BACKGROUND: A high frequency of single nucleotide somatic mutations in the placenta has been recently described, but its relationship to placental dysfunction is unknown.
METHODS: We performed a pilot case-control study using paired fetal, maternal, and placental samples collected from healthy live birth controls (n = 10), live births with fetal growth restriction (FGR) due to placental insufficiency (n = 7), and stillbirths with FGR and placental insufficiency (n = 11). We quantified single nucleotide and structural somatic variants using bulk whole genome sequencing (30-60X coverage) in four biopsies from each placenta. We also assessed their association with clinical and histological evidence of placental dysfunction.
RESULTS: Seventeen pregnancies had sufficiently high-quality placental, fetal, and maternal DNA for analysis. Each placenta had a median of 473 variants (range 111-870), with 95 % arising in just one biopsy within each placenta. In controls, live births with FGR, and stillbirths, the median variant counts per placenta were 514 (IQR 381-779), 582 (450-735), and 338 (245-441), respectively. After adjusting for depth of sequencing coverage and gestational age at birth, the somatic mutation burden was similar between groups (FGR live births vs. controls, adjusted diff. 59, 95 % CI -218 to +336; stillbirths vs controls, adjusted diff. -34, -351 to +419), and with no association with placental dysfunction (p = 0.7).
CONCLUSIONS: We confirmed the high prevalence of somatic mutation in the human placenta and conclude that the placenta is highly clonal. We were not able to identify any relationship between somatic mutation burden and clinical or histologic placental insufficiency.

Placental abruption is a serious medical condition that can occur during pregnancy, involving the premature separation of the placenta from the inner uterine wall before childbirth. This detachment often leads to severe bleeding, and if conventional methods prove ineffective in managing the bleeding, a hysterectomy may be deemed necessary to ensure the mother\'s safety. This case report details the management of a 22-year-old female, gravida IV, para III, who experienced placental abruption during her fourth pregnancy. An emergent cesarean section resulted in severe postpartum hemorrhage and disseminated intravascular coagulation (DIC). Positive drug tests for cocaine and methamphetamines added further complexity, leading to an unplanned hysterectomy for life-saving measures. This case underscores the critical importance of early recognition, multidisciplinary collaboration, and timely intervention in managing obstetric emergencies within the context of substance abuse.

BACKGROUND: Pregnant women have an increased risk of getting infected with SARS-CoV-2 and are more prone to severe illness. Data on foetal demise in affected pregnancies and its underlying aetiology is scarce and pathomechanisms remain largely unclear.
METHODS: Herein we present the case of a pregnant woman with COVID-19 and intrauterine foetal demise. She had no previous obstetric or gynaecological history, and presented with mild symptoms at 34 + 3 weeks and no signs of foetal distress. At 35 + 6 weeks intrauterine foetal death was diagnosed. In the placental histopathology evaluation, we found inter- and perivillous fibrin depositions including viral particles in areas of degraded placental anatomy without presence of viral entry receptors and SARS-CoV-2 infection of the placenta.
CONCLUSIONS: This case demonstrates that maternal SARS-CoV-2 infection in the third trimester may lead to an unfavourable outcome for the foetus due to placental fibrin deposition in maternal COVID-19 disease possibly via a thrombogenic microenvironment, even when the foetus itself is not infected.

We aimed to investigate whether maternal serum kisspeptin levels are associated with late-onset FGR and contribute to adverse perinatal outcomes.
In this case-control study, a total of 90 pregnant women admitted to the perinatology clinic were enrolled. Forty-five of them were diagnosed with FGR and 45 women with healthy pregnancies formed the control group. Maternal serum levels of kisspeptin 1 were compared.
Median kisspeptin1 serum levels were higher in the group of patients with FGR according to gestational age than in the control group [79.4(3.9-230.2) pg/mL vs. 39.8(0.4-188.3) pg/mL; p = 0.001]. The optimal cut-off value for kisspeptin1 was 30.32 pg/mL, with a positive predictive value of 64.6% (95% CI; 0.54-0.86), negative predictive value of 87.5% (95% CI; 0.44-0.72), positive likelihood ratio 1.75 (95% CI; 1.31-2.32), negative likelihood ratio 0.14 (95% CI; 0.04-0.44).
Kisspeptin1 differed significantly in late-onset FGR compared with the control group. This difference from the control group can be used to estimate late-onset FGR.

SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood.
To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress.
The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks\' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain.
We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

OBJECTIVE: Determine clinical risk factors for vasculo-placental disorders in singleton pregnancies.
METHODS: Prospective case-control study nested in HEMOTHEPP French cohort.
METHODS: Women delivered between June, 2015 and January, 2019 in any maternity ward of Finistère.
METHODS: Cases were women with vasculo-placental disorders (pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption or stillbirth). Controls were women matched for age at delivery and parity.
METHODS: Clinical data were collected by obstetricians or midwives during antenatal care visits and delivery, and recorded by trained research assistants.
METHODS: Occurrence of a vasculo-placental disorder.
RESULTS: 505 women with vasculo-placental disorder (299 pre-eclampsia, 253 IUGR, 44 placental abruptions, 11 stillbirths) and 1515 matched controls were selected out of 20,075 participants. In multivariable analysis, four clinical parameters were associated with pre-eclampsia: obesity (Odd ratio (OR) = 3.11, 95%CI 2.11-4.58), French overseas origin (OR = 4.41, 95%CI 1.87-10.42), previous vasculo-placental disorder (OR = 5.14, 95%CI 2.72-9.70), aspirin during pregnancy (OR = 10.10, 95%CI 1.99-51.08). Three clinical parameters were associated with IUGR: auto-immune/inflammatory disorder (OR = 3.75, 95%CI 1.83-7.68), previous vasculo-placental disorder (OR = 3.63, 95%CI 2.06-6.41), smoking during pregnancy (OR = 2.66, 95%CI 1.91- 3.71). A previous venous thromboembolism (VTE) was associated with IUGR in univariable but not in multivariable analysis (OR = 3.72, 95%CI 0.82-17.00, p = 0.09).
CONCLUSIONS: Clinical risk factors differ between IUGR and pre-eclampsia, the later, but not the former, being associated with cardiovascular risk factors.

Cohort study of singleton pregnancies with risk factors for placental insufficiency, managed at St. Michael\'s Hospital in Toronto, Canada. Patients undergone UA Doppler assessment at 18-22 weeks\' gestation and 6 weeks postpartum. 15 pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR) (cases) were compared to 17 unaffected pregnancies (controls). Cases with preeclampsia and/or IUGR had higher UA PI at 18-22 weeks than controls. By 6 weeks\' postpartum, the corresponding mean values were 2.60 and 2.14 (p = 0.20). This preliminary study suggests a potential different trajectory for physiologic recovery of UA flow after a pregnancy affected by placental insufficiency.

Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls.
A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups.
Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P < 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons.
Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons.

The coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion.
We analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings.
Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case.
METHODS: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition.
CONCLUSIONS: This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.