Open Fetal Surgery for Ventricular-Amniotic Valve Implantation in Aqueductal Stenosis-Dependent Severe Fetal Hydrocephalus: A Case Report with 7-Year Follow-Up.

INTRODUCTION: Fetal ventriculomegaly is one of the most commonly diagnosed central nervous system pathologies of the second trimester, occurring with a frequency of 0.3-0.5/1,000 births. Severe fetal ventriculomegaly (SVM) may necessitate intrauterine intervention. Most such interventions have been made percutaneously with ultrasound guidance insertion of a pigtail catheter, which sadly often became obstructed or migrated. CASE PRESENTATION: Our case report presents the possibility of ventriculo-amniotic valve implantation (VAVI) by classic hysterotomy in isolated severe fetal hydrocephalus (IVSM) due to aqueductal stenosis. The patient was operated on similarly to open fetal surgery MOMS criteria at 24+4/7 GA, with an initial lateral ventricular dimension of 22.5 mm. A female newborn was delivered by elective cesarean section at 31+1/7 GA due to PPROM (Apgar 10' 8 points, birth weight 1,600 g), required CPAP, and removal of the drainage system due to infection and narrow lateral ventricles. Evans index (EI) gradual increase and clinical symptoms of high-pressure hydrocephalus after 10 days required a ventricle-peritoneal shunt (VPS) implantation. The newborn was discharged home after 28 days with stabile hydrocephalus (EI: 0.59-0.6), in good clinical condition. The 7-year follow-up was complicated by epilepsy, VPS shunt infections, delay in motor and intellectual functions (mild to moderate), and symptoms of atypical autism, the phenotype possibly related to a variant in ZEB2 gene. CONCLUSION: Intrauterine VAVI is a one-step procedure that is effective in draining CFS. The limitations of the method remain complications due to preterm labor and infection of the drainage system.

The Use of Indomethacin with Complete Amniotic Fluid Replacement and Classic Hysterotomy for the Reduction of Perinatal Complications of Intrauterine Myelomeningocele Repair.

OBJECTIVE: This study presented outcomes of classical hysterotomy with modified antiprostaglandin therapy for intrauterine repair of foetal myelomeningocele (fMMC) performed in a single perinatal centre. STUDY DESIGN: Forty-nine pregnant women diagnosed with fMMC underwent classic hysterotomy with anti-prostaglandin management, complete amniotic fluid replacement and high dose indomethacin application. RESULTS: The average gestational age (GA) at delivery was 34.4 ± 3.4 weeks, with no births before 30 weeks GA. There were 2 foetal deaths. Complete reversal of hindbrain herniation (HH), assessed in magnetic resonance imaging at 30-31 weeks GA was found in 72% of foetuses (mostly with HH grade I prior to fMMC repair). Our protocol resulted in rare use of magnesium sulphate (6%), low incidence of chorioamniotic membrane separation - chorioamniotic membrane separation (6%), preterm premature rupture of membranes - preterm premature rupture of membranes (pPROM; 15%) and preterm labour - preterm labour (PTL; 17%). The postoperative wound continuity of the uterus was usually stable (in 72% of patients), with low frequency of scar thinning (23%). CONCLUSION: Our protocol results in rare use of tocolytics, and the low occurrences of CMS, pPROM and PTL in relation to other study cohorts: Management of Myelomeningocele Study, Children's Hospital of Philadelphia, and Vanderbilt University Medical Centre.

Baseline Diameters of Inferior Vena Cava and Abdominal Aorta Measured by Ultrasonography in Healthy Term Neonates During Early Neonatal Adaptation Period.

OBJECTIVES: To evaluate normative sonographic measurements of the inferior vena cava (IVC), aorta (Ao), and IVC/Ao ratio in the first 2 days of life in term neonates. METHODS: We prospectively observed 200 term (more than 36 and 6/7 weeks of gestation), single, healthy neonates born in a city hospital. The exclusion criteria were congenital abnormalities, an Apgar score of less than 8, and hyperbilirubinemia requiring phototherapy. Maximum IVC (distal to the hepatic-IVC junction) and Ao (above the superior mesenteric artery) diameters were measured in the first 2 days of life in the longitudinal plane. Neonatal weight loss was calculated as a percentage lost from birth weight (BW). RESULTS: A total of 200 (50% born vaginally, 53% male) neonates were enrolled. Correlations between IVC and aortic diameters as a function of gestational age, method of birth, weight loss, and body surface area (BSA) were calculated using the Spearman's rank correlation coefficient. The correlation coefficients were statistically significant for the IVC (P = .017) and Ao (P = .006) abdominal diameters versus gestational age. The Ao diameter correlated with BSA (P = .0001). In neonates with weight loss less than 8% of BW, the IVC/Ao ratio remained constant at 0.62 (95% confidence interval, 0.60-0.63). CONCLUSIONS: Sonographic measurements of IVC and Ao maximum diameters in term neonates suggests a significant positive correlation among gestational age, BSA, and IVC and Ao diameters. The IVC/Ao ratios remain constant over 48 hours after birth in neonates with weight loss up to 8% of BW, and appear to be lower than previously reported ratios for healthy children.

Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a highly sensitive and specific marker of acute kidney injury (AKI). The aim of this study was to assess the factors affecting serum and urine total NGAL in preterm newborns, limiting the role of this new potential marker of AKI. METHODS: Serum and urinary total NGAL concentrations were determined in 57 preterm infants admitted to the Neonatal Intensive Care Unit in the following points of time: first week of life, between 8 and 14 days of life, and after the fourth week of life. Patients' clinical conditions were evaluated based on NTISS (Neonatal Therapeutic Intervention Scoring System). Two gestational age subgroups were distinguished: ≤29 and 30 to 35 weeks of gestation. We sought correlation between total NGAL values and gestational age, birth weight, Apgar score and severity of clinical condition, with particular interest in inflammatory status. RESULTS: Serum and urinary total NGAL concentration correlated with inflammatory markers, such as CRP and procalcitonin, as well as with NTISS values. Birth weight and gestational age influence urinary NGAL (uNGAL) values in the first two weeks of life. In AKI (N = 8) patients uNGAL values were significantly higher than in non-AKI newborns. CONCLUSIONS: We conclude that inflammatory status and prematurity limits the specificity of total NGAL measurement as a marker of AKI.

[Copeptin - stable C-terminal fragment of pre-provasopressin as a new stress marker in newborns]. / Kopeptyna ­ stabilny peptyd C-koncowy preprowazopresyny jako nowy marker stresu u noworodka.

Stress stimuli, including diseases, disturb homeostasis of the body and enhance secretion of various hypothalamus, pituitary and adrenal gland hormones. One of the main hypothalamic hormones secreted in stress conditions is arginine vasopressin (AVP). Vasopressin concentration in the blood reflects the severity of disease and disorders of blood volume. Measurement of vasopressin is difficult and subjected to considerable laboratory error because of the short half-life in serum and its instability in withdrawn blood samples. This hormone and copeptin are peptides produced during the cleavage of a larger precursor polypeptide: pre-provasopressin. Both peptides are formed in equimolar amounts. Copeptin is a more stable peptide, measurement of which can be performed with higher accuracy. This paper presents the importance of copeptin as a marker of stress, with particular emphasis on the neonatal period, analyzing the impact of gestational age and the route of delivery. Its potential application for assessing the degree of hydration in the adaptation period is also discussed.

[Hypertension in the course of primary aldosteronism during pregnancy]. / Nadcisnienie tetnicze w przebiegu pierwotnego hiperaldosteronizmu u kobiet w ciazy

Hypertension is one of the most common cardiovascular diseases during pregnancy. Primary hyperaldosteronism (PHA) is the most frequent endocrinological, secondary cause of hypertension, rarely diagnosed in pregnant women. In the available literature about 50 cases of PHA in pregnant women have been described. PHA is often a cause of resistant hypertension. PHA can cause life-threatening complications both for the pregnant woman and the fetus. Diagnosis of PHA in pregnancy is difficult due to the antagonistic effect of progesterone on aldosterone, physiological increase of aldosterone release during gestation and frequent normokalaemic clinical course. Typical pharmacological treatment of PHA is limited due to the anti­androgenic effect of spironolactone, lack of data concerning the safety of eplerenone and limited access to amiloride in Poland. Surgical treatment is a therapeutic option only in early pregnancy. This paper presents the current state of knowledge on diagnostic methods and treatment of PHA in pregnant women and a systematic review of cases described in the literature.

[Pheochromocytoma in pregnancy]. / Guz chromochlonny w ciazy.

Pheochromocytoma occurs with a frequency estimated at 2-7 per 100,000 pregnant women. Unrecognized, and thus untreated pheochromocytoma is associated with very high (40-50%) maternal and fetal mortality. Pheochromocytoma occurs sporadically or as a family trait. Its presence should be suspected in women with paroxysmal or established hypertension, especially before the 20th week of pregnancy, accompanied by headaches and palpitations, and excessive sweating, muscle tremors, vomiting, anxiety, vasomotor disturbances and blurred vision. The variety of clinical presentations and rarity are the cause of not including the disease in differential diagnosis of hypertension in pregnancy. Biochemical tests are essential in the diagnosis of pheochromocytoma, and involving the assessment of methoxycatecholamine urinary excretion. The second step in the diagnostics is magnetic resonance imaging of adrenal glands. Adrenalectomy is the treatment of choice for pheochromocytoma with adrenal location, which depends on the timing of the tumor diagnosis. Conservative treatment for 10-14 days with pharmacological blockade of alpha-adrenergic receptors should precede the surgery. Early diagnosis and properly planned treatment of pheochromocytoma significantly reduces the risk to the mother and fetus.

Frailty and Survivability of Polish Caucasian Nonagenarians and Centenarians.

Frailty is a major geriatric problem leading to an increased risk of disability and death. Prevention, identification, and treatment of frailty are important challenges in gerontology and public health. The study aimed to estimate the prevalence of the frailty phenotype (FP) among the oldest-old Polish Caucasians and investigate the relationship between the FP and mortality. Baseline data were collected from 289 long-lived individuals, including 87 centenarians and 202 subjects aged 94-99. Mortality was obtained from population registers over the following 5 years. Sixty percent of subjects were classified as frail, 33% as prefrail, and 7% as robust. Frailty was more common in women than men and among centenarians than nonagenarians. During the 5-year observation period, 92.6% of the frail women and all frail men died, while mortality rates were lower among prefrail, 78.8% and 66.7%, and robust individuals, 60% and 54.5%, respectively. In the survival analysis, frailty was the strongest negative risk factor: HR = 0.328 (95% CI: 0.200-0.539). The inability to perform handgrip strength measurement was an additional predictor of short survival. In conclusion, the FP is prevalent in nonagenarians and centenarians and correlates with lower survivability. Future studies should address differences between unavoidable age-associated frailty and reversible disability in long-lived individuals.

Decreased Maternal Morbidity and Improved Perinatal Results of Magnesium-Free Tocolysis and Classical Hysterotomy in Fetal Open Surgery for Myelomeningocele Repair: A Single-Center Study.

Fetal and maternal risks associated with open fetal surgery (OFS) in the management of meningomyelocele (MMC) are considerable and necessitate improvement. A modified technique of hysterotomy (without a uterine stapler) and magnesium-free tocolysis (with Sevoflurane as the only uterine muscle relaxant) was implemented in our new magnesium-free tocolysis and classical hysterotomy (MgFTCH) protocol. The aim of the study was to assess the introduction of the MgFTCH protocol in reducing maternal and fetal complications. The prospective study cohort (SC) included 64 OFS performed with MgFTCH at the Fetal Surgery Centre Bytom (FSCB) (2015-2020). Fetal and maternal outcomes were compared with the retrospective cohort (RC; n = 46), and data from the Zurich Center for Fetal Diagnosis and Therapy (ZCFDT; n = 40) and the Children's Hospital of Philadelphia (CHOP; n = 100), all using traditional tocolysis. The analysis included five major perinatal complications (Clavien-Dindo classification, C-Dc) which developed before the end of 34 weeks of gestation (GA, gestational age). None of the newborns was delivered before 30 GA. Only two women presented with grade 3 complications and none with 4th or 5th grade (C-Dc). The incidence of perinatal death (3.3%) was comparable with the RC (4.3%) and CHOP data (6.1%). MgFTCH lowers the risk of major maternal and fetal complications.

Is serum cystatin C a better marker of kidney function than serum creatinine in septic newborns?

INTRODUCTION: Several studies have claimed that the estimation of serum cystatin C could be a better marker of kidney excretory function than serum creatinine. However, its role in the diagnosis of reduced kidney function was not unquestionably confirmed. The aim of this study was to analyze the concentrations of serum cystatin C in neonates with sepsis. MATERIAL/METHODS: Thirty-two neonates (gestational age from 34 to 40 weeks) admitted to the NICU during the first 14 days of life were enrolled. Serum cystatin C concentrations were estimated by ELISA during three successive days in neonates treated for infection. The study group consisted of 9 newborns with sepsis, 14 with severe sepsis and 9 with septic shock. RESULTS/DISCUSSION: At the beginning of the observational period the mean serum concentration of cystatin C in the study group was 1.35 mg/L (95% CI 1.20-1.49). Surprisingly, the lowest concentration of cystatin was observed in patients with septic shock (1.23 mg/L; 95%CI 0.92-1.54) within the observation period. Higher concentrations were found in neonates with sepsis (1.47 mg/L; 95%CI 1.04-1.90) and severe sepsis (1.50; 1.12-1.87). There was no correlation between serum cystatin C concentration and serum creatinine or gestational age. A significant correlation was discovered between chronological age and cystatin C (R=-0.439, p=0.01). There was a tendency for cystatin C to decline during the second observational day in patients with sepsis (to 1.53 mg/L; 95%CI: 1.19-1.86) and severe sepsis (to 1.32 mg/L; 95%CI: 1.07-1.57), while a slight insignificant increase in patient with septic shock (to 1.28 mg/L; 95%CI: 0.88-1.68) was revealed. The interrelation between age and cystatin C concentration disappeared in the following days of stay in the NICU. Even in patients who died in the course of septic shock the observed changes in cystatin C levels were small and did not exceed those of serum creatinine. CONCLUSIONS: Cystatin C is not a useful marker of kidney function in neonates with sepsis.

Copeptin Concentrations in Plasma of Healthy Neonates in Relation to Water-Electrolyte Homeostasis in the Early Adaptation Period.

Copeptin (CTproAVP) is a stable by-product of arginine-vasopressin synthesis and reflects its secretion by the pituitary gland, considered as a potential new marker of dehydration. The objective of the study was to investigate CTproAVP measured after the first 48 h of postnatal life in relation to serum effective osmolality, urine osmolality, and vessels filling according to the following variables: delivery mode, postnatal weight loss, fluids administered intravenously to the mother, and fluids given orally to the neonate. A prospective observational study was conducted with 200 healthy term infants (53% male) enrolled. Serum CTproAVP concentrations were measured using the ELISA kit; haematocrit, urine osmolality, serum effective osmolality were assessed after 48 h of life. Sonographic measurements of inferior vena cava (IVC) and aorta (Ao) were performed and IVC/Ao ratios were calculated. No correlations were found between CTproAVP concentrations and both serum effective osmolality and urine osmolality. There was also no association between CTproAVP concentrations and vessel filling represented by IVC/Ao index at 48 h of life.

Fetoscopic Myelomeningocele Repair with Complete Release of the Tethered Spinal Cord Using a Three-Port Technique: Twelve-Month Follow-Up-A Case Report.

Open spina bifida is one of the most common congenital defects of the central nervous system. Open fetal surgery, which is one of the available therapeutic options, remains the gold standard for prenatal repairs. Fetoscopic closure may lower the number of maternal complications associated with open fetal surgery. Regardless of the approach, the outcome may be compromised by the development of tethered spinal cord (TSC) syndrome. At 24.2 weeks of gestation, a primipara was admitted due to fetal myelomeningocele and was deemed eligible for fetoscopic repair. Fetal surgery was performed at 25.0 weeks of gestation. It was the first complete untethering of the spinal cord and anatomic reconstruction (dura mater, spinal erectors, skin) achieved during a fetoscopic repair of spina bifida. Cesarean section due to placental abruption was performed at 31.1 weeks of gestation. VP shunting, with no need for revision, was performed at 5 weeks postdelivery due to progressing ventriculomegaly. No clinical or radiological signs of secondary tethering were observed. Neurological examination at 11 months postdelivery revealed cranial nerves without any signs of damage, axial hypotonia, decreased muscle tone in the lower extremities, and absent pathological reflexes. Motor development was slightly retarded. Complete untethering of the neural structures should always be performed, regardless of the surgical approach, as it is the only course of action that lowers the risk for developing secondary TSC.

[Pregnancy in a woman with chronic renal failure--the case of two successfully completed pregnancies and the review of the literature]. / Ciaza u chorej z przewlekla niewydolnoscia nerek--opis przebiegu dwóch ciaz zakonczonych powodzeniem i przeglad pismiennictwa.

Together with the prolongation and improving the quality of life of young women with chronic renal failure (CRF), procreation becomes an important issue. Pregnancies in women on renal replacement therapy are associated with an increased risk of health complications, both for mothers and for fetuses. Medical management of pregnant women with CRF is a great challenge and requires a close co-operation of nephrologists, transplantologists, gynecologists and neonatologists. The complexity of problems in these particular pregnancies has urged us to describe the case of a woman with CRF who successfully delivered two babies. We also review the current state of knowledge on the topic. The first pregnancy five years after renal transplantation, was completed with the delivery of term newborn with Tetralogy of Fallot. Also the second pregnancy on hemodialysis therapy was finished by the birth of a healthy neonate at term. The described case indicates that the gynecologists should be prepared for the challenge of the care for pregnancies in women suffering from chronic renal failure on renal replacement therapy.

Mutations in the human laminin beta2 (LAMB2) gene and the associated phenotypic spectrum.

Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin beta2, which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin beta2 function is the molecular basis of Pierson syndrome. Although truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist.

[Microdialysis: its application in experimental and clinical studies of disturbances in tissue metabolism]. / Mikrodializa--zastosowanie metody w badaniach eksperymentalnych i klinicznych zaburzen metabolizmu tkanek.

Homeostasis of human and animal organisms and its disturbance are explored mainly by evaluating metabolic substrates and metabolite concentrations and their changes under different clinical conditions. This review describes a method of tissue biochemistry monitoring by analysis of extracellular fluid dialysate. Microdialysis not only provides information about the general disturbances of the body, but allows insight into the local metabolism of tissues and organs. It can be applied both in experimental conditions (e.g. animal neurophysiology) and in clinical practice (episodes of brain ischemia, glycemic disturbances, pharmacodynamic studies). The technique of microdialysis is relatively simple and is based on microdialysis probe implantation into the studied organ or tissue, followed by measurement of the obtained samples of extracellular fluid dialysate. During the last twenty years, microdialysis probes have been inserted into different part of the living organism: brain, skeletal muscles, subcutaneous adipose tissue, transplanted tissues (myocutaneous flap) and organs (liver), tendons, skin, breast gland, lungs, heart muscle, intestines, and body cavities. The possibility of frequent sampling (every 20-60 minutes) and measuring the concentrations of glucose, glycerol, lactates, and pyruvates with a bedside analyzer in an average time of 2-3 minutes is considered a great advantage of this method. Microdialysis gives many opportunities for a better understanding of how living organisms are functioning, but it requires cautious application and validation in clinical observations in order to make standards and recommendations (diseases and clinical conditions, substances for monitoring, referenced values and trends) for its common medical usage.

Zonulin: A Potential Marker of Intestine Injury in Newborns.

INTRODUCTION: Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. MATERIAL AND METHODS: Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0-43.2) and 20.3 (1-3Q: 17.7-28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7-4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. CONCLUSIONS: Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

[The genetic basis of childhood nephrotic syndrome]. / Podloze genetyczne zespolów nerczycowych u dzieci.

Great progress has been made of late in understanding the mechanisms of proteinuria, the structure and function of the slit diaphragm, and the genetic background of congenital nephrotic syndromes in new borns and infants. This paper presents recent achievements of molecular genetics in unraveling the causes of inherited disorders, e.g. Finnish-type nephrotic, Denys-Drash and Frasier's syndromes, as well as sporadic focal-segmental glomerulosclerosis. A change in the routine policy used in evaluating the causes of childhood nephrotic syndrome is discussed.

[Intestinal colonization of newborns treated in intensive care units by multiple drug resistant microorganisms]. / Zasiedlanie wieloopornymi drobnoustrojami szpitalnymi przewodu pokarmowego noworodków leczonych w oddzialach intensywnej terapii.

The aim of the study was to examine the digestive tract colonisation of the newborns by multiple drug resistant bacteria during hospitalization. On the day of admission, after 5 days of hospitalization and at the day of discharge swabs from the anus of the 31 newborns hospitalized in OITiPN were taken and cultured on nutrient and selective media for staphylococci, enterococci, gram negative bacilli and fungi. Susceptibility to antibiotics of bacteria was determined, with giving attention to such resistance mechanisms as: methicillin resistant staphylococci (MRS), high level aminoglycoside resistant (HLAR) and vancomycin resistant enterococci (VRE) and the production of extended spectrum beta-lactamases (type ESBL) by gram negative bacilli. On the day of admission in 7 newborns methicillin resistant staphylococci (MRSCN) were grown in 24 no multiple drug resistant bacteria were found. Among those in 23 already after 5 days of hospitalization, colonization by multiple drug resistant strains was determined: coagulase-negative methicillin resistant staphylococci (MRSCN) were found in 16 children, strains of enterococci (HLAR) in 3 newborns and gram negative ESBL (+) bacilli also in 3 cases. On the day of discharge from hospital (after 13-141 days) in 23 out of 24 newborns enteric tract colonization by multiple drug resistant strains was assessed. In the enteric tract of 3 newborns hospitalized up to 2 weeks coagulase-negative methicillin resistant staphylococci (MRSCN) and/or HLAR enterococci were found; gram negative bacilli that produce ESBL appeared in newborns hospitalized for longer than 14 days. They were isolated in 12 out of 21 newborns. Forming of the enteric tract bacterial flora of the long hospitalized newborns depends on the time of hospitalization as well as on the used therapy.