Gastroschisis and septo-optic-pituitary dysplasia: Is there an association?

AIM: There are several case reports describing patients with both optic nerve hypoplasia/septo-optic-pituitary dysplasia (ONH/SOD) and gastroschisis (GS). Our aim was to investigate whether ONH/SOD is associated with GS. METHODS: A retrospective population-based study was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada to investigate if any patient with ONH/SOD also had GS. In addition, Winnipeg's Surgical Database of Outcomes and Management (WiSDOM), a hospital-based paediatric surgical database, was searched to ascertain if any of the patients with GS also have ONH/SOD. RESULTS: Cases were 124 patients with ONH/SOD diagnosed during 1990-2019. None had GS. The surgical database had 188 patients from Manitoba with GS during 1991-2019. None had ONH/SOD. CONCLUSION: There does not appear to be an association between ONH/SOD and GS in our cohorts of patients with these two disorders.

Visual Acuity Outcomes in Children With Optic Nerve Hypoplasia and Septo-Optic-Pituitary Dysplasia.

BACKGROUND: To investigate best-corrected visual acuity (BCVA) outcomes in patients with optic nerve hypoplasia (ONH)/septo-optic-pituitary dysplasia (SOD). Our primary hypothesis was that BCVA in patients with ONH/SOD does not change significantly over time. METHODS: A chart review was undertaken in patients with a confirmed diagnosis of ONH/SOD. Demographic and clinical ophthalmologic data were extracted. Quantitative BCVA data were investigated across clinic visits after converting acuities to the logarithm of the minimum angle of resolution (logMAR). RESULTS: There were 102 patients (56 males). Median age at the end of the study was 12.7 years. Median duration of follow-up was 4.5 years. BCVA significantly worsened slightly in the most affected eyes (0.056 average increase in logMAR/year, 95% confidence interval [CI]: 0.037 to 0.075) and significantly improved mildly in the lesser or equally affected eyes (0.014 average decrease in logMAR/year, 95% CI: 0.009 to 0.019) (P < 0.0001). CONCLUSIONS: Although the overall BCVA data showed a statistically significant change with time, the actual changes were small and are of doubtful meaningful clinical significance (less than one line change on a Snellen chart). Our data suggest that ONH/SOD are nonprogressive neurodevelopmental disorders. The mild worsening of BCVA in the most affected eyes may be caused by amblyopia, whereas the small improvement in the lesser or equally affected eyes may be caused by developmental maturation. In addition, the changes in BCVA may also be due to increasing reliability of visual assessments with increasing age.

Selected Ophthalmological Features in Children with Septo-Optic Dysplasia and Optic Nerve Hypoplasia.

Septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH) cause congenital visual impairment. Their aetiology is mostly unknown. Our aim was to investigate the prevalence of selected ophthalmological features in patients with these disorders. A chart review was performed on patients with SOD/ONH. Ophthalmological data were extracted. There were 102 patients (56 males). The median age at the end of the study was 12.7 years. Best-corrected visual acuity ranged from normal to no light perception. Bilateral ONH was more common than unilateral ONH. Strabismus (85%) and to a lesser extent nystagmus (52%) were both very common in our cohort. Patients with esotropia had worse visual acuity than those who had exotropia. The presence of nystagmus was more likely in cases with bilateral ONH. Therefore, patients with SOD/ONH may have normal visual acuity. Many have strabismus, which may cause amblyopia thereby further decreasing visual acuity. Nystagmus occurs commonly and its presence typically indicates bilateral ONH.

School Readiness Among Children Born Preterm in Manitoba, Canada.

Importance: Children born preterm may experience learning challenges at school. However, there is a paucity of data on the school readiness of these children as they prepare to begin grade 1. Objective: To examine the association between prematurity and school readiness in a population-based cohort of children. Design, Setting, and Participants: This cohort study was conducted in the province of Manitoba, Canada, and involved 2 cohorts of children in kindergarten at the time of data collection. The population-based cohort included children born between January 1, 2000, and December 31, 2011, whose school readiness was assessed in kindergarten using the Early Development Instrument (EDI) data. The sibling cohort comprised children born preterm and their closest-in-age siblings born full term. Data were analyzed between March 12 and September 28, 2021. Exposures: Preterm birth, defined as gestational age (GA) less than 37 weeks. Main Outcomes and Measures: The primary outcome was vulnerability in the EDI, defined as a score below the tenth percentile of the Canadian population norms for any 1 or more of the 5 EDI domains (physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge). Logistic regression models were used to identify the factors associated with vulnerability in the EDI. P values were adjusted for multiplicity using the Simes false discovery method. Results: Of 86 829 eligible children, 63 277 were included, of whom 4352 were preterm (mean [SD] GA, 34 [2] weeks; 2315 boys [53%]) and 58 925 were full term (mean [SD] GA, 39 (1) weeks; 29 885 boys [51%]). Overall, 35% of children (1536 of 4352) born preterm were vulnerable in the EDI compared with 28% of children (16 449 of 58 925) born full term (adjusted odds ratio [AOR], 1.32; 95% CI, 1.23-1.41; P < .001]). Compared with children born full term, those born preterm had a higher percentage of vulnerability in each of the 5 EDI domains. In the population-based cohort, prematurity (34-36 weeks' GA: AOR, 1.23 [95% CI, 1.14-1.33]; <34 weeks' GA: AOR, 1.72 [95% CI, 1.48-1.99]), male sex (AOR, 2.24; 95% CI, 2.16-2.33), small for gestational age (AOR, 1.31; 95% CI, 1.23-1.40), and various maternal medical and sociodemographic factors were associated with EDI vulnerability. In the sibling cohort, EDI outcomes were similar for both children born preterm and their siblings born full term except for the communication skills and general knowledge domain (AOR, 1.39; 95% CI, 1.07-1.80) and Multiple Challenge Index (AOR, 1.43; 95% CI, 1.06-1.92), whereas male sex (AOR, 2.19; 95% CI, 1.62-2.96) and maternal age at delivery (AOR, 1.53; 95% CI, 1.38-1.70) were associated with EDI vulnerability. Conclusions and Relevance: Results of this study suggest that, in a population-based cohort, children born preterm had a lower school-readiness rate than children born full term, but this difference was not observed in the sibling cohort. Child and maternal factors were associated with lack of school readiness among this population-based cohort.

Revisiting the association between maternal and offspring preterm birth using a sibling design.

BACKGROUND: Previous studies have reported an intergenerational association between maternal and offspring preterm birth (PTB) but the nature of the association remains unclear. We assessed the association between maternal and offspring preterm birth using a quasi-experimental sibling design and distinguishing between preterm birth types. METHODS: We conducted a retrospective intergenerational cohort study of 39,573 women born singleton in Manitoba, Canada (1980-2002) who gave birth to 79,198 singleton infants (1995-2016). To account for familial confounding we defined a subcohort of 1033 sisters with discordant PTB status who subsequently gave birth and compared offspring PTB rates between 2499 differentially exposed cousins using log-binomial fixed-effects generalized estimating equation models. PTB was defined as a delivery < 37 gestation weeks, divided into spontaneous and provider-initiated. RESULTS: In the population cohort, mothers born preterm were more likely to give birth preterm [Adjusted Relative Risk (ARR): 1.39; 95% Confidence Interval (CI): 1.25, 1.54] and very preterm birth [ARR: 1.76; 95% CI: 1.29, 2.41]. However, in the siblings cohort, the intergenerational association was not apparent among births to sisters with discordant PTB status [ARR: 1.02; 95% CI: 0.77, 1.34 for preterm birth and ARR: 0.88; 95% CI: 0.38, 2.02 for very preterm birth]. Mothers born at term with a sister born preterm had a similarly elevated risk of delivering a preterm infant (10%) than their preterm sisters. Intergenerational patterns were observed for spontaneous PTB but not for provider-initiated PTB. CONCLUSIONS: Our findings suggest that it is not the fact of having been born preterm that puts women at higher risk of delivering preterm, but the fact of having been born to a mother who ever delivered preterm. Consideration of a female family history of PTB may better identify women at higher risk of preterm delivery than relying on maternal preterm birth status alone. Further research may benefit from distinguishing preterm birth types.

Examining Early Childhood Health Outcomes of Children Born Late Preterm in Urban Manitoba.

Objective The late preterm population [34-36 weeks gestational age (GA)] is known to incur increased morbidity in the infancy stage compared to the population born at term (39-41 weeks GA). This study aimed to examine the health of these children during their early childhood years, with specific attention to the role of socioeconomic status. Methods A retrospective cohort study was conducted using data from the Manitoba Centre for Health Policy, including all live-born children born at 34-36 and 39-41 weeks GA in urban Manitoba between 2000 and 2005 (n = 28,100). Multivariable logistic regression was used to examine the association of GA with early childhood morbidity after controlling for maternal, child and family level variables. Results The late preterm population was found to have significantly greater adjusted odds of lower respiratory tract infections in the preschool years (aOR = 1.59 [1.24, 2.04]) and asthma at school age (aOR = 1.33 [1.18, 1.47]) compared to the population born at term. The groups also differed in health care utilization at ages 4 (aOR = 1.19 [1.06,1.34]) and 7 years (aOR = 1.24 [1.09, 1.42]). Additional variables associated with poor outcomes suggest that social deprivation and GA simultaneously have a negative impact on early childhood development. Conclusions for Practice Adjustment for predictors of poor early childhood development, including socioeconomic status, were found to attenuate but not eliminate health differences between children born late preterm and children born at term. Poorer health outcomes that extend into childhood have implications for practice at the population level and suggest a need for further follow-up post discharge.

Maternal depression and anxiety disorders (MDAD) and child development: A Manitoba population-based study.

OBJECTIVE: To examine the association between maternal depression and anxiety disorders (MDAD) and child development assessed during the kindergarten year. METHODS: Administrative data from several health and social databases in Manitoba, Canada, were used to study 18,331 mother-child pairs. MDAD over the period from one year prior to the child's birth to the kindergarten year was defined using physician diagnoses and filled prescriptions. Child development was assessed during the kindergarten year using the Early Development Instrument (EDI) which measures vulnerability across five domains of development. Structural equation modeling was used to examine associations between timing, recurrence and severity of MDAD and child outcomes. Health at Birth (preterm, low birth weight, neonatal intensive care stay and long birth hospitalization), Family Context (teen mother, lone parent, socio-economic status (SES)), child age and child sex were covariates. RESULTS: MDAD had a modest negative association with child EDI scores across all models tested, particularly for social, emotional and physical development. Prenatal MDAD had a stronger negative association with outcomes than other time periods; however, recurrent MDAD had a stronger negative association with outcomes than any specific time period or MDAD severity. The influence of MDAD was mediated by Family Context, which had a strong, negative association with outcomes, particularly language and cognitive development. CONCLUSION: The number of time periods a child was exposed to MDAD in early childhood was more negatively associated with five areas of child development than timing or severity. Prenatal exposure may be more sensitive to MDAD than other time periods. The familial context (teen mother, lone parenthood and low SES) had a stronger influence on child outcomes than MDAD. Findings can be used to inform interventions which address maternal mental health from the prenatal period onward, and to support disadvantaged families to encourage healthy birth outcomes, early childhood development and school readiness.

High frequency jet ventilation versus high frequency oscillatory ventilation for pulmonary dysfunction in preterm infants.

BACKGROUND: Respiratory distress syndrome (RDS) is considered one of the major contributors to severe pulmonary dysfunction and consequent death in preterm infants. Despite widespread improvements in care, including increased utilization of antenatal steroids, use of surfactant replacement therapy, and advances in conventional mechanical ventilation (CMV), chronic lung disease (CLD) occurs in 42% of surviving preterm infants born at less than 28 weeks gestational age (GA). High frequency ventilation (HFV) aims to optimize lung expansion while minimizing tidal volume (Vt) to decrease lung injury. Two methods of HFV - high frequency oscillatory ventilation (HFOV) and high frequency jet ventilation (HFJV) - are widely used, but neither has demonstrated clear superiority in elective or rescue mode. OBJECTIVES: To compare the benefits and side effects of HFJV versus HFOV for mortality and morbidity in preterm infants born at less than 37 weeks GA with pulmonary dysfunction in both elective and rescue modes. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE via PubMed (1966 to November 30, 2015), EMBASE (1980 to November 30, 2015), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to November 30, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We imposed no date, language, or publication restrictions. SELECTION CRITERIA: We planned to include randomized, cluster-randomized, and quasi-randomized controlled trials if study authors stated explicitly that groups compared in the trial were established by a random or systematic method of allocation. We planned to exclude cross-over studies, as they would not allow assessment of the outcomes of interest. DATA COLLECTION AND ANALYSIS: We used the standard methods of the Neonatal Cochrane Review Group, including independent trial assessment and data extraction. We intended to analyze the data by using risk ratios (RRs) and risk differences (RDs) and 1/RD. We planned to calculate the number needed to treat for an additional beneficial outcome (NNTB) or the number needed to treat for an additional harmful outcome (NNTH). MAIN RESULTS: We found no studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: We found no evidence to support the superiority of HFJV or HFOV as elective or rescue therapy. Until such evidence is available, comparison of potential side effects or presumed benefits of either mode is not feasible.

Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of chronic kidney disease in children. The relevance of timing of diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown. STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS: Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada, identified using administrative data housed at the Manitoba Centre for Health Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and gestational (>20 weeks) DM and relevant confounders (maternal age; renin-angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol, illicit drug, and smoking use during pregnancy; region of residence; and size for gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by International Classification of Diseases codes. RESULTS: 945 case patients with CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%) of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional multivariable logistic regression model, pregestational DM was associated with CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29; 95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA: OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic control and body mass index. CONCLUSIONS: This study suggests that DM in the first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The association between CAKUT and LGA suggests that poor glycemic control increases risk. Screening and intervention studies in women of childbearing age with DM are warranted to determine whether the risk of chronic kidney disease in children can be modified.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.

BACKGROUND: Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation to replace intravascular volume, yet they have been increasingly associated with adverse effects on kidney function. This is an update of a Cochrane review first published in 2010. OBJECTIVES: To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH METHODS: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. The most recent search was completed on November 19, 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. DATA COLLECTION AND ANALYSIS: Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. All outcomes were analysed using relative risk (RR) and 95% confidence intervals (95% CI). Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random-effects model. MAIN RESULTS: This review included 42 studies (11,399 patients) including 19 studies from the original review (2010), as well as 23 new studies. Fifteen studies were excluded from the original review (nine retracted from publication due to concerns about integrity of data and six lacking individual patient creatinine data for the calculation of RIFLE criteria). Overall, there was a significant increase in the need for RRT in the HES treated individuals compared to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, 9857 patients) and the number with author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402 participants). The risk of meeting urine output and creatinine based RIFLE-R (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95% CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output based outcomes were excluded as per study protocol, the direction of AKI risk again favoured the other fluid type, with a non-significant RR of AKI in HES treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (≥ 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. ≥ 2 L versus < 2 L). There were differences identified between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based outcomes only, which may reflect the differing renal response to fluid resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological quality of the studies was good. AUTHORS' CONCLUSIONS: The current evidence suggests that all HES products increase the risk in AKI and RRT in all patient populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products.

'The influence of gestational age and socioeconomic status on neonatal outcomes in late preterm and early term gestation: a population based study'.

BACKGROUND: Infants born late preterm (34 + 0 to 36 + 6 weeks GA (gestational age)) are known to have higher neonatal morbidity than term (37 + 0 to 41 + 6 weeks GA) infants. There is emerging evidence that these risks may not be homogenous within the term cohort and may be higher in early term (37 + 0 to 38 + 6 weeks GA). These risks may also be affected by socioeconomic status, a risk factor for preterm birth. METHODS: A retrospective population based cohort of infants born at 34 to 41 weeks of GA was assembled; individual and area-level income was used to develop three socioeconomic (SES) groups. Neonatal morbidity was grouped into respiratory distress syndrome (RDS), other respiratory disorders, other complications of prematurity, admission to a Level II/III nursery and receipt of phototherapy. Regression models were constructed to examine the relationship of GA and SES to neonatal morbidity while controlling for other perinatal variables. RESULTS: The cohort contained 25 312 infants of whom 6.1% (n = 1524) were born preterm and 32.4% (n = 8203) were of low SES. Using 39/40 weeks GA as the reference group there was a decrease in neonatal morbidity at each week of gestation. The odds ratios remained significantly higher at 37 weeks for RDS or other respiratory disorders, and at 38 weeks for all other outcomes. SES had an independent effect, increasing morbidity with odds ratios ranging from 1.2-1.5 for all outcomes except for the RDS group, where it was not significant. CONCLUSIONS: The risks of morbidity fell throughout late preterm and early term gestation for both respiratory and non-respiratory morbidity. Low SES was associated with an independent increased risk. Recognition that the morbidities associated with prematurity continue into early term gestation and are further compounded by SES is important to develop strategies for improving care of early term infants, avoiding iatrogenic complications and prioritizing public health interventions.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.

BACKGROUND: Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation, yet controversy exists about their impact on kidney function. OBJECTIVES: To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. Secondary outcomes included serum creatinine and creatinine clearance. DATA COLLECTION AND ANALYSIS: Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random effects model. MAIN RESULTS: The review included 34 studies (2607 patients). Overall, the RR of author-defined kidney failure was 1.50 (95% CI 1.20 to 1.87; n = 1199) and 1.38 for requiring RRT (95% CI 0.89 to 2.16; n = 1236) in HES treated individuals compared with other fluid therapies. Subgroup analyses suggested increased risk in septic patients compared to non-septic (surgical/trauma) patients. Non-septic patient studies were smaller and had lower event rates, so subgroup differences may have been due to lack of statistical power in these studies. Only limited data was obtained for analysis of kidney outcomes by the RIFLE criteria. Overall, methodological quality of studies was good but subjective outcomes were potentially biased because most studies were unblinded. AUTHORS' CONCLUSIONS: Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.