Evidence Of Placental Dysfunction Research Articles

Polystyrene micro- and nanoplastics cause placental dysfunction in mice†.

Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106ng/L of 5μm polystyrene microplastics or 106ng/L of 50nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls. Maternal exposure to both microplastics and nanoplastics resulted in evidence of placental dysfunction that was highly dependent on the particle size. The umbilical artery blood flow increased by 48% in the microplastic-exposed group and decreased by 25% in the nanoplastic-exposed group compared to controls (p < 0.05). The microplastic- and nanoplastic-exposed fetuses showed a significant decrease in the middle cerebral artery pulsatility index of 10% and 13%, respectively, compared to controls (p < 0.05), indicating vasodilation of the cerebral circulation, a fetal adaptation that is part of the brain sparing response to preserve oxygen delivery. Hemodynamic markers of placental dysfunction and fetal hypoxia were more pronounced in the group exposed to polystyrene nanoplastics, suggesting nanoplastic exposure during human pregnancy has the potential to disrupt fetal brain development, which in turn may cause suboptimal neurodevelopmental outcomes.

Ophthalmic artery Doppler at 19–23 weeks' gestation in pregnancies that deliver small‐for‐gestational‐age neonates

ABSTRACTObjectivesFirst, to explore hemodynamic differences between pregnancies delivering a small‐for‐gestational‐age (SGA) neonate in the absence of hypertensive disorders and those that develop pre‐eclampsia (PE) or gestational hypertension (GH), by comparing the ophthalmic artery peak systolic velocity (PSV) ratio and first (PSV1) and second (PSV2) PSV at 19–23 weeks' gestation, and second, to compare these pregnancies for markers of placental perfusion and function.MethodsThis was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for assessment of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, PSV1, PSV2, mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and serum placental growth factor (PlGF). The values of PSV ratio, PSV1, PSV2, MAP, UtA‐PI and PlGF were converted to multiples of the median (MoM) or deltas. Mean MoMs or deltas of these biomarkers in the SGA, PE and GH groups were compared with those in the unaffected group. The definition of SGA was birth weight below the 10th percentile in the absence of PE or GH.ResultsThe study population of 5214 pregnancies contained 4375 (83.9%) that were unaffected by SGA, PE or GH, 563 (10.8%) complicated by SGA, 157 (3.0%) with PE and 119 (2.3%) with GH. There were three main findings of the study. First, in the SGA, PE and GH groups, compared with unaffected pregnancies, the PSV ratio delta, PSV2 MoM, MAP MoM and UtA‐PI MoM were increased and PlGF MoM was decreased; however, the magnitude of most changes was smaller in the SGA group than in PE and GH groups. Second, in the PE and GH groups, but not in the SGA group, PSV1 MoM was increased. Third, in general, in the pathological pregnancies, the magnitude of deviation of biomarkers from unaffected pregnancies was greater for those delivering at &lt; 37 than at ≥ 37 weeks' gestation.ConclusionIn mid‐gestation, pregnancies that subsequently develop hypertensive disorders and those delivering a SGA neonate, compared with unaffected pregnancies, have abnormal uteroplacental measurements and increased maternal ophthalmic artery PSV ratio. These data suggest similar pathophysiology in the two conditions, with evidence of placental dysfunction and increased peripheral vascular resistance, but the magnitude of abnormalities is greater in hypertensive disorders. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Opthalmic artery doppler measurements and cardiovascular assessment in pregnancies with placental dysfunction

Abstract Women affected by hypertensive disorders of pregnancy and fetal growth restriction frequently present alterations in the cardiovascular system, even before the clinical onset of the pathology. The objective of this study is to assess the relationship between peripheral vascular system (ophthalmic and uterine arteries), cardiac output and adverse fetomaternal outcomes. Methods Women with singleton pregnancies from mid second trimester until delivery were prospectively included in this observational study performed at our Hospital, between December 2020 and July 2021. The inclusion criteria included women with evidence of placental dysfunction (preeclampsia and fetal growth restriction) and normotensive controls. Vascular systemic resistance (VSR), arterial stiffness and cardiac output were measured by ultrasound (uterine and ophthalmic arteries), plethysmography and continuous Doppler. Study variables were compared using t-test and Chi-squared test according to whether they were normally distributed or not. Results The analysis included 32% women with hypertensive disorders of pregnancy and 67% normal pregnancies. Statistically significant difference was observed in the Second to First Peak Systolic Velocity Ratio (2PSVR) of the ophthalmic artery (p=0.011), heart Rate (p=0.03), stroke volume (p=0.004) and cardiac output (0.094) between the two groups. There were significant correlation between parameters of the central haemodynamics and those of the uteroplacental circulation, as well as ophthalmic artery Doppler. Conclusion Ophthalmic artery 2PSVR is a simple and potentially promising measurement to assess women with hypertensive disorders of pregnancy. However, this parameter must be validated against the well described Uterine artery Doppler. A bigger cohort is needed to clarify and determine its effectiveness. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): iPlacenta

Fetal major cardiac defects and placental dysfunction at 11-13 weeks' gestation.

To investigate the relationship between fetal major cardiac defects and markers of placental perfusion and function. This was a prospective screening study in singleton pregnancies at 11-13 weeks' gestation. Uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were measured and the values were converted into multiples of the normal median (MoM). Median MoM values in fetuses with isolated major cardiac defects were compared with those in fetuses without major defects. The 50 094 singleton pregnancies fulfilling the entry criteria included 49 898 pregnancies with normal cardiac anatomy and 196 (0.39%) with major congenital cardiac defects: 73 (37.2%) with conotruncal defects, 63 (32.1%) with left ventricular outflow tract defects and 60 (30.6%) with valvular defects. In the group with cardiac defects, compared with controls, there was lower median PAPP-A MoM (0.81 vs 1.00, P < 0.0001) and PlGF MoM (0.78 vs 1.00, P < 0.0001) but no significant difference in UtA-PI MoM (1.01 vs 1.00, P = 0.162). In pregnancies with isolated fetal major cardiac defects, there is evidence of placental dysfunction in the absence of impaired placental perfusion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Ex vivo dual perfusion of a human placental cotelydon – modifications of access to the intervillous space

Ex vivo dual perfusion of a human placental cotelydon – modifications of access to the intervillous space

Does altered placental morphology and function explain increased incidence of poor pregnancy outcome in advanced maternal age

Does altered placental morphology and function explain increased incidence of poor pregnancy outcome in advanced maternal age

Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia

Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Antenatal corticosteroids: the controversy continues

Purpose of review Maternal administration of glucocorticoids remains the mainstay of perinatal medicine for the fetus at risk of premature delivery. The reductions of severity of respiratory distress syndrome, incidence of intraventricular hemorrhage, and neonatal death have all been well documented. Findings from both experimental studies in animals as well as clinical investigation in humans have raised issues of concern and controversy. These include the use of repetitive courses of corticosteroids. Questions have been raised regarding the postnatal neurobehavioral and prenatal cardiovascular responses to corticosteroids. The purpose of this review is to address the current data pertaining to these controversies. Recent findings Animal studies reflect the concerns of the use of multiple courses of steroids with alterations of brain growth and histology. Human data suggest that multiple courses of corticosteroids might reduce the risk of respiratory distress syndrome, but at the expense of alterations of lung architecture. There are concerns about decreased somatic and head size. Neurobehavioral abnormalities are more frequently seen in children exposed to multiple courses. In growth-restricted fetuses with evidence of placental dysfunction, there may be a risk of sudden in-utero decompensation. Summary Repetitive courses of corticosteroids have deleterious effects with little improvement in neonatal outcome. A ‘rescue dose’ given to a fetus previously yet remotely treated may be of some benefit. Animal studies suggest acute vascular changes with maternal steroids. This has not been consistently borne out with the indirect assessment using Doppler in the human. A select group of severely growth restricted fetuses with umbilical artery absent end diastolic flow may actually deteriorate with maternal corticosteroids.

Monitoring daily insulin needs--an important follow-up parameter in late pregnancy in diabetic mothers?

Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range < 5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near-normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Haemoconcentration in Severe Pre-eclampsia

The last maternal haemoglobin (Hb) concentration before delivery was related to the perinatal outcome in 87 non-anaemic women suffering from severe pre-eclampsia. Abnormally high Hb concentrations were found in most women with evidence of placental dysfunction. An inverse correlation was found between the centile weight of the newborn and the maternal Hb. Significantly higher Hb levels were found in pregnancies complicated by fetal growth retardation and perinatal distress compared with those in pregnancies with good outcomes. Particularly high levels were found in pregnancies that ended in perinatal deaths. The hypothesis is put forward that raised haemoconcentration during severe pre-eclampsia causes increased blood viscosity which predisposes to placental pathology and initiates a vicious circle.

Haemoconcentration in severe pre-eclampsia.

The last maternal haemoglobin (Hb) concentration before delivery was related to the perinatal outcome in 87 non-anaemic women suffering from severe pre-eclampsia. Abnormally high Hb concentrations were found in most women with evidence of placental dysfunction. An inverse correlation was found between the centile weight of the newborn and the maternal Hb. Significantly higher Hb levels were found in pregnancies complicated by fetal growth retardation and perinatal distress compared with those in pregnancies with good outcomes. Particularly high levels were found in pregnancies that ended in perinatal deaths. The hypothesis is put forward that raised haemoconcentration during severe pre-eclampsia causes increased blood viscosity which predisposes to placental pathology and initiates a vicious circle.

STATUS OF NEONATES DELIVERED BY ELECTIVE CAESAREAN SECTION

A series of 144 elective Caesarean sections is reported. One hundred and five patients had no evidence of placental dysfunction (group A), of whom 57 (40 with vertex presentation) received extradural analgesia. The remaining 39 patients comprised group B. The uterine incision to delivery (U-D) interval was little influenced by presentation, but was longer with extradural block. Among group A patients Apgar-minus-colour scores and the time to sustained respiration after general anaesthesia were poorer than after extradural analgesia, breech presenting infants being prominent in this regard. The contrast was marked when the U-D interval was relatively prolonged. When the U-D interval was less than 90 s the infants born under extradural analgesia were marginally more acidotic than those born under general anaesthesia; in the latter there was a correlation between the duration of the U-D interval and neonatal acidosis, a feature which was not evident in the extradural series. The small numbers of group B cases precluded statistical evaluation, but the results reflected contrasts similar to those found among group A patients.