Association between fetoplacental Doppler results, placental pathology, and angiogenic factors among pregnant women with anxiety.

OBJECTIVE: This study aimed to evaluate whether state and trait anxiety among pregnant women were associated with fetoplacental Doppler findings, abnormal placental pathology, and placental angiogenic factors. MATERIALS AND METHODS: A total of 102 pregnant women at 32-35 gestational weeks were recruited and examined prospectively. State and trait anxiety were measured using the State-Trait Anxiety Inventory. Using Doppler ultrasound, pulsatility index (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and uterine artery (UtA) and cerebroplacental ratio (CPR) were determined. Doppler parameters were converted into multiples of the median (MoM). Abnormal placental pathology was classified into 2 groups: vascular underperfusion (VU) and histological chorioamnionitis (HCA). Immunohistochemical analysis was performed to examine placental cells staining positive for placental growth factor (PLGF) and hypoxia-inducible factor-1-α (HIF-1α), which are markers for angiogenesis and hypoxic status, respectively. RESULTS: Women with high state anxiety scores had low MCA-PI MoM and CPR MoM, while those with high trait anxiety scores had low MCA-PI MoM. VU was associated with a higher incidence of high trait anxiety scores, and HCA was associated with a higher incidence of high state and trait anxiety scores. Regression analysis showed a relationship between maternal state anxiety on MCA-PI MoM and HCA after controlling for covariates. Maternal trait anxiety exhibited relationships with VU and HCA after adjustment. CONCLUSION: Our results demonstrated that maternal anxiety is associated with altered fetal cerebral blood flow and abnormal placental pathology but is not associated with uteroplacental insufficiency and placental angiogenic factors.

Adrenocorticotropic Hormone and PI3K/Akt Inhibition Reduce eNOS Phosphorylation and Increase Cortisol Biosynthesis in Long-Term Hypoxic Ovine Fetal Adrenal Cortical Cells.

This study was designed to determine the role of the MEK/ERK1/2 and PI3K/Akt pathways in cortisol production and endothelial nitric oxide synthase (eNOS) phosphorylation (peNOS) in the ovine fetal adrenal in response to long-term hypoxia (LTH). Pregnant ewes were maintained at high altitude (3820 m) for the last 100 days of gestation (dGa). At 138 to 142 dGa, fetal adrenal cortical cells (FACs) were collected from LTH and age-matched normoxic fetuses. Cortisol production and peNOS were measured in response to pretreatment with the MEK/ERK1/2 pathway inhibitor UO126 (UO) and adrenocorticotropic hormone (ACTH) stimulation. UO126 reduced ACTH-stimulated cortisol in both normoxic and LTH FACs. UO126 alone or in combination with ACTH reduced peNOS in the normoxic group, while ACTH alone or ACTH + UO inhibited peNOS in LTH FACs. Additionally, cortisol was measured in response to pretreatment with UO and treatment with 22R-hydroxycholesterol (22R-OHC) or water-soluble cholesterol (WSC) with and without ACTH stimulation. UO126 had no effect on 22R-OHC-treated cells, but reduced cortisol in cells treated with WSC and/or ACTH. Cortisol and peNOS were also measured in response to pretreatment with PI3K/Akt pathway inhibitor Wortmannin (WT) and ACTH stimulation. Wortmannin further increased cortisol under ACTH-stimulated conditions and, like ACTH, reduced peNOS in LTH but not normoxic FACs. Together, these data suggest that in LTH FACs MEK/ERK1/2 does not regulate peNOS but that UO acts downstream from eNOS, possibly at cholesterol transport, to affect cortisol production in LTH FACs, while the PI3K/Akt pathway, along with ACTH, regulates peNOS and plays a role in the fetal adaptation to LTH in FACs.

Fetal akinesia deformation sequence with delayed skeletal muscle maturation and polymicrogyria: evidence for a hypoxic/ischemic pathogenesis.

Multiple congenital contractures, also known as fetal akinesia deformation sequence (FADS) and related terms, result from decreased fetal movement. The underlying etiologies are diverse and include central nervous system (CNS) dysgeneses and primary myopathies. Persistent central nuclei or the presence of myotubes is often regarded as evidence of a primary myopathic etiology; however, these findings are also associated with impaired fetal innervation. We report 7 fetuses, estimated gestational age 20 to 23 weeks, with persistent myotubular morphology, a change that could be (mis)interpreted as a primary myopathy. In 4 of the patients, CNS histology showed hypoxic/ischemic injury, polymicrogyria, mineralized neurons, and microinfarcts with or without loss of anterior horn neurons. FADS cases with polymicrogyria have frequently been interpreted as a consequence of a primary brain malformation. Only a few descriptions of FADS associate polymicrogyria with CNS hypoxic/ischemic injury, however, and do not describe skeletal muscle maturation delay. We hypothesize that this combination of neural and muscular pathology is an under-recognized pattern in FADS, which results from diffuse hypoxic/ischemic injury involving the brain and spinal cord during early to middle gestation.

Low doses of nicotine-induced fetal cardiovascular responses, hypoxia, and brain cellular activation in ovine fetuses.

Prenatal exposure to nicotine is associated with a variety of adverse outcomes. The present study investigated the effect of low doses of nicotine during pregnancy on fetal blood gases, cardiovascular system, and cellular activation in the brain. Intravenous administration of nicotine 10 or 25 microg/kg into ewe did not affect maternal blood gases, blood pressure, and heart rate. Maternal administration of nicotine also had no effect on fetal blood electrolyte concentrations, osmolality levels, and lactic acid levels. However, it significantly reduced fetal blood pO2 levels and oxygen saturation, increased fetal arterial blood pressure and decreased heart rate in utero. In addition, exposure to low doses of nicotine increased the expression of Fos in the paraventricular nucleus (PVN) and subfornic organ (SFO) in the fetal brain. The data demonstrated that even low doses of nicotine could impact significantly on fetal cardiovascular and central nervous systems, as well as oxygen status, and suggested a toxic risk to fetuses of exposure to low levels nicotine or second-hand smoking during pregnancy.