Fetal Defects Research Articles

SAT436 Endocrine Disruptor Of Organochlorine Pesticides Levels In Saudi Arabian Produce

Abstract Disclosure: M.S. Alokail: None. N.M. Al-Daghri: None. A.M. Alnaami: None. S. Sabico: None. S.D. Hussain: None. O.E. Amer: None. S.H. Abd-Alrahman: None. Food monitoring (FM) is a system used to evaluate and monitor hazardous contaminants, including pollutants such as organochlorine pesticides (OCPs). Long term exposure to organochlorine pesticides (OCPs) can lead to a variety of endocrine and reproductive disruptors including gonadal changes, changes in reproductive behavior, reduced sperm quality, an increase in organ malformations, testicular failure, fetal defects, thyroid dysfunction, and lactation. The present study aimed to determine and quantify OCPs in different local produce collected from different regions in Saudi Arabia. A total of 179 local produce samples were obtained in four regions in Saudi Arabia: Riyadh (N=55), Qassim (N=61), Eastern province (N=38) and Western region (N=25). Solid phase extraction method (QuEChERS) was used to detect OCP residues in samples and levels were quantified using gas chromatograph-electron capture detector (GC-ECD). The results have shown that a total of 11 OCPs were detected overall (9 OCPs in Qassim, Eastern province and Riyadh; 8 in Western region). Levels of alpha BHC was highest in Riyadh; 6 OCPs were highest in Qassim (Beta-BHC, Delta BCH, Dieldrin, Gamma-BHC, heptachlorepoxide and heptachlor); 4 OCPs were highest in the Eastern province (DDD, DDE, endosulfan and endrin), with endrin and endosulfan having the highest levels among all OCPs assessed. A total of 6 OCPs were found in all regions at varying concentrations (Beta-BHC, DDE, Delta-BCH, Dieldrin, endosulfan and heptachlor. Worthy to note is that heptachlorepoxide was found only in Qassim. In conclusion, the endocrine disruptor pesticides such as OCP residues require further investigation for a possible etiologic role in some hormone related cancers such as breast cancer. Presentation: Saturday, June 17, 2023

Cryopreserved human umbilical cord as a meningeal patch during in utero spina bifida repair in a modified ovine model.

Despite in utero spina bifida (SB) repair, more than two-thirds of patients with SB are unable to ambulate independently, and 1 in 4 children need surgery for tethered cord by school age. The objective of this study was to test the cryopreserved human umbilical cord (HUC) as an antiscarring material to reduce tethering and improve function in a modified in utero SB repair model. An SB defect (L2-6 levels) without myelotomy was created in fetuses of timed-pregnant ewes at gestational day (GD) 75. On GD 96, the fetal defect was exposed, and the arachnoid layer was removed to disrupt the barrier and expose the spinal cord to simulate human in utero SB repair. The fetuses were randomly assigned to two groups according to the method used to cover the spinal cord: the conventional repair (CR) group, for which myofascial closure was used (n = 7), and the HUC meningeal patch group, for which HUC was used as a meningeal patch (n = 6), followed by primary skin closure. The lambs were delivered at GD 140. Blinded clinical assessment of spinal cord function was performed using the Texas Spinal Cord Injury Scale (TSCIS). Histology of the spine was performed for quantitative assessment of spinal cord tethering, inflammatory markers, and arachnoid layer regeneration. The TSCIS scores were significantly lower in the CR than the HUC meningeal patch group (p = 0.0015) and the controls (p = 0.0018). The loss of spinal cord function in the CR group was mainly due to ataxia and loss of proprioception (p = 0.01 and 0.005 vs control and HUC, respectively). The histology at the repair site showed higher rates of spinal cord tethering in the CR lambs than the HUC lambs at all levels of the repair site (p = 0.01 and 0.02 vs control and HUC, respectively). In the CR with tethering compared with the HUC repair, there was a lower arachnoid layer covering at the repair site (p = 0.001). There was greater astrocyte activation in the posterior column in the CR than in the HUC repair group (p = 0.01). In a modified ovine SB model, the HUC as a meningeal patch allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero SB repair.

OC11.04: Diagnostic value of chromosomal microarray analysis for fetal congenital heart defects with different cardiac phenotypes and extracardiac abnormalities

OC11.04: Diagnostic value of chromosomal microarray analysis for fetal congenital heart defects with different cardiac phenotypes and extracardiac abnormalities

OP10.04: Detection of fetal structural defects in the first trimester with a structured protocol and newer markers: an 18‐year experience of regular audits

OP10.04: Detection of fetal structural defects in the first trimester with a structured protocol and newer markers: an 18‐year experience of regular audits

Assessment of the course of the gestational process using survey method and depending on the laboratory confirmed prenatal alcohol use (cross-section study)

Background. Studying the problem of alcohol consumption by pregnant women using modern laboratory research methods has valuable theoretical and practical significance. The aim of the study. To determine the characteristics of the pregnancy course in women consuming alcohol in the prenatal period confirmed by survey and laboratory tests, depending on the phosphatidylethanol levels. Materials and methods. We examined 863 women under observation at the Irkutsk Regional Perinatal Center for the period from 2014 to 2021. To confirm the fact of alcohol consumption in the prenatal period, 545 women were surveyed, 318 women were examined using laboratory analysis. The diagnostic biomarker for alcohol was PEth:16:0/18:1. To assign pregnant women to the control group, a PEth concentration of ≤ 8 ng/ml was taken. If the PEth concentration was > 8 ng/ml, pregnant women were classified as heavy drinkers. Clinical and laboratory indicators of the course of pregnancy and childbirth were carried out in comparative groups. Results. It has been established that every second woman of reproductive age took alcohol before pregnancy. 24.2 % of women did not stop consuming alcohol in the prenatal period. At the same time, the risk of congenital malformations was high, since 20.4 % of women consumed alcohol in the first trimester of pregnancy. Based on the results of the survey, it was revealed that in women who consumed alcohol in the prenatal period, the following pathological conditions are statistically significantly more common: anemia, congenital heart defects in fetuses, prematurity of gestational age, labor anomalies, uterus subinvolution. Based on the results of laboratory confirmation of alcohol consumption, it was established that parity of birth, intrauterine growth retardation, and premature birth were statistically significantly more often in pregnant women who drink. Conclusion. Thus, in order to obtain the most meaningful and high-quality results, it is necessary to conduct larger studies. In addition, maternal blood biomarkers should be used to confirm levels of alcohol consumption throughout all trimesters of pregnancy.

Плацентарні фактори у вагітних з ізольованими вадами серця в плода

The placenta, as a unique and transient organ in humans, ensures the development and protection of the fetus, the expression of angiogenic and antiangiogenic factors and their receptors. The integrity of the fetoplacental endothelial barrier is critical for the development of fetal organs, especially the cardiovascular system. Placental growth factor (PLGF) regulates the morphologic and functional development of the uteroplacental vasculature and can vary with gestational age and in various pathologic conditions of the pregnant woman. Since there is a differential expression of PLGF and soluble form of fms-like tyrosine kinase (sFlt-1) at different gestational ages and their competitive interaction, it is advisable to study their level in the blood of a pregnant woman as indicators of regulation of the placental vascular system in pathological conditions of the woman and fetus. Purpose - to determine the levels of placental factors, namely PLGF and sFlt-1, in the serum of pregnant women with isolated congenital heart disease (CHD) in the fetus to increase the effectiveness of diagnostics and the ability to predict heart diseases. Materials and methods. The work was based on a prospective clinical study of a hospital sample, using the case-control study method, with the evaluation of some clinical and laboratory data in 30 pregnant women with isolated fetal CHD (study group) and 60 pregnant women with a healthy fetus (control group). In order to minimize the influence of various risk factors for fetal heart disease, the criteria for selecting pregnant women with non-syndromic forms of CHD and the control group were defined. Clinical, laboratory and statistical methods were used in the study. The level of angiogenesis indicators in blood serum of pregnant women of both groups was determined by enzyme-linked immunosorbent assay in units of pg/ml in the third trimester of pregnancy. The statistical analysis was carried out using the R software package. ROC analysis and AUC (area under the ROC curve) were used for quantitative interpretation. Differences with p<0.05 were considered statistically significant. Results. According to the results of the study, the age of the women in the study group ranged from 17 to 39 years with a mean of 28.36±5.12, and the age of the women in the control group was 29.63±5.39 (p=0.239). The mean gestational age of women in the study group at enrollment was 28.26±8.45 weeks. The mean PLGF level was 93.73±77.32 pg/mL in the study group and 198.63±168.27 pg/mL in the control group (p=0.002). The average level of sFlt-1 in the blood serum of the women in the study group was 9779.44±5407.53 pg/ml, while in the pregnant women in the control group it was 3124.6±1624.53 (p<0.001). The sFlt/PlGF ratio was 180.9±151.1 in the study group and 15.76±14.7 in the control group (p<0.001). Conclusions. The obtained results in the form of a decrease of the placental growth factor in the blood of pregnant women with congenital heart defects in the fetus and an increase of the antiangiogenic factor in this group in the III trimester compared to a healthy fetus indicate a violation of angiogenesis in the fetoplacental system. Analysis of data on the age of pregnant women of both groups did not reveal a statistically significant difference between them. Due to the usage of multifactor logistic regression model, was created the CHD “risk calculator” which, using the placental factors of the pregnant woman, calculates the probability of the occurrence of a heart defect in fetus. The study was conducted in accordance with the tenets of the Declaration of Helsinki. The local ethics committee approved the study protocol for all participants. Informed consent was obtained from patients. No conflict of interests was declared by the author.

Risk factor analysis for adverse prognosis of the fetal ventricular septal defect (VSD)

BackgroundVentricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses.MethodsFetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated.ResultsChromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome.ConclusionsThe current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo.

Zika virus (ZIKV) is a Flavivirus responsible for recent epidemics in Pacific Islands and in the Americas. In humans, the consequences of ZIKV infection range from asymptomatic infection to severe neurological disease such as Guillain-Barré syndrome or fetal neurodevelopmental defects, suggesting, among other factors, the influence of host genetic variants. We previously reported similar diverse outcomes of ZIKV infection in mice of the Collaborative Cross (CC), a collection of inbred strains with large genetic diversity. CC071/TauUnc (CC071) was the most susceptible CC strain with severe symptoms and lethality. Notably, CC071 has been recently reported to be also susceptible to other flaviviruses including dengue virus, Powassan virus, West Nile virus, and to Rift Valley fever virus. To identify the genetic origin of this broad susceptibility, we investigated ZIKV replication in mouse embryonic fibroblasts (MEFs) from CC071 and two resistant strains. CC071 showed uncontrolled ZIKV replication associated with delayed induction of type-I interferons (IFN-I). Genetic analysis identified a mutation in the Irf3 gene specific to the CC071 strain which prevents the protein phosphorylation required to activate interferon beta transcription. We demonstrated that this mutation induces the same defective IFN-I response and uncontrolled viral replication in MEFs as an Irf3 knock-out allele. By contrast, we also showed that Irf3 deficiency did not induce the high plasma viral load and clinical severity observed in CC071 mice and that susceptibility alleles at other genes, not associated with the IFN-I response, are required. Our results provide new insight into the in vitro and in vivo roles of Irf3, and into the genetic complexity of host responses to flaviviruses.

Maternal periconceptional folic acid supplementation and risk for fetal congenital genitourinary system defects.

Taking folic acid supplementation could reduce the risk of neural tube defects for offspring in the maternal periconceptional period, but the relationship between folic acid use and other birth defects remains unclear, such as genitourinary system birth defects. The data from a Prenatal Health Care System and Birth Defects Surveillance System in Tongzhou, Beijing, China, were collected from 2013 to 2018. We adjusted for differences in characteristics between comparison groups using propensity score inverse probability weighting and assessed associations with Poisson regression modeling. A total of 65,418 live births and stillbirths were included, and there were 194 cases with congenital genitourinary defects among them. The prevalence of genitourinary system birth defects was 29.2 (34.9) per 10,000 for FA/MMFA users (nonusers). Compared to nonusers, FA/MMFA users had a lower risk for genitourinary system birth defects (adjusted risk ratio [aRR] 0.81, 95% confidence interval [CI] 0.67, 0.98), and for hypospadias (aRR 0.55, 95% CI 0.40, 0.76). FA or MMFA supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. More mechanisms should be explored for the protective effect. Folic acid (FA) or multiple micronutrients containing folic acid (MMFA) supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. Maternal FA/MMFA supplementation during the periconceptional period may reduce the risk for hypospadias.

Prevalence of congenital anomalies and related factors in live births in Zahedan, Southeast of Iran: A cross-sectional study.

The term congenital anomalies (CAs) refers to structural or functional abnormalities at the time of conception. Approximately 12 deaths related to congenital disabilities occur in every 10,000 babies born. This study aimed to evaluate the prevalence and associated factors of single and multiple CAs in live births in Zahedan, Southeast Iran. This cross-sectional study was conducted on 59,087 live births in a referral hospital in Zahedan located in the southeast of Iran from 2009 to 2019. All live births were examined by pediatricians and the CAs and categorized based on the international classification of diseases. Of 59,085 live births, at least 883 had a significant anomaly, and the prevalence rate of CAs was about 149 per 10,000. Anomalies of the nervous (24.1%) and cardiovascular systems (21.10%) were the most frequent, occurring in 213 and 187 of the live births, respectively. Spina bifida is the most common anomaly of the central nervous system. The most common anomalies in the cardiovascular system were unspecified heart malformations (17.1%), cardiovascular malformations (18.7%), and patent ductus arteriosus (11.7%). Significant correlations were found between the parent's consanguinity marriage, the mother's age, an existing anomaly in the family, and relatives in single and multiple CAs (p = 0.02, p = 0.02, p 0.001, p = 0.01, respectively). The prevalence of CAs was 149 per 10,000 live births. The highest prevalence of CAs was related to the central nervous system. Increasing the public's knowledge about fetal defects can reduce the prevalence of CAs.

Maternal and neonatal complications in pregnancies with and without pre-gestational diabetes mellitus.

To compare pregnancy complications in pregnancies with and without pre-gestational diabetes mellitus (DM) managed in a multidisciplinary high-risk diabetes antenatal clinic. This screening cohort study was undertaken at alarge maternity unit in the United Kingdom between January 2010 and December 2022. We included singleton pregnancies that booked at our unit at 11-13weeks' gestation. Univariate and multivariate logistic regression analysis was carried out to determine risks of complications in pregnancies with type 1 and type 2 DM after adjusting formaternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (AR) and odds ratio (OR) (95 % confidence intervals [CI]). The study population included 53,649 singleton pregnancies, including 509 (1.0 %) with pre-existing DM and49,122 (99.0 %) without diabetes. Multivariate logistic regression analysis demonstrated that there was a significant contribution from pre-existing DM in prediction of adverse outcomes, including antenatal complications such as fetal defects, stillbirth, preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age (LGA) neonates; intrapartum complications such as caesarean delivery (CS) and post-partum haemorrhage; and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and hypoxic ischaemic encephalopathy (HIE). In particular, there was a 5-fold increased risk of stillbirth and HIE. The maternal and neonatal complications inpregnancies with pre-existing DM are significantly increased compared to those without DM despite a decade of intensive multidisciplinary antenatal care. Further research is required to investigate strategies and interventions toprevent morbidity and mortality in pregnancies with pre-gestational DM.

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk: a multicenter maternal-fetal medicine study.

Evidence remains limited on the association between maternal ozone (O3) exposure and congenital heart defects (CHDs) in offspring, and few studies have investigated the interaction and modification of paternal smoking on this association. Using a sample including pregnant women at high risk of fetal CHD (with metabolic disease, first-trimester viral infection, family history of CHD, etc.) from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021, we examined the associations between maternal O3 exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association. CHD was diagnosed by fetal echocardiograms, maximum daily 8-hour average O3 exposure data at a 10 km × 10 km spatial resolution came from the Tracking Air Pollution in China dataset, and paternal smoking was collected using questionnaires. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Among 27,834 pregnant women at high risk of fetal CHD, 17.4% of fetuses were diagnosed with CHD. Each 10 μg/m3 increase in maternal O3 exposure was associated with a 17% increased risk of CHD in offspring (OR= 1.17, 95% CI =1.14-1.20). Compared with paternal nonsmoking and maternal low O3 exposure, the ORs (95% CI) of CHD for smoking and low O3 exposure, nonsmoking and high O3 exposure, and smoking and high O3 exposure were 1.25 (1.08-1.45), 1.81 (1.56-2.08), and 2.23 (1.84-2.71), respectively. Paternal smoking cessation seemingly mitigated the increased risk of CHD. Maternal O3 exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring, which calls for effective measures to decrease maternal exposure to O3 pollution and secondhand smoke for CHD prevention.

Four-section approach of fetal congenital heart disease at 11-13+6 weeks.

The objective of the study is to explore the value of the four-section approach in detecting fetal heart defects in the first trimester (11-13+6 weeks), analyze the reasons for the inconsistency between the results of ultrasound examination in the first trimester and subsequent verification, and describe the most common abnormal flow patterns of four sections. Between June 2019 and June 2021, a prenatal four-section approach (upper abdominal transverse section, four-chamber section, three vessel-trachea section, and bilateral subclavian artery section) with verification results in early pregnancy was analyzed. In total, 9,533 fetuses were included. Finally, 176 fetuses with congenital heart disease (CHD), containing 34 types, were identified. The total detection rate of cardiac abnormalities was 1.85%. 102 cases were accurately diagnosed by ultrasonography during early pregnancy. A total of 74 fetuses who had inconsistent results between fetal cardiac ultrasound and verification in early pregnancy were reported, of which the cases of 22 fetuses were inconsistent due to disease evolution and progression and the cases of 52 fetuses were inconsistent due to missed diagnosis and misdiagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of the four-section approach were 67.05%, 99.96%, 96.58%, and 99.33%, respectively. In this study, a total of 30 abnormal ultrasonic imaging patterns in four sections were summarized. We confirmed that the four-section approach in early pregnancy has a good diagnostic efficacy for fetal CHD. Intrauterine evolution of the fetal heart, missed diagnosis, and misdiagnosis are the reasons for the inconsistency between the results of early pregnancy ultrasound and subsequent verification. This study also presents the abnormal imaging patterns of four scan sections of CHD in early pregnancy, which are instructive for the rapid identification and diagnosis of CHD in the first trimester.

Fetal pulmonary artery stiffness is a strong predictor of persistent pulmonary hypertension of the newborn - An echocardiographic study

ObjectivePulmonary artery stiffness (PAS) is a strong and independent predictor of mortality in adult patients with pulmonary hypertension (PH). But the change in PAS during perinatal period remains unknown. Here, we aimed to explore the feasibility and performance of PAS on predicting persistent pulmonary hypertension of the newborn (PPHN). Methods1325 fetuses underwent a dedicated echocardiography screening for fetal heart defects during second trimester, third-trimester and neonatal period with the measurement of acceleration time (PAAT) and maximal frequency shift (MFS) of pulmonary artery flow. PAS (MFS/PAAT ratio) was calculated. ResultsSix fetuses were diagnosed as PPHN. Compared with the normal fetuses, those with PH had greater values of PAS during each period of time (second trimester, 52.6(46.2–54.5) vs. 32.4(28.0–39.4) kHz/s, p = 0.0003; third trimester, 52.9(46.1–55.3) vs. 29.7(27.3–33.3) kHz/s, p = 0.0002; neonatal period, 127.4(85.2–150.8) vs. 26.6(22.7–35.0) kHz/s, p < 0.0001). There was a statistically significant correlation between PAS and mean pulmonary artery pressure (p < 0.05) but no correlation between PAS and gestational age (p > 0.05) whether in normal fetuses or not. The area under receiver operating characteristic curve (AUC) of 0.97 for PAS during third trimester was superior to that for PAS during second trimester (AUC, 0.94) in predicting PPHN. The optimal cutoff value of PAS during third trimester was 37.40 KHz/s, with a sensitivity of 100%, a specificity of 91%, and an accuracy of 92%. ConclusionThere was a significant difference in PAS between normal fetuses and those with PH. PAS has a power performance on predicting PPHN.

Reliability of Magnetic Resonance Imaging in the Detection of Congenital Anomalies of Iraqi Women

Background: Prior to birth, fetal anomalies must be identified using antenatal imaging so that during utero interventions may be planned and the baby's postpartum care can be chosen. Aim: This paper aims to study the reliability of magnetic resonance imaging in the detection of congenital anomalies of Iraqi women. Patients and methods: This study was a cross-sectional study in the analysis of the reliability of magnetic resonance imaging in the detection of congenital anomalies of Iraqi women in the Baghdad-Iraq from 17th August 2021 to 24th May 2022. The collected data of the MRI technique for using with congenital anomalies of Iraqi women was analysed into 90 patients by the SPSS program. Results and Discussion: 26 participants (28.89%) in our study had hydrocephalus. As a result, MRI can be used in addition to ultrasonography to diagnose embryonic genitourinary abnormalities, particularly in cases of oligohydramnios. In one instance of the diaphragm eventration, MRI was helpful in making the diagnosis. In 70 cases, MRI was successful; in the other 20, it was not. Our findings indicated that CNS received helpful information with 66% and without useful information with 34%, Gut received useful information with 77% and without useful information with 33%, and Multiple received useful information with 57% and without useful information with 43%. Conclusion: According to the findings, MRI showed the highest scored for detecting ventriculomegaly and the worst score for detecting cerebral haemorrhage and cortical abnormalities. Additionally, our study discovered that prenatal MRI has become a more potent tool for detecting fetal defects when ultrasound results are insufficient or equivocal.

Efficacy of Systematic Early-Second-Trimester Ultrasound Screening for Facial Anomalies: A Comparison between Prenatal Ultrasound and Postmortem Findings.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model

Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5mg/kg), or 5xDTG (12.5mg/kg) both administered orally with 50mg/kg tenofovir disoproxil fumarate 33.3mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network.

A multicenter study on two-stage transfer learning model for duct-dependent CHDs screening in fetal echocardiography

Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects.

The Physiological, Cognitive, and Developmental Effects of Prenatal Caffeine Consumption on Foetal Pregnancy Outcomes

Introduction: Maternal caffeine consumption during pregnancy may confer developmental risk to the foetus due to caffeine’s ability to cross the blood brain barrier (BBB) and blood placental barrier (BPB). This literature review investigated caffeine’s properties and mechanism of passage through the BBB and BPB. The subsequent effects of moderate-to-excessive maternal caffeine consumption (≥ 200mg of caffeine daily) on physical development, cognition, and behaviour were further explored. Methods: The review was conducted using PubMED, NCBI, and Google Scholar, using key terms such as “pregnancy”, “caffeine”, “prenatal”, “adverse effect”, “development”, and “embryo development”. Articles selected were published within the last 15 years (2008-2023) and longitudinal studies, cohort studies, and experimental methods using animal models were included. Results: It was found prenatal caffeine exposure poses a variety of potential consequences for the infant prior to and after delivery. Notably, physical developmental risks include fetal growth restriction, birth defect(s), and changes in neuronal structure and blood flow. Cognitive and behavioural consequences include possible links to externalizing behaviour problems, decreased intelligence quotient (IQ), attentive deficit and hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) during childhood. Discussion: This research is primarily restricted to animal models and cohort studies. Moroever, there were several conflicting conclusions surrounding behavioural and cognitive effects of prenatal caffeine exposure. This drives inquiry into how further research can both solidify causal relationships and be conducted ethically to help inform parents about the potential risks of prenatal caffeine exposure. Conclusion: With a global trend of increasing caffeine consumption, through coffee, black tea, and recently, matcha, this review provided insight into this ever-growing aspect of our lifestyles. It is paramount to understand the effect of caffeine on foetuses to promote safe and healthy pregnancy outcomes.

Intergenerational association of gut microbiota and metabolism with perinatal folate metabolism and neural tube defects

Disorders of folic acid metabolism during pregnancy lead to fetal neural tube defects (NTDs). However, the mechanisms still require further investigation. Here, we aim to analyze the brain metabolic profiles of 30 NTDs and 30 healthy fetuses. Our results indicated that low-folate diet during early life played a causal role in cerebral metabolism, especially in lipometabolic disturbance, highlighting the importance of folate in modulating brain development and metabolism. Next, we established a mouse model of NTDs. Interestingly, the differential metabolites are mainly involved in glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids both in human and mice fetal brain. Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, we further found the abundances of Firmicutes and Bacteroidetes in the gut of pregnant mice were correlated with the abundances of lipid metabolism related metabolites in the fetal brain. This finding probably reflects the intergenerational microbial-metabolism biomarkers of NTDs.