Narang, Kavita

Abstract Preeclampsia and other hypertensive disorders of pregnancy are major contributors to maternal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia. The body undergoes important physiological changes during pregnancy to allow for normal placental and fetal development. Several mechanisms have been proposed that may lead to preeclampsia, including abnormal placentation and placental hypoxia, impaired angiogenesis, excessive pro‐inflammatory response, immune system imbalance, abnormalities of cellular senescence, alterations in regulation and activity of angiotensin II, and oxidative stress, ultimately resulting in upregulation of multiple mediators of endothelial cell dysfunction leading to maternal disease. The clinical implications of preeclampsia are significant as there are important short‐term and long‐term health consequences for those affected. Preeclampsia leads to increased risk of preterm delivery and increased morbidity and mortality of both the developing fetus and mother. Preeclampsia also commonly leads to acute kidney injury, and women who experience preeclampsia or another hypertensive disorder of pregnancy are at increased lifetime risk of chronic kidney disease and cardiovascular disease. An understanding of normal pregnancy physiology and the pathophysiology of preeclampsia is essential to develop novel treatment approaches and manage patients with preeclampsia and hypertensive disorders of pregnancy. © 2023 American Physiological Society. Compr Physiol 13:4231‐4267, 2023.

AbstractPurposeTo report the longitudinal lung growth and prognosis of fetuses with severe left sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) in a single institution.MethodsFetal lung size (observed‐to‐expected lung area to head circumference [o/e‐LHR]) was measured in seven consecutive fetuses with isolated severe left‐sided CDH who underwent FETO. Fetal lung growth was used to prognosticate survival and need for ECMO.ResultsSeven consecutive fetuses had a FETO procedure in the timeframe of this study. A total of 44 longitudinal ultrasound were performed to evaluate lung development. FETO was performed at GA 28.5 ± 0.5 weeks. Five (71.4%) infants survived to one‐year follow‐up and ECMO was needed in three patients (42.8%). Fetal lung response was observed in all fetuses; mean o/e‐LHR increased from 22.5% ± 1.4 before FETO to 44.4% ± 9.8 before delivery. Infants who survived had a higher percentage of fetal lung growth (21.8%) than those who died (8.25%).ConclusionOur study supports the hypothesis that FETO promotes fetal lung growth in fetuses with severe left‐sided CDH, and the fetal pulmonary response seems to be associated with improved outcomes after the procedure.

Importance Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. Objective The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. Evidence Acquisition Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. Results This article summarizes management for each specific type of MC complication in a structured and clear manner. Conclusions Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery. Relevance Improve perinatal outcomes in MC twin pregnancies. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner should be better able to describe the sonographic findings used to establish the diagnosis of MC twin pregnancies; identify complications unique to MC twins pregnancies, including twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, twin anemia polycythemia syndrome, co-twin demise, cord entanglement, and conjoined twins; and explain the management of complications associated with MC twin pregnancies.

Key Points Women with severe preeclampsia demonstrate abnormal levels of the complement alternative pathway components. Genetic variants in the complement alternative pathway are more prevalent in those with severe phenotype preeclampsia compared with the general population. Future studies should explore the role of medications that block the complement alternative pathway in treatment of preeclampsia. Background Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy. Methods We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery ≤34 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls ( n =25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components. Results Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean±SD, 32±8 versus 25±4 kg/m 2 ; P =0.002) and earlier gestational age at delivery (32.5±3.6 versus 40.3±1 weeks; P <0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5–4.3] versus 0.6 [0.5–1] μ g/ml; P<0.001), complement C5 concentration (28 [18–33] versus 24 [15–34] mg/dl; P =0.03), and sMAC (371 [167–761] versus 184 [112–249] ng/ml; P<0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes. Conclusion Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.