Guideline No. 441: Antenatal Fetal Health Surveillance.

OBJECTIVE: To summarize the current evidence and to make recommendations for antenatal fetal health surveillance (FHS) to detect perinatal risk factors and potential fetal decompensation in the antenatal period and to allow for timely intervention to prevent perinatal morbidity and/or mortality. TARGET POPULATION: Pregnant individuals with or without maternal, fetal, or pregnancy-associated perinatal risk factors for antenatal fetal decompensation. OPTIONS: To use basic and/or advanced antenatal testing modalities, based on risk factors for potential fetal decompensation. OUTCOMES: Early identification of potential fetal decompensation allows for interventions that may support fetal adaptation to maintain well-being or expedite delivery. BENEFITS, HARMS, AND COSTS: Antenatal FHS in pregnant individuals with identified perinatal risk factors may reduce the chance of adverse outcomes. Given the high false-positive rate, FHS may increase unnecessary interventions, which may result in harm, including parental anxiety, premature or operative birth, and increased use of health care resources. Optimization of surveillance protocols based on evidence-informed practice may improve perinatal outcomes and reduce harm. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to January 2022, using medical subject headings (MeSH) and key words related to pregnancy, fetal monitoring, fetal movement, stillbirth, pregnancy complications, and fetal sonography. This document represents an abstraction of the evidence rather than a methodological review. 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 of strong and weak recommendations). INTENDED AUDIENCE: All health care team members who provide care for or education to obstetrical patients, including maternal fetal medicine specialists, obstetricians, family physicians, midwives, nurses, nurse practitioners, and radiologists. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 441 : Surveillance prénatale du bien-être fœtal.

OBJECTIF: Résumer les données probantes actuelles et formuler des recommandations pour la surveillance prénatale du bien-être fœtal afin de détecter les facteurs de risque périnatal et toute potentielle décompensation fœtale et de permettre une intervention rapide en prévention de la morbidité et la mortalité périnatales. POPULATION CIBLE: Personnes enceintes avec ou sans facteurs maternels, fœtaux ou gravidiques associés à des risques périnataux et à la décompensation fœtale. OPTIONS: Utiliser des examens prénataux par technologie de base et/ou avancée en fonction des facteurs de risque de décompensation fœtale. RéSULTATS: La reconnaissance précoce de toute décompensation fœtale potentielle permet d'intervenir de façon à favoriser l'adaptation fœtale pour maintenir le bien-être ou à accélérer l'accouchement. BéNéFICES, RISQUES ET COûTS: Chez les personnes enceintes ayant des facteurs de risque périnatal confirmés, la surveillance du bien-être fœtal contribue à réduire le risque d'issue défavorable. Compte tenu du taux élevé de faux positifs, la surveillance du bien-être fœtal peut augmenter le risque d'interventions inutiles, ce qui peut avoir des effets nuisibles, dont l'anxiété parentale, l'accouchement prématuré ou assisté et l'utilisation accrue des ressources de soins de santé. L'optimisation des protocoles de surveillance d'après des pratiques fondées sur des données probantes peut améliorer les issues périnatales et réduire les effets nuisibles. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à janvier 2022, à partir de termes MeSH et de mots clés liés à la grossesse, à la surveillance fœtale, aux mouvements fœtaux, à la mortinaissance, aux complications de grossesse et à l'échographie fœtale. Le présent document est un résumé des données probantes et non pas une revue méthodologique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les membres de l'équipe de soins qui prodiguent des soins ou donnent de l'information aux patientes en obstétrique, notamment les spécialistes en médecine fœto-maternelle, les obstétriciens, les médecins de famille, les sages-femmes, les infirmières, les infirmières praticiennes et les radiologistes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review.

BACKGROUND: Sickle cell disease (SCD) is associated with hematologic complications including delayed hemolytic transfusion reactions (DHTRs) and pregnancy-related morbidity and mortality. Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells are destroyed. Further transfusions are avoided after a history of HS. Immunosuppressive agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesis-stimulating agents (ESA) in pregnant SCD patients. CASE REPORT: We present a case of a pregnant patient with SCD and a previous history of HS. HS prophylaxis was given before transfusion with corticosteroids, intravenous immunoglobulin, and rituximab. In addition, HU was continued during pregnancy to control SCD, along with the use of concomitant ESA to maintain adequate hemoglobin levels and avoid transfusion. We describe a multidisciplinary approach to pregnancy and delivery management including tailored anesthetic and obstetric planning. CONCLUSION: This is the first published case of HS prophylaxis in a pregnant SCD patient, with good maternal and fetal outcomes after transfusion. HU and ESAs were able to control SCD and mitigate anemia in lieu of prophylactic transfusions during pregnancy. Further prospective studies are necessary to elucidate the ideal management of pregnant SCD patients with a history of HS or other contraindications to chronic transfusion.

Myometrial Defect in a Subsequent Pregnancy After Uterine Artery Embolization for Postpartum Hemorrhage, in the Absence of Leiomyomas or Previous Uterine Surgery.

BACKGROUND: Pregnancy occurring after uterine artery embolization are often complicated by adverse fetal and obstetric outcomes. CASE: This report describes the case of a myometrial defect in a subsequent pregnancy after uterine artery embolization for postpartum hemorrhage. A 26-year-old G2, P2 woman had a vaginal delivery of twins 2 years earlier that required uterine artery embolization for postpartum hemorrhage. In this case, she presented at 183 weeks gestation with pelvic pain and an ultrasound scan revealing an area of myometrium measuring 3.2 mm. The myometrium progressively thinned to 0.7 mm at 32 weeks. After cesarean hysterectomy, pathologic examination revealed large myometrial defects separate from the placenta increta. CONCLUSION: Given the myometrial defects and placenta increta observed in a pregnancy after uterine artery embolization without documented fibroids or uterine surgery, consideration should be given to antenatal myometrial thickness surveillance.

The impact of maternal diabetes on birth to placental weight ratio and umbilical cord oxygen values with implications for fetal-placental development.

INTRODUCTION: We determined the impact of gestational diabetes (GDM) and pre-existing diabetes (DM) on birth/placental weight and cord oxygen values with implications for placental efficiency and fetal-placental growth and development. METHODS: A hospital database was used to obtain birth/placental weight, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA >34 weeks (N = 69,854). Oxygen saturation was calculated from the cord PO2 and pH data, while fetal O2 extraction was calculated from the oxygen saturation data. The effect of diabetic status on birth/placental weight and cord oxygen values was examined adjusting for covariates. RESULTS: Birth/placental weights were stepwise decreased in GDM and DM compared to non-diabetics with placentas disproportionally larger indicating decreasing placental efficiency. Umbilical vein oxygen was marginally increased in GDM but decreased in DM attributed to the previously reported hyper-vascularization in diabetic placentas with absorbing surface area of capillaries initially increased, but then constrained by increasing distance from maternal blood within the intervillous space. Umbilical artery oxygen was unchanged in GDM and DM, with fetal O2 extraction decreased in DM indicating that fetal O2 delivery must be increased relative to O2 consumption and likely due to increased umbilical blood flow. DISCUSSION: Increased villous density/hyper-vascularization in GDM and DM with placentas disproportionately larger and umbilical blood flow increased, are postulated to normalize umbilical artery oxygen despite increased birth weights and growth-related O2 consumption. These findings have implications for mechanisms signaling fetal-placental growth and development in diabetic pregnancies and differ from that reported with maternal obesity.

Gestational age impacts birth to placental weight ratio and umbilical cord oxygen values with implications for the fetal oxygen margin of safety.

BACKGROUND: We determined the impact of gestational age (GA) from near term to term to post-term on birth/placental weight ratio and cord oxygen values with implications for placental transport efficiency for oxygen, fetal O2 consumption relative to delivery or fractional O2 extraction, and oxygen margin of safety. MATERIALS AND METHODS: A hospital database was used to obtain birth/placental weight ratios, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA > 34 completed weeks (N = 69,852). Oxygen saturation was calculated from the cord PO2 and pH data, while fractional O2 extraction was calculated from the oxygen saturation data. The effect of GA grouping on birth/placental weight ratio, cord PO2, O2 saturation, and fractional O2 extraction values, was examined in all patients adjusting for pregnancy and labor/delivery covariates, and in a subset of low-risk patients. RESULTS: Birth/placental weight ratio and umbilical venous O2 values increased with advancing GA, supporting the conjecture of increasing placental transport efficiency for oxygen. However, umbilical arterial O2 values decreased while fractional O2 extraction increased with successive GA groupings, indicating that fetal O2 consumption must be increasing relative to delivery. CONCLUSIONS: Fetal O2 consumption can be seen as ever 'outgrowing' O2 delivery over the last weeks of pregnancy and leading to a continued lowering in systemic oxygen levels. While this lowering in oxygen may trigger feedback mechanisms with survival benefit, the 'oxygen margin of safety' will also be lowered increasing perinatal morbidity and mortality which appear to be hypoxia related.

14-3-3 mediated regulation of the tumor suppressor protein, RASSF1A.

Death receptor-dependent apoptosis is an important mechanism of growth control. It has been demonstrated that Ras association domain family protein 1A (RASSF1A) is a tumor suppressor protein involved in death receptor-dependent apoptosis. However, it is unclear how RASSF1A-mediated cell death is initiated. We have now detailed 14-3-3 dependent regulation of RASSF1A-mediated cell death. We demonstrate that basal association of RASSF1A with 14-3-3 was lost following stimulation with tumor necrosis factor alpha (TNFalpha) or TNFalpha related apoptosis inducing ligand (TRAIL). Subsequent to the loss of 14-3-3 association, RASSF1A associated with modulator of apoptosis (MOAP-1) followed by death receptor association with either TNFalpha receptor 1 (TNF-R1) or TRAIL receptor 1 (TRAIL-R1). 14-3-3 association required basal phosphorylation by the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta), on serine 175, 178, and 179. Mutation of these critical serines resulted in the loss of 14-3-3 association and earlier recruitment of RASSF1A to MOAP-1, TNF-R1, and TRAIL-R1. Furthermore, stable cells containing a triple serine mutant of RASSF1A [serine (S) 175 to alanine (A) [S175A], S178A, and S179A] resulted in increased basal cell death, enhanced Annexin V staining and enhanced cleavage of poly (ADP-ribose) polymerase (PARP) following TNFalpha stimulation when compared to stable cells containing wild type RASSF1A. RASSF1A-mediated cell death is, therefore, tightly controlled by 14-3-3 association.

Dynamics of RASSF1A/MOAP-1 association with death receptors.

RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis utilizing the Bax-interacting protein MOAP-1 (previously referred to as MAP-1). However, the dynamics of death receptor recruitment of RASSF1A and MOAP-1 are still not understood. We have now detailed recruitment to death receptors (tumor necrosis factor receptor 1 [TNF-R1] and TRAIL-R1/DR4) and identified domains of RASSF1A and MOAP-1 that are required for death receptor interaction. Upon TNF-alpha stimulation, the C-terminal region of MOAP-1 associated with the death domain of TNF-R1; subsequently, RASSF1A was recruited to MOAP-1/TNF-R1 complexes. Prior to recruitment to TNF-R1/MOAP-1 complexes, RASSF1A homodimerization was lost. RASSF1A associated with the TNF-R1/MOAP-1 or TRAIL-R1/MOAP-1 complex via its N-terminal cysteine-rich (C1) domain containing a potential zinc finger binding motif. Importantly, TNF-R1 association domains on both MOAP-1 and RASSF1A were essential for death receptor-dependent apoptosis. The association of RASSF1A and MOAP-1 with death receptors involves an ordered recruitment to receptor complexes to promote cell death and inhibit tumor formation.