Has the introduction of increased genetic prenatal testing affected rates of termination of pregnancy due to fetal abnormality?

OBJECTIVE: Genetic high-resolution analyses and improved diagnostic imaging have impacted the ability to detect fetal disorders. It is unknown if this resulted in an alteration in the number of terminations of pregnancy due to fetal anomalies (TOPFA). The objective was to describe the incidence and indication of TOPFA. METHODS: A descriptive study based on records from the Regional Abortion Council in the Central Denmark Region from 2008 to 2021 consisting of 1895 TOPFA. RESULTS: A consistent incidence of TOPFA was observed, accounting for 0.96% of the total births during that period. When examining fetal indications, there was a small increase in the occurrence of genetic aberrations, primarily caused by deletions, duplications, and single nucleotide variations, whereas the number of chromosomal aberrations remained stable. Of 35.5% of the cases with malformations, the central nervous system was the most affected organ system, followed by malformations of the heart 29.6%. Overall, the total number of cases remained stable. DISCUSSION AND CONCLUSION: Unexpectedly, despite the development of new diagnostic tools, the incidence of TOPFA from 2008 to 2021 remained stable. However, the number of cases with genetic aberrations increased. This may be attributed to increased genetic testing for fetuses with identified malformations, resulting in more accurate diagnoses.

Abnormal fetal heart rate patterns caused by pathophysiologic processes other than fetal acidemia.

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid-base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid-base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid-base status at birth as the gold standard for determining the appropriateness of the timing of our interventions.

Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study.

OBJECTIVES: To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection. METHODS: In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection. RESULTS: One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as ≥100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12. CONCLUSIONS: Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load.

Postnatal Outcomes in Infants With a History of Fetal Supraventricular Tachycardia.

BACKGROUND: Fetal supraventricular tachycardia (SVT) is rare and proposed predictors of postnatal outcomes in fetal SVT have not been validated. Valid predictors can guide postnatal management. OBJECTIVES: The authors correlated fetal characteristics to the incidence of postnatal SVT and compared SVT outcomes in infants with and without a history of fetal SVT. METHODS: Mother-fetus dyads with fetal SVT and a structurally normal heart were described and compared with a second cohort of infants with a postnatal diagnosis of SVT. RESULTS: SVT was observed in 78 fetuses and 76 survived to delivery. Maternally administered transplacental antiarrhythmics were used in 49 mother-fetus dyads. Rhythm control was achieved in 37 of 49 (76%). Among fetuses with intermittent SVT, there was no ventricular dysfunction or hydrops. Postnatal SVT occurred in one-half of infants (37 of 76), and 94% presented within the first 2 days of life. The following fetal characteristics were associated with postnatal SVT on univariable analysis: sustained SVT (87% vs 56%), ventricular dysfunction (41% vs 15%), lack of conversion to sinus rhythm (49% vs 10%), and earlier gestational age at delivery (37.6 weeks vs 38.9 weeks; P ≤ 0.01 for each comparison). Compared with infants with a postnatal diagnosis of SVT, infants with a fetal diagnosis presented earlier (median age 0 days vs 17 days; P < 0.01) and had a lower incidence ventricular dysfunction at presentation (5% vs 42%; P < 0.01). CONCLUSIONS: One-half of infants with fetal SVT had postnatal SVT, nearly all within 2 days of life. These data and predictors of postnatal SVT may influence parental counseling and postnatal clinical decision-making.

Fetal congenital heart disease - mode of delivery and obstetrical complications.

BACKGROUND: The optimal mode of delivery in cases of fetal congenital heart disease (CHD) is not established. The few relevant studies did not address operative vaginal delivery. The aim of this study was to assess the impact of fetal CHD on mode of delivery during a trial of labor, and to secondarily describe some obstetric complications. METHODS: The database of a tertiary medical center was searched for women who gave birth to a singleton, liveborn neonate in 2015-2018. Mode of delivery was compared between women carrying a fetus with known CHD and women with a healthy fetus matched 1:5 for maternal age, parity, body mass index, and gestational age. RESULTS: The cohort included 616 women, 105 in the CHD group and 511 in the control group. The rate of operative vaginal delivery was significantly higher in the CHD group (18.09% vs 9.78%, OR 2.03, 95% CI 1.13-3.63, p = 0.01); the difference remained significant after adjustment for nulliparity and gestational age at delivery (aOR 2.58, 95% CI 1.36-4.9, p < 0.01). There was no difference between the CHD and control group in rate of intrapartum cesarean delivery (9.52% vs 10.76%, respectively, OR 0.97, 95% CI 0.47-1.98, p = 0.93). The most common indication for operative vaginal delivery was non-reassuring fetal heart rate (78.94% vs 64%, respectively). Median birth weight percentile was significantly lower in the CHD group (45th vs 53rd percentile, p = 0.04). CONCLUSIONS: Our findings suggest that operative vaginal delivery, performed mostly because of non-reassuring fetal heart rate, is more common in pregnancies complicated by a prenatal diagnosis of CHD than non-anomalous pregnancies.

Implications of fetal premature atrial contractions: systematic review.

OBJECTIVE: Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may be associated with cardiac defects and tachyarrhythmia. We aimed to determine the incidence of congenital heart defects (CHDs) and complications in fetuses with PAC. METHODS: This was a systematic review and meta-analysis conducted in accordance with the PRISMA statement for reporting items for systematic reviews and meta-analyses. MEDLINE and EMBASE were searched from 1990 to June 2021 to identify studies on fetuses with PAC. The primary outcome was CHD; secondary outcomes were complications using the endpoints supraventricular tachyarrhythmia (SVT), cardiac failure and intrauterine fetal demise. Meta-analysis of proportions was performed, subdivided into high-risk and low-risk populations based on reason for referral. Pooled incidences with 95% CIs were calculated. RESULTS: Of 2443 unique articles identified, 19 cohort studies including 2260 fetuses were included. The pooled incidence of CHD in fetuses with PAC was 2.8% (95% CI, 1.5-4.1%), when 0.6% is the incidence expected in the general population. The pooled incidence of CHD was 7.2% (95% CI, 3.5-10.9%) in the high-risk population and 0.9% (95% CI, 0.0-2.0%) in the low-risk population. SVT occurred in 1.4% (95% CI, 0.6-3.4%) of fetuses diagnosed with PAC. Cardiac failure was described in 16 fetuses (1.4% (95% CI, 0.5-3.5%)), of which eight were CHD-related. Intrauterine fetal demise occurred in four fetuses (0.9% (95% CI, 0.5-1.7%)) and was related to CHD in two cases. CONCLUSIONS: Our findings suggest that the risk of CHD in fetuses with PAC is 4-5 times higher than that in the general population. CHD was present more frequently in the high-risk population. Consequently, an advanced ultrasound examination to diagnose PAC correctly and exclude CHD is recommended. Complications of PAC are rare but can result in fetal demise, thus weekly fetal heart-rate monitoring remains advisable to enable early detection of SVT and to prevent cardiac failure. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Trends in the Prenatal Detection of Major Congenital Heart Disease in Alberta From 2008-2018.

OBJECTIVE: The effect of expanded obstetrical ultrasound cardiac views on the diagnosis of fetal congenital heart disease (CHD) has not been fully examined at a population level. We hypothesized there has been a significant increase in the prenatal detection of CHD in Alberta, particularly for CHD associated with cardiac outflow tract and 3-vessel view abnormalities. METHODS: Using provincial databases, we retrospectively identified all fetuses and infants diagnosed between 2008 and 2018 in Alberta with major CHD requiring surgical intervention within the first postnatal year. We evaluated individual lesions and categorized CHDs into the following groups based on the obstetrical ultrasound cardiac views required for detection: (1) 4-chamber view (e.g., hypoplastic left heart syndrome, Ebstein's anomaly, single ventricle); (2) outflow tract view (e.g., tetralogy of Fallot, d-transposition, truncus arteriosus); (3) 3-vessel or other non-standard cardiac views (e.g., coarctation, anomalous pulmonary veins); and (4) isolated ventricular septal defects using any view. RESULTS: Of 1405 cases of major CHD, 814 (58%) were prenatally diagnosed. Over the study period, prenatal detection increased in all groups, with the greatest increase observed for groups 1 and 2 (75%-88%; P = 0.008 and 56%-79%; P = 0.0002, respectively). Although rates of prenatal detection also increased for groups 3 and 4 (27%-43%; P = 0.007 and 13%-30%; P = 0.04, respectively), fewer than half of the cases in each group were detected prenatally, even in more recent years. CONCLUSIONS: While rates of prenatal detection of CHD have significantly improved during the past decade, many defects with abnormal 3-vessel and non-standard views, as well as isolated ventricular septal defects, still go undetected.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Maternal sociodemographic characteristics, early pregnancy behaviours, and livebirth outcomes as congenital heart defects risk factors - Northern Ireland 2010-2014.

BACKGROUND: Congenital Heart Defects (CHD) is the most commonly occurring congenital anomaly in Europe and a major paediatric health care concern. Investigations are needed to enable identification of CHD risk factors as studies have given conflicting results. This study aim was to identify maternal sociodemographic characteristics, behaviours, and birth outcomes as risk factors for CHD. This was a population based, data linkage cohort study using anonymised data from Northern Ireland (NI) covering the period 2010-2014. The study cohort composed of 94,067 live births with an outcome of 1162 cases of CHD using the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes and based on the European Surveillance of Congenital Anomalies (EUROCAT) grouping system for CHD. CHD cases were obtained from the HeartSuite database (HSD) at the Royal Belfast Hospital for Sick Children (RBHSC), maternal data were extracted from the Northern Ireland Maternity System (NIMATS), and medication data were extracted from the Enhanced Prescribing Database (EPD). STATA version 14 was used for the statistical analysis in this study, Odds Ratio (OR), 95% Confident intervals (CI), P value, and logistic regression were used in the analysis. Ethical approval was granted from the National Health Service (NHS) Research Ethics Committee. RESULT: In this study, a number of potential risk factors were assessed for statistically significant association with CHD, however only certain risk factors demonstrated a statistically significant association with CHD which included: gestational age at first booking (AOR = 1.21; 95% CI = 1.04-1.41; P < 0.05), family history of CHD or congenital abnormalities and syndromes (AOR = 4.14; 95% CI = 2.47-6.96; P < 0.05), woman's smoking in pregnancy (AOR = 1.22; 95% CI = 1.04-1.43; P < 0.05), preterm birth (AOR = 3.01; 95% CI = 2.44-3.01; P < 0.05), multiple births (AOR = 1.89; 95% CI = 1.58-2.60; P < 0.05), history of abortion (AOR = 1.12; 95% CI = 1.03-1.28; P < 0.05), small for gestational age (SGA) (AOR = 1.44; 95% CI = 1.22-1.78; P < 0.05), and low birth weight (LBW) (AOR = 3.10; 95% CI = 2.22-3.55; P < 0.05). Prescriptions and redemptions of antidiabetic (AOR = 2.68; 95% CI = 1.85-3.98; P < 0.05), antiepileptic (AOR = 1.77; 95% CI = 1.10-2.81; P < 0.05), and dihydrofolate reductase inhibitors (DHFRI) (AOR = 2.13; 95% CI = 1.17-5.85; P < 0.05) in early pregnancy also showed evidence of statistically significant association with CHD. CONCLUSION: The results of this study suggested that there are certain maternal sociodemographic characteristics, behaviours and birth outcomes that are statistically significantly associated with higher risk of CHD. Appropriate prevention policy to target groups with higher risk for CHD may help to reduce CHD prevalence. These results are important for policy makers, obstetricians, cardiologists, paediatricians, midwives and the public.

Prenatal detection of congenital heart disease - results of a Swedish screening program 2013-2017.

BACKGROUND: This report evaluates results of a screening program on prenatal detection of congenital heart defects in a geographical cohort of western Sweden between January 1st, 2013 and June 31st, 2017. During the study period 88,230 children were born in VGR. METHODS: Retrospective data on pregnant women from the Västra Götaland region that were referred to fetal cardiologists in Gothenburg were retrieved. To determine prenatal detection rate, all neonates who underwent surgery or catheter intervention for a critical congenital heart defect born between January 1st, 2014 and December 31st, 2016 were included. The four-chamber view was implemented into the routine scan in 2009 and implementation of the ISUOG guidelines, including the outflow tracts, started in the region in 2015. RESULTS: 113 fetuses received a prenatal diagnosis of a major congenital heart defect. 89% of these were referred because of a suspected cardiac malformation and 88% were diagnosed before 22 completed weeks. 59% of the patients diagnosed before 22 completed weeks opted for termination of pregnancy. During 2014-2016, 61 fetuses had a prenatal diagnosis of a critical congenital heart defect and a further 47 were diagnosed after birth, hence 56% were diagnosed prenatally, 82% for those which had a combination with an extracardiac abnormality and/or chromosomal aberration compared to 50% if an isolated critical congenital heart defect was diagnosed. For single ventricle cardiac defects such as hypoplastic left heart syndrome, double inlet left ventricle and tricuspid atresia, the detection rate was 100%. The detection rate for transposition of the great arteries and coarctation of the aorta was 9 and 18% respectively. CONCLUSIONS: 56% of all fetuses with a critical congenital heart defect were diagnosed prenatally during 2014-2016 and approximately 53% of all major congenital heart defects 2013-2017 as compared to 13.8% in 2009 in the same region. An increased focus towards the fetal heart in the routine scan improved the prenatal detection rate of major congenital heart defects. The detection of congenital heart defects affecting the four-chamber view seems sufficient, but more training is needed to improve the quality of the examination of the outflow tracts.

Increased Fetal Cardiovascular Disease Risk: Potential Synergy Between Gestational Diabetes Mellitus and Maternal Hypercholesterolemia.

Cardiovascular diseases (CVD) remain a major cause of death worldwide. Evidence suggests that the risk for CVD can increase at the fetal stages due to maternal metabolic diseases, such as gestational diabetes mellitus (GDM) and maternal supraphysiological hypercholesterolemia (MSPH). GDM is a hyperglycemic, inflammatory, and insulin-resistant state that increases plasma levels of free fatty acids and triglycerides, impairs endothelial vascular tone regulation, and due to the increased nutrient transport, exposes the fetus to the altered metabolic conditions of the mother. MSPH involves increased levels of cholesterol (mainly as low-density lipoprotein cholesterol) which also causes endothelial dysfunction and alters nutrient transport to the fetus. Despite that an association has already been established between MSPH and increased CVD risk, however, little is known about the cellular processes underlying this relationship. Our knowledge is further obscured when the simultaneous presentation of MSPH and GDM takes place. In this context, GDM and MSPH may substantially increase fetal CVD risk due to synergistic impairment of placental nutrient transport and endothelial dysfunction. More studies on the separate and/or cumulative role of both processes are warranted to suggest specific treatment options.

Cardiac Risk Score to Predict Small for Gestational Age Infants in Pregnant Women With Heart Disease.

BACKGROUND: One of the most common fetal complications in pregnant women with cardiovascular disease is a small for gestational age (SGA) neonate, which is associated with a higher risk of perinatal morbidity/mortality and poor long-term health outcomes. The objective of this study was to identify cardiac determinants and derive a risk score for clinically relevant SGA < 5th percentile (SGA-5th). METHODS: A prospective cohort of 1812 pregnancies in women with heart disease were studied. SGA-5th was the outcome of interest, defined as birth weight < 5th percentile for gestational age and sex. Multivariable logistic regression analysis was used to identify predictors for SGA-5th. Based on the regression coefficients, a weighted risk score was created. RESULTS: SGA-5th complicated 10% of pregnancies, 11 predictors of SGA-5th were identified, and each was assigned a weighted score: maternal cyanosis (8), Fontan palliation (7), smoking (3), moderate or severe valvular regurgitation (3), ß-blocker use throughout pregnancy (4) or only in the 2nd and 3rd trimesters (2), high baseline ß-blocker dose (4), body mass index < 18.5 kg/m2 (3) or 18.5-24.9 kg/m2 (1), Asian/other ethnicity (2), and significant outflow tract obstruction (1). In the absence of these identified risk factors, the risk of SGA-5th was approximately 4%. Pregnancies with risk scores of 1 had a rate of 5%; 2, 7%; 3, 9%; 4, 12%; 5, 14%; 6, 18%; 7, 23%; 8, 28%; and ≥ 9, 34%. CONCLUSIONS: There are a number of cardiac predictors that are associated with increased risk of SGA-5th. This is a prognostically important outcome, and consideration should be given to routinely predicting and modifying the risk whenever possible.

Knowledge of Preconception Healthcare and Associated Factors: A Study among Mothers in Jinka Town, Southern Region, Ethiopia.

BACKGROUND: Preconception healthcare is promising to improve the reproductive health status of women and couples if they receive care three months to two years before conception. In the current context of Ethiopia, however, preconception healthcare is overlooked in the continuum of care. Therefore, this study aimed to assess the knowledge of preconception healthcare and associated factors: a study among mothers in Jinka town, southern region, Ethiopia. METHODS: A community-based cross-sectional study was employed among 522 randomly selected women of childbearing age who are living in Jinka town from March to April 2018. The study considers all the kebeles in the town. Study subjects were determined using proportionate-to-population size allocation. Then, a systematic random sampling technique was applied. Data were collected using a semistructured and pretested questionnaire. Descriptive summary data and binary logistic regression analysis were carried out to identify factors with the 95% confidence level and a p value of less than 0.05. RESULTS: A total of 513 study subjects participated in this study. The overall preconception healthcare knowledge score of women in Jinka town was 51.1%. In the multivariable analysis, housewives (AOR = 2.93; 95% CI: 1.38-6.19), an education level of at least college (AOR = 3.79; 95% CI: 1.75-8.23), no history of neonatal death (AOR = 4.13; 95% CI = 1.39-12.25), and the use of family planning methods (AOR = 2.38; 95% CI: 1.49-3.79) increased the probability of preconception healthcare knowledge compared to the counterparts. CONCLUSION: In this study, women's knowledge of preconception healthcare was found borderline. The identified factors were housewife, education level of at least college, no history of neonatal death, and using family planning methods. Therefore, emphasizing these factors for the enhancement of women's knowledge of preconception healthcare is a necessary step.

Maternal pre-pregnancy body mass index and foetal acidosis in vaginal and caesarean deliveries: The Japan Environment and Children's Study.

A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children's Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011-2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI < 18.5 kg/m2), G2 (18.5 to < 20.0 kg/m2), G3 (20.0 to < 23.0 kg/m2), G4 (23.0 to < 25.0 kg/m2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) < 7.20 or < 7.10. Multiple logistic regression analyses were used to evaluate the effect of pre-pregnancy BMI on foetal acidosis risk, accounting for the mode of delivery. In Japanese women, pre-pregnancy BMI ≥ 25.0 kg/m2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis.

The occurrence of fetal and neonatal disorders in pregnant women with Zika virus infection in the literature is not consistent. This study aims to estimate the prevalence rate of these disorders in fetuses/neonates of pregnant women with confirmed or probable infection by Zika virus. A systematic review with meta-analysis was conducted in November 2020. Cohort studies that contained primary data on the prevalence of unfavorable outcomes in fetuses or neonates of women with confirmed or probable Zika virus infection during pregnancy were included. A total of 21 cohort studies were included, with a total of 35,568 pregnant women. The meta-analysis showed that central nervous system abnormalities had the highest prevalence ratio of 0.06 (95% CI 0.03-0.09). Intracranial calcifications had a prevalence ratio of 0.01 (95% CI 0.01-0.02), and ventriculomegaly 0.01 (95% CI 0.01-0.02). The prevalence ratio of microcephaly was 0.03 (95% CI 0.02-0.05), fetal loss (miscarriage and stillbirth) was 0.04 (95% CI 0.02-0.06), Small for Gestational Age was 0.04 (95% CI 0.00-0,09), Low Birth Weight was 0.05 (95% CI 0.03-0.08) and Prematurity was 0.07 (95% CI 0.04-0.10). The positivity in RT-PCR for ZIKV performed in neonates born to infected mothers during pregnancy was 0.25 (95% CI 0.06-0.44). We also performed the meta-analysis of meta-analysis for microcephaly with the prevalence ratios from other two previously systematic reviews: 0.03 (95% CI 0.00-0.25). Our results contribute to measuring the impact of Zika virus infection during pregnancy on children's health. The continuous knowledge of this magnitude is essential for the implementation development of health initiatives and programs, in addition to promoting disease prevention, especially in the development of a vaccine for Zika virus. PROSPERO protocol registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019125543.

Prenatal disorders and congenital Zika syndrome in squirrel monkeys.

During the Zika virus (ZIKV) outbreak in Brazil (2015-2016), the clinical manifestations associated with its infection were complex and included miscarriage and congenital malformations, not previously described. In this study, we evaluated the prenatal conditions of pregnant female squirrel monkeys (Saimiri collinsi) infected during different gestational thirds (GTs) and assessed all clinical aspects, diagnostic imaging, viremia and the immune response. In our study, 75% of the infected animals in the 1st GT group had significant clinical manifestations, such as miscarriage and prolonged viremia associated with a late immune response. Consequently, their neonates showed fetal neuropathology, such as cerebral hemorrhage, lissencephaly or malformations of the brain grooves, ventriculomegaly, and craniofacial malformations. Thus, our study demonstrated the relevance of pregnant squirrel monkeys as a model for the study of ZIKV infection in neonates due to the broad clinical manifestations presented, including the typical congenital Zika syndrome manifestations described in humans.

Patterns of discordant growth and adverse neonatal outcomes in twins.

BACKGROUND: Intertwin size discordance is an independent risk factor for adverse neonatal outcomes in twin pregnancies. However, size discordance at a given point in gestation fails to take into consideration information, such as the timing of onset and the rate of progression of discordance, that may be of prognostic value. OBJECTIVE: In this study, we aimed to identify distinct patterns of discordant fetal growth in twin pregnancies and to determine whether these patterns are predictive of adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancies in a single tertiary referral center between January 2011 and April 2020, who had at least 3 ultrasound examinations during pregnancy that included assessment of fetal biometry. Size discordance was calculated at each ultrasound examination, and pregnancies were classified into 1 of 4 predetermined patterns based on the timing of onset and the progression of discordance: pattern 1, no significant discordance group (referent); pattern 2, early (<24 weeks' gestation) progressive discordance group; pattern 3, early discordance with plateau group; or pattern 4, late (≥24 weeks' gestation) discordance group. The associations of discordance pattern (using pattern 1 as referent) with preterm birth, preeclampsia, size discordance at birth, and birthweight<10th percentile were expressed as adjusted relative risk with 95% confidence intervals and were compared with those observed for a single measurement of size discordance at 32 weeks' gestation. RESULTS: Of 2075 women with a twin gestation who were identified during the study period, 1059 met the study criteria. Of the 1059 women, 599 (57%) were classified as no significant discordance (pattern 1), 23 (2%) as early progressive discordance (pattern 2), 160 (15%) as early discordance with plateau (pattern 3), and 277 (26%) as late discordance (pattern 4). The associations of discordance pattern with preterm birth at <34 weeks' gestation and preeclampsia were strongest for pattern 2 (rates of 43% [adjusted relative risk, 3.43; 95% confidence interval, 2.10-5.62] and 17% [adjusted relative risk, 5.81; 95% confidence interval, 2.31-14.60], respectively), intermediate for pattern 3 (rates of 23% [adjusted relative risk, 1.82; 95% confidence interval, 1.28-2.59] and 6% [adjusted relative risk, 2.08; 95% confidence interval, 1.01-4.43], respectively), and weakest for pattern 4 (rates of 12% [adjusted relative risk, 0.96; 95% confidence interval, 0.65-1.42] and 4% [adjusted relative risk, 1.41; 0.68-2.92], respectively). In contrast, a single measurement of size discordance at 32 weeks' gestation showed no association with preeclampsia and only a weak association with preterm birth at <34 weeks' gestation. CONCLUSION: We identified 4 distinct discordance growth patterns among twins that demonstrated a dose-response relationship with adverse outcomes and seemed to be more informative than a single measurement of size discordance.

Fetal heart rhabdomyomatosis: a single-center experience.

Objectives: The primary aim of the study was to evaluate the prevalence of fetal heart tumors in a single tertiary referral center over a period of 15 years. The secondary aim was to confirm the presence of tuberous sclerosis complex (TSC) through the evaluation of germline mutation in TSC1/TSC2 and assess the outcomes in affected fetuses and newborns.Methods: A retrospective study was conducted between 2003 and 2017. Fetal echocardiography was performed in the second trimester of pregnancy in the study population. The identification of heart tumors and further follow-up were performed by a pediatric cardiologist. Molecular genetic analysis was conducted on fetuses and children in cases where TSC was suspected.Results: In total, 39,018 fetuses were examined between 2003 and 2017. Heart tumors were detected in nine fetuses and were diagnosed as rhabdomyoma in all cases. We identified mutations in one of the TSC1 or TSC2 genes in all cases with multiple rhabdomyomas (8/9). In all born children (5/9), the genetically confirmed diagnosis of TSC was established, and clinically pathological deposits in the brain were found.Conclusion: Fetal heart tumors are usually represented by rhabdomyomas having a good cardiac prognosis. However, rhabdomyoma is usually the first symptom of TSC with a subsequent brain disorder and impaired neurological development.

How often do we identify fetal abnormalities during routine third-trimester ultrasound? A systematic review and meta-analysis.

BACKGROUND: Routine third-trimester ultrasound is frequently offered to pregnant women to identify fetuses with abnormal growth. Infrequently, a congenital anomaly is incidentally detected. OBJECTIVE: To establish the prevalence and type of fetal anomalies detected during routine third-trimester scans using a systematic review and meta-analysis. SEARCH STRATEGY: Electronic databases (MEDLINE, Embase and the Cochrane library) from inception until August 2019. SELECTION CRITERIA: Population-based studies (randomised control trials, prospective and retrospective cohorts) reporting abnormalities detected at the routine third-trimester ultrasound performed in unselected populations with prior screening. Case reports, case series, case-control studies and reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Prevalence and type of anomalies detected in the third trimester. We calculated pooled prevalence as the number of anomalies per 1000 scans with 95% confidence intervals. Publication bias was assessed. MAIN RESULTS: The literature search identified 9594 citations: 13 studies were eligible representing 141 717 women; 643 were diagnosed with an unexpected abnormality. The pooled prevalence of a new abnormality diagnosed was 3.68 per 1000 women scanned (95% CI 2.72-4.78). The largest groups of abnormalities were urogenital (55%), central nervous system abnormalities (18%) and cardiac abnormalities (14%). CONCLUSION: Combining data from 13 studies and over 140 000 women, we show that during routine third-trimester ultrasound, an incidental fetal anomaly will be found in about 1 in 300 scanned women. This information should be taken into account when taking consent from women for third-trimester ultrasound and when designing and assessing cost of third-trimester ultrasound screening programmes. TWEETABLE ABSTRACT: One in 300 women attending a third-trimester scan will have a finding of a fetal abnormality.