OBJECTIVE:To assess whether deferred cord clamping (DCC) is associated with reduced death and/or severe brain injury compared to early cord clamping (ECC) in very and extremely preterm monochorionic-diamniotic (MCDA) twins. STUDY DESIGN:This multicenter retrospective cohort study included liveborn MCDA twins born under 32 weeks of gestation and admitted to any tertiary-level neonatal intensive care unit (NICU) participating in the Canadian Neonatal Network (CNN) in Canada between 2018 and 2023. We compared DCC ≥30s to ECC<30s. The primary composite outcome was death before discharge and/or severe brain injury (intraventricular hemorrhage ≥ grade III and/or cystic periventricular leukomalacia). Secondary outcomes included neonatal morbidities and interventions. Adjusted odds ratios (aORs) for categorical variables and ratio of means for continuous variables were estimated with 95% confidence intervals (CIs). Generalized estimating equation (GEE) models accounted for the correlation between twins. RESULTS:Approximately 42% of first-born and 54% of second-born MCDA twins received DCC. The primary composite outcome of death and/or severe brain injury occurred in 10% (48/488) of twins who received DCC and 16% (82/529) of those who received ECC (aOR 0.93; 95% CI 0.60-1.45). Among secondary outcomes, there were no significant differences in neonatal morbidities or interventions, except for a significant reduction in red blood cell transfusions, with 24% (115/488) of twins in the DCC group receiving at least one transfusion versus 43% (229/529) in the ECC group (aOR 0.46; 95% CI 0.33-0.66). CONCLUSIONS:Among MCDA twins born at < 32 gestational weeks, DCC did not impact the risk of death and/or severe brain injury compared to ECC but it was associated with decreased need for transfusions.

Aspirin can prevent most preterm preeclampsia in high-risk women. The risk can be estimated either by considering clinical factors or by using the Fetal Medicine Foundation (FMF) algorithm, which considers placental growth factor with blood pressure and other markers. Among nulliparous women, a low FMF risk is associated with low incidences of preeclampsia (<2.5%) and preterm preeclampsia (<0.5%), and a high FMF risk is associated with high incidences of preeclampsia (>6%) and preterm preeclampsia (>1.5%; P < 0.001), regardless of clinical risk factors. Where available, the FMF algorithm including placental growth factor should be the only tool used for preeclampsia screening.

OBJECTIVES:Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a complication of preeclampsia. We aimed to estimate the association between first-trimester placental growth factor (PlGF) and other preeclampsia risk factors with HELLP syndrome. METHODS:We performed a secondary analysis of a prospective cohort of nulliparous women recruited at 11 weeks 0 days - 14 weeks 0 days gestation and stratified according to pregnancy outcome: HELLP syndrome, preeclampsia without HELLP syndrome, or neither (controls). We compared the 3 groups for first-trimester maternal age, BMI, mean arterial pressure, uterine artery pulsatility index, and serum PlGF in multiples of the median (MoM), using non-parametric and receiver-operator characteristics curve analyses. RESULTS:Of the 7325 eligible participants, 27 (0.4%) developed HELLP syndrome and 228 (3.1%) developed preeclampsia without HELLP. Median PlGF was lower in the preeclampsia (median: 0.85 MoM; IQR 0.61-1.15; P < 0.001), and HELLP syndrome (0.72 MoM; IQR 0.55-1.09, P < 0.001) groups than in controls (1.02 MoM; IQR 0.72-1.43). At PlGF ≤0.7 MoM, the prediction rate for preterm and term HELLP was 56% and 33%, respectively, and the respective values for preeclampsia without HELLP were 50% and 30%, respectively, at a false-positive rate of 17%. In HELLP syndrome, unlike preeclampsia without HELLP, there was no association with first-trimester BMI, mean arterial pressure, or uterine artery pulsatility index. CONCLUSIONS:First-trimester low PlGF was the only factor associated with HELLP syndrome.

Abstract Background Patient-reported experience measures are valuable instruments for assessing care quality in alignment with the Triple Aim framework. We sought to validate the PREM-PS questionnaire (Patient Reported Experience Measure – Prenatal Screening) by evaluating its psychometric properties (structural validity, internal consistency, and cross-cultural validity) for Canadian French-and English-speaking populations. Methodology This secondary analysis used data from a prospective, open-label, multicenter randomized trial in Quebec and British Columbia (2019–2023). Pregnant women aged 19+ were randomized 2:1 to receive either first-tier cell-free DNA (cfDNA) or traditional biochemical screening for chromosomal anomalies (T21, T18, T13). Participants completed the PREM-PS, a 10-item questionnaire on a 5-point Likert scale, at 22 weeks of pregnancy. Exploratory factor analysis, conducted separately for French and English questionnaires, used half the data to identify underlying factors. Confirmatory factor analysis of the remaining data evaluated structural validity. Internal consistency was assessed using Cronbach’s alpha, and cross-cultural validity through measurement invariance analyses. Mean scores were compared across arms using linear mixed models. Results Of 7815 enrolled pregnant women, 3398 completed the French questionnaire and 2875 the English version (80.3% response rate, 96.4% completion rate). Mean age was 32.11 years (SD = 4.01), with 65.1% identifying as White. Factor analyses retained seven items grouped into two latent factors interpreted as Communication and Professionalism. Standardized loadings from exploratory factor analysis ranged from 0.66–0.93 (French) and 0.69–0.96 (English), while standardized parameter estimates from the confirmatory factor analysis ranged from 0.67–0.98 (French) and 0.62–0.98 (English). Cronbach’s alpha exceeded 0.85 for both factors in French and 0.88 in English. No significant differences were observed between the two study arms for either Professionalism or Communication scores, indicating comparable patient-reported experiences regardless of screening method. Conclusion The PREM-PS demonstrates adequate validity for assessing patient-reported experiences of pregnant women undergoing prenatal screening in both Canadian French and English, with potential to guide improvements in prenatal care. Trial registration ClinicalTrials.gov, NCT03831256. Registered February 5th, 2019, https://clinicaltrials.gov/study/NCT03831256?term=NCT03831256&rank=1

ObjectiveEvaluate the impact of prenatal workshops for parents whose baby would be admitted to the NICU because of prematurity or congenital anomalies.Study designThe workshop was developed and optimized in a needs assessment and pilot phase. During the prospective phase, future NICU parents were offered participation in the workshop; their perspectives were investigated using mixed methods.ResultsA total of 152 parents participated. They evaluated the workshop at 9.6/10 on average. Almost all (98%) agreed/strongly agreed that the workshop was useful, that it helped them prepare for the birth (95%), made them feel less lonely (90%) and that exchanges with other parents were beneficial (92%). All answers to open-ended questions were positive. After the birth, 90% remembered the workshop and 90% would recommend it to other parents.ConclusionPrenatal educational workshop provides a unique and useful means to support future NICU parents and prepare them for the NICU hospitalization.

OBJECTIVES:This study aimed to estimate the association between low first-trimester maternal serum PlGF (placental growth factor) and PAPP-A (pregnancy-associated plasma protein A) and the risk of placenta-mediated complications. METHODS:We performed a secondary analysis of the PREDICTION study, including nulliparous participants recruited at 11 to 14 weeks of pregnancy. First-trimester PlGF and PAPP-A levels were reported in multiples of the median (MoM) adjusted for maternal characteristics and gestational age. Participants were stratified into 4 groups based on absence/presence of low (<0.4 MoM) PlGF and PAPP-A values. A composite of adverse pregnancy outcomes (including preeclampsia, fetal growth restriction, fetal death, and placental abruption) was calculated for deliveries occurring before 34 weeks, before 37 weeks, and at or after 37 weeks. RESULTS:Out of the 7262 participants, 86 (1.2%) experienced the composite outcome before 37 weeks of gestation, including 35 (0.4%) before 34 weeks. The combination of low PAPP-A and low PlGF levels was associated with the greatest risk of adverse outcomes before 37 weeks (21%) and before 34 weeks (12%) compared with low PlGF alone (7% and 3%), low PAPP-A alone (2% and 1%), or neither marker (1% and 0.4%, respectively; P < 0.001). For preterm preeclampsia specifically, the combination of low PAPP-A and low PlGF was also associated with a greater risk (12%) compared with low PlGF alone (6%), low PAPP-A alone (0.5%), or neither marker (0.7%; P < 0.001). CONCLUSIONS:The combination of low PAPP-A and low PlGF levels is associated with a very high risk for adverse outcomes before 34 and 37 weeks. An isolated low PAPP-A should not be considered a risk factor for adverse pregnancy outcomes.

INTRODUCTION:Twin-to-twin transfusion syndrome (TTTS) is associated with high perinatal morbidity and mortality. Krispin et al. [Ultrasound Obstet Gynecol. 2023;61(4):511-7] developed a prediction model to estimate the likelihood of dual twin survival after fetoscopic laser photocoagulation (FLPC). This study aimed to evaluate the predictive value of sonographic parameters at diagnosis of TTTS treated with FLPC for postnatal dual twin survival and to validate Krispin et al.'s calculator. METHODS:This is a retrospective cohort study of cases of TTTS treated by FLPC. The primary outcome was dual survival 30 days after delivery. The calculator used preoperative variables: donor's estimated fetal weight (EFW) <10th centile, intertwin growth discordance >25%, anterior placenta, pulsatility index (PI) in the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA), with scores ranging 0-300. RESULTS:Among 157 patients, 84 (53.5%) had dual twin survival (Group A), compared to 73 (46.5%) with one or no survivors (Group B). No significant differences were seen in donor's EFW <10th centile (57.1% [A] vs. 57.5% [B], p = 0.96), intertwin growth discordance (26.2% [A] vs. 38.4% [B] p = 0.95), rates of PI >95th centile in the donor's UA and DV, and PI <5th centile in the MCA (p > 0.05). However, a significant difference was found for anterior placenta (38.1% [A] vs. 58.9% [B], p = 0.009). The observed dual survival was higher than predicted for scores ≥100. CONCLUSION:We were not able to externally validate the calculator of dual survival after laser for TTTS, especially for elevated scores. Among the parameters analyzed, only anterior placenta was significantly associated with poorer outcomes.

The rate of multiple births has surged. Twins, especially those with monochorionic placentation, face a higher risk of neonatal mortality, morbidity and very preterm birth compared to singletons. Deferred cord clamping (DCC) is the standard for preterm singletons. While DCC is known to reduce the risk of mortality and morbidity in preterm singletons, its efficacy and safety in very preterm twins, especially monochorionic twins, remain scarcely explored. This study aimed to assess whether DCC, compared with early cord clamping (ECC), was associated with a reduction in death and/or severe brain injury in very and extremely preterm monochorionic-diamniotic twins. This multicenter retrospective cohort study included liveborn monochorionic-diamniotic twins of <32 gestational weeks admitted to a tertiary-level neonatal intensive care unit (NICU) in Canada between 2018 and 2023 using the Canadian Neonatal/Preterm Birth Network (CNN/CPTBN) database. We compared DCC ≥30s and ECC <30s. The primary outcome was a composite of death before discharge and/or severe brain injury. Secondary outcomes included neonatal morbidity and clinical outcomes. We calculated crude odds ratios (ORs) and adjusted ORs for categorical variables and ratio of means for continuous variables, along with 95% confidence intervals (CI). Models were fitted with generalized estimated equations accounting for twin correlation. 1017 neonates were included (DCC 488 [48.0%]; ECC 529 [52.0%]). Death and/or severe brain injury occurred in 10% (n=48) of twins who received DCC and in 16% (n=82) of those who received ECC. There was no significant difference between the groups (aOR 0.93; 95% CI 0.60-1.45). There was a significant reduction in red blood cell transfusions (aOR 0.46; 95% CI 0.33-0.66). Among monochorionic-diamniotic twins born before 32 weeks of gestation, DCC did not impact the incidence of death and/or severe brain injury compared to ECC but was associated with decreased need for transfusions.

OBJECTIVES:To examine the associations of circulating very long-chain saturated fatty acids (VLSFAs) with maternal blood pressure (BP), weight gain, and incidence of gestational hypertension (GH)/preeclampsia (PE) in a retrospective longitudinal study. METHODS:Blood samples from 92 pregnant women, including normotensive (n = 64) and hypertensive pregnancies (GH/PE, n = 28), from the International Trial of Antioxidants in the Prevention of PE (INTAPP; ISRCTN 85024310) were used at 8-14 weeks (visit 1) and 20-24 weeks (visit 2). Plasma Fatty acids (FA) profiles were measured by gas chromatography with flame ionization detection. Partial correlations and mixed models assessed BP and FA associations. Logistic regression models were used to assess GH/PE risks using FAs. RESULTS:Weight gain adjusted for pre-pregnancy BMI was inversely correlated to arachidic acid at visit 1 (r = -0.364, P < 0.001). VLSFAs, arachidic acid, and tricosylic acid were negatively correlated with both systolic BP and diastolic BP (DBP) at visit 1 (r < -0.274, P < 0.03). Higher levels of VLSFAs were also associated with the lower quartile of DBP (P = 0.01). Integrating clinical parameters with FA profiles (palmitoleic acid and eicosapentaenoic acid) presented a promising predictive model for GH/PE. CONCLUSIONS:VLSFA levels in circulating phospholipids, especially arachidic acid, are associated with weight gain and BP, and with tricosylic acid, could be linked to a potentially protective role within FAs in a more complex lipid signature against hypertension in pregnancy.

Purpose:Insufficient fetal fraction is a significant cause of prenatal cell-free DNA (cfDNA) screening failure, affecting 2% to 5% of samples, particularly among women with high body mass index (BMI). We evaluated the clinical impacts of in vitro fetal enrichment in a public prenatal cfDNA screening laboratory, hypothesizing that it would lower failure rates. Methods:This cohort study analyzed 8551 consecutive samples from pregnant women at an ISO15189-accredited prenatal cfDNA screening laboratory. We compared 4893 samples tested before and 3651 samples after implementing fetal enrichment. Samples were collected from January 2021 to October 2023 from high-risk (4809) pregnant women enrolled in the public Quebec Prenatal Screening Program (including 7 lost to follow-up and who were excluded from the analysis) and low-risk (3550) pregnancies from the Pegasus-2 project and divided into 4 groups. A total of 192 low-risk twin pregnancies were also included. Results:Fetal enrichment doubled fetal fraction and reduced the assay failure rate by more than 10-fold (from 1.6% to 0.14%, P < .0001), enabling all women to receive a risk estimate at their first blood draw, even with a high BMI. It also improved clinical performance metrics. Conclusion:Prenatal cfDNA screening with in vitro fetal enrichment enhances accessibility and reliability of prenatal screening, nearly eliminating test failures and providing timely results for all samples, regardless of maternal BMI.

Congenital cytomegalovirus infections (cCMV) are an important cause of childhood neurodevelopmental deficits. Most cCMV are the result of maternal non-primary infections during pregnancy, which can be due to reactivation or reinfection. To identify the rate of CMV reinfection during pregnancy and its risk factors. We performed a secondary analysis of CMV seropositive participants from two prospective cohort studies in Quebec, Canada. Antibody responses to four strain-specific CMV epitopes located in glycoproteins B and H were measured by enzyme-linked immunosorbent assay. CMV reinfection was defined as the appearance of an antibody response to a new epitope in the third compared to the first trimester. Risk factors for reinfection were assessed. Among 1614 participants, CMV reinfection was identified in 2.7% of participants, representing an incidence of 54.99 per 1000 person-years at risk (95% confidence interval 39.95-73.82). Age, marital status, household income, continent of birth or ethnicity were not associated with reinfection during pregnancy. The incidence of CMV reinfection during pregnancy is like what has been reported for primary infection in Quebec. A greater understanding of the patterns of reinfection is needed to inform strategies to reduce the burden of disease from cCMV.

BACKGROUND:Little is known on the vertical transmission of human papillomavirus (HPV) and on the dynamics of HPV among children. Our objective was to determine the risk of HPV recurrence, persistence, and incidence over 2 years of age among children born to HPV-positive mothers. METHODS:We conducted the HERITAGE study among pregnant women recruited between 2010 and 2016 in Canada. HPV DNA testing was done on vaginal samples collected during the first and third trimesters of pregnancy, and on conjunctival, oral, pharyngeal, and genital samples collected in children from birth and at every 3-6 months up to 2 years. We estimated the probability of HPV vertical transmission, and of HPV recurrence, persistence, and incidence among children during follow-up. Time to clear HPV among children was estimated using Kaplan-Meier technique. RESULTS:Among the 422 women with HPV during pregnancy, 390 carried pregnancy to term, and 395 children were born alive including twins/triplets. HPV vertical transmission was estimated at 7.3% (95% confidence interval [CI], 5.0%-10.4%) with a genotype concordance of 85.2%. During the entire follow-up, we observed 91 HPV detections (among 51 children) including 2 recurrent and 1 persistent. Incident genotypes occurred in 26 of the 270 (9.6%) children with valid HPV testing during follow-up. Most HPV infections detected in children cleared with a mean time of 3.9 months (95% CI, 3.6-4.2 months). CONCLUSIONS:HPV vertical transmission and incident HPV occasionally occur during infancy, but the risk of persistence or recurrence is overall very low.

Fetal growth discordance (FGD) and selective fetal growth restriction (sFGR), which often accompany twin-twin transfusion syndrome (TTTS), are caused by discordant placental territories. The objective of this study was to determine the impact of FGD and sFGR on survival following fetoscopic laser surgery for the primary diagnosis of TTTS. This was a retrospective cohort study of cases of fetoscopic laser performed for TTTS in monochorionic diamniotic twin pregnancies in the North American Fetal Therapy Network (NAFTNet) Complicated MC Twin Registry. FGD was defined as a ≥25% weight discordance and sFGR as FGD with one fetus >10th percentile for gestational age (GA). Exclusion criteria were loss to follow-up, selective termination, monoamniotic pregnancies and triplet or higher order multiples. Primary outcome was fetal survival and secondary outcomes were GA at delivery and fetal complications. 2880 pregnancies were identified in the registry, of which 1194 were excluded. Of the 1686 pregnancies who were included for analysis, 688 had FGD and 377 qualified as sFGR. The table shows the pre-laser ultrasound evaluation. Dual survival was 75.15% in TTTS only, 62.50% in the TTTS+FGD and 61.01% in TTTS+sFGR (p< 0.001). Donor survival was 86.24%, 69.72% and 67.90% respectively (p< 0.001). Compared to TTTS alone, odds ratios for dual survival were 0.546 (0.442-0.675) in TTTS+FGD and 0.540 (0.421-0.692) in TTTS+sFGR. Odds ratios for donor survival were 0.367 (0.288-0.468) and 0.384 (0.292-0.506) respectively. Results remained statistically significant after adjusting for TTTS stage, Doppler anomalies and GA at laser. GA at delivery did not differ between groups. Fetal complications occurred in 2.56% of the TTTS-only group, 3.05% of the TTTS+FGD and 4.51% of the TTTS+sFGR. Fetal dual survival is affected by the presence of FGD, even without sFGR, at the expense of the smaller twin.

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36–48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03–12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10–17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.

Objective: To review the available prenatal aneuploidy screening options and to provide updated clinical guidelines for reproductive care providers. Target Population: All pregnant persons receiving counselling and providing informed consent for prenatal screening. Benefits, Harms, and Costs: Implementation of the recommendations in this guideline should increase clinician competency to offer counselling for prenatal screening options and provide appropriate interventions. Given the variety of available options for prenatal screening with different performance, cost, and availability across Canada, appropriate counselling is of paramount importance to offer the best individual choice to Canadian pregnant persons. Prenatal screening may cause anxiety, and the decisions about prenatal diagnostic procedures are complex given the potential risk of fetal loss. Evidence: Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to July 2023, using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1995 to July 2023. 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 online Appendix A (Tables A1 for definitions and A2 for interpretations). Intended Audience: Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal-fetal medicine specialists, geneticists, and radiologists. Social Media Abstract: Non-invasive prenatal screening is the most accurate method for detecting major aneuploidies. It is not universally available in the public health system and has some limitations.