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OBJECTIVE: To compare the neurodevelopmental outcomes of infants born at <29 weeks' gestation and exposed to diabetes in pregnancy with those unexposed. STUDY DESIGN: This was a retrospective cohort study using the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases. Infants born <29 weeks' gestation and admitted to a level 3 NICU from 2009 through 2018 who had neurodevelopmental assessments at 18 to 24 months corrected age (CA) were eligible. The two primary outcomes were: i) Neurodevelopmental Impairment (NDI) (≥1 of Bayley-III scores < 85 in any domain, cerebral palsy, or vision or hearing impairment); and ii) significant NDI (sNDI) (≥1 of Bayley-III scores < 70 in any domain, cerebral palsy GMFCS ≥ 3, bilateral blindness, or need for hearing aids or cochlear implants). Secondary outcomes were the individual components of NDI and sNDI. Adjusted odds ratios with 95% CIs were calculated to determine outcomes between groups. RESULTS: Of 13,988 eligible infants, 55% attended neurodevelopmental follow-up assessments. Infants exposed to diabetes had increased odds of NDI compared with those unexposed (aOR 1.09 (95% CI 1.08-1.54); there was no difference in sNDI (aOR 1.07 (95% CI 0.84-1.36). Language and motor delays were more common in those exposed to maternal diabetes. CONCLUSIONS: Higher rates of NDI, language, or motor delays were present in infants born at < 29 weeks' gestation exposed to diabetes in utero. Future research is needed to determine the etiology and clinical significance of these findings.

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OBJECTIVE: Despite the well-recognized association between pre-existing diabetes mellitus and stillbirth or perinatal mortality, there remain knowledge gaps about the strength of association across different populations. The primary objective of this systematic review and meta-analysis was to quantify the association between pre-existing diabetes and stillbirth or perinatal mortality, and secondarily, to identify risk factors predictive of stillbirth or perinatal mortality among those with pre-existing diabetes. DATA SOURCES: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to April 2022. METHODS OF STUDY SELECTION: Cohort studies and randomized controlled trials in English or French that examined the association between pre-existing diabetes and stillbirth or perinatal mortality (as defined by the original authors) or identified risk factors for stillbirth and perinatal mortality in individuals with pre-existing diabetes were included. Data extraction was performed independently and in duplicate with the use of prespecified inclusion and exclusion criteria. Assessment for heterogeneity and risk of bias was performed. Meta-analyses were completed with a random-effects model. TABULATION, INTEGRATION, AND RESULTS: From 7,777 citations, 91 studies met the inclusion criteria. Pre-existing diabetes was associated with higher odds of stillbirth (37 studies; pooled odds ratio [OR] 3.74, 95% CI, 3.17-4.41, I2=82.5%) and perinatal mortality (14 studies; pooled OR 3.22, 95% CI, 2.54-4.07, I2=82.7%). Individuals with type 1 diabetes had lower odds of stillbirth (pooled OR 0.81, 95% CI, 0.68-0.95, I2=0%) and perinatal mortality (pooled OR 0.73, 95% CI, 0.61-0.87, I2=0%) compared with those with type 2 diabetes. Prenatal care and prepregnancy diabetes care were significantly associated with lower odds of stillbirth (OR 0.26, 95% CI, 0.11-0.62, I2=87.0%) and perinatal mortality (OR 0.41, 95% CI, 0.29-0.59, I2=0%). CONCLUSION: Pre-existing diabetes confers a more than threefold increased odds of both stillbirth and perinatal mortality. Maternal type 2 diabetes was associated with a higher risk of stillbirth and perinatal mortality compared with maternal type 1 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022303112.

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OBJECTIVE: Syphilis-related stillbirths (SRSBs) disproportionately affect marginalized women with 11% of all local stillbirths having maternal syphilis as a contributory factor in 2020. This study describes the incidence and perinatal factors associated with SRSB. METHODS: This was a retrospective cohort study of all stillbirths occurring from 1 January 2017 to 31 December 2020, at a single tertiary-level referral hospital in Winnipeg, Manitoba. Cases that met criteria for SRSB were identified from hospital records and included in the final analysis. Maternal demographics, comorbidities, prenatal care attendance, sexually transmitted infection testing, treatment, and diagnostic investigations at time of stillbirth were collected from hospital charts using a standardized data collection form. Descriptive statistics were performed to present the results. RESULTS: The proportion of SRSB increased over the period of study from 0%-11%. Eleven cases were identified as SRSB, with diagnosis occurring intrapartum in 7 cases and antenatally in 4 cases. Of the 4 antenatal cases, only 2 had identifiable treatment responses indicated by microbiological and pathology workup. Commonly identified risk factors for SRSB were homelessness, mental illness, substance use, sexually transmitted co-infections, and lack of prenatal care. CONCLUSIONS: Cases of SRSB are rising in Winnipeg with 11% of all stillbirths having maternal syphilis as a contributory factor by 2020. SRSBs disproportionately affect marginalized women. The dramatic and rapid changes in the epidemiology of syphilis in Winnipeg are likely shared by other Canadian regions and warrant increased prevention strategies to improve outcomes.

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BACKGROUND: Our aim was to examine the association between preterm delivery and incident maternal mental disorders using a population-based cohort of mothers in Canada. METHODS: Retrospective matched cohort study using Manitoba Centre for Health Policy (MCHP) administrative data in Manitoba. Mothers who delivered preterm babies (<37 weeks gestational age) between 1998 and 2013 were matched 1:5 to mothers of term babies using socio-demographic variables. Primary outcome was any incident mental disorder within 5 years of delivery defined as any of (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders, and (d) suicide or suicide attempts. Multivariable Poisson regression model was used to estimate the 5-year adjusted incidence rate ratios (IRRs). RESULTS: Mothers of preterm children (N = 5,361) had similar incidence rates of any mental disorder (17.4% vs. 16.6%, IRR = 0.99, 95% CI, 0.91 to 1.07) compared to mothers of term children (N = 24,932). Mothers of term children had a higher rate of any mental disorder in the first year while mothers of preterm children had higher rates from 2 to 5 years. Being the mother of a child born <28 week (IRR = 1.5, 95% CI, 1.14 to 2.04), but not 28-33 weeks (IRR = 1.03, 95% CI, 0.86 to 1.19) or 34-36 weeks (IRR = 0.96, 95% CI, 0.88 to 1.05), was associated with any mental disorder. INTERPRETATION: Mothers of preterm and term children had similar rates of incident mental disorders within 5-years post-delivery. Extreme prematurity was a risk factor for any mental disorder. Targeted screening and support of this latter group may be beneficial.

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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.

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OBJECTIVE: To study the association between prematurity and grade 3 school performance in a contemporary cohort of children. METHODS: Population-based retrospective cohort study in Manitoba, Canada. Children born between 1999 and 2011 who had their grade 3 school performance data available were eligible. Preterm birth (<37 weeks) was the exposure of interest assessed using multivariable logistic regression models. Our primary outcomes were 'needs ongoing help' or 'outside the range' in at least two of each of the (1) four numeracy and (2) three reading competencies. RESULTS: Of the 186 956 eligible children, 101 436 children (7187 preterm (gestational age, median (IQR) 35 weeks (34, 36)) and 94 249 term (40 weeks (39,40)) were included. Overall, 19% of preterm and 14% of term children had the numeracy outcome (adjusted OR (aOR) 1.38; 95% CI 1.29 to 1.47, p<0.001), while 19% and 13% had the reading outcome (aOR 1.38; 1.29 to 1.48, p<0.001). These differences showed a gestational age gradient. Gestational age (for numeracy, <28 weeks aOR 4.93 (3.45 to 7.03), 28-33 weeks 1.72 (1.50 to 1.98), 34-36 weeks 1.24 (1.15 to 1.34); for reading, <28 weeks 3.51 (2.40 to 5.14), 28-33 weeks 1.72 (1.49 to 1.98), 34-36 weeks 1.24 (1.17-1.37)), male sex, small for gestational age and maternal medical and sociodemographic factors were associated with the numeracy and reading outcomes in this cohort. CONCLUSIONS AND RELEVANCE: Children born preterm had poorer performance in grade 3 numeracy and reading proficiencies than children born full term. All children born preterm, not just those born extremely preterm, should be screened for reading and numeracy performance in school and strategies implemented to address any deficits.

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OBJECTIVE: To provide clear and concise guidelines for the diagnosis and management of preterm prelabour rupture of membranes (PPROM) TARGET POPULATION: All patients with PPROM <37 weeks gestation BENEFITS, HARMS, AND COSTS: This guideline aims to provide the first Canadian general guideline on the management of preterm membrane rupture. It includes a comprehensive and up-to-date review of the evidence on the diagnosis, management, timing and method of delivery. EVIDENCE: The following search terms were entered into PubMed/Medline and Cochrane in 2021: preterm premature rupture of membranes, PPROM, chorioamnionitis, Nitrazine test, ferning, commercial tests, placental alpha microglobulin-1 (PAMG-1) test, insulin-like growth factor-binding protein-1 (IGFBP-1) test, ultrasonography, PPROM/antenatal corticosteroids, PPROM/Magnesium sulphate, PPROM/ antibiotic treatment, PPROM/tocolysis, PPROM/preterm labour, PPROM/Neonatal outcomes, PPROM/mortality, PPROM/outpatient/inpatient, PPROM/cerclage, previable PPROM. Articles included were randomized controlled trials, meta-analyses, systematic reviews, guidelines, and observational studies. Additional publications were identified from the bibliographies of these articles. Only English-language articles were reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All prenatal and perinatal health care providers. SUMMARY STATEMENTS: RECOMMENDATIONS.

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Fournir des directives claires et concises pour le diagnostic et la prise en charge de la rupture prématurée des membranes avant terme (RPMAT). Population cible Toute patiente manifestant une rupture prématurée des membranes avant 37 semaines d'aménorrhée. Bénéfices, risques et coûts La présente directive clinique vise à fournir les premières recommandations générales canadiennes sur la prise en charge de la rupture des membranes avant terme. Elle repose sur un examen complet et à jour des données probantes sur le diagnostic de la rupture et sur la prise en charge, le bon moment et les modes d'accouchement. Données probantes Des recherches ont été effectuées dans PubMed-Medline et Cochrane en 2021 en utilisant les termes suivants : preterm premature rupture of membranes, PPROM, chorioamnionitis, Nitrazine test, ferning, commercial tests, PAMG-1, IGFBP-1 test, ultrasonography, PPROM/antenatal corticosteroids, PPROM/Magnesium sulphate, PPROM/antibiotic treatment, PPROM/tocolysis, PPROM/preterm labour, PPROM/neonatal outcomes, PPROM/mortality, PPROM/outpatient/inpatient, PPROM/cerclage, previable PPROM.

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OBJECTIF: Fournir des directives claires et concises pour le diagnostic et la prise en charge de la rupture prématurée des membranes avant terme (RPMAT). POPULATION CIBLE: Toute patiente manifestant une rupture prématurée des membranes avant 37 semaines d'aménorrhée. BéNéFICES, RISQUES ET COûTS: La présente directive clinique vise à fournir les premières recommandations générales canadiennes sur la prise en charge de la rupture des membranes avant terme. Elle repose sur un examen complet et à jour des données probantes sur le diagnostic de la rupture et sur la prise en charge, le bon moment et les modes d'accouchement. DONNéES PROBANTES: Des recherches ont été effectuées dans PubMed-Medline et Cochrane en 2021 en utilisant les termes suivants : preterm premature rupture of membranes, PPROM, chorioamnionitis, Nitrazine test, ferning, commercial tests, PAMG-1, IGFBP-1 test, ultrasonography, PPROM/antenatal corticosteroids, PPROM/Magnesium sulphate, PPROM/antibiotic treatment, PPROM/tocolysis, PPROM/preterm labour, PPROM/neonatal outcomes, PPROM/mortality, PPROM/outpatient/inpatient, PPROM/cerclage, previable PPROM. Les articles retenus sont des essais cliniques randomisés, des méta-analyses, des revues systématiques, des directives cliniques et des études observationnelles. D'autres publications pertinentes ont été sélectionnées à partir des notices bibliographiques de ces articles. Seuls les articles en anglais ont été examinés. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé prénatale ou périnatale. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

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Objective: To describe the early neurodevelopmental outcomes following fetal exposure to previable preterm prelabour rupture of membranes (pPPROM). Methods: This was a secondary analysis of a subgroup of neonates born following pPPROM from a retrospective cohort study (2009-2015). Surviving infants who underwent standardized neurodevelopmental evaluation at 18-24 months corrected age (CA) between 2017 and 2019 were eligible for inclusion. Data abstracted from hospital charts were linked to prospectively collected developmental outcomes stored in an electronic database from a regional neonatal follow-up clinic. The primary outcome was Bayley-III composite scores (compared to the population mean 100, standard deviation (SD) 15). Secondary outcomes included presence of cerebral palsy, vision loss, hearing impairment, and requirement of rehabilitation therapy. Descriptive statistics were used to present results. Results: 25.7% (19/74) of neonates born after pPPROM survived to hospital discharge, but only 21.6% (16/74) survived to 18-24 months CA. Of these, 9 infants were eligible for follow-up at the regional clinic and 7 had developmental outcomes stored in the electronic database. Infants exposed to pPPROM exhibited Bayley-III scores more than 1 SD below the population mean across all three domains: cognitive 84.9 (SD 12.2); motor 82.3 (SD 11.5); and language 66.4 (SD 18.9). There were particular deficiencies in language development with 71% (5/7) scoring more than 2 SDs below the population mean. There were no cases of cerebral palsy. Conclusions: Only 1 in 5 infants born following expectantly managed pPPROM survived to 18-24 months CA. These infants born after pPPROM had significantly lower Bayley-III scores and particular deficiencies in language development. Better understanding of early neurodevelopmental challenges following pPPROM will help refine counselling of families contemplating expectant management and provide insights into the postnatal educational resources required to improve long-term developmental outcomes for these children.

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BACKGROUND: First Nation people living in Canada experience a high prevalence of type 2 diabetes in pregnancy. In this study, we aimed to describe maternal and neonatal outcomes in First Nation and all other females with type 2 diabetes living in Manitoba, Canada. METHODS: This was a population-level retrospective cohort study using linked administrative data from Manitoba (2012-2017). We compared First Nation females with type 2 diabetes with all other Manitoban females with type 2 diabetes, using relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 2181 females with type 2 diabetes were included, and 1218 (55.8%) were First Nation. First Nation females with type 2 diabetes were significantly more likely to experience stillbirth (RR 2.14, 95% CI 1.11-4.13) and perinatal death (RR 2.39, 95% CI 1.37-4.17) than all other Manitoban females with type 2 diabetes. Offspring of First Nation females with type 2 diabetes had a higher risk of most neonatal complications than offspring of all other Manitoban females with type 2 diabetes, including a higher risk of congenital malformations (RR 1.97, 95% CI 1.30-2.99), but First Nation people did not have a higher risk of most maternal complications. INTERPRETATION: First Nation pregnant individuals living with type 2 diabetes experienced a higher risk for adverse pregnancy outcomes than all other Manitoban females with type 2 diabetes. Additional studies are needed to identify both high-risk and protective factors for pregnancy complications in First Nation people living with type 2 diabetes in pregnancy.

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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.

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Objective: To evaluate the utility of measuring fetal cavum septum pellucidum (CSP) width during routine, mid-pregnancy ultrasound for improving diagnosis of 22q11.2 deletion syndrome amongst fetuses with and without conotruncal anomalies. Patients and Methods: This was a retrospective case-control study (2005-2016). Fetuses and newborns with 22q11.2 deletion and/or conotruncal cardiac anomalies were identified using a regional, clinical database. A control group was assembled in a 2:1 ratio to create three groups for comparison: i) 22q11.2 deletion syndrome; ii) isolated conotruncal anomalies; and iii) controls. Eligibility was restricted to those with stored ultrasound images between 18-22 weeks' gestation and a minimum biparietal diameter of 40 mm. Post-processing measurement of CSP width was performed in a standardized fashion by two blinded and independent study personnel. Descriptive and inferential statistics, regression modeling, and receiver operator curves (ROC) were used to compare outcomes between groups and evaluate sensitivity/specificity of CSP width as a marker of 22q11.2 deletion syndrome. Results: Twenty-nine cases of 22q11.2 deletion and 64 cases of isolated conotruncal anomalies were matched to 186 healthy controls. Cases with 22q11.2 deletion syndrome had significantly larger CSP widths (5.36 mm; SD=1.2) compared to those with isolated conotruncal anomalies (3.75 mm; SD=1.11) and healthy controls (2.93 mm; SD=0.57; p<0.0001). There was no difference in CSP width amongst those with 22q11.2 deletion irrespective of the presence/absence of a conotruncal anomaly (p=0.362), or by type of conotruncal anomaly (p=0.211). Using a CSP width cutoff >4.3 mm, fetuses with 22q11.2 deletion can be accurately identified with good sensitivity (89.7%) and specificity (84%). Conclusion: Fetuses with 22q11.2 deletion syndrome have dilated CSPs when compared to those with isolated conotruncal anomalies or controls. Because CSP dilation can be evaluated during routine mid-pregnancy ultrasound using standard images of the fetal head, measurement could easily be incorporated to enhance prenatal diagnosis of this phenotypically diverse condition.

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Objectives: To determine the prevalence and factors associated with antenatal promotion of breastfeeding in high-risk pregnancies. Study design: This was a cross-sectional study of trends in breastfeeding promotion during antenatal consultation of pregnancies at high-risk for newborn admission to the neonatal intensive care unit (NICU) between January 2017 and December 2020. Eligible high-risk pregnant patients undergoing antenatal consultation in a tertiary-level fetal assessment unit were identified using an electronic clinic repository. Consult letters and fetal assessment reports were reviewed to determine baseline demographics, pregnancy history, fetal findings, and communication about breastfeeding. Descriptive and inferential statistics were used to present findings and compare outcomes between groups. Results: 316 pregnancies were included for final analysis. The mean maternal age was 28.7 years (SD 6.2) and 65 % were multiparas. Median gestational age at time of antenatal consult was 32 weeks [IQR 29-34]. The main indication for consultation was fetal anomalies (72.8%), namely cardiac defects (21.2 %). There was a significant improvement in prevalence of antenatal discussions about breastfeeding over the study period, from 48.8 % early in the study period compared to 73.7 % in the past year (p = 0.036). However, amongst consults where breastfeeding was discussed, almost one-quarter (23.8 %) of patients indicated that they were not planning on breastfeeding postnatally. Conclusion: There has been a significant improvement in promoting breastfeeding antenatally amongst high-risk pregnancies. However, no follow-up or supports were offered to one-quarter of patients who indicated no intention of breastfeeding or using donor milk postnatally. Ongoing work is required to further advance breastfeeding promotion antenatally, increase parental supports and education, and optimize breastfeeding rates postnatally for improving outcomes of this high-risk group.

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Objectives: To determine the relationship between exposure to pregestational type 2 diabetes (T2D) and renal size and subcutaneous fat thickness in fetuses during routine obstetrical ultrasound. Methods: This was a case-control study (January 1, 2019 to December 31, 2019). Routine obstetrical ultrasounds performed between 18 and 22 weeks' gestation at a tertiary-care fetal assessment unit were reviewed. "Cases" comprised ultrasounds of fetuses exposed to pregestational T2D in utero. The control group was assembled from ultrasounds of healthy controls. Postprocessing measurements of fetal renal size and abdominal wall thickness from stored images were performed by two independent observers, and findings were compared between groups. Results: There were 54 cases and 428 ultrasounds of healthy controls. The mean maternal age of cases was 32.1 years (SD 6.2) compared to 33.2 years (SD 5.3) for healthy controls, and the majority of ultrasounds were performed in multiparous patients (83%). At the 18 to 22 week ultrasound, there was a significant reduction in renal size amongst fetuses exposed to maternal T2D in utero compared to controls; among cases, the mean renal width was 8.0 mm (95% CI 7.8-8.1) compared to 11.4 mm (95% CI 10.6-12.7) in controls (p < 0.0001); the mean renal thickness among cases was 8.1 mm (95% CI 7.9-8.2) compared to 11.5 mm (95% CI 10.7-12.9) in controls (p=0.001). There was no obvious difference in estimated fetal weight between groups, yet fetuses exposed to maternal T2D had increased subcutaneous abdominal wall fat thickness at this early gestational age (p=0.008). Conclusions: Fetal renal size in cases exposed to pregestational T2D is significantly smaller compared to controls, and subcutaneous abdominal wall fat is significantly thicker. Given emerging evidence about the developmental origins of disease, further study is needed to correlate the association between fetal renal size and fat distribution in the fetus and the long-term risk of chronic renal disease and diabetes in these offspring.

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Objectives: To determine the most common fetal ultrasound markers of total anomalous pulmonary venous return (TAPVR) during mid-trimester ultrasound using standardly obtained images and evaluate the performance of diagnostic algorithms for improving prenatal diagnosis. Methods: This was a matched case-control study at a regional referral centre (2005 to 2019). Cases of TAPVR were matched to controls 1 : 4 by date of birth and biologic sex. Postprocessing review of stored fetal ultrasound images was performed by two blinded and independent observers in a standardized fashion using nine sonographic markers: (i) left/right heart disproportion; (ii) abnormal distribution of great vessels; (iii) pulmonary vein entry into the left atrium (LA); (iv) confluence behind the LA; (v) abnormal coronary sinus; (vi) absence of the Coumadin ridge; (vii) aortic diameter; (viii) distance between LA and aorta; and (ix) post-LA space index >1.27. Descriptive and inferential statistics were used to present results and compare cases and controls. Diagnostic algorithms were compared by sensitivity/specificity. Results: 21 cases of isolated TAPVR were matched to 84 controls (n = 105). The most common ultrasound marker of TAPVR was absence of pulmonary vein entry into the LA (42.9%), followed by abnormal Coumadin ridge (38.1%). Cases of TAPVR had significantly larger post-LA spaces than controls (p < 0.0001) and wider aortic diameters (p=0.006). A diagnostic algorithm stratifying on absence of pulmonary veins followed by an abnormal Coumadin ridge, can correctly identify cases of TAPVR with high specificity (90.5%) and moderate sensitivity (61.9%). Conversely, a diagnostic algorithm using the presence of any 3 abnormal markers had improved specificity (94.1%) but poorer sensitivity (23.8%). Conclusions: Using standardly obtained images from routine fetal ultrasound, improved prenatal detection of isolated TAPVR is possible. A standardized diagnostic approach can be highly specific for fetal TAPVR, however, algorithms that are sufficiently sensitive for screening in the general population are still needed.

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AIMS/HYPOTHESIS: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth. METHODS: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case-control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939). RESULTS: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I2 86.1%) or in case-control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis. CONCLUSIONS/INTERPRETATION: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously.

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OBJECTIVE: Clinical detection and management of chorioamnionitis is challenging given the gold-standard for diagnosis remains placental pathology, the results of which are only available after delivery. Moreover, recommended diagnostic criteria for clinical chorioamnionitis have evolved over time. The goal of this study was to describe trends and differences in chorioamnionitis diagnostic and management practices in Canada. METHODS: We surveyed obstetric care providers participating in the Canadian Preterm Birth Network. Questionnaires were distributed electronically to all 29 sites and completed by 1 maternal-fetal medicine investigator at each site. RESULTS: The response rate was 82.8% (n = 24). There was considerable variation in the clinical criteria used to diagnose chorioamnionitis with 9 of 22 sites stating this occurs "frequently" or "very frequently." Isolated fever was "always" or "most of the time" used as an indication to start empiric antibiotic therapy in 14 of 24 sites, and 21 of 23 sites used the same diagnostic criteria for term and preterm deliveries. Placental histology (15 sites) and white blood cell count (14 sites) were the most common clinical tests performed to confirm chorioamnionitis. A combination of ampicillin and aminoglycoside antibiotics was used at 12 sites. Another frequently used antibiotic therapy was cefazolin and metronidazole (4 sites). CONCLUSION: There is a wide variation in practices for the diagnosis and management of chorioamnionitis across Canada. The results of this study will guide efforts to improve and standardize the management of this condition.

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BACKGROUND: Multiple-marker, maternal serum screening (MSS) has been the cornerstone of prenatal diagnosis since the 1980s. While combinations of these markers are used to predict fetal risk of Down syndrome and other genetic conditions, there is some evidence that individual markers may also predict nongenetic pregnancy complications, particularly those related to placental dysfunction. The objective of this meta-analysis was to investigate the utility of false-positive, second-trimester MSS for Down syndrome as a marker of placentally mediated complications amongst singleton pregnancies globally. METHODS: Electronic searches of PubMed, Medline, Embase, CINAHL, Web of Science, Scopus, and grey literature to 2019 were performed to identify observational studies comparing risk of pregnancy complications amongst pregnancies with false-positive MSS versus controls. A random-effects model of pooled odds ratios by outcome of interest (stillbirth, preeclampsia, fetal growth restriction, and preterm birth) and subgrouped by type of MSS test (double-, triple-, and quadruple-marker MSS) was used. RESULTS: 16 studies enrolling 68515 pregnancies were included. There were increased odds of preeclampsia (OR 1.28, 95% CI 1.09-1.51) and stillbirth (OR 2.46, 95% CI 1.94-3.12) amongst pregnancies with false-positive MSS. There was no significant association with preterm birth or growth restriction. CONCLUSIONS: There is some evidence of an association between false-positive, second-trimester MSS for Down syndrome and increased odds of preeclampsia and stillbirth. Future large-scale prospective studies are still needed to best determine the predictive value of false-positive MSS as a marker of placentally mediated complications later in pregnancy and evaluate potential clinical interventions to reduce these risks.

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OBJECTIVES: To evaluate the utility of fetal abdominal wall thickness (AWT) for predicting intrapartum complications amongst mothers with pregestational type 2 diabetes. METHODS: This was a historical cohort study of pregnant mothers with pregestational type 2 diabetes delivering at a Canadian tertiary-care center between January 1, 2014, and December 31, 2018. Delivery records were reviewed to collect information about demographics and peripartum complications. Stored fetal ultrasound images from 36 weeks' gestation were reviewed to collect fetal biometry and postprocessing measurement of AWT performed in a standardized fashion by 2 blinded and independent observers. The relationship between fetal AWT was then correlated with risk of intrapartum complications including emergency Caesarean section (CS) and shoulder dystocia. RESULTS: 216 pregnant women with type 2 diabetes had planned vaginal deliveries and were eligible for inclusion. Mean maternal age was 31.3 years, and almost all were overweight or obese at the time of delivery (96.8%). Overall, the incidence of shoulder dystocia and emergency intrapartum CS was 7.4% and 17.6%, respectively. There was no difference in mean fetal AWT between those having a spontaneous vaginal delivery (8.2 mm (95% CI 7.9-8.5)) and those needing emergency intrapartum CS (8.1 mm (95% CI 7.4-8.8); p = 0.71) or shoulder dystocia (8.7 mm (95% CI 7.9-9.5); p = 0.23). There was strong interobserver correlation of AWT measurements (r = 0.838; p < 0.00001). The strongest association with intrapartum complications was birthweight (p = 0.003): with birthweight > 4000 grams, the relative risk of shoulder dystocia or CS is 2.75 (95% CI 1.74-4.36; p < 0.001). CONCLUSIONS: There was no obvious benefit of AWT measurement at 36 weeks for predicting shoulder dystocia or intrapartum CS amongst women with type 2 diabetes in our population. The strongest predictor of intrapartum complications remained birthweight, and so studies for improving estimation of fetal weight and evaluating the role of intrapartum ultrasound for predicting risk of delivery complications are still needed.

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