Gestation Research Articles

67 A population-based cohort study of endocrine outcomes within the first 5 years of life in children born preterm

Abstract Background Preterm birth (<37 weeks’ gestational age [GA]) occurs in 8% of live births in Canada. While advancements in neonatal medicine have led to increased survival in preterm births, infants born preterm continue to sustain short- and long-term health sequelae. There is paucity of large population studies evaluating childhood health care outcomes, including endocrine-related outcomes, in recent birth cohorts. Objectives To evaluate the rates of endocrine conditions during the first 5 years of life in children born preterm and term. Design/Methods The study cohort included liveborn infants at 22-44 weeks’ GA in British Columbia, Canada between 2004-2014. Follow-up data to December 2019 included linked health services use information from four BC provincial databases (perinatal database, hospitalizations, outpatient services, and outpatient prescriptions). Rates of outcomes were compared by GA at birth (37-44 weeks reference category) using robust Poisson regression. Results There were 455,960 children included in this study with 42,820 (9.4%) born at <37 weeks GA. Results are summarized in Table 1 and Table 2. Compared to children born at 37-44 weeks’ gestations, infants born at 36 weeks’ gestation or younger have an increased rate of thyroid disorders between 0 months and 5 years (rate ratio [RR]: 1.45, 95% confidence interval [CI]: 0.78-2.43; RR: 1.83, 95% CI 1.51-2.20; RR: 1.41 95% CI 1.26-1.57 for 22-27 weeks, 28-33 weeks and 34-36 weeks GA, respectively). Similarly, infants born at 36 weeks’ gestation or younger have a higher rate of conditions in growth and development (RR: 3.05, 95% CI: 0.76-7.96; RR: 3.20, 95% CI 2.04-4.76; RR: 1.42 95% CI 1.02-1.94 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively) and bone health conditions (RR: 1.38, 95% CI: 1.27-1.49; RR: 1.04, 95% CI 1.00-1.08; RR: 1.05 95% CI 1.03-1.07 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively). There was no difference in rates of conditions related to glucose metabolism such as diabetes mellitus or hypoglycemia. Conclusion Children born preterm have increased rates of endocrine conditions by age 5. Disorders of thyroid, growth and development are increased in infants born preterm. Children born preterm have an increase rate of bone-related disorders, including those born late-preterm. These results provide useful prognostic information for follow-up care for preterm children and for healthcare resource planning. Furthermore, these results highlight areas of future research in endocrine health among preterm infants.

72 Hospital level of service, rural-urban hospital location, and neonatal resuscitation interventions at birth: A population-based study in Alberta, Canada from 2000-2020

Abstract Background Advanced neonatal resuscitation interventions (ANRIs: endotracheal intubation, chest compressions, and epinephrine) are rarely needed for infants born at ≥34 weeks gestational age (GA). However, healthcare providers (HCPs) in community hospitals can encounter the need for ANRIs, while having less experience and resources than HCPs in centers with neonatal intensive care units (NICUs). Understanding practice differences between hospitals of different levels of service (LofS) and rural/urban location can inform quality improvement to reduce health disparities. Objectives To examine how hospital level of service and rural/urban location relate to ANRI rates in Alberta, Canada, a universal public health system with standardized Neonatal Resuscitation Program (NRP) training. Design/Methods All live births ≥34 weeks GA in Alberta from 2000-2020 inclusive were examined using retrospective, population-level administrative data from the Alberta Perinatal Health Program (APHP). Hospitals (n=97) were contacted to determine annual LofS during the study period, with levels (0,1A/B/C,2,3) based on provincial obstetrical triage for availability of delivery support, cesarean-sections, obstetricians, paediatricians/neonatologists, and NICUs. Hospitals were further subcategorized by population and proximity to metropolitan centers.(Table 1) Rates of individual interventions or any ANRI were compared. Results There were 971,403 live births during the study period with a mean GA of 38.9 weeks; 1.6% were missing ANRI data, 955,835 births were included. Most occurred in hospitals with level 2 (57.4%) or level 3 (21.8%) NICUs; few occurred at sites with no delivery support (Level 0, 0.1%). ANRI rates were intubation (0.8%), chest compression (0.2%), and epinephrine (0.02%), any ANRI (0.96%, ~1/1000 live births). However, chest compression rates progressively decrease, and intubation rates progressively increase as LofS increases.(Table 1, Figure 1) When considering rural/urban location, there were outliers in chest compression rates in remote 0 (25.4/1000 live births) and metro-influenced 1A (30.2/1000 live births), intubation in remote 1C (33.3/1000 live births) and metro 0 (193.5/1000 live births) and epinephrine in metro 0 (64.5/1000 live births). Conclusion In this population-based cohort study of ≥34 weeks births, there were higher chest compressions rates and lower intubations rates at hospitals without NICUs despite standardized training. Reasons for this difference require further investigation; potential solutions such as targeted outreach education and introduction of laryngeal mask airways could be explored.

65 Neonatal ventilator-associated pneumonia: A tale of three cities in Canada West

Abstract Background Preterm infants are at increased risk for acquired infections related to invasive devices such as endotracheal tubes (ETT). Wide heterogeneity exists in diagnostic criteria and management of ventilator-associated pneumonias (VAP), which have not been validated in the neonatal population. Objectives To determine the demographic characteristics and prevalence of VAP according to three different existing criteria used in the neonatal intensive care unit (NICU). Design/Methods In this retrospective study, we included infants born at <33 weeks gestational age from 3 different NICUs in western Canada, who have been diagnosed with VAP during 2018 – 2022. Infants were diagnosed per three diagnostic criteria: (1) Diagnosed per physician diagnoses (mechanically ventilated infants with stability or improvement ≥48 hours and deterioration at the physician’s discretion); (2) VAP diagnostic consensus adopted by some Canadian NICUs (Canadian criteria) (including escalation in respiratory support such as increase in FiO2 by minimum 0.25, increase in MAP by minimum 4 or change in ventilation mode); and (3) Criteria of a paediatric ventilator-associated condition (PVAC) with a positive respiratory diagnostic test (PVAC criteria) (including escalation in respiratory support such as increase in FiO2 by minimum 0.1, increase in MAP by minimum 2 or change in ventilation mode). Results There were 185 neonates diagnosed to have VAP at physicians’ discretion during the study period, with incidences of 4.6%, 8.9%, and 5.7% in the three NICUs. They had a median GA of 25 weeks, a median birth weight of 748-849 grams, and a median onset of VAP ranging from 16-31 days. Among the VAP per physicians’ diagnoses, 18.2-55.0% of infants fulfilled the VAP criteria of Canadian consensus, and 10.9-12.5% of them fulfilled the PVAC criteria with a positive respiratory diagnostic test. The demographic distribution showed similar patterns across the three criteria. Staphylococcus aureus, Enterobacter cloacae complex, Klebsiella species, and oral flora were found to be the most common organisms yielded from ETT aspirate cultures. Conclusion We found that 4.6-8.9% of infants born at <33 weeks GA had VAP diagnosed during their NICU stay. Only around one-ninth of infants fulfilled the PVAC criteria with a positive respiratory diagnostic test. Therefore, there is an urgency to develop neonatal-specific and validated diagnostic criteria for VAP.

Semi-Automated Analysis of Dome-Shaped Macula in Preterm and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography.

Dome-shaped macula (DSM) is known to occur in highly myopic adults and, recently, preterm infants. This study uses investigational handheld swept-source optical coherence tomography (SS-OCT) to further characterize infantile DSM. In this prospective, observational study, preterm infants undergoing retinopathy of prematurity screening and full-term infants within 72 hours of birth were imaged. Two trained graders assessed macular features, including DSM, subretinal fluid, and macular edema. A semi-automated program measured foveal immaturity, dome height, and diameter. Two hundred seventeen imaging sessions from 50 full-term and 30 preterm infants were included (46% female, preterm birth weight 1038 ± 335 g, and gestational age 28.7 ± 3.1 weeks). DSM occurred in 40% preterm versus 14% full-term infants (P = 0.01). Mean postmenstrual age at first DSM diagnosis was 38.4 ± 0.0 weeks among preterm and 40.4 ± 1.1 weeks among full-term infants (P < 0.001). Dome height and diameter measured 55.67 ± 44.22 µm and 3583.15 ± 1090.35 µm for preterm versus 88.37 ± 44.73 µm and 3581.97 ± 355.07 µm for full-term infants (P = 0.24 and P = 0.96, respectively). All 27 images (11 preterm and 7 full-term infants) with 3-dimensional analysis had round dome configuration. No other associations were seen, including macular fluid (P = 0.17). Infants frequently exhibit DSM without an association with macular fluid. Preterm infants were more likely than full-term infants to have DSM. Unlike DSM in children and adults, infantile DSM configuration is mostly round rather than ridge-shaped.

Complications among assisted reproductive technique (ART) twin gestations versus spontaneously conceived twin gestations (SC): A retrospective outcome analysis among an Afro-Caribbean population at a university-based hospital in Jamaica

Aim: The aim of the study is to compare the frequency of maternal and neonatal complications among pregnant women with twin pregnancies conceived spontaneously versus conceived by assisted reproductive technique (ART). Methods: Univariate and bivariate analyses of maternal characteristics and neonatal outcomes were performed in this retrospective cohort study at a university-based hospital between 2006 and 2016 in Jamaica, a middle-income Caribbean country. Neonatal data were the primary outcomes: APGAR scores, gestational age, birth weight, admission to the neonatal intensive care unit (NICU), and the level of ventilatory support required. Maternal characteristics, comorbidities, and pregnancy complications were other outcomes studied. Results: There were 157 SC and 27 ART twin gestations. Women conceiving via ART were more likely to be advanced maternal age (p greater 0.001), have uterine fibroids (p greater 0.001), previous myomectomy (p=0.001), and incompetent cervix (p=0.003), delivery by cesarean section (p=0.007), and experience hemorrhage (p=0.017) than SC. There were no statistically significant differences in rates of preterm births, birth weight, APGAR scores, or NICU admissions. Assisted reproductive technique twins were more likely to require continuous positive airway pressure (CPAP) (p=0.025), with no differences observed between the two groups for neonatal respiratory distress. Conclusion: In our predominantly Afro-Caribbean population, ART mothers were observed to have more poor maternal outcomes than mothers who conceived spontaneously. Assisted reproductive technique and SC twins had similar neonatal outcomes; however, ART twins were more likely to require CPAP.

Seasonal variation in home blood pressure during pregnancy and frequency of hypertensive disorders of pregnancy: a multicenter prospective study of home blood pressure measurements in pregnant women using information technology.

This multicenter prospective study investigated seasonal variation in home blood pressure (HBP) during pregnancy and its association with the frequency of hypertensive disorders of pregnancy (HDP) and developed trimester-specific upper limits of HBP according to season. Low-risk women with singleton pregnancies were recruited at six university hospitals and three maternity clinics. HBP was measured by a sphygmomanometer twice daily and recorded online using a mobile application. HBP was evaluated according to season (winter, spring, summer, and autumn) and gestational age. Of 705 women recruited, 603 were finally included. Mean diastolic HBP values were lowest in summer and highest in winter throughout pregnancy (mean difference between summer and winter, 3.5-4.6 mmHg). Mean systolic HBP values were also lowest in summer and highest in winter except during the early period of the second trimester (mean difference between summer and the season with the highest value, 2.5-3.4 mmHg). HDP was diagnosed in 32 women (5.3%). The risk of HDP was significantly higher in women who delivered in spring and autumn but not in winter compared with summer. The rounded upper limit of HBP was 120/80 mmHg in the first trimester, 120/75 mmHg in the second trimester, and 125/80 mmHg in the third trimester for summer and 125/85 mmHg, 125/80 mmHg, and 130/85 mmHg, respectively, for other seasons. Systolic and diastolic HBP were lowest in summer throughout pregnancy. Seasonal variation should be considered when interpreting HBP and the risk of HDP during pregnancy.

Mode of delivery in chorioamnionitis: impact on neonatal and maternal outcomes

BackgroundThe impact of mode of delivery in chorioamnionitis on neonatal outcomes is unclear. This retrospective cohort study compares the rate of early onset neonatal sepsis between vaginal delivery and cesarean section.MethodsSingleton pregnancies at greater than 24 + 0 weeks gestation with live birth and clinically-diagnosed chorioamnionitis from January 1, 2019 to December 31, 2021 were included. Cases with multiple gestations, terminations or histological chorioamnionitis alone were excluded. Rates of early onset neonatal sepsis, select secondary neonatal outcomes and a composite outcome of maternal infectious morbidity were compared using propensity score weighting. Subgroup analysis was done by indication for cesarean section.ResultsAfter chart review, 378 cases were included with 197 delivering vaginally and 181 delivering via cesarean section. The groups differed on age, parity, hypertension, renal disease, gestational age, corticosteroid use, magnesium sulfate use, presence of meconium and percentage meeting Gibbs criteria before propensity score weighting. Rate of early onset neonatal sepsis was greater in the cesarean section group (13.8% versus 3.1%, adjusted risk difference 8.3% [3.5–13.1], p < 0.001). Secondary neonatal outcomes were similar between groups. When compared by indication, the rate of early onset neonatal sepsis was greater in the cesarean section for abnormal fetal surveillance group compared to vaginal delivery but not in the cesarean section for other reasons group. Adjusted rates of secondary neonatal outcomes did not differ between groups. The rate of maternal infectious morbidity was greater with cesarean section. (13.8% versus 1.5% [adjusted risk difference 13.0% [7.1–18.9], p < 0.0001). No other difference in maternal secondary outcomes was identified.ConclusionsThe rate of early onset neonatal sepsis was highest in the cesarean section group, particularly in those with abnormal fetal surveillance. Fetuses affected by or vulnerable to sepsis likely have a greater need for cesarean section.

Outcomes of COVID-19 in Pregnant Women: A Retrospective Analysis of 300 Cases in Jordan

Background: The impact of COVID-19 on pregnancy remains a critical area of research, with growing evidence suggesting that maternal infection, particularly in the third trimester, may lead to significant complications Aims: The primary aim was to investigate the maternal and neonatal outcome of pregnant Jordanian women with COVID-19. The secondary aim included exploring demographics, obstetrics characteristics, and comorbidities among these women. Methods: A retrospective comprehensive review of the records of 300 cases of pregnant women with COVID-19, who were treated between November 2020 and April 2021 at Queen Alia Military Hospital (a main referral center for patients with COVID-19) in Jordan. All cases were confirmed by the rapid antigen test (RAT) + long polymerase chain reaction (PCR) test used to detect SARS-CoV-2 by amplifying viral RNA from patient samples. Women infected with COVID-19 were categorized into four groups according to the RCOG guidelines for COVID-19 infection in pregnancy: asymptomatic, mild, moderate, and severe cases. All cases were managed following the Royal College of Obstetricians and Gynecologists protocol for COVID-19 in pregnancy. Data extracted from patient’s records included demographic information, COVID-19 clinical manifestations, obstetric history, diagnostic findings, treatment plans, comorbidities, gestational age at diagnosis, treatment protocols, and maternal and neonatal outcomes. Results: The mean age was 29.7 years; 98.3% were nonsmokers; 8% had previous miscarriages, and 67.3% had the infection in the third trimester. Iron deficiency anemia affected 30.3%, while 18.3% had comorbidities, mainly hypothyroidism. Most women were asymptomatic 61.7%, but 33% had respiratory symptoms, 4.7% needed intensive care unit (ICU) admission, and 2.7% resulted in maternal deaths. First-trimester and second-trimester miscarriages were recorded in 2.67% and 3.67% of cases, respectively, while preterm labor occurred in 3.0% of pregnancies. Additionally, age and hospitalization duration had a positive correlation with the neonatal outcomes (r = 0.349, p &lt; 0.01), (r = 0.376, p &lt; 0.01), respectively. Furthermore, COVID-19 presentation and treatment options demonstrated a strong positive correlation (p-value &lt;0.01). On the other hand, maternal death had a strong negative correlation with poor neonatal outcomes (r = −0.776, p &lt; 0.01). Conclusion: The study showed that COVID-19 in pregnant women, particularly in the third trimester, is associated with significant neonatal complications, with age, hospitalization duration, and COVID-19 severity strongly impacting outcomes.

86 Sociodemographic and family characteristics of children with and without neurodevelopmental impairment in a Canadian cohort of extreme preterm children

Abstract Background Despite improved survival of extreme preterm infants (&amp;lt;29 weeks’ gestation), neurodevelopmental impairment (NDI) remains high. Certain sociodemographic characteristics (SDC) and limited family resources are known to adversely affect children health and development, particularly those born preterm. There is a dearth of recent data from large cohorts examining the impact of social determinants of health on the neurodevelopment of preterm children. Objectives (1) to describe SDC and family composition in a population-based cohort of extreme preterm children using the Canadian Neonatal Follow Up Network (CNFUN) database; (2) to develop a logistic regression model examining the association of significant NDI (sNDI any of: CP ≥ GMFCS stage 3, Bayley III &amp;lt; 70 in any domain, deafness requiring aids, or bilateral blindness) with SDC using a unique family descriptor. Design/Methods A retrospective review of a national cohort of extreme preterm infants (230 -286 weeks) born between April 2009 and December 2018. We included children who had neurodevelopmental assessment at 18-24 month corrected age at a CNFUN participating Centre. We compared SDC of infants and caregivers and family descriptors (moderating variables) between children with no NDI and those with any NDI and sNDI. Multivariate logistic regression models were developed in two steps to evaluate the effect of SDC (Model 1) and family composition (Model 2) on the primary outcome of sNDI. GEE was used to account for clustering by multiples and within site. Results Out of 10833 eligible infants, 6219 (57%) were included. Of those, 3412 (55%) had no NDI and 2807 (45%) had any NDI. sNDI accounted for 17% of the cohort and 37% of those with NDI. Comparison of the SDC and family descriptors between the three groups are shown in Table 1. On multivariate analysis using SDC, infant’s gestational age and male sex, and primary caregiver’s ethnicity and level of education were independently associated with sNDI. Immigration and employment status were associated with sNDI when family descriptors were added to the first model (Table 2). Conclusion In this national cohort, half of extreme preterm children developed NDI and 1 in 7 had sNDI. There were differences in sociodemographic and family characteristics between those with and without sNDI. The degree of prematurity and caregiver’s education, employment and immigration status were independently associated with sNDI in those children. Future research is needed to determine what interventions and support to benefit those children at risk.

73 Predictors of neurodevelopmental impairment in extreme preterm infants with unremarkable cranial ultrasound: A Canadian population-based cohort

Abstract Background Extreme preterm infants are at high-risk of brain injury and neurodevelopmental impairment (NDI). Previous studies reported significant NDI (sNDI) in preterm infants with no abnormalities on routine cranial ultrasound screening (CUS), traditionally perceived to have favorable outcomes. Recent data from population-based outlining clinical predictors of sNDI in those infants are lacking. Objectives (1) to describe the incidence, perinatal and neonatal characteristics of NDI and sNDI in a large population-based cohort of extreme preterm infants with unremarkable CUS; (2) to develop a prediction model of sNDI (any of: CP ≥ GMFCS stage 3, Bayley III &amp;lt; 70 in any domain, deafness requiring aids, or bilateral blindness) in those infants. Design/Methods A retrospective review of a national cohort of preterm infants born at &amp;lt;29 weeks’ gestation between April 2009 and December 2018. We included surviving infants with unremarkable routine CUS (no hemorrhage, periventricular leukomalacia or ventricular dilatation) who had neurodevelopmental assessment at 18-24 month corrected age at one of participating centres in the Canadian Neonatal Follow Up Network. We compared the baseline characteristics between infants with no NDI and those with any NDI and sNDI. The population sample was then randomly split into training and testing datasets in 70:30 ratio for prediction model’s development and validation, respectively. Multivariate logistic regression with GEE accounting for clustering within site was used, adjusted for variables with p-value&amp;lt;0.1 using backward selection procedure. The AUC and the diagnostic properties of the model developed using training dataset was then validated in the testing dataset. Results Out of 7463 eligible infants, 4327 (58%) were included. Of those, 2501 (59%) had no NDI and 1736 (41%) had NDI. sNDI accounted for 14% of the cohort and one third of those with NDI. Perinatal and neonatal characteristics of the three groups are shown in Table 1. On internal validation, maternal hypertension, maternal level of education, gestational age, male sex, ROP≥ stage 3 and systemic steroids were predictive of sNDI (Table 2). The prediction model had Sensitivity 0.91, NPV 0.90, and AUC 0.69 (95% CI 0.64-0.73). Conclusion In this national cohort, 2 out of 5 extreme preterm infants with unremarkable CUS had NDI and 1 in 7 had sNDI. The developed prediction model had high sensitivity and NPV, but poor discrimination. The findings of this study can help clinicians to identify at-risk infants who may benefit from early targeted interventions.

Changes in the prevalence of intellectual disability among 10-year-old children in Sweden during 2011 through 2021: a total population study

BackgroundRecent studies have suggested an increasing prevalence of intellectual disability diagnoses in some countries. Our aim was to describe the trend in the prevalence of intellectual disability diagnoses in Sweden and explore whether associated sociodemographic and perinatal factors can explain changes in the prevalence.MethodsWe used a register-based nationwide cohort of residents in Sweden born between 2001 and 2011. We calculated the prevalence of intellectual disability diagnoses by age 10 for each birth cohort and the prevalence ratios in relation to the baseline year 2011, overall and by severity of intellectual disability, and comorbidity of autism and attention-deficit/hyperactivity disorder. The prevalence ratios were stratified and adjusted for associated sociodemographic and perinatal factors.ResultsAmong 1,096,800 individuals, 8,577 were diagnosed with intellectual disability by age 10. Among these, 3,949 (46%) and 2,768 (32%) were also diagnosed with autism and attention-deficit/hyperactivity disorder, respectively, and 4% were diagnosed with profound, 8% severe, 20% moderate, 52% mild, and 16% other/unspecific intellectual disability. The recorded age-10 prevalence of intellectual disability diagnoses increased from 0.64% (95% confidence interval 0.59–0.69%) in 2011 to 1.00% (0.94–1.06%) in 2021, corresponding to an annual prevalence ratio of 1.04 (1.04–1.05). The increase was, however, restricted to mild, moderate, and other/unspecific intellectual disability diagnoses, while the trends for profound and severe intellectual disability diagnoses were stable. The increasing trend was perhaps less pronounced among females and children with diagnosed attention-deficit/hyperactivity disorder, but independent of the co-occurrence of autism. The prevalence ratios did not change with stratification or adjustment for other associated demographic and perinatal factors.ConclusionThe recorded prevalence of diagnosed mild and moderate intellectual disability among 10-year-olds in Sweden has increased over the recent decade. This increase could not be explained by changes in associated sociodemographic or perinatal factors, including birth weight, gestational age, and parental age, migration status, and education at the child’s birth. The increase instead may be due to changes in diagnostic practices in Sweden over time.

77 Antenatal MgS04 in very preterm babies is not related to improved 36 month neurodevelopmental outcomes once accounting for neonatal interventions

Abstract Background Magnesium Sulphate (MgSO4) has become a standard practice for fetal neuroprotection prior to delivery of very-preterm babies due to an association with MgSO4 and reduction of cerebral palsy at 2 years of age in randomized clinical trials. Objectives In a prospective cohort of very preterm babies, we aimed to define the association between antenatal MgSO4 administration and neurodevelopmental outcome. Design/Methods We included a prospective cohort of 265 infants born ≤ 32 weeks’ gestation recruited at three tertiary neonatal intensive care units (NICU). Infants underwent two brain MRIs, one in the initial weeks after birth and one at term-equivalent age. Neurodevelopmental follow-up assessments were completed using the Bayley-3 at 3 years. Univariate analysis was undertaken to determine whether MgSO4 was associated with outcome. Multiple maternal and neonatal factors were analyzed according to their relationship with outcome. Gestational age was accounted for in all models. Maternal factors associated with MgSO4 administration were hypertension, multiple births and antenatal corticosteroid administration. Neonatal factors were sex, neonatal resuscitation, major surgery, and moderate-severe white matter injury (volume &amp;gt;40mm3). Multivariable linear regression models of maternal and neonatal risk factors were used to account for potential confounders based on those factors that were significantly (p&amp;lt;0.05) associated in univariate analysis. Results On univariate analysis, MgSO4 administration was inversely associated with 36-month motor scores (p&amp;lt;0.05). On the multivariable analysis, no maternal confounders had an impact on the relationship between MgSO4 and outcome (Table 2). MgS04 was no longer statistically related to any Bayley outcomes after adjusting for confounders at 36 months (Table 2). Neonatal surgery was related to poorer 36-month motor and cognitive outcomes. Conclusion Antenatal MgSO4 exposure was not associated with improved measures on the Bayley scales at 3 years after adjusting for potential confounders. However, neonatal interventions remained significant risk factors for poorer neurodevelopmental outcome.

69 Urinary tract infections in preterm infants: Review in two Canadian tertiary centers

Abstract Background Urinary tract infections (UTI) in premature infants are commonly seen in the neonatal intensive care unit (NICU). The reported prevalence of UTI in this population ranges from 1.9-12.2% due to the lack of standardized criteria for UTI among infants less than two months of age. Enterococcus and Enterobacteriaceae are well known to cause UTI and their resistance pattern has been reported to be rising in the neonatal nosocomial infections worldwide. Objectives To describe the epidemiology, microbiology, and antimicrobial treatment for UTI in premature infants based on different diagnostic criteria. Design/Methods This retrospective study (2019-2022) included infants born at &amp;lt;33 weeks of gestational age (GA) with positive urine cultures and ≥5 days of antimicrobials treatment. We collected data from two tertiary level NICUs in Canada, including demographics, microbial susceptibility patterns, urinalysis and imaging results, and antibiotic treatment. Results We identified 43 infants managed as UTI based on physicians’ discretions. The median GA at birth was 26-27 weeks, while the median onset of first UTI ranged 39-80 days, with male predominance [Table 2]. Mixed growth of organisms constituted 21-42% of cases of UTI [Table 1]. Among UTI cases with only single growth organism, we found 53.5% and 18.6% cases fulfilled UTI diagnostic criteria based on the concentration of colony forming units (CFU) of &amp;gt;104/mL or &amp;gt;107/L and &amp;gt;105/mL or &amp;gt;108/L, respectively [Table 1]. Of these cases, 67.4% of infants had urinalysis sent with the culture, and the higher the concentration of CFU, the more likely the samples showed positive nitrites on urinalysis, with 100% correlation among those with CFU &amp;gt;105/mL or &amp;gt;108/L. [Table 1] The most common pathogens were Enterococcus species, E.Coli, Klebsiella species, Citrobacter species and Enterobacter cloacae complex [Table 2]. Among gram negative bacilli (E. Coli and Klebsiella species), greater than 42-80% were resistant to 3rd generation cephalosporins (3GC). We did not identify any vancomycin-resistant Enterococcus strains. Median duration of antimicrobial treatment ranged from 8-13 days, depending on the diagnostic criteria applied. At least 10% of infants with UTI showed abnormalities on kidney ultrasound [Table 2]. Conclusion There exists a large variation in UTI prevalence according to different diagnostic criteria. Abnormal urinalysis with presence of nitrites were frequently associated with UTI of high CFU count. High resistance to 3GC among gram negative bacilli was concerning and carried an impact on the appropriate empirical treatment choice.

Systemic Inflammatory Indices as Predictors of Lung Maturation in Preterm Infants Born Before 32 Weeks of Gestation

AbstractIncreased inflammation in premature infants in the prenatal period reduces respiratory distress syndrome (RDS). Several systemic inflammatory indices have been used to evaluate inflammatory responses in different pathologies. Our study aimed to determine the systemic inflammatory indices as predictors of lung maturation in preterm infants born before 32 weeks of gestation. In this study, preterm infants born before 32 weeks of gestation were enrolled and categorized based on the diagnosis of RDS. At birth, infants were assessed for various systemic inflammatory indices, including the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The study included 365 infants, of whom 211 had RDS. The median gestational ages (GA) were 27 (range: 25–29) and 30 (range: 29–31) weeks, and the median birth weights were 850 (range: 660–1,360) and 1,375 (1,090–1,600) g in the RDS and control groups, respectively. Infants in the RDS group had significantly lower MLR, NLR, PIV, SII, and SIRI values (p = 0.001) compared to the control group. The cutoff values for predicting RDS in the whole group were 239 for SII, 0.44 for SIRI, and 78 for PIV. For the group of preterm infants born at ≤28 weeks of gestation, values of 171, 0.5, and 87 for SII, SIRI and PIV, respectively, provided the best ability to predict RDS. For the whole cohort, SII level ≥239 was associated with a reduced risk of RDS, as revealed by multivariate analyses (p = 0.001). To account for GA, we performed regression analyses for infants born at ≤28 weeks. SII ≥171 (odds ratio [OR]: 0.12; 95% confidence interval [CI]: 0.05–0.3), PIV ≥87 (OR: 0.08; 95% CI: 0.03–0.21), and SIRI ≥0.5 (OR: 0.08; 95% CI: 0.03–0.2) were associated with a reduced risk of RDS. Inflammation in the perinatal period may reduce the frequency of RDS in premature infants.

Impact of gestational age on the management of acute appendicitis during pregnancy: A nationwide observational study.

To compare conservative management and appendectomy for acute appendicitis during pregnancy by trimester. This retrospective cohort study used data from a national inpatient database from July 2010 to March 2022. Pregnant women diagnosed with acute appendicitis were included. Multivariable analysis using generalized estimating equations was performed to compare outcomes between conservative management and appendectomy across trimesters. The main outcomes were preterm labor, preterm delivery, or abortion; antepartum hemorrhage; duration of hospitalization; and duration of antibiotic use. A total of 3158 individuals from 632 acute-care hospitals were eligible. The proportion of conservative management versus appendectomy by trimester were 507 (49.1%) versus 525 (50.9%) in the first, 690 (44.6%) versus 856 (55.4%) in the second, and 337 (58.1%) versus 243 (41.9%) in the third. In the second trimester, appendectomy was associated with a higher rate of preterm delivery, preterm labor, or abortion (odds ratio [OR], 2.91 [95% confidence interval (CI), 1.62-5.25]). Antepartum hemorrhage occurred more frequently for appendectomy in the first (OR, 2.12 [95% CI, 1.31-3.43]) and third (OR, 2.43 [95% CI, 1.79-3.31]) trimesters. Appendectomy was associated with a longer duration of hospitalization in the second (2.15 days; 95% CI, 1.14-3.17 days) and third (3.97 days; 95% CI, 2.22-5.71 days) trimesters. Antibiotic use duration was shorter for appendectomy in the first (-1.20 days [95% CI -1.51 to -0.90 days]) and second (-0.61 days [95% CI -0.90 to -0.32 days]) trimesters. Clinical outcomes of acute appendicitis during pregnancy vary by trimester. Considering the appendectomy risks, conservative management may be viable depending on the clinical context and trimester.

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1-2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented. The main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN. All of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents. Fifty-five children (81% of answers) with a median age of 36 months (11-68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age. This study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

64 Respiratory outcomes by five years of age among children born preterm: A population-based study using health services data

Abstract Background While neonatal care advancements have led to increased survival of preterm infants, many experience ongoing respiratory complications. Objectives Healthcare administrative data offers a comprehensive measure of neonatal outcomes. Our study used population-based data to describe rates of healthcare contacts for respiratory disease among children born preterm. Design/Methods A retrospective cohort of infants born in British Columbia between 2004-2014 was identified using a provincial birth registry. By linking to population-based healthcare data, we captured population demographics, birth data, and healthcare visits for respiratory causes [outpatient visits, hospitalizations, and intensive care (ICU) admissions] up to 5 years of age. The rate of healthcare visits due to asthma, bronchiolitis, and pneumonia were compared between preterm (22-36 weeks) and term/post-date infants (37-44 weeks GA) using Poisson regression. Results Children born at term (n=413,140) were compared to children born at 34-36 week GA (n=33,227), 28-33 week GA (n=8362), and 22-27 week GA (n=1231). Compared to term infants, rates of hospitalizations and ICU admission for all respiratory causes were higher among children born preterm. Children born 22-27 weeks GA had the highest rates of hospitalization for asthma [rate ratio (RR) 9.4, 95% CI 7.9-11.1], bronchiolitis (RR 10.5, 95% CI 9.3-11.8) and pneumonia (RR 15.9, 95% CI 14.3-17.7). Rates of ICU admission for asthma (RR 27.1, 95% CI 17.2-40.4) and pneumonia (RR 58.1, 95% CI 46.6-71.7) were highest among 22-27 week GA infants. Increased rates persist among children born 34-36 weeks GA, with higher rates of hospitalization for asthma (RR 1.8, 95% CI 1.6-1.9), bronchiolitis (RR 2.1, 95% CI 2.0-2.2), and pneumonia (RR 1.8, 95% CI 1.7-2.0) compared to term infants. Conclusion Preterm infants experience significantly higher rates of outpatient visits, hospitalizations, and ICU admissions for respiratory disease compared to term infants. Healthcare utilization, including ICU admissions, increased with decreasing gestational age. Of note, increased rates of respiratory disease were also found among infants born 34-36 weeks GA. Our study is the first to use population based data to describe rates of healthcare contacts for respiratory disease among preterm infants, providing insight to long-term respiratory disease burden.

Associations of fetal and infant growth patterns with behavior and cognitive outcomes in early adolescence

AbstractBackgroundFetal life and infancy might be critical periods for brain development leading to increased risks of neurocognitive disorders and psychopathology later in life. We examined the associations of fetal and infant weight growth patterns and birth characteristics with behavior and cognitive outcomes at the age of 13 years.MethodsPopulation‐based prospective cohort study from fetal life until adolescence. Pregnant women with a delivery date between April 2002 and January 2006 were eligible. Follow‐up measurements were available for 4716 children. Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD greater than 0.67 between time points. Total, internalizing and externalizing problems and attention‐deficit hyperactivity disorder (ADHD) symptoms were measured using Child Behavior Checklist (CBCL/6–18), autistic traits by the Social Responsiveness Scale (SRS) and intelligence quotient (IQ) by the Wechsler Intelligence Scale for Children‐Fifth Edition (WISC‐V).ResultsOne week longer gestational age at birth was associated with a −0.03 SDS (95% Confidence Interval (CI): −0.04, −0.01) lower total behavior problems score, a −0.02 SDS (95% CI: −0.04, −0.01) lower ADHD symptoms score. Also an increase in birth weight of 500 g was associated with a lower odds of having high externalizing problems (OR 0.92 (95% CI: 0.86, 0.98) and of having a low IQ score (OR 0.79 (95% CI: 0.71, 0.88). Compared to children with normal fetal and infant growth, those with accelerated fetal and infant growth had a 0.27 SDS higher IQ (95% Confidence Interval 0.11, 0.44).ConclusionsBoth fetal and infant weight development are associated with behavioral and cognitive outcomes in early adolescence. Follow‐up studies are needed to assess whether these associations link to later life mental health outcomes.

76 White matter microstructure and motor function at 8 years of age in children born preterm

Abstract Background White matter injury (WMI) in preterm neonates is characterized by focal areas of white matter necrosis (punctate WMI) and more diffuse impairments in white matter (dysmaturation). White matter dysmaturation is reflected as lower fractional anisotropy (FA) measured by diffusion tensor imaging (DTI). Reduced white matter FA in neonatal DTI has been associated with adverse motor function at early ages in children born preterm. Yet, how white matter FA at school-age relates to motor function at this later age is largely unknown. Objectives To assess the relationship between white matter FA and motor function at 8 years of age in children born very preterm. Design/Methods 110 children born very preterm (mean birth gestational age [GA] 28.19 weeks, range 24-32 weeks) completed MRI scans in the neonatal period and again at 8 years of age (mean age 8.35 years, SD = 0.38). Neonatal WMI was quantified on the neonatal T1-weighted images with significant WMI defined as WMI volume &amp;gt; 40 mm3. FA at 8 years was assessed using tract-based spatial statistics (TBSS). Movement Assessment Battery for Children, 2nd Ed (M-ABC-2) was used to assess fine and gross motor function at 8 years of age. Motor outcomes from the M-ABC total score were grouped as: Significant Movement Difficulty &amp;lt; 56 (below 5th percentile, n = 31), At-risk of Movement Difficulty 57-67 (5th-15th percentile, n = 23), and Unlikely to Have Movement Difficulty &amp;gt; 68 (above 15th percentile, n = 56). FA in the white matter skeleton was compared between motor outcome groups using threshold-free cluster enhancement (TFCE), adjusting for birth GA and significant WMI, and correcting for multiple comparisons across skeleton voxels using permutation testing with 5000 permutations. Results Table 1 outlines descriptive differences in the three motor outcome groups. Children born preterm who are Unlikely to Have Movement Difficulty at 8 years had significantly higher FA (p &amp;lt; .05) compared to those At-risk of or with Significant Movement Difficulty, especially in the corpus collosum (Figure 1), controlling for birth GA and significant neonatal WMI. Those with Significant Movement Difficulty had the lowest FA. Conclusion In children born preterm at age 8 years, white matter FA is associated with motor performance, independent of significant neonatal WMI. Our findings indicate that white matter dysmaturation persists and has functional significance through school-age.

A Multiscale Mathematical Model for the Fetal Blood Circulation of the Second Half of Pregnancy.

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging. Several influences, including wave reflections, fetal growth, vessel stiffness, and resistance distal to the vessel, contribute to these indices. Understanding these data is essential for making informed clinical decisions. Mathematical models can be used to investigate the relation between velocity profiles and physiological properties. This study presents a mathematical model designed to simulate velocity wave propagation throughout the fetal cardiovascular system, facilitating the assessment of factors influencing velocity-based indices. The model combines a one-fiber model of the heart with a 1D wave propagation model describing the larger vessels of the circulatory system and a lumped parameter model for the microcirculation. Fetal growth from 20 to 40 weeks of gestational age is incorporated by adjusting cardiac and circulatory parameter settings according to scaling laws. The model's results, including cardiac function, cardiac output distribution, and volume distribution, show a good agreement with literature studies for a growing healthy fetus from 20 to 40 weeks. In addition, Doppler indices are simulated in various vessels and agree with literature as well. In conclusion, this study introduces a novel closed-loop 0D-1D mathematical model that has been verified against literature studies. This model offers a valuable platform for analyzing factors influencing velocity-based indices in the fetal cardiovascular system.