Association of free maternal and fetal ropivacaine after epidural analgesia for intrapartum caesarean delivery: a prospective observational trial.

BACKGROUND: Ropivacaine is present in plasma in both protein-bound and free forms. The free form is responsible for the occurrence of toxic side effects. During obstetric epidural analgesia, free ropivacaine enters the fetal circulation depending on various factors. The aim of this study was to analyse a potential association between ropivacaine concentrations in maternal and fetal plasma and hence the extent of fetal exposure to ropivacaine. METHODS: In this prospective monocentre study, parturients who met the following criteria were included in the study: 1. epidural administration as part of obstetric anaesthesia, and 2. subsequent intrapartum caesarean delivery, which 3. was performed after an epidural bolus administration of ropivacaine within the existing epidural analgesia. Total and free ropivacaine concentrations were analysed in maternal blood at baseline, prior to epidural bolus administration for caesarean delivery, and in maternal and fetal (umbilical venous, oxygenated) blood at delivery. The results are presented as mean ±â€¯SD or median (25/75th percentile). RESULTS: We screened 128 parturients who went into labour at term and requested epidural analgesia, of whom 39 were ultimately included in the study. An intrapartum caesarean delivery was performed after the epidural application of 207 (166/276) mg ropivacaine during an epidural treatment period of 577 (360/1010) min. Total and free ropivacaine concentrations were 1402 ±â€¯357 ng/ml and 53 ±â€¯46 ng/ml, respectively, in maternal venous blood and 457 ±â€¯243 ng/ml and 43 ±â€¯27 ng/ml, respectively, in fetal blood. The maternal total and free ropivacaine concentrations were significantly correlated (r = 0.873; P < 0.0001). CONCLUSION: The results of the present study suggest that determining the concentration of free ropivacaine in maternal blood may be a feasible option for estimating neonatal exposure to ropivacaine.

Percentiles of Lymphocyte Subsets in Preterm Infants According to Gestational Age Compared to Children and Adolescents.

Preterm newborns show an increased susceptibility to infections, conceivably related to their immature immune system. To gain further knowledge about the immune development in early preterm infants, we aimed to establish references for lymphocyte subsets and compare the maturation process during hospitalization to healthy term-born children and adolescents. For this purpose, peripheral blood samples (n = 153) were collected from 40 preterm infants, gestational age (GA) 26-30 week between 2nd and 6th day of life, and were monitored in intervals of every 2 or rather 4 weeks until the end of hospitalization. Furthermore, we analysed single sample controls of 10 term neonates. We compared these data with results of a study in healthy children and adolescent (n = 176). Flow cytometry of immune cell subsets was performed as single-platform analysis using 10-colour flow cytometry. Based on preterm's age, our percentile model allows readout of absolute cell count for lymphocytes, B cells, T cells, NK cells, T8 and T4 cells. The median (minimum) value of T-, B- and NK cells after birth was 2800 (600), 790 (120) and 140 (20) cells/µl, respectively. Major differences were found in absolute cell numbers of B cells, and in the frequency of regulatory T cells, most pronounced in the earliest preterm infants (GA 26). Compared to healthy children and adolescents, preterm infants reached lymphocyte counts in between the 5th and 50th percentile when discharging the hospital. This prospective observational study provides reference percentiles for lymphocytes subsets of preterm infants. These data are conducive to interpret immunological capability of preterm infants with possible immune disorders appropriate.

Maternal CD4+ microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section.

BACKGROUND: Maternal CD4+ cell microchimerism may be greater after caesarean section compared to spontaneous vaginal delivery and could cause mother-to-child transmission (MTCT) in HIV-exposed newborns. AIMS: To evaluate maternal CD4+ cell microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. STUDY DESIGN AND SUBJECTS: In this prospective single-centre study, neonates whose mothers were infected with HIV and had normal MTCT risk according to the German Austrian Guidelines were considered for study enrolment. Maternal CD4+ cell microchimerism in the newborns' umbilical cord blood was measured and compared by mode of delivery. RESULTS: Thirty-seven HIV-infected mothers and their 39 newborns were included in the study. None of the 17 (0.0%) newborns delivered vaginally had quantifiable maternal CD4+ cells (95% confidence interval (CI): 0.00-0.00) in their circulation at birth compared with four of 16 (25.0%) newborns delivered via planned caesarean section, who showed 0.01-0.66% maternal cells (95% CI: -0.06-0.16; P=0.02) in their circulation. The intention to treat analysis, which included six additional newborns delivered by unplanned caesarean section, showed quantifiable maternal CD4+ cells in one (0.05%; 95% CI: -0.02-0.04) of 23 (4.3%) newborn at birth compared to four of 16 (25.0%) born via planned caesarean section (95% CI: -0.06-0.16; P=0.04). There was no MTCT in any of the newborns. CONCLUSION: In this small cohort, spontaneous vaginal delivery in HIV-infected women with normal MTCT risk was associated with lower maternal CD4+ cell transfer to newborns compared to planned caesarean section.

Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection: a retrospective study.

OBJECTIVE: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. STUDY DESIGN: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. RESULTS: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20-22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. CONCLUSION: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken.

Prenatal management of diaphragmatic rhabdomyosarcoma presenting with fetal hydrops.

Fetal malignant tumors are rare. We present a case of intrauterine diagnosis of a diaphragmatic tumor presenting with fetal hydrops at 32 weeks' gestation. The sonographic findings were bilateral pleural effusion, ascites and skin edema. A large right-sided diaphragmatic tumor was identified. Owing to the findings on ultrasound and magnetic resonance imaging a solid malignant tumor was suspected. The pleural effusions were drained and malignant cells identified. Because of rapid tumor progression Cesarean section was performed and a hydropic female newborn was delivered at 34 + 0 weeks' gestation. There was no sign of metastatic disease. Postnatally tumor biopsy revealed an alveolar rhabdomyosarcoma. Therapy included chemotherapy and secondary surgical intervention. After a good primary response with complete remission after 6 months, the rhabdomyosarcoma relapsed at 12 months with cerebral metastasis. The prognosis was poor.

Three-dimensional body scanning: a new method to estimate body surface area in neonates.

BACKGROUND: Body surface area (BSA) is usually estimated by calculation with mathematical formulae. Three-dimensional body scanning (3D scan) offers a suitable alternative. OBJECTIVES: We determined the BSA in healthy term and near-term neonates by 3D scanning. This system should be useful in the setting of intensive care medicine. METHODS: The measuring system consisted of a projector, two cameras, mirrors and a computer, and used the fringe projection technique with visible light. The infants were examined in a supine position; the hidden parts of the bodies were corrected for using a mathematical factor developed with a baby doll model. Results of the 3D scans were compared with those from five mathematical formulae for each subject. RESULTS: A total of 209 infants were studied by 3D scanning, of whom 53 had acceptable images and were selected for further analysis. The mean BSA was 2,139 cm(2) (SD 223.72). The minimal BSA was 1,587 cm(2), the maximal 2,670 cm(2), with a good correlation to body weight and length. One mathematical formula (Du Bois and Du Bois) showed a distinct underestimation of BSA compared to 3D scanning, the others an overestimation. Mean percentage similarity was from 96.8 to 100.9%. CONCLUSIONS: 3D scanning is an accurate and practical method to estimate BSA in newborns. Individual and repeated measurements from day to day are possible. Further studies are warranted in preterm and sick neonates.

[Doppler studies of gestational diabetes in the third trimester]. / Plazentare Widerstandsmessung bei Gestationsdiabetes im III. Trimenon.

PURPOSE: Gestational diabetes (GDM) is related to increased maternal and neonatal morbidity. Maternal hyperglycemia causes fetal hyperglycemia and consequently fetal hyperinsulinism. The impaired glucose metabolism will lead to prenatal and postnatal complications. The main issue of this study is the influence of GDM in evaluating Doppler flow measurements in the umbilical artery (UA). MATERIALS AND METHODS: Pregnancies from gestational age > 34 + 0 were included in this case control study. The study period was 18 months. The last Doppler measurement in pregnancies with GDM (diet-controlled and insulin-dependent) was compared to the healthy control group. Our collected data included the last prenatal Doppler flow recordings (resistance index (RI) in the umbilical artery (UA)). RESULTS: In women with diet-controlled GDM, a significant decrease in the RI (p = 0.002) in the UA has been observed. Insulin-treated diabetic and healthy control pregnancies showed no difference in the RI. CONCLUSION: Doppler flow examinations with RI measurements in patients with GDM differ significantly with respect to healthy controls. In insulin-treated women the RI indices are not different from the control group, while in the diet-controlled group a significant decrease was noted and additionally might show a possible maternal metabolic dysfunction.

Fetal hydrops, hyperechogenic arteries and pathological doppler findings at 29 weeks: prenatal presentation of generalized arterial calcification of infancy - a novel mutation in ENPP1.

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.

Meningitis due to multiple-resistant penicillin- and cefotaxime-intermediate Streptococcus pneumoniae in a German child after bone marrow transplantation.

The incidence of infection with penicillin-non-susceptible Streptococcus pneumoniae is increasing rapidly worldwide. Spain and France are highly affected, whereas the level of penicillin resistance in Germany, Italy, The Netherlands and Scandinavia is low. We report a lethal episode of meningitis due to penicillin- and cefotaxime-intermediate S. pneumoniae in a 7-year-old, allogene bone marrow transplanted German boy, 5 weeks after a holiday in Spain. Three days prior to the infection the patient showed good performance status. He was in complete remission without signs of graft-versus-host disease (GVHD). He died on day 341 post bone marrow transplant (BMT), 2 days after the onset of meningitis. Penicillin-non-susceptible S. pneumoniae should be regarded as a potential infectious agent even in countries with a low prevalence of resistance.

Congenital nemaline myopathy due to ACTA1-gene mutation and carnitine insufficiency: a case report.

A premature boy with a congenital form of nemaline myopathy due to mutation in the ACTA1-gene showed decreased carnitine levels in the eighth week of life. After sufficient oral carnitine substitution he improved gradually. In the first 15 months of life he made good progress; he reached full head control, learned to sit unsupported and was able to raise objects. At that time the carnitine levels were normal without substitution. Nemaline myopathy is clinically and genetically heterogenous. The pathogenesis of the muscle weakness is poorly understood. Disturbances of carnitine metabolism in this group of patients as one possibility are conceivable. Further investigations of carnitine metabolism in patients with nemaline myopathy may shed light on the pathogenesis of this entity.