Maternal Underperfusion Research Articles

Clinical Characteristics of Hypospadias and Its Association with Very Low Birth Weight Infants with Small for Gestational Age

Purpose: To investigate the risk factors associated with hypospadias in very low birth weight (VLBW) infants (VLBWIs).Methods: We retrospectively analyzed 729 infants born at ≥24 weeks of gestational age and weighing <1,500 g from January 2012 to December 2022. We assessed the prevalence of hypospadias by birth weight percentiles and also compared the demographics and placental histopathology of the infants with hypospadias (n=52) and those without hypospadias (n=677).Results: Of the 729 patients analysed, hypospadias was recorded in 26 (20.3%), 14 (26.9%), and 12 (2.5%) infants in the <3rd, ≥3rd–<10th, and ≥10th–<90th percentiles, respectively. Of all of the patients with hypospadias, 50% had birth weights <3rd percentile (p<0.001). The hypospadias group demonstrated a longer mean gestational age (30.1 weeks vs. 27.9 weeks, p<0.001), lower incidence of maternal pregnancy-induced hypertension (48.1% vs. 17.3%, p<0.001), lower incidence of premature rupture of membrane (11.5% vs. 27.1%, p=0.013), lower acute chorioamniotic maternal response (9.1% vs. 35.2%, p<0.001), and higher maternal underperfusion (95.5% vs. 71.9%, p<0.001).Conclusion: The frequency of hypospadias was found to be the highest among VBLWIs <3rd percentile, who were severely small for their gestational age (SGA). Additionally, the incidence increased with a decreasing birth weight. Physical examination is necessary at birth for VLBWIs classified as SGA. Moreover, the data on the incidence of hypospadias among VLBWIs in neonatal intensive care units can assist in tracking counseling from the prenatal to the postnatal period for patients born <3rd percentile.

Utility of First Trimester Maternal Serum Alpha Fetoprotein to Predict Placental Ischemic Disease [18S

INTRODUCTION: While elevated second trimester maternal serum alpha fetoprotein (msAFP) has been associated with adverse pregnancy outcomes, the utility of first trimester msAFP for prediction of placental ischemic disease is not known. We sought to investigate whether first trimester msAFP correlates with pathology findings suggestive of ischemic placental disease. METHODS: An IRB-approved, multi-site retrospective cohort study was performed among patients with first trimester msAFP as part of routine aneuploidy screening and subsequent placental evaluation from April 2015-August 2016. Pathology report findings were reviewed and classified according to placental diagnostic criteria by the Perinatal Section of the Society for Pediatric Pathology. This classification included 1) amniotic fluid infection 2) maternal underperfusion 3) fetal vascular thrombo-occlusive disease and 4) inflammatory changes (ie. chronic villitis). Spearman correlation coefficient determined the relationship between first trimester msAFP and placental weight. Chi-square and Fisher exact test determined whether an elevated first trimester msAFP is associated with placental pathologic findings. RESULTS: We evaluated 368 patients with first trimester msAFP and placental pathology reports available for review. First trimester msAFP >2.0 MoM is predictive of a placental weight <10th percentile and is suggestive of placental ischemic disease 81.6% vs 57.7% (OR 3.24, 95% CI 1.37-7.66). First trimester msAFP > 2.0 is also associated with pathology findings consistent with fetal vascular occlusive disease 21.4% vs 6.1% (OR 4.17, 95% CI 1.76-9.91). CONCLUSION: Elevated first trimester msAFP is predictive of placental insufficiency and placental ischemic disease which can help identify at risk pregnancies in the first trimester.

Placental pathologic changes and perinatal outcomes in placenta previa

Placenta previa is a condition in which the placenta implants in the poorly vascularized lower uterine segment, which may result in inadequate uteroplacental perfusion, in turn, adversely affect the neonatal outcome. Abnormal placentation may also lead to severe postpartum hemorrhage as placenta separation proceeds. We aimed to evaluate the differences in placental histopathology and perinatal outcomes in pregnancies complicated with placenta previa and controls. We undertook a retrospective case-control study of 93 pregnancies with placenta previa and 81 controls between 2011 and 2017. Gross findings of the placenta showed that the placentas in placenta previa had significantly higher mean large chorionic plate diameters (18.5 ± 3.2 vs 17.5 ± 2.6 cm, P = .0298), chorionic plate areas (218.4 ± 62.9 cm2 vs 198.7 ± 56.0 cm2, P = .0344), and marginal cord insertion (19.8% vs 8.6%, P = .0411) than control groups. Placental histopathological findings showed that placentas in placenta previa was significantly associated with maternal underperfusion, including villous infarction (50.5% vs 25.9%, P = .0009) and increased intervillous fibrin deposition (38.7% vs 7.4%, P < .0001). Also, women in the placenta previa group had a higher rate of abnormally invasive placenta and severe postpartum hemorrhage. However, placenta previa was not associated with the increased risk of neonatal mortality and morbidity. Abnormal placentation into the poorly vascularized lower uterine segment induces compensatory placental growth and increased surface area in response to reduced placental perfusion, which was consistent with the histopathological findings of coagulative necrosis of chorionic villi and fibrin deposition in the intervillous space. The morphological changes occurring in placenta previa may have important roles in maintaining adequate uteroplacental-fetal perfusion, which may prevent adverse neonatal outcomes.

Placental Lesions in Meconium Aspiration Syndrome

BackgroundMeconium aspiration syndrome (MAS) is defined by respiratory distress requiring supplemental oxygen in a meconium-stained neonate. MAS is clinically subclassified as mild, moderate, and severe according to the oxygen requirement. The aims of this study were to compare the histological findings in the placentas of MAS neonates with those of meconium-stained but non-MAS neonates and to analyze the correlation between the severity of MAS and the grade of its histological parameters.MethodsWe collected 160 singleton term placentas from neonates with meconium staining at birth from a tertiary medical center, Seoul, Republic of Korea. We reviewed hematoxylin and eosin sections of tissue samples (full-thickness placental disc, chorioamniotic membranes, and umbilical cord).ResultsFunisitis was present more frequently in MAS than in non-MAS (p < .01), of which the stage was correlated with the severity of MAS (p < .001). The histological findings consistent with maternal underperfusion and chronic deciduitis were more frequent in MAS than in non-MAS (p < .05). There was a correlation between the degree of chorionic vascular muscle necrosis and the severity of MAS (p < .05).ConclusionsOur results suggest that fetal inflammatory response evidenced by funisitis occurs prenatally in MAS and that the stage of funisitis and of chorionic vascular muscle necrosis may be a predictive marker of the severity of MAS.

Inflammatory and vascular placental lesions are associated with neonatal amplitude integrated EEG recording in early premature neonates.

IntroductionPlacental histologic examination can assist in revealing the mechanism leading to preterm birth. Accumulating evidence suggests an association between intrauterine pathological processes, morbidity and mortality of premature infants, and their long term outcome. Neonatal brain activity is increasingly monitored in neonatal intensive care units by amplitude integrated EEG (aEEG) and indices of background activity and sleep cycling patterns were correlated with long term outcome. We hypothesized an association between types of placental lesions and abnormal neonatal aEEG patterns.ObjectiveTo determine the association between the placental lesions observed in extreme preterm deliveries, and their neonatal aEEG patterns and survival.Patients and methodsThis prospective cohort study included extreme premature infants, who were born ≤ 28 weeks of gestation, their placentas were available for histologic examination, and had a continues aEEG, soon after birth)n = 34). Infants and maternal clinical data were collected. aEEG data was assessed for percentage of depressed daily activity in the first 3 days of life and for sleep cycling. Associations of placental histology with clinical findings and aEEG activity were explored using parametric and non-parametric statistics.ResultsTwenty two out of the 34 newborns survived to discharge. Preterm prelabor rupture of membranes (PPROM) or chorioamnionitis were associated with placental lesions consistent with fetal amniotic fluid infection (AFI) or maternal under perfusion (MUP) (P < 0.05). Lesions consistent with fetal response to AFI were associated with absence of SWC pattern during the 1st day of life. Fetal-vascular-thrombo-occlusive lesions of inflammatory type were negatively associated with depressed cerebral activity during the 1st day of life, and with aEEG cycling during the 2nd day of life (P<0.05). Placental lesions associated with MUP were associated with depressed neonatal cerebral activity during the first 3 days of life (P = 0.007).ConclusionsDepressed neonatal aEEG patterns are associated with placental lesions consistent with maternal under perfusion, and amniotic fluid infection of fetal type, but not with fetal thrombo-oclusive vascular disease of inflammatory type. Our findings highlight the association between the intrauterine mechanisms leading to preterm parturition and subsequent depressed neonatal cerebral function early after birth, which eventually may put premature infants at risk for abnormal neurodevelopmental outcome.

Abnormal umbilical artery Doppler velocimetry and placental histopathological correlation in fetal growth restriction

Background . Doppler velocimetry (DV) is widely used to assess the vascular formation of the placenta in fetal growth restriction (FGR) and to estimate the haemodynamic condition of the growth-restricted fetus. Umbilical artery (UA) flow is essentially placental, rather than fetal. Hence, DV provides information about the fetal side of the placenta and, alongside placental histopathology, it could possibly help to decipher aetiopathogenesis in FGR cases. Objective . To correlate UA DV findings occurring in FGR with placental findings. Methods. The study was prospective and conducted in a low-income setting. A total of 130 non-anomalous singleton FGR pregnancies (≥24 weeks) were included in the study. All pregnancies were confirmed to be small for gestational age (SGA) after the birth of the neonate. The placental lesions and neonatal outcomes were correlated with DV findings before delivery: 65 cases with normal DV results constituted group 1, and group 2 had 65 cases with abnormal DV results such as reduced flow, absent UA end diastolic flow or reversal of UA end diastolic flow. Results . Group 2 had significantly lower mean (standard deviation) birth weights of 1.59 (0.4) kg v. 1.87 (0.23) kg for group 1 ( p <0.001). Considerably higher NICU mortality was seen in group 2 (30.5%) compared with group 1 (6.7%) ( p <0.001). The group 2 placentas weighed less, had a higher number of maternal underperfusion (MUP) lesions, higher levels of calcification. Among lesions of MUP, 4 lesions i.e. villous infarction ( p <0.001), villous agglutination ( p <0.001), syncytial knots ( p =0.003) and intervillous fibrin deposition ( p =0.001) were present in significantly higher numbers in the abnormal Doppler group compared with the normal Doppler group. Abnormal Doppler had a sensitivity of 80% and specificity of 92.3% for abnormal placental pathology (placental lesions ≥3). Conclusions. There was a significantly higher number of MUP lesions and neonatal morbidity in SGA patients with abnormal DV findings

Placental histopathological findings in preterm/term and early/late onset small for gestation age: Are they significant?

We undertook a prospective comparison of placental histopathological findings in preterm versus term and early onset versus late onset small for gestation age (SGA) to find more information on the etiological aspects of this disorder. A total of 130 women with nonanomalous SGA were allocated into preterm (n = 60); term (n = 70); early onset (n = 9) and late onset (n = 121) groups. The blinded intergroup placental histopathology comparison was performed both qualitatively (type of lesion) and quantitatively (number of the lesion). All SGA placentae showed varying number of maternal underperfusion (MUP), fetal under perfusion, inflammatory, and others lesions. There was a slight higher percentage of placenta having MUP in preterm and early onset SGA. Perivillous fibrin deposition was peculiar for placenta of preterm SGA (P = 0.043). Both preterm and early onset SGA had a higher number of placental lesions, but there was no statistical difference either in type or number of the placental lesion in any of the examined groups.

Placental examination: prognosis after delivery of the growth-restricted fetus.

This article describes the role of placental examination in the prognostic evaluation of fetal growth restriction (FGR) infants. A new comprehensive placental classification system was reported. Maternal underperfusion, fetal thrombotic vasculopathy (FTV), villitis (including villitis of unknown etiology and infectious villitis), inflammation, and immature/dysmature villi are important factors affecting FGR prognosis, whereas genomic imprinting is a key factor affecting growth and diseases, as well as placental abnormality. We discuss the role of placental examination in determining FGR prognosis. Maternal underperfusion, fetal thrombotic vasculopathy, and villitis (including villitis of unknown etiology and infectious villitis) are the most important findings affecting FGR prognosis. Although limited, data have suggested an association of inflammation and immature/dysmature villi with postnatal growth in FGR infants. Placental size also contributes postnatally through fetal programming. In addition, placental imprinting can be a key of pre and postnatal growth and diseases, including imprinting disorders, as well as placental abnormalities such as placental mesenchymal dysplasia.

Macroscopic and histological characteristics of retained placenta: A prospectively collected case-control study

IntroductionRetained placenta is a potentially fatal obstetric disorder due to postpartum hemorrhage, its pathophysiology is however unknown. We aimed to assess if retained placenta was associated with increased macroscopic and histological signs of placental maternal underperfusion, a pattern otherwise seen in preeclampsia and other disorders of defective placentation. MethodsThis was a case-control study of retained (n = 49) and non-retained (n = 47) placentas, collected from full-term singleton and otherwise healthy pregnancies, carried out at a tertiary level obstetric department. Macroscopic and histological analysis was performed. Signs of maternal placental underperfusion and signs of placental inflammation, fetal vascular thrombo-occlusive disease and increased placental attachment were recorded in a primary and secondary analysis respectively. Variables were compared groupwise using unconditional logistic regression or comparison of median or mean values. ResultsCompared to non-retained placentas retained placentas had a significantly smaller surface area (p = 0.05), were more oblong in shape (OR 5.24 95% CI:1.34–20.21) and showed overall more signs of maternal underperfusion (OR 2.52 95% CI: 1.07–5.87). There was no significant difference in signs of placental inflammation, fetal vascular thrombo-occlusive disease or placenta accreta but basal plate myometrial fibers were more common among retained placentas. ConclusionIn regard to shape, surface area and histological signs of maternal placental underperfusion, retained placentas showed a histological pattern similar to that seen in preeclamptic placentas.

Decrease in Sphingomyelin (d18:1/16:0) in Stem Villi and Phosphatidylcholine (16:0/20:4) in Terminal Villi of Human Term Placentas with Pathohistological Maternal Malperfusion.

Placental villi play pivotal roles in feto-maternal transportation and phospholipids constitute a major part of the villous membrane. We have been developing and optimizing an imaging system based on a matrix-assisted laser desorption/ionization (MALDI)-based mass spectrometer, which provides clear two-dimensional molecular distribution patterns using highly sensitive mass spectrometry from mixtures of ions generated on tissue surfaces. We recently applied this technology to normal human uncomplicated term placentas and detected the specific distribution of sphingomyelin (SM) (d18:1/16:0) in stem villi and phosphatidylcholine (PC) (16:0/20:4) in terminal villi. In the present study, we applied this technology to nine placentas with maternal or fetal complications, and determined whether a relationship existed between these specific distribution patterns of phospholipid molecules and the six representative pathological findings of placentas, i.e., villitis of unknown etiology (VUE), thrombus, atherosis, chorioamnionitis (CAM), immature terminal villi, and multiple branched terminal villi. In two placentas with the first and second largest total number of positive pathological findings, i.e., five and three positive findings, the specific distribution of SM (d18:1/16:0) in stem villi and PC (16:0/20:4) in terminal villi disappeared. The common pathological findings in these two placentas were atherosis, immature terminal villi, and multiple branched terminal villi, suggesting the possible involvement of the underperfusion of maternal blood into the intervillous space. On the other hand, the number of pathological findings were two or less in the seven other placentas, in which no specific relationships were observed between the differential expression patterns of these two phospholipids in stem and terminal villi and the pathological findings of the placentas; however, the specific distribution pattern of SM (d18:1/16:0) in stem villi disappeared in four placentas, while that of PC (16:0/20:4) in terminal villi was preserved. These results suggested that the absence of the specific distribution of PC (16:0/20:4) in terminal villi, possibly in combination with the absence of SM (d18:1/16:0) in stem villi, was linked to placental morphological changes in response to maternal underperfusion of the placenta.

Expression and function of placental uric acid transporter GLUT9

Expression and function of placental uric acid transporter GLUT9

796: Comparison of three methods for estimated fetal weight during active labor: a prospective study

795 Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate Eran Weiner, Jacob Bar, Nataly Fainstein, Letizia Schreiber, Avi Ben-Haroush, Michal Kovo Wolfson Medical Center, Holon, Israel, Rabin Medical Center, PetachTikva, Israel OBJECTIVE: To correlate between intra-operative findings, placental histopathology and neonatal outcome in emergent cesarean deliveries (ECD) for non-reassuring fetal heart rate (NRFHR). STUDY DESIGN: Data on ECD for NRFHR were reviewed for labor, documented intraoperative findings, neonatal outcome parameters and placental histopathology reports. Results were compared between those with and without intraoperative findings. Placental lesions were classified to those related to maternal underperfusion or fetal thrombo-occlusive disease, and those related to maternal (MIR) and fetal (FIR) inflammatory responses. Neonatal outcome consisted of low Apgar score ( 7 at 5 min), cord blood pH<7.0, and evidence of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy, or death. RESULTS: Intraoperative findings were observed in 49.5% of 543 women and included: cord entanglements in 77%, placental abruptions in 25.5%%, true knots in 6.6%, short cord in 6.3%, uterine rupture & dehiscence in 1.5 %, and cord prolapse in 1.5% (more than one cause was possible). Placental lesions were more common in those without intraoperative findings as compared to those with intraoperative findings: placental lesions related to maternal under-perfusion, vascular lesions , 9.1% vs. 4.1%, p1⁄40.024, and villous changes, 39.2% vs. 30.7%, p1⁄40.047, lesions consistent with fetal thrombo-occlusive disease, 13.6% vs. 7.4%, p1⁄40.024, and inflammatory lesions, MIR and FIR, p1⁄40.033, p1⁄40.001, respectively. By using multivariate logistic regression analysis, adverse neonatal outcome was found to be dependent on maternal age, gestational age, preeclampsia placental weight <10 %, and MIR. CONCLUSION: NRFHR necessitating ECD may originate from different underlying mechanisms. In about half, the insult is probably acute and can be identified intraoperatively. In the remaining half, underlying placental compromise may be involved.

Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate

ObjectiveTo correlate between intraoperative findings, placental histopathology and neonatal outcome in emergent cesarean deliveries (ECD) for non-reassuring fetal heart rate (NRFHR). Study designData on ECD for NRFHR were reviewed for labor, documented intraoperative findings, neonatal outcome parameters and placental histopathology reports. Results were compared between those with and without intraoperative findings. Placental lesions were classified to those related to maternal underperfusion or fetal thrombo-occlusive disease, and those related to maternal (MIR) and fetal (FIR) inflammatory responses. Neonatal outcome consisted of low Apgar score (≤7 at 5min), cord blood pH<7.0, and evidence of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic–ischemic encephalopathy, phototherapy, or death. ResultsIntraoperative findings were observed in 49.5% of 543 women, mostly cord complications (77%). Placental lesions were more common in those without intraoperative findings as compared to those with intraoperative findings: placental lesions related to maternal under-perfusion, vascular lesions, 9.1% vs. 4.1%, p=0.024, and villous changes, 39.2% vs. 30.7%, p=0.047, lesions consistent with fetal thrombo-occlusive disease, 13.6% vs. 7.4%, p=0.024, and inflammatory lesions, MIR and FIR, p=0.033, p=0.001, respectively. By using multivariate logistic regression analysis, adverse neonatal outcome was found to be dependent on maternal age, gestational age, preeclampsia placental weight <10th%, and MIR. ConclusionNRFHR necessitating ECD may originate from different underlying mechanisms. In about half, the insult is probably acute and can be identified intraoperatively. In the remaining half, underlying placental compromise may be involved.

Placental lesions associated with acute atherosis

Objective: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion (MVU), amniotic fluid infection (AFI), fetal vascular thrombo-occlusive disease (FVTOD) or chronic inflammation.Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women’s Hospital/Detroit Medical Center was conducted examine 16 457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis.Results: Among 16 457 women who were enrolled, 10.2% (1671/16 457) were excluded, leaving 14 786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14 786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio – aOR: 6.7; 95% CI 5.2–8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with FVTOD (aOR 1.7; 95% CI 1.2–2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3–3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with AFI, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3–0.5).Conclusions: Acute atherosis is associated with increased risks of having placental lesions consistent with MVU, and to a lesser extent, chronic chorioamnionitis and those consistent with FVTOD.

Cerebroplacental Doppler ratio and placental histopathological features in pregnancies complicated by fetal growth restriction

To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9±3.6 weeks, 1552±561 g, and 1.33±0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR]=3.14; 95% confidence intervals [CI]=1.58-6.28, P=0.001), mural hypertrophy (OR=2.35; 95% CI=1.26-4.4, P=0.008), immature intermediate trophoblast (OR=2.0; 95% CI=1.07-3.71, P=0.03) and maternal vascular underperfusion (OR=2.32; 95% CI=1.25-4.23, P=0.007) were the only parameters associated with severity of CPR. The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance.

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

ObjectivesTo describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. MethodsA 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. ResultsA 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). DiscussionIn 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. ConclusionsA significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.

The placental factor in early- and late-onset normotensive fetal growth restriction

ObjectiveOur objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA). Study designPlacentas from normotensive women who gave birth at 24–42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates. ResultsThe early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153). ConclusionEarly- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR.

Placental histopathological correlates of umbilical artery Doppler velocimetry in pregnancies complicated by fetal growth restriction

The objective of the study was to evaluate the association between placental histological patterns and umbilical artery (UA) Doppler velocimetry in pregnancies complicated by fetal growth restriction (FGR). A cohort of 126 FGR pregnancies was followed according to a standard protocol. Placental lesions were diagnosed according to consensus nomenclature and standardized criteria. Pulsatility index was normal in 45 (35.7%) and increased in 44 (34.9%) women. End-diastolic UA Doppler flow was absent in 27 (21.4%) and reversed in 10 (7.9%). Fifty-four women (42.9%) had preeclampsia. In preeclampsia, increasing Doppler abnormalities, from normal to reversed UA end-diastolic flow, were directly associated only with an increased number of placental syncytial knots. In normotensive pregnancies, Doppler abnormalities were associated with increased intervillous fibrin deposits, villous hypoplasia, syncytial knots, placental site giant cells, immature intermediate trophoblast, and with pattern of lesions indicating superficial implantation and maternal vascular underperfusion. In the whole cohort, increase of syncytial knots [odds ratio (OR) = 28.7; 95% confidence interval (CI) = 2.75-298.5], intervillous fibrin deposits (OR = 2.1; 95% CI = 1.04-4.28), placental site giant cells (OR = 3.0; 95% CI = 1.05-8.84), and patterns suggesting maternal underperfusion (OR = 2.9; 95% CI = 1.0-7.1) were independently associated with increased rates of absent/reversed UA end-diastolic flow. In pregnancies complicated by FGR, abnormalities of UA Doppler velocimetry were associated with placental lesions indicating superficial implantation and maternal vascular underperfusion.

The placental vascular component in early and late intrauterine fetal death

ObjectiveTo compare the placental histopathological findings between pregnancies complicated by early (<34weeks' gestation) and late (≥34weeks' gestation) intrauterine fetal death (IUFD) and pregnancies with live births. Material & MethodsPlacentas of patients with unexplained IUFD between 22–42weeks of gestation were analyzed for maternal vascular supply lesions that include those related to maternal underperfusion (villous changes and vascular lesions), fetal vascular supply lesions that include findings consistent with fetal thrombo-occlusive disease (villous changes and vascular lesions) and maternal and fetal inflammatory response lesions. The clinical characteristics and placental findings were compared with those from live birth controls adjusted for gestational age. ResultsIn the early IUFD group (n=28), compared to controls with early delivery, a higher rate of vascular lesions consistent with fetal thrombo-occlusive disease (28.6% vs. 0, p=0.002), villous changes consistent with fetal thrombo-occlusive disease (21.4 vs. 3.6%, p=0.043), and cord related lesions (46.4% vs. 0, p<0.001), respectively, were observed. A similar high rate of maternal vascular supply lesions was detected in both groups. In the late IUFD group (n=30), compared to controls, a higher rate of cord related lesions, 40% vs. 0, respectively, p<0.001, were found. In contrast, maternal and fetal inflammatory response lesions were more common in controls than in placentas from early and late IUFD. ConclusionsThe involvement of placental fetal vascular supply lesions is more extensive in early IUFD than in late IUFD, when compared with matched controls.

The placental component in early‐onset and late‐onset preeclampsia in relation to fetal growth restriction

To identify pathological placental differences between early-onset and late-onset preeclampsia, in relation to fetal growth restriction (FGR). Placentas from patients with preeclampsia were analyzed for lesions of maternal vascular supply consistent with maternal underperfusion and lesions of fetal vascular supply consistent with fetal thrombo-occlusive disease. Findings were compared between patients who gave birth before 34 weeks (early-onset preeclampsia) and after 34 weeks (late-onset preeclampsia). Compared with the late-onset group (n = 93), the early-onset group (n = 37) had higher rates of FGR (62.2% vs 25.8%, P < 0.001) and lesions of maternal vascular supply (95% vs 60%, P < 0.001). Within the early-onset group, cases with FGR (n = 23) had more lesions of fetal vascular supply (47.8% vs 7%, P = 0.01), with similar high rates of lesions of maternal vascular supply (91% vs 100%) compared with those without FGR. Within the late-onset preeclampsia group, cases with FGR (n = 24) had higher rates of maternal vascular supply lesions (88% vs 51%, P = 0.003) than those without FGR, but similar rates of fetal vascular supply lesions (25% vs 16%, P = 0.32). The placental fetal vascular supply lesions in combination with maternal vascular lesions are more dominant in early-onset preeclampsia with FGR as compared with early-onset preeclampsia without FGR.