Band 36, Heft 5

Objective: This study was undertaken to determine whether premature labor is associated with changes in the maternal plasma concentration of soluble CD40 ligand (sCD40L), a marker of platelet activation. Methods: A cross-sectional study included patients in the following groups: 1) non-pregnant (n=21); 2) normal pregnancy (n=71); 3) normal pregnancy at term with (n=67) and without labor (n=88); 4) preterm labor (PTL) with intact membranes (n=136) that was divided into the following sub-groups: 4a) PTL who delivered at term (n=49); 4b) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered preterm (n=54); and 4c) PTL with IAI who delivered preterm (n=33). sCD40L concentrations were measured by ELISA. Results: The median maternal plasma sCD40L concentration was higher in pregnant than non-pregnant women (P=0.017). Patients with PTL had a higher median maternal plasma sCD40L concentration than women with normal pregnancies, regardless of the presence or absence of IAI and gestational age at delivery (P<0.001 for all comparisons). IAI was not associated with a higher median maternal plasma concentration of sCD40L. Conclusions: Normal pregnancy is a state in which there is a physiologic increase of sCD40L. PTL was associated with an increased median maternal plasma sCD40L concentration that could not be accounted for by IAI. Thus, our findings suggest that platelet activation occurs during an episode of preterm labor.

Objective: The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE. Study design: Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14–18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration ≥2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant. Results: 1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively). Conclusion: Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation.

Objective: The receptor for advanced glycation end products, RAGE, plays an important role in the pathogenesis of several diseases. sRAGE, soluble receptor for advanced glycation end products, is an inhibitor of the pathological effect mediated via RAGE. The aim of this study was to assess the usefulness of measuring sRAGE concentration in pregnant women with threatening preterm labor. Methods: Serum levels of sRAGE, interleukin-6 (IL-6) and routine markers of inflammation were determined in 46 pregnant women with threatening preterm labor, 35 healthy pregnant women and 15 non-pregnant controls. Results: Serum levels of sRAGE in healthy pregnant women were significantly lower than in non-pregnant controls (669±296 vs. 1929±727 pg/mL, P<0.05). Women with threatening preterm birth had a significantly higher concentration of serum sRAGE in comparison with healthy pregnant women (819±329 pg/mL vs. 669±296 pg/mL, P<0.05). Conversely, patients with PPROM had significantly lower levels of sRAGE compared with patients with threatening premature labor (600±324 pg/mL, P<0.05). sRAGE correlated negatively with leukocyte counts (r=−0.325, P<0.05). Conclusions: sRAGE might be a new and promising marker of premature labor, especially with the symptoms of PPROM.

Weight gain during pregnancy is of great importance for the health of mother and child. There is considerable individual variability with regard to the weight gain, with maternal height and pre-pregnancy body weight being important determinants. We aim to assess the usefulness of the maternal body mass index (BMI) and other ways of combining maternal weight and height in predicting weight gain during pregnancy. We analyzed data of more than 2.2 million pregnancies taken from the German perinatal statistics of 1995–2000. We found that BMI is not useful as a predictor of weight gain during pregnancy. We developed an alternative system of using maternal weight and height to predict weight gain by classifying pregnant women according to their weight and height. This allows an assessment of weight gain by comparing a given pregnant woman to other women with similar weights and heights.

Objectives : To assess the effects of applying a tight vs. a less tight control of mild chronic essential or gestational non-proteinuric hypertension in pregnancy. Methods : A randomized trial was conducted in 2006–2007 in the University of Ain Shams, Egypt. Eligible participants (n=125) were randomly assigned to either tight or less tight control of mild chronic (essential) or gestational (non-proteinuric) hypertension. The primary outcome measure was the development of severe hypertension during follow-up. Analysis was by intention-to-treat. Results : In the tight target group, adjustment of the dose with an increment of 191 mg yielded a mean dose of methyldopa of 1267±406 mg. Both systolic and diastolic BP levels were significantly less than in the tight target group. More women in the less tight group had severe hypertension during follow up (RR 3.167 and 95% CI 1.36–7.37). The rate of antenatal hospitalization was significantly higher in the less tight target group with a relative risk of 2.57 and 95% CI 1.16–5.70. The gestational age at delivery was significantly better in the tight target group. Preterm delivery and birth weight were not significantly different between the study groups. Conclusion : Tight control of blood pressure reduces the rate of antenatal hospitalization and does not adversely affect perinatal outcomes in women with mild essential or gestational hypertension.

Objective: To characterize the clinical features of women with singleton pregnancies who develop proteinuria in the absence of hypertension after mid-gestation. Methods: Seventy-nine women who developed proteinuria and/or hypertension at and after 20 weeks of gestation were reviewed, focusing on the gestational week at which significant proteinuria (>0.3 g/day) and/or hypertension developed. Results: Thirty-seven (47%) women exhibited new-onset proteinuria (>0.3 g/day) in the absence of hypertension, 33 (42%) exhibited new-onset hypertension in the absence of proteinuria, and 9 (11%) exhibited both proteinuria and hypertension. Nineteen (51%) of 37 women who exhibited new proteinuria in the absence of hypertension and 5 (15%) of 33 women who exhibited new hypertension in the absence of proteinuria progressed to preeclampsia (P=0.002). Among women who exhibited new proteinuria, 10 (77%) out of 13 women and 9 (38%) out of 24 women who developed proteinuria at <32 weeks and ≥32 weeks, respectively, progressed to preeclampsia (P=0.022). Conclusions: Women with new-onset proteinuria in the absence of hypertension may be more likely to progress to preeclampsia than women with a presumptive diagnosis of gestational hypertension, and the likelihood of progression may be significantly greater among women with earlier presentation.

Objective: To evaluate the relationship between assisted reproduction technology (ART) and anxiety symptoms during late pregnancy and early parenthood. Method: Women with ART pregnancies were prospectively compared to their partners and to women with spontaneous pregnancies. The sample of 87 subjects, 48 ART (25 mothers and 23 fathers) and 39 non-ART mothers were given the ASQ-IPAT Anxiety Scale at 30–32 weeks of gestation, and at one week and three months after delivery. Results: The main socio-demographic and obstetrical characteristics were similar between groups. ART women showed higher scores for latent anxiety than non-ART women at three months after birth and showed no difference from ART men in all assessments. Manifest anxiety scores in ART women were higher, compared to non-ART women during the third trimester of pregnancy and one week after birth and were higher in all assessments when compared to ART men. Overall level of anxiety was higher in ART women in all assessments when compared to non-ART women and higher than in ART men during the two postnatal assessments. Conclusion: We confirm the higher level of anxiety that characterizes the pregnancy-birth process in ART pregnancies. In addition, the higher manifest anxiety present before delivery and one week post-partum can be explained by the special nature of these pregnancies. Psychological support should be offered to ART patients because anxiety is an important risk factor for maternal post-partum depression and can lead to negative effects on the neonate and on child emotional and behavioral development.

Aim: To describe developmental aspects of the sympatho-vagal heart rate regulation in the human fetus by applying numerics to visual descriptions of fetal heart rate patterns throughout the third trimester of pregnancy. The focus is to determine potential benefits of this alternative means of assessing the maturation of the fetal autonomic nervous system by analysis of fetal heart rate variability (fHRV). Subjects and methods: The magnetocardiograms of 103 normal fetuses between 24+1 and 41+6 weeks of gestation were studied. Fetal heart beat intervals were determined with a temporal precision of 1 ms. The levels of fetal activity were estimated according to characteristic heart rate patterns (I–III) prior to 32, between 32–35 and beyond 35 (groups 1–3) completed weeks. Mean heart rate (mHR), standard deviation of normal-to-normal beat intervals (SDNN) and root mean square of successive differences of normal beats (RMSSD) served as fHRV indices, mean permutation entropy (PE_Mean) as complexity measure. SDNN/RMSSD was introduced as a potential marker for sympatho-vagal balance. Results: Low activity fHRP (I) were characterized by significantly lower level fHRV indices and higher PE_Mean when compared to fHRP II. We found that SDNN/RMSSD decreases with gestation in fHRP I, which suggests increasing vagal influence. In fHRP III (assigned to active awake fetuses only after 32 weeks), highest level SDNN and mHR are associated with a dramatically reduced complexity. fHRV indices cluster characteristically with the activity levels. Conclusions: We conclude that a combined analysis of fHRV, based on SDNN/RMSSD and PE_Mean, and fHRP is advantageous in the assessment of maturation of the fetal autonomic nervous system.

We reviewed the literature on the use of inhaled nitric oxide and the influence of supplemental oxygen on bronchopulmonary dysplasia (BPD), and the role of endogenous nitric oxide-synthase, vascular endothelial growth factor, the interplay of nitric oxide and superoxide, protein nitration and the nuclear factor kappa B-pathway. BPD is a major cause of neonatal mortality and morbidity leading to arrested lung development in newborns. Several studies indicate that inhaled nitric oxide (iNO) improves pulmonary angiogenesis, lung alveolarization, distal lung growth and pulmonary function in preterm infants. Given the inconclusive results of clinical studies, however, it is unclear which subpopulations of infants might benefit. Moreover, data on iNO are conflicting whether exogenous nitric oxide is protective or damaging in the presence of hyperoxia. The toxicology of iNO is poorly understood and its potential interaction with oxygen has to be considered given that infants treated with iNO are also supplemented with oxygen. The underlying mechanisms of the effects of iNO in the newborn lung need further analysis. New data clarifying the role of endogenous nitric oxide-synthases, vascular endothelial growth factor (VEGF), the interplay of nitric oxide and superoxide, and protein nitration with concurrent iNO-therapy might answer some of these questions.

Aim: To analyze the side effects of captopril, an angiotensin converting enzyme inhibitor (ACEI) in newborn and young infants. Methods: Retrospective analysis of side effects in 43 patients with congenital heart disease after cardiac surgery treated with captopril for heart failure during a two-year period. Results : Median age of the patients was 26 days (range 6–310 days), median weight 3.5 kg (range 1.9–7.9 kg). Initial median dose of captopril was 0.17 mg/kg/day (range 0.05–0.55 mg/kg/day), slowly increased over 3–33 days to a maximal median dose of 1.86 mg/kg/day (range 0.2–2.3 mg/kg/day). All patients were additionally treated with diuretics. Side effects occurred in 17 patients (renal impairment or failure in 6, low blood pressure in 8, and oxygen saturation deficit in 3) requiring cessation or interruption in seven patients with renal impairment/failure (n=4), hypotension (n=1) and aorto-pulmonary shunting with low pulmonary perfusion (n=2). The six children who developed renal impairment or failure did so following a median delay of nine days after reaching the final dose and weighed on average 500 g less than the other patients (P=0.046). All side effects were fully reversible. Conclusion : Side effects due to captopril were not dose-related in newborns and infants in this study. However, renal side effects occurred more often in smaller infants. Routine monitoring of infants on ACEI should include renal function tests, blood pressure and transcutaneous oxygen saturation measurements.