Intrauterine Fetal Death Research Articles

Perinatal Outcomes in Foetuses with Increased Nuchal Translucency and Normal Karyotype: A Retrospective Cohort Study from the United Arab Emirates.

This retrospective case-controlled study analysed the outcome of pregnancies with first-trimester enlarged nuchal translucency (NT) and a normal karyotype. A total of 479 pregnancies with first-trimester NT measurements were grouped as control (370 cases; normal NT) and study (109 cases; enlarged NT, ≥95th percentile; with normal karyotype). Adverse outcomes included miscarriage, intrauterine foetal death, termination of pregnancy, neonatal death, and structural/chromosomal/genetic abnormalities. The study was conducted between June 2016 and June 2022 at the Foetal Maternal Unit of Kanad Hospital, UAE. Overall, the live birth rate in the study group was significantly lower (74.3%) compared to the control (94.1%, p < 0.001). All pregnancy outcomes of this group significantly differed compared to the control. The observed miscarriage level was 9.2% (vs. 1.1%, p < 0.001), intrauterine foetal death was 2.8% (vs. 0%, p = 0.001), spontaneous preterm birthwas 11% (vs. 4.9%, p = 0.020), and termination of pregnancy was 3.7% (vs. 0%, p < 0.001). The presence of foetal abnormalities was also significantly higher in the enlarged NT group at 21% (vs. 3.3%, p < 0.001). Results indicate that enlarged NT is associated with adverse pregnancy outcomes even when the karyotype is normal. Based on these results, a comprehensive review of the guidelines for counselling and managing pregnancies with enlarged NT and a normal karyotype is recommended.

Intrauterine death in vasa previa without hemorrhage: case reports

Antepartum and intrapartum hemorrhage from vasa previa (VP) is one of the main causes of intrauterine fetal death (IUFD). Here, we present two cases with type I VP in which velamentous cord insertion below the fetal head and overlying the cervix were reported by prenatal ultrasound scanning, and IUFD occoured after 35 weeks with no signs of prenatal bleeding but with engaged fetal head at presentation. We hypothesized that the IUFD may attributed to the compression of the unprotected umbilical vessels by the engaged fetal head. Thus we suggest that VP with a velamentous cord insertion should be considered for earlier termination of the pregnancy to avoid the risk of non-hemorrhagic adverse fetal outcomes.

Successful Pregnancy in Morbidly Obese Women of Polycystic Ovary Syndrome With Various Treatment Options With Individual Consequences: Case Series

Objective: The objective of the study was to compare the effectiveness of different treatment options in the management of infertility across three cases in morbidly obese women with polycystic ovary syndrome (PCOS). Case study &amp; results: The first case is 30 years old with secondary infertility for two years with two abortions and a body mass index (BMI) is 69, she tried all lifestyle modifications with no response to weight reduction and she was conceived spontaneously without fertility treatment and subsequent antenatal care progressed without any complications until 36 weeks complicated with raised blood sugar beyond the normal level but not so high and intrauterine fetal death one week later ended by spontaneous normal vaginal delivery. The second case is 24 years old with BMI 66 is undergone weight reduction, ovulation induction with clomiphene citrate and gonadotropin injections with good ovulation response but no pregnancy, in vitro fertilization was performed but aborted at 8 weeks gestation, one year later after the use of metformin and ovulation induction with injections patient conceived and her pregnancy complicated by pre-eclampsia, gestational diabetes treated with insulin and preterm delivery. The third case is 40 years old with primary infertility for 5 years with BMI 70, she is known case diabetes mellitus 10 years back controlled with insulin, and hypertension on treatment, undergone bariatric surgery and one year later IVF was done after the failure of multiple ovulation induction, her diabetes mellitus and hypertension control well with treatment and delivered at 39 weeks by elective cesarean section with a birth weight of 4.5 kg. Discussion: PCOS is a genetic condition, worsened by obesity. The prevalence of obesity in PCOS women is up to 80%. There is a strong relationship between PCOS and obesity making the condition more complex. The majority of women with PCOS are either overweight or obese and the pathogenesis of obesity in PCOS has not yet been exactly identified. Obesity has adverse effects on fertility through anovulation, poor implantation, and quality oocyte. Conclusion: The ideal treatment of infertility in morbidly obese PCOS women has not been defined, but generally, before deciding which treatment option is preferred, proper weight loss and control of the metabolic state are carried out for successful pregnancy

Role of fetal autopsy and its importance in intrauterine fetal death: Histopathological diagnosis

Role of fetal autopsy and its importance in intrauterine fetal death: Histopathological diagnosis

Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report

BackgroundCongenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3–9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case.Case presentationA 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses’ umbilical cord, third fetus’ placenta, and the fourth fetus’ blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth.ConclusionsThis report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.

Effect of low-molecular-weight heparin on placenta-mediated fetal growth restriction in a tertiary referral hospital: A 7-year retrospective cohort study.

To investigate the effect of low-molecular-weight heparin (LMWH) on placenta-mediated fetal growth restriction (FGR). A cohort of 570 pregnant women diagnosed with placenta-mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1-week prescription from diagnosis of placenta-mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self-administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes. After controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35-4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14-5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36-3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48-3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early-onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late-onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non-severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001). Use of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta-mediated FGR, particularly reducing the risk of intrauterine fetal death.

The effect of anti-phospholipid syndrome on pregnancy outcomes in patients with habitual abortus

Objective: The aim of this study was to research the pregnancy outcomes of women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and to determine the association with pregnancy morbidity.&#x0D; Materials and methods: This retrospective study contained pregnant women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and a control group without these antibodies. Totally 190 serum samples sent from Obstetrics and Gynecology clinics between January 2019 and January 2023 were analyzed in the medical microbiology laboratory of xx.&#x0D; Results: In a patient population separated into antibody-positive and antibody-negative groups, the gravida was found to be 3.8±0.1 and 3.5±0.3 respectively (p=0.333). Parity was 1.1±0.1 and 0.8±0.1 (p=0.071), abortion rates were 2.3±0.1 and 2.5±0.2 (p=0.659), and gestational age was 35.7±0.8 and 34±1.5 (p=0.047). Intrauterine fetal death was found to be higher in the antibody-positive group compared to the antibody-negative group (p=0.03). There was no noteworthy distinction noted between the two groups regarding additional pregnancy complications such as intrauterine growth restriction, oligohydramnios, gestational diabetes, and gestational hypertension (respectively p=0.623, 0.074, 0.312, 0.626). However, smoking was significantly higher in the antibody-positive group (p=0.049).&#x0D; Conclusion: Antiphospholipid syndrome adversely affects pregnancy outcomes. During the initial visit, a thorough patient history should be obtained, and in pregnant women with a history of poor obstetric outcomes or habitual abortions, this syndrome should be considered.

Does cesarean section prevent adverse neonatal outcomes associated with meconium amniotic fluid?

BackgroundMaking decisions regarding the mode of delivery in the cases of meconium amniotic fluid (MAF) presents a challenge for healthcare providers. We aimed to compare the neonatal outcome of MAF cases delivered via cesarean section (CS) versus those delivered vaginally to determine if CS is a protective factor against the adverse neonatal outcomes. MethodsIn this retrospective study, we assessed singleton pregnant mothers diagnosed with MAF who gave birth at a tertiary hospital in Bandar Abbas, Iran, between January 2020-2022. Mothers with certain adverse pregnancy conditions were excluded from the study. These conditions included: abnormal fetal heart rate and pattern, bloody amniotic fluid, malpresentation, abnormal placentation, chorioamnionitis, intrauterine growth restriction, intrauterine fetal death, obstructed labor, and maternal comorbidities. The MAF mothers were divided into two groups based on the method of delivery: those who had CS and those who had a normal vaginal delivery (NVD). Demographic factors, obstetrical factors, and neonatal outcomes were compared between the two groups. ResultsOut of 746 MAF mothers, 213 (28.5%) underwent CS, while 533 (71.4%) had NVD. There were no significant differences between the groups in terms of demographic characteristics. Among MAF mothers who had CS, 66.2% were primiparous, and 33.8% were multiparous. For those who had NVD, 35.1% were primiparous, and 64.9% were multiparous. The first and 5-min Apgar values, rates of asphyxia, neonatal intensive care unit (NICU) admission, and neonatal death were not statistically different between the two delivery modes. The rate of newborns who breastfed within the first hour did not differ depending on the mode of delivery. Although initial resuscitation steps were required more frequently in MAF mothers with NVD than in those with CS (11.1% vs. 2.3%), no correlation was found between the mode of delivery and the need for resuscitation using logistic regression. ConclusionsOur research findings suggest that there were no superior neonatal outcomes in terms of CS compared to NVD in MAF mothers. Further studies are needed to provide more substantial evidence to support this conclusion.

The clinical characteristics of COVID-19 omicron variant infection in pregnant women and their neonates.

The objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China. The clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay. Seventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment. Although preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.

Neonatal Outcome of Mothers With COVID-19 in King Salman Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia.

This study was conducted to assess the neonatal outcome of mothers with COVID-19 in King Salman Armed Forces Hospital, Tabuk, Saudi Arabia. This was a hospital record-based, retrospective cohort study. The case group included neonates born to mothers who were positive for the COVID-19 virus during pregnancy, whereas the control group included neonates born to mothers who were not infected with the COVID-19 virus during pregnancy. The data were collected from the records and were analyzed using the Statistical Package for the Social Sciences software (IBM Corp., Armonk, NY, USA). This study covered the hospital records of 342 women (114 cases and 228 control). The rates of cesarean sections and small for gestational age were significantly higher among the cases compared to the controls (71.1% versus 43.4%, p < 0.001 and 24.6% versus 11.8%, p = 0.003; respectively). The mean birth weight was significantly lower among the cases group (3.0 ± 0.6 versus 3.3 ± 0.6 kg, p = 0.022). Only the case group reported the occurrence of neonatal COVID-19 infection (7.9%, p < 0.001). The study reported only a single case of intrauterine fetal death and one stillbirth in the cases group, but no neonatal deaths (p> 0.05). Maternal COVID-19 may be associated with undesirable neonatal outcomes. There is a possibility of vertical transmission of COVID-19 from the mother to the neonate, but this cannot be confirmed.

Seroprevalence, Risk Factors and Maternal-Fetal Outcomes of Toxoplasma gondii in Pregnant Women from WHO Eastern Mediterranean Region: Systematic Review and Meta-Analysis.

The protozoan parasite Toxoplasma gondii may cause serious illness in the immunocompromised. The Toxoplasma gondii seropositive prevalence in pregnant women in WHO Eastern Mediterranean Region countries is inconsistent in the literature and it is associated with outcomes that have not be fully elucidated, hence the need for a better understanding of the pooled seroprevalence and associated maternal and fetal outcomes. The objective was to conduct a systematic literature review and determine the pooled prevalence of WHO Eastern Mediterranean Regional countries' pregnant women's seroprevalence of Toxoplasma gondii and the maternal-fetal outcomes. This quantitative study examined WHO Eastern Mediterranean countries' maternal-fetal outcomes and Toxoplasma gondii prevalence in pregnant women. The targeted population was pregnant women, while the primary outcome was seropositivity of Toxoplasma gondii, while other outcomes such as maternal and fetal associations and risk factors were determined PubMed, SCOPUS, MEDLINE, and Index Medicus for the Eastern Mediterranean Region (IMEMR) databases were searched up until 30 January 2023. The search terms used were "Toxoplasma gondii" OR "Toxoplasma infection" AND "Pregnant woman" or pregnan* OR Antenatal OR Prenatal OR Gravidity OR Parturition OR Maternal AND WHO Eastern Mediterranean Region). OpenMeta-Analyst and Jamovi were used to analyze the generated data. In total, 95 of 2947 articles meeting the inclusion criteria examined Toxoplasma gondii prevalence in pregnant women from WHO Eastern Mediterranean countries. The pooled prevalence of Toxoplasma gondii in pregnant women was 36.5% (95%CI: 32.6-40.4) with a median value of 35.64%, range values of 1.38-75.30%, with 99.61% heterogeneity. The pooled seroprevalence of IgG of Toxoplasma gondii was 33.5% (95%CI: 29.8-37.2) with a median value of 33.51%, and a range values of 1.38-69.92%; the pooled seroprevalence of IgM was 3.6% (95%CI: 3.1-4.1)) with a median value of 3.62 and range values of 0.20-17.47%, while cases of pooled seroprevalence of both IgG and IgM positivity was 3.0% (95%CI: 1.9-4.4) with a median value of 2.05 and a range values of 0.05-16.62%. Of the Toxoplasma gondii seropositive women, 1281/3389 (34.8%) 174/1765 (32.9%), 1311/3101 (43.7%), and 715/1683 (40.8%) of them had contact with cats, drank unprocessed milk, ate raw or undercooked meat and ate unwashed raw vegetables, respectively. The maternal-fetal outcomes associated with Toxoplasma gondii seropositivity were a history of abortions, miscarriage, stillbirth, intrauterine fetal death, and premature birth, which were found in 868/2990 (32.5%), 112/300 (36.1%), 111/375 (25.7%), 3/157 (1.9%) and 96/362 (20.1%) of women who tested positive for Toxoplasma gondii antibodies. The study found a high proportion of Toxoplasma gondii seroprevalence in pregnant women in the WHO Eastern Mediterranean Region, which may be linked to poor outcomes for mothers and their babies. Thus, pregnant women require monitoring and comprehensive prevention strategies for Toxoplasma gondii infection.

Pregnancy, delivery and neonatal outcomes among women with hypoparathyroidism-A population-based study.

Data are inconclusive regarding pregnancy complications associated with maternal chronic hypoparathyroidism. Therefore, we aimed to compare pregnancy, delivery and neonatal outcomes in patients affected by chronic hypoparathyroidism to those without chronic hypoparathyroidism. A retrospective population-based study utilising data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database over 11 years from 2004 to 2014 inclusively. Multivariate logistic regression was used to control for confounders. Patients with chronic hypoparathyroidism compared with those without. Obstetric and neonatal outcomes. We identified 204 pregnancies in mothers with chronic hypoparathyroidism and 9,096,584 pregnancies without chronic hypoparathyroidism. After adjusting for age, insurance plan type, obesity, chronic hypertension, thyroid disease, pregestational diabetes mellitus, and previous caesarean section, patients in the hypoparathyroidism group, compared with those without hypoparathyroidism, were found to have an increased rate of preterm birth (<37 weeks) (19.1% vs. 7.2%, aOR: 2.49, 95% confidence interval [CI]: 1.74-3.54, p < 0.0001, respectively); and blood transfusions (4.9% vs. 1.0%, aOR: 4.07, 95% CI: 2.15-7.73, p < -0.0001). Neonates to mothers with chronic hypoparathyroidism had a higher rate of congenital anomalies (4.4% vs. 0.4%, aOR: 6.50, 95% CI: 3.31-12.75, p < 0.0001), with comparable rates of small-for-gestational-age neonates and intrauterine foetal death. This is the largest study of chronic hypoparathyroidism in pregnancy to date. We found significant increases in the rates of preterm birth, blood transfusions and congenital anomalies in chronic hypoparathyroidism. Our findings highlight the importance of identifying chronic hypoparathyroidism as a risk factor for pregnancy and neonatal complications, although it remains unknown if maintaining calcium in the target range will mitigate these risks.

Maternal COVID-19 causing intrauterine foetal demise with microthrombotic placental insufficiency: a case report

BackgroundPregnant 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.CaseHerein 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.ConclusionThis 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.

Maternal and Fetal Outcome in Cases of Preeclampsia and Eclampsia in Tertiary Care Center of Nepal

INTRODUCTION Hypertensive disorders of pregnancy includes Gestational Hypertension, Preeclampsia and Eclampsia, Chronic Hypertension and Preeclampsia superimposed in Chronic Hypertension. These condition complicates around 5 to 10 percent of pregnancies and have significant contributions on maternal and fetal adverse outcome. This study was done to find out the maternal and fetal outcome in cases of Pre-eclampsia and Eclampsia. MATERIAL AND METHODS It was a hospital based cross sectional observational study done in department of Obstetrics and Gynecology of Universal College of Medical Sciences from August 2021 to June 2022. Maternal and fetal outcome in Preeclampsia and eclampsia were studied in 116 cases. RESULTS Incidence of diseases was 5.94%, preeclampsia 33(28.4%), eclampsia 23(19.8%) and severe preeclampsia 60 (57.7%). Adverse maternal outcome were HELLP (Hemolysis, Elevated liver enzyme and Low platelets counts) syndrome 15 (12.93%), Abruption placenta 7(6.03%), need of blood transfusion 20 (17.24%), Pulmonary Oedema 3(2.58%), Post-Partum Hemorrhage 3(2.58%) and one case had maternal death. Total 121 babies were born, 42(36.20%) admitted in NICU, 10(8.26%) were intra uterine fetal death (IUFD), 3 (2.48%) were neonatal death (NND), 10(8.26%) refused treatment and leave against medical advice. Common fetal morbidities were intra uterine growth restriction (IUGR) 29 (23.76%), preterm Low birth weight 22(18.18%), anomalous baby 3(2.48%) and congenital pneumonia 1 (0.83%). CONCLUSION Proper Antenatal care and screening, timely referral and prompt management favoured the outcome in positive way.

Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome.

Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype. Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband. Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G>C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband's kidney tissue. Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.

Risk of perinatal mortality among the offspring of workers employed at production with radiation hazards

Studies that address risks of perinatal mortality among the offspring of people exposed to ionizing radiation in the workplace are significant for developing hygienic standards at production facilities with radiation hazards. The purpose was to analyze perinatal mortality (stillbirths and early neonatal deaths) among the offspring of workers employed by Mayak Production Association (Mayak PA), the first atomic production facility in Russia. A retrospective analysis was performed among 25,007 children born in 1949–1973; parents of 14,580 of these children were exposed to long-term occupational radiation at Mayak PA. The study provides frequency and dynamics of perinatal mortality and comparative analysis of perinatal mortality by sex, year of birth, parental age at childbirth, and dose categories of radiation exposure. Research data were analyzed by methods of non-parametric statistics. We calculated a relative risk (RR) of perinatal mortality among the offspring of exposed and unexposed parents with 95 % CI. The rate of perinatal mortality was generally the same in both groups, 19.9 for 103 in the test group and 17.9 for 103 in the control, p &gt; 0.05. Stillbirths among male offspring were statistically significantly more often observed in the test group due to contribution of the children with only mothers exposed to occupational radiation exposure at Mayak PA prior to conception and offspring exposed in utero. Intrauterine fetal death was observed statistically significantly more often among boys of the test group compared to controls: 2.9 against 0.9 for 103. Rates of stillbirths and perinatal mortality in the main group statistically significantly exceeded the values in the comparison group in 1949–1953: RR = 2.69 (CI: 1.46–4.95) and 2.12 (1.38–3.28) respectively. Significant statistical differences in the perinatal mortality risk were established in certain categories of preconception and intrauterine gamma-exposure. The identified peculiarities of unfavorable outcomes in the perinatal period that were detected among the offspring of Mayak PA workers could be eligible for further epidemiological monitoring. Polyetiology character of perinatal mortality requires further follow up of the cohort of the offspring born to atomic production workers.

Association Between Marked Fetal Heart Rate Variability and Neonatal Acidosis: A Prospective Cohort Study

ABSTRACT Monitoring of fetal heart rate (FHR) is an important indicator of fetal well-being during labor, but it is subject to low specificity and interpretation variability; this causes the clinical effectiveness for preventing adverse outcomes to remain controversial. Fetal heart rate has inherent variability, but reduced or marked variability can reflect poor autonomic activity, indicating conditions such as fetal acidosis. Recent research has highlighted that marked variability can indicate fetal distress; more research is needed to validate and investigate this claim. This study aimed to understand the association between marked FHR variability during labor and subsequent neonatal acidosis. Data were collected from 2 French maternity units; inclusion criteria extended to women at 37 weeks' gestation or greater, with continuous FHR monitoring during labor. Exclusion criteria were intrauterine fetal death, medical termination, multiple pregnancies, noncephalic presentation, and cesarean delivery. The primary outcome for this study was neonatal acidosis, or an umbilical artery pH of less than or equal to 7.10. Secondary outcomes included severe acidosis (pH ≤7.0), a 5-minute Apgar score of less than 7, respiratory distress, neonatal intensive care unit admission, neonatal infection, and neonatal death. Final analysis included 4394 women who gave birth between January 1 and December 31, 2019. Of this population, 177 neonates experienced marked variability in FHR within 1 hour before delivery, with a median duration of marked variability of 2 minutes. Prevalence of neonatal acidosis was 15.3% in neonates who experienced marked FHR variability and 5.6% in those who did not (aRR, 2.30; 95% confidence interval [CI], 1.53–3.44). In addition, those with marked FHR variability more often experienced respiratory distress (aRR, 1.73; 95% CI, 1.15–2.58). Analysis was subsequently performed according to the National Institute of Child Health and Human Development category of FHR; the association between FHR variability and neonatal acidosis was significant in category I (aRR, 5.48; 95% CI, 1.88–15.96) and category II (aRR, 2.29; 95% CI, 1.40–3.74) groups. Category III FHR, however, had no significant association. Strengths of this study include the prospective cohort design, as well as generalizability. Subcategory assessment of the FHR patterns allowed for more accurate examination of the risk of neonatal acidosis. Limitations include an observational design and the strict exclusion criteria required to minimize bias, which reduces generalizability to low-risk groups. The findings of this study are consistent with previous literature in that FHR variability can be a significant marker for fetal outcomes. Clinically, these results can help providers recognize the risk of fetal and neonatal acidosis. Further research is needed to delineate further associations and assess interpretations of pattern variability.

РИСК ПЕРИНАТАЛЬНЫХ ПОТЕРЬ СРЕДИ ПОТОМКОВ ПЕРСОНАЛА РАДИАЦИОННО ОПАСНОГО ПРОИЗВОДСТВА

A retrospective analysis was performed among 25,007 children born in 1949–1973; parents of 14,580 of these children were exposed to long-term occupational radiation at Mayak PA. The study provides frequency and dynamics of perinatal mortality and comparative analysis of perinatal mortality by sex, year of birth, parental age at childbirth, and dose categories of radiation exposure. Research data were analyzed by methods of non-parametric statistics. We calculated a relative risk (RR) of perinatal mortality among the offspring of exposed and unexposed parents with 95 % CI. The rate of perinatal mortality was generally the same in both groups, 19.9 for 103 in the test group and 17.9 for 103 in the control, p &gt; 0.05. Stillbirths among male offspring were statistically significantly more often observed in the test group due to contribution of the children with only mothers exposed to occupational radiation exposure at Mayak PA prior to conception and offspring exposed in utero. Intrauterine fetal death was observed statistically significantly more often among boys of the test group compared to controls: 2.9 against 0.9 for 103. Rates of stillbirths and perinatal mortality in the main group statistically significantly exceeded the values in the comparison group in 1949–1953: RR = 2.69 (CI: 1.46–4.95) and 2.12 (1.38–3.28) respectively. Significant statistical differences in the perinatal mortality risk were established in certain categories of preconception and intrauterine gamma-exposure. The identified peculiarities of unfavorable outcomes in the perinatal period that were detected among the offspring of Mayak PA workers could be eligible for further epidemiological monitoring. Poly-etiology character of perinatal mortality requires further follow up of the cohort of the offspring born to atomic production workers.

A case of chorioamnionitis preceded by sudden intrauterine fetal death at 25 weeks 5 days gestation

A case of chorioamnionitis preceded by sudden intrauterine fetal death at 25 weeks 5 days gestation

A case of non-immune hydrops fetalis with cystic hygroma complicated by intrauterine fetal death

Hydrops fetalis refers to the excessive accumulation of fluid in the extracellular compartment of the fetus. Cystic hygroma is a congenital malformation of the cervical lymphatic system responsible for an accumulation of lymphatic fluid commonly in the retrocervical region. Cystic hygromas are most often associated with chromosomal abnormalities. When a cystic hygroma is diagnosed in utero, the fetal survival rate is only 2-6%. When hydrops fetalis is present with cystic hygroma, the mortality rate is close to 100%. We present here the case of a 23-year-old primigravida in whom an ultrasound performed at 17 weeks of amenorrhea revealed a posterior cervical cystic hygroma associated with hydrops fetalis, the evolution of which was marked by intrauterine fetal death two weeks later. Keywords: Hydrops fetalis, Cystic hygroma, Chromosomal abnormalities, Prenatal diagnosis.