Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study.

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Prolonged abdominal pregnancy incidentally discovered during cesarean section: a case report.

BACKGROUND: Abdominal pregnancy is a rare medical condition that is still missed in developing countries due to inadequate medical facilities. The clinical indicators manifest in various forms and are nonspecific, making it challenging to diagnose and often leading to delayed detection. However, obstetric ultrasound serves as an essential tool in early detection. Our objective was to share our experience dealing with this condition and emphasise the importance of early ultrasound diagnosis through efficient pregnancy monitoring in our regions. CASE PRESENTATION: 35-year-old Black African woman who had ten months of amenorrhea sought consultation due to an absence of active foetal movements. Her pregnancy was of 39 weeks with fetal demise which was confirmed following clinical examination and ultrasound. She underwent cesarean section in view of transverse position of fetus. During cesarean section, the fetus was found within the abdominal cavity with the placenta attached over the left iliac fossa including surface of left ovary. The uterus and right adnexa were within normal limits. A 2600 g macerated fetus with placenta and membranes were extracted without any complications. The maternal outcome was successful. CONCLUSIONS: Abdominal pregnancy remained an inadequately diagnosed condition in developing countries. It is imperative to increase awareness among pregnant women regarding high-quality prenatal care, including early obstetric ultrasound, from conception. Meanwhile, healthcare professionals should receive continuous training and the technical platform modernised. To ensure accurate diagnosis, the location of the gestational sac must be identified for every pregnant woman during their initial ultrasound appointment.

Nursing care for parents who have experienced fetal demise: integrative review.

OBJECTIVES: to identify scientific evidence regarding nursing care for parents who have experienced grief following fetal demise. METHODS: an integrative review of original studies was conducted across six databases. The studies were classified according to the level of evidence. RESULTS: the qualitative analysis of the nine studies comprising the sample involved thematic categories, exploring the impact of perinatal loss on families, inadequate communication by healthcare professionals, and the importance of a holistic approach in care. The role of the nurse is highlighted in making a positive contribution to the team, emphasizing participation in training and the provision of essential information. FINAL CONSIDERATIONS: grieving affects not only family dynamics but also the social environment, emphasizing the urgency of a more empathetic and comprehensive approach. Care should be holistic, going beyond technical nursing assistance, and addressing the biopsychosocial context of the parents.

Pregnancy, antiseizure medications and unexplained intrauterine foetal death.

OBJECTIVE: To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR). RESULTS: IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR. Factors associated with IUFD occurrence included older maternal age, enrolment in the APR at an earlier stage of pregnancy, history of pregnancies which did not result in livebirths, parental history of foetal malformations, and maternal use of carbamazepine, lamotrigine or ethosuximide. Individual ASM dosages were not associated with IUFD occurrence. Relative to no exposure, the risk of IUFD increased with the increasing number of ASMs used in combination (2 ASMs: relative risk, RR = 5.45 [95 % CI: 0.73-41.80]; 3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), >3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), but this finding was attenuated after adjusting for other factors implicated in IUFD occurrence. Several ASM pairs were associated with an increased risk of IUFD relative to no exposure, but these associations were lost after accounting for confounders. CONCLUSIONS: Although it is possible that prenatal ASM exposure may increase the risk of IUFD, other non-pharmacological factors are more relevant to the occurrence to IUFD in pregnant WWE.

Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

OBJECTIVES: To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). METHODS: A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. RESULTS: The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p = 1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p < 0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39 weeks in neither the cohort (38.7 weeks) nor the pooled literature (37.6 weeks). CONCLUSION: An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39 weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39 weeks of gestation. After 39 weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.

Missing Black males among preterm births in the US, 1995 to 2019.

BACKGROUND: In the US, non-Hispanic (NH) Black birthing persons show a two-fold greater risk of fetal death relative to NH white birthing persons. Since males more than females show a greater risk of fetal death, such loss in utero may affect the sex composition of live births born preterm (PTB; <37 weeks gestational age). We examine US birth data from 1995 to 2019 to determine whether the ratio of male to female preterm (i.e., PTB sex ratios) among NH Black births falls below that of NH whites and Hispanics. METHODS: We acquired data on all live births in the US from January 1995 to December 2019. We arrayed 63 million live births into 293 "conception cohort" months of which 2,475,928 NH Black, 5,746,953 NH white, and 2,511,450 Hispanic infants were PTB. We used linear regression methods to identify trend and seasonal patterns in PTB sex ratios. We also examined subgroup differences in PTB sex ratios (e.g., advanced maternal ages, twin gestations, and narrower gestational age ranges). RESULTS: The mean PTB sex ratio for NH Black births over the entire test period (1.06, 95% Confidence Interval [CI]: 1.05, 1.07) is much lower than that for NH white births (1.18, 95% CI: 1.17, 1.19). NH Black PTB sex ratios are especially low for twins and for births to mothers 35 years or older. Only NH white PTB sex ratios show a trend over the test period. CONCLUSIONS: Analysis of over 10 million PTBs reveals a persistently low male PTB frequency among NH Black conception cohorts relative to NH white cohorts. Low PTB sex ratios among NH Black births concentrate among subgroups that show an elevated risk of fetal death. PTB sex ratios may serve as an indicator of racial/ethnic and subgroup differences in fetal death, especially among male gestations.

Novel premature termination codon in the FOXP3 gene as the cause of familial hydrops fetalis in males.

A 19-year-old, G1P0, pregnant person was referred at 20w2d gestation for evaluation due to non-immune hydrops fetalis (NIHF), which was confirmed at the time of evaluation. Amniocentesis was performed at 20 w4d, and FISH, karyotype, chromosomal microarray, and exome sequencing (ES) were ordered. Trio ES identified a novel hemizygous c.142 C > T (p.Arg48*; maternally inherited) variant in the FOXP3 gene, resulting in a premature termination codon and establishing the diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Intrauterine fetal demise (IUFD) was diagnosed at 21w3d. CVS was performed at 12w1d in a subsequent pregnancy (male fetus) and the known familial variant was identified. NIHF was identified at 18w1d. Ultrasound at 19w2d revealed IUFD. This is the first report of this variant in a diagnosis of IPEX syndrome, presenting with NIHF and male fetal demise. Genotype-phenotype correlations are not available in many cases of IPEX syndrome, as the same genotype can be present with variable severity in different individuals. Given the near identical presentations in this family, we anticipate a more severe phenotype with this variant. We propose a novel variant resulting in an early premature termination codon as an explanation for the severe presentation of IPEX syndrome in two successive fetuses in this family.

Fetal maceration and partial retention of fetal bones in 2 mares.

Pregnancy loss after Day 40 in mares usually results in the expulsion (abortion) of the fetus and placental membranes. However, fetal retention within the uterus is also a possible outcome, leading to either fetal mummification or maceration. Fetal maceration is septic decomposition of fetal tissues within the uterus following failure of expulsion. It requires the presence of bacteria and oxygen within the uterus, likely originating from an open cervix, and results in tissue autolysis, leaving only fetal bones remaining in the mare. Fetal maceration is a rare complication of pregnancy in mares that is usually associated with a recent history of abortion, a persistent vaginal discharge, and retention of numerous fetal bones. Here, we report 2 cases of fetal maceration with retention of only a few fetal bones in mares that were presented without noticeable clinical signs. Key clinical message: The unusual presentation of fetal maceration in these mares (only a few fetal bones and no noticeable clinical signs) brings attention to the potential insidious nature of fetal retention. It highlights the importance of a thorough reproductive examination before breeding, along with careful and ongoing monitoring after breeding and throughout pregnancy.

Macération fœtale et rétention partielle d'os fœtaux chez 2 juments. L'interruption de gestation après le Jour 40 chez les juments résulte généralement par l'expulsion (avortement) du fœtus et des membranes fœtales. Toutefois, une rétention fœtale dans l'utérus est également un résultat possible, entraînant soit une momification ou une macération fœtale. La macération fœtale est la décomposition septique des tissus fœtaux à l'intérieur de l'utérus à la suite d'un échec d'expulsion. Elle nécessite la présence de bactéries et d'oxygène dans l'utérus, résultant probablement d'une ouverture du cervix, et résulte en une autolyse des tissus, laissant uniquement des os fœtaux à l'intérieur de la jument. La macération fœtale est une complication rare de la gestation chez les juments qui est généralement associée avec une histoire récente d'avortement, une décharge vaginale persistante, et la rétention de nombreux os fœtaux. Nous rapportons ici 2 cas de macération fœtale avec rétention de seulement quelques os chez des juments présentées avec aucun signe clinique notable.Message clinique clé :La présentation inhabituelle de macération fœtale chez ces juments (uniquement quelques os fœtaux et aucun signe clinque notable) met en lumière la nature potentiellement insidieuse de la rétention fœtale. Elle souligne l'importance d'un examen reproducteur complet avant l'accouplement, avec un suivi minutieux et continu après l'accouplement et durant toute la gestation.(Traduit par Dr Serge Messier).

A Comparison of the Efficacy and Safety of Mifepristone and Misoprostol Versus Misoprostol alone for Induction of Labour in Nigerian Women with Intrauterine Fetal Death: A Triple Blind Randomized Controlled Trial.

BACKGROUND: Intrauterine foetal death (IUFD) is an unpleasant pregnancy outcome and prompt delivery of the dead foetus is usually desired by mothers. Unfortunately, spontaneous labour and delivery may not occur early and prolonged retention of the dead foetus in utero is life-threatening. Many of the agents currently used for the induction of labour may result in a prolonged delivery process. OBJECTIVES: To compare the efficacy and safety of mifepristone and misoprostol versus misoprostol alone for induction of labour in women with intrauterine foetal death. MATERIALS AND METHODS: This was a triple-blind randomized controlled trial. Eighty women were randomized into two groups. The intervention group received a single oral dose of 200 mg mifepristone, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The control group received a placebo, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The primary outcome measure was the induction to delivery interval. RESULTS: Maternal age, gestational age, parity and pre-induction bishop's score were comparable between the two groups. The mean induction to the delivery interval in the intervention group was significantly less in the intervention group than the control group (18.78 ± 6.51 hours versus 37.10 ± 10.10; P < 0.001). The total dose of misoprostol required for induction of labour; the need for oxytocin augmentation of labour; and the observed side effects of misoprostol were all significantly less in intervention group than control group (P < 0.001; P < 0.01; and P = 0.03, respectively). CONCLUSION: The combination of mifepristone and misoprostol has greater efficacy and better safety profile than the use of misoprostol alone for induction of labour. This combination should be considered when induction of labour is indicated for IUFD.

The application of the ICD-10 for antepartum stillbirth patients in a referral centre of Eastern China: a retrospective study from 2015 to 2022.

BACKGROUND: The causes of some stillbirths are unclear, and additional work must be done to investigate the risk factors for stillbirths. OBJECTIVE: To apply the International Classification of Disease-10 (ICD-10) for antepartum stillbirth at a referral center in eastern China. METHODS: Antepartum stillbirths were grouped according to the cause of death according to the International Classification of Disease-10 (ICD-10) criteria. The main maternal condition at the time of antepartum stillbirth was assigned to each patient. RESULTS: Antepartum stillbirths were mostly classified as fetal deaths of unspecified cause, antepartum hypoxia. Although more than half of the mothers were without an identified condition at the time of the antepartum stillbirth, where there was a maternal condition associated with perinatal death, maternal medical and surgical conditions and maternal complications during pregnancy were most common. Of all the stillbirths, 51.2% occurred between 28 and 37 weeks of gestation, the main causes of stillbirth at different gestational ages also differed. Autopsy and chromosomal microarray analysis (CMA) were recommended in all stillbirths, but only 3.6% received autopsy and 10.5% underwent chromosomal microarray analysis. CONCLUSIONS: The ICD-10 is helpful in classifying the causes of stillbirths, but more than half of the stillbirths in our study were unexplained; therefore, additional work must be done. And the ICD-10 score may need to be improved, such as by classifying stillbirths according to gestational age. Autopsy and CMA could help determine the cause of stillbirth, but the acceptance of these methods is currently low.

Maternal COVID-19 infection and intrauterine fetal death: Impact on the placenta and fetus.

BACKGROUND: Placental damage due to viral infections increases risk of adverse perinatal outcomes. Histopathologic examination of placenta can provide information regarding association between infection and outcome. There is paucity of data describing placental pathology with respect to intrauterine fetal death (IUFD) in pregnant mothers affected with COVID-19. METHODS: 4 fetuses and 10 placentas, including one twin placenta from 9 women with history of IUFD and SARS-CoV-2 infection underwent evaluation. These findings were contrasted with 3 fetuses and 21 gestational age matched placentas from non-infected women with history of IUFD. RESULTS: Extensive gross placental lesions, mixture of histologic features (maternal/ fetal vascular malperfusion) and isolated cases of massive perivillous fibrin depositon and chronic intervillositis were observed in COVID-IUFD group. There were no distinguishing histologic findings when compared to control. Three fetuses showed signs of intraventricular/intraparenchymal hemorrhage in autopsy. CONCLUSION: These findings demonstrate that IUFD does not correspond with maternal symptoms and lacks distinctive lesion. However, there was significant placental damage which developed rapidly. These results show that SARS-CoV-2 infection results in rapid placental deterioration and fetal death. This information can be used to educate infected mothers and remind medical professionals, value of monitoring placental function especially following diagnosis of infection.

A case report of single umbilical artery combined with fetal bladder exstrophy in singleton pregnancy and related literature review.

BACKGROUND: According to prenatal ultrasonographic studies, single umbilical artery may be present alone or in association with other fetal abnormalities. So far, the exact pathogenesis of bladder exstrophy is unclear. Some scholars believe that bladder exstrophy and cloacal exstrophy should be regarded as a disease spectrum to explore their pathogenesis. If bladder exstrophy and cloacal exstrophy are regarded as the same disease spectrum, then we can speculate that the single umbilical artery should have the probability of being accompanied by bladder exstrophy at the same time. CASE PRESENTATION: For the first time, we report a rare case of fetal bladder exstrophy with single umbilical artery in single pregnancy. This patient underwent targeted color Doppler ultrasound at 26 weeks of pregnancy which first suspected bladder exstrophy with single umbilical artery and fetal MRI for diagnosis at 38 + 3 weeks of pregnancy which confirmed the suspicion. After the diagnosis was confirmed, the patient was scheduled for a multidisciplinary discussion. Ultimately the patient opted for induced fetal demise at 38 + 5 weeks of pregnancy and the physical appearance of the fetal demise affirmed previous ultrasound and MRI examination results. CONCLUSIONS: Our report is the first finding of single umbilical artery combined with bladder exstrophy in a singleton pregnancy. Accordingly, our case enhances the evidence that cloacal exstrophy and bladder exstrophy should be treated as the same disease spectrum. In addition, we conducted a literature review on the diagnostic progress of single umbilical artery combined with bladder exstrophy, hoping to provide useful references for the diagnosis of this disease.

Monochorionic triplet pregnancy complicated by conjoined twins and early twin-twin transfusion syndrome.

BACKGROUND: The condition of monozygotic, monochorionic triplet fetuses with a pair of conjoined twins is extremely rare (close to one in a million births), presents challenges in its management, and with poor prognosis. CASE REPORT: We report a case of monochorionic diamniotic triplet pregnancy, ultrasound at 14 weeks shows a pair of conjoined thoracopagus fetuses, sharing heart, liver, and umbilical cord, in addition to omphalocele. The third fetus, without malformations, presents signs of early heart failure compatible with twin-to-twin transfusion syndrome. It was decided to carry out expectant management where at 18 weeks, intrauterine death of the three fetuses occurs. An abortion is performed by hysterotomy. CONCLUSIONS: The treatment in these cases is discussed, three management options have been proposed: expectant management, selective reduction of the conjoined fetuses, or termination of the pregnancy. A review of the literature found only 12 cases with this combination of pathologies, in which only 3 normal fetuses (25%) survived and none of the conjoined twins survived. To our knowledge, this case is the first of a monochorionic triplet pregnancy with conjoined fetuses complicated with early twin-to-twin transfusion.

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Predictors of fetal death, neonatal survival and neurological outcomes in severe twin-twin transfusion syndrome treated by laser ablation of placental vessels.

OBJECTIVES: To identify predictors of outcomes in severe twin oligo-polyhydramnios sequence (TOPS) with or without twin anemia-polycythemia sequence (TAPS) and/or selective fetal growth restriction (SFGR) treated by laser ablation of placental vessels (LAPV). METHODS: Analysis of cases treated from 2011 to 2022. Variables evaluated Prenatal predictors: stages of TOPS, presence of TAPS and/or SFGR; pre-LAPV fetal ultrasound parameters; peri-LAPV variables. Perinatal predictors: GA at birth; birthweight; Apgar scores; transfontanellar ultrasonography (TFUS). OUTCOME VARIABLES: fetal death, neonatal survival, infant's neurodevelopment. Binary logistic regression analyses were performed to detect predictors of outcomes. RESULTS: 265 cases were included. Predictors of post-LAPV donor fetus' death were delta EFW (p:0.045) and absent/reverse end-diastolic flow in the umbilical artery (AREDF-UA) (p < 0.001). The predictor of post-LAPV recipient fetus' death was hydrops (p:0.009). Predictors of neonatal survival were GA at birth and Apgar scores. Predictors of infant's neurodevelopment were TFUS and pre-LAPV middle cerebral artery Doppler (MCAD) for the donor twin; and pre-LAPV ductus venosus' flow and MCAD for the recipient twin. CONCLUSIONS: Prediction of fetal death, neonatal survival and infant's neurodevelopment is possible in cases of TOPS associated or not with SFGR and/or TAPS that were treated by LAPV.

Clinically significant findings in a decade-long retrospective study of prenatal chromosomal microarray testing.

BACKGROUND: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results. METHODS: In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. RESULTS: In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. CONCLUSION: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

Genomics of stillbirth.

Stillbirth, defined as fetal death at 20 weeks gestation or later, is a devastating pregnancy outcome affecting 1 in 175 pregnancies in the United States. Although efforts to understand the etiology of stillbirth have expanded, 25 % of cases remain unexplained and some cases previously thought to be explained may have additional unknown causative factors. Determining an etiology for stillbirth is important for clinical management and for grieving families to obtain closure, to find meaning, and to understand recurrence risks. However, the evaluation of stillbirth is not completed uniformly despite American College of Obstetrics and Gynecology (ACOG) guidelines and stillbirth data is frequently incomplete due to lack of genomic analysis, fetal autopsy, and placental pathology. Karyotype and chromosomal microarray have been the gold standard in genetic analysis in perinatal medicine for many years, but next generation sequencing holds promise towards improving diagnostic yields and providing clarity for both clinicians and patients.