Balancing Benefits and Risks of Indomethacin in the Management of Antenatal Bartter Syndrome: A Case Report.

Background: Bartter syndrome, a very rare inherited renal tubular disorder, characterized by urinary salt wastage, hypokalemia, polyuria, and metabolic alkalosis, may manifest antenatally as severe isolated polyhydramnios. Indomethacin is known to reduce salt wastage and subsequent polyhydramnios during pregnancy; however, it reduces the Ductus Arteriosus diameter among other potential complications, such as inhibition of gastrointestinal perfusion and increasing the risk of renal toxicity. Case: A 36-year-old multigravida presented with severe isolated polyhydramnios at 30 weeks of gestation. Based on a history of a previous pregnancy affected with Bartter syndrome, indomethacin was initiated. Amniotic fluid volume and Ductus Arteriosus diameter were monitored. As evidence lacks on optimal dose and duration of indomethacin, multiple-dose adjustments were made to reduce the amniotic fluid volume while maintaining normal Ductus Arteriosus diameter. Progressive polyhydramnios led to Cesarean section at 34+ weeks of gestation resulting in a healthy fetus diagnosed with Bartter syndrome in the early neonatal period. Conclusion: We share our experience in the adjustment of the dose and duration of Indomethacin therapy in the treatment of severe polyhydramnios associated with antenatal Bartter syndrome. Amniotic fluid index, Ductus Arteriosus diameter, and umbilical artery doppler work together as key indicators to guide the success and safety of the therapy.

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.

Clinical diagnosis and treatment of ectopic pregnancy.

BACKGROUND: Implantation of the zygote outside the uterine cavity occurs in 2% of all pregnancies. The product of conception can be removed safely by laparoscopic surgery and be submitted for histological examination. The rate of ectopic pregnancies has increased from 0.5% in 1970 to 2% today. The prevalence of ectopic pregnancy in all women presenting to an emergency department with first-trimester bleeding, lower abdominal pain, or a combination of the 2 is between 6% and 16%. DESIGNATION: Workup of all localizations of ectopic pregnancies at a university department of obstetrics and gynecology. METHODS: Comparison of diagnostic and therapeutic modalities from the surgical laparoscopic approach to nonsurgical, medical options. SURGICAL TREATMENT: Tubal pregnancies: (1) to preserve tubal function, salpingotomy, partial salpingectomy followed by laparoscopic anastomosis, or fimbrial milking is performed. (2) Tubectomy or salpingectomy is performed only in severely damaged or ruptured tubes or if the patient does not desire further pregnancies. Nontubal ectopic pregnancies (ovarian pregnancy, ectopic abdominal pregnancy, interstitial or cornual pregnancy/rudimentary horn, intraligamental and cervical pregnancies) all require their own specific treatment. MEDICAL TREATMENT: The predominant drug is methotrexate, but other systemic drugs, such as actinomycin D, prostaglandins, and RU 486, can also be applied. COMPLICATIONS: Tubal rupture is a complication of late diagnosed tubal pregnancy that is more difficult to treat conservatively and often indicates tubectomy or segmental resection. In 5% to 15% of treated ectopic pregnancy cases, remnant conception product parts may require a final methotrexate injection. CONCLUSIONS: This article is a review to aid clinical diagnosis of ectopic pregnancies that now can be diagnosed earlier and treated effectively by laparoscopic surgery.

The study of fetal neurobehavior in twins in all three trimesters of pregnancy.

AIM: The aim was to assess the onset and the frequencies of the first intertwin contacts by four-dimensional ultrasound (4D US) in the 1st trimester of pregnancy. In the second part of the study, fetal behavior and Kurjak Antenatal Neurodevelopmental Test (KANET) score of twins compared to singletons in the 2nd and the 3rd trimesters was assessed. PATIENTS AND METHODS: Transvaginal 4D assessment was performed in 20 women in the 1st trimester between 56 and 69 postmenstrual days (PMD), while trans-abdominal approach was performed from 70 PMD onwards and at weekly intervals until 112 PMD. Fetal behavior was assessed by 4D UD US between 28 and 36 gestational weeks in 49 twin pregnancies. RESULTS: The first intertwin contacts appeared at 61 PMD, while complex body movements appeared at 68 PMD. The complexity of intertwin contacts increased from 84 PMD. With increasing gestational age, a higher frequency of movements was observed. The number of abnormal, borderline, and normal KANET scores between singletons and twins was not statistically significant. Scores for isolated eye blinking, mouthing, grimacing, hand to head movement, finger movements, Gestalt perception and general movements differed significantly in twins and singletons. CONCLUSIONS: Two types of activities were observed: spontaneous and reactive. Although twins showed less activity and different behavioral pattern than singletons, a considerable proportion of overall motility was due to intertwin contacts.

Comparison between antenatal neurodevelopmental test and fetal Doppler in the assessment of fetal well being.

AIMS: The primary aim of this study was to compare circulatory changes in the fetal brain under certain pathological conditions with alterations in fetal behavior. PATIENTS AND METHODS: A prospective longitudinal cohort study on fetal behavior of fetuses from singleton pregnancies between the 28th and 38th gestational week in the period from March 2009 to October 2011 was undertaken. There were 596 fetuses in the high-risk group and 273 fetuses in the low-risk group. Elevated umbilical artery Doppler pulsatility index and reduced middle cerebral artery pulsatility index obtained in the absence of fetal movements were considered abnormal. The Kurjak Antenatal Neurodevelopmental Test (KANET) was used to assess fetal behavior. RESULTS: Statistically significant differences in the distribution of normal, abnormal, and borderline KANET scores between low-risk and high-risk groups were found. Furthermore, 596 fetuses from the high-risk group were subdivided into subgroups according to the risk factor. The largest proportion of abnormal KANET scores (23.9%) was in the subgroup of fetuses whose mothers had an offspring diagnosed with cerebral palsy (23.9%), followed by the proportion of borderline KANET scores in the subgroup of fetuses from febrile mothers (12.7%). Fetal behavior was significantly different between the normal group and the following subgroups of fetuses: fetal growth restriction (FGR), gestational diabetes mellitus, threatened preterm birth, antepartal hemorrhage, maternal fever, sibling with cerebral palsy, and polyhydramnios. CONCLUSIONS: A new clinical application of the KANET test in early identification of fetuses at risk for adverse neurological outcome was demonstrated.

The clinical value of KANET in studying fetal neurobehavior in normal and at-risk pregnancies.

OBJECTIVES: The aim of this study was to evaluate the clinical value of Kurjak's Antenatal Neurodevelopmental Test (KANET), a new test for fetal neurodevelopment. METHODS: One hundred seventeen prenatal neurological tests were performed by the KANET scoring system between 28 and 38 weeks of gestation in 24 low-risk (24 fetuses) and 26 at-risk pregnancies (32 fetuses). The study was completed within 12 months from July 2011 onward. All 56 babies were assessed for early neurological outcome at birth by neonatologists. RESULTS: There were no abnormal KANET scores. Two thirds of all borderline scores were found in the at-risk group. Because KANET was performed more than once in most pregnancies, we introduced the average KANET score. Only one fetus of the "at-risk group" had a borderline average score. This fetus had the only abnormal early neurological outcome of all 56 fetuses. When we compared all 18 borderline KANET scores with fetal diurnal rhythm based on maternal observation, we found that 89% of the borderline scores of the "at-risk" group were at times characterized by the mother as usually "active" periods compared with 33.3% in the low-risk group. CONCLUSION: KANET is suggestive of expressing the risk for neurodevelopmental fetal disorders. Studies designed to investigate the potential connectivity of fetal diurnal rhythm and pregnancy risk status should follow.

Intrauterine growth restriction and cerebral palsy.

Intrauterine growth restriction (IUGR) can be described as condition in which fetus fails to reach his potential growth. It is common diagnosis in obstetrics, and carries an increased risk of perinatal mortality and morbidity. Moreover, IUGR has lifelong implications on health, especially on neurological outcome. There is a need for additional neurological assessment during monitoring of fetal well-being, in order to better predict antenatally which fetuses are at risk for adverse neurological outcome. Studies have revealed that the behavior of the fetus reflects the maturational processes of the central nervous system (CNS). Hence, ultrasound investigation of the fetal behavior can give us insight into the integrity and functioning of the fetal CNS. Furthermore, investigations carried out using modern method, four-dimensional (4D) sonography, have produced invaluable details of fetal behavior and its development, opening the door to a better understanding of the prenatal functional development of the CNS. Based on previous observations and several years of investigation, our reaserch group has proposed a new scoring system for the assessment of fetal neurological status by 4D sonography named Kurjak antenatal neurodevelopmental test (KANET). The value of KANET in distinguishing fetal brain and neurodevelopmental alterations due to the early brain impairment in utero is yet to be assessed in large population studies. However, preliminary results are very encouraging.

The assessment of fetal brain function in fetuses with ventrikulomegaly: the role of the KANET test.

OBJECTIVE: To assess differences in fetal behavior in both normal fetuses and fetuses with cerebral ventriculomegaly (VM). METHODS: In a period of eighteen months, in a longitudinal prospective cohort study, Kurjak Antenatal NeuorogicalTest (KANET) was applied to assess fetal behavior in both normal pregnancies and pregnancies with cerebral VM using four-dimensional ultrasound (4D US). According to the degree of enlargement of the ventricles, VM was divided into three groups: mild, moderate and severe. Moreover fetuses with isolated VM were separated from those with additional abnormalities. According to the KANET, fetuses with scores ≥ 14 were considered normal, those with scores 6-13 borderline and abnormal if the score was ≤ 5. Differences between two groups were examined by Fisher's exact test. Differences within the subgroups were examined by Kruskal-Wallis test and contingency table test. RESULTS: KANET scores in normal pregnancies and pregnancies with VM showed statistically significant differences. Most of the abnormal KANET scores as well as most of the borderline-scores were found among the fetuses with severe VM associated with additional abnormalities. There were no statistically significant differences between the control group and the groups with isolated and mild and /or moderate VM. CONCLUSION: Evaluation of the fetal behavior in fetuses with cerebral VM using KANET test has the potential to detect fetuses with abnormal behavior, and to add the dimension of CNS function to the morphological criteria of VM. Long-term postnatal neurodevelopmental follow-up should confirm the data from prenatal investigation of fetal behavior.