Patterns of Placental Injury in Congenital Anomalies in Second Half of Pregnancy

Abstract

Background Placental pathology in fetal congenital anomalies in second half of pregnancy is largely unknown. Methods Twenty-six clinical and 45 independent placental phenotypes from pregnancies ≥20 weeks of gestation with congenital anomalies divided into 4 groups were retrospectively compared with analysis of variance or χ 2 with 3 degrees of freedom and with Bonferroni correction for multiple comparisons: group 1 : 112 cases with heart malformations (with or without chromosomal anomalies), group 2 : 41 cases with abnormal karyotypes and anomalies other than heart malformations, group 3 : 87 cases with intrathoracic or intraabdominal mass-forming anomalies (mostly congenital diaphragmatic hernias and adenomatoid airway malformation), and group 4 : 291 miscellaneous cases with mostly skeletal, renal, and central nervous system anomalies not fulfilling the criteria of inclusion into groups 1 to 3. Results Eight of 26 clinical (30.8%) and 16 of 45 (35.5%) placental phenotypes varied statistically significantly among the 4 groups ( P < .05), of those, 7 (26.9%) and 4 (8.9%), respectively, remained statistically significant after Bonferroni correction ( P Bonferroni ≤ .002). Those placental phenotypes were placental weight, chorionic disc chorionic microcysts, fetal vascular ectasia, and luminal vascular abnormalities of chorionic villi. Conclusions Fetal anomalies in second half of pregnancy feature abnormal clinical phenotypes much more frequently than abnormal placental phenotypes. Chromosomal abnormalities with or without heart malformations tend to feature villous edema, and erythroblastosis of fetal blood, likely due to fetal heart failure. Mass-forming fetal anomalies feature placental histological lesions of shallow placental implantation, diffuse chronic hypoxic patterns of placental injury, and lesions of fetal vascular malperfusion, likely stasis-induced.

Grading placental fetal vascular malperfusion and short-term perinatal outcome

“…Although perinatal mortality, the most severe fetal pregnancy complication, is 3 times more frequent in this material of FVM than in our database of high-risk pregnancy [27], there were no statistically significant differences in this outcome rate among the 3 groups (Table I), which reflects various time intervals between the onset of FVM and delivery (temporal heterogeneity) more than etiology. We documented previously the characteristic association with mass-forming fetal anomalies and the lesions of FVM [36]. Some authors observed a trend towards more segmental FVM and higher grade FVM in cases of neonatal encephalopathy [11], but we observed intracerebral vascular thrombi even in low-grade SFVM diagnosed by CD34 immunohistochemistry only [32].…”

“…The lower rate of villous infarction in global FVM may be due to partial umbilical cord compromise in the etiology of this type of FVM that is known not to be associated with lesions of maternal vascular malperfusion. The same is true about the 2 features of shallow placental implantation which were previously reported in association with mass-forming fetal anomalies [36], but not with umbilical cord compromise [23]. It is difficult to explain why hypertrophic decidual arteriolopathy is more common in high-grade SFVM (Table II), particularly as there is no characteristic distribution in maternal hypertensive conditions among the 3 groups (Table I).…”

Placental recent/on-going foetal vascular malperfusion with endothelial fragmentation is diagnostically equivalent to established distal villous lesions of foetal vascular malperfusion

“…Other authors reported 8.7%, with a similar frequency of global and segmental FVM, with high-grade FVM more common than low-grade FVM [26]. We reported FVM in 10-24% of placentas from pregnancies complicated by congenital malformations, depending on the type of malformation, but in that material distal FVM was diagnosed traditionally based on clustered avascularity of distal villi on H&E staining (27). In the currently analysed population of high-risk pregnancies dominated by foetal congenital malformations, the prevalence of FVM was substantially higher because of expanding the inclusion criteria (endothelial fragmentation and hypovascularity by CD34, and segmental villous mineralization in addition to clusters of sclerotic distal villi and clusters of villi with stromal vascular karyorrhexis).…”

“…The absence of statistically significant differences in many clinical or placental phenotypes between Groups 1 and Group 2, but also among all 3 groups, indicates that FVM is only one of the patterns of placental injury having an impact on the foetal condition in this specific type of pathology dominated by frequently severe foetal congenital anomalies. Previously we reported that foetal anomalies in the second half of pregnancy show abnormal clinical phenotypes much more frequently than abnormal placental phenotypes, the mass-forming anomalies featuring diffuse chronic hypoxic patterns of placental injury and lesions of FVM, which are probably stasis-induced [27]. Our current material obtained in the Children's Hospital contained few hypertensive conditions of pregnancy, diabetes mellitus, infections, chronic FHR abnormalities, genetic thrombophilia, FGR, and oligohydramnios, i.e.…”

“…Although numerically predisposing to FVM, as discussed above, various clinical conditions are not specifically associated with various types of FVM, which reflect the temporal heterogeneity thereof related to the time of onset before delivery or stillbirth [13]. The pathomechanism of FVM is therefore mostly similar to UC compromise (stasis-induced FVM), the difference being the absence of associated features of shallow placental implantation and chronic hypoxic patterns of placental injury [8,27] but not in this material dominated by congenital anomalies. The discussed distal lesions are the manifestation of the same continuous process [1,38] as stromal vascular karyorrhexis and clusters of sclerotic villi cluster together [25].…”