbilirubinemia. RESULTS: For UGT1A1, we found minor allele A of rs4148323 (G211A, UGT1A1*6) contributed to higher daily bilirubin levels on days 4-6 (with contributions to variations increasing from 4.8% to 12.3%), minor allele T of rs887829 (c-364t) contributed to lower daily bilirubin levels for days 6 and 7 (with contributions to variations increasing from 7.0% to 10.2%) (P < .03 for all). In addition, minor alleles of rs887829 and (TA)n repeat (UGT1A1*28), and haplotype T-long-G at rs887829-(TA)n-rs4148323 were associated with a decrease in bilirubin levels from day 5 to day 6 (P < .01 for all). No contribution from HMOX1 was found. CONCLUSION: Bilirubin levels and changes during the middle and late parts of the first week were attributed to variants and haplotypes in UGT1A1. This quantitative trait study may provide a more robust statistical method for determining the association of genetic factors and bilirubin kinetics to predict the development of neonatal bilirubin in early postnatal life.

Association of UGT1A1 variants and hyperbilirubinemia in breast-fed full-term Chinese infants.

A retrospective case control study of breast-fed full-term infants was carried out to determine whether variants in Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) and Heme Oxygenase-1 (HMOX1) were associated with neonatal hyperbilirubinemia. Eight genetic variants of UGT1A1 and 3 genetic variants of HMOX1 were genotyped in 170 hyperbilirubinemic newborns and 779 controls. Five significant associations with breast-fed hyperbilirubinemia were detected after adjusting for gender, birth season, birth weight, delivery mode, gestational age and False Discovery Rate (FDR) correction: the dominant effect of rs887829 (c-364t) (Odds Ratio (OR): 0.55; 95% Confidence Interval (CI): 0.34-0.89; p = 0.014), the additive effect of (TA)n repeat (OR: 0.59; 95%CI: 0.38-0.91; p = 0.017), the dominant effect of rs4148323 (Gly71Arg, G211A) (OR: 2.02; 95%CI: 1.44-2.85; p = 5.0×10-5), the recessive effect of rs6717546 (g+914a) (OR: 0.30; 95%CI: 0.11-0.83; p = 0.021) and rs6719561 (t+2558c) (OR: 0.38; 95%CI: 0.20-0.75; p = 0.005). Neonates carrying the minor allele of rs887829 (TA)n repeat had significantly lower peak bilirubin than wild types, while the minor allele carriers of rs4148323 had significantly higher peak bilirubin than wild types. No association was found in HMOX1. Our findings added to the understanding of the significance of UGT1A1 in association with neonatal hyperbilirubinemia in East Asian population. Additional studies were required to investigate the mechanisms of the protective effects.

[Application of umbilical venous catheter combined with peripherally inserted central catheter in very low birth weight infants].

OBJECTIVE: To study the application of umbilical venous catheter (UVC) combined with peripherally inserted central catheter (PICC) in very low birth weight infants (VLBWIs). METHODS: A retrospective analysis was performed on the VLBWIs in the neonatal intensive care unit who received UVC combined with PICC (catheter group, n=63) or did not receive the catheter treatment (non-catheter group, n=38) to compare the differences in nosocomial infection, weight gain, and length of hospital stay between the two groups. RESULTS: The rate of nosocomial infection was 17% in the catheter group and 24% in the non-catheter group (P>0.05). Compared with the non-catheter group, the catheter group had a significantly higher weight gain (11.7±2.0 g/kg•d vs 10.6±2.3 g/kg•d; P<0.05) and a significantly shorter length of hospital stay (40±11 days vs 45±14 days; P<0.05). There was no significant difference in the incidence of complications between the two groups. CONCLUSIONS: Compared with those not receiving catheter treatment, the VLBWIs receiving UVC combined with PICC have a markedly higher weight gain and a markedly shorter length of hospital stay and show a declining trend in the rate of nosocomial infection.

[SLC26A4 mutations in a Chinese deafness family discovered by next-generation sequencing technology].

OBJECTIVE: To identify the molecular etiopathogenesis for a non-syndromic hearing loss patient. METHODS: The core family, consists of the patient and his parents, was recruited. Genomic DNA was extracted from peripheral blood. Mutation analysis was carried out by SNaPshot and next-generation sequencing technology. Mutations in SLC26A4 gene were verified by polymerase chain reaction and direct sequencing. RESULTS: Compound heterozygous mutations p.V306GfsX24 and p.P516PfsX11 in SLC26A4 gene were detected in the patient, heterozygous mutation p.V306GfsX24 was detected in the father, heterozygous mutation p.P516PfsX11 was detected in the mother. CONCLUSIONS: Compound heterozygous mutations p.V306GfsX24 and p.P516PfsX11 contributed to patient's hearing loss. Next-generation sequencing technology is a useful tool for detecting de novo mutations of deafness genes, and is suitable for clinical application.