Association Between Maternal Body Mass Index and Fetal Acidosis in Term Twin Pregnancies: A Retrospective Cohort Study.

OBJECTIVES: Given the increased risk of fetal acidosis in singleton neonates born to pregnant people with an elevated BMI, our objective was to evaluate the association between pre-pregnancy/first-trimester BMI and fetal acidosis among term twin pregnancies. METHODS: Retrospective study of pregnant people with twin gestation and their term infants admitted to our centre between 2014 and 2019. Using a generalized estimating equation, the association between maternal BMI and fetal acidosis was determined using odds ratios (ORs) with 95% CIs. A two-sided P < 0.05 was considered significant. RESULTS: A total of 275 pregnant people and 550 infants were analyzed. The number (%) of pregnancies in each BMI class were 10 (4%) underweight, 155 (56%) normal weight, 66 (24%) overweight, 22 (8%) class I, 9 (3%) class II, and 13 (5%) class III. The prevalence of maternal diabetes and hypertension was highest in class III (31%) and class II (44%), respectively. Fetal acidosis was diagnosed in 35 (6%) infants. After adjusting for confounders (maternal age, diabetes, and hypertension), infants born to those with elevated BMI did not have increased odds of fetal acidosis compared to those born to underweight and normal weight group (OR 1.29; 95% CI 0.38-4.41 for class I, P = 0.67 and OR 2.80; 95% CI 0.62-12.62 for the combined classes II and III, P = 0.18). CONCLUSIONS: Maternal BMI was not associated with fetal acidosis in term twin pregnancies. Further research is required to corroborate study findings due to small sample size.

Eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials.

To describe the eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials (RCTs). We screened citations published 2017-2019 in the three highest impact psychiatry and five highest impact general medicine journals. We excluded male, pediatric, geriatric, and postmenopausal-focused RCTs and publications reporting subgroup, pooled, or secondary analyses of RCTs. We reviewed appendices, protocols, and registries for additional data. In total 108 RCTs were included. Three (2.8%) permitted enrollment of pregnant women; 59/108 (55%) and 46/108 (43%) explicitly excluded pregnant women or did not report pregnancy inclusion criteria, respectively. All RCTs including pregnant women evaluated non-pharmacological interventions for depression during pregnancy or postpartum. Among RCTs excluding pregnant women, 5/59 (8.5%) provided a rationale for exclusion. Contraception and/or negative pregnancy testing were required for women with reproductive capacity in 31/59 (53%). Three (2.8%) RCTs permitted enrollment of breastfeeding women and 3/41 (7.3%) RCTs excluding breastfeeding women provided a rationale for exclusion. This study demonstrates a major gap in psychiatry research involving pregnant and breastfeeding women. A shift from exclusion by default to inclusion and integration of this population into the clinical research agenda is needed to ensure they receive evidence-based care for mental illness.

A review of COVID-19 therapeutics in pregnancy and lactation.

Pregnant people have an elevated risk of severe COVID-19-related complications compared to their non-pregnant counterparts, underscoring the need for safe and effective therapies. In this review, we summarize published data on COVID-19 therapeutics in pregnancy and lactation to help inform clinical decision-making about their use in this population. Although no serious safety signals have been raised for many agents, data clearly have serious limitations and there are many important knowledge gaps about the safety and efficacy of key therapeutics used for COVID-19. Moving forward, diligent follow-up and documentation of outcomes in pregnant people treated with these agents will be essential to advance our understanding. Greater regulatory push and incentives are needed to ensure studies to obtain pregnancy data are expedited.

Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials.

BACKGROUND: There is an urgent need to prioritize and expedite the inclusion of pregnant and breastfeeding women in research. Characterizing trials that have successfully included these populations could inform the design and execution of future studies. In addition, up-to-date data on their inclusion in clinical research could assist in setting benchmarks, establishing targets, and monitoring progress toward more equitable inclusion. OBJECTIVE: This study aimed to characterize the eligibility and enrollment of pregnant and breastfeeding women in randomized controlled trials evaluating interventions for nonobstetrical conditions experienced by, but not limited to, these populations. STUDY DESIGN: We developed a literature search in collaboration with an information specialist. We included randomized controlled trials published between 2017 and 2019 in the 5 highest-impact general medicine journals and the 3 highest-impact specialty journals in cardiovascular disease, critical care, general infectious diseases, HIV, and psychiatry. We included randomized controlled trials that evaluated screening, diagnosis, prevention, or treatment of nonobstetrical medical conditions. We excluded randomized controlled trials exclusively focused on males, pediatrics, geriatrics, oncology, or postmenopausal women, and publications reporting subgroup, pooled, or follow-up analyses of previously published randomized controlled trials. We screened titles and abstracts independently and in duplicate, with discrepancies resolved by a third reviewer. We entered data into a standardized electronic case report form. We reviewed study protocols, appendices, and trial registries for additional data. RESULTS: Of the 1333 randomized controlled trials, pregnant and breastfeeding women were eligible for 13 (1.0%) and 6 (0.5%), respectively. Pregnancy and breastfeeding eligibility criteria were not addressed in 383 of 1333 (28.7%) and 710 of 1333 (53.3%) randomized controlled trials, respectively. In total, 102 of 937 (10.9%) and 33 of 617 (5.3%) randomized controlled trials that explicitly excluded pregnant and breastfeeding women documented the rationale. Most studies excluding pregnant women (542/937; 57.8%) required at least 1 method of contraception and/or pregnancy testing as part of trial participation for women with reproductive capacity. Among the 13 randomized controlled trials that allowed inclusion of pregnant women, 3 restricted eligibility to specific trimesters. Two randomized controlled trials enrolled pregnant women after the first year of the study following interim review of safety results in nonpregnant participants. Four randomized controlled trials reported the number of pregnant women enrolled, which ranged from 0.7% to 3.4% of the study population. None of the studies reported on pregnancy or perinatal outcomes. Compared with randomized controlled trials that excluded pregnant women, those including them more commonly had an infectious disease focus (12/13 [92.3%] vs 270/937 [28.8%]; p<.0001), including HIV (5/13 [38.5%] vs 96/937 [10.2%]; p=.0079), enrolled participants in sub-Saharan Africa (5/13 [38.5%] vs 111/937 [11.8%]; p=.0143), and had exclusively nonindustry sponsorship (13/13 [100%] vs 559/937 [59.7%]; p=.0025); inclusion varied by study phase, randomization level, and intervention type. CONCLUSION: This study illustrates a major inequity in research involving pregnant and breastfeeding women. As new health challenges arise, including novel pandemics, and the research community mobilizes to develop therapies and innovate in patient care, it is crucial that pregnant and breastfeeding women not be left behind. Greater regulatory support, in the form of explicit requirements and incentives, will be needed to ensure these populations are integrated into the research agenda.

Characterizing the inclusion of pregnant and breastfeeding people in infectious diseases randomized controlled trials: a targeted literature review.

OBJECTIVES: Severe complications of infectious diseases can occur during pregnancy. Evidence-based prevention and treatment strategies are critical to improve maternal and neonatal health outcomes. Despite this medical need, pregnant and breastfeeding people have been systematically excluded from biomedical research. The objective of this study was to characterize representation of pregnant and breastfeeding people in randomized controlled trials (RCTs) evaluating a broad range of interventions for infectious diseases. METHODS: Pregnancy and breastfeeding inclusion criteria were examined in infectious diseases RCTs published between 1 January 2017, and 31 December 2019, in the top five highest impact general medicine and the top three highest impact infectious diseases and HIV journals. RESULTS: Of 376 RCTs, 5.3% and 1.9% included pregnant and breastfeeding people, respectively. Justification for exclusion was documented in 36/271 (13.3%) studies that explicitly excluded pregnant people. Most studies excluding pregnant people (177/271, 65.3%) required at least one form of contraception, abstinence and/or negative pregnancy test(s) as part of participation. Only 11/271 (4.1%) studies excluding pregnant people allowed participants to continue the intervention if unintended pregnancy occurred during the study. When both pregnant and non-pregnant people were eligible, pregnant people made up <3% of participants. Only 2/48 (4.2%) vaccine studies included pregnant people; 13/234 (5.5%) drug studies included pregnant people. All studies of procedures, devices, behaviour/education and supplements/vitamins explicitly excluded or did not address pregnancy eligibility criteria. Only 2/20 (10.0%) RCTs including pregnant people collected pharmacokinetic data. DISCUSSION: This study demonstrates widespread exclusion of pregnant and breastfeeding people from infectious disease RCTs.

Role of maternal COVID-19 vaccination in providing immunological protection to the newborn.

Pregnant and postpartum individuals are known to have an elevated risk of severe COVID-19 compared with their non-pregnant counterparts. Vaccination is the most important intervention to protect these populations from COVID-19-related morbidity and mortality. An added benefit of maternal COVID-19 vaccination is transfer of maternal immunity to newborns and infants, for whom a vaccine is not (yet) approved. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific binding and neutralizing antibodies are present in infant cord blood and breast milk following natural maternal infection and transfer of maternal immunity following COVID-19 vaccination is an area of active research. In this review, we synthesize the available research, discuss knowledge gaps, and outline factors that should be evaluated and reported when studying the transfer of maternal immunity following COVID-19 vaccination. The data reviewed herein suggest that maternal SARS-CoV-2-specific binding antibodies are efficiently transferred via the placenta and breast milk following maternal mRNA COVID-19 vaccination. Moreover, antibodies retain strong neutralizing capacity. Antibody concentrations appear to be at least as high in infant cord blood as in the maternal serum, but lower in breast milk. Breast milk IgA rises rapidly following maternal vaccination, whereas IgG rises later but may persist longer. At least two COVID-19 vaccine doses appear to be required to reach maximal antibody concentrations in cord blood and breast milk. There is no indication that infants consuming breast milk from vaccinated mothers experience serious adverse effects, although follow-up is limited. No clear pattern has emerged regarding changes in milk supply following maternal vaccination. The heterogeneity in important methodological aspects of reviewed studies underscores the need to establish standard best practices related to research on the transfer of maternal COVID-19 vaccine-induced immunity.

Intranasal Fentanyl for Procedural Analgesia in Preterm Infants.

Background: Despite the availability of evidence-based analgesic strategies, neonatal pain management continues to be suboptimal. Intranasal (IN) fentanyl is an alternative pharmacotherapy for procedural pain in neonatal units. The objective was to evaluate the effectiveness and safety of IN fentanyl for procedural pain in preterm infants. Methods: A retrospective cohort study was conducted in infants who received IN fentanyl between May 2019 and December 2020 at an academic neonatal intensive care unit. Main outcome measures were pain responses, physiological parameters before and up to 60 min after IN fentanyl administration, and adverse events. Paired t-test and analysis of variance were used to compare pain scores and physiological parameters, respectively. Results: Thirteen infants received IN fentanyl on 22 occasions. Median (interquartile range [IQR]) gestational age and birthweight were 27 (25, 27.6) weeks and 850 (530, 1,030) grams, while median (IQR) post-menstrual age and weight were 30.9 (28.9, 32.9) weeks and 1,280 (945, 1,623) grams at the time of IN fentanyl administration. IN fentanyl was most used for lumbar puncture (55%) followed by insertion of epicutaneo-caval catheters (27%). There was a difference between the mean pre- and post-procedure Premature Infant Pain Profile scores of 1.3 (95% CI = 0.07, 2.5; p = 0.04). Physiological parameters did not differ before and up to 60 min post IN fentanyl administration (p > 0.05). Two adverse events (one apnea and one desaturation) were noted. Conclusion: In our limited experience, IN fentanyl appears to be an alternative pharmacotherapy for procedural pain management in the absence of intravenous access in preterm infants.

Detecting Delirium in Hospitalized Elderly Patients: A Review of Practice Compliance.

Background: The Ontario Senior Friendly Hospital Strategy recognizes delirium prevention and management as a top priority and recommends implementation of delirium screening as well as management protocols. This strategy proposes that hospitals monitor 2 specific indicators: (1) rate of baseline delirium screening and (2) rate of hospital-acquired delirium. Objective: To (1) determine compliance with the Ontario Senior Friendly Hospital Strategy indicators; (2) describe the use of pharmacological and nonpharmacological interventions for management of delirious patients; and (3) identify predictors of screening compliance. Methods: We conducted a retrospective review of patients aged ≥65 years admitted to 4 different inpatient units for ≥48 hours. Data were extracted for 7 two-month time blocks chosen between September 2010 and October 2013, following the implementation of various geriatric and delirium related initiatives at the hospital. Results: A total of 786 patients met study inclusion criteria. Overall, 68.2% had baseline delirium screening (indicator 1), with screening rates increasing over time (P < .001). Inpatient unit and year of study were both statistically significant predictors of delirium screening. Among those screened, the overall rate of hospital-acquired delirium was 17.2% (indicator 2). Early mobilization and device removal were the most common nonpharmacological interventions, while initiation of an antipsychotic and discontinuation of benzodiazepines were the most common pharmacological interventions. Conclusions: Although the rates of baseline delirium screening have significantly increased over the sampled time period, rates are still below the averages referenced in other literature. Our study suggests we need additional efforts to improve compliance with delirium screening in our institution.