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.

Maternal, Fetal, and Neonatal Outcomes of Elective Fetal Reduction Among Multiple Gestation Pregnancies: A Systematic Review.

OBJECTIVE: To review the existing literature on fetal and maternal health outcomes following elective pregnancy reduction. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register. STUDY SELECTION: Studies involving women pregnant with dichorionic twins, trichorionic triplets, or quadra-chorionic quadruplets who underwent elective fetal reduction of 1 or more fetuses to reduce the risks associated with multiple gestation pregnancies. DATA EXTRACTION: The main fetal health outcomes measured were gestational age at delivery, preterm birth, miscarriage, birth weight, and small for gestational age at delivery. The main maternal health outcomes measured were gestational diabetes, hypertensive disorders of pregnancy, and cesarean delivery. DATA SYNTHESIS: Of 7678 studies identified, 24 were included (n = 425 dichorionic twin pregnancies, n = 2753 trichorionic triplet pregnancies, and n = 111 quadra-chorionic quadruplet pregnancies). Fifteen studies (62.5%) did not report maternal health outcomes, while every study reported at least 1 fetal health outcome. Fetal reduction was associated with higher gestational age at birth, lower preterm birth, higher birth weight, and lower rates of small for gestational age infants and intrauterine growth restriction. No consistent pattern was observed for miscarriage and neonatal mortality rates. Following fetal reduction, cesarean delivery rates were lower in most studies. There were no appreciable trends with respect to gestational diabetes or hypertensive disorders of pregnancy. CONCLUSION: Fetal reduction reliably optimizes gestational age at birth and neonatal birth weight. Miscarriage rates and other adverse procedural outcomes did not increase following transabdominal reduction. Further research on maternal outcomes is needed given a paucity of information in the literature.

An audit of outcome in intravascular transfusions using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis.

INTRODUCTION: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). METHODS: Over an 8-year period, 1997-2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19-43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23-29 weeks). RESULTS: A median number of three IUT were performed in each fetus (IQR 2-5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6-8.8 g%) (73% < or =5 SD and 27% < or =2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were 'transient' bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21-38) with a birth weight centile of 50 (range 3-90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher's exact test, p < 0.47). CONCLUSION: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset.

Summary CD4+ CD25+ T regulatory cells (TReg), suppress antigen-specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune-suppressive TReg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of TReg cells was assessed in the blood of 25 non-pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating TReg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25+ CD4+ cells expressed FoxP3 messenger RNA, a marker of TReg cells, and suppressed proliferative responses of autologous CD4+ CD25- T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of TReg cells which may be important in maintaining materno-fetal tolerance.