Should gestational weight gain charts exclude individuals with excess postpartum weight retention?

BACKGROUND: High gestational weight gain is associated with excess postpartum weight retention, yet excess postpartum weight retention is not an exclusion criterion for current gestational weight gain charts. We aimed to assess the impact of excluding individuals with high interpregnancy weight change (a proxy for excess postpartum weight retention) on gestational weight gain distributions. METHODS: We included individuals with an index birth from 2008 to 2014 and a subsequent birth before 2019, in the population-based Stockholm-Gotland Perinatal Cohort. We estimated gestational weight gain (kg) at 25 and 37 weeks, using weight at first prenatal visit (<14 weeks) as the reference. We calculated high interpregnancy weight change (≥10 kg and ≥5 kg) using the difference between weight at the start of an index and subsequent pregnancy. We compared gestational weight gain distributions and percentiles (stratified by early-pregnancy body mass index) before and after excluding participants with high interpregnancy weight change. RESULTS: Among 55,723 participants, 17% had ≥10 kg and 34% had ≥5 kg interpregnancy weight change. The third, tenth, 50th, 90th and 97th percentiles of gestational weight gain were similar (largely within 1 kg) before versus after excluding participants with high interpregnancy weight change, at both 25 and 37 weeks. For example, among normal weight participants at 37 weeks, the 50th and 97th percentiles were 14 kg and 23 kg including versus 13 kg and 23 kg excluding participants with ≥5 kg interpregnancy weight change. CONCLUSIONS: Excluding individuals with excess postpartum weight retention from normative gestational weight gain charts may not meaningfully impact the charts' percentiles.

Antenatal corticosteroids and newborn respiratory outcomes in twins: A regression discontinuity study.

OBJECTIVE: To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. DESIGN: Regression discontinuity applied to population-based birth registry data. SETTING: British Columbia, Canada, 2008-2018. POPULATION: Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. METHODS: During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut-point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). MAIN OUTCOME MEASURES: Our primary outcome was a composite of newborn respiratory distress or in-hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in-hospital death. RESULTS: Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut-point were exposed. The risk of newborn respiratory distress or in-hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53-0.90; risk difference [RD] -12 cases per 100 births, 95% CI -20 to -4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in-hospital death (RR 0.89, 95% CI 0.70-1.13; RD -4.2 per 100, 95% CI -13 to +4.2). CONCLUSIONS: Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins.

Subgroup effects should be examined using both relative and absolute effect measures.

Treatment effects can be measured on the relative scale (eg, risk ratios, odds ratios) or the absolute scale (eg, risk differences). If the baseline risk of an outcome is different between subgroups, the effect of the treatment will differ between subgroups on at least one scale (relative, absolute, or both). We illustrate this using two examples from the literature where only relative effects were estimated, but conclusions about subgroup differences would likely have changed had absolute effects also been considered. To identify all meaningful subgroup differences, researchers and clinicians should compare effects on the relative and absolute scale.

Technical Update No. 439: Antenatal Corticosteroids at Late Preterm Gestation.

OBJECTIVE: To update recommendations for administration of antenatal corticosteroids in the late preterm period. TARGET POPULATION: Pregnant individuals at risk of preterm birth from 340 to 366 weeks gestation. OPTIONS: Administration or non-administration of a single course of antenatal corticosteroids at 340 to 366 weeks gestation. OUTCOMES: Neonatal morbidity (respiratory distress, hypoglycemia), long-term neurodevelopment, and other long-term outcomes (growth, cardiac/metabolic, respiratory). BENEFITS, HARMS, AND COSTS: Administration of antenatal corticosteroids from 340 to 366 weeks gestation decreases the risk of neonatal respiratory distress but increases the risk of neonatal hypoglycemia. The long-term impacts of antenatal corticosteroid administration from 340 to 366 weeks gestation are uncertain. EVIDENCE: For evidence on the neonatal effects of antenatal corticosteroid administration at late preterm gestation, we summarized evidence from the 2020 Cochrane review of antenatal corticosteroids and combined this with evidence from published randomized trials identified by searching Ovid MEDLINE from January 1, 2020, to May 11, 2022. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on neurodevelopmental outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on neurodevelopmental outcomes using the following sources: (1) the 2020 Cochrane review; and (2) evidence obtained by searching Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to January 5, 2022. We did not apply date or language restrictions. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on other long-term outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on other long-term outcomes by combining findings from the 2020 Cochrane review with evidence obtained by searching Ovid MEDLINE for observational studies related to long-term cardiometabolic, respiratory, and growth effects of antenatal corticosteroids from inception to October 22, 2021. We reviewed reference lists of included studies and relevant systematic reviews for additional references. See Appendix A for search terms and summaries. 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 B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Maternity care providers, including midwives, family physicians, and obstetricians. SUMMARY STATEMENTS: RECOMMENDATIONS.

The Impact of Cannabis Decriminalization and Legalization on Road Safety Outcomes: A Systematic Review.

INTRODUCTION: There is substantial debate concerning the impact of cannabis decriminalization and legalization on road safety outcomes. METHODS: Seven databases were systematically searched: Embase, MEDLINE, and PsycINFO through Ovid as well as Web of Science Core Collection, SafetyLit, Criminal Justice Database (ProQuest), and Transport Research International Documentation (from inception to June 16, 2021). Eligible primary studies examined group-level cannabis decriminalization or legalization and a road safety outcome in any population. RESULTS: A total of 65 reports of 64 observational studies were eligible, including 39 that applied a quasi-experimental design. Studies examined recreational cannabis legalization (n=50), medical cannabis legalization (n=22), and cannabis decriminalization (n=5). All studies except 1 used data from the U.S. or Canada. Studies found mixed impacts of legalization on attitudes, beliefs, and self-reported driving under the influence. Medical legalization, recreational legalization, and decriminalization were associated with increases in positive cannabis tests among drivers. Few studies examined impacts on alcohol or other drug use, although findings suggested a decrease in positive alcohol tests among drivers associated with medical legalization. Medical legalization was associated with reductions in fatal motor-vehicle collisions, whereas recreational legalization was conversely associated with increases in fatal collisions. DISCUSSION: Increased cannabis positivity may reflect changes in cannabis use; however, it does not in itself indicate increased impaired driving. Subgroups impacted by medical and recreational legalization, respectively, likely explain opposing findings for fatal collisions. More research is needed concerning cannabis decriminalization; the impacts of decriminalization and legalization on nonfatal injuries, alcohol and other drugs; and the mechanisms by which legalization impacts road safety outcomes.

Antenatal Corticosteroids and Neonatal Outcomes in Twins: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess whether antenatal corticosteroid treatment is associated with improved neonatal outcomes in twins. DATA SOURCES: We searched MEDLINE, PubMed, EMBASE, and the Cochrane Library, from inception through August 12, 2021. We did not search ClinicalTrials.gov because our inclusion criteria were restricted to nonrandomized studies. METHODS OF STUDY SELECTION: Records (n=7,802) were screened in Rayyan by two independent reviewers. We included all nonrandomized studies that compared antenatal corticosteroid treatment with no treatment in twins. Our outcomes of interest were neonatal mortality, respiratory distress syndrome (RDS), intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity. TABULATION, INTEGRATION, AND RESULTS: We used the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) to assess risk of bias. We performed random-effects meta-analyses of estimates from studies without critical risk of bias due to confounding, and reported summary adjusted odds ratios (aORs) and 95% CIs. Eighteen cohort studies (that reported on 33,152 neonates) met inclusion criteria. Sixteen studies restricted to preterm gestational ages, and 11 defined exposed neonates based on an optimal corticosteroid administration-to-birth interval. Limitations due to confounding and selection bias were common concerns for the risk-of-bias assessments (n=14 at critical or higher), and 11 studies did not account for clustering within twin pairs in their analyses. All included studies had at least moderate risk of bias. Meta-analysis showed that antenatal corticosteroid administration was associated with lower odds of neonatal mortality (aOR 0.59, 95% CI 0.43-0.80, I2 69%, five studies, 20,312 neonates) and RDS (aOR 0.70, 95% CI 0.57-0.86, I2 67%, seven studies, 20,628 neonates) in twins. Results were inconclusive for the other outcomes. CONCLUSION: Evidence from nonrandomized studies suggests antenatal corticosteroids are associated with lower incidence of neonatal mortality and RDS in twins. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020205302.

Antenatal corticosteroid administration and attention-deficit/hyperactivity disorder in childhood: a regression discontinuity study.

BACKGROUND: Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34-36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies. METHODS: We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks' gestation in 2000-2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000-2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks' gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders. RESULTS: Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks' gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI -2.5 to 5.7). INTERPRETATION: We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome.

Molecular characterization and evolution of carnivorous sundew (Drosera rotundifolia L.) class V ß-1,3-glucanase.

MAIN CONCLUSION: A gene for ß-1,3-glucanase was isolated from carnivorous sundew. It is active in leaves and roots, but not in digestive glands. Analyses in transgenic tobacco suggest its function in germination. Ancestral plant ß-1,3-glucanases (EC 3.2.1.39) played a role in cell division and cell wall remodelling, but divergent evolution has extended their roles in plant defense against stresses to decomposition of prey in carnivorous plants. As available gene sequences from carnivorous plants are rare, we isolated a glucanase gene from roundleaf sundew (Drosera rotundifolia L.) by a genome walking approach. Computational predictions recognized typical gene features and protein motifs described for other plant ß-1,3-glucanases. Phylogenetic reconstructions suggest strong support for evolutionary relatedness to class V ß-1,3-glucanases, including homologs that are active in the traps of related carnivorous species. The gene is expressed in sundew vegetative tissues but not in flowers and digestive glands, and encodes for a functional enzyme when expressed in transgenic tobacco. Detailed analyses of the supposed promoter both in silico and in transgenic tobacco suggest that this glucanase plays a role in development. Specific spatiotemporal activity was observed during transgenic seed germination. Later during growth, the sundew promoter was active in marginal and sub-marginal areas of apical true leaf meristems of young tobacco plants. These results suggest that the isolated glucanase gene is regulated endogenously, possibly by auxin. This is the first report on a nuclear gene study from sundew.

Plant chitinase responses to different metal-type stresses reveal specificity.

KEY MESSAGE: Chitinases in Glycine max roots specifically respond to different metal types and reveal a polymorphism that coincides with sensitivity to metal toxicity. Plants evolved various defense mechanisms to cope with metal toxicity. Chitinases (EC 3.2.1.14), belonging to so-called pathogenesis-related proteins, act as possible second line defense compounds in plants exposed to metals. In this work their activity was studied and compared in two selected soybean (Glycine max L.) cultivars, the metal-tolerant cv. Chernyatka and the sensitive cv. Kyivska 98. Roots were exposed to different metal(loid)s such as cadmium, arsenic and aluminum that are expected to cause toxicity in different ways. For comparison, a non-metal, NaCl, was applied as well. The results showed that the sensitivity of roots to different stressors coincides with the responsiveness of chitinases in total protein extracts. Moreover, detailed analyses of acidic and neutral proteins identified one polymorphic chitinase isoform that distinguishes between the two cultivars studied. This isoform was stress responsive and thus could reflect the evolutionary adaptation of soybean to environmental cues. Activities of the individual chitinases were dependent on metal type as well as the cultivar pointing to their more complex role in plant defense during this type of stress.

Glucan-rich diet is digested and taken up by the carnivorous sundew (Drosera rotundifolia L.): implication for a novel role of plant ß-1,3-glucanases.

Carnivory in plants evolved as an adaptation strategy to nutrient-poor environments. Thanks to specialized traps, carnivorous plants can gain nutrients from various heterotrophic sources such as small insects. Digestion in traps requires a coordinated action of several hydrolytic enzymes that break down complex substances into simple absorbable nutrients. Among these, several pathogenesis-related proteins including ß-1,3-glucanases have previously been identified in digestive fluid of some carnivorous species. Here we show that a single acidic endo-ß-1,3-glucanase of ~50 kDa is present in the digestive fluid of the flypaper-trapped sundew (Drosera rotundifolia L.). The enzyme is inducible with a complex plant ß-glucan laminarin from which it releases simple saccharides when supplied to leaves as a substrate. Moreover, thin-layer chromatography of digestive exudates showed that the simplest degradation products (especially glucose) are taken up by the leaves. These results for the first time point on involvement of ß-1,3-glucanases in digestion of carnivorous plants and demonstrate the uptake of saccharide-based compounds by traps. Such a strategy could enable the plant to utilize other types of nutritional sources e.g., pollen grains, fungal spores or detritus from environment. Possible multiple roles of ß-1,3-glucanases in the digestive fluid of carnivorous sundew are also discussed.