A prediction tool for mode of delivery in twin pregnancies-a secondary analysis of the Twin Birth Study.

BACKGROUND: One of the controversies regarding the management of twin gestations relates to the mode of delivery. Currently, counseling regarding the mode of delivery and the chance of successful vaginal twin delivery is based on the average risk for intrapartum cesarean delivery in the general population of twin pregnancies. Decision support tools that provide an individualized risk for intrapartum cesarean delivery based on the unique characteristics of each patient can improve counseling and decision-making regarding the choice of mode of delivery in twin pregnancies. OBJECTIVE: This study aimed to develop and validate a prediction model to determine the risk for intrapartum cesarean delivery in twin pregnancies. STUDY DESIGN: In this secondary analysis of the Twin Birth Study, a multicenter randomized controlled trial, we considered the subgroup of individuals who underwent a trial of vaginal delivery. Candidate predictors included maternal age, parity, previous cesarean delivery, conception method, chorionicity, diabetes and hypertension in pregnancy, gestational age at birth, the onset of labor, presentation of the second twin, sonographic fetal weight estimation, and fetal sex. The co-primary outcomes were overall intrapartum cesarean delivery and cesarean delivery of the second twin. Multivariable logistic regression models were used to estimate the probability of the study outcomes. Model performance was evaluated using measures of discrimination (the area under the receiver operating characteristic curve), calibration, and predictive accuracy. Internal validation was performed using the bootstrap resampling technique. RESULTS: A total of 1221 individuals met the study criteria. The rate of overall intrapartum cesarean delivery and cesarean delivery for the second twin was 25.4% and 5.7%, respectively. The most contributory predictor variables were nulliparity, term birth (≥37 weeks), a noncephalic presentation of the second twin, previous cesarean delivery, and labor induction. The models for overall intrapartum cesarean delivery and cesarean delivery of the second twin had good overall discriminatory accuracy (area under the receiver operating characteristic curve, 0.720; 95% confidence interval, 0.688-0.752 and 0.736; 95% confidence interval, 0.669-0.803, respectively) and calibration (as illustrated by the calibration plot and Brier scores of 0.168; 95% confidence interval, 0.156-0.180 and 0.051; 95% confidence interval, 0.040-0.061, respectively). The models achieved good specificity (66.7% and 81.6%, respectively), high negative predictive value (86.0% and 96.9%, respectively), and moderate sensitivity (68.1% and 57.1%, respectively). CONCLUSION: The prediction models developed in this study may assist care providers in counseling individuals regarding the optimal timing and mode of delivery in twin pregnancies by providing individualized estimates of the risk for intrapartum cesarean delivery.

Prediction of birthweight and risk of macrosomia in pregnancies complicated by diabetes.

BACKGROUND: Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management. Sonographic fetal weight estimation is the most commonly used tool to predict birthweight and macrosomia. However, the predictive accuracy of sonographic fetal weight estimation for these outcomes is limited. In addition, an up-to-date sonographic fetal weight estimation is often unavailable before birth. This may result in a failure to identify macrosomia, especially in pregnancies complicated by diabetes mellitus where care providers might underestimate fetal growth rate. Therefore, there is a need for better tools to detect and alert care providers to the potential risk of accelerated fetal growth and macrosomia. OBJECTIVE: This study aimed to develop and validate prediction models for birthweight and macrosomia in pregnancies complicated by diabetes mellitus. STUDY DESIGN: This was a completed retrospective cohort study of all patients with a singleton live birth at ≥36 weeks of gestation complicated by preexisting or gestational diabetes mellitus observed at a single tertiary center between January 2011 and May 2022. Candidate predictors included maternal age, parity, type of diabetes mellitus, information from the most recent sonographic fetal weight estimation (including estimated fetal weight, abdominal circumference z score, head circumference-to-abdomen circumference z score ratio, and amniotic fluid), fetal sex, and the interval between ultrasound examination and birth. The study outcomes were macrosomia (defined as birthweights >4000 and >4500 g), large for gestational age (defined as a birthweight >90th percentile for gestational age), and birthweight (in grams). Multivariable logistic regression models were used to estimate the probability of dichotomous outcomes, and multivariable linear regression models were used to estimate birthweight. Model discrimination and predictive accuracy were calculated. Internal validation was performed using the bootstrap resampling technique. RESULTS: A total of 2465 patients met the study criteria. Most patients had gestational diabetes mellitus (90%), 6% of patients had type 2 diabetes mellitus, and 4% of patients had type 1 diabetes mellitus. The overall proportions of infants with birthweights >4000 g, >4500 g, and >90th percentile for gestational age were 8%, 1%, and 12%, respectively. The most contributory predictor variables were estimated fetal weight, abdominal circumference z score, ultrasound examination to birth interval, and type of diabetes mellitus. The models for the 3 dichotomous outcomes had high discriminative accuracy (area under the curve receiver operating characteristic curve, 0.929-0.979), which was higher than that achieved with estimated fetal weight alone (area under the curve receiver operating characteristic curve, 0.880-0.931). The predictive accuracy of the models had high sensitivity (87%-100%), specificity (84%-92%), and negative predictive values (84%-92%). The predictive accuracy of the model for birthweight had low systematic and random errors (0.6% and 7.5%, respectively), which were considerably smaller than the corresponding errors achieved with estimated fetal weight alone (-5.9% and 10.8%, respectively). The proportions of estimates within 5%, 10%, and 15% of the actual birthweight were high (52.3%, 82.9%, and 94.9%, respectively). CONCLUSION: The prediction models developed in the current study were associated with greater predictive accuracy for macrosomia, large for gestational age, and birthweight than the current standard of care that includes estimated fetal weight alone. These models may assist care providers in counseling patients regarding the optimal timing and mode of delivery.

Variability in antimicrobial use among infants born at <33 weeks gestational age.

Excessive antimicrobial use is associated with adverse neonatal outcomes. In our cohort of 27,163 infants born at <33 weeks gestational age, the first week after birth accounted for the highest rates of antimicrobial use, and variability across sites persisted after adjustment for patient characteristics correlated with illness severity.

Perinatal Factors Associated With Breastfeeding Trends After Preterm Birth <29 Weeks Gestation: Can We Predict Early Discontinuation?

OBJECTIVE: To determine the rates and perinatal factors associated with initiation and early discontinuation of breastfeeding among very preterm neonates. METHODS: This was a retrospective cohort study of very preterm infants (<29 weeks gestation) admitted to 2 regional Level III neonatal intensive care units (NICUs) from January 1, 2015, to December 31, 2019. A national neonatal database was used to evaluate initiation and continuation rates of breastfeeding and associated perinatal factors. Stored nutrition profiles and delivery record books were used to determine feeding volumes associated with continuation of breastfeeding to hospital discharge for a subgroup of infants at a single site. Descriptive and inferential statistics were used to present the results between groups, and logistic regression modeling was used to calculate crude and adjusted odds ratios (OR) and 95% CI. RESULTS: Of 391 eligible neonates, 84% initiated breastfeeding but only 38% continued to discharge. Interestingly, frequency of breastfeeding initiation (P < 0.001) and continuation (P < 0.001) declined over the study period. After adjustment for confounders, younger maternal age, earlier gestational age, cigarette smoking, and multiparity were significantly associated with early discontinuation of breastfeeding prior to hospital discharge. Early discontinuation of breastfeeding was also related to lower volumes of breastmilk by day 7 of life (P = 0.004). CONCLUSION: Very preterm neonates are at high risk for non-initiation and early discontinuation of breastfeeding. The early postnatal period represents a critical time to establish breastmilk volumes, and the identification of key perinatal risk factors allows for early and targeted breastfeeding support.

Optimal timing of labor induction after prelabor rupture of membranes at term: a secondary analysis of the TERMPROM study.

BACKGROUND: In the case of prelabor rupture of membranes at term, the risk for neonatal and maternal infectious morbidity increases progressively with time from prelabor rupture of membranes. Although most studies identified a benefit associated with early induction within the first 24 hours following term prelabor rupture of membranes, there is currently no precise data regarding how early should induction be scheduled. OBJECTIVE: This study aimed to identify the optimal timing of labor induction among women with term prelabor rupture of membranes by comparing the maternal and neonatal outcomes associated with labor induction with those of expectant management at any given 1-hour interval following prelabor rupture of membranes. STUDY DESIGN: This was a secondary analysis of data from the TERMPROM trial, an international, multicenter, randomized clinical trial on immediate delivery vs expectant management of women with prelaor rupture of membranes at term (≥37+0/7 weeks' gestation). We considered all participants as a single cohort of women with term prelabor rupture of membranes, irrespective of the original randomized study group allocation. For each given 1-hour time interval within the first 36 hours following prelabor rupture of membranes, we compared the outcomes of subjects for whom labor induction was initiated during this interval with those of subjects managed expectantly at the same time interval. The primary neonatal outcome was a composite of neonatal infection and admission to the neonatal intensive care unit. The primary maternal outcomes included maternal infection (clinical chorioamnionitis or postpartum fever) and cesarean delivery. RESULTS: Of the 4742 subjects who met the study criteria, 2622 underwent labor induction, and 2120 experienced a spontaneous onset of labor. The rates of the neonatal composite outcome, neonatal admission to intensive care unit, and maternal infection increased progressively with time after prelabor rupture of membranes. The risk for these outcomes was lower among women who underwent induction when compared with those managed expectantly within the first 15 to 20 hours after prelabor rupture of membranes without affecting the risk for cesarean delivery. In addition, women who underwent labor induction within the first 30 to 36 hours had a shorter prelabor rupture of membranes to delivery time and a shorter total maternal hospital stay when compared with those managed expectantly at the same time interval. Among women managed expectantly, less than two-thirds (64%; 1365/2120) experienced a spontaneous onset of labor within the first 24 hours following prelabor rupture of membranes. CONCLUSION: These findings suggest that immediate labor induction seems to be the optimal management strategy to minimize neonatal and maternal morbidity in the setting of prelabor rupture of membranes at term gestations. In cases for which immediate induction is not feasible, labor induction remains the preferred option over expectant management if performed within the first 15 to 20 hours after prelabor rupture of membranes.

Outcomes of infants with hypoxic-ischemic encephalopathy during COVID-19 pandemic lockdown in Canada: a cohort study.

PURPOSE: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada. METHODS: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI). RESULTS: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use. CONCLUSIONS: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada.

Antimicrobial utilization in very-low-birth-weight infants: association with probiotic use.

OBJECTIVE: To examine the association between probiotic use and antimicrobial utilization. STUDY DESIGN: We retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days. RESULT: Of 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]). CONCLUSION: Probiotic use was associated with a significant reduction in AUR among VLBW infants.

Rates and Determinants of Home Nasogastric Tube Feeding in Infants Born Very Preterm.

OBJECTIVE: To examine rates and determinants of home nasogastric (NG)-tube feeding at hospital discharge in a cohort of very preterm infants within the Canadian Neonatal Network (CNN). STUDY DESIGN: This was a population-based cohort study of infants born <33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2010, and December 31, 2018. We excluded infants who had major congenital anomalies, required gastrostomy-tube, or were discharged to non-CNN facilities. Multivariable logistic regression analysis was used to identify independent determinants of home NG-tube feeding at hospital discharge. RESULTS: Among the 13 232 infants born very preterm during the study period, 333 (2.5%) were discharged home to receive NG-tube feeding. Rates of home NG-tube feeding varied across Canadian NICUs, from 0% to 12%. Determinants of home NG-tube feeding were gestational age (aOR 0.94 per each gestational week increase, 95% CI 0.88-0.99); duration of mechanical ventilation (aOR 1.02 per each day increase, 95% CI 1.01-1.02); high illness severity at birth (aOR 1.32, 95% CI 1.01-1.74); small for gestational age (aOR 2.06, 95% CI 1.52-2.78); male sex (aOR 0.61, 95% CI 0.49-0.77); severe brain injury (aOR 1.60, 95% CI 1.10-2.32); and bronchopulmonary dysplasia (aOR 2.22, 95% CI 1.67-2.94). CONCLUSIONS: Rates of home NG-tube feeding varied widely between Canadian NICUs. Higher gestational age and male sex reduced the odds of discharge home to receive NG-tube feeding; and in contrast small for gestational age, severe brain injury, prolonged duration on mechanical ventilation and bronchopulmonary dysplasia increased the odds.

2% aqueous vs alcohol-based chlorhexidine for skin antisepsis in VLBW neonates undergoing peripheral venipuncture: a non-inferiority trial.

OBJECTIVE: To compare 2% aqueous chlorhexidine gluconate (AQC) vs. 2% chlorhexidine gluconate in 70% isopropyl alcohol (ALC) for pre-venipuncture skin antisepsis in very-low-birth-weight neonates (VLBW, birth-weight <1500 grams). STUDY DESIGN: Double-blind, non-inferiority trial randomized 199 VLBW neonates, age 2-28 days, to receive pre-venipuncture skin preparation using single application of swabstick impregnated with AQC (n = 99) or ALC (n = 100). Skin clearance rate (percentage post-cleansing skin swabs with <15 bacterial colony forming units) with a 10% non-inferiority margin for AQC was primary outcome. Absolute and relative CFU reduction and adverse skin reactions were compared. RESULTS: AQC's clearance was non-inferior to ALC (91% vs. 88%; 95% CI -6.6%, +12.4%). Median (interquartile range) absolute [61 (16, 110) vs. 63 (18, 100); p = 0.65] and relative [100% (97%, 100%) vs. 100% (99.7%, 100%); p = 0.20] CFU reductions were similar. Neither group experienced any adverse reactions. CONCLUSION: AQC may provide non-inferior skin disinfection to ALC in VLBW neonates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01270776.

Predictors of successful trial off continuous positive airway pressure and high flow nasal cannula in preterm infants <30 weeks' gestation: A retrospective study.

OBJECTIVES: To identify the predictors of successful first trial off nasal continuous positive airway pressure (nCPAP). METHODS: A retrospective cohort study of infants ≤29 weeks' gestation who required nCPAP for >24 h was conducted. Logistic regression was used to detect predictors for successful trial off nCPAP. Statistical analysis was performed using the SAS software. RESULTS: A total of 727 infants were included in the analysis. Infants who were successful in their first trial off nCPAP (n = 313) were of higher gestational age (GA) and birth weight (BW), as well as a higher proportion of female infants, compared with those who were not successful (p < 0.01). When stratified by GA, a negative correlation was noted between GA and postmenstrual age at successful trial off nCPAP or high flow nasal cannula (HFNC) (r = 0.45, p < 0.01). Logistic regression analysis showed that GA (odds ratio [OR] 1.13, 95% confidence interval [CI] [1.03-1.24], p = 0.01) and percentage of time spent with an oxygen saturation over 89% in the 24 h preceding the trial off nCPAP (OR 1.08, 95% CI [1.05-1.11], p = 0.00) were independent predictors for successful trial off nCPAP. CONCLUSION: Successful trial off nCPAP or HFNC in preterm infants is significantly associated with higher GA, BW, female gender, and the specific oxygen saturation histogram in the preceding 24-h period.

Maternal weight gain and pregnancy outcomes in twin gestations.

BACKGROUND: Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population. OBJECTIVE: This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group. RESULTS: A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the <10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the <10th centile. Associations were less consistent in the overweight and obese groups. CONCLUSION: These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies.

Gestational diabetes and fetal growth in twin compared with singleton pregnancies.

BACKGROUND: Gestational diabetes mellitus is associated with accelerated fetal growth in singleton pregnancies but may affect twin pregnancies differently because of the slower growth of twin fetuses during the third trimester of pregnancy and their greater predisposition to fetal growth restriction. OBJECTIVE: This study aimed to evaluate the association of gestational diabetes mellitus with longitudinal fetal growth in twin pregnancies and to compare this association with that observed in singleton pregnancies. STUDY DESIGN: This was a retrospective cohort study of all women with a singleton or twin pregnancy who were followed up at a single tertiary referral center between January 2011 and April 2020. Data on estimated fetal weight and individual fetal biometric indices were extracted from ultrasound examinations of eligible women. Generalized linear models were used to model and compare the change in fetal weight and individual biometric indices as a function of gestational age between women with and without gestational diabetes mellitus in twin pregnancies and between women with and without gestational diabetes mellitus in singleton pregnancies. The primary outcome was estimated fetal weight as a function of gestational age. The secondary outcomes were longitudinal growth of individual fetal biometric indices and the rate of small for gestational age and large for gestational age at birth. RESULTS: A total of 26,651 women (94,437 ultrasound examinations) were included in the analysis: 1881 with a twin pregnancy and 24,770 with a singleton pregnancy. The rate of gestational diabetes mellitus in the twin and singleton groups was 9.6% (n=180) and 7.6% (n=1893), respectively. The estimated fetal weight in singleton pregnancies with gestational diabetes mellitus was significantly higher than that in pregnancies without gestational diabetes mellitus (P<.001) starting at approximately 30 weeks of gestation. The differences remained similar after adjusting for maternal age, chronic hypertension, nulliparity, and neonatal sex (P<.001). In twin pregnancies, fetal growth was similar between pregnancies with and without gestational diabetes mellitus (P=.105 and P=.483 for unadjusted and adjusted models, respectively). The findings were similar to the association of gestational diabetes mellitus with the risk of large for gestational fetuses and the growth of each biometric index. When stratified by type of gestational diabetes mellitus treatment, twin pregnancies with gestational diabetes mellitus was associated with accelerated fetal growth only in the subgroup of women with medically treated gestational diabetes mellitus (P<.001), which represented 12% (n=21) of the twin pregnancy group with gestational diabetes mellitus. CONCLUSION: In contrast to singleton pregnancies, twin pregnancies with gestational diabetes mellitus is less likely to be associated with accelerated fetal growth. This finding has raised the question of whether the diagnostic criteria for gestational diabetes mellitus and the blood glucose targets in women diagnosed with gestational diabetes mellitus should be individualized for twin pregnancies.

Patterns of discordant growth and adverse neonatal outcomes in twins.

BACKGROUND: Intertwin size discordance is an independent risk factor for adverse neonatal outcomes in twin pregnancies. However, size discordance at a given point in gestation fails to take into consideration information, such as the timing of onset and the rate of progression of discordance, that may be of prognostic value. OBJECTIVE: In this study, we aimed to identify distinct patterns of discordant fetal growth in twin pregnancies and to determine whether these patterns are predictive of adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancies in a single tertiary referral center between January 2011 and April 2020, who had at least 3 ultrasound examinations during pregnancy that included assessment of fetal biometry. Size discordance was calculated at each ultrasound examination, and pregnancies were classified into 1 of 4 predetermined patterns based on the timing of onset and the progression of discordance: pattern 1, no significant discordance group (referent); pattern 2, early (<24 weeks' gestation) progressive discordance group; pattern 3, early discordance with plateau group; or pattern 4, late (≥24 weeks' gestation) discordance group. The associations of discordance pattern (using pattern 1 as referent) with preterm birth, preeclampsia, size discordance at birth, and birthweight<10th percentile were expressed as adjusted relative risk with 95% confidence intervals and were compared with those observed for a single measurement of size discordance at 32 weeks' gestation. RESULTS: Of 2075 women with a twin gestation who were identified during the study period, 1059 met the study criteria. Of the 1059 women, 599 (57%) were classified as no significant discordance (pattern 1), 23 (2%) as early progressive discordance (pattern 2), 160 (15%) as early discordance with plateau (pattern 3), and 277 (26%) as late discordance (pattern 4). The associations of discordance pattern with preterm birth at <34 weeks' gestation and preeclampsia were strongest for pattern 2 (rates of 43% [adjusted relative risk, 3.43; 95% confidence interval, 2.10-5.62] and 17% [adjusted relative risk, 5.81; 95% confidence interval, 2.31-14.60], respectively), intermediate for pattern 3 (rates of 23% [adjusted relative risk, 1.82; 95% confidence interval, 1.28-2.59] and 6% [adjusted relative risk, 2.08; 95% confidence interval, 1.01-4.43], respectively), and weakest for pattern 4 (rates of 12% [adjusted relative risk, 0.96; 95% confidence interval, 0.65-1.42] and 4% [adjusted relative risk, 1.41; 0.68-2.92], respectively). In contrast, a single measurement of size discordance at 32 weeks' gestation showed no association with preeclampsia and only a weak association with preterm birth at <34 weeks' gestation. CONCLUSION: We identified 4 distinct discordance growth patterns among twins that demonstrated a dose-response relationship with adverse outcomes and seemed to be more informative than a single measurement of size discordance.

Duration of and trends in respiratory support among extremely preterm infants.

OBJECTIVE: To evaluate annual trends in the administration and duration of respiratory support among preterm infants. DESIGN: Retrospective cohort study. SETTING: Tertiary neonatal intensive care units in the Canadian Neonatal Network. PATIENTS: 8881 extremely preterm infants born from 2010 to 2017 treated with endotracheal and/or non-invasive positive pressure support (PPS). MAIN OUTCOME MEASURES: Competing risks methods were used to investigate the outcomes of mortality and time to first successful extubation, definitive extubation, weaning off PPS, and weaning PPS and/or low-flow oxygen, according to gestational age (GA). Cox proportional hazards and regression models were fitted to evaluate the trend in duration of respiratory support, survival and surfactant treatment over the study period. RESULTS: The percentages of infants who died or were weaned from respiratory support were presented graphically over time by GA. Advancing GA was associated with ordinally earlier weaning from respiratory support. Year over year, infants born at 23 weeks were initially and definitively weaned from endotracheal and all PPS earlier (HR 1.06, 95% CI 1.01 to 1.11, for all outcomes), while survival simultaneously increased (OR 1.11, 95% CI 1.03 to 1.18). Infants born at 26 and 27 weeks remained on non-invasive PPS longer (HR 0.97, 95% CI 0.95 to 0.98 and HR 0.97, 95% CI 0.95 to 0.99, respectively). Early surfactant treatment declined among infants born at 24-27 weeks GA. CONCLUSIONS: Infants at the borderline of viability have experienced improved survival and earlier weaning from all forms of PPS, while those born at 26 and 27 weeks are spending more time on PPS in recent years. GA-based estimates of the duration of respiratory support and survival may assist in counselling, benchmarking, quality improvement and resource planning.

Characteristics and outcomes of preterm neonates according to number of doses of surfactant received.

OBJECTIVES: To identify characteristics and outcomes of infants who received multiple doses of surfactant vs those who received one dose or none. STUDY DESIGN: In this retrospective study, we included neonates of 22-28 weeks' gestation admitted to NICUs in the Canadian Neonatal Network. Patients were divided into three groups: no surfactant, single dose, and multiple doses. The primary outcome was a composite of mortality or any of the major morbidities, including severe neurological injury, bronchopulmonary dysplasia, or ≥stage 3 retinopathy of prematurity. RESULTS: Of 8024 eligible neonates, 2461 (31%) did not receive surfactant, 3545 (44%) received one dose, and 2018 (25%) received >1 dose. Receiving one or more doses of surfactant was associated with significantly higher adjusted odds of mortality or major morbidities in a dose-dependent manner. CONCLUSIONS: Receiving one or more doses of surfactant was associated with adverse neonatal outcomes. Receipt of more than one dose may reflect underlying severe lung immaturity.

Development of a national neonatal intensive care unit-specific antimicrobial stewardship programme in Canada: protocol for a cohort study.

INTRODUCTION: Early empiric treatment with broad-spectrum antimicrobials is common in neonatal intensive care units (NICU) due to the non-specific clinical presentation of infection. However, excessive and inappropriate antimicrobial use can lead to the emergence of drug-resistant organisms and adverse neonatal outcomes. This study aims to develop and implement a nationwide NICU-specific antimicrobial stewardship programme (ASP) to promote judicious antimicrobial use and control the emergence of multidrug-resistant organisms (MDROs) in Canada. METHODS AND ANALYSIS: Our study population will include all very low-birth-weight neonates admitted to participating tertiary NICU in Canada. Based on the existing limited literature, we will develop consensus on NICU antimicrobial stewardship interventions to enhance best practices. Using an expanded Canadian Neonatal Network (CNN) platform, we will collect data on antimicrobial use and the susceptibility of organisms identified in clinical samples from blood and cerebrospinal fluid over a period of 2 years. These data will be used to provide all NICU stakeholders with benchmarked centre-adjusted antimicrobial use and MDRO prevalence reports. An ASP plan will be developed at both individual unit and national levels in the subsequent years. Knowledge translation strategies will be implemented through the well-established Evidence-based Practice for Improving Quality methodology. ETHICS AND DISSEMINATION: Ethics for the study has been granted by the University of British Columbia Children's & Women's Research Ethics Board (H19-02490) and supported by CNN Executive Committee. The study results will be disseminated through national organisations and open access peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04388293.

Actuarial Survival Based on Gestational Age in Days at Birth for Infants Born at <26 Weeks of Gestation.

OBJECTIVE: To provide comprehensive, contemporary information on the actuarial survival of infants born at 22-25 weeks of gestation in Canada. STUDY DESIGN: In a retrospective cohort study, we included data from preterm infants of 22-25 weeks of gestation admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 2010 and 2017. Infants with major congenital anomalies were excluded. We calculated gestational age using in vitro fertilization date, antenatal ultrasound dating, last menstrual period, obstetrical estimate, or neonatal estimate (in that order). Infants were followed until either discharge or death. Each day of gestational age was considered a category except for births at 22 weeks, where the first 4 days were grouped into one category and the last 3 days were grouped into another category. For each day of life, an actuarial survival rate was obtained by calculating how many infants survived to discharge out of those who had survived up to that day. RESULTS: Of 4335 included infants, 85, 679, 1504, and 2067 were born at 22, 23, 24, and 25 weeks of gestation, respectively. Survival increased from 32% at 22 weeks to 83% at 254-6/7 weeks. Graphs of actuarial survival developed for the first 6 weeks after birth in male and female children indicated a steep increase in survival during the first 7-10 days postnatally. CONCLUSIONS: Survival increased steadily with postnatal survival and was dependent on gestational age in days and sex of the child.

Epidemiology of thrombosis in Canadian neonatal intensive care units.

OBJECTIVE: To assess the rate, location, risk factors, management, and outcomes of neonatal thrombosis (NT). DESIGN: A retrospective study investigating infants admitted to NICUs in Canadian Neonatal Network between January 2014 and December 2016 and diagnosed with NT. Each infant with NT was matched with an infant without NT. RESULTS: Of 39,971 infants, 587 (1.5%) were diagnosed with NT: 440 (75%) venous, 112 (19%) arterial, 29 (5%) both. NT rate was 1.4% in full-term and 1.7% in preterm infants. Venous thrombi occurred most commonly in the portal vein and arterial thrombi in the cerebral artery. Conservative management and low molecular weight heparin were the most common treatment modalities. Hospital stay was longer (p < 0.001) in the NT patients, but mortality was similar. CONCLUSIONS: NT was diagnosed in ~15/1000 NICU admissions and most commonly in the portal vein and cerebral arteries. Management varied based on the type and location of thrombi. Large multicenter trials are needed to address the best management strategies.

Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?

OBJECTIVE: To examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks' gestation. DESIGN: A retrospective cohort study. SETTING: Data collected by the Canadian Neonatal Network. PATIENTS: Neonates born at <29 weeks' gestation between January 2007 and December 2016. MAIN OUTCOME MEASURES: We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities. RESULTS: Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25-28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was -0.043 (95% CI -0.071 to -0.015) and for girls was -0.012 (95% CI -0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes. CONCLUSION: The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia.

OBJECTIVE: To compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care. STUDY DESIGN: We conducted a retrospective cohort study of neonates ≥35 weeks' gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities. RESULTS: Of 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22-0.52) compared with standard care group. CONCLUSION: Despite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.