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.

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.

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.

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.

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.

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.

Central Line-Associated Blood Stream Infections and Non-Central Line-Associated Blood Stream Infections Surveillance in Canadian Tertiary Care Neonatal Intensive Care Units.

OBJECTIVE: To determine if the reported reduction in hospital-acquired infections is due to reduced central line-associated blood stream infections (CLABSI) or non-CLABSIs. STUDY DESIGN: A retrospective cohort study design was used to describe the change in organism pattern and incidence of hospital-acquired infections (CLABSIs and non-CLABSIs) in neonates <33 weeks of gestation admitted to tertiary neonatal intensive care units in the Canadian Neonatal Network between January 1, 2010, and December 31, 2016. Hospital-acquired infection was diagnosed when a pathogenic organism was isolated from blood or cerebrospinal fluid in a neonate with suspected sepsis. CLABSI was diagnosed when a central venous catheter was present at the time or removed in the 2 days before a hospital-acquired infection diagnosis. Cochran-Armitage and Mann-Kendall trend tests and linear regression models were used for statistical analyses. RESULTS: Of 28 144 eligible neonates from 30 Canadian Neonatal Network neonatal intensive care units, 3306 (11.7%) developed hospital-acquired infections. There was a significant decrease in the rate of hospital-acquired infections (14.2% in 2010 and 9.2% in 2016; P < .01), and the rate of both CLABSIs and non-CLABSIs (P < .01) over the study period concomitant with a significant decrease in the duration of central line use (P = .01). The rates of meningitis also decreased during the study period (1.2% in 2010 and 0.9% in 2016; P < .01). Infections owing to gram-positive cocci significantly decreased, but infections owing to gram-negative organisms remained unchanged. CONCLUSION: Although there was a significant decrease in CLABSIs and non-CLABSIs, hospital-acquired infections in preterm neonates remained high. Infections owing to gram-negative organisms remained unchanged and are a target for future preventative efforts.

Antibiotic exposure and development of necrotizing enterocolitis in very preterm neonates.

OBJECTIVE: To examine the association between the duration of antibiotic exposure and development of stage 2 or 3 necrotizing enterocolitis (NEC) in very preterm neonates. STUDY DESIGN: A retrospective case-control study was conducted from Canadian Neonatal Network data for preterm neonates born before 29 weeks' gestation and admitted 2010 through 2013. Efforts were made to match each NEC case to two controls for gestational age, birth weight (±100 g) and sex. RESULTS: A total of 224 cases and 447 controls were identified. The incidence of antenatal steroid administration, the number of days nil-per-os and the number of antibiotic days prior to onset of NEC were significantly different in neonates with NEC. A multiple regression analysis revealed that the duration of antibiotic use was higher among NEC cases compared to controls (P<0.01). Empiric antibiotic treatment of 5 or more days was associated with significantly increased odds of NEC as compared with antibiotic exposure of 0 to 4 days (adjusted odds ratio: 2.02; 95% CI 1.55, 3.13). CONCLUSION: Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks' gestation was associated with an increased risk of NEC.

Narcotics and Sedative Use in Preterm Neonates.

OBJECTIVES: To evaluate patterns of narcotic and sedative use in neonatal intensive care units (NICUs) across Canada using data collected by the Canadian Neonatal Network. STUDY DESIGN: We conducted a retrospective observational cohort study of preterm neonates at <33 weeks' gestation and admitted to a participating Canadian Neonatal Network NICU. The proportion of all neonates who received sedative(s), narcotic(s), or either sedative(s), narcotic(s), or both during their NICU stay was calculated for each year. Because opioids are used for premedication before intubation, only continuous infusions of a narcotic drug were included. Variation in narcotics and sedative usage between sites in 2014 was determined using logistic regression analysis, with adjustment for gestational age, surgery, and mechanical ventilation. RESULTS: Of 20 744 neonates, 29% of neonates received a narcotic, a sedative, or both; 23% received a narcotic and 17% a sedative. Although no clinically significant changes in drug exposure were documented during the 5-year period, there were statistically significant differences in narcotic and sedative use between sites, ranging from 3% to 41% for narcotic and 2% to 48% for sedative use (aORs 0.2-5.7 and 0.1-15, respectively, P < .05). CONCLUSIONS: Exposure to narcotic or sedative agents is highly variable in preterm neonates across Canada despite concerns of adverse outcomes associated with these drugs. The tremendous variation in practice suggests that further research on their current usage, as well as identifying optimal practice procedures is warranted.

The role of antenatal corticosteroids in twin pregnancies complicated by preterm birth.

BACKGROUND: Data regarding the effects of antenatal corticosteroids in twin pregnancies are limited because of the insufficient number of women with twins enrolled in randomized controlled trials on antenatal corticosteroids. Furthermore, the interpretation of available data is limited by the fact that the interval from the administration of antenatal corticosteroids to delivery is greater than 7 days in a large proportion of twins, a factor that has been shown to affect the efficacy of antenatal corticosteroids and has not been controlled for in previous studies. OBJECTIVE: The objective of the study was to compare neonatal mortality and morbidity in preterm twins receiving a complete course of antenatal corticosteroids 1-7 days before birth to those who did not receive antenatal corticosteroids and to compare these outcome effects with those observed in singletons. STUDY DESIGN: We performed a retrospective cohort study using data collected on singleton and twin neonates born between 24(0/7) and 33(6/7) weeks' gestational age and were admitted to tertiary neonatal units in Canada between 2010 and 2014. A comparison of neonatal outcomes between twin neonates who received a complete course of antenatal corticosteroids 1-7 days before birth (n = 1758) and those who did not receive antenatal corticosteroids (n = 758) and between singleton neonates who received a complete course of antenatal corticosteroids 1-7 days before birth (n = 4638) and those did not receive antenatal corticosteroids (n = 2312) was conducted after adjusting for gestational age, sex, hypertension, outborn status, small for gestational age, parity, and cesarean birth. Adjusted odds ratios and 95% confidence intervals for various neonatal outcomes were calculated. RESULTS: Administration of a complete course of antenatal corticosteroids within 1-7 days before birth in both twins and singletons was associated with similar reduced odds of neonatal death (for twins adjusted odds ratio 0.42 [95% confidence interval, 0.24-0.76] and for singletons adjusted odds ratios, 0.38 [95% confidence interval, 0.28-0.50]; P = .7 for comparison of twins vs singletons), mechanical ventilation (for twins adjusted odds ratio, 0.47 [95% confidence interval, 0.35-0.63] and for singletons adjusted odds ratio, 0.47 [95% confidence interval, 0.41-0.55]; P = .9), respiratory distress syndrome (for twins adjusted odds ratio, 0.53 [95% confidence interval, 0.40-0.69], and for singletons adjusted odds ratio, 0.54 [95% confidence interval, 0.47-0.62]; P = .9) and severe neurological injury (for twins adjusted odds ratio, 0.50 [95% confidence interval, 0.30-0.83] and for singletons adjusted odds ratio, 0.45 [95% confidence interval, 0.34-0.59]; P = .7). Administration of a complete course of antenatal corticosteroids was not associated with a reduced odds of bronchopulmonary dysplasia, severe retinopathy of prematurity, or necrotizing enterocolitis in both twins and singletons. CONCLUSION: Administration of a complete course of antenatal corticosteroids 1-7 days before birth in twin pregnancies is associated with a clinically significant decrease in neonatal mortality, short-term respiratory morbidity, and severe neurological injury that is similar in magnitude to that observed among singletons.

Risk Factors and Outcomes of Late-Onset Bacterial Sepsis in Preterm Neonates Born at < 32 Weeks' Gestation.

OBJECTIVE: This study aims to identify the incidence, risk factors, and outcomes of late-onset sepsis in preterm neonates in Canadian neonatal intensive care units (NICUs). STUDY DESIGN: This retrospective analysis included preterm infants born at < 32 weeks' gestation and admitted to 29 NICUs in the Canadian Neonatal Network during the years 2010 and 2011. Infants were classified into three groups: no infection, gram-positive infection, and gram-negative infection. Late-onset sepsis was defined as positive blood and/or spinal fluid cultures after 3 days of birth. Risk factors and the primary outcome of mortality or bronchopulmonary dysplasia (BPD) were compared between the groups. RESULTS: Out of the 7,509 neonates, 6,405 (85%) had no infection, 909 (12%) had gram-positive, and 195 (3%) had gram-negative infections. Lower gestation, higher Score for Neonatal Acute Physiology, version II scores, the presence of central catheters for > 4 days, parenteral nutrition for > 7 days, and prolonged duration of nothing by mouth were associated with late-onset sepsis. After controlling for confounders, the odds ratio (OR) of mortality/BPD were higher in infants who had gram-negative (OR 2.79, 95% confidence interval [CI] 1.96-3.97) and gram-positive (OR 1.44, 95% CI 1.21-1.71) sepsis as compared with no infection. CONCLUSIONS: Bacterial late-onset sepsis in very preterm neonates was associated with mortality and BPD. Neonates with gram-negative sepsis had the highest risk of adverse outcomes as compared with gram-positive sepsis or no sepsis.

Nil-per-os days and necrotizing enterocolitis in extremely preterm infants.

OBJECTIVE: This study aims to evaluate the association between nil-per-os (NPO) days and development of necrotizing enterocolitis (NEC) in extremely preterm neonates (<29 weeks gestational age). STUDY DESIGN: A case-control study of 234 extremely preterm neonates who developed stage II or III NEC and 467 matched control infants admitted to participating sites in the Canadian Neonatal Network between 2010 and 2011 was conducted. The number and percentage of NPO days before the development of NEC was compared with the equivalent period in control infants using logistic regression. RESULTS: Infants with NEC were NPO on average 5.6 days (28% of days before NEC) versus 3.7 days (19% of equivalent days; p < 0.01) among controls. NEC cases required more days of inotropic support, antibiotic use, and had higher rates of patent ductus arteriosus (PDA). After adjusting for inotrope use, PDA, antibiotics, and severity of illness, for each additional NPO day the adjusted odds for NEC increased by 1.08 (95% confidence interval: 1.04-1.12). CONCLUSION: Among extremely preterm neonates, those who developed NEC were NPO for a longer period of time than control infants who were NEC-free. We speculate that delayed initiation or interruption of feeding may be a potent risk factor for NEC.

Inotrope use among extremely preterm infants in Canadian neonatal intensive care units: variation and outcomes.

OBJECTIVE: To compare neonatal outcomes between infants who received inotropes and those who did not, and identify variation in inotrope use. STUDY DESIGN: Retrospective review of data from neonates < 29 weeks gestation collected by the Canadian Neonatal Network during 2003 to 2010. After controlling for confounders and maternal/infant characteristics, rates of mortality and major morbidity were compared between those who received inotropes on days 1 and 3 of admission and those who did not. Rate of inotrope use was compared between sites. RESULTS: Inotropes were administered to 772 (10%) of the 7,913 neonates. Infants who received inotropes had significantly higher illness severity, surfactant use, and need for mechanical ventilation. Inotrope use was also associated with significantly higher rates of mortality (adjusted odds ratio [AOR] = 2.05 [1.64, 2.57]), retinopathy of prematurity (AOR = 2.04 [1.54, 2.71]), intraventricular hemorrhage (AOR = 1.59 [1.29, 1.93]), bronchopulmonary dysplasia (AOR = 1.38 [1.11, 1.72]), and necrotizing enterocolitis (AOR = 2.06 [1.59, 2.67]). Rates of inotrope use varied significantly between participating sites (0-36%; AOR = 0 [0, 0.1]-7.7 [2.9, 21]). CONCLUSION: Risk of mortality and major morbidities were significantly higher in neonates who received inotropes. Inotrope use varied significantly among Canadian neonatal intensive care units.

Intermediate vs. High Oxygen Saturation Targets in Preterm Infants: A National Cohort Study.

INTRODUCTION: Optimal oxygen saturation targets remain unknown for extremely preterm infants. METHODS: Cohort analysis of eligible preterm infants born <29 weeks' gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88-93%) or high (90-95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. RESULTS: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). CONCLUSION: For neonates <29 weeks' gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.

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.

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.

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.

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.