Acute kidney injury that occurs during pregnancy or in the post-partum period (PR-AKI) is a serious obstetric complication with risk of significant associated maternal and fetal morbidity and mortality. Recent data indicates that the incidence of PR-AKI is increasing, although accurate calculation is limited by the lack of a uniform diagnostic criteria that is validated in pregnancy. Hypertensive and thrombotic microangiopathic disorders of pregnancy have been identified as major contributors to the burden of PR-AKI. As is now accepted regarding preeclampsia, HELLP syndrome and atypical hemolytic uremic syndrome, it is believed that PR-AKI may have long-term renal, cardiovascular and neurocognitive consequences that persist beyond the post-partum period. Further research regarding PR-AKI could be advanced by the development of a pregnancy-specific validated definition and classification system; and the establishment of refined animal models that would allow researchers to further elucidate the mechanisms and sequelae of the disorder.

Using an animal model of hemolysis elevated liver enzymes low platelets (HELLP) that has systemic inflammation and neuroinflammation we wanted to determine if blood brain barrier (BBB) permeability, cerebral edema, vascular tone, and occludin expression were altered in pregnant rats. Anti-angiogenic proteins sFlt-1 and sEng (4.7 and 7 µg/kg/day, respectively) were chronically infused into normal pregnant (NP) rats beginning on gestational day 12 via a mini-osmotic pump. On gestational day 19, blood pressure was measured via a carotid catheter and brains were collected. BBB permeability was assessed in select brain regions from rats infused with 0.5 mg/mL Texas Red Dextran and phenylephrine. Occludin, sFlt-1, and sEng were analyzed via western blot or ELISA. Infusion of sFlt-1 and sEng into NP rats increased hemolysis and liver enzymes, and decreased platelets and led to hypertension. HELLP rats had significant impairment in the myogenic response and increased BBB permeability in the posterior cortex and brainstem. Brain water content in the posterior cortex was increased and sEng protein expression in the brainstem was significantly increased in HELLP rats. The results from this study suggest that a peripheral anti-angiogenic imbalance during pregnancy is associated with decreased myogenic tone, vasogenic edema, and an increase in BBB permeability, but not anti-angiogenic imbalance in the brain.

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Introduction Marfan syndrome is a connective tissue disorder caused by mutations in the fibrillar FBN‐1 gene. Aortic dissection and rupture are major causes of morbidity and mortality and are of special concern during pregnancy. Materials and Methods The authors report four cases of aortic root repair with preservation of the native aortic valve that have has created a discussion between cardiothoracic surgeons, obstetricians, and gynecologists regarding the best care for Marfan syndrome patients. We present these cases here with a review of the literature. Results Surgery of the aorta and valves in Marfan syndrome is less risky than in previous eras and surgical management guidelines are generally accepted. Yet, we may be unnecessarily referring women to terminate pregnancies or to avoid pregnancy. We believe there may be alternative options for these patients. Conclusions Marfan syndrome during pregnancy can be navigated with preconception counseling, antepartum care, and close postpartum follow‐up involving an appropriate multidisciplinary team.

Among women presenting at resource-limited settings with a history suspicious of preterm premature rupture of membranes between 24 and 36 weeks of gestation, our analysis provides evidence suggesting that PAMG-1 is the most cost-effective testing strategy.

Background The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20–40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome. Methods On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 μg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 μg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey’s test for post hoc analysis. Results Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34). Conclusion The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.

Certainly, the reduction of adverse outcomes would be improved with early knowledge of Marfan syndrome in the mother which would aid in preparation and clinical consideration during the perioperative period and, of course, in general. Each of the cases presented in our paper had established diagnoses and lends weight to this suggestion. The work by Meijboom et al 1 was indeed encouraging as we constructed our recommendations for evaluating the risk to a potential mother. The conclusion of that paper, as we discussed in our review, was that pregnancy is likely safe up to an aortic root diameter of 45 mm 2 , and speaks to the value of early detection of disease. 1 The recently released work by Dr Harky identifies the Marfans population in England and Wales undergoing planned and nonplanned aortic root surgery, and assesses outcomes. While it does not specifically address Marfans in pregnancy, it reported satisfactory outcomes for 306 Marfans patients, 100 of which were female, and suggests, as our paper does, that Aortic root surgery in this cohort remains an evolving but achievable challenge. 2 The call for an international registry to assess the work up and outcomes of this patient population is a worthy one which we would be happy to participate in.

INTRODUCTION: During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL) which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP decreases inflammation, placental apoptosis, improves endothelial damage and improves hypertension. METHODS: On gestational day (GD) 12 rats were chronically infused with placental anti-angiogenic factors sFlt-1 and sEng to induce HELLP. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another groups of NP and HELLP rats on GD13 was used as a control for FasL antibody. and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis and the degree of placental debris activation of endothelial cells. RESULTS: Administration of MFL4 to HELLP rats significantly decreased blood pressure compared to HELLP rats and HELLP+IgG rats and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were attenuated in response to MFL4 as were levels of placental and circulating TNF-alpha when compared to HELLP rats and HELLP+IgG rats. Endothelial cells exposed to placental debris and media from HP+MFL4 rats secreted significantly less endothelin-1 compared to stimulated endothelial cells from HELLP placentas. CONCLUSIONS: Neutralization of FasL is associated with decreased MAP, improvement in placental inflammation and endothelial damage in a model of HELLP syndrome.