Piotr Sieroszewski

Ultrasound evaluation of intrauterine growth restriction therapy by a nitric oxide donor (L-arginine)

Objective: There are numerous methods available of treating intrauterine growth restriction but their results are still not satisfactory. Currently, we are conducting a research project whose main aim is based on the use of the nitric oxide (NO) donor L-arginine in growth restriction therapy. The main aim of this study was the ultrasound evaluation of the efficacy of this therapy based on biometric measurements (the estimated fetal weight) compared with the estimated weight of newborn children. Study design: The investigated group comprised two randomly chosen groups of pregnant women with ultrasound-diagnosed intrauterine growth restriction (biometry < 10th centile for gestation age): 78 patients were treated by L-arginine 3 g daily orally for 20 days; and 30 patients, not treated, acted as the control group. Results: The ultrasound estimation of fetal weight at the start and at the end of the treatment showed a mean increase of 642 g (SE 90 g) using the Shepard method, and 648 g (SE 94 g) using the Hadlock method, respectively. By comparison, within the control group a mean value increase of 395 g (SE 77 g) was found, using the Shepard method, and 404 g (SE 82 g) using the Hadlock method, respectively. There was a significant statistical difference when comparing the estimated fetal weight increase in both methods: p = 0.008 for the Shepard calculation and p = 0.012 for the Hadlock calculation. The weight of the newborn infants was also evaluated: in the treated group the mean value was 2823 g (SE 85 g) and in the untreated group the mean value was 2495 g (SE 147 g). There was a significant (p = 0.027) difference, showing a positive effect of the treatment on the weight of newborns. In the treated group the percentage of growth-retarded newborns was 29% while in the untreated group it was 73%. A significant difference has been found (p < 0.01) between both of the groups of newborns. Conclusions: The ultrasound evaluation of the estimated fetal weight and the birth weight of the newborns showed an improvement: there was an acceleration of fetal development in the L-arginine-treated group of pregnant women as compared with the untreated group. The ultrasound evaluation of the estimated fetal weight is a good diagnostic tool, properly monitoring the efficacy of the L-arginine treatment of the growth-retarded fetuses.

The Arabin pessary for the treatment of threatened mid-trimester miscarriage or premature labour and miscarriage: a case series

Objective. The Arabin pessary may be beneficial in the treatment of cervical incompetence. The aim of the study was to analyse the efficacy of the treatment method of pregnant women with cervical incompetence. Methods. A non-randomised study performed in the obstetrical wards in Lodz, Poland utilising 54 pregnant women with cervical incompetence was developed to assess the efficiency of treatment methods of cervically incompetent women. These women were diagnosed by vaginal ultrasound examination during the course of the study. Patients with a cervical length of 15–30 mm before 28 weeks an Arabin cervical pessary were inserted, women whose cervical length was less than 15 mm were treated with cervical cerclage. The main end points of the study were preterm or term delivery. Results. In the Arabin pessary group, 1.9% of women delivered before the 29th week of gestation and 83.3% of women delivered after 37 weeks of pregnancy. Eighty-seven per cent of pregnant women treated for cervical incompetence by Arabin pessary delivered by normal spontaneous labour, 1.9% delivered by forceps labour and 11.1% of patients by caesarean section. Among pregnant women treated by Arabin pessary, 3.7% of newborns were estimated as having a score of 0–4 on the Apgar scale, 13% a score of 5–7 and 83.3% a score of 8–10. Conclusions. Cervical incompetence treatment effectively prolongs the duration of gestation. Application of the Arabin pessary is an effective method of cervical incompetence treatment.

The significance of -786T > C polymorphism of endothelial NO synthase (eNOS) gene in severe preeclampsia.

Objective. Preeclampsia (PE) is believed to be induced by endothelial cell dysfunction in placenta. Highly polymorphic endothelial nitric oxide synthase (eNOS) activity belongs to the factors significantly influencing vaso-motor tone in placenta and PE susceptibility. The aim of this study was to evaluate prevalence of −786T/C polymorphism of eNOS gene in the groups of women with mild and severe PE. Study design. The study was performed in the group of 218 preeclamptic (including 136 with severe PE) and of 400 normotensive healthy women delivered normally after a healthy gestation. The eNOS −786T/C polymorphism was determined using PCR/RFLP assay. Additionally, detailed correlation between eNOS genotypes and clinical/laboratory data in the PE group has been analyzed. Results. The higher frequency of mutated homozygous CC genotypes (17.4% vs. 11.5% in controls, OR 1.62, n.s.) and of C alleles (allelic frequency 44.1 vs. 36.6%; OR 1.36, p = 0.012) in the group of PE has been determined. Furthermore, in the group of severe PE the overrepresentation of mutated CC genotypes (23.5% vs. 11.5%, OR 2.37, p = 0.0014) and mutated C alleles (47.8 vs. 36.6%, OR 1.58, p = 0.0016) has been found. Conclusions. The presence of mutated homozygous CC genotype and C allele of −786T/C polymorphism of eNOS gene influences the higher susceptibility to develop severe PE development.

Surfactant administration without intubation in preterm infants with respiratory distress syndrome - our experiences

Abstract Background: Surfactant replacement therapy is crucial in the management of respiratory distress syndrome (RDS) in preterm infants. Classic strategies of surfactant administration required intubation. To reduce the need of intubation and mechanical ventilation (MV), we applied surfactant via a thin endotracheal catheter without intubation. Patients and methods: We compared 26 preterm infants threatened by RDS treated with surfactant via a thin endotracheal catheter without intubation (studied group – SG) with a retrospective group of preterm infants managed on MV with early surfactant treatment using INtubation SURfactant Extubation (INSURE) method (control group – CG). Study had an approval from the ethics committee (RNN/6/14/KE). Results: In the SG, 26 preterm infants were treated with one dose of surfactant (Curosurf®) administered via endotracheal catheter without intubation while receiving nasal continuous positive airway pressure (nCPAP)/SiPAP (Infant Flow). After surfactant administration, significantly less patients in SG required intubation and MV (19.2%) versus 65% necessity of second intubation in the CG. The median of time of MV in SG was 5 d versus 3.5 d in CG. Median time spent on nCPAP was 5.5 d versus 4.0 d in CG. The incidence of intraventricular hemorrhage (IVH) in the SG was 53.9%, including 50% with ≥IVH II versus 36.7% (30% ≥IVH II) in CG. The incidence of other complications of prematurity in the SG, such as necrotizing enterocolitis was 11.5% versus 23.3% in CG, the hemodynamically important patent ductus arteriosus was observed in 53.9% in SG versus 45% in CG. Bronchopulmonary dysplasia level in SG was significantly lower (15.4%) than in CG (40%), and the incidence of retinopathy of prematurity in SG was also lower (3.9%) versus 11.7% in MV group. Conclusion: Surfactant application via a thin endotracheal catheter without intubation seems to be a beneficial therapy for preterm infants with slight and mild degree of RDS. This new method of surfactant application was associated with a lower prevalence of intubation and MV and better pulmonary outcome than implementation of traditional surfactant therapy (INSURE) and MV. Prospective randomized controlled trial is required.

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns

Abstract Aim: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA). Materials: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010–2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4–6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov–Smirnov test. Significance level: p < 0.05. Results: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group. Conclusions: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

Genetic causes of recurrent miscarriages

Recurrent miscarriage is an important problem in reproductive health, which affects 1-5% of couples. The aim of this article is to summarize current knowledge on the genetic causes of recurrent miscarriage. It presents the most common parental genetic disorders (karyotype abnormalities, recessive diseases carrier status, dominant diseases and thrombophilia) connected with recurrent pregnancy loss, as well as research into other possible genetic causes. This review also sets out to demonstrate changes in the embryonic/fetal genome that may lead to abortions, and discusses the methods used to assess miscarried material, together with their advantages and disadvantages. Knowledge of the genetic background of miscarriages is important for prognosis, as well as the potential planning of prenatal diagnostics in subsequent pregnancies.

Ultrasound diagnostic schema for the determination of increased risk for chromosomal fetal aneuploidies in the first half of pregnancy

The aim of the study was to develop an early ultrasound diagnostic schema for the determination of increased risk for fetal chromosomal aneuploidies. The study was conducted on a population of 1318 pregnant women divided into 2 groups: 1255 women with the normal course of pregnancy and 63 women with diagnosed fetal abnormalities. There were 34 cases of chromosomal abnormalities (trisomy 21,18,13; triploidy; unbalanced inversion 9; deletion 16) and 29 cases of structural malformations. The estimation of the range of normal values was performed for the nuchal translucency (NT) measurement between 11 and 13 weeks and the nasal bone length (NB) measurement between 12 and 20 week. The results obtained in the collective set of normal pregnancies constituted the basis for the calculation of the range of normal values. The measurements of NB and NT showed a linear value increase with the pregnancy course. The following test characteristics (correlation to CRL) were recorded: NB — sensitivity 60%, specificity 98%, positive predictive value (PPV+) 43%, negative predictive value (NPV−) 98.9%. For the assumption that the test outcome means the presence or absence of the nasal bone in the ultrasound scan the sensitivity was 40%, but specificity 100%; NT — sensitivity 63.6%, specificity 98.2%, PPV+ 38.9%, NPV — 98.2%; NT + NB — presents similar characteristic to the NB or NT alone — sensitivity 55.6%, specificity 98.6%, PPV+ 50%, NPV — 98.9%. The following test characteristics for chromosomal aberration markers (correlation to BPD) were observed: NB — sensitivity 68.4%, specificity 97.4%, PPV+ 56.5%, NPV — 98.4%; NT — sensitivity 73.9%, specificity 97.9%, PPV+ 54.8%, NPV− 99.2%; NT + NB − sensitivity 94.7%, specificity 98.9%, PPV+ 90%, NPV — 99.7%, respectively. The “genetic sonogram” protocol for the structural defect detection was analysed: sensitivity was 80%, specificity 100%, PPV+ 100%, NPV — 99.7%. It is concluded that the new biometric parameter— nasal bone length (NB) and the corrected one — nuchal translucency thickness (NT) are useful markers for fetal abnormalities, especially for chromosomal aberrations. High predictive values of the diagnostic schema for the detection of aneuploidies and structural defects indicate that its application in correlation with the biparietal diameter (BPD) is highly recommended. The proposed schema is an effective algorithm for prenatal diagnostics characterised by high prognostic values. The possible introduction of the schema could result in a decrease of the invasive procedure rates, which could minimise the rate of miscarriages as a complication of amniocenteses.

Invasive ultrasound in the management of cervical ectopic pregnancy

Invasive ultrasound management of a 6-week live cervical pregnancy in a 26-year old primipara is described. The patient was given methotrexate three times at seven-day intervals with no effect. Then 15% KCl was administered intra-amniotically via the transvaginal and transcervical route under ultrasound guidance. The procedure was successful, causing fetal death and loss of trophoblastic blood flow on Doppler examination. Over the subsequent four weeks, there was a steady decrease of serum β-hCG concentration. After four weeks, curettage of the cervical canal and uterine cavity was performed successfully. This method of treatment enabled avoidance of invasive surgical procedures, which might have limited future fertility.

Association between uterine leiomyomas and the biochemical screening test results in the first and second trimester of pregnancy: a pilot study

Objectives. The presence of the uterine leiomyomas may change the concentrations of the screening serum markers and so after the risk calculation of the fetal chromosomal abnormalities. Purpose. To estimate the influence of the uterine leiomyomas on the first and second trimester serum markers concentrations. Material and methods. The studied group consisted of 127 women between 11 and 20 weeks of normal singleton pregnancy. In each patient, the uterine leiomyomas were diagnosed – over 20 mm in the diameter and located in the uterine wall. Seventy-seven patients had undergone the first trimester screening, 50 patients the second trimester screening. The control group consisted of 1020 women between 11 and 20 weeks of normal singleton pregnancy without uterine leiomyomas. Results. In the first trimester group, the pregnancy-associated plasma protein A serum concentrations were not different from the controls. The median concentrations of free beta-human chorionic gonadotrophin (β-hCG) were significantly higher (1.43 MoM). In the second trimester group, no significant differences in AFP and estriol median concentrations were observed, while the median value for free β-hCG was significantly higher (2.01 MoM) than in control group. Conclusions. The presence of the uterine leiomyomas may increase maternal serum concentration of the β-hCG and so after the rate of the false positive results of the prenatal screening tests.

Conservative treatment of abnormally located intrauterine pregnancies (cervical and cesarean scar pregnancies): a multicenter analysis (Polish series)

Abstract Objectives: To analyze the effectiveness and outcome of conservative treatment in cases of abnormally located intrauterine pregnancies (cervical and cesarean scar). Study design: A retrospective analysis was performed of 30 pregnant women hospitalized due to abnormally located intrauterine pregnancies. The analyzed group comprised 24 pregnant women with abnormally located pregnancies. The patients were divided into two groups: the first group consisted of patients treated systemically with methotrexate, while the second of those treated locally by administration of methotrexate (MTX) and/or potassium chloride (KCl) by gestational sac puncture. Results: The analyzed group comprised 24 pregnant women with abnormally located pregnancies. Eight patients were diagnosed with cervical pregnancy (CP) and 16 patients were diagnosed with cesarean scar pregnancy (CSP). Six patients were excluded from the study: two with spontaneous abortions, two heterotopic pregnancies, and two cornual pregnancies. Twelve analyzed patients underwent MTX systemic administration (five patients with CP, seven with CSP). In five patients, systemic treatment was ineffective; they were qualified for additional local therapy with gestational sac (GS) puncture and MTX or KCl administration to the sac and additional administration of MTX to the trophoblast area. In second group of 12 patients (three CP, nine CSP), local treatment (GS puncture with MTX or MTX + KCl) was used as the first line treatment. One patient underwent combined treatment (local + systemic). Conclusions: Conservative treatment should be the gold standard procedure in abnormally located intrauterine pregnancies. It is noticeable that MTX / KCl is more effective in a direct administration to the GS. In four cases, systemic MTX did not produce the desired effects. In these cases, the treatment was assisted by local administration of MTX or KCl, resulting in the termination of an abnormally located pregnancy.