Intrauterine deaths - an unsolved problem in Polish perinatology.

OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

Multidisciplinary management of a large microcystic congenital pulmonary airway malformation: case report and literature review.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small hyperechogenic cysts (<5 mm). Hydrops often develops secondarily, and the fetal survival rate is approximately 5% in this setting. CASE PRESENTATION: We present a case of a large type 3 CPAM complicated by fetal hydrops. The lesion was detected at 19 gestational weeks (GW) and confirmed by fetal MRI at 29 GW. At 22 GW, a course of maternal steroids was given as a possible treatment of type 3 CPAM. Peritoneal-amniotic shunt was placed twice to reduce fetal ascites, with unsatisfactory results. Similarly, polyhydramnios was relieved by two amnioreductions, but redeveloped soon after. A baby girl was delivered spontaneously at 33 GW and received a two-stage partial lobectomy in the first three months of life. Desaturations necessitated challenging invasive oscillatory ventilation between stages. Her outcome is unexpectedly positive and she may expect a good quality of life. She now approaches one year of age, with near-to-normal growth and developmental milestones. DISCUSSION: Type 3 CPAMs complicated by fetal hydrops are associated with high perinatal mortality. While open fetal surgery remains a viable option in select specialist centers, antenatal interventions are typically ineffective. The survival of this infant can be attributed to prenatal management and early postnatal surgical intervention. The lack of guidelines for ventilation in this setting was a significant challenge for neonatal intensivists. Multidisciplinary vigilance and collaboration with frequent specialist follow ups were the key to success for both mother and child.

Pathophysiology of Pre-Eclampsia-Two Theories of the Development of the Disease.

Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the pathomechanisms of PE, the pathophysiology of the disease is still not fully understood. While the "two-stage model" of the development of PE is the most widely accepted theory, stating that the placenta is the main source of the disease, there are some other pathophysiological models of PE. Among these other theories, the one considering heart dysfunction as serving as the primary cause of PE seems to be gaining increasing prominence. In this review, we aim to elucidate these two divergent concepts concerning the development of PE. Despite some differences in their proposed pathomechanisms, both theories share vital pathophysiological elements in common. A central and critical component in both models is impaired placental perfusion, which appears to be a crucial phenomenon in PE. A comprehensive understanding of the different pathomechanisms involved in PE may be helpful in clinical practice, prompting a more individual approach to care of patients with PE.

Multispecialty Approach to a Very Large Congenital Head and Neck Cystic Lymphatic Malformation in an Infant Born by SARS-CoV-2 Positive Mother-A Case Report.

Masses of the head and neck are often diagnosed prenatally and require special care due to the risk of airway obstruction. The EXIT procedure is a preferable mode of delivery. A congenital cystic lymphatic malformation is one of the most common lesions of the cervical region described in neonates. The treatment consists of different strategies and involves the cooperation of multiple specialists. Up to now, no guidelines or protocols are available. We report a case of a congenital cystic lymphatic malformation of the head and neck delivered during the EXIT procedure by a mother who was SARS-CoV-2 positive. We analyzed clinical characteristics, radiologic features, and treatment with injections of sclerotic agents and orally administrated sirolimus. Sirolimus seems a valuable and safe therapeutic option for treating lymphatic malformations, especially with adjunct therapies.

The Assessment of Maternal and Fetal Intima-Media Thickness in Perinatology.

Intima-media thickness (IMT) measurement is a non-invasive method of arterial wall assessment. An increased IMT is a common manifestation of atherosclerosis associated with endothelial dysfunction. In the course of pregnancy, various maternal organs, including the endothelium, are prepared for their new role. However, several pre-gestational conditions involving endothelial dysfunction, such as diabetes, chronic hypertension, and obesity, may impair the adaptation to pregnancy, whereas vascular changes may also affect fetal development, thus, influencing the fetal IMT. In the conducted studies, a correlation was found between an increased fetal abdominal aorta IMT (aIMT) and placental dysfunctions, which may subsequently impact both the mother and the fetus, and contribute to gestational hypertension, preeclampsia (PE), and fetal growth restriction (FGR). In fact, data indicate that following the delivery, the endothelial dysfunction persists and influences the future health of the mother and the newborn. Hypertensive disorders in pregnancy increase the maternal risk of chronic hypertension, obesity, and vascular events. Moreover, individuals born from pregnancies complicated by preeclampsia or fetal growth restriction are at high risk of obesity, diabetes, hypertension, and cardiovascular disease. Therefore, understanding the pathomechanism underlying an increased aIMT in preeclampsia and FGR, as well as subsequent placental dysfunctions, is essential for developing targeted therapies. This review summarizes recent publications regarding IMT and demonstrates how IMT measurements affect predicting perinatal complications.

Serum levels of soluble FMS-like tyrosine kinase 1 and endothelial glycocalyx components in early- and late-onset preeclampsia.

INTRODUCTION: The most popular model of preeclampsia (PE) is a two-stage one in which the first stage involves a decreased perfusion of the placenta and the second stage is characterized by maternal endothelial injury and dysfunction. This model seems to be more appropriate for early-onset PE, than for the late-onset disease, as in the case of the latter the event of reduced placental perfusion seems is less obvious.The aim of the study was to assess the possible correlations between the serum levels of soluble FMS-like tyrosine kinase 1 (sFlt-1) and the components of endothelial glycocalyx (EG), namely syndecan -1 (SDC-1) and hyaluronan (HA), as the markers of endothelial damage, in patients with early- and late-onset PE. MATERIALS AND METHODS: The study was conducted among 60 women in their late second and third trimester of the singleton pregnancy, including 20 patients with early-onset PE, 20 with late-onset PE, and 20 women with normal pregnancy, who served as the control group. All patients were hospitalized between 2015 and 2018 at the Division of Reproduction of Poznan University of Medical Sciences. The women in the control group were matched by gestational age with the patients in the study groups. RESULTS: The median serum level of sFlt-1 was the highest in the patients with early-onset PE (3.53 (2.73-4.5) pg/ml) but it was not statistically different from the level in the patients with late-onset PE (3.14 (2.2-3.4) pg/ml). The mean serum level of SDC-1 also did not differ significantly between the two groups of patients with PE (6.17 ± 2.2 ng/ml in early-onset PE; 6.42 ± 2.2 ng/ml in late-onset PE). Both values of SDC-1 were significantly lower than that in the healthy pregnant women (11 ± 2.62 ng/ml, p < .001). The median concentrations of HA did not differ between patients with early- (236.6 (101.1-351.9) ng/ml) and late-onset PE (234.7 (46.8-324.2) ng/ml). However, the levels in these study groups were significantly higher than in the control group (113.9 (30.9-379.8) ng/ml, p < .001). There was no significant correlation found between the serum concentrations of sFlt-1 and both HA and SDC-1; however, such trend was noticed between the serum concentrations of sFlt-1 and HA in patients with early-onset PE, but not in those with the late-onset disease. CONCLUSIONS: Evaluation of serum concentrations of HA in patients with PE was found to be more useful in the assessment of endothelial injury, compared to the assessment of SDC-1.The degree of EG damage was comparable in patients with early- and late-onset PE. The pathomechanism of the damage seems to be more sFlt-1 dependent in patients withearly- onset PE than in the case of late-onset disease. The two-stage model of PE is more appropriate for early - onset PE, whereas the pathophysiology of the late-onset disease is rather more complex and heterogenous.

Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus.

Preeclampsia (PE) is one of the leading causes of mortality and morbidity in pregnant women. Pregestational diabetes (PGDM) patients are prone to vascular complications and preeclampsia, whereas vascular exposure to hyperglycemia induces inflammation, vascular remodeling, and arterial stiffness. Corin is a serine protease, converting inactive pro-atrial natriuretic peptide (pro-ANP) into an active form. It also promotes salt and water excretion by activating atrial natriuretic peptide (ANP), and significantly increases trophoblast invasion. The study aimed to determine whether corin may be a predictor of PE in a high-risk group-women with long-term PGDM. The nested case-control prospective study involved 63 patients with long-term pregestational type 1 diabetes (PGDM). In total, 17 patients developed preeclampsia (the study group), whereas 43 patients without PE constituted the control group. To assess corin concentration, blood samples were collected at two time points: between 18th-22nd week of gestation and 28th-32nd week of gestation. PE patients presented significantly higher mid-gestation corin levels, urine protein loss in each trimester, serum creatinine in the third trimester, and lower creatinine clearance in the third trimester. The results of our study indicate that serum corin assessment may play a role in predicting preeclampsia. Thus, it may be included in the PE risk calculator, initially in high-risk groups, such as patients with PGDM.

Endothelial Dysfunction in Pregnancy Complications.

The endothelium, which constitutes the inner layer of blood vessels and lymphatic structures, plays an important role in various physiological functions. Alterations in structure, integrity and function of the endothelial layer during pregnancy have been associated with numerous gestational complications, including clinically significant disorders, such as preeclampsia, fetal growth restriction, and diabetes. While numerous experimental studies have focused on establishing the role of endothelial dysfunction in pathophysiology of these gestational complications, their mechanisms remain unknown. Numerous biomarkers of endothelial dysfunction have been proposed, together with the mechanisms by which they relate to individual gestational complications. However, more studies are required to determine clinically relevant markers specific to a gestational complication of interest, as currently most of them present a significant overlap. Although the independent diagnostic value of such markers remains to be insufficient for implementation in standard clinical practice at the moment, inclusion of certain markers in predictive multifactorial models can improve their prognostic value. The future of the research in this field lies in the fine tuning of the clinical markers to be used, as well as identifying possible therapeutic techniques to prevent or reverse endothelial damage.

Diagnosis of preeclampsia in women with diabetic kidney disease.

Objective: assessing the incidence of preeclampisa (PE) in women with diabetic kidney disease (DKD) and analyzing the significance of clinical characteristics and changes in laboratory findings throughout the pregnancy on the onset of PE.Methods: the study included 79 patients with DKD. All patients had elevated urinary protein loss (30-299 mg/24 h) or proteinuria (≥300 mg/24 h) in the first trimester of pregnancy. PE was diagnosed in 22,8% patients with DKD.Results: women with proteinuria and/or proliferative retinopathy at the admission developed preeclampsia significantly more frequently than those without these findings. The degree of proteinuria was significantly associated with the risk of PE development in each trimester of pregnancy. Patients with chronic hypertension developed PE significantly more frequently than those who had no chronic hypertension.Conclusion: chronic hypertension and the degree of primary kidney injury and dysfunction are crucial determinants of PE development in women with DKD. Proteinuria seems to be the best renal predictive factors of PE.

Utility of biochemical tests in prediction, diagnostics and clinical management of preeclampsia: a review.

The most widely accepted theory for the development of preeclampsia is the "two-stage theory". An imbalance between antiangiogenic and proangiogenic factors is considered the link between the two stages. Nowadays, an increasing amount of data is available on the use of measurements of serum concentrations of these factors in the prediction, diagnosis and management of preeclampsia. The most useful, modern biochemical test that may help in making crucial clinical decisions in patients with preeclampsia is the sFlt-1/PlGF (soluble fms-like tyrosine kinase 1/placental growth factor) ratio. The aim of this review is to present the current use of different biochemical tests in the prediction, diagnosis and management of preeclampsia. Development of these diagnostic methods in recent years and a belief in their ground-breaking role in modern management of preeclampsia make this review especially important.

Pregnancy Outcomes in Women with Long-Duration Type 1 Diabetes-25 Years of Experience.

AIMS: Our study aimed to examine the pregnancy outcomes (maternal and fetal) concerning different models of antenatal care across a period of over 25 years (1993-2018) in 459 women with type 1 diabetes. Data from patients with a history of the condition lasting at least 15 years were considered eligible for analysis. METHODS: The study group was divided into three cohorts based on the different models of treatment used in Poznan University Hospital, Poland: 1993-2000 (cohort I, n = 91), 2001-2005 (cohort II, n = 83), 2006-2018 (cohort III, n = 284). To identify predictors for the selected dichotomous outcomes, we calculated the risks for fetal or maternal complications as dependent variables for cohorts II and III against cohort I, using multivariate logistic regression analysis. RESULTS: The mean gestational age was 36.8 ± 2.4 weeks in the total cohort. The percentages of deliveries before the 33rd and the 37th weeks was high. We observed a decreasing percentage during the following periods, from 41.5% in the first period to 30.4% in the third group. There was a tendency for newborn weight to show a gradual increase across three time periods (2850, 3189, 3321 g, p < 0.0001). In the last period, we noticed significantly more newborns delivered after 36 weeks with a weight above 4000 g and below 2500 g. Caesarean section was performed in 88% of patients from the whole group, but in the subsequent periods this number visibly decreased (from 97.6%, 86.7%, to 71%, p = 0.001). The number of emergency caesarean sections was lowest in the third period (27.5%, 16.7%, 11.2%, p = 0.006). We observed a decreasing number of "small for gestational age" newborns (SGA) in consecutive periods of treatment (from 24.4% to 8.7%, p = 0.002), but also a higher percentage of "large for gestational age" (LGA) newborns (from 6.1% to 21.6%, p = 0.001). Modification of treatment might be associated with the gradual reduction of SGA rates (cohort I 3.6%, cohort III 2.3% p < 0,0005). CONCLUSIONS: Strict glycemic and blood pressure control from the very beginning of pregnancy, as well as modern fetal surveillance techniques, may contribute to the improvement of perinatal outcomes in women with long-duration type 1 diabetes.

Markers of Endothelial Injury and Dysfunction in Early- and Late-Onset Preeclampsia.

With regard to differences in the clinical symptoms of preeclampsia (PE), the degree of endothelial dysfunction may differ between early and late-onset preeclampsia (EOP and LOP). The authors of this study examined it by assessing the endothelial injury level in women with EOP (20 patients) and LOP (20 patients) and in normotensive pregnant women (20 patients) in their late second and third trimesters of pregnancy, using the two markers-the serum concentration of hyaluronan (HA) and the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1). The serum concentrations of HA and sVCAM-1 did not differ significantly between the EOP and LOP patients. However, these were statistically higher than that of the control group participants (p < 0.05; p < 0.001). A significant correlation between the levels of HA and sVCAM-1 was found both in the entire group of patients with preeclampsia (p = 0.0277) and in women with late-onset disease (p = 0.0364), but not in the patients with early-onset preeclampsia (p = 0.331). The obtained results indicated a comparable level of endothelial injury in the two types of PE. The presence of a similar degree of endothelial injury in patients with EOP and LOP should create awareness among all clinicians about the possible fatal complications in both groups of patients with PE.

Levels of syndecan-1 and hyaluronan in early- and late-onset preeclampsia.

OBJECTIVE: The study aimed to assess serum levels of syndecan-1 (SDC-1) and hyaluronan (HA) in patients with early- and late-onset preeclampsia (PE). STUDY DESIGN: Blood samples were collected in the third trimester of pregnancy from 20 women with early-onset PE, 20 with late-onset PE, and 20 with normal pregnancy for the assessment of serum levels of SDC-1 and HA as markers of endothelial injury. PE was categorized as early-onset when diagnosed at <34 weeks of gestation and as late-onset when diagnosed at ≥34 weeks of gestation. MAIN OUTCOME MEASURES: The degree of endothelial injury in different forms of preeclampsia expressed by serum concentrations of SDC-1 and HA. RESULTS: Concentration of HA was significantly higher and the level of SDC-1 was significantly lower in patients with PE than in the control group. However, the concentrations of both HA and SDC-1 did not differ significantly between the two groups of PE. CONCLUSIONS: Degree of endothelium injury is comparable in patients with early- and late-onset PE.

Follow-up of children with antenatally diagnosed idiopathic polyhydramnios.

OBJECTIVES: The aim of our work was to assess the development of children with antenatally diagnosed idiopathic poly- hydramnios, over 12 months from the end of pregnancy. MATERIAL AND METHODS: The study included 91 healthy pregnant patients with idiopathic polyhydramnios. Diagnostic tests results and perinatal medical history were obtained retrospectively. Parents of children were contacted by phone and by mail. The answers were obtained from 64 (70%) parents. For statistical analysis SigmaStat3.5 software was used. RESULTS: Ninety six percent of parents declared that in their opinion the development of children was normal. Abnormali- ties were found in 44% of the children. Thirty percent of neonates demonstrated mild abnormalities which may be due to organic or functional neuromuscular disorders: abnormal muscle tone, speech apparatus and development disorders, swallowing and breathing problems (manifested as vomiting, excessive regurgitation, idiopathic apnoeas). Isolated small malformations were diagnosed in 12 (19%) children. Two children (3%) with SGA were diagnosed with genetic syndromes. More than one of the abnormalities described above were diagnosed in 14% of children. Gestational age at the time of polyhydramnios diagnosis and its severity were not prognostic factors for abnormalities. Seventy percent of newborns were male. CONCLUSIONS: Despite the subjectively positive assessment of the development of children by the majority of parents, groups of common disorders requiring long-term follow-up have been identified. Functional disorders of the gastrointestinal tract, CNS and the group of neuromuscular disorders may be responsible for idiopathic polyhydramnios. SGA with co-existing idiopathic polyhydramnios is associated with the risk of genetic diseases. The more frequent incidence of idiopathic poly- hydramnios in male fetuses requires further research.

Use of ex utero intrapartum treatment procedure in fetal neck and high airway anomalies - report of four clinical cases.

PURPOSE: To present antenatal management and use of ex utero intrapartum treatment (EXIT) in different fetal neck and high airway anomalies. MATERIAL AND METHODS: We have presented four different cases of fetal neck or airway pathology which were indications for EXIT, at our department. RESULTS: In three cases of fetal neck tumors, the primary precise antenatal diagnoses of tumors were confirmed after birth. The airways of all three fetuses were properly secured during EXIT by laryngologist. All these newborns survived. In the fourth case, a primary, antenatal diagnosis of congenital high airway obstruction syndrome due to severe trachea obstruction was not confirmed after birth. Finally, due to complete trachea dysgenesis, neither tracheoscopy nor tracheostomy was done during EXIT and the baby died. CONCLUSION: Despite a failure of intrapartum treatment in the fourth case, we strongly recommend this procedure for deliveries of fetuses with a suspicion of airway obstruction.

Perinatal and cardiovascular outcomes in a pregnant patient with Marfan syndrome.

A 25-year-old primigravida with Marfan syndrome (MFS) was admitted at 36 weeks of gestation (WOG).

Polyhydramnios - frequency of congenital anomalies in relation to the value of the amniotic fluid index.

OBJECTIVES: The aims of our study were to assess the correlation between the amniotic fluid index (AFI) value and the frequency and type of fetal anomalies. MATERIAL AND METHODS: The material included 94 patients at the third trimester of pregnancy, 60 with mild polyhydramnios, 19 with moderate one, and 15 with severe one. Polyhydramnios was diagnosed if AFI was > 24 cm. All patients were divided into three groups based on the value of AFI: 1) mild polyhydramnios with AFI between 24.1 and 29.9 cm, 2) moderate polyhydramnios with AFI between 30-34.9 cm, and 3) severe polyhydramnios with AFI ≥ 35 cm. RESULTS: The incidence of fetal malformations correlated significantly with the degree of polyhydramnios and was the highest in patients with severe polyhydramnios (53.3%, p = 0.002). Congenital malformations of the gastrointestinal tract were the most frequent fetal anomalies in the whole group of patients (5.3%). Trisomy 18 was the most frequent aneuploidy found in women with polyhydramnios (2.1%). CONCLUSIONS: The incidence of fetal congenital anomalies significantly increases with the degree of polyhydramnios, being most frequent in severe one and rather rare in a mild one. Congenital malformations of the gastrointestinal tract were the most frequent anomalies in patients with polyhy-dramnios, especially in women with severe polyhydramnios.

Fetal neck tumors - antenatal and intrapartum management.

In this review article we describe the ante- and perinatal management of fetal neck tumors. Although there are rare congenital anomalies, the clinical consequences for the fetus may be fatal and include airways obstruction, heart insufficiency, pulmonary hypoplasia and cosmetic effect. The right management allows to decrease the fetal and neonatal mortality and morbidity associated with the disease. It includes intrauterine therapy in some cases, mostly in a goitrus hypothyroidism of the fetus, but firstly, an assessment of the fetal airways patency with a subsequent, eventual Ex-Utero Intrapartum Treatment (EXIT).

[Long-term follow-up of children with prenatally found increased nuchal translucency and normal karyotype]. / Dalsze losy dzieci ze stwierdzonym prenatalnie poszerzeniem przeziernosci karkowej oraz prawidlowym kariotypem.

OBJECTIVE: The aim of the study was a long-term follow-up of children with prenatally found increased nuchal translucency (NT) and normal karyotype. MATERIAL AND METHODS: The study was conducted among 147 pregnant women who underwent amniocentesis due to increased fetal NT with or without other structural anomalies in the fetus. The final analysis concerned children with prenatally found increased NT and normal karyotype who were at least 2 years of age. A questionnaire was sent to all patients who underwent amniocentesis in order to assess the development of the children. RESULTS: Normal karyotype was found in 101 (68.7%) fetuses with increased NT Complete information on the outcome of pregnancy and further development of the children was submitted by 70 patients (69.3%). An abnormal outcome of pregnancy congenital structural anomalies and abnormal development was found finally in 17.1% of the children. In case of normal result of the second-trimester fetal ultrasound scan, normal further development was found in 93% of the children. CONCLUSIONS: 1. Further development of the children with prenatally found increased NT and normal karyotype is usually normal. 2. The degree of NT increase and the result of the second-trimester fetal anatomy scan seem to play the key role in the prognosis of further, postnatal outcome of the fetuses with increased NT 3. Normal karyotype in fetuses with increased NT does not exclude the possibility of an existing genetic syndrome.