Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4+ T cells expressing Foxp3, IFN-γ, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4+CD25high, CD4+CD127lowCD25+, and CD4+Foxp3+ cells was significantly higher in normal compared with preeclamptic pregnancies. CD4+CD25high and CD4+CD127lowCD25+ populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4+Foxp3+ cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4+CD127lowCD25+ Treg cells was not significantly different between the three study groups. The percentage of CD4+IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4+IL-10- and CD4+IFN-γ-producing cells remained unchanged. Consequently, the ratio of Foxp3+ Treg to IL-17-expressing CD4+ T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3+ expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-β receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4+ T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment.

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Regulatory T (Treg) cell expansion is required for tolerance of the semi-allogeneic fetus in healthy pregnancy and impaired in preeclampsia in humans. However, the reasons remain unknown. Herein, we show that expansion of CD4(+)Helios(-)Foxp3(+) adaptive Treg (iTreg) cells, rather than CD4(+)Helios(+)Foxp3(+) natural Treg cells, accounts for this expansion in healthy pregnancy. This expansion is even more pronounced in the decidua, where there is an overrepresentation of iTreg cells. In preeclampsia, however, there is impaired systemic iTreg cell expansion, associated with a lack of iTreg cell overrepresentation in the decidua. Because decidual antigen-presenting cells (APCs) may be important for iTreg cell induction, we studied decidual CD14(+) APCs using immunohistochemistry and flow cytometry. We show that decidual CD14(+)DC-SIGN(+) APCs are closely associated with Foxp3(+) Treg cells. Furthermore, CD14(+)DC-SIGN(+) cells display a distinct phenotype compared with their CD14(+)DC-SIGN(-) counterparts. In particular, they have increased expression of tolerogenic molecules, HLA-G, and immunoglobulin-like transcript 4. In vitro, CD14(+)DC-SIGN(+) APCs from healthy pregnant women induced iTreg cells significantly more efficiently than CD14(+)DC-SIGN(-) APCs. Conversely, in preeclampsia, both CD14(+)DC-SIGN(+) and CD14(+)DC-SIGN(-) APCs induced iTreg cells poorly. These results suggest that decidual CD14(+)DC-SIGN(+) APCs may play important roles in iTreg cell induction, a process that is defective in preeclampsia and likely contributes to its pathogenesis.

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ObjectiveEstimate the incidence of placenta accreta and describe risk factors, clinical practice and perinatal outcomes.DesignCase–control study.SettingSites in Australia and New Zealand with at least 50 births per year.ParticipantsCases were women giving birth (≥20 weeks or fetus ≥400 g) who were diagnosed with placenta accreta by antenatal imaging, at operation or by pathology specimens between 2010 and 2012. Controls were two births immediately prior to a case. A total of 295 cases were included and 570 controls.MethodsData were collected using the Australasian Maternity Outcomes Surveillance System.Primary and secondary outcome measuresIncidence, risk factors (eg, prior caesarean section (CS), maternal age) and clinical outcomes of placenta accreta (eg CS, hysterectomy and death).ResultsThe incidence of placenta accreta was 44.2/100 000 women giving birth (95% CI 39.4 to 49.5); however, this may overestimated due to the case definition used. In primiparous women, an increased odds of placenta accreta was observed in older women (adjusted OR (AOR) women≥40 vs <30: 19.1, 95% CI 4.6 to 80.3) and current multiple birth (AOR: 6.1, 95% CI 1.1 to 34.1). In multiparous women, independent risk factors were prior CS (AOR ≥2 prior sections vs 0: 13.8, 95% CI 7.4 to 26.1) and current placenta praevia (AOR: 36.3, 95% CI 14.0 to 93.7). There were two maternal deaths (case fatality rate 0.7%).Women with placenta accreta were more likely to have a caesarean section (AOR: 4.6, 95% CI 2.7 to 7.6) to be admitted to the intensive care unit (ICU)/high dependency unit (AOR: 46.1, 95% CI 22.3 to 95.4) and to have a hysterectomy (AOR: 209.0, 95% CI 19.9 to 875.0). Babies born to women with placenta accreta were more likely to be preterm, be admitted to neonatal ICU and require resuscitation.

A review of 212 cases of renal cell carcinoma diagnosed during a 40-year period revealed an increasing number of cases detected during imaging studies performed for nonurological reasons. These so-called incidentally detected renal cell carcinomas are increasing in incidence, generally of low stage and associated with significantly improved survival, and they constitute the majority of the patients with improved prognosis during the recent 2 decades. The clinical course and disease stage in patients who continue to present with symptoms of the disease have not changed in the last 40 years. These data suggest that with currently available treatments for renal cell carcinoma a principal method to improve the prognosis of this disease would be through earlier detection. Low disease incidence would mitigate against morphological screening but case finding techniques may prove useful.

SFT at 18-22 weeks gestation is better than BMI as a marker for obesity-related pregnancy outcomes. As SFT is considered a surrogate measure for visceral fat, these results suggest that central obesity is a stronger risk factor than general adiposity in pregnancy.