The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study.

BACKGROUND: Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. OBJECTIVE: This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. STUDY DESIGN: This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. RESULTS: Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. CONCLUSION: This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.

Is it possible to estimate the minimal clinically important treatment effect needed to change practice in preterm birth prevention? Results of an obstetrician survey used to support the design of a trial.

BACKGROUND: Sample sizes for obstetrical trials are often based on the opinion of investigators about clinically important effect size. We surveyed Canadian obstetricians to investigate clinically important effect sizes required before introducing new treatments into practice to prevent preterm birth. METHODS: Questionnaires were mailed to practicing obstetricians, asking the magnitude of pregnancy prolongation required to introduce treatments into practice. The three prophylactic treatments were of increasing invasiveness: vaginal progesterone, intramuscular progesterone, and cervical cerclage. We also asked about the perceived most relevant outcome measures for obstetrical trials and current obstetrical practice in preterm birth prevention. RESULTS: 544/1293(42.1%) completed questionnaires were received. The majority of respondents required one or two weeks' increase in length of gestation before introducing vaginal (372,77.1%), and intramuscular progesterone(354,67.9%). At least three weeks increase was required before introducing prophylactic cervical cerclage(326,62.8%). Clinicians who already used a treatment required a smaller difference before introducing it into practice. Decreasing neonatal morbidity was cited as the most important outcome for obstetrical trials (349,72.2%). CONCLUSION: Obstetricians would require a larger increase in treatment effect before introducing more invasive treatments into practice. Although infant morbidity was perceived as a more important outcome, clinicians appeared willing to change practice on the basis of prolongation of pregnancy, a surrogate outcome. We found that there is not a single minimum clinically important treatment effect that will influence all practising clinicians: rather the effect size that will influence physicians is affected by the nature of the treatment, the reported outcome measure and the clinician's own current clinical practice.

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review.

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.

Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy.

Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. We investigated the dy mouse model, which has congenital muscular dystrophy due to a defect in laminin alpha 2, for evidence of cochlear dysfunction. Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate 3-month-old homozygous dy/dy and age-matched C57 control mice. The average ABR thresholds to tone-burst stimuli for four frequencies (4, 8, 16, and 32 kHz) were determined and statistically compared by ANOVA. The dy/dy mice demonstrated elevated auditory thresholds ranging from 25 to 27 dB at each frequency tested (p<0.0001). Anatomic evaluations of the ears revealed pathology ranging from extensive connective tissue infiltration within the inner ear to possible minor defects in the cells of the organ of Corti. These anatomic and physiologic observations suggest that the extracellular matrix protein laminin plays a crucial role in normal cochlear function. Furthermore, the dy congenital muscular dystrophy mouse offers a novel model for evaluation of sensorineural hearing loss associated with muscular dystrophy.