Fetal deaths from birth defects in Hunan Province, China, 2016-2020.

To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016-2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13-51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of < 20 weeks, 59.05% (7059 cases) were at a gestational age of 20-27 weeks, and 25.17% (3009 cases) were at a gestational age of ≥ 28 weeks. Fetal death rate of birth defects was higher in females than in males (OR = 1.25, 95% CI 1.18-1.32), in rural than in urban areas (OR = 1.43, 95% CI 1.36-1.50), in maternal age 20-24 years (OR = 1.35, 95% CI 1.25-1.47), and ≥ 35 years (OR = 1.19, 95% CI 1.11-1.29) compared to maternal age of 25-29 years, in diagnosed by chromosomal analysis than ultrasound (OR = 6.24, 95% CI 5.15-7.55), and lower in multiple births than in singletons (OR = 0.41, 95% CI 0.36-0.47). The fetal death rate of birth defects increased with the number of previous pregnancies (χ2trend = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ2trend = 4318.91, P < 0.01). Many fetal deaths were associated with birth defects. We found several demographic characteristics associated with fetal deaths from birth defects, which may be related to the severity of the birth defects, economic and medical conditions, and parental attitudes toward birth defects.

Asymptomatic acute massive abruptio placenta at 30 weeks' gestation in a primigravida with no risk factors - clinical presentation and management.

Abruptio placenta can be a catastrophic event with a high association with adverse maternal and fetal outcomes. We present a case of massive abruptio placenta occurring in a young asymptomatic mother at 30 weeks' gestation. Although electronic fetal monitoring and ultrasound allowed a prompt diagnosis of an 8 × 5 cm retroplacental hematoma, the fetus died at the time of emergency cesarean section. The fetus was intubated, but could not be resuscitated. Histologic examination of the placenta documented thinning and stacked hypercapillarized villi, with syncytial buds and foci of fibrinoid necrosis in the presence of hyaline streaks on both the maternal and fetal sides.

Characteristics of unilateral and bilateral bovine twin foetuses.

Twin pregnancy in cattle is undesirable for a number of reasons, including a higher abortion risk compared to pregnancies with a single foetus. Yet, the abortion risk is significantly influenced by the intrauterine location of the foetuses, that is, the abortion risk is several times higher if they are implanted in the same uterine horn (unilateral twin pregnancy) than if they are implanted with one foetus in each uterine horn (bilateral twin pregnancy). The reason for the higher abortion risk in unilateral twin pregnancies is unknown, but it may be related to malnutrition of the outermost foetus due to a limited placental capacity, as is the case for equine twin foetuses. A slaughterhouse study was performed and the foetuses of cattle pregnant with twins were measured. We identified 65 cases of twin pregnancies, of which 35 were unilateral twin pregnancies and 30 were bilateral twin pregnancies. There was no significant difference between the outermost and the more centrally located foetus in unilateral twin pregnancies in terms of body weight and length of the metacarpal diaphysis. Growth retardation of the outermost foetus could therefore not be confirmed as the cause of the higher abortion risk in unilateral bovine twin pregnancies. Four cases of pre-slaughter foetal mortality were identified. In three of these cases, both twins were dead, of equal size and at a comparable level of degradation. In the fourth case, with approximately 40-day-old twin foetuses of equal size, only one of the foetuses showed signs of pre-slaughter death.

Challenging Diagnosis of Late Abdominal Pregnancy: A Case Study of Misdiagnosis and Fetal Death in the Third Trimester.

BACKGROUND Abdominal pregnancy is a rare form of extrauterine pregnancy that usually results in a poor outcome; it is associated with serious fetal and maternal morbidity. The diagnosis of advanced abdominal pregnancy is sometimes challenging and should be identified early, at a routine antenatal examination. There are still no evidence-based management strategies for late abdominal pregnancy. This report presents a case of a patient with an abdominal pregnancy and a non-viable fetus. CASE REPORT A 34-year-old woman presented as an emergency 2 months after the diagnosis of intrauterine fetal death at 33 weeks of gestation. During subsequent surgery, the pregnancy was found to be an undiagnosed abdominal pregnancy. The patient had been admitted due to abdominal pain and increasingly deteriorating general condition. On admission, clinical examination and abdominal ultrasound were carried out and the diagnosis of fetal death was confirmed. The diagnosis of extrauterine pregnancy, however, was initially missed, and a decision to induce labor was made. After unsuccessful induction of labor and deterioration of the patient's general condition, a laparotomy was performed, and the diagnosis of abdominal pregnancy was confirmed. A severely macerated fetus and placenta were delivered. Relative to others with this condition, the patient had a very good postoperative outcome with prolonged healing of the surgical incision. Informed consent for publication was obtained from the patient. CONCLUSIONS The diagnosis of late abdominal pregnancy can be missed despite clinical and sonographic examination. This diagnosis should be considered and excluded in similar suspected clinical findings. Proper operative planning in a tertiary center with a well-experienced team is crucial.

The association between maternal obesity and fetomaternal outcomes in twin pregnancies.

The prevalence of overweight and obese people worldwide has dramatically increased in the last decades and is yet to peak. At the same time and partly due to obesity and associated assisted reproduction, twinning rates showed a clear rise in the last years. Adverse fetomaternal outcomes are known to occur in singleton and twin pregnancies in overweight and obese women. However, the impact of the obesity levels as defined by the World Health Organization on the outcomes of twin pregnancies has not been thoroughly studied. Therefore, the purpose of this study is to examine how maternal overweight, and the level of obesity affect fetomaternal outcomes in twin pregnancies, hypothesizing a higher likelihood for adverse outcomes with overweight and each obesity level. This is a retrospective cohort study with 2,349 twin pregnancies that delivered at the Buergerhospital Frankfurt, Germany between 2005 and 2020. The mothers were divided into exposure groups depending on their pre-gestational body mass index; these were normal weight (reference group), overweight and obesity levels I, II, and III. A multivariate logistic regression analysis was performed to assess the influence of overweight and obesity on gestational diabetes mellitus, preeclampsia, postpartum hemorrhage, intrauterine fetal death, and a five-minutes Apgar score below seven. The adjusted odds ratio for gestational diabetes compared to normal weight mothers were 1.47, 2.79, 4.05, and 6.40 for overweight and obesity levels I, II and III respectively (p = 0.015 for overweight and p < 0.001 for each obesity level). Maternal BMI had a significant association with the risk of preeclampsia (OR 1.04, p = 0.028). Overweight and obesity did not affect the odds of postpartum hemorrhage, fetal demise, or a low Apgar score. While maternal overweight and obesity did not influence the fetal outcomes in twin pregnancies, they significantly increased the risk of gestational diabetes and preeclampsia, and that risk is incremental with increasing level of obesity.

Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

Receipt of hepatitis E vaccine and fetal loss in rural Bangladesh: further analysis of a double-blind, cluster-randomised, controlled trial.

BACKGROUND: Vaccination constitutes an attractive control measure for hepatitis E virus (HEV), a major cause of maternal and perinatal mortality globally. Analysis of pregnant participants in an effectiveness trial of the HEV vaccine HEV239 showed possible HEV239-associated fetal losses. We aimed to conduct a detailed analysis of this safety signal. METHODS: In a double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomly allocated (1:1) to two vaccine groups, in which non-pregnant women aged 16-39 years received either HEV239 (HEV239 group) or Hepa-B (a hepatitis B vaccine; control group). We implemented weekly surveillance for pregnancy detection, and follow-up of pregnancies once every 2 weeks, using physician-confirmed diagnoses to evaluate fetal loss outcomes (miscarriage [spontaneous abortion], stillbirth, and elective termination). Data from a parallel system of reproductive health surveillance in Matlab were used to clarify study diagnoses when necessary. Miscarriage was assessed only among participants whose first positive pregnancy test and vaccination date (for whichever dose was closest to the date of last menstrual period [LMP]) were before 20 weeks' gestation. We defined the following analysis periods of interest: from 90 days before the LMP until the pregnancy outcome (the proximal period); from the LMP date until the pregnancy outcome (the pregnancy period); from 90 days before the LMP until the LMP date (90 days pre-LMP period); and from enrolment until 90 days before the LMP (the distal period). Both Poisson and Cox regression models were used to assess the associations between receipt of HEV239 and fetal loss outcomes. The trial was registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Among the 19 460 non-pregnant participants enrolled in the trial, 5011 were identified as having pregnancies within 2 years following vaccination and met the criteria for analysis (2407 in the HEV239 group and 2604 in the control group). Among participants vaccinated in the proximal period and evaluated for miscarriage, miscarriage occurred in 54 (8·9%) of 607 in the HEV239 group and 32 (4·5%) of 719 in the control group (adjusted relative risk [aRR] 2·0 [95% CI 1·3-3·1], p=0·0009). Similarly, the risk of miscarriages was increased in the HEV239 group versus the control group among participants inadvertently vaccinated during pregnancy (22 [10·5%] miscarriages among 209 participants in the HEV239 group vs 14 [5·3%] of 266 in the control group; aRR 2·1 [95% CI 1·1-4·1], p=0·036) and among those vaccinated within 90 days pre-LMP (32 [8·0%] of 398 vs 18 [4·0%] of 453; 1·9 [1·1-3·2], p=0·013). No increased risk of miscarriage was observed in those who received HEV239 in the distal period (93 [5·6%] of 1647 vs 80 [4·5%] of 1773; 1·3 [0·8-1·9], p=0·295). Stillbirth and elective termination showed no increased risk among women administered HEV239 versus those administered Hepa-B in any of the analysis periods. INTERPRETATION: HEV239 given shortly before or during pregnancy was associated with an elevated risk of miscarriage. This association poses a possible safety concern for programmatic use of HEV239 in women of childbearing age. FUNDING: Research Council of Norway and Innovax.

Prognosis of remaining fetus in twin pregnancy after demise of one fetus according to its location.

BACKGROUND: To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus. METHODS: This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed. RESULTS: A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery. CONCLUSIONS: When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

Impact of cord entanglement on perinatal outcome.

OBJECTIVE: To evaluate the impact of umbilical cord entanglement around various fetal organs on perinatal outcomes. STUDY DESIGN: A retrospective population-based study of all deliveries between 1988 and 2016 at a tertiary medical center. Immediate perinatal outcomes of newborns with and without cord entanglement were compared. RESULTS: The prevalence of any cord entanglement in our population was 16.62 % (45,312 cases out of 272,713 deliveries during the study period). Cord entanglement was found to be significantly associated with antepartum fetal death (OR = 2.13, 95 % CI 1.77-2.57, p < 0.001) and one-minute Apgar score less than 7 (OR = 1.21, 95 % CI 1.16-1.27, p < 0.001). There was no association between cord entanglement and small for gestational age (SGA) babies. CONCLUSION: Cord entanglement is associated with antepartum fetal death, but not with SGA.

A systematic review to assess the utility of genomic autopsy using exome or genome sequencing in cases of congenital anomalies and perinatal death.

PURPOSE: Exome or genome sequencing (ES or GS) can identify genetic causes of otherwise unexplained congenital anomaly and perinatal death (PND) but is not routine practice. The evidence base for "genomic autopsy" after termination of pregnancy for fetal anomaly (TOPFA) and PND has been synthesized to determine the value of this investigation. METHODS: We conducted a systematic review and meta-analysis of studies meeting prespecified inclusion criteria and containing ≥10 cases of TOPFA or PND (with or without major congenital abnormality), in which ES or GS was conducted. We determined test performance, including diagnostic yield, accuracy, and reliability. We also reported outcomes associated with clinical utility and harms, where described. RESULTS: From 2245 potentially eligible studies, 32 publications were eligible and had data extracted, representing 2120 cases that could be meta-analyzed. No diagnostic accuracy or comparative studies were identified, although some analysis of concordance between different ES/GS methodologies could be performed. Studies reporting parent-related outcomes or long-term follow-up did not do so in a systematic or quantifiable manner. CONCLUSION: Evidence suggests that approximately one-fourth to one-third of fetal losses associated with TOPFA or unexplained PND are associated with a genetic cause identifiable on ES or GS-albeit this estimate varies depending on phenotypic and background risk factors. Despite the large body of evidence on ES and GS, little research has attempted to validate the accuracy of testing, nor measure the clinical or societal outcomes in families that follow the diagnostic investigation in this context.

Anatomic parameters of omphaloceles and their association with anatomic, genetic, or syndromic malformations: a retrospective study.

PURPOSE: This retrospective study aims to describe anatomical parameters of omphaloceles and to analyze their association with anatomical, genetic, or syndromic malformations. METHODS: Cases were selected from digital records of two university centers, a certified regional registry and personal records. Patients from 1998 to 2018 with omphalocele and live birth (LB), termination of pregnancy due to fetal anomaly (TOPFA) and fetal death (FD) were included. Cases born outside Western Switzerland and/or with upper or lower coelosomy were excluded. RESULTS: We analyzed 162 cases with the following distribution: 57 (35%) LB, 91 (56%) TOPFA and 14 (9%) FD. TOPFA was significantly more frequently performed in cases with non-isolated omphalocele, i.e., omphaloceles with associated major malformations (especially cardiovascular and genitourinary), genetic/chromosomal anomalies, or syndromes. For LB, associated anatomical malformations, genetic or chromosomal anomalies were not significantly associated with the size of the omphalocele or the liver involvement. CONCLUSIONS: The proportion of cases resulting in TOPFA was higher among fetuses with major malformations, genetic or chromosomal anomalies. Despite the large size of this cohort, and in contrary to previous publications, the size of the omphalocele and/or liver involvement does not allow for conclusions regarding the presence or number of associated malformations, genetic or chromosomal anomalies.

Stillbirths: results of a pilot population-based surveillance system in Italy (SPItOSS)

OBJECTIVES: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes. DESIGN: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily). SETTING AND PARTICIPANTS: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death. MAIN OUTCOMES MEASURES: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered. RESULTS: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively. CONCLUSIONS: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Perinatal outcomes and growth discordance of triplet pregnancies based on chorionicity: a retrospective cohort study.

BACKGROUND: The worldwide occurrence of triplet pregnancy is estimated to be 0.093%, with a natural incidence of approximately 1 in 8000. This study aims to analyze the neonatal health status and birth weight discordance (BWD) of triplets based on chorionicity from birth until discharge. METHODS: This was a retrospective study. We reviewed a total of 136 triplet pregnancies at our tertiary hospital between January 1, 2001, and December 31, 2021. Maternal and neonatal outcomes, inter-triplet BWD, neonatal morbidity, and mortality were analyzed. RESULTS: Among all cases, the rates of intrauterine death, neonatal death, and perinatal death were 10.29, 13.07, and 24.26%, respectively. Thirty-seven of the cases resulted in fetal loss, including 13 with fetal anomalies. The maternal complications and neonatal outcomes of the 99 triplet pregnancies without fetal loss were compared across different chorionicities, including a dichorionic (DC) group (41 cases), trichorionic (TC) group (37 cases), and monochorionic (MC) group (21 cases). Neonatal hypoproteinemia (P < 0.001), hyperbilirubinemia (P < 0.019), and anemia (P < 0.003) exhibited significant differences according to chorionicity, as did the distribution of BWD (P < 0.001). More than half of the cases in the DC and TC groups had a BWD < 15%, while those in the MC group had a BWD < 50% (47.6%). TC pregnancy decreased the risk of neonatal anemia (adjusted odds ratio [AOR] = 0.084) and need for blood transfusion therapy after birth (AOR = 0.119). In contrast, a BWD > 25% increased the risk of neonatal anemia (AOR = 10.135) and need for blood transfusion after birth (AOR = 7.127). TC pregnancy, MCDA or MCTA, and BWD > 25% increased neonatal hypoproteinemia, with AORs of 4.629, 5.123, and 5.343, respectively. CONCLUSIONS: The BWD differed significantly according to chorionicity. Additionally, TC pregnancies reduced the risk of neonatal anemia and need for blood transfusion, but increased the risk of neonatal hypoproteinemia. In contrast, the BWD between the largest and smallest triplets increased the risk of neonatal anemia and the need for blood transfusion. TC pregnancy, MCDA or MCTA, and BWD > 25% increased the risks of neonatal hypoproteinemia. However, due to the limited number of triplet pregnancies, further exploration of the underlying mechanism is warranted.

Clomiphene Citrate Administered in Periconception Phase Causes Fetal Loss and Developmental Impairment in Mice.

Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated the consequences in mice for fetal development and pregnancy outcome of periconception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 hours after mating was seen, with a moderate dose of 0.75 mg/kg sufficient to cause altered reproductive outcomes in 3 independent cohorts. Viable pregnancy was reduced by 30%, late gestation fetal weight was reduced by 16%, and ∼30% of fetuses exhibited delayed development and/or congenital abnormalities not seen in control dams, including defects of the lung, kidney, liver, eye, skin, limbs, and umbilicus. Clomiphene citrate also caused a 30-hour average delay in time of birth, and elevated rate of pup death in the early postnatal phase. In surviving offspring, growth trajectory tracking and body morphometry analysis at 20 weeks of age showed postweaning growth and development similar to controls. A dysregulated inflammatory response in the endometrium was observed and may contribute to the underlying pathophysiological mechanism. These results demonstrate that in utero exposure to clomiphene citrate during early pregnancy can compromise implantation and impact fetal growth and development, causing adverse perinatal outcomes. The findings raise the prospect of similar iatrogenic effects in women where clomiphene citrate may be present in the periconception phase unless its use is well-supervised.

An unfavorable and a successful pregnancy outcome during and after treatment of gamma heavy chain disease.

Gamma heavy chain disease (gHCD) is a rare B-cell lymphoproliferative disorder that mostly occurs after childbearing age. Here we report the first case of gHCD in a pregnant patient that was diagnosed in the second trimester, and another pregnancy in the same patient after initial treatment for gHCD. The former pregnancy ended in intrauterine fetal death, believed to be caused by insufficient maternal blood flow due to multiple placental infarcts. The latter pregnancy course was uneventful. Although we cannot rule out the possibility that the poor outcome of the former pregnancy was due to an unfortunate complication independent of gHCD, the courses of these pregnancies suggest that non-lymphomatous gamma heavy chain may have a significant impact on pregnancy and that its removal by treatment may improve outcomes.

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.

Invasive group A streptococcal infection can be fatal to pregnant women in restricted medical resources remote areas-Emergent alert after COVID-19 pandemic.

Invasive group A streptococcal (iGAS) infection is a leading cause of maternal death. The increase in the number of patients with iGAS in Japan is markedly greater than before the coronavirus pandemic. We encountered a case of iGAS infection, on a remote island with restricted medical resources, in a third-trimester pregnant woman, resulting in both maternal and fetal death. A 34-year-old woman was admitted via a local general hospital with a high fever. Intrauterine fetal death disseminated intravascular coagulation, and septic shock were confirmed. Broad-spectrum antibiotics were started, and the patient was returned to the local general hospital. Eight hours after arrival, the patient died of circulatory and respiratory dysfunction complications. iGAS infections in remote areas may directly lead to life-threatening conditions and should be treated as an emergency, comparable to the serious conditions of placental abruption or placenta previa.

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.