Left atrial strain in fetal echocardiography - could it be introduced to everyday clinical practice?

OBJECTIVES: Prenatal cardiology is a part of preventive cardiology based on fetal echocardiography and fetal interventional cardiology, which facilitates treatment of congenital heart defects (CHD) in pediatric patients and consequently in adults. Timely prenatal detection of CHD plays a pivotal role in facilitating the appropriate referral of pregnant women to facilities equipped to provide thorough perinatal care within the framework of a well-structured healthcare system. The aim of this paper is to highlight the role of left atrial strain (LAS) in prenatal evaluation of fetal heart and prediction of structural and functional disorders. METHODS: We conducted a comprehensive literature review searching PubMed for articles published from inception up until August 2023, including the search terms "left atrial strain", "fetal echocardiography", and "prenatal cardiology" combined through Boolean operators. In addition, references lists of identified articles were further reviewed for inclusion. RESULTS: Our review underscores the significance of LAS parameters in fetal echocardiography as a screening tool during specific gestational windows (starting from 11 to 14 weeks of gestation, followed by better visualization between 18 and 22 weeks of gestation). The left atrial strain technique and its parameters serve as valuable indicators, not only for identifying cardiac complications but also for predicting and guiding therapeutic interventions in cases of both cardiac and noncardiac pregnancy complications in fetuses. Evidence suggests establishment of second-trimester reference strain and strain rate values by speckle-tracking echocardiography in the healthy fetal cohort is essential for the evaluation of myocardial pathologies during pregnancy. CONCLUSIONS: Finding of LAS of fetal heart is feasible and probably can have potential for clinical and prognostic implications.

Hemispherotomy in an infant with hemimegalencephaly and Ohtahara syndrome.

We represent the case of a premature twin neonate born from uncomplicated pregnancy who developed seizures at the age of 24 h. Two-dimensional ultrasound and magnetic resonance imaging revealed left-sided hemimegalencephaly. Further extensive diagnostic evaluation revealed a diagnosis of Ohtahara syndrome. Resistance of the seizures to antiepileptic therapy led to hemispherotomy that was performed at the age of 10 months. Our patient is now a 4-year-old child, walking, eating without a nasogastric tube, still with right hemiparesis and lateral strabismus but without seizures.

Why maternal mortality in the world remains tragedy in low-income countries and shame for high-income ones: will sustainable development goals (SDG) help?

Maternal death is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and the site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management. Maternal mortality (MM) and morbidity are a public health issue, with scarce knowledge on their levels and causes in low-income (LIC) countries. The data on MM and morbidity should rely on population-based studies which are non-existent. Therefore, maternal mortality ratio (MMR) estimates are based mostly on the mathematical models. MMR declined from 430 per 100,000 live births (LB) in 1990 to 211 in 2017. Absolute numbers of maternal deaths were 585,000 in 1990, 514,500 in 1995 and less than 300,000 nowadays. Regardless of reduction, MM remains neglected tragedy especially in LIC. Millennium Development Goals (MDGs) declared reduction MMR by three quarters between 2000 and 2015, which failed. Target of Sustainable Development Goals (SDGs) was to decrease MMR to 70 per 100,000 LB. Based on the data from the country report on SDGs in 10 countries with the highest absolute number of maternal deaths it can be concluded that the progress has not been made in reaching the targeted MMR. To reduce MMR, inequalities in access to and quality of reproductive, maternal, and newborn health care services should be addressed, together with strengthening health systems to respond to the needs and priorities of women and girls, ensuring accountability to improve quality of care and equity.

Use and misuse of ultrasound in obstetrics with reference to developing countries.

Maternal and neonatal health is one of the main global health challenges. Every day, approximately 800 women and 7,000 newborns die due to complications during pregnancy, delivery, and neonatal period. The leading causes of maternal death in sub-Saharan Africa are obstetric hemorrhage (28.8%), hypertensive disorders in pregnancy (22.1%), non-obstetric complications (18.8%), and pregnancy-related infections (11.5%). Diagnostic ultrasound examinations can be used in a variety of specific circumstances during pregnancy. Because adverse outcomes may also arise in low-risk pregnancies, it is assumed that routine ultrasound in all pregnancies will enable earlier detection and improved management of pregnancy complications. The World Health Organization (WHO) estimated in 1997 that 50% of developing countries had no access to ultrasound imaging, and available equipment was outdated or broken. Unfortunately, besides all the exceptional benefits of ultrasound in obstetrics, its inappropriate use and abuse are reported. Using ultrasound to view, take a picture, or determine the sex of a fetus without a medical indication can be considered ethically unjustifiable. Ultrasound assessment when indicated should be every woman's right in the new era. However, it is still only a privilege in some parts of the world. Investment in both equipment and human resources has been clearly shown to be cost-effective and should be an obligatory step in the improvement of health care. Well-developed health systems should guide developing countries, creating principles for the organization of the health system with an accent on the correct, legal, and ethical use of diagnostic ultrasound in pregnancy to avoid its misuse. The aim of the article is to present the importance of correct and appropriate use of ultrasound in obstetrics and gynecology with reference to developing countries.

Pre-eclampsia and maternal health through the prism of low-income countries.

Hypertensive syndrome in pregnancy complicates up to 15% of pregnancies, and preeclampsia (PE) occurs in about 3-10% of pregnant women. Inadequate prenatal care is associated with higher mortality from PE, possibly due to reduced monitoring, detection, and missed opportunities for early intervention. The imperative of the clinician's work is to monitor the symptoms and clinical signs of PE, and stratification of patients in relation to the risk of PE is essential. PE represents a multisystem inflammatory response, and the consequences can be expected in all organs. The question of the effect of PE on long-term maternal health is raised. The aim of the paper is to present the effect of PE on the patient's health through the prism of low-income countries.

Facts and doubts on the beginning of human life - scientific, legal, philosophical and religious controversies.

It is very complicated to give correct answer to the question "How to define human life?" Nowadays dilemmas consider the respect of human life from the birth to death involve not just biology but also other sciences like philosophy, theology, sociology, psychology, law and politics. These sciences evaluate the topic from different points of view. Integration of all of these perspectives could result with a proper definition. The principal purpose of this paper is to try to determine when a human individual begins. If this proves to be too difficult, we might have to settle for a specific stage in the reproductive process before which it would be impossible to say with any plausibility that a human individual exists. It is necessary to return the moral dimension of observation to the science of life. The point is to reconcile the universal ethical principles concerning the absolute value of life with the everyday challenges and dilemmas. It is our deepest conviction that life has an absolute value and that there always remains something indestructible and substantial in life, which may neither be evaluated by anything final, nor completely reduced to the material biological equivalent and the genetic substratum.

Neonatal and child mortality - are they different in developing and developed countries?

Aim is to present the neonatal and child mortality in high-(HIC) and low-income (LIC) countries and possible influence of COVID-19 pandemic. In recently published sustainable development goals (SDGs) report and other sources the data on infant and under-five mortality (U-5MR) in HIC and LIC are presented. SDG 3.2 has targeted elimination of preventable child mortality, reduction of neonatal mortality rate (NMR) to less than 12 per 1,000 live births, and reduction of U-5MR to less than 25 per 1,000 live births by 2030. Negative influence of COVID-19 pandemic on performance of SDG 3.2 has been discussed. The lowest NMR was in HIC, almost 10 times lower than in LIC and sub-Saharan Africa (SSA). Data on the U-5MR between HIC and LIC are even worse because the difference was between 13 and 15 times lower in HIC. More children are dying after the neonatal period in LIC. In HIC, NMR comprises 56.3% of U-5MR, while in LIC it is 40.3%, and in SSA, it is 36.8%. Births attended by skilled birth personnel in HIC was 99.0% and in LIC it was only 58.6%, which might affect early NMR. The COVID-19 pandemic is affecting the delivery of perinatal health, with possible negative effects on stillbirth rates, NMR, U-5MR, maternal mortality rates, and many other indicators. The gap of the NMR and U-5MR between HIC and LIC has increasing tendency regardless of COVID-19 pandemic, affecting adversely perinatal health indicators in HIC and LIC.

Association between maternal thyroid function and risk of gestational hypertension and preeclampsia.

OBJECTIVES: To investigate the influence of maternal level of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) one by one or in combination on incidence of gestational hypertension and preeclampsia. METHODS: The study included pregnant women (n=107) hospitalized in the period from July 1, 2020 to October 10, 2021 at the Department of Pathology of Pregnancy of the University Clinic of Obstetrics and Gynecology, University Clinical Center Sarajevo (UCCS) (Bosnia and Herzegovina), due to hypertensive disorder in pregnancy without symptoms of impaired thyroid function. In all patients fulfilling inclusion criteria TSH, FT3, and FT4 using electrochemiluminescence immunoassay (ECLIA, Roche Diagnostics, Basel, Switzerland) were checked. There were two groups of patients: one with gestational hypertension (G1) and the other with preeclampsia (G2). The programs SPSS for Windows 25.0, SPSS Inc, Chicago, IL, USA and Microsoft Excel 11, Microsoft Corporation, Redmond, WA, USA were used for statistical analysis using nonparametric Mann-Whitney U test because the distribution of the data was not normal. The result was considered statistically significant if p<0.05. RESULTS: Gestational age at delivery (G2 36.86 ± 3.79 vs. G1 38.94 ± 2.15; p=0.002) and birth weight (G2 2,841.36 ± 1,006.39 vs. G2 3,290.73 ± 745.6; p=0,032) were significantly different between the investigated groups. The difference between the peak systolic (p=0.002), peak diastolic blood pressure (p=0.007), TSH (p=0.044), and FT3 (p=0.045) were statistically significant. Impaired thyroid function was observed more often in G2 than in G1. CONCLUSIONS: Thyroid function was more often affected adversely in pregnancies complicated with preeclampsia than with gestational hypertension. Based on the results of our study it might be prudent to check thyroid hormones in all asymptomatic pregnancies with preeclampsia or gestational hypertension. These findings need confirmation in larger better designed prospective studies.

The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine foundation.

This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the use of antenatal corticosteroids (ACS) for fetal maturation. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of ACS with the aim to increase the timely administration and avoid unnecessary or excessive use. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world and serves as a guideline for use in clinical practice.

LIMITS OF VIABILITY: SHOULD WE PLAY GOD?

Aim is to show that the definition of the infants born at the limits of viability within the countries is dependent on the social and medical conditions in which the infant is born, and even in one country in which neonatal intensive care is available, it depends on the place of birth and organization of perinatal care. With decreasing gestational age mortality, short- and long-term morbidity of preterm infants are increasing while their survival to discharge is decreasing. It is questionable how to define viability and where the limit of viability can be set. The definition of the limits of viability is not quite clear. There are at least two ways of understanding it: the first, defining the gestational age and/or birth weight at which human fetus has the capability of survival outside the uterus; and the second, gestational age and/or birth weight at which more than 50% of infants survive to discharge home from the hospital. While in developing countries infants of less than 28 weeks of gestation without neonatal intensive care have 95% probability of dying, survival of infants between 22 and 25 gestational weeks in developed countries is reaching 90%. Up to now the definition of the limits of viability has not be established, and precise definition of viability scientifically has not been produced yet. Currently, the World Health Organization sets lower limit of viability at 22 weeks of gestation, or 500 g birth weight, or 25 cm of birth length. The universal definition of the limit of viability is probably not possible, because of its variability from one individual to the other, from one setting to the other and from one community to the other.

Are Covid-19-positive mothers dangerous for their term and well newborn babies? Is there an answer?

Background The pandemic caused by the new coronavirus SARS-CoV-2 (Covid-19) is quite a challenging experience for the world. At the moment of birth, the fetus is prepared to face the challenge of labor and the exposure to the outside world, meaning that labor and birth represent the first extrauterine major exposure to a complex microbiota. The vagina, which is a canal for reproduction, is by evolution separated (but not far) from the anus and urethra. Passing through the birthing canal is a mechanism for intergenerational transmission of vaginal and gut microorganisms for the vertical transmission of microbiota not only from our mothers and grandmothers but also from earlier ancestors. Methods Many national and international instructions have been developed since the beginning of the Covid-19 outbreak in January 2020 in Wuhan in China. All of them pointed out hygiene measures, social distancing and avoidance of social contacts as the most important epidemiological preventive measures. Pregnancy and neonatal periods are considered as high risk for Covid-19 infection. Results The instructions defined the care for pregnant women in the delivery room, during a hospital stay and after discharge. The controversial procedures in the care of Covid-19-suspected or -positive asymptomatic women in labor were: mode of delivery, companion during birth and labor, skin-to-skin contact, breastfeeding, and visits during a hospital stay. Conclusion There is a hope that instruction on coping with the coronavirus (Covid-19) infection in pregnancy with all proposed interventions affecting mothers, babies and families, besides saving lives, are beneficial and efficient by exerting no harm.

Professionally responsible advocacy for women and children first during the COVID-19 pandemic: guidance from World Association of Perinatal Medicine and International Academy of Perinatal Medicine.

The goal of perinatal medicine is to provide professionally responsible clinical management of the conditions and diagnoses of pregnant, fetal, and neonatal patients. The New York Declaration of the International Academy of Perinatal Medicine, "Women and children First - or Last?" was directed toward the ethical challenges of perinatal medicine in middle-income and low-income countries. The global COVID-19 pandemic presents common ethical challenges in all countries, independent of their national wealth. In this paper the World Association of Perinatal Medicine provides ethics-based guidance for professionally responsible advocacy for women and children first during the COVID-19 pandemic. We first present an ethical framework that explains ethical reasoning, clinically relevant ethical principles and professional virtues, and decision making with pregnant patients and parents. We then apply this ethical framework to evidence-based treatment and its improvement, planned home birth, ring-fencing obstetric services, attendance of spouse or partner at birth, and the responsible management of organizational resources. Perinatal physicians should focus on the mission of perinatal medicine to put women and children first and frame-shifting when necessary to put the lives and health of the population of patients served by a hospital first.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas.

BACKGROUND: It is still controversial whether an increased proliferation index is correlated with the tumor invasiveness of pituitary adenomas. A homogeneous large monocentric series of pituitary adenomas was retrospectively analyzed. The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas. METHOD: Four hundred thirty-nine patients after resection of pituitary adenomas were retrospectively included (43 recurrent tumors, 196 null cell adenomas, 86 somatotroph adenomas, 55 corticotroph adenomas, 55 prolactinomas, 4 thyreotroph adenomas). The maximum tumor diameter and tumor invasiveness in Knosp grading were assessed and Ki-67 and p53 immunostaining was performed. The role of invasiveness was evaluated using a cumulative odds ordinal logistic regression. For calculating the effect of tumor size, a one-way analysis of variance (ANOVA) was conducted. RESULTS: Overall and in the subgroups, no significant correlation between proliferation indices and mean tumor diameter was found. No significant predictive expression value of Ki-67 and p53 on tumor invasiveness and in recurrent tumors could be demonstrated. There was a tendency that Ki-67 LI and p53 LI are higher in recurrent corticotroph adenomas and lactotroph adenomas but values did not reach the significant level. CONCLUSION: Invasive character of pituitary adenomas is neither correlated with increased Ki-67 LI nor with increased p53 expression. Proliferation parameters are independent from adenoma size at initial presentation. The partly elevated expression of Ki-67 in recurrent tumors underlines the clinical importance of the marker.

Multi-center results on the clinical use of KANET.

An extensive review of the literature on the diagnostic and clinical accuracy of Kurjak's antenatal neurodevelopmental test (KANET) and the summarized results of the multi-center study involving 10 centers revealed that four-dimensional ultrasonography (4D US) has become a powerful tool and KANET a valuable test that empowers the clinicians worldwide to evaluate the fetal behavior in a systematic way and contribute to the detection of fetuses that might be at high risk for neurological impairments and in particular cerebral palsy (CP). After 10 years of clinical use, many published papers and multi-center studies, hundreds of trained physicians and numerous tests performed all over the world, KANET has proven its value and has been showing encouraging results so far. The aim of this paper is to show the results from the studies done so far and to reveal the clinical value of the KANET. We expect that data from the larger ongoing collaborative study, the short- and long-term postnatal follow-up will continue to improve our knowledge. Ultimately, we all strive to prevent the CP disorders, autism spectrum disorder (ASD) and other neurological impairments and we are convinced that KANET might be helpful in the realization of this important aim.

Is Four-Dimensional (4D) Ultrasound Entering a New Field of Fetal Psychiatry?

The aim of is to explore whether by observing the fetus by 4D US it is possible to enter fetal behavior, emotions, mental status, consciousness, awareness and other states connected with fetal mind and ability of self-regulation. It is well known that fetal motoric activity is enabling the development of central and peripheral nervous system and the muscles. It is 4D US which enabled to investigate fetal movement patterns from the first trimester of pregnancy throughout the whole pregnancy. Based on the evaluation of fetal spontaneous motor activity by 4D US, a prenatal neurologic scoring test named Kurjak Antenatal Neurodevelopmental Test (KANET) was created. This test has been used to assess almost 2000 fetuses and our results have indicated that KANET has an ability to recognize normal, borderline, and abnormal behavior in fetuses from normal and abnormal pregnancies. The fetus is able to process tactile, vestibular, taste, olfactory, auditory and visual sensations. The fetus responds to painful stimuli with a wide spectrum of reactions. Important external signs of emotion are facial expressions. The existence of a wide range of facial expressions, including grimacing, smiling, crying, similar to emotional expressions in adults, has been revealed by 4D sonography in the 2nd and 3rd trimesters of pregnancy. It is questionable if mental, emotional and behavioral conditions of the fetus were covered in this paper and whether we are able to perceive the fetus as the patient who may develop communication or some other psychiatric disorders which we will be hopefully able to recognize prenatally. Although it seems as the speculation from the point of view of our recent diagnostic possibilities, it is apparent that the day when this will be a reality is rapidly approaching.

Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there any improvement?

With all of our present knowledge, high technology diagnostic equipment, electronic databases and other available supporting resources, detection of fetal syndromes is still a challenge for healthcare providers in prenatal as well as in the postnatal period. Prenatal diagnosis of fetal syndromes is not straightforward, and it is a difficult puzzle that needs to be assembled and solved. Detection of one anomaly should always raise a suspicion of the existence of more anomalies, and can be a trigger to investigate further and raise awareness of possible syndromes. Highly specialized software systems for three- and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal anatomy and assessment of the dynamics of fetal structural and functional development in real time. With recent advances in 3D/4D US technology, antenatal diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st trimester of pregnancy. It is questionable what can and should be done after the prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved detection accuracy of fetal abnormalities and syndromes from early pregnancy onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools which help like online integrated databases are needed to increase diagnostic precision. The aim of this paper is to present the possibilities of different US techniques in the detection of some fetal syndromes prenatally.

Multicentric studies of the fetal neurobehavior by KANET test.

Assessment of fetal neurobehavior and detection of neurological impairment prenatally has been a great challenge in perinatal medicine. The evolution of four-dimensional (4D) ultrasound not only enabled a better visualization of fetal anatomy but also allowed the study of fetal behavior in real time. Kurjak Antenatal Neurodevelopmental Test (KANET) was developed for the assessment of fetal neurobehavior and the detection of neurological disorders, based on the assessment of the fetus by application of 4D ultrasound in the same way that a neonate is assessed postnatally. KANET is a method that has been applied for the past 10 years and studies show that it is a strong diagnostic tool and can be introduced into everyday clinical practice. We present all data from studies performed up to now on KANET.

Epidemiology and Outcomes of Congenital Diaphragmatic Hernia in Croatia: A Population-Based Study.

BACKGROUND: Outcomes of neonates with congenital diaphragmatic hernia (CDH) are variable; reports are frequently limited to the experience of single tertiary care centres-a possible source of bias. Population-based studies decrease survivor bias and provide additional insight into this high-mortality condition. The objective of this study was to examine the incidence and outcomes of CDH in Croatia. METHODS: All cases of CDH in Croatia from 2001 through 2013 were ascertained from public health records. Overall and sex- and region-specific incidence rates were calculated, and characteristics associated with 1-year survival were assessed. RESULTS: We identified 145 cases of CDH during the study period, for an incidence of 2.67 per 10 000 total births. The incidence did not differ by calendar year (P = 0.38) or geographic region (P = 0.67). There was a slightly higher incidence among males (rate ratio, 1.37, 95% CI 0.99, 1.91). The 1-year survival rate was 33.1% for the entire cohort and 47.9% for liveborns who received any treatment at an intensive care unit. From multivariable analysis, survival was decreased in neonates with left CDH, liver up (odds ratio 0.1, 95% CI, 0.03, 0.4) and increased when treated in a centre with higher case volume (odds ratio 12.8, 95% CI, 2.2, 72.1). CONCLUSIONS: The incidence of CDH in Croatia is within the range of previous reports. Survival was substantially higher in neonates treated in a centre with higher case volume, which suggests that centralisation of medical care for CDH may be warranted in Croatia.