OBJECTIVE: We present high-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 21, prenatal progressive decrease of the trisomy 21 cell line, acute fatty liver of pregnancy and intrauterine fetal death (IUFD) in late gestation.
METHODS: A 32-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 21 at 12 weeks of gestation. This pregnancy was conceived by in vitro fertilization. She did not have obesity, diabetes mellitus, hepatic biliary disorders and preeclampsia. Amniocentesis revealed a karyotype of 47,XY,+21[10]/46,XY[11], and array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 2-3. She was referred for genetic counseling, and repeat amniocentesis performed at 21 weeks of gestation revealed the karyotype of 47,XY,+21[10]/46,XY[28]. The parental karyotypes and fetal ultrasound findings were normal. Simultaneous molecular analysis on uncultured amniocytes showed no uniparental disomy 21, but a maternal origin of trisomy 21 by quantitative fluorescent polymerase chain reaction (QF-PCR) and the result of arr 21q11.2q22.3 × 2.5 by aCGH analysis. At 27 weeks of gestation, she underwent a third amniocentesis, of which conventional cytogenetic analysis revealed the result of 47,XY,+21[5]/46,XY[17] in cultured amniocytes, and aCGH analysis revealed arr 21q11.2q22.3 × 2.48, and interphase fluorescence in situ hybridization (FISH) analysis revealed 39% (39/100 cells) mosaicism fro trisomy 21 in uncultured amniocytes. At 36 weeks of gestation, the woman suffered from a sudden onset of acute fatty liver and IUFD. A 3522-g male baby was delivered without Down syndrome phenotype. The umbilical cord had a karyotype of 47,XY,+21[10]/46,XY[30]. aCGH analysis on the skin and placenta showed arr 21q11.2q22.3 × 2.73 and arr 21q11.2q22.3 × 2.75, respectively. QF-PCR analysis of umbilical cord, placenta and skin showed a maternal origin of trisomy 21.
CONCLUSIONS: High-level mosaic trisomy 21 at amniocentesis can be associated with prenatal progressive decrease of the trisomy 21 cell line in cultured amniocytes and perinatal fetal mortality and maternal morbidity.

Intrauterine fetal demise (IUFD) - fetal loss after 20 weeks - affects 6 pregnancies per 1,000 live births in the United States, and the majority are of unknown etiology. Maternal systemic regulatory T cell (Treg) deficits have been implicated in fetal loss, but whether mucosal immune cells at the maternal-fetal interface contribute to fetal loss is under-explored. We hypothesized that the immune cell composition and function of the uterine mucosa would contribute to the pathogenesis of IUFD. To investigate local immune mechanisms of IUFD, we used the CBA mouse strain, which naturally has mid-late gestation fetal loss. We performed a Treg adoptive transfer and interrogated both pregnancy outcomes and the impact of systemic maternal Tregs on mucosal immune populations at the maternal-fetal interface. Treg transfer prevented fetal loss and increased an MHC-IIlow population of uterine macrophages. Single-cell RNA-sequencing was utilized to precisely evaluate the impact of systemic Tregs on uterine myeloid populations. A population of C1q+, Trem2+, MHC-IIlow uterine macrophages were increased in Treg-recipient mice. The transcriptional signature of this novel uterine macrophage subtype is enriched in multiple studies of human healthy decidual macrophages, suggesting a conserved role for these macrophages in preventing fetal loss.

UNASSIGNED: Timely prenatal diagnosis, regular checkups, and comprehensive counseling are vital in preventing and managing complications in high-risk pregnancies like partial molar pregnancy with hydrops fetalis.
UNASSIGNED: A live singleton fetus with partial molar pregnancy is a rare condition. We report a case of partial mole with hydrops fetalis causing intrauterine fetal demise (IUFD) in the third trimester. Our case involves a 20-year primigravid without prior antenatal checkups who presented to outpatient department at 31 weeks and 5 days of gestation with lower abdominal pain, backache, vaginal spotting, and decreased fetal movement. Ultrasound revealed partial mole, hydrops fetalis, and IUFD. The patient underwent induced delivery expelling a 1900 gm female fetus with no viability and a placenta containing 650 gm of molar tissue. Placental tissue with cystic component was confirmed as molar tissue by histopathological examination. She was discharged a few days afterward and had undetectable beta-human chorionic gonadotropin levels after a month. Prenatal diagnosis, counseling, rigorous antepartum surveillance, and appropriate postpartum follow-up are essential for the best possible mother and fetal outcomes.

UNASSIGNED: This study aimed to evaluate the potential value of placental anatomic features and various types of normal and abnormal cord insertion types in predicting adverse maternal-fetal outcomes in singleton pregnancies. We also tried to assess the association between these outcomes and various types of placental cord insertion.
UNASSIGNED: This prospective observational study was performed on singleton pregnancies. For each patient placental features including diameter, thickness, type of cord insertion, and the shortest distance between the cord insertion point and placental edge were recorded. The relationship between these factors and the development of multiple adverse pregnancy outcomes including preterm labor, intrauterine fetal death (IUFD), and the rate of neonatal intensive care unit (NICU) admissions were evaluated and reported.
UNASSIGNED: Overall 308 patients were enrolled in the study. Smoker mothers had significantly smaller placentas (P-value = .008), and those with lower diameter placentas were more likely to suffer from IUFD (P-value = .0001). Shorter placental cord insertion distances led to more episodes of preterm labor (P-value = .057). Eccentric-type placental cord insertion was significantly associated with the development of preeclampsia (P-value = .006).
UNASSIGNED: Abnormalities in placental diameter and cord insertion can lead to significant maternal-fetal complications including preterm labor, IUFD, and preeclampsia.

OBJECTIVE: We present mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 16, placental trisomy 16, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.
METHODS: A 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 16 at 12 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+16 [10]/46,XX[17], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (16) × 3 [0.43] consistent with 43% mosaicism for trisomy 16. She was referred for genetic counseling at 19 weeks of gestation, and a fetus with IUGR was noted to have a size equivalent to 16 weeks of gestation. At 23 weeks of gestation, the fetus manifested oligohydramnios, fetal cardiomegaly and severe IUGR (fetal size equivalent to 20 weeks of gestation). Repeat amniocentesis revealed a karyotype of 46,XX (20/20 colonies) in cultured amniocytes and mosaic trisomy 16 by aCGH in uncultured amniocytes. aCGH analysis on uncultured amniocytes revealed the result of arr 16p13.3q24.3 × 2.3, consistent with 30% (log2 ratio = 0.2) mosaicism for trisomy 16. Quantitative fluorescence polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 16. The parental karyotypes were normal. IUFD was noted at amniocentesis. The pregnancy was subsequently terminated, and a 288-g female fetus was delivered with no phenotypic abnormalities. The umbilical cord had a karyotype of 46,XX (40/40 cells), and the placenta had a karyotype of 47,XX,+16 (40/40 cells). QF-PCR assays of the placenta confirmed a maternal origin of trisomy 16.
CONCLUSIONS: Mosaic trisomy 16 at amniocentesis can be associated with positive NIPT for trisomy 16, placental trisomy 16, IUGR, IUFD, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.

An actual knot that forms during pregnancy is known as a true knot of the umbilical cord (TKUC) which is seen in 0.3% to 1.2% of pregnancies. TKUC is noteworthy because it can lead to a variety of adverse perinatal outcomes, including infants with low Apgar scores, small for gestational age (SGA) fetuses, fetal hypoxia, and also in some cases fetal death. Here, we present instances of TKUC of three patients and the various associated perinatal outcomes.

The furcate insertion of the umbilical cord is an uncommon abnormality, often asymptomatic, potentially dangerous, or lethal for the fetus and the mother. This report shows the case of a healthy 29-year-old patient, at 37 weeks of gestation, admitted to the hospital two days before the due date because of the appearance of uterine contractions; clinical exams were regular. The following day, no fetal movements were perceived, a cardiotocography was performed, showing the absence of fetal heartbeat. A dead fetus was delivered. Autopsy showed furcate insertion of the umbilical cord and the rupture of the umbilical vessel, which caused fetal hemorrhagic shock. Furcate insertion still remains mostly undiagnosed and rarely it can be identified prenatally (only three cases are reported in literature). Future research, mainly in forensic fields, could improve the knowledge about this condition, helping prenatal diagnosis and providing warnings that can prevent similar deaths in the future.

UNASSIGNED: Antenatal fetal surveillance has been recommended for moderate/severe idiopathic polyhydramnios but not for mild idiopathic polyhydramnios. The purpose of this study is to determine if pregnancies with mild idiopathic polyhydramnios have an increased risk for an intrauterine fetal demise (IUFD).
UNASSIGNED: Medical records and amniotic fluid volume ultrasound data from 2016 to 2021 at a university medical center were examined. Pregnancies with fetal anomalies, fetal infection, isoimmunization, multiple gestation, maternal diabetes and oligohydramnios were excluded. Normal amniotic fluid volume was defined as an amniotic fluid index (AFI) <24 cm which was compared to mild idiopathic polyhydramnios, AFI of ≥24.0 cm-29.9 cm, and moderate/severe polyhydramnios which is an AFI ≥30 cm.
UNASSIGNED: Of 12,725 patients meeting inclusion study criteria, there were 249 with idiopathic polyhydramnios (n = 249) which was associated with an increased odds of IUFD (aOR) of 3.27 (CI 1.50-7.15), NICU admission (aOR 1.28, CI 0.96-1.70), 5-minute APGAR score less than 7 (aOR 2.16, CI 1.52-3.07), and large for gestational age infant (LGA) (aOR 4.04, CI 2.83-5.78) compared to normal amniotic fluid volume (AFV). In the mild polyhydramnios group (n = 204, out of the 249 women with polyhydramnios) compared to the 12,476 pregnancies with normal AFV group, IUFD (aOR 3.38, CI 1.46-7.82), NICU admission (aOR 1.19, CI 0.87-1.64), 5-minute APGAR score less than 7 (aOR 1.68, CI 1.10-2.55) and LGA (aOR 3.87, CI 2.59-5.78). In moderate/severe polyhydramnios group (n = 45) compared to the normal AFV group, there was no increased odds of IUFD (aOR 2.78, CI 0.38-20.29) or NICU admission (aOR 1.74, CI 0.93-3.26) but an increased odds for a 5-minute APGAR score less than 7 (aOR 4.94, CI 2.57-9.53) and LGA fetus (aOR 4.80, CI 2.26-10.22).
UNASSIGNED: There is an increased odds of IUFD in pregnancies complicated by mild idiopathic polyhydramnios. Patients should be counseled on an increased odds of adverse pregnancy outcomes associated with idiopathic polyhydramnios, and in those pregnancies with mild idiopathic polyhydramnios, antenatal fetal surveillance should be considered.

OBJECTIVE: This study describes the fetal and neonatal outcomes and their predictive factors in pregnancies with preterm premature rupture of membranes (PPROM) before 24 weeks of gestation.
METHODS: A retrospective study was conducted using the patient database of a tertiary university hospital in Lyon, France. All of the medical data of women diagnosed with PPROM before 24 weeks of gestation from 2008 to 2018 were extracted. R software was used for descriptive and analytical statistics.
RESULTS: The study included 78 women. Mean gestational age (GA) at PPROM was 19.6 weeks (13.1 to 23.9 weeks). Fifteen (19.2%) pregnancies were terminated, 37 (47.4%) resulted in intrauterine fetal death (IUFD), and 26 (33.3%) children were born alive at an average of 26.9 weeks of gestation. Fourteen children survived and 12 died after birth; 50% of survivors had pulmonary hypoplasia. Within 7 days after PPROM, 46% of IUFD occurred and 36% of pregnancies ended. PPROM before 20 weeks of gestation and chorioamnionitis are statistically associated with IUFD, whereas a latency period of more than 2 weeks is statistically related to live birth.
CONCLUSIONS: PPROM before 24 weeks of gestation is associated with a high rate of IUFD, preterm birth, and postpartum mortality.

We report the case of a 31-year-old woman with a history suggestive of obstetric antiphospholipid syndrome (APS) with recurrent miscarriages, preterm labour and intrauterine fetal death. During her last pregnancy, she was referred to the Rheumatology Clinic at King Fahad Military Medical Complex, Dhahran, Saudi Arabia. Serology for connective tissue diseases and APS was negative on multiple occasions. During previous pregnancies, her obstetrician had initiated several trials of baby aspirin with and without prophylactic heparin, without success. We diagnosed her with seronegative obstetric APS (SN-APS). A specific regimen, consisting of combination therapy with baby aspirin, low-molecular-weight heparin, hydroxychloroquine (<5 mg/kg/day) and low-dose prednisolone, was attempted. She delivered a healthy baby even though it was born preterm at 30 weeks of gestation because of abruptio placentae. Obstetric SN-APS is rare and should be considered and, if the history is highly suggestive, treated similarly to seropositive obstetric APS to reduce mortality.
CONCLUSIONS: Seronegative antiphospholipid syndrome (SN-APS) is very rare and often missed clinically.SN-APS should be treated similarly to seropositive obstetric APS to reduce recurrence.The antimalarial drug hydroxychloroquine should be considered 3 months before attempts at conception as it appears to decrease antiphospholipid levels.