Band 30, Heft 4

Taurine, a non-protein sulfur amino-acid, is the most abundant free amino-acid in the body and plays an important role in several essential biological processes. Apart from its role in cholesterol degradation, it acts as neurotransmitter, and has a function as osmoregulator and antioxydant in most body tissues. During pregnancy, taurine accumulates in the maternal tissues, to be released in the perinatal period to the fetus via the placenta and to the newborn via the maternal milk. It is accumulated especially in the fetal and neonatal brain. Low maternal taurine levels result in low fetal taurine levels. Taurine-deficiency in the mother leads to growth retardation of the offspring, and to impaired perinatal development of the central nervous system and of the endocrine pancreas. The adult offspring of taurine-deficient mothers display signs of impaired neurological function, impaired glucose tolerance and vascular dysfunction; they may develop gestational diabetes and transmit the effects to the next generation. This transgeneration effect of taurine-deficiency in the perinatal period fits into the concept of fetal origin of adult disease.

Objective: To study the effect of betamethasone therapy on maternal white blood cell count, C-reactive protein and erythrocyte sedimentation rate in women at high risk for preterm delivery. Study design: We included women at gestational age of 24 to 34 weeks who were treated by betamethasone for enhancement of fetal lung maturity, because of imminent preterm labor with intact membranes. Blood tests for white blood cell and differential count, C-reactive protein and erythrocyte sedimentation rate were drawn before betamethasone injection, 2 hours after, and then every 24 hours for three days. Results: 105 women were included. The mean white blood cell count increased by 33% on day one, and returned to baseline level three days after the first injection of betamethasone. A significant rise in neutrophil count, and drop in lymphocyte count was noted as early as two hours after the first injection and lasted for two days. Mean C-reactive protein and erythrocyte sedimentation rate levels were not changed significantly by betamethasone treatment. Conclusions: Antenatal betamethasone therapy causes a transient increase in maternal leukocyte count but has no effect on serum C-reactive protein and erythrocyte sedimentation rate. This information is relevant for preterm pregnant women who are at high risk for chorioamnionitis.

Aims: To determine interleukin (IL)-6 and IL-8 concentrations in the lower uterine segment in patients with chorioamnionitis compared to those without. Methods: Biopsy specimens from the lower uterine segment of 33 patients with chorioamnionitis were matched to specimens of 33 patients without. The biopsies had been taken during cesarean section. The concentrations of IL-6 and IL-8 in protein extracts of these specimens were determined by enzyme linked immunosorbent assays. Results: Compared to the controls patients with chorioamnionitis showed significantly lower gestational age and higher parity, and were more likely to receive fenoterol or betamethasone. In the chorioamnionitis group the median IL-6 concentrations were higher than in the controls (61.5 and 19.4 pg/mg protein, respectively [p < 0.01]). The same applies to the median IL-8 concentrations (162.3 and 13.4 pg/mg protein, respectively [p < 0.001]). Conclusions: To our knowledge this is the first study which could clearly demonstrate significantly increased IL-6 and IL-8 levels in the lower uterine segment of patients with chorioamnionitis. Increased concentrations of pro-inflammatory cytokines may play a pivotal role in cervical softening and dilatation during chorioamniotic infection.

Objective: We tested whether lipopolysaccharide (LPS)-induced murine preterm birth was delayed by tyrphostins (inhibitors of tyrosine kinases). Study design: The tyrphostins, AG126 or AG1288, or the prostaglandin endoperoxide H synthase-2 (PGHS-2) inhibitor, NS-398, were administered 2 h before LPS, with LPS, or 2 h after LPS and their effect on gestational length was measured. Results: Only tyrphostins and NS-398 administered 2h before LPS successfully delayed preterm birth (p < 0.05). Conclusions: Both tyrphostins AG126 and AG1288 as well as NS-398 inhibited LPS induced preterm birth to the time of normal birth.

Aims: To examine if increased concentrations of matrix metalloproteinase-8 (MMP-8) in amniotic fluid are associated with the development of cerebral palsy at the age of three years. Methods: The relationship between amniotic fluid concentrations of MMP-8 and the development of cerebral palsy was examined in 116 preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers who underwent amniocentesis and were followed for at least 3 years. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8 concentrations were measured by specific immunoassays. Cerebral palsy was diagnosed by neuro developmental assessment at the age of three years. Results: Median amniotic fluid concentration of MMP-8 was significantly higher in mothers whose newborns developed cerebral palsy than in mothers whose newborns did not develop cerebral palsy (median 153.9 [range < 0.3–1535.9] ng/ml vs median 6.4 [range < 0.3–3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were delivered at earlier gestational age than those without cerebral palsy. After adjustment for the gestational age at birth and the results of amniotic fluid culture, elevated concentrations of amniotic fluid MMP-8 significantly increased the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence interval, 1.1–33.0; p < 0.05). Conclusion: Increased concentrations of amniotic fluid MMP-8 are associated with the subsequent development of cerebral palsy at the age of 3 years.

Objectives: To assess the effectiveness and potential cost of an echocardiographic screening program for congenital heart disease (CHD). Patients and methods: Between 01/11/94 and 28/02/98 there were 9697 deliveries in The Royal Maternity Hospital Belfast. Mothers were randomized before delivery. 4875 infants were allocated to the scan group, while 4822 were assigned to clinical assessment alone. High-risk infants were considered separately. Cases of CHD detected before hospital discharge were documented. The annual cost of screening was estimated and the time to accurate diagnosis in each group was assessed. Results: During the study 124 scan allocated infants and 50 controls were identified as having significant CHD before hospital discharge. With a minimum of 3 years follow-up there were 27 additional late diagnoses in controls and 1 in scanned infants. During a single year of the study the mean time to complete diagnosis was 2 days for scanned cases and 110 in controls. The projected cost of screening for all infants was £ 22/infant for the first year. Conclusions: Adding echocardiography to clinical examination greatly enhances early detection of CHD. Although screening is expensive, once established it may reduce the cost of unnecessary outpatient referrals.

Aim: The current therapeutic strategies to reduce macrosomia rates in gestational diabetes (GDM) have focused on the normalizing of maternal glucose levels. The aim of our study was 1.) to compare maternal glycemic values with the presence of fetal macrosomia at different gestational ages (GA) and with LGA at birth in a cohort of women with glucose intolerance and standard diabetic therapy. Methods: 306 women with GDM and 97 with impaired glucose tolerance underwent ultrasound examinations at entry and, after initiation of therapy, monthly in addition to standard diabetic therapy. Measurements from the entry diagnostic oGTT, glucose profile and HbA1c and from subsequent glucose profiles obtained within 3 days of the ultrasound at 5 categories of GA age (20–23, 24–27 etc) were retrospectively compared between pregnancies with and without fetal macrosomia, defined as an abdominal circumference (AC) ≥90th percentile. Maternal prepregnancy BMI was adjusted for and BMI ≥30 kg/m 2 was defined as obesity. Results: At entry, neither the hourly oGTT values, HbA1c, nor the entry glucose profile differed significantly between pregnancies with and without fetal macrosomia. In a total of 919 pairs of ultrasound/glucose profiles there was no significant difference in glucose levels at every GA category neither in lean nor in obese woman except for the fasting glucose of 32–35 GA. The fetal macrosomia rate in each GA category and the rate of LGA were significantly higher in obese women: e.g. 14.5 vs 28% at diagnosis, 15.7 vs 26.7% at 32–35 weeks, 15.5 vs 25.0% at birth (p < 0.05 for each comparison). Conclusion: The association of maternal glucose values and fetal macrosomia was limited to the fasting glucose values between 32–35 weeks while maternal obesity appeared to be a strong risk factor for macrosomia throughout pregnancies with GDM. In obese women the high fetal macrosomia rate did not appear to be normalized

Thrombomodulin (TM) is a cell surface receptor playing an important role in endothelial cell anticoagulant activity. TM is also known as a factor of angiogenesis; low TM activity correlates with impaired angiogenesis. Since vascular lesions with disorders of the placental coagulation and inadequate angiogenesis can be associated with IUGR, we hypothesized that thrombomodulin expression in the villous vasculature and syncytiotrophoblast of placentae complicated by IUGR might differ from those of normal pregnancies. Representative tissue samples of normal, IUGR as well as 1 st and 2 nd trimester (n = 12) placentae were collected. Immunohistochemistry (APAAP) of paraffin tissue sections was performed using monoclonal antibodies specific for TM and PECAM. The percentage of immunopositive vessels and the intensity of immunoreactivity was assessed. Vascular endothelium and syncytiotrophoblast stained positive for TM. Immunoreactivity for TM in villous vasculature rose significantly with gestational age. Villous vessels of IUGR placentae, showed a higher expression of TM, compared to placentae of appropriately grown fetus (p < 0.05). The number of terminal villi and the number of blood vessels per intermediate villi was significantly reduced in IUGR placentae (p < 0.05). These differences reflect inadequate vascularisation and impaired angiogenesis in IUGR.

In order to evaluate serum amyloid A as an early diagnostic marker of late-onset sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40 healthy matched controls were assayed for serum amyloid A. In parallel, clinical and biochemical variables that are used to evaluate neonatal sepsis were compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels were elevated in the sepsis group (187.6 ± 78.3 μg/ml), compared with infants who had no sepsis (10.2±8.3 μg/ml) and the control group (6.9 ± 3.3 μg/ml), and were significantly higher in gram-negative compared to gram-positive sepsis (221.8 ± 84.4 μg/ml vs.48.5 ± 22.2 μg/ml). Analysis of the data suggests serum amyloid A has the highest sensitivity (100%), specificity (93%) and positive predictive value (96%) for sepsis among the clinical and biochemical parameters that were tested. In conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis of late-onset sepsis in preterm infants.

Knowing how long an infant with chronic lung disease (CLD) might require oxygen is a useful tool for counseling parents. We aimed to determine if carbon dioxide levels (PCO2) measured near term in newborn infants with CLD still requiring low flow oxygen would be useful in predicting their duration of oxygen requirement. A retrospective study was conducted on infants with CLD discharged from the neonatal unit on home oxygen treatment. The PCO2 levels of 64 infants measured by capillary gas after 34 weeks corrected gestation was correlated with duration of home oxygen requirement. We have shown that PCO 2 levels measured near to term on a capillary gas sample in infants with chronic lung disease correlate with length of oxygen dependency (r = 0.55; p < 0.0001). However it was impossible to accurately predict the length of oxygen dependency in an individual case. We conclude that it would be unwise to predict an individual infant's duration of oxygen requirement using the PCO 2 levels prior to discharge. However it might be possible to counsel parents in general that infants with lower PCO 2 levels prior to discharge are likely to have their oxygen withdrawn more rapidly than those with higher PCO 2 .

All previously reported cases of anterior diaphragmatic hernia with massive pericardial effusion were treated by pericardiocentesis and radical surgery during the early neonatal period. However, we initially followed the course of our patient in the neonatal period. Subsequently, elective surgery was performed at 70 days of age. Including our case, cardiac tamponade has not been observed in any previously reported cases of congenital anterior diaphragmatic hernia with massive pericardial effusion. Conclusion: Emergency pericardiocentesis and surgery are not always required immediately after birth, even when the presence of this condition is suspected by prenatal diagnosis. Our observation may be beneficial to preterm low birth weight infants with this condition.

Peripherally inserted central venous catheters (PICCs) have allowed central venous access via peripheral veins for a long period. PICCs have become an indispensable tool in neonatal medicine. Despite their benefits, PICCs involve some risks, which include infection, thrombosis, malpositioning, and extravascular collection of fluid. We presented two patients with extravascular collection of fluid around the vertebra resulting from malpositioning of PICCs. The PICCs were placed via the saphenous veins in both patients. The PICCs were judged to be centrally placed in the inferior vena cava by means of supine abdominal roentgenograms. The next day one patient exhibited frequent apneic attacks and the other exhibited twitching movements. A lumbar puncture revealed extravascular collection of fluid around the vertebra. In lateral view chest-abdominal roentgenograms, the PICC tips were observed to be in the vertebral lumen. The PICCs were removed immediately and the condition of the patients improved. We stressed the usefulness of the lateral view abdominal roentgenograms for revealing the malpositioning of PICCs in the inferior vena cava.

IgG antibodies to varicella-zoster virus (VZV) were analyzed in cord and the corresponding maternal blood samples using the indirect fluorescence antibody test and the fluorescent antibody to membrane antigen test. The investigations revealed protective antibody levels in 96.7% of both newborns and mothers. In the cord blood samples, significantly higher titers were detected being indicative of an active placental transfer of VZV-specific IgG.

Aims: We provide the reader with clinical tools for enhancing decision-making by depressed pregnant patients. Results: Ethical principles and the concept of fetus as patient support four clinical strategies for enhancing the autonomy of these patients: screening for depression; assessing the effects of depression on decision-making capacity; counseling about the adverse consequences of depression for pregnancy; and informing patients about the options for treatment of depression. Conclusion: These four strategies can be used to prevent ethical conflict in decisions about the management of pregnancy in patients with depression.