Band 34, Heft 4

Acute postpartum hemorrhage is the leading worldwide cause of maternal mortality, such deaths being usually related to the development of hemorrhagic shock and its consequences, especially the multiple organ dysfunction syndrome. Obstetricians should be aware of the clinical manifestations and principles of management of hemorrhagic shock. Initial assessment of the bleeding patient requires monitoring blood pressure, pulse, capillary refill, mental status and urinary output. This allows estimation of the amount and the rate of blood loss and helps direct treatment. Hemorrhagic shock is a condition in which inadequate perfusion of organs results in insufficient availability of oxygen to satisfy the metabolic needs of the tissues. A catabolic state develops. The consequences of these changes are inflammation, endothelial dysfunction, and disruption of normal metabolic processes in vital organs. Once these events become established, the process of shock is often irreversible, even if volume and red cell deficits are corrected. The principal goals of management are controlling the source of the blood loss; restoring adequate oxygen carrying capacity; and maintaining adequate tissue perfusion. Patients with severe postpartum hemorrhage are at risk of developing hypothermia, an insidious complication that contributes substantially to morbidity and mortality. It must be prevented or treated promptly. Successful treatment of exsanguinating postpartum hemorrhage depends on efficient collaboration among all members of the patient care team, and a management plan based on an understanding of the pathophysiology of shock and tailored to the individual patient's situation.

Adaptation of uteroplacental arteries in patients with early-onset preeclampsia combined with IUGR is compromized due to insufficient invasion of extravillous trophoblast cells (EVT) into the spiral artery wall. The underlying molecular mechanisms are widely unknown. We investigated expression and possible mechanisms of regulation of different matrix-metalloproteases (MMPs) by EVT in placental bed biopsies from patients with early onset preeclampsia combined with IUGR and healthy pregnant women. Expression of MMP-3 and MMP-7 by EVT was markedly reduced in preeclamptic patients, especially close to spiral arteries. In contrast to healthy pregnancies these cells strongly expressed the receptor for leukemia inhibitory factor (LIF). LIF is known to suppress MMP-expression and is produced by uterine natural killer (uNK) cells which we found to be present in higher concentrations in the placental bed of preeclamptic patients, and accumulating aside the spiral arteries. We speculate that in preeclampsia a maternal immune cell network accumulating and interfering in the placental bed leads to an altered cytokine environment, resulting in disturbed trophoblast cell function such as impaired MMP expression and reduced invasiveness.

Aim: Little data exist on the impact of chronic low dose corticosteroid therapy during pregnancy on gestational diabetes mellitus (GDM). Method: We compared 25 pregnant women receiving long-term (>4 weeks) corticosteroid for newly diagnosed idiopathic thrombocytopenic purpura (ITP) (study group) and 108 normal pregnant women (control group) in this case-control study. Main outcome measures were 1-h, 50-g and 3-h, 100-g glucose tolerance tests (GTTs). Women in both groups were also screened with 75-g GTT 6 weeks after delivery. Results: The mean duration of corticosteroid therapy was 9.8±4.9 (range 6–25) weeks. Compared with controls, study group patients had a greater prevalence of diagnosed GDM (24.0 vs. 2.8%, P=0.01). Of these patients, 83.3% were diagnosed with GDM at 16 weeks gestation. An impaired 75-g GTT was also more frequent in the study group (P=0.01). Conclusion: Our findings suggest that long-term corticosteroid therapy may be associated with the development of diabetes in pregnant women and early GTT should be performed in pregnant women on corticosteroid therapy.

Objective: In Germany, urine analysis with dip sticks are used for screening of gestational diabetes. Our goal was to find the cut-off levels of glucose dip sticks and evaluate the influence of ascorbic acid on the result. Study design: We took urine samples of 152 pregnant patients between 01/2004 and 10/2004. The glucose content of the urine was analyzed using several dip sticks (Combur10 ® Roche ® , Multistix ® 8SG Bayer ® , Diabur5000 ® Roche ® ) and by the hexokinase method. The ascorbic acid concentration of the specimen was determined. Results: Glycosuria test dip sticks have a good sensitivity and specificity of the expected positive/negative-reaction compared with the hexokinase method but showed a significant reduction of the color reaction at high concentrations of ascorbic acid. Conclusion: High ascorbic acid concentrations cause a reduction in the color reaction of urine dip sticks. False-negative test stick measurements can appear in patients with low glycosuria. The rate of glycosuria shows high individual differences and dependent on the concentration of vitamin C. We conclude that dip sticks are not useful in prenatal management.

Objectives: The main components of protein C anticoagulant system are protein C (PC), protein S (PS) and thrombomodulin (TM); the system plays a protective role in pregnancy, mainly because it prevents the utero–placental circulation from local thrombosis. It is unknown whether the protein C anticoagulant pathway exists in amniotic fluid. The aim of the present study is to find out whether these three components are present in amniotic fluid. Study design: The study group consisted of 50 parturients with an uneventful pregnancy and birth and 25 non-pregnant controls. Amniotic fluid and blood were sampled at the end of the 1st stage of labor. PC, PS and TM were measured by immunoenzymatic method. Results: All the samples of amniotic fluid contained measurable amounts of antigens of PC, PS and TM, although their concentrations were significantly lower than in the mother's blood: (i) The concentration of PC in amniotic fluid was 6.24±3.50% and PS 2.40±1.64%, while in the mothers' plasma it was 138.26±12.38% and 93.15±13.24%, respectively (P<0.0001). (ii) TM con-centration in amniotic fluid constituted 63.92% of the concentration in the mother's blood (2.71±1.21 ng/mL vs. 4.24±0.88 ng/mL, P<0.001). Conclusion: Protein C, protein S and thrombomodulin are physiological constituents of the amniotic fluid. As their concentrations are low, it is reasonable to assume that they cannot counterbalance the procoagulant activity of amniotic fluid.

Although cord cutting has been performed since the beginning of mankind, the timing and advantages of early versus delayed cord clamping are still controversial. Early cord clamping (within the first 30 s after birth) is usually justified for potential prevention of postpartum hemorrhage and for immediate treatment of the newborn, but at the same time, may increase Rh-sensitization. Delayed cord clamping is performed after a period of 30 s during which ‘placental transfusion’ of approximately 80 mL of blood occurs. This amount seems to protect the baby from childhood anemia without increasing hypervolemia-related risks. In preterm infants, delayed clamping appears to reduce the risk of intraventricular hemorrhage and the need for neonatal transfusion. Obtaining cord blood for future autologous transplantation of stem cells needs early clamping and seems to conflict with the infant's best interest. Although a tailored approach is required in the case of cord clamping, the balance of available data suggests that delayed cord clamping should be the method of choice.

Objective: To evaluate and compare interobserver variation in interpretation of intrapartum cardiotocograms. Subjects: Fifteen senior (experience >4 years) and 16 junior (experience ≤4 years) obstetricians from 10 delivery units. Design: Thirty-one obstetricians interpreted intrapartum cardiotocographic (CTG) readings from 22 parturients. Methods: Inter-observer agreement in CTG interpretation and decision-making was assessed via proportions of agreement (Pa), with 95% confidence intervals (CI). Main outcome measures: The level of inter-observer agreement was analyzed by calculating Pa values for CTG baseline, variability, early, variable and late decelerations, uterine tonus, power of contractions, hypertonus and clinical decision. Results: In assessments of normal cases the Pa were acceptable or good (0.63–0.82) as regards all CTG interpretation elements except for the power of contractions (0.24), but in assessments of abnormal cases the Pa values were lower (0.18–0.60). As regards clinical decisions, a higher Pa was found in cases without recommendation for intervention (0.63, 95% CI 0.62–0.64) than in cases with such recommendation (0.55, 95% CI 0.54–0.56). The Pa in the abnormal cases was better among senior than among junior obstetricians. Conclusions: Inter-observer variation in interpretation of abnormal CTG readings and recommendations for intervention is relatively wide. To improve reliability, uniform classification and standardized training in CTG interpretation are needed, as well as increased use of computerized CTG.

Aims: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS). This study was initiated to assess the physiological- and maturational development of the ANS by comparing HRV data of healthy prematures with term infants. Methods: Short-term recordings of HRV in 39 premature healthy infants (29–35 weeks' gestation) were performed and compared with normative data of term infants. Frequency domain HRV parameters are computed in three frequency bands . Results: Gestational age of newborn infants is correlated with HRV. Prematures showed significant lower HRV parameters than term infants. The most significant differences were discerned for HRV parameters reflecting parasympathetic activity, whereas the pulse of the baro-receptor reflex was similar for prematures and term infants at 0.07 Hz (0.1 Hz adults). A respiratory peak in the HF-band according to respiratory sinus arrhythmia (RSA), as is common in adults, was not detected for prematures as it is not detected in term infants. Conclusions: Maturation of the ANS is accompanied by increasing HRV with a pronounced increase of parasympathetic activity. These changes are measurable by short-term recordings . The physiological pulses concerning baroreceptor reflex activity and respiratory modulation were similar in prematures and term infants.

Objective: To test the efficacy of a recently introduced ultrasonic scanning plane (three vessel and trachea view -3VTV- plus color flow mapping -3VTVC) on a low-risk population for detection of congenital heart disease (CHD). Patients and setting: Antenatal clinic dealing with local low-risk population. All antenatal patients having a second trimester scan in a 1 year period. All patients had a 3VT plus 3VTC views added to routine four chamber view. Postnatal examinations were performed according to standard hospital protocol. Results: 2847 patients were examined. The plane was achievable in all 23 fetuses with CHD detected, three false negative (aortic coarctation) and two false positive. Sensitivity of the examination was 88.5%, as high as more sophisticated and difficult targeted cardiac scanning. The extra time necessary to perform the test was minimal. Conclusion: 3VTV and 3VTCV were satisfactory used as imaging planes in a busy antenatal clinic in a low-risk population. They could be easily added to the four chamber view as routine screening for CHD and increase the detection rate to 90%.

Objective: To distinguish congenital chylothorax from other causes of hydrothorax in utero . Methods: Serum and pleural fluid samples from 8 fetuses with congenital chylothorax and 5 control fetuses with other causes of hydrothorax were tested for total protein, albumin, IgG, IgA, and IgM. Results: Fetuses with congenital chylothorax had higher levels of IgG in pleural fluid, but not the other four proteins, than control fetuses (P<0.05). There were no significant differences in serum proteins among fetuses. When we examined pleural fluid to serum ratios, the IgG ratio in fetuses with congenital chylothorax was significantly higher than that of control fetuses (P<0.05). The IgG ratio in chylothorax was greater than 0.6 regardless of lymphocyte count. Conclusion: Pleural fluid/serum IgG ratio may be a diagnostic marker for congenital chylothorax in utero .

Background: Doppler ultrasound examination has become an established method of clinical surveillance in high-risk pregnancies. Doppler indication of fetal brain sparing (BS) is an acknowledged sign of circulation redistribution during chronic hypoxia. Objectives: To evaluate the relationship between placental vascular resistance and signs of BS in middle cerebral artery (MCA) blood flow velocity. Methods: The MCA, uterine artery, and umbilical artery (UA) were located by color Doppler ultrasound in 103 high-risk pregnancies at risk for intrauterine fetal hypoxia. The blood velocity spectrum was analyzed for the following parameters: pulsatility index (PI) and signs of notching in the uterine arteries. Z-score was calculated for the MCA PI. Results: Signs of BS in the MCA were correlated to increased placental vascular impedance. The degree of BS in the MCA expressed as Z-scores was correlated to increasing vascular impedance, both in the umbilical and uterine arteries, and to adverse outcome of pregnancy. The greatest deviation in MCA PI Z-scores was seen in preterm pregnancies. Conclusion: A clear correlation exists between increasing placental vascular impedance and BS in the MCA. Preterm pregnancies express the greatest deviation from the mean MCA PI.

Objective: To investigate the effects of pregestational diabetes on pregnancy outcome. Methods: Data of 126 women with pregestational diabetes prospectively collected and controlled in a single tertiary center. HbA 1C levels at early pregnancy were registered. Adverse pregnancy outcome was defined as spontaneous abortion, congenital defect, stillbirth, or neonatal death. Results: There were 10 spontaneous abortions (7.9%) and 17 fetuses with congenital anomalies (13.4%), including 8 major malformations (6.3%). Compared with pregnancies with a favorable outcome, a higher HbA 1C concentration in early pregnancy was observed in pregnancies with adverse perinatal outcome [mean (SD): 6.3 (1.6) vs. 7.2 (1.7), P=0.001]. A positive correlation between increased maternal HbA 1C levels and the rate of fetal malformations was observed, and the group of women with poor metabolic control (early maternal HbA 1c concentration >7%) showed a 3 to 5-fold increase in the major malformation rate. Cardiovascular and genitourinary defects accounted for 58.8% of the anomalies, and the ultrasound examinations detected seven of them (41.2%). For major malformations, the detection rate was 50% (4/8). Perinatal mortality rate was 26‰ (3/116). There was almost 5-fold increase in the total pregnancy loss rate in the poor control group compared with the group with fair control [22.2% vs. 5.3%, OR (95% CI): 5.1 (1.4–17.1)]. Only 11.9% of mothers used a preconception care program. Conclusions: Pregestational diabetes mellitus is a significant risk factor for the developing fetus. Spontaneous abortions and congenital defects are more common when a poor metabolic control is present in early pregnancy. It is most important to improve access to preconception care programs for achieving a good metabolic control in early pregnancy. Ultrasound examinations have a low performance for detecting congenital defects in diabetic pregnancies.

Aim: To determine whether inhaled nitric oxide might reduce the need for excessive respiratory alkalosis to maintain systemic oxygenation in infants with persistent pulmonary hypertension of the newborn (PPHN). Materials and methods: A retrospective historical cohort study of 34 infants with PPHN with oxygenation index (OI) of 25 or more, including 19 infants without inhaled nitric oxide (i-NO) therapy (control group) and 15 infants with inhaled nitric oxide therapy (i-NO group) was performed. The initial dose of 10 ppm of i-NO was administered and no responders received the maximum dose of 25 ppm. We evaluated the mortality rate and the change of OI index and PaCO 2 during the first 6 days. Results: There were no significant differences in characteristics between groups. Two of 15 in the i-NO group and 6 of 19 infants in the control group died during the first 48 h. Baseline OI, PaCO 2 and arterial pH were similar in the two groups. OI in the i-NO group was significantly higher than in the control group between 12 and 96 h. PaCO 2 in the i-NO group was higher than in the control group between 24 and 144 h. Conclusion: i-NO therapy for PPHN might improve systemic oxygenation without excessive hypocapnia. However there was no reduction in duration of ventilation support or oxygen supply.

Aims: The optimal surgical treatment for extremely-low-birth-weight (ELBW) neonates with pneumoperitoneum is controversial. This study aimed to identify clinical factors associated with two known causes of pneumoperitoneum-necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP), and assesses the treatment outcome with primary peritoneal drainage (PPD) vs. laparotomy. Methods: We reviewed and analyzed clinical characteristics and outcome from records of neonates with pneumoperitoneum treated at our institution from January 1999 to January 2003. Results: Forty-six neonates (31 NEC, 15 SIP) were treated with either PPD (20 with NEC, 13 with SIP) or laparotomy (11 with NEC, 2 with SIP). In neonates who underwent PPD, those with NEC (vs. SIP) were less likely to have a patent ductus arteriosus, but were more likely to have been fed, have drains placed later in life, have a subsequent laparotomy, a longer total parental nutrition course, a higher 30-day mortality, and to take more days to begin enteral feeds. Conclusion: The etiology of pneumoperitoneum (NEC vs. SIP) in ELBW neonates can usually be determined preoperatively. Neonates with SIP should have a drain placed while those with NEC should undergo laparotomy.

Presentation is made of a rare case of infective puerperal endocarditis involving the native mitral valve in a young puerpera after cesarean section, without a history of pre-existing heart disease, inflammation focus or intravenous drug abuse.

Background: We hypothesize that urine levels might be reliable to assess the therapeutic range of caffeine. Objectives: We correlated plasma and urinary levels of caffeine in preterm infants treated with this drug for apnea of prematurity. Methods: Infants (n=56) were given a loading dose of caffeine citrate (10 mg/kg, per os) and 24 h later a maintenance dose (2 mg/kg, per os, once a day). Plasma and urinary levels of caffeine were determined 24 h after the loading dose (before administration of the maintenance dose) and then weekly. Results: Plasma and urinary levels correlate at all examined ages: 29 weeks (r=0.92, P<0.001), 30 weeks (r=0.97, P<0.001), 31 weeks (r=0.82, P<0.001), 32 weeks (r=0.92, P<0.001), 33 weeks (r=0.87, P<0.001), 34 weeks (r=0.81, P<0.001). Conclusion: Urinary levels of caffeine might be a useful means to assess therapeutic ranges.