Prenatal predisposing factors associated with neonatal lupus erythematosus

Objectives To identify the prenatal predisposing factors related to neonatal lupus erythematosus (NLE). Materials and Methods A retrospective case-control study was made of 131 pregnant women with positive anti-Ro or anti-La autoantibodies and known neonatal outcomes between January 2002 and December 2019 at Siriraj Hospital, Bangkok, Thailand. There were 101 unaffected neonates and 30 NLE cases confirmed postnatally. Demographic and clinical data of the mothers and neonates with and without NLE were statistically compared. Results NLE was diagnosed in 30 out of 131 cases. A multivariate analysis identified the following significant factors for NLE: maternal anti-La antibodies (odds ratio (OR), 3.591; p = 0.030); and maternal treatment with either hydroxychloroquine (OR, 0.082; p = 0.001) or prednisolone (OR, 0.136; p = 0.017). Of the significant variables examined in the multivariate analysis models, high levels of maternal anti-La antibodies were found to be the strongest predictor of noncardiac NLE (OR, 4.558; p = 0.032), while a female baby was significantly higher in pregnancies complicated by cardiac NLE (OR, 5.374; p = 0.046). Hydroxychloroquine still provided a protective effect for both cardiac and noncardiac NLE ( p = 0.039 and 0.032, respectively). Conclusions The maternal anti-La antibodies were a beneficial predictor for NLE, especially as their high titers were influentially associated with noncardiac features. A female fetus seemed to present an increased risk for developing a congenital heart block. Nevertheless, the treatment with hydroxychloroquine during the pregnancies demonstrated a potentially protective factor against both cardiac and noncardiac manifestations.

Single cell profiling of Hofbauer cells and fetal brain microglia reveals shared programs and functions

SummaryMaternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many of which are mediated by in utero microglial programming. Microglia remain inaccessible at birth and throughout development, thus identification of noninvasive biomarkers that can reflect fetal brain microglial programming may permit screening and intervention during critical developmental windows. Here we used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells). Single-cell RNA sequencing of murine fetal brain and placental macrophages demonstrated shared transcriptional programs. Comparison with human datasets demonstrated that placental resident macrophage signatures are highly conserved between mice and humans. Single-cell RNA-seq identified sex differences in fetal microglial and Hofbauer cell programs, and robust differences between placenta-associated maternal macrophage/monocyte (PAMM) populations in the context of a male versus a female fetus. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, potentially facilitating the early identification of offspring most vulnerable to neurodevelopmental disorders.

X-linked sideroblastic anaemia in a female fetus: a case report and a literature review

Background X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width. However, in females with XLSA the characteristic laboratory findings can be dimorphic and present with macrocytic (elevated MCV) in addition to microcytic red cells. Case presentation We report a case of fetal anaemia, presenting in the early third trimester of pregnancy, in a female fetus. Ultrasound findings at 29 weeks were of cardiomegaly, prominent umbilical veins, a small rim of ascites, and mean cerebral artery peak systolic velocity (PSV) value above 1.5 Multiples of the Median (MoM). She underwent non-invasive prenatal testing that determined the rhesus genotype of the fetus to be rhesus B negative. No red blood cell antibodies were reported. Other investigations to determine the underlying cause of fetal anaemia included microarray comparative genomic hybridization, serology to exclude congenital infection and a peripheral blood film and fetal bilirubin to detect haemolysis. The maternal grandmother had a history of sideroblastic anaemia diagnosed at the age of 17 years. The mother had mild macrocytic anaemia with haemoglobin of 10.4 g/dl and MCV of 104 fl. The fetal anaemia was successfully treated with two in utero transfusions (IUTs), and delivery occurred via caesarean section at 37 weeks of gestation. The red cell gene sequencing in both the mother and fetus were heterozygous for an ALAS2 mutation causing in utero manifestations of XLSA. The haemoglobin on discharge to the local hospital at five days of age was 19.1 g/dl. Subsequently, the infant became anaemic, requiring regular 3–4 monthly blood transfusions and demonstrating overall normal development. Her anaemia was unresponsive to pyridoxine. Conclusions This is one of four cases reporting multiple female members presenting with discordant clinical features of XLSA from being entirely asymptomatic to hydropic in utero. Our report is novel in that there are no previous cases in the literature of anaemia in a female fetus heterozygous for ALAS2 mutation.

Fetus diagnosed with cervical teratoma delivered by exit procedure (Extra uterine intrapartum treatment)

Congenital cervical teratomas are rare tumours of germ cells that should be diagnosed antenatally by ultrasound during anomaly scan or even earlier. The incidence of teratomas of the head and neck is 3-5%. We are presenting a case of rare cervical teratoma.1 Congenital cervical tumours are often clinically dramatic, though basically benign. Prognosis is favourable only if the airway is quickly stabilized and necessarily surgical procedure is planned and executed effectively.2 Case presentation: A 34-year-old female presented at 32 weeks of gestation, at Al Amal National Hospital where an ultrasound examination revealed a single viable cephalic fetus with a huge irregular heterogeneous anterior neck mass suspected as congenital cervical neck teratoma. The delivery was planned at 37 weeks gestation. The team was assembled for EXIT procedure which includes the obstetricians, neonatologist, anthologist, ENT surgeons. At 37 weeks of gestation, the child was maintained on maternal circulation after caesarean section until successfully intubated (Extra Uterine Intrapartum Treatment (EXIT) was performed at Al Amal National Hospital after liaison with the anesthetist, neonatologist and the pediatric surgeon. A female fetus weighing 3.8 kg was delivered and intubated immediately. Unfortunately, the newborn died at 48hours of age. Conclusion: Prenatally diagnosed head and neck teratomas can result in early neonatal death if the delivery was not planned correctly with right multidisciplinary team. In this case EXIT is the procedure of choice.

Prenatal Diagnosis of Combined Maternal 4q Interstitial Deletion and Paternal 15q Microduplication

The 4q deletion syndrome is a well-known rare genetic condition caused by partial, terminal, or interstitial deletion in the long arm (q) of chromosome 4. The phenotype of this syndrome shows a broad spectrum of clinical manifestations due to the great variability in the size and location of the deletion. In the literature, the mostly terminal deletions of chromosome 4q and the relative phenotypes are described, while the interstitial deletions of the long arm of chromosome 4 are rarely cited. Here, we report on a female fetus presenting no abnormal ultrasound evidence but with multiple chromosome aberrations. Comparative genomic hybridization (aCGH) revealed an interstitial 10.09 Mb deletion at the chromosome at the region of 4q28, arr[hg19] 4q28.1q28.3 (124068262_134158728)x1 combined with a 386.81 Kb microduplication at chromosome 15q11.1, arr[hg19] 15.11 (20249932_20636742)x3. At birth, and after 11 months, the baby was confirmed healthy and normal. The identification of this case allows for a deeper understanding of 4q syndrome and provides an explanation for the wide genetic/phenotypic spectrum of this pathology. This report can provide a reference for prenatal diagnosis and genetic counseling in patients who have similar cytogenetic abnormalities, and underlines the importance of reporting unusual variant chromosomes for diagnostic genetic purposes.

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.

Echogenic Intestine: a Case of Intrauterine Fetal Demise at Term

Introduction/Objective Parvovirus B19 is a non-enveloped, single-stranded DNA virus that preferentially infects early erythroids, and is commonly associated with second trimester hydrops fetalis. Third trimester non-hydropic intrauterine fetal demise due to parvovirus B19 infection with associated pathologic changes has rarely been described, particularly in the context of IgG seroconverted mother. Methods/Case Report We present a case of a 37 weeks’ gestation stillborn female fetus born to a 29 year-old mother who presented with lack of fetal movement for one day. Fetal ultrasound demonstrated diffuse intestinal echogenicity. Maternal parvovirus B19 IgG level was high (5.48, reference: <=0.90 Index). Postmortem examination revealed a non-dysmorphic fetus. Gross examination was unremarkable. Microscopic examination of small intestine revealed mucosal inflammation and multifocal calcifications. Prominent extramedullary hematopoiesis was present in the liver. Viral cytopathic effect was noted microscopically within nucleated red blood cells present intravascularly within chorionic villi, small intestine, liver, and spleen. Parvovirus B19 infection was confirmed by immunohistochemistry. Results (if a Case Study enter NA) NA Conclusion The cause of clinically puzzling intrauterine fetal demise at term with prominent intestinal echogenicity on ultrasound was determined to be parvovirus B19 infection on postmortem examination. We emphasize the possibility of this diagnostic differential in non-hydropic, third trimester fetal demise in presence of maternal IgG seroconversion and lack of signs of active infection.

Maternal C-Peptide and Insulin Sensitivity, but Not BMI, Associate with Fatty Acids in the First Trimester of Pregnancy

Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids in the first trimester of human pregnancy. This cross-sectional study included 123 non-smoking women with singleton pregnancy. In maternal serum, cotinine, leptin, and C-peptide (ELISA), glucose (hexokinase-based test) and fatty acids (gas chromatography) were quantified, and the insulin sensitivity index (ISHOMA) was calculated. Concentrations of fatty acid classes and total fatty acids did not differ between BMI or leptin categories. However, n-3 polyunsaturated fatty acids (PUFA) were decreased in the category with the highest C-peptide concentration (n-3 PUFA: CI −35.82–−6.28, p < 0.006) and in the lowest ISHOMA category (n-3 PUFA: CI −36.48–−5.61, p < 0.008). In a subcohort, in which fetal sex was determined (RT-qPCR of placental tissue), C-peptide was significantly associated with docosahexaenoic acid (DHA) in mothers bearing a female (n = 46), but not male (n = 37) fetus. In conclusion, pregnant women with high fasting C-peptide and low ISHOMA had decreased n-3 PUFA, and DHA was lower with higher C-peptide only in mothers bearing a female fetus.

Placental mesenchymal dysplasia- A case report

Placental mesenchymal dysplasia is a rare disorder mainly characterized by enlarged placenta. Patients on antenatal visits present with normal or slightly raised Beta-HCG, raised Alfa-fetoprotein and cystic structures on USG resembling a molar pregnancy. It has to be differentiated from molar pregnancies to avoid unnecessary termination of pregnancy. This condition is associated with IUGR or IUFD. Mostly the fetus are females. Due to lack of awareness of this condition it remains underreported. Here we present a case report of 20 years old female 37 week pregnant with IUGR with clinical suspicion of molar pregnancy gave birth to alive female fetus and on histopathological examination of placenta was diagnosed with PMD.