Impact of COVID-19 and vaccination on first and second trimester screening results.

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (ßHCG) between infected women and controls. Moreover, these levels were not different between "Infected + vaccinated" and "Only vaccinated" groups. However, median values of PAPP-A and ßHCG were higher in "Infected + vaccinated" and "Only vaccinated" groups compared with "Infected" and "Control" groups (P < 0.001). Median values of unconjugated Estriol (uE3) and ßHCG markers were not different between "Only vaccinated" and "Control" groups, yet both markers were elevated in "Infected" and "Infected + vaccinated" groups compared with other groups. AFP values were higher in "Infected" group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in "Infected" and "Vaccinated" groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS.

Prenatal diagnosis of VACTERL association after early-first trimester SARS-COV-2 infection.

Organogenesis is a period of fetal development with a special vulnerability to biological and environmental agents. There are some viral infections whose transmission in the first trimester carries a significant risk for the development of congenital anomalies. Although the possibility of vertical transmission of SARS-CoV-2 during pregnancy has been demonstrated, there are no studies evaluating the impact of SARS-CoV-2 infection in the first trimester and its possible association with congenital anomalies. In this communication, we present the case of a pregnant woman with early SARS-CoV-2 infection, prenatally diagnosed with fetal VACTERL association by mid-trimester ultrasound. Further studies are needed to determine the causal association.

Decision-making process about prenatal genetic screening: how deeply do moms-to-be want to know from Non-Invasive Prenatal Testing?

BACKGROUND: Prenatal information may be obtained through invasive diagnostic procedures and non-invasive screening procedures. Several psychological factors are involved in the decision to undergo a non-invasive prenatal testing (NIPT) but little is known about the decision-making strategies involved in choosing a specific level of in-depth NIPT, considering the increased availability and complexity of NIPT options. The main aim of this work is to assess the impact of psychological factors (anxiety about pregnancy, perception of risk in pregnancy, intolerance to uncertainty), and COVID-19 pandemic on the type of NIPT chosen, in terms of the number of conditions that are tested. METHODS: A self-administered survey evaluated the decision-making process about NIPT. The final sample comprised 191 women (Mage = 35.53; SD = 4.79) who underwent a NIPT from one private Italian genetic company. Based on the test date, the sample of women was divided between "NIPT before COVID-19" and "NIPT during COVID-19". RESULTS: Almost all of the participants reported being aware of the existence of different types of NIPT and more than half reported having been informed by their gynecologist. Results showed no significant association between the period in which women underwent NIPT (before COVID-19 or during COVID-19) and the preferences for more expanded screening panel. Furthermore, regarding psychological variables, results showed a significant difference between perceived risk for the fetus based on the NIPT type groups, revealing that pregnant women who underwent the more expanded panel had a significantly higher level of perceived risk for the fetus than that reported by pregnant women who underwent the basic one. There was no statistically significant difference between the other psychological variables and NIPT type. CONCLUSIONS: Our findings indicate the paramount role of gynecologist and other health care providers, such as geneticists and psychologists, is to support decision-making process in NIPT, in order to overcome people's deficits in genetic knowledge, promote awareness about their preferences, and control anxiety related to the unborn child. Decision-support strategies are critical during the onset of prenatal care, according to the advances in prenatal genomics and to parent's needs.

The incidence of congenital anomalies in newborns before and during the Covid-19 pandemic.

BACKGROUND: Pregnant women are one of the most vulnerable groups in the Covid-19 pandemic. Due to the lack of knowledge about fetal and perinatal complications following Covid-19 infection, the association of Covid-19 pandemic and congenital anomalies in babies conceived and born during this pandemic is unclear. Current study aimed to investigate the association between the Covid-19 pandemic and congenital birth anomalies in Iran. The population of newborns whose embryonic period coincided with the Covid-19 crises were compared with a similar group born during the pre-Covid-19 period. METHODS: This is a retrospective comparative analysis of congenital birth anomalies in Iran; desired data was extracted from national birth registry database. All registered congenital anomalies in hospital births were compared between two time periods: During Covid-19 (1st November 2020- 28th February 2021) and Before Covid-19 (1st November 2019-29th February 2020). Incidence of congenital anomalies at birth were compared and analyzed between these two time periods. RESULTS: The incidence of congenital birth anomalies are significantly increased during Covid-19 pandemic compared with before Covid-19 (P value < 0.00001). The number of all types of anomalies has increased in the current pandemic, but the congenital anomalies of the central nervous system (P value = 0.04) and Genitourinary (P value = 0.03) have a larger contribution than before. CONCLUSION: Covid-19 pandemic are associated with congenital anomalies at birth. There are several factors in the Covid-19 pandemic which can affect fetal development in the first trimester of pregnancy. Possible reasons include vertical transmission of Covid-19 infection; maternal fever, stress and anxiety; insufficient preconception and prenatal care; neglect of fetal screening; and poverty imposed by this pandemic.

A dPCR-NIPT assay for detections of trisomies 21, 18 and 13 in a single-tube reaction-could it replace serum biochemical tests as a primary maternal plasma screening tool?

BACKGROUND: The next generation sequencing (NGS) based non-invasive prenatal test (NIPT) has outplayed the traditional serum biochemical tests (SBT) in screen of fetal aneuploidies with a high sensitivity and specificity. However, it has not been widely used as a primary screen tool due to its high cost and the cheaper SBT is still the choice for primary screen even with well-known shortages in sensitivity and specificity. Here, we report a multiplex droplet digital PCR NIPT (dPCR-NIPT) assay that can detect trisomies 21, 18 and 13 (T21, T18 and T13) in a single tube reaction with a better sensitivity and specificity than the SBT and a much cheaper price than the NGS-NIPT. METHODS: In this study, the dPCR-NIPT assay's non-clinical characteristics were evaluated to verify the cell free fetal DNA (cffDNA) fraction enrichment efficiencies, the target cell free DNA (cfDNA) concentration enrichment, the analytical sensitivity, and the sample quality control on the minimum concentration of cfDNA required for the assay. We validated the clinical performance for this assay by blindly testing 283 clinical maternal plasma samples, including 36 trisomic positive samples, from high risk pregnancies to access its sensitivity and specificity. The cost effectiveness of using the dPCR-NIPT assay as the primary screen tool was also analyzed and compared to that of the existing contingent strategy (CS) using the SBT as the primary screen tool and the strategy of NGS-NIPT as the first-tier screen tool in a simulating situation. RESULTS: For the non-clinical characteristics, the sample processing reagents could enrich the cffDNA fraction by around 2 folds, and the analytical sensitivity showed that the assay was able to detect trisomies at a cffDNA fraction as low as 5% and the extracted cfDNA concentration as low as 0.2 ng/µL. By testing the 283 clinical samples, the dPCR-NIPT assay demonstrated a detection sensitivity of 100% and a specificity of 95.12%. Compared to the existing CS and the NGS-NIPT as the first-tier screen strategy, dPCR-NIPT assay used as a primary screen tool followed by the NGS-NIPT rescreen is the most economical approach to screen pregnant women for fetal aneuploidies without sacrificing the positive detection rate. CONCLUSION: This is the first report on a dPCR-NIPT assay, consisting of all the necessary reagents from sample processing to multiplex dPCR amplification, can detect T21, T18 and T13 in a single tube reaction. The study results reveal that this assay has a sensitivity and specificity superior to the SBT and a cost much lower than the NGS-NIPT. Thus, from both the test performance and the economic benefit points of views, using the dPCR-NIPT assay to replace the SBT as a primary screen tool followed by the NGS-NIPT rescreen would be a better approach than the existing CS for detection of fetal aneuploidies in maternal plasma.

Impact of a Hybrid Model of Prenatal Care on the Diagnosis of Fetal Growth Restriction.

OBJECTIVE: Fetal growth restriction (FGR) is associated with poor neonatal outcomes and stillbirth, and screening via fundal height or ultrasound is routinely performed. During the novel coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid model of prenatal care which decreased the frequency of in-person visits and incorporated telemedicine visits. We sought to determine if prenatal FGR diagnoses decreased with this hybrid model compared with routine prenatal care. STUDY DESIGN: This was a retrospective cohort study of singleton nonanomalous neonates with birth weights <10th percentile at term. The "routine care" group was consisted of those who born between April and July 2019 with in-person prenatal care, and the "hybrid care" group was consisted of those who born between April and July 2020 with both in-person and telemedicine prenatal cares at a collaborative academic practice. The primary outcome was the rate of diagnosis of small for gestational age (SGA) as defined as infant birth weight <10th percentile without a prenatal diagnosis of FGR. The secondary outcome was timing of diagnosis of FGR. RESULTS: Overall, 1,345 and 1,296 women gave birth in the routine and hybrid groups, respectively. The number of in-person prenatal care visits decreased from 15,024 in the routine period to 7,727 in the hybrid period; 3,265 telemedicine visits occurred during the hybrid period. The total number of prenatal patients remained relatively stable at 3,993 and 3,753 between periods. Third trimester ultrasounds decreased from 2,929 to 2,014 between periods. Birth weights <10 percentile occurred in 115 (8.6%) births during the routine period and 79 (6.1%) births during the hybrid period. Of 115, 44 (38.3%) cases were prenatally diagnosed with FGR in the routine versus 28 of 79 (35.4%) in the hybrid group (p = 0.76). Median gestational age at diagnosis did not vary between groups (36 vs. 37 weeks, p = 0.44). CONCLUSION: A hybrid prenatal care model did not alter the detection of FGR. Future efforts should further explore the benefits of incorporating telemedicine into prenatal care. KEY POINTS: · Telemedicine visits can provide comprehensive prenatal care.. · FGR was diagnosed equally with hybrid versus routine prenatal care.. · FGR diagnosis was not delayed with hybrid care..

Antenatal screening of depressive and manic symptoms in south Brazilian childbearing women: A transversal study in advance of the pandemic scenario.

BACKGROUND: The diagnosis of mood disorders (MD) during pregnancy is challenging and may bring negative consequences to the maternal-fetal binomial. The long waitlist for specialized psychiatric evaluation in Brazil contributes to the treatment omission. Almost 20.0% of women treated with antidepressants have a positive screening for bipolar disorder. Therefore, it has been recommended the investigation of depressive and bipolar disorder during prenatal care. Unfortunately, the screening for mood disorders is not a reality in Brazil and many childbearing women remain undiagnosed. The objective of this study is to observe the frequency of MD and the effectiveness of screening scales for routine use by health professionals during prenatal care in high-risk pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 61 childbearing women in their second trimester who were interviewed using the Edinburgh Postnatal Depression Scale (EPDS) and the Mood Disorder Questionnaire (MDQ). The cut-off point was EPDS ≥ 13 and MDQ ≥ 7 and the SCID-5 was the gold standard diagnosis. MD were diagnosed in 24.6% of the high-risk pregnancies. EDPS was positive in 19.7% and the frequency of major depression was 8.2%. 16.4% of the childbearing women were diagnosed with bipolar disorder, while MDQ was positive in 36.1%. 11.5% of the women had EPDS and MDQ positive. EPDS sensitivity was 80.0% and specificity 92.1%, whereas MDQ presented a sensitivity of 70.0% and specificity of 70.6%. CONCLUSION/SIGNIFICANCE: There is a high prevalence of MD in high-risk pregnancies. The routine use of EPDS simultaneously to MDQ during antenatal care is effective and plays an important role in early diagnosis, counselling, and promotion of perinatal mental health.

How COVID-19 pandemic is changing the practice of prenatal screening and diagnosis?

OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on prenatal screening and diagnostic tests. METHODS: We conducted a retrospective study with pregnant women attending to the perinatology department of a tertiary referral center. The pre-COVID-19 period between 11 March 2019 and 10 March 2020 and COVID-19 period between 11 March 2020 and 10 March 2021 were evaluated. Both periods were compared in terms of outpatient visits, ultrasound examinations, prenatal screening and diagnostic tests. The correlation of deaths related to COVID-19 pandemic on these parameters was also assessed. RESULTS: A total of 38,918 patients were examined and 28,452 ultrasound examinations, 26,672 prenatal screening tests and 1,471 prenatal diagnostic tests were performed over two years. During COVID-19 pandemic, number of outpatient visits decreased by 25.2%, ultrasound examinations decreased by 44.2%, prenatal screening tests decreased by 36.2% and prenatal diagnostic tests decreased by 30.7%. Statistically significant correlation was not observed between deaths related to COVID-19 and outpatient visits (p=0.210), ultrasound examinations (p=0.265), prenatal screening (p=0.781) and diagnostic tests (p=0.158). Among indications of prenatal diagnostic tests, maternal anxiety was significantly higher in COVID-19 period (p=0.023). There was significant decrease in the detection of fetuses with trisomy 21 (p=0.047) and a significant increase in the detection of fetuses with Turner syndrome (p=0.017) during COVID-19 period. CONCLUSIONS: The COVID-19 pandemic has severely impacted antenatal care. Prenatal fetal screening and diagnosis was adversely affected by the pandemic in terms of detecting genetic and structural anomalies.

The impact of the emergence of COVID-19 on women's prenatal genetic testing decisions.

OBJECTIVE: We conducted a study to examine the impact of COVID on patients' access and utilization of prenatal genetic screens and diagnostic tests at the onset of the COVID-19 pandemic in the United States. METHODS: We conducted telephone interviews with 40 patients to examine how the pandemic affected prenatal genetic screening and diagnostic testing decisions during the initial months of the pandemic in the United States. An interview guide queried experiences with the ability to access information about prenatal genetic testing options and to utilize the tests when desired. Audio recordings were transcribed and coded using NVivo 12. Analysis was conducted using Grounded Theory. RESULTS: The pandemic did not alter most participants' decisions to undergo prenatal genetic testing. Yet, it did impact how participants viewed the risks and benefits of testing and timing of testing. There was heightened anxiety among those who underwent testing, stemming from the risk of viral exposure and the fear of being alone if pregnancy loss or fetal abnormality was identified at the time of an ultrasound-based procedure. CONCLUSION: The pandemic may impact patients' access and utilization of prenatal genetic tests. More research is needed to determine how best to meet pregnant patients' decision-making needs during this time.

Human placental biology at single-cell resolution: a contemporaneous review.

Single-cell technologies capture cellular heterogeneity to focus on previously poorly described subpopulations of cells. Work by our laboratory and many others has metagenomically characterised a low biomass intrauterine microbial community, alongside microbial transcripts, antigens and metabolites, but the functional importance of low biomass microbial communities in placental immuno-microenvironments is still being elucidated. Given their hypothesised role in modulating inflammation and immune ontogeny to enable tolerance of beneficial microbes while warding off pathogens, there is a need for single-cell resolution. Herein, we summarise the potential for mechanistic understanding of these and other key fundamental early developmental processes by applying single-cell approaches.

Do Males Affect Twinning Events? A Review of Current Findings/Twin Research Reviews: Monozygotic Twins Discordant for Parkinson's Disease; Fetal Loss in Twin Pregnancies Following Prenatal Diagnosis; Uterine Rupture and Repair in an Early Twin Pregnancy; Twin Study of Affectionate Communication/Human Interest: Conjoined Twins in a Triplet Set; Identical Twin Nurses Deliver Identical Twins; Identical Twins Discordant for COVID-19 Recovery Course; Identical Twins Pass Away from COVID-19; Archeological Finds of Oldest Identical Twins.

Research into the origins of twinning has focused mostly on contributions from the female side of the family. A review of current findings suggests that possible male contributions to twinning events have been overlooked. This section is followed by brief reviews of twin research concerning monozygotic twins discordant for Parkinson's disease, fetal loss in twin pregnancies following prenatal diagnosis, uterine rupture and repair in an early twin pregnancy and a twin study of affectionate communication. The concluding portion of this article presents human interest stories involving twins that are both informative and poignant, namely conjoined twins in a triplet set, identical twin nurses who delivered identical twins, identical twins discordant for COVID-19 recovery course, identical twins who passed away from COVID-19 and archeological finds of the oldest identical twins.

Maternal infections: revisiting the need for screening in pregnancy.

The decision to implement screening for infections during pregnancy depends upon epidemiological, economic, therapeutic and test performance criteria. It therefore varies with public health priorities from country to country. When screening is implemented, the first trimester has become the best time slot to build individual care pathways in this field. This is most relevant for evaluating the risk of embryonic consequences, planning diagnostic testing, initiating primary or secondary prevention and optimising the accuracy of ultrasound follow-up. This article is a critical appraisal of epidemiological data and current international screening recommendations for infections in pregnancy. TWEETABLE ABSTRACT: Screening for infections in pregnancy: a critical review of current epidemiological evidence and international guidelines.

Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait.

BACKGROUND: The effect of SARS-CoV-2 infection in pregnant women and newborns is incompletely understood. Preliminary data shows a rather fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. However, it is not clear whether the disease increases the risk of pregnancy-related complications. The aim of the study is to describe the maternal and neonatal clinical characteristics and outcome of pregnancies with SARS-CoV-2 infection. METHODS: In this retrospective national-based study, we analyzed the medical records of all pregnant women infected with SARS-CoV-2 and their neonates who were admitted to New-Jahra Hospital (NJH), Kuwait, between March 15th 2020 and May 31st 2020. During the study period and as part of the public health measures, a total of 185 pregnant women infected with SARS-CoV-2, regardless of symptoms, were hospitalized at NJH, and were included. Maternal and neonatal clinical manifestations, laboratory tests and treatments were collected. The outcomes of pregnancies included miscarriage, intrauterine fetal death (IUFD), preterm birth and live birth were assessed until the end date of the outcomes follow-up (November 10th 2020). RESULTS: A total of 185 pregnant women infected with SARS-CoV-2 were enrolled with a median age of 31 years (interquartile range, IQR: 27.5-34), and median gestational age at diagnosis of SARS-CoV2 infection was 29 weeks (IQR: 18-34). The majority (88%) of these women had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). At the time of the analysis, out of the 185, 3 (1.6%) of the pregnant women had a miscarriage, 1 (0.54%) had IUFD which was not related to COVID-19, 16 (8.6%) had ongoing pregnancies and 165 (89%) had a live birth. Only 2 (1.1%) of these women developed severe pneumonia and required intensive care. A total of 167 neonates with two sets of twins were born with median gestational age at birth was 38 (IQR: 36-39) weeks. Most of the neonates were asymptomatic, and only 2 of them tested positive on day 5 by nasopharyngeal swab testing. CONCLUSIONS: In this national-based study, most of the pregnant women infected with SARS-CoV-2 showed mild symptoms. Although mother-to-child vertical transmission of SARS-CoV-2 is possible, COVID-19 infection during pregnancy may not lead to unfavorable maternal and neonatal outcomes.