Uteroplacental Ischemia Is Associated with Increased PAPP-A2.

Residence at high altitude (> 2500 m) has been associated with an increased frequency of preeclampsia. Pappalysin-2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease that is elevated in preeclampsia, and up-regulated by hypoxia in placental explants. The relationships between PAPP-A2, altitude, and indices of uteroplacental ischemia are unknown. We aimed to evaluate the association of altitude, preeclampsia, and uterine artery flow or vascular resistance with PAPP-A2 levels. PAPP-A2, uterine artery diameter, volumetric blood flow, and pulsatility indices were measured longitudinally in normotensive Andean women residing at low or high altitudes in Bolivia and in a separate Andean high-altitude cohort with or without preeclampsia. PAPP-A2 levels increased with advancing gestation, with the rise tending to be greater at high compared to low altitude, and higher in early-onset preeclamptic compared to normotensive women at high altitude. Uterine artery blood flow was markedly lower and pulsatility index higher in early-onset preeclamptic normotensive women compared to normotensive women. PAPP-A2 was unrelated to uterine artery pulsatility index in normotensive women but positively correlated in the early-onset preeclampsia cases. We concluded that PAPP-A2 is elevated at high altitude and especially in cases of early-onset preeclampsia with Doppler indices of uteroplacental ischemia.

Detailed Fetal Anatomic Ultrasound Examination: Effect of the 2014 Consensus Report on a Tertiary Referral Center.

This study evaluates the impact of extended cardiac views on examination time, repeat imaging, and anomaly detection before and after implementation of 76811 guidelines (American Institute of Ultrasound in Medicine Consensus 2014). It is a retrospective study of singleton pregnancies undergoing detailed ultrasound imaging at 18 weeks' gestation or greater before and after the protocol change in an academic, tertiary care fetal center. Views required prior to 2014: 4-chamber, left outflow tract, right outflow tract. Additional views required after 2014: bicaval, aortic arch, 3-vessel, and 3-vessel trachea. Fetuses with known anomalies were excluded. Rates of detection of congenital heart disease (CHD), examination completion, repeat examination recommendation, fetal echocardiogram recommendation, completion by body mass index, and cardiac examination time were determined. Six hundred twenty-four subjects were included, 217 before and 407 after protocol change. Views obtained were as stated in the American Institute of Ultrasound in Medicine/Society for Maternal-Fetal Medicine consensus. Detection of CHD was not improved. Examination times increased by 20% (6.4 vs 7.7 minutes, P < 0.05). Number of incomplete studies increased by 130% (11% to 26%, P < 0.05). Twice as many patients were referred for repeat examination (6% vs 13%, P < 0.05). Completion rates were negatively correlated with body mass index. Recommendations for fetal echocardiogram were unchanged (5% vs 6%, P = 0.6). Additional imaging did not increase detection rate of CHD (3% vs 2%, P = 0.3). Extended cardiac views resulted in increased examination time, more incomplete examinations, and more repeat examinations without changing detection rates of CHD.

Novel mutation in CCBE 1 as a cause of recurrent hydrops fetalis from Hennekam lymphangiectasia-lymphedema syndrome-1.

Whole exome sequencing (WES) was used to determine the etiology of recurrent hydrops fetalis in this case of Hennekam lymphangiectasia-lymphedema syndrome-1. WES is a useful approach for diagnosing rare single-gene conditions with nonspecific phenotypes and should be considered early in the diagnostic process of investigating fetal abnormalities.

Differential expression of human placental PAPP-A2 over gestation and in preeclampsia.

INTRODUCTION: Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia. METHODS: Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera. RESULTS: PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood. DISCUSSION: PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation.

Furcate Umbilical Cord Insertion: Disparate Outcomes of a Rare Obstetrical Finding. A Case Report.

BACKGROUND: Furcate umbilical cord insertions are rare obstetrical findings. This variant is defined by an umbilical cord which branches prior to contacting the placental surface. The vessels are left vulnerable to injury as they often separate from the cord substance. CASES: In case 1, a duplex placenta and bifurcate umbilical cord were diagnosed at routine anatomy ultrasound, and no significant fetal anomalies were associated with these findings. There was difficulty with placental extraction, leading to postpartum dilation and curettage. In case 2, the furcate umbilical cord was diagnosed on postpartum evaluation after emergent delivery. It was found in conjunction with VACTERL association of the fetus. CONCLUSION: Abnormal placentation and umbilical cord insertion can be diagnosed prenatally. Earlier recognition will allow for earlier identification of possible associated fetal anomalies, delivery planning, and close observation for maternal and fetal complications.

Maternal-fetal transfer of anti-N-methyl-D-aspartate receptor antibodies.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a neuroautoimmune disease commonly associated with ovarian teratomas. It is characterized by neuropsychiatric symptoms, seizures, and autonomic instability. Few cases are described in pregnancy, and little is known about potential fetal effects. CASE: Anti-NMDA receptor encephalitis was diagnosed at 24 weeks of gestation. No improvement occurred with intravenous immunoglobulin, methylprednisolone, and plasmapheresis. Imaging was unremarkable. Cesarean delivery with concurrent bilateral oophorectomy resulted in prompt maternal improvement. Antibody titers were positive in cord blood. CONCLUSION: Anti-N-methyl-D-aspartate receptor encephalitis in pregnancy can lead to NMDA receptor antibodies in the fetal circulation. Pregnancy interruption through early delivery with or without oophorectomy may accelerate maternal recovery.