2D-ultrasound and endocrinologic evaluation of placentation in early pregnancy and its relationship to fetal birthweight in normal pregnancies and pre-eclampsia

Objectives

To study the relationships between 2D ultrasound measurements of placentation and maternal serum (MS) levels of PAPP-A, inhibin A and fβhCG in early pregnancy and subsequent fetal growth in pregnancies with a normal and abnormal outcome.

Study design

Prospective population-based cohort study of 301 pregnancies with a normal outcome, 18 with a pregnancy complicated by pre-term delivery (PTD) and 14 with subsequent pre-eclampsia (PE).

Main outcome measures

Basal placental surface area, placental thickness, ellipsivity and volume; MS PAPP-A and fβhCG at 11–13 + 6 weeks, MS inhibin A at 15–22 weeks and birthweight centile at delivery.

Results

In the normal group, the basal surface area showed a significantly (P < 0.001) positive correlation with placental thickness and placental ellipsivity. With the exception of placental ellipsivity, all other placental ultrasound parameters were significantly related with birthweight centile. Inhibin A showed a significant (P < 0.005) correlation with birthweight centiles. The basal plate surface area and MS PAPP-A were significantly (P < 0.01 and P < 0.001, respectively) lower and MS inhibin A significantly (P < 0.01) higher in PE than in controls. No changes were found in pregnancies complicated by PTD.

Conclusion

The basal plate surface area at 11–14 weeks reflects indirectly normal and abnormal placentation and development of the definitive placenta. Combined with MS PAPP-A and/or inhibin A levels this parameter could be useful in identifying from the end of the first trimester, pregnancies subsequently complicated with PE.     

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion

Objective

This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP).

Methods

In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters.

Results

A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025–0.57]; p = 0.008).

Discussion

Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates.

Conclusions

Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.     

Effect of pregestational diabetes mellitus on first trimester placental characteristics: Three-dimensional placental volume and power Doppler indices

Objective

To investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester.

Methods

This was a prospective case–control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β human chorionic gonadotrophin (β-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group.

Results

3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p < 0.02) and negatively correlated with the degree of maternal metabolic control at first trimester.

Conclusions

Pregestational DM induces demonstrable alterations in first trimester placental development, with significantly reduced placental vascularization indices and PAPP-A values. This effect is independent of the later development of PAHC.     

The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: A systematic review and meta-analysis

Introduction

Several epidemiological studies have found a positive association between chronic hepatitis B virus (CHB) infection and the risk of placental abruption and placenta previa, but various studies have reported conflicting findings. The objective was to systematically review the literature to determine a possible association between CHB infection and these two placental complications.

Methods

We conducted a computerized search in electronic database through March 1, 2014, supplemented with a manual search of reference lists, to identify original published research on placental abruption and placenta previa rates in women with CHB infection. Data were independently extracted, and relative risks were calculated. The meta-analysis was performed using Stata version 10.0 software.

Results

Five studies involving 9088 placenta previa cases were identified. No significant association between CHB infection and placenta previa was identified (OR = 0.98, 95% CI = 0.60–1.62). Five studies involving 15571 placental abruption cases were identified. No significant association between CHB infection and placental abruption was identified (OR = 1.42, 95% CI, 0.93–2.15).

Discussion

The immune response against the virus represents a key factor in determining infection outcomes. No observation of significant increased risk of the placental complications could be partially explained by the complex immune response during CHB infection.

Conclusions

Our meta-analysis found no evidence of significant associations between CHB infection and increased risk of placental abruption as well as placenta previa. Further well-designed studies were warranted to assess any potential association between CHB infection and increased risk of placental abruption as well as placenta previa.     

Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion

Objective

To evaluate 2-year neurodevelopmental outcomes of near-term, small-for-gestational-age (SGA) newborns segregated by presence or absence of histopathology reflecting placental underperfusion (PUP).

Patients and methods

A cohort of consecutive near-term (≥34.0 weeks) SGA newborns with normal prenatal umbilical artery Doppler studies was selected. All placentas were inspected for evidence of underperfusion and classified in accordance with established histologic criteria. Neurodevelopmental outcomes at 24 months (age-corrected) were then evaluated, applying the Bayley Scale for Infant and Toddler Development, Third Edition (Bayley-III) to assess cognitive, language, and motor competencies. The impact of PUP on each domain was measured via analysis of covariance, logistic and ordinal regression, with adjustment for smoking, socioeconomic status, gestational age at birth, gender, and breastfeeding.

Results

A total of 83 near-term SGA deliveries were studied, 46 (55.4%) of which showed signs of PUP. At 2 years, adjusted neurodevelopmental outcomes were significantly poorer in births involving PUP (relative to SGA infants without PUP) for all three domains of the Bayley scale: cognitive (105.5 vs 96.3, adjusted-p = 0.03), language (98.6 vs 87.8, adjusted-p<0.001), and motor (102.7 vs 94.5, adjusted-p = 0.007). Similarly, the adjusted likelihood of abnormal cognitive, language, and motor competencies in instances of underperfusion was 9.3-, 17.5-, and 1.44-fold higher, respectively, differing significantly for the former two domains.

Conclusions

In a substantial fraction of near-term SGA babies without Doppler evidence of placental insufficiency, histologic changes compatible with PUP are still identifiable. These infants are at greater risk of abnormal neurodevelopmental outcomes at 2 years.     

The clinical significance of large placental lakes

Objective

The aim of our study was to establish whether there is a correlation between the size of placental lakes and adverse pregnancy outcome.

Study design

Target ultrasonography for diagnosis of placental lake was performed in the 2nd trimester of pregnancy and followed up in the 3rd trimester. Placental lakes were defined as homogenous sonolucent avillous lesions greater than 2 cm × 2 cm in diameter. The 109 pregnant women enrolled in this study were divided into four groups according to the size and change in size of placental lakes. Clinical characteristics and pregnancy outcomes in each group were compared.

Results

Some placental lakes decreased and disappeared, whereas others persisted. There were no significant differences in clinical characteristics among the four investigated groups. Fetal small-for-gestational-age status was significantly correlated with large placental lakes, compared to small.

Conclusion

Large placental lakes were correlated with the fetal status of small for gestational age. Therefore, if a large placental lake is identified in the 2nd trimester of pregnancy, appropriate surveillance should be considered for the remainder of the pregnancy.     

Do placental histologic findings of chorion-decidual hemorrhage or inflammation in spontaneous preterm birth influence outcomes in the subsequent pregnancy?

Introduction

Spontaneous preterm birth (SPTB) is the common endpoint of different underlying etiologies, including chorion-decidual bleeding and inflammation. However, specific histologic findings from a prior pregnancy do not always inform clinical management in subsequent pregnancies secondary to few prior studies having evaluated the relationship between prior pregnancy pathology and subsequent outcomes in patients with SPTB.

Methods

Included subjects had: 1) a SPTB with available placental pathology and 2) a subsequent consecutive delivery at >20 weeks gestational age at our institution. For included subjects archived placenta and membrane paraffin blocks from the index SPTB were cut, stained with Prussian Blue and evaluated by a perinatal pathologist for the presence of hemosiderin. The association between histologic findings and subsequent pregnancy outcomes were evaluated through logistic and linear regression.

Results

A total of 131 subjects were included, of whom 39.7% had a recurrent SPTB. Funisitis at the time of preterm delivery significantly increased the risk of early (<34 weeks) recurrent preterm birth (OR 3.38, p = 0.016), though this may have been confounded by gestational age at delivery. Several histologic features were significantly associated with reductions in birth weight in the subsequent pregnancies, even if they did not increase the risk of recurrent preterm birth.

Discussion

The presence of chorion-decidual bleeding or inflammation in a prior pregnancy can signal an increased risk in a future pregnancy beyond the recurrent risk of SPTB itself.

Conclusions

Placental histologic findings after SPTB maybe associated with differences in birth weight in a subsequent pregnancy.     

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency

Objectives

To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking.

Methods

A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation.

Results

A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161).

Discussion

In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease.

Conclusions

A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.     

Systematic review of placental pathology reported in association with stillbirth

Introduction

Histopathological examination of the placenta is recommended to determine the cause of stillbirth. Although some reports find causal or contributory placental abnormalities in up to 60% of stillbirths, the significance of such findings in this clinical setting remains uncertain. A systematic review was conducted to i) investigate the likelihood of diagnosing a cause of stillbirth from placental examination and ii) to identify the specific causes of death that can be diagnosed from placental pathology.

Methods

Medline, Embase, Biosis, and Web of Science were searched using the terms “stillbirth”, “histopathology”, “pathology”, and “placenta”. Case-reports, narrative review articles and studies that failed to define diagnostic sub-groups were excluded. 473 potential studies were identified. Relevant studies (n = 41) were subdivided into those that investigated causes of stillbirth (n = 13), and those that identified conditions associated with stillbirth (n = 5). The contributory value of placental examination to stillbirth classification was evaluated in 10 studies and the role of specific placental abnormalities in the aetiology of stillbirth in 20 studies.

Results

The proportion of stillbirths attributed to a placental cause ranged from 11 to 65%. Classification systems which included multiple placental categories and allowed placental findings to supersede other disorders reported higher rates of placental causes and fewer unexplained stillbirths. Diagnoses were frequently based on qualitative, non-specific terminology.

Conclusions

The utility of histopathological examination of the placenta is affected by the classification system used. International consensus is required for both diagnostic criteria and terminology to describe placental abnormalities and on classification of stillbirths..     

The role of Hofbauer cells on the pathogenesis of early pregnancy loss

Introduction

Hofbauer cells (HC) are the placental macrophages that play a significant role in many important placental events. The aim of this retrospective study is to investigate the role of HC in the pathogenesis of early pregnancy loss (EPL).

Methods

The slides were obtained from archival blocks of missed abortion (MA, n = 15) and blighted ovum (BO, n = 15) cases. Unwanted pregnancies materials constituted the control group (n = 15). HC and endothelial cells were identified using immunohistochemical methods. HC were counted under light microscope. The extent of villous vasculature was evaluated using two methods; the Chalkey method and microvessel scoring.

Results

The mean number of villous HC was found to be significantly higher in both MA and BO groups in contrast to the control group. MA group also showed a higher number of HC in comparison with the BO group. Higher microvessel scoring was also found in MA group in contrast to other two groups. Chalkey method revealed no significant difference in the extent of villous vasculature for the control group in comparison with MA and BO.

Discussion

As we identified relatively low quantity of HC in BO associated with defective vasculature, we hypothesize that an inadequate microvessel formation after hypoxic insult can explain the pathogenesis of BO. We believe that HC are increased in MA due to their divergent roles on immunity and inflammation.

Conclusion

We therefore conclude that HC may be of biological importance in the pathogenesis of EPL.     

Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model

Objective

We tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR).

Methods

Timed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis.

Results

Compared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways.

Conclusion

This novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI.

Condensation

A new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.     

Is hyperemesis gravidarum associated with placental weight and the placental weight-to-birth weight ratio? A population-based Norwegian cohort study

Introduction

Studies have suggested a link between placental weight, placental weight-to-birth weight ratio (PW/BW) and adult health. Hyperemesis gravidarum (HG) may also have implications for adult health. No studies on HG and placental characteristics have been identified. We therefore explored the relationship between HG, placental weight and the PW/BW-ratio in a population-based cohort.

Methods

Singleton births to primiparous women between 1999 and 2009 with data on HG, placental weight and birth weight in the Medical Birth Registry of Norway (MBRN) comprised the study base (n = 200,390). HG was defined through ICD-10 code 021.0, 021.1 and 021.9. Gender and gestational age specific percentile curves for placenta weight and PW/BW ratio were used to define those below the 10th and above the 90th percentile of both outcomes. Associations between HG and dichotomous outcomes were studied by multiple logistic regression. Multiple linear regression was applied to study placental weight as a continuous variable. Male and female offspring were analyzed separately.

Results

The prevalence of HG was 1.2%. Women with HG and female offspring had significantly higher risk of a PW/BW-ratio above the 90th percentile (OR = 1.17, 95% CI: 1.03–1.34). HG and PW/BW-ratio below the 10th percentile were inversely associated (OR = 0.70, 95% CI: 0.56–0.89). For male offspring no association was observed for HG and PW/BW-ratio below the 10th or above the 90th percentile.

Discussion/conclusions

We observed positive associations between HG and high PW/BW ratio limited to female offspring only. The high PW/BW-ratio suggests that there may be a possible link between HG and adult health.     

A new method for measurement of placental elasticity: Acoustic radiation force impulse imaging

Introduction

The velocities of the lateral shear waves (Vs; m s⁻¹) generated by an acoustic radiation force impulse (ARFI) correlate with Young's modulus. Therefore, ARFI can be used as a new method to evaluate tissue elasticity. The aim of this study was to investigate the safety of ARFI imaging and the differences in placental elasticity in complicated cases.

Methods

The study population included 115 patients between 26 and 41 weeks gestation, who were divided into three groups, namely normal, fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH). After delivery, the Vs values of the placenta were measured ex vivo. After ARFI imaging, microscopic examination was performed, the Vs values were compared among the three groups and the relationship between the Vs values and neonatal birthweight Z-score was investigated.

Results

No histological changes were noted even after ARFI imaging. The Vs values in the FGR group were significantly higher than those in the normal group (1.94 ± 0.74 and 1.31 ± 0.35 m s⁻¹, respectively; p < 0.05). The Vs values demonstrated a significant negative correlation with the Z-score. Moreover, as the Z-score became lower, the Vs values became higher in the range of Z-scores under −0.5 standard deviation (SD).

Discussion

We speculate that the increased Vs values in the FGR group may have been caused by histological changes, and that a more severe FGR might result in increased Vs values.

Conclusion

ARFI imaging was observed to have no apparent histological damage to the placental tissue. Ex vivo placentas from the FGR group were significantly more firm. Moreover, Vs values and Z-scores of birthweight had a significant negative correlation. Additional investigations are needed about the utility of this method for the evaluation of placental function in vivo.     

Effect of maternal nutrient restriction and melatonin supplementation from mid to late gestation on vascular reactivity of maternal and fetal placental arteries

Introduction

Maternal nutrient restriction and decreased scotophase concentrations of melatonin have been associated with severely compromised pregnancies. We hypothesized that melatonin supplementation in a compromised pregnancy enhances the bradykinin (BK)-induced relaxations of placental arteries thereby ensuring sufficient umbilical blood flow to the developing fetus.

Methods

Pregnant ewes (n = 31) were fed an adequate (ADQ) or nutrient restricted (RES) diet supplemented with 5 mg of melatonin (MEL) or without melatonin (CON) from day 50 to 130 of gestation. On day 130 of gestation, the maternal (caruncular; CAR) and fetal (cotyledonary; COT) placental arteries were suspended in organ chambers for isometric tension recording.

Results

There were no treatment or dietary effects on CAR arteries for any vasoactive agent. However, in COT arteries, MEL ewes were more sensitive (P < 0.01) to bradykinin-induced relaxation than CON ewes. There was a melatonin by nutritional level interaction (P < 0.01) with sodium nitroprusside-induced relaxation of COT arteries where CON-RES were more sensitive to sodium nitroprusside compared to CON-ADQ, which was in contrast to when ewes were fed MEL. There was a significant melatonin by nutritional interaction (P = 0.04) for responsiveness to norepinephrine. The sensitivity of the COT arteries to norepinephrine in CON-RES ewes was decreased compared to CON-ADQ. Melatonin supplementation, regardless of maternal dietary intake, resulted in COT arteries having similar responsiveness to CON-RES ewes.

Conclusion

An increase in placental vessel sensitivity to bradykinin-induced relaxation may contribute to melatonin-induced increases in umbilical artery blood flow.     

Reduction of maternal circulating endothelial progenitor cells in human pregnancies with intrauterine growth restriction

Introduction

Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion.

Methods

Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45^dim/CD34⁺/KDR⁺ cells by flow cytometry. Plasmatic cytokines were measured by ELISA.

Results

We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment.

Conclusions

EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.     

Placental perfusion in normal pregnancy and early and late preeclampsia: A magnetic resonance imaging study

Objective

Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy.

Methods

The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated.

Results

Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001).

Conclusion

Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.     

First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction

Objective

We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR).

Study design

Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used.

Results

The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia.

Conclusion

First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.     

Association between first-trimester placental volume and birth weight

Objective

To estimate the correlation between first-trimester placental volume, birth weight, small-for-gestational-age (SGA), and preeclampsia.

Methods

A prospective study of women with singleton pregnancy at 11–13 weeks of gestation was conducted. First-trimester placental volume was measured using three-dimensional ultrasound and reported as multiple of median (MoM) for gestational age. Participants were followed until delivery where birth weight, placental weight, and occurrence of preeclampsia were collected. Non-parametric analyses were performed.

Results

We reached a complete follow-up for 543 eligible women. First-trimester placental volume was significantly correlated with birth weight (correlation coefficient: 0.18; p < 0.0001) and placental weight (cc: 0.22; p < 0.0001) adjusted for gestational age. First-trimester placental volume was smaller in women who delivered SGA neonates (median MoM: 0.79; interquartile range: 0.62–1.00; p < 0.001) and greater in women who delivered large-for-gestational-age neonates (median MoM: 1.13; 0.95–1.49; p < 0.001) when compared to women with neonates between the 10th and 90th percentile (median MoM: 1.00; 0.81–1.25). First-trimester placental volume was not associated with the risk of preeclampsia (cc: 0.01; p = 0.87).

Conclusion

First-trimester placental volume is strongly associated with fetal and placental growth. However, we did not observe a correlation between placental volume and the risk of preeclampsia.     

Decidual vasculopathy in preeclampsia: Lesion characteristics relate to disease severity and perinatal outcome

Objective

In a proportion of patients with preeclampsia, unremodeled spiral arteries develop additional pathological changes, termed decidual vasculopathy (DV), or acute atherosis. DV has been correlated to adverse clinical outcome and increased placental pathology. However, it was unclear whether these effects pertained to individual features of DV.

Methods

We performed a reanalysis of placental samples from preeclamptic pregnancies (n = 76), recording the number of vessels with DV, their location in the decidua and their morphological features. Results were correlated with clinical and placental parameters, using Spearman's rho test. P-value < 0.05 was considered significant.

Results

Total number of vessels with DV (totalDV) correlated with higher diastolic blood pressure, higher urine protein-to-creatinine ratio, shorter gestational age, lower birth weight, 5 min APGAR score and umbilical artery pH, and with increased accelerated villous maturity, infarction and hematoma formation, but not with HELLP syndrome markers. Additionally, there was a striking correlation of increased perinatal mortality with the number of vessels located in the decidua basalis (DVbas), and with vessels showing DV with thrombosis (DVthrom). Other morphological features, such as foam cell infiltration, did not increase correlation strength.

Discussion

In our study of preeclamptic placental samples, totalDV related to worse clinical outcome and increased placental pathology. Moreover, DVbas and DVthrom related to perinatal death. DV could be a manifestation of an underlying (vascular) pathology, increasing the risk of adverse pregnancy outcome.

Conclusions

In preeclampsia, totalDV, DVbas and DVthrom correlated with increased placental pathology and adverse maternal and fetal outcome, most relevantly with perinatal mortality.     

Social disparity affects the incidence of placental abruption among multiparous but not nulliparous women: a register-based analysis of 1,162,126 singleton births

Objectives

To identify risk factors for placental abruption and to evaluate associations between adverse perinatal outcomes and placental abruption stratified by parity among women with singleton births from 1991 to 2010 in Finland.

Study design

A retrospective population-based case–control study of singleton births in Finland from 1991 to 2010 (n = 1,162,126 from the Finnish Medical Birth Register). We modelled the group-specific risk factors for placental abruption in unadjusted and adjusted models.

Results

In total 3.5 and 3.7 per 1000 nulliparous and multiparous women, respectively, were affected by placental abruption. The recurrence rate was 8.6 per 1000 births. The adjusted risk for placental abruption increased in pregnancies characterised by advanced maternal age, low birth weight, smoking, major congenital anomaly, preeclampsia and male foetal sex in both parity groups. In vitro fertilisation increased the risk only in nulliparae whereas anaemia, a prior caesarean section and the lowest socioeconomic status increased the risk in multiparae. Births affected by placental abruption were associated with an increased admission for neonatal intensive care, preterm birth, low birth weight (<2500 g), small for gestational age infants, low Apgar scores, and low newborn umbilical vein pH (<7.15). Placental abruption resulted in increased risks of stillbirth and early neonatal death in both parity groups.

Conclusions

The burden of placental abruption is equal in nulliparae and multiparae, but risk factors vary substantially. Social disparity only affects the incidence of placental abruption among multiparous women, indicating that factors related to lifestyle and health behaviour have different effects on the parity groups.