Characteristics of red blood cell transfusion among very preterm infants in China.

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants.

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24-28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65-083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57-0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58-0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52-0.66), and early extubating (aOR, 0.42; 95%CI 0.37-0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. CONCLUSION: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. WHAT IS NEW: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.

The performance of the practices associated with the occurrence of severe intraventricular hemorrhage in the very premature infants: data analysis from the Chinese neonatal network.

BACKGROUND: The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. METHODS: This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0-31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. RESULTS: A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. CONCLUSIONS: The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

OBJECTIVE: We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. STUDY DESIGN: This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. RESULTS: A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9-100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5-37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15-1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0-36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09-1.83) and 1.93 (95% CI, 1.31-2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. CONCLUSION: Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. KEY POINTS: · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

Survey on human milk feeding and enteral feeding practices for very-low-birth-weight infants in NICUs in China Neonatal Network.

BACKGROUND: The breastfeeding rate in China is lower than that in many other countries and the extent of adoption of the "Feeding Recommendations for Preterm Infants and Low Birth Weight Infants" guideline in NICUs remains unclear. METHOD: A web-based survey about the current status of human milk feeding and enteral feeding practices at NICUs was sent to all China Neonatal Network's cooperation units on September 7, 2021, and the respondents were given a month to send their responses. RESULTS: All sixty NICUs responded to the survey, the reply rate was 100%. All units encouraged breastfeeding and provided regular breastfeeding education. Thirty-six units (60.0%) had a dedicated breastfeeding/pumping room, 55 (91.7%) provided kangaroo care, 20 (33.3%) had family rooms, and 33 (55.0%) routinely provided family integrated care. Twenty hospitals (33.3%) had their own human milk banks, and only 13 (21.7%) used donor human milk. Eight units (13.3%) did not have written standard nutrition management guidelines for infants with body weight < 1500 g. Most units initiated minimal enteral nutrition with mother's milk for infants with birth weight ˂1500 g within 24 h after birth. Fifty NICUs (83.3%) increased the volume of enteral feeding at 10-20 ml/kg daily. Thirty-one NICUs (51.7%) assessed gastric residual content before every feeding session. Forty-one NICUs (68.3%) did not change the course of enteral nutrition management during drug treatment for patent ductus arteriosus, and 29 NICUs (48.3%) instated NPO for 1 or 2 feeds during blood transfusion. CONCLUSION: There were significant differences in human milk feeding and enteral feeding strategies between the NICUs in CHNN, but also similarities. The data obtained would be useful in the establishment of national enteral feeding guidelines for preterm infants and quality improvement of cooperation at the national level.

Impact of Maternal Diabetes Mellitus on Neonatal Outcomes among Infants <32 Weeks of Gestation in China: A Multicenter Cohort Study.

OBJECTIVE: Our study aimed to determine the relationship between maternal diabetes mellitus (MDM) and mortality and major morbidities for very preterm infants, as well as the effects of insulin-treated MDM, in the Chinese population. STUDY DESIGN: This retrospective cohort study included all preterm infants born at 240/7 to 316/7 weeks of gestation and admitted to 57 tertiary neonatal intensive care units participating in the Chinese Neonatal Network in 2019. All infants were followed up until discharging from the hospitals. RESULTS: A total of 9,244 very preterm infants were enrolled, with 1,584 (17.1%) born to mothers with MDM. The rates of mortality or any major morbidity in the MDM and non-MDM groups were 45.9% (727/1,584) and 48.1% (3,682/7,660), respectively. After adjustment, the risk of mortality or any morbidity was not significantly increased in the MDM group (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 0.94-1.22) compared with the non-MDM group. Among MDM mothers with treatment data, 18.0% (256/1,420) were treated with insulin. Insulin-treated MDM was not independently associated with the risk of mortality or any morbidity (aOR, 1.01; 95% CI, 0.76-1.34) among very preterm infants, but it was associated with an elevated risk of severe retinopathy of prematurity (aOR, 2.39; 95% CI, 1.13-5.04). CONCLUSION: While the MDM diagnostic rate for mothers of very preterm infants was high in China, MDM was not associated with mortality or major morbidities for very preterm infants. KEY POINTS: · A total of 17% of very preterm infants in Chinese neonatal intensive care units were born to mothers with MDM.. · MDM was not related to mortality or major morbidities in very preterm infants.. · MDM treated by insulin was associated with severe retinopathy of prematurity..

Neurodevelopmental Outcomes of Infants at <29 Weeks of Gestation Born in Canada Between 2009 and 2016.

OBJECTIVE: To evaluate changes in mortality or significant neurodevelopmental impairment (NDI) in children born at <29 weeks of gestation in association with national quality improvement initiatives. STUDY DESIGN: This longitudinal cohort study included children born at 220/7 to 286/7 weeks of gestation who were admitted to Canadian neonatal intensive care units between 2009 and 2016. The primary outcome was a composite rate of death or significant NDI (Bayley Scales of Infant and Toddler Development, Third Edition score <70, severe cerebral palsy, blindness, or deafness requiring amplification) at 18-24 months corrected age. To evaluate temporal changes, outcomes were compared between epoch 1 (2009-2012) and epoch 2 (2013-2016). aORs were calculated for differences between the 2 epochs accounting for differences in patient characteristics. RESULTS: The 4426 children included 1895 (43%) born in epoch 1 and 2531 (57%) born in epoch 2. Compared with epoch 1, in epoch 2 more mothers received magnesium sulfate (56% vs 28%), antibiotics (69% vs 65%), and delayed cord clamping (37% vs 31%) and fewer infants had a Score for Neonatal Acute Physiology, version II >20 (31% vs 35%) and late-onset sepsis (23% vs 27%). Death or significant NDI occurred in 30% of children in epoch 2 versus 32% of children in epoch 1 (aOR, 0.86; 95% CI, 0.75-0.99). In epoch 2, there were reductions in the need for hearing aids or cochlear implants (1.4% vs 2.6%; aOR, 0.50; 95% CI, 0.31-0.82) and in blindness (0.6% vs.1.4%; aOR, 0.38; 95% CI, 0.18-0.80). CONCLUSIONS: Among preterm infants born at <29 weeks of gestation, composite rates of death or significant NDI and rates of visual and hearing impairment were significantly lower in 2013-2016 compared with 2009-2012.

The Trend in Costs of Tertiary-Level Neonatal Intensive Care for Neonates Born Preterm at 220/7-286/7 Weeks of Gestation from 2010 to 2019 in Canada.

OBJECTIVE: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 220/7-286/7 weeks of gestation during an ongoing Canadian national quality improvement project. STUDY DESIGN: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7 weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs. RESULTS: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable. CONCLUSIONS: The total costs and length of stay for infants 220/7-286/7 weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Survey of Mode of Delivery and Maternal and Perinatal Outcomes in Canada.

OBJECTIVE: To identify determinants of cesarean delivery (CD) and examine associations between mode of delivery (MOD) and maternal and perinatal outcomes. METHODS: We conducted a retrospective analysis of a Canadian multicentre birth cohort derived from provincial data collected in 2008/2009. Maternal and perinatal characteristics and outcomes were compared between vaginal and cesarean birth and between the following MOD subgroups: spontaneous vaginal delivery (VD), assisted VD, planned cesarean delivery (CD), and intrapartum CD. Multivariate regression identified determinants of CD and the effects of MOD and previous CD on maternal and perinatal outcomes. RESULTS: The cohort included 264 755 births (72.1% VD and 27.9% CD) from 91 participating institutions. Determinants of CD included maternal age, parity, previous CD, chronic hypertension, diabetes, urinary tract infection or pyelonephritis, gestational hypertension, vaginal bleeding, labour induction, pre-term gestational age, low birth weight, large for gestational age, malpresentation, and male sex. CD was associated with greater risk of maternal and perinatal morbidity and mortality. Subgroup analysis demonstrated higher risk of adverse pregnancy outcomes with assisted VD and intrapartum CD than spontaneous VD. Planned CD reduced the risk of obstetric wound hematoma and perinatal mortality but increased maternal and neonatal morbidity. Previous CD increased the risk of maternal and neonatal morbidity among multiparous women. CONCLUSIONS: The CD rate in Canada is consistent with global trends reflecting demographic and obstetric intervention factors. The risk of adverse pregnancy outcomes with CD warrants evaluation of interventions to safely prevent nonessential cesarean birth.

Antibiotic Use in Neonatal Intensive Care Units in China: A Multicenter Cohort Study.

OBJECTIVE: To provide national-level antibiotic use data from Chinese neonatal intensive care units to inform future antimicrobial stewardship using a large contemporary cohort of preterm infants in China. STUDY DESIGN: This retrospective cohort study enrolled all infants less than 340/7 weeks of gestation admitted to 25 tertiary neonatal intensive care units across China between May 1, 2015, and April 30, 2018. The antibiotic use rate (AUR) was defined as the number of days an infant was prescribed with 1 or more antibiotics divided by the total length of hospital stay. RESULTS: Among 24 597 eligible infants, 21 736 (88.4%) infants received antibiotics. The median AUR was 441 per 1000 patient-days (IQR, 242-692 per 1000 patient-days). The median duration of each antibiotic course was 9 days (IQR, 6-14 days). Overall, 64.6% infants received broad-spectrum antibiotics, with a median broad-spectrum AUR of 250 per 1000 patient-days (IQR, 0-500 per 1000 patient-days), accounting for 70.7% of all antibiotic use days. Overall, 68.7% of all antibiotic use occurred among infants without infection-related morbidities, with a median duration of 8 days (IQR, 6-13 days) for each course. Only 22.9% episodes of culture-negative sepsis were prescribed with antibiotics for 7 or fewer days, and 34.7% were treated with antibiotics for more than 14 days. For early antibiotic use, the median duration of antibiotic therapy within 7 days after birth was 7 days (IQR, 4-7 days). CONCLUSIONS: A high AUR among infants without infections, prolonged antibiotic durations, and excessive use of broad-spectrum antibiotics were the main problems of antibiotic use in Chinese neonatal intensive care units and should be high-impact focuses for future stewardship interventions.

Costs of Neonatal Intensive Care for Canadian Infants with Preterm Birth.

OBJECTIVE: To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses. STUDY DESIGN: We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates. RESULTS: We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of <29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada. CONCLUSIONS: NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.

Association of Co-Exposure of Antenatal Steroid and Prophylactic Indomethacin with Spontaneous Intestinal Perforation.

OBJECTIVE: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at <26 weeks of gestation or <750 g birth weight. STUDY DESIGN: We conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (>7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. RESULTS: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. CONCLUSIONS: In preterm neonates of <26 weeks of gestation or birth weight <750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality.

Family Integrated Care for Preterm Infants in China: A Cluster Randomized Controlled Trial.

OBJECTIVE: To explore whether family integrated care (FICare) is feasible and improves the outcomes of preterm infants in China. STUDY DESIGN: This was a multicenter prospective cluster-randomized controlled trial comparing FICare and standard care. The primary outcome was length of stay (LOS). Secondary outcomes were nosocomial infections, duration of supplemental oxygen, breastfeeding, and weight gain. Outcomes were compared using univariate and multivariable analyses adjusted for potential confounders and clustering. RESULTS: We enrolled 601 preterm infants from 11 neonatal intensive care units (FICare, n = 298; control, n = 303). The unadjusted LOS was 30.81 vs 30.26 days (mean ratio, 1.02; 95% CI, 0.85-1.22; P = .85). After adjustment, outcomes in the FICare group were improved compared with the control group, including LOS (28.26 vs 35.04 days; mean ratio, 0.81; 95% CI, 0.72-0.91), total medical expenditures (mean ratio, 0.69; 95% CI, 0.53-0.90), weight gain velocity (15.73 vs 10.30 g/day; mean difference, 5.43; 95% CI, 3.65-7.21), duration of supplemental oxygen (13.11 vs 21.42 days; mean difference, 0.71; 95% CI, 0.50-1.00), nosocomial infection rates (4.13 vs 5.84/1000 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), antibiotic exposure (38.63 vs 57.32/100 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), breastfeeding rates (87.25% vs 55.78%; OR, 5.42; 95% CI, 3.25-9.05), and rehospitalization rates (3.65% vs 7.48%; OR, 0.47; 95% CI, 0.28-0.77). At follow-up to 18 months, breastfeeding rates and weight were significantly (P < .05) higher over time in the FICare group. CONCLUSIONS: FICare was feasible in Chinese neonatal intensive care units and was associated with reduced hospital LOS, medical expenditures, and rates of adverse outcomes.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Admissions and Emergency Visits by Late Preterm Singletons and Twins in the First 5 Years: A Population-Based Cohort Study.

OBJECTIVE: To compare admission and emergency visits of late preterm (340/7-366/7 weeks) versus term infants (370/7-416/7 weeks) in the first 5 years. STUDY DESIGN: This population-based cohort study included all singletons and twins born alive at 340/7 to 416/7 weeks' gestation registered in a health administrative database in Ontario, Canada, between April 1, 2002 and December 31, 2012. Admissions and emergency visits from initial postnatal discharge to 5 years were compared between late preterm and term infants adjusting for maternal and infant characteristics. RESULTS: A total of 1,316,931 infants (75,364 late preterm infants) were included. Late preterm infants had more frequent admissions than term infants in the first 5 years in both singletons (adjusted incidence rate ratio [95% confidence interval] = 1.46 [1.42-1.49]) and twins (1.21 [1.11-1.31]). The difference in admissions between late preterm and term infants were smaller in twins than singletons and decreased with children's ages. Twins had less frequent admissions than singletons for late preterm infants, but not for term infants. The emergency visits were more frequent in late preterm than term infants in all the periods. CONCLUSION: Admissions and emergency visits were more frequent in late preterm than term infants through the first 5 years. Admissions were less frequent in late preterm twins than singletons.

Evaluating the effect of Family Integrated Care on maternal stress and anxiety in neonatal intensive care units.

Objective: To identify how Family Integrated Care (FICare) affected maternal stress and anxiety. Study Design: This secondary analysis of the FICare cluster randomised controlled trial included infants born between 1 April 2013 and 31 August 2015 at ≤33 weeks' gestation. Mothers completed the PSS:NICU and STAI questionnaires at enrolment and study day 21. Results: 1383 mothers completed the surveys at one or both time-points. The mean PSS:NICU and STAI scores at day 21 were significantly lower in the FICare mothers than controls (PSS:NICU mean [standard deviation] FICare 2.32 [0.75], control 2.48 [0.78], p = 0.0005; STAI FICare 70.8 [20.0], control 74.2 [19.6], p = 0.0004). The sights and sounds, looks and behaviour, and parental role PSS:NICU subscales and the state and trait STAI subscales were all significantly different between FIC are and controls at day 21. The magnitude of change in all stress and anxiety subscales was greater in the FICare group than controls. These differences remained significant after adjustment for confounders with the greatest change in the parental role (least-squares mean [95% confidence interval] FICare -0.65 [-0.72, 0.57], control -0.31 [-0.38, -0.24], p < 0.0001) and state anxiety subscales. Conclusion: FICare is effective at reducing NICU-related maternal stress and anxiety.

Corrigendum to: Refining evidence-based retinopathy of prematurity screening guidelines: The SCREENROP study.

[This corrects the article DOI: 10.1093/pch/pxz085.].

Hospital Care Cost and Resource Use of Early Discharge of Healthy Late Preterm and Term Singletons: A Population-based Cohort Study and Cost Analysis.

OBJECTIVE: To assess the hospital care cost and resource use associated with discharge timings after late preterm and term births. STUDY DESIGN: This population-based cohort study and cost analysis included all healthy singleton late preterm (35-36 weeks gestational age) and term infants (37-41 weeks gestational age) born vaginally in hospitals in Ontario, Canada, from 2003 to 2012. Early, late, and very late discharge (<48, 48-71, and 72-95 hours after birth, respectively) were compared using generalized linear models. The primary outcome was the total hospital care cost (hospitalizations and emergency department visits) per infant within 28 days of birth. RESULTS: Among 860 693 singletons (3.7% late preterm), early discharge increased significantly over 10 years for term infants (from 69% to 82%; P < .001), but not late preterm infants (from 32% to 35%; P = .75). The mean total cost within 28 days after birth was not significantly different for late preterm infants between early discharge and late discharge after adjustment. However, for term infants, the adjusted cost was higher with early discharge than late discharge (aMCD $311 [95% CI, $211-$412] per infant; $366 [95% CI, $355-$377] per mother-infant dyad). The neonatal readmission rates were higher after early than late discharge for late preterm and term infants. CONCLUSIONS: Early discharge was not associated with cost savings for vaginally born healthy singleton late preterm infants, and instead was associated with a cost increase for term infants. Early discharge was associated with higher neonatal readmission rates. Individualized approach balancing the risk and benefit is appropriate to determine the discharge timings.