Nafisa K. Dajani

A comprehensive analysis of the human placenta transcriptome

As the conduit for nutrients and growth signals, the placenta is critical to establishing an environment sufficient for fetal growth and development. To better understand the mechanisms regulating placental development and gene expression, we characterized the transcriptome of term placenta from 20 healthy women with uncomplicated pregnancies using RNA-seq. To identify genes that were highly expressed and unique to the placenta we compared placental RNA-seq data to data from 7 other tissues (adipose, breast, hear, kidney, liver, lung, and smooth muscle) and identified several genes novel to placental biology (QSOX1, DLG5, and SEMA7A). Semi-quantitative RT-PCR confirmed the RNA-seq results and immunohistochemistry indicated these proteins were highly expressed in the placental syncytium. Additionally, we mined our RNA-seq data to map the relative expression of key developmental gene families (Fox, Sox, Gata, Tead, and Wnt) within the placenta. We identified FOXO4, GATA3, and WNT7A to be amongst the highest expressed members of these families. Overall, these findings provide a new reference for understanding of placental transcriptome and can aid in the identification of novel pathways regulating placenta physiology that may be dysregulated in placental disease.

Prolonged morphine exposure in utero causes fetal and placental vasoconstriction: A case report

Vasoconstriction was observed in the fetal middle cerebral and umbilical arteries by Doppler assessment at 27 weeks gestation in a patient requiring continuous morphine infusion for pain control. Fetal heart tracings were also concerning. Fetal status improved after a change to fentanyl infusion, a shorter acting opioid. Caution is recommended when long-term chronic narcotic infusion is used in pregnancy.

Complications of shoulder dystocia.

Complications of shoulder dystocia are divided into fetal and maternal. Fetal brachial plexus injury (BPI) is the most common fetal complication occurring in 4-40% of cases. BPI has also been reported in abdominal deliveries and in deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of shoulder dystocia. The risk correlates with the duration of head-to-body delivery and is especially increased when the duration is >5 min. Fetal death is rare and is reported in 0.4% of cases. Maternal complications of shoulder dystocia include post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The psychological stress impact of shoulder dystocia is under-recognized and deserves counseling prior to home discharge.

GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake

Significance Our findings provide insight on the molecular mechanism in which insulin regulates the dissociation of ERp44, an endoplasmic reticulum chaperon, from the serotonin (5-HT) transporter (SERT) following the completion of disulfide bond formation. Furthermore, our data show that gestational diabetes mellitus-associated defects in insulin signaling tethers SERT with ERp44, at the intracellular compartment which down-regulates 5-HT uptake rates of the placental trophoblast. All the trophoblast used in these studies were isolated and purified directly from healthy or GDM placentas in our laboratories. Serotonin (5-HT) transporter (SERT) regulates the level of 5-HT in placenta. Initially, we found that in gestational diabetes mellitus (GDM), whereas free plasma 5-HT levels were elevated, the 5-HT uptake rates of trophoblast were significantly down-regulated, due to impairment in the translocation of SERT molecules to the cell surface. We sought to determine the factors mediating the down-regulation of SERT in GDM trophoblast. We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond. Following this posttranslational modification, before trafficking to the plasma membrane, SERT must be dissociated from ERp44; and this process is facilitated by insulin signaling and reversed by the insulin receptor blocker AGL2263. However, the GDM-associated defect in insulin signaling hampers the dissociation of ERp44 from SERT. Furthermore, whereas ERp44 constitutively occupies Cys200/Cys209 residues, one of the SERT glycosylation sites, Asp208 located between the two Cys residues, cannot undergo proper glycosylation, which plays an important role in the uptake efficiency of SERT. Herein, we show that the decrease in 5-HT uptake rates of GDM trophoblast is the consequence of defective insulin signaling, which entraps SERT with ERp44 and impairs its glycosylation. In this regard, restoring the normal expression of SERT on the trophoblast surface may represent a novel approach to alleviating some GDM-associated complications.

Correlation of ultrasound estimated with dye-determined or directly measured amniotic fluid volume revisited.

Background/Aims: To examine the relationship of the amniotic fluid index (AFI) and single deepest pocket (SDP) with an AFV as modelled by Brace or Magann. Methods: AFI and SDP were evaluated for their correlation with an actual AFV using the Spearman correlation coefficient. Results: 482 AFI and 468 SDP pregnancies were evaluated. There was a significant association between the AFI and SDP and an actual AFV (p < 0.0001). The AFI range of 5.1-20 was better correlated than 5.1-24 for normal AFVs Brace (κ = 0.175) and Magann (κ = 0.356) versus 5.1-24 (κ = 0.150 and κ = 0.319), respectively. The agreement level t for the AFI (κ = 0.175) and SDP (κ = 0.126) using Brace was slight and for the AFI (κ = 0.356) and SDP (κ = 0.295) using Magann was fair. Conclusions: Both the AFI and SDP were correlated with actual AFV using both models. AFI of 5.1-20 better categorizes normal volumes. Although the Magann model correlates AFI/SDP and AFV better, the superiority is minimal.

Depression and diabetes: Establishing the pharmacist's role in detecting comorbidity in pregnant women

Objectives To determine the prevalence of depression in women with diabetes receiving prenatal care and to determine whether pregnant women with comorbid depression and diabetes are receiving adequate care for depression.OBJECTIVES To determine the prevalence of depression in women with diabetes receiving prenatal care and to determine whether pregnant women with comorbid depression and diabetes are receiving adequate care for depression. SETTING Little Rock, AR, between June and August 2007. PRACTICE DESCRIPTION At a womens health clinic providing obstetrical services to local and statewide patients, the clinical pharmacist functions as a diabetes educator, provides treatment recommendations for the OB/GYN medical residents, and precepts fourth-year student pharmacists. PRACTICE INNOVATION The pharmacist and student pharmacists screened patients with diabetes for depression using the Beck Depression Inventory, 2nd ed. (BDI-II). MAIN OUTCOME MEASURES Patient demographics, including obstetrical history, type of diabetes, depression history, and current treatments. RESULTS 50 patients were screened in this pilot study. Of participants, 42% reported scores that indicated clinical depression. Among patients with clinical depression, only 19% were receiving treatment for depression. Obstetrical history (number of pregnancies) showed a positive correlation with the BDI-II total scores (P = 0.0078). CONCLUSION This population had a high prevalence of depressive symptoms, but very few women were receiving treatment for depression. Depression screenings should be integrated into routine prenatal care, offering adequate treatment when needed. This study implies that pharmacists can assist with screening for depression in diabetes and thus ensure that at-risk patients receive the attention needed to better manage their illnesses.

Discrepancy in insulin regulation between GDM-platelets and -placenta

Earlier findings have identified the requirement of insulin signaling on maturation and the translocation of serotonin (5-HT) transporter, SERT to the plasma membrane of the trophoblast in placenta. Because of the defect on insulin receptor (IR) in the trophoblast of the gestational diabetes mellitus (GDM)-associated placenta, SERT is found entrapped in the cytoplasm of the GDM-trophoblast. SERT is encoded by the same gene expressed in trophoblast and platelets. Additionally, alteration in plasma 5-HT levels and the 5-HT uptake rates are associated with the aggregation rates of platelets. Therefore, here, we investigated a novel hypothesis that GDM-associated defects in platelet IR should change their 5-HT uptake rates, and this should be a leading factor for thrombosis in GDM maternal blood. The maternal blood and the placentas were obtained at the time of cesarean section from the GDM and non-diabetic subjects (n = 6 for each group), and the platelets and trophoblasts were isolated to determine the IR activity, surface level of SERT, and their 5-HT uptake rates. Interestingly, no significant differences were evident in IR tyrosine phosphorylation or the downstream elements, AKT and S6K in platelets and their aggregation rates in both groups. Furthermore, insulin stimulation up-regulated 5-HT uptake rates of GDM-platelets as it does in the control group. However, the phosphorylation of IR and the downstream elements were significantly lower in GDM-trophoblast and showed no response to the insulin stimulation while they showed 4-fold increase to insulin stimulation in control group. Similarly, the 5-HT uptake rates of GDM-trophoblast and the SERT expression on their surface were severalfold lower compared with control subjects. IR is expressed in all tissues, but it is not known if diabetes affects IR in all tissues equally. Here, for the first time, our findings with clinical samples show that in GDM-associated defect on IR is tissue type-dependent. While IR is impaired in GDM-placenta, it is unaffected in GDM-platelet.

Antenatal management of at-risk pregnancies from a distance

This study was undertaken to determine whether antenatal care can be achieved in women with at‐risk pregnancies residing in rural areas with limited access to antenatal care and maternal fetal medicine (MFM) specialists. Over a period of 15 months, 156 women with high‐risk pregnancies (diabetes, hypertensive disorders, suspected fetal anomalies, prior caesarean complications) from six different healthcare units had 350 visits managed by telemedicine.

Special FeatureDepression and diabetes: Establishing the pharmacist's role in detecting comorbidity in pregnant womenDisclosurePrevious presentation

Objectives To determine the prevalence of depression in women with diabetes receiving prenatal care and to determine whether pregnant women with comorbid depression and diabetes are receiving adequate care for depression.OBJECTIVES To determine the prevalence of depression in women with diabetes receiving prenatal care and to determine whether pregnant women with comorbid depression and diabetes are receiving adequate care for depression. SETTING Little Rock, AR, between June and August 2007. PRACTICE DESCRIPTION At a womens health clinic providing obstetrical services to local and statewide patients, the clinical pharmacist functions as a diabetes educator, provides treatment recommendations for the OB/GYN medical residents, and precepts fourth-year student pharmacists. PRACTICE INNOVATION The pharmacist and student pharmacists screened patients with diabetes for depression using the Beck Depression Inventory, 2nd ed. (BDI-II). MAIN OUTCOME MEASURES Patient demographics, including obstetrical history, type of diabetes, depression history, and current treatments. RESULTS 50 patients were screened in this pilot study. Of participants, 42% reported scores that indicated clinical depression. Among patients with clinical depression, only 19% were receiving treatment for depression. Obstetrical history (number of pregnancies) showed a positive correlation with the BDI-II total scores (P = 0.0078). CONCLUSION This population had a high prevalence of depressive symptoms, but very few women were receiving treatment for depression. Depression screenings should be integrated into routine prenatal care, offering adequate treatment when needed. This study implies that pharmacists can assist with screening for depression in diabetes and thus ensure that at-risk patients receive the attention needed to better manage their illnesses.

Role of serial MRI assessment in the management of an abdominal pregnancy

A 33-year-old woman was admitted to the hospital with an abdominal pregnancy at a gestational age of 20 weeks. An initial MRI mapping of fetal location and placental vascular invasion was obtained. The patient refused surgical intervention until fetal survival would be possible. Serial MRIs were essential in timing delivery and avoiding an emergency surgical situation. The baby was delivered at 24 weeks with the assistance of a multidisciplinary surgical team. The mother as well as the baby survived. This case report highlights the role of serial MRI evaluations in the diagnosis and expectant management of an abdominal pregnancy. It also highlights the importance of interdisciplinary communication for a successful outcome.