Placental Calcification Research Articles

The influence of gestational diabetes mellitus (GDM) and gestational hypertension (GH) on placental morphological changes.

Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are some of the most common medical conditions associated with pregnancy. These can be correlated with placental morphopathological changes and implicitly can influence good fetal development. The age and weight of the mother can be correlated directly proportionally with those of the fetus but also with histoarchitecture and placental vascularization. The placental appearance associated with GDM and GH reveals macroscopic features, such as calcifications, fibrin deposits and placental infarcts, but the most relevant pathological features are the microscopic ones, highlighted by the classical staining techniques: Hematoxylin–Eosin (HE), Periodic Acid–Schiff (PAS)–Hematoxylin and Masson’s trichrome (MT), but also by immunohistochemical technique with the help of the anti-cluster of differentiation 34 (CD34) antibody that labeled the capital endothelium in the structure of the placental terminal villi and thus we were able to quantify the vascular density according to the associated medical pathology. The microscopic changes identified were represented by intravillous and extravillous fibrin depositions, massive placental infarctions caused by vascular suppression due to various causes, such as thrombosis, but also placental calcifications. All these macroscopic and microscopic morphopathological changes, together with the clinical data of the mother and the newborn, we have demonstrated that they are interconnected and that they can vary depending on the pathology, GH or GDM.

Clinical course of pregnancy and postpartum in a multidrug-resistant tuberculosis/HIV co-infected patient receiving bedaquiline-containing regimen as antimycobacterial therapy

Background. According to World Health Organization (WHO), experimental studies performed in rats and rabbits have revealed no evidence of harmful side effects of bedaquiline to the fetus. WHO points out that, given the lack of adequate and controlled studies on the effects of bedaquiline on the fetus in pregnant women, and the fact that drug data regarding teratogenicity are limited to nonclinical animal data, this drug may be used when an effective treatment regimen cannot otherwise be provided. However, WHO recommends thorough registering treatment, pregnancy, and postpartum bedaquiline-related outcomes to provide data on appropriate dosing for multidrug-resistant tuberculosis (MDR-TB) treatment during pregnancy and postpartum. However, in the modern literature, there are no data about attributable to bedaquiline adverse events in MDR-TB/HIV co-infected pregnant women and their fetus as well as during the postpartum period.
 Objective. To update the literature data with the clinical features of pregnancy and postpartum period in a MDR-TB/HIV co-infected patient receiving a bedaquiline-containing regimen as antimycobacterial therapy in the third trimester based on an example from own clinical experience.
 Methods. We report the clinical case of pregnancy course in the MDR-TB/HIV co-infected woman treated with the bedaquiline-containing regimen as antimycobacterial therapy in the third trimester.
 Results. In the clinical case presented, the patient demonstrated an initial poor adherence to treatment for both MDR-TB and HIV infection resulting in tuberculous process and HIV rapid progression. Since the patient refused the option of undergoing the therapeutic abortion prior to 22 gestational weeks as the pregnancy was intended, the antimycobacterial therapy regimen was modified by bedaquiline inclusion at 30 weeks’ gestation (the third trimester) for the maternal and neonatal mortality prevention. However, there was no sputum smear conversion on the antimycobacterial therapy regimen including bedaquiline, the patient presented with the signs of endogenous intoxication and nephropathy. Relatedly, neonatal transabdominal ultrasound revealed intrauterine growth retardation, worsening fetoplacental insufficiency (reverse flow) and intrauterine dystrophy. There was abundant placental calcification. Taking into account breech presentation, II degree intrauterine growth retardation, III degree fetoplacental insufficiency (reverse flow), oligohydramnios, fetal distress syndrome and bilateral pyelectasis, the patient was transferred to the Perinatal Centre for planned caesarean section at the 32nd week of gestation. The premature female infant was declared dead some hours later. In the postpartum period, the patient continued the initiated bedaquilinebased antimycobacterial therapy and antiretroviral therapy. However, positive clinical-radiological dynamics and sputum smear conversion have not been achieved.
 Conclusions. The clinical case presented confirms the literature data that the features of pregnancy and postpartum period in patients with MDR-TB/HIV co-infection are characterized by such complications development as preterm delivery, early neonatal mortality, intrauterine growth retardation, distress syndrome, etc.

EP18.04: Relationship between placental calcification and estimated fetal weight percentile at 30–34 weeks of pregnancy

EP18.04: Relationship between placental calcification and estimated fetal weight percentile at 30–34 weeks of pregnancy

Murine Placental-Fetal Phosphate Dyshomeostasis Caused by an Xpr1 Deficiency Accelerates Placental Calcification and Restricts Fetal Growth in Late Gestation.

Phosphorus is a necessary component of all living organisms. This nutrient is mainly transported from the maternal blood to the fetus via the placenta, and insufficient phosphorus availability via the placenta disturbs the normal development of the fetus, especially fetal bone formation in late gestation. Key proteins (phosphate transporters and exporters) that are responsible for the maintenance of placental-fetal phosphorus homeostasis have been identified. A deficiency in the phosphate transporter Pit2 has been shown to result in placental calcification and the retardation of fetal development in mice. What roles does XPR1 (the only known phosphate exporter) play in maintaining placental-fetal phosphorus homeostasis? In this study, we found that Xpr1 expression is strong in the murine placenta and increases with age during gestation. We generated a global Xpr1 knockout mouse and found that heterozygous (Xpr1+/- ) and homozygous (Xpr1-/- ) fetuses have lower inorganic phosphate (Pi) levels in amniotic fluid and serum and a decreased skeletal mineral content. Xpr1-deficient placentas show abnormal Pi exchange during gestation. Therefore, Xpr1 deficiency in the placenta disrupts placental-fetal Pi homeostasis. We also discovered that the placentas of the Xpr1+/- and Xpr1-/- embryos are severely calcified. Mendelian inheritance statistics for offspring outcomes indicated that Xpr1-deficient embryos are significantly reduced in late gestation. In addition, Xpr1-/- mice die perinatally and a small proportion of Xpr1+/- mice die neonatally. RNA sequence (RNA-Seq) analysis of placental mRNA revealed that many of the transcripts are significantly differentially expressed due to Xpr1 deficiency and are linked to dysfunction of the placenta. This study is the first to reveal that XPR1 plays an important role in maintaining placental-fetal Pi homeostasis, disruption of which causes severe placental calcification, delays normal placental function, and restricts fetal growth. © 2019 American Society for Bone and Mineral Research.

Abstract 775: Interaction of Phosphate Transport and Calcification in Placenta Vasculature

Phosphate transport has been associated with pathological vascular calcification, but this relationship remains largely unexplored in placenta tissue. In this study we investigated the interaction of maternal-fetal phosphate transport and placental calcification using in vitro and in vivo models. Sodium-dependent phosphate transporter transcriptomics validated by quantitative RT-PCR revealed that the type III sodium-dependent phosphate transporter family members Slc20a1 and Slc20a2 are the predominant sodium-dependent symporters in both mouse and human placenta. Global loss of Slc20a2 generates multiple maternal and fetal phenotypes. We examined Slc20a2 promoter activity and protein localization of Slc20a2 throughout placentation. Slc20a2 was detected in embryonic structures that give rise to the maternal-fetal interface and in regions of the placenta that are susceptible to vascular calcification in the absence of Slc20a2. Pathologically, vascular malformations were found to precede calcium deposition in the absence of Slc20a2. Activation of osteocalcin in the placenta suggested that physiological calcification mechanisms may potentiate the mineral deposition observed with Slc20a2 loss. Histological analyses of human placenta revealed focal localization of Slc20a2 protein and distinct calcification deposition patterns. Lastly, the BeWo trophoblast model confirmed cellular competency for active, sodium-dependent phosphate symport as well as extracellular matrix calcification. Taken together, our findings support that normal growth and maintenance of the placenta requires Slc20a2. Moving forward, we now propose the working hypothesis that Slc20a2-mediated placental phosphate transport contributes to the energy requirements for rapid placental vascular development, enabling vascular patterning that maximizes surface area and minimizes tissue damage caused by aberrant flow, thereby promoting organ health and transport of nutrients, including phosphorus, across the placenta.

Relationship Between Placental Calcification and Estimated Fetal Weight Percentile at 30-34 Weeks of Pregnancy

Objectives: The identification of at-risk fetus is considered as one of the most difficult challenges for clinicians and researchers although the clinical significance of placental calcifications (PCs) and its relation to adverse pregnancy outcome are controversial. Therefore, the present study aimed to evaluate the relationship between PC and estimated fetal weight (EFW) percentile at 30-34 weeks of pregnancy. Materials and Methods: This prospective cross-sectional study was carried out on all pregnant women except for multiple pregnancy subjects who were admitted to an outpatient perinatal center from October 2016 to September 2018. Several parameters were measured at 30-34 weeks of pregnancy, including EFW, umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio (CPR), right and left uterine artery PI, along with right and left uterine artery notch. Finally, the calcification of the placenta with any shape and degree was determined as well. Results: In this study, 739 pregnant women were evaluated for PC, including patients with PC (9.87%), small-for-gestational age (SGA, 3.65%), and those with at least one abnormal Doppler index (23.95%). Patients with PC and those with at least one abnormal Doppler index had significantly higher SGA (29.62% and 12.42%, respectively). In addition, there were 55.55% and 30.13% patients with SGA and PC in the group with at least one abnormality in terms of Doppler indices. Conclusions: In general, the findings showed that PC is more common in SGA. Based on the results, at least one abnormality in Doppler indices was more common in PC and SGA, and uterine artery Doppler abnormality was the most prevalent abnormal findings in the arterial Doppler. Thus, PC may be an important marker for adverse pregnancy outcomes.

Evaluation of thyroid function in a sample of newborns through different modes of delivery

Background and objective: Congenital hypothyroidism is the most common preventable cause of mental retardation detected during early childhood. Its early diagnosis is crucial for a better outcome. Many factors are contributed to this problem including maternal, fetal and others. This study aimed to assess thyroid hormone status in relation to certain obstetrical especially mode of delivery and neonatal factors Methods: A descriptive cross-sectional study conducted in postnatal care and delivery room (operative and vaginal) of Maternity teaching hospital in Erbil city. Ninety-two babies were included and subdivided into three groups according to their route of delivery. A thyroid stimulating hormone cut off value of 10 was selected as the upper normal level for the purpose of the study. Results: A significant proportion of babies with cord thyroid stimulating hormone concentration more than 10 mIU/L (25 out of 92) were noticed, and this is near to many previous studies used the same cut off value. Mean of This hormone is relatively increased among newborns of the elective cesarean section while maternal total triiodothyronine and total thyroxine were higher within the elective group. Prenatal evidence of placental calcification and first born babies were associated with higher thyroid stimulating hormone levels. Conclusion: Emergency cesarean section is less likely to be associated with elevated cord blood thyroid stimulating hormone level compared to other routes of delivery/but this is not confirmatory and recall test is recommended to exclude hypothyroidism.

Nano-analytical characterization of endogenous minerals in healthy placental tissue: mineral distribution, composition and ultrastructure.

Despite its crucial role, the placenta is the least understood human organ. Recent clinical studies indicate a direct association between placental calcification and maternal and offspring health. This study reveals distinct characteristics of minerals formed during gestational ageing using cutting-edge nano-analytical characterization and paves the way for investigations focused on the identification of potential markers for disease risks in a clinical setting based on atypical placental mineral fingerprints.

154. Placental structure and vascularization in IVF/ICSI-pregnancies compared to naturally conceived pregnancies

Objectives Although pregnancy rates of artificial reproductive techniques (ART) pregnancies have been optimized, these pregnancies have a higher risk of pregnancy complications due to impaired placentation during early pregnancy and thereby affecting placental vascularization, -structure and later on fetal growth. The aim of this study is to investigate if there are placental ultrasonographic differences between ART- and naturally conceived pregnancies. Methods A cross-sectional pilot study included 35 ART- and 30 naturally conceived (NC) pregnancies at the Maastricht University Medical Centre, between October 2017 and March 2018. Inclusion criteria were singleton pregnancies (NC, IVF/ICSI), maternal age ⩾18 years and body-mass-index (BMI) Results Placental calcifications at 12 and 16 weeks of gestation showed no significant difference between the ART and NC-group. However, placental lakes at 16 weeks were more prominent in the ART-group (59.5%) compared to the NC-group (26.1% (p = 0.017). Vascularization index at the umbilical cord insertion (UCI) and in the peripheral parts of the placenta was measured. At 12 weeks, the ART-group compared to the NC-group, showed a lower VI at the UCI (0.73 ± 0.81% vs. 2.00 ± 2.46%, p = 0.156) and in the peripheral parts of the placenta (1.73 ± 3.43% vs. 4.14 ± 4.92%, p = 0.023). At 16 weeks, no significant differences were found. Conclusions Reduced early placental vascularisation in ART-compared to NC-pregnancies may reflect the underlying aetiology of impaired placentation. These results provide promising possibilities for a more extended prospective trial and using placental ultrasonography as a predictor in the future.

Placental Peripartum Pathologies in Women with Preeclampsia and Eclampsia.

Objective To determine the pattern of pathological changes in placentas of preeclamptic/eclamptic parturients and its correlation with the clinical severity as well as the perinatal outcome. Methods A cross-sectional analytical study of placental pathologies in preeclamptic/eclamptic patients was performed in a blinded pattern and compared with matched normal controls. Data were analyzed using Epi-Info 2008 version 3.5.1. Results Placental pathologies were evaluated in 61 preeclamptic/eclamptic patients and in 122 controls. Of the 61 placentas, 53 (4.7%) were of preeclampsia while 8 (0.71%) were of eclampsia. Of the preeclamptic group, 14 (23%) had mild preeclampsia while 39 (63.9%) had severe preeclampsia. Infarction, haematoma, and some histological changes increased with the severity of preeclampsia (p < 0.001). When comparing placentas in eclampsia, severe preeclampsia, mild preeclampsia, and normal controls, there was respective increase in the presence of any infarction (75%, 66.7%, 35.7% vs. 12.3%) or any haematoma (100%, 100%, 71.4% vs. 35.2%), decidual arteriopathy (87.5%, 76.9%, 64.3% vs. 35.2%), cytotrophoblastic proliferation (75%, 71.8%, 42.9% vs. 25.4%), and accelerated villous maturation (75%, 69.2%, 57.1% vs. 31.1%). There was no statistically significant difference in placental calcifications, stromal oedema, stromal fibrosis, and syncytial knots. Degree of placental infarction was correlated with the fetal birth weight. The fetal birth weight with placental involvement of >10% was significant (p=0.01). Conclusion In mild or severe preeclampsia/eclampsia, placentas had significant histological signs of ischaemia and degree of placental involvement by infarction is inversely proportional to fetal birth weight. While feto-placental ratio was higher with increased severity of the disease, the mean weight was less. This trial is registered with researchregistry3503.

Placental Vascular Calcification and Cardiovascular Health: It Is Time to Determine How Much of Maternal and Offspring Health Is Written in Stone.

Vascular calcification is the deposition of calcium phosphate minerals in vascular tissue. Vascular calcification occurs by both active and passive processes. Extent and tissue-specific patterns of vascular calcification are predictors of cardiovascular morbidity and mortality. The placenta is a highly vascularized organ with specialized vasculature that mediates communication between two circulatory systems. At delivery the placenta often contains calcified tissue and calcification can be considered a marker of viral infection, but the mechanisms, histoanatomical specificity, and pathophysiological significance of placental calcification are poorly understood. In this review, we outline the current understanding of vascular calcification mechanisms, biomedical consequences, and therapeutic interventions in the context of histoanatomical types. We summarize available placental calcification data and clinical grading systems for placental calcification. We report on studies that have examined the association between placental calcification and acute adverse maternal and fetal outcomes. We then review the intersection between placental dysfunction and long-term cardiovascular health, including subsequent occurrence of maternal vascular calcification. Possible maternal phenotypes and trigger mechanisms that may predispose for calcification and cardiovascular disease are discussed. We go on to highlight the potential diagnostic value of placental calcification. Finally, we suggest avenues of research to evaluate placental calcification as a research model for investigating the relationship between placental dysfunction and cardiovascular health, as well as a biomarker for placental dysfunction, adverse clinical outcomes, and increased risk of subsequent maternal and offspring cardiovascular events.

Progression of gestational hypertension to pre-eclampsia: A cohort study of 20,103 pregnancies.

To investigate previously un-identified risk factors for the progression of gestational hypertension (GH) to pre-eclampsia (PE) by considering Grade III preterm placental calcification (PPC) and excessive weight gain (≧10kgw) at 28weeks gestation. At a tertiary teaching hospital, obstetric ultrasonography was performed at 28weeks gestation to establish a diagnosis of grade III PPC. Weight gain during pregnancy was recorded at the same time. Pregnancies complicated with chronic hypertension, major fetal congenital anomalies, termination before 24weeks gestation, and abortion before 20 weeks gestation were excluded. In the current cohort study, 20,103 pregnancies were enrolled and categorized as normal blood pressure (NBP; n=18,223) and GH-PE (n=1880) groups. According to severity of the diseases, the GH-PE group was further divided into GH (n=1088), PE (n=792), and severe PE (n=209) groups. There were significant differences between the NBP and GH-PE groups in known factors, including maternal age, BMI, parity, multi-fetal pregnancy, and co-morbidities (all p<0.001), all of which increased the risk for GH-PE. Regarding the progression of GH to PE and severe PE, there was a much greater frequency of excessive weight gain (51.2% and 49.0% vs. 9.3%) or PPC (63.2% and 61.6% vs. 12.1%) in the severe PE and PE groups than the GH group. Logistic regression analysis revealed that PPC was a significant and independent risk factor for progression of GH to PE (OR, 13.71; 95% CI, 10.25-18.33) and severe PE (OR, 12.42; 95% CI, 8.89-17.35), as well as excessive weight gain during pregnancy (OR, 8.92; 95% CI, 6.67-11.92 and OR, 10.25; 95% CI, 7.30-12.40). Being a pathologic implication, the presence of PPC or excessive weight gain during pregnancy may precede progression of GH, and can serve as a warning or marker that requires closer surveillance for maternal and fetal well-being. Based on the findings of PPC and excessive weight gain, at-risk pregnant woman should be counseled to facilitate early intervention or referral. In addition, avoiding excessive weight gain during pregnancy may reduce the risk of GH progression to PE.

Is preterm placental calcification related to adverse maternal and foetal outcome?

This prospective cohort study aimed to evaluate the role of premature placental calcification in adverse pregnancy outcomes and identify its associated potential risk factors. We consecutively enrolled 293 women who presented to three academic medical centres from September 2011 to March 2013. Participants underwent transabdominal sonographies between 28–36 weeks of gestation in an attempt to determine placental maturity. We compared maternal and foetal outcomes between two groups of women, those with grade III placenta (n = 69) and those without grade III placenta (n = 224). Passive smoking was the only predictor of early placental calcification. There were more abnormal Doppler, low birth weight (LBW) and caesarean section (CS) deliveries observed in the preterm calcification group. No definite relationship existed between maternal hypertension (HTN), diabetes and other medical diseases with placental calcification. In conclusion, umbilical artery (UA) resistance index (RI) and absent or reversed end-diastolic velocity (AREDV) were observed more often in preterm placental calcification. Serious antepartum follow-up should be advised for these mothers.Impact Statement • Placental calcification is a physiological phenomenon but normally, a grade III placenta is not frequently found until 36 weeks of gestation (so is called preterm placental calcification – PPC). There is currently a lack of consistent evidence on the clinical significance of PPC and pregnancy outcome. The present study was designed to evaluate the role of PPC in adverse pregnancy outcomes. • In our study, although none of the pregnant women were smokers, we found that passive smoking was the only predictor of PPC. Abnormal umbilical artery Doppler waveforms considerably and absent end diastolic velocity pattern significantly were observed more often in the PPC group. • We observed that PPC can be a landmark for high-risk pregnancy and an alarm sign for placental dysfunction. So, close antepartum follow up should be advised for these mothers. Regular and frequent foetal wellbeing tests should be done to prevent pregnancy complications. Certainly larger and more extensive study can provide more valid results.

Sonographically abnormal placenta: an association with an increased risk poor pregnancy outcomes.

The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Placental abnormalities, therefore, can be an "early warning system" for fetal problems. A complete prenatal sonographic examination of the placenta is an essential component as its abnormalities can have a direct effect on fetal or maternal outcomes, obstetrical management and future fertility. To determine whether any association exists between the finding of an increased thickness of placenta, abnormal placenta shape, placental calcification, placental lake and abnormal cord insertion site at 20-22 and 30-32 weeks gestation with an increased risk of uteroplacental complications or a poor pregnancy outcome. A real-time ultrasound was used at the time of detail scan (at 20-22 weeks gestation) and at 30-32 weeks gestation to look for placenta appearance, fetal growth and anomaly. The main outcome measures were risk of hypertension disease in pregnancy, fetal growth restriction and poor fetal outcomes such as low Apgar score and low cord pH. The majority of the participants were Malay (77.9%). Abnormal placenta found at both gestations were placental lakes and thickness, and only one case had marginal cord insertion. Approximately 6% of the cases were confirmed placenta previa. No abnormal shape or abnormal calcification found at both gestations. About 10% patient developed hypertensive disease in pregnancy, 15% of the fetus was found to have growth restriction and another 16% have low umbilical cord pH. Majority of them delivered at term (90%) and via vaginal delivery (81%). There was no significance between presence of abnormal placental lake and thickness at both gestations with the maternal and fetal outcome. Presence of abnormal placental thickness and lakes at 30-32 weeks scan associated with maternal hypertensive disease, fetal growth restriction and low umbilical cord pH, however these were not statistically significant.

Distribution and potential significance of intravillous and intrafibrinous particulate microcalcification

Radiologic studies indicate that placental calcifications seen at 28–32 weeks' gestation are associated with adverse fetal outcome. One type of placental calcification is typically located at the basement membrane of chorionic villi. It has a fine particulate appearance and can only be seen microscopically. We have designated these calcifications as Intravillous and Intrafibrinous Particulate MicroCalcification (IPMC). In this study we examined the distribution and potential significance of IPMC. Placentas from 14 groups of fetal and maternal outcomes are examined histologically for IPMC. These groups were preterm birth, post term birth, intrauterine fetal demise, fetuses with non-reassuring heart rates, intrauterine growth restriction, fetal anomalies, mothers with gestational hypertension, gestational diabetes, placental abruption, pre-eclampsia and placentas of normal spontaneous vaginal births and placentas with chorioamnionitis, chronic villitis and infarcts. We observed fine dust-like particulates deposited in continuous and discrete patches. The particulates were predominantly located in the basement membranes of fibrotic chorionic villi and in perivillous fibrin. Compared to placentas without adverse outcomes, a higher incidence of IPMC was seen in intrauterine fetal demise cases and in cases with infarcts which suggests that hypoxia played a role in the etiology of IPMC.

Is there a role for 3 dimensional power Doppler placental ultrasound and computerised assessment of calcification in post-term pregnancies?

PurposeTo assess if three dimensional power Doppler (3DPD) placental ultrasound, evaluating volume, vascularisation, and blood flow in post-term pregnancies differs from normal pre-term third trimester pregnancies and to examine whether computer analysis identifies the continual increase in calcification in post-term pregnancies. Materials and methodsA prospective cohort study of 50 women with post-term pregnancies (40 + 0 to 41 + 6 weeks) and 58 controls (36–40 weeks). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Calcification percentage was calculated, by computer analysis. Results were compared with previously determined normal values and correlated with uterine, middle cerebral and umbilical artery Doppler values and placental histology. ResultsPlacental volume, VI, FI and VFI are not influenced by GA beyond 40 weeks gestation and are similar between post-term and normal pregnancies (36–40 weeks). Placental volume decreased as the mean uterine artery pulsatility index (UtA PI) increased; p = 0.047. FI was reduced where chorangiosis was found at histology (p = 0.033). Computer analysis of placental calcification identified the increased calcification expected after 40 weeks, and showed that calcification continues to increase between 40 and 42 weeks (p = 0.029). ConclusionAlthough the sample size limits the generalisability of the findings, we found that calcification of the placenta continues to increase between 40 and 42 weeks gestation, that there is an association between an increasing UtA PI and a decreasing placental volume and that FI measurement may be useful in the identification of chorangiosis in post-term pregnancies.

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

The essential nutrient phosphorus must be taken up by the mammalian embryo during gestation. The mechanism(s) and key proteins responsible for maternal to fetal phosphate transport have not been identified. Established parameters for placental phosphate transport match those of the type III phosphate transporters, Slc20a1 and Slc20a2. Both members are expressed in human placenta, and their altered expression is linked to preeclampsia. In this study, we tested the hypothesis that Slc20a2 is required for placental function. Indeed, complete deficiency of Slc20a2 in either the maternal or embryonic placental compartment results in fetal growth restriction. We found that Slc20a2 null mice can reproduce, but are subviable; ∼50% are lost prior to weaning age. We also observed that 23% of Slc20a2 deficient females develop pregnancy complications at full term, with tremors and placental abnormalities including abnormal vascular structure, increased basement membrane deposition, abundant calcification, and accumulation of novel CD13 and lamininα1 positive cells. Together these data support that Slc20a2 deficiency impacts both maternal and neonatal health, and Slc20a2 is required for normal placental function. In humans, decreased levels of placental Slc20a1 and Slc20a2 have been correlated with early onset preeclampsia, a disorder that can manifest from placental dysfunction. In addition, preterm placental calcification has been associated with poor pregnancy outcomes. We surveyed placental calcification in human preeclamptic placenta samples, and detected basement membrane-associated placental calcification as well as a comparable lamininα1 positive cell type, indicating that similar mechanisms may underlie both human and mouse placental calcification.

Vitamin D deficiency and placental calcification in low-risk obstetric population: are they related?

Objective: We aimed to evaluate the relationship between placental calcification and maternal and cord blood 25-hydroxyvitamin-D3 [25(OH)D] and calcium concentrations in low-risk obstetric population at term and their consequences.Methods: Sixty non-complicated pregnant women at term admitted to maternity clinic were included in this prospective case-control study and classified into one of two groups according to grade of placental calcification by defined the Grannum classification: Group 1 (n=30), with Grade 3 placenta and Group 2 (n=30), the control group, no placental calcification noted. Baseline characteristics, maternal serum and umbilical cord 25(OH)D and calcium levels were compared between groups.Results: The mean age of subjects was 26.4 ± 5.7 years. The mean serum 25(OH)D concentration of women (n=60) was 9.3 ± 3.4 (range 5.59–15.48) ng/mL. The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 100%. Maternal serum and cord blood calcium levels were significantly higher in Group 1 (p=0.036; p=0.037, respectively). In Group 2, maternal serum and cord blood 25(OH)D levels were higher than Group 1 (11.35 ± 6.54 and 10.22 ± 3.59 versus 9.6 ± 4.2 and 9.07 ± 2.43 ng/mL); but the difference is not statistically significant.Conclusions: Higher maternal calcium and lower 25(OH)D levels detected in patients with Grade 3 placental calcification indicated the importance of placenta on vitamin D regulation.

Placental volume, vasculature and calcification in pregnancies complicated by pre-eclampsia and intra-uterine growth restriction

ObjectivePre-eclampsia (PET) and intrauterine growth restriction (IUGR), often associated with impaired placental function, are among the most common conditions contributing to increased perinatal mortality and morbidity. This study investigates if three dimensional power Doppler (3DPD) of the placenta and computerised analysis of placental calcification is different between PET/IUGR and normal pregnancies. Study designThis was a prospective cohort study involving 50 women with pre-eclampsia and/or IUGR, or with IUGR only from 24 to 40 weeks’ gestation. 3DPD ultrasound was used to calculate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Following each scan the percentage of placental calcification was also calculated, by computer analysis. Results were compared with normal (control) values, and findings correlated with maternal and fetal Doppler parameters and placental histology. ResultsVolume, VI, and VFI are not influenced by gestational age in PET/IUGR pregnancies. FI was found to increase with gestational age (p=0.009) and was lower than normal in the total study group from 24 to 30 weeks (p=0.006). In the pregnancies affected by PET, whether or not IUGR was present, all three indices were lower than normal values between 24 and 30 weeks (VI: p=0.038, FI: p=0.004, VFI: p=0.015). Vascularisation and flow indices were less than the normal 50th centile in the majority of cases of utero-placental insufficiency (p=0.047), and vascularisation and vascularisation flow indices were lower in cases of accelerated placental maturation (p=0.016 and 0.041 respectively). Placental volume greater than the 50th centile between 24 and 30 weeks was associated with the presence of infarction on histology (p=0.021). Flow index (p=0.002) and vascularisation flow index (p=0.036) were lower in the presence of bilateral uterine artery notches. Calcification, similar to the control group, was related to an increasing UAPI (p=0.041) and MCA PI <5th centile (p=0.010). ConclusionsThe study findings suggest that there may be a role for 3DPD placental assessment of volume, vascularisation and blood flow and computer analysis of placental calcification in the identification and management of PET/IUGR pregnancy.

The role of preterm placental calcification on assessing risks of stillbirth.

Stillbirth is an important issue in antenatal care and much remains unknown. This cohort study aims to explore the previously un-identified risk factor of third-trimester stillbirth to determine if Grade III preterm placental calcification (PPC) is associated with stillbirth. At a tertiary teaching hospital, obstetric ultrasonography was performed at 28 weeks' gestation to establish a diagnosis of PPC. Pregnancies with multifetal gestations, major fetal congenital anomalies, termination, cord accidents, apparent intrauterine infection, and antepartum complications were excluded. 15,122 eligible pregnancies were categorized as stillbirth (n=99) and livebirth (n=15,023) groups. Between these two groups, there were no significant differences in maternal age, BMI, and parity, but significant differences in smoking and in PPC (35.4% vs 6.3%, p<0.001) were observed. The peak occurrence of stillbirths was at 30 and 37 weeks' gestation, with a bimodal distribution of 11 and 17 stillbirths, respectively. For pregnancies with or without PPC, the incidences of stillbirths per-1000-births were 35.9 and 4.5, respectively. Using Kaplan-Meier survival analysis, at 40 weeks' gestation the cumulative stillbirth risk for pregnancies with PPC was higher compared to those without PPC. Logistic regression revealed that after adjusting for the effects of smoking and demographic factors, the risk of stillbirth (adjusted OR:7.62; 95% CI:5.00-11.62) was much higher when PPC was present. Grade III PPC is associated with a higher incidence of stillbirth, and identified an independent risk factor. Being a pathologic implication, it may precede this negative outcome and can serve as a warning sign or marker when noted on ultrasonography.