Increased plasma concentrations of activin a predict intraventricular hemorrhage in preterm newborns

BACKGROUND: Intraventricular hemorrhage (IVH) is a major cause of neurologic disabilities in preterm newborns. We evaluated the use of plasma activin A concentrations to predict the development of perinatal IVH. METHODS: We measured nucleated erythrocyte (NRBC) counts, plasma activin A, hypoxanthine (Hyp), and xanthine (Xan) in arterial blood samples obtained from 53 preterm infants during the first hour after birth. Cerebral ultrasound was performed within 48 h of birth and repeated at 5- or 6-day intervals until the age of 4 weeks. RESULTS: Grade I or II IVH was detected during the first 10 days of life in 11 of 53 patients (21%). Activin A, Hyp, and Xan concentrations and NRBC counts were higher in preterm newborns who subsequently developed IVH than in those who did not (P<0.0001, except P=0.019 for Xan). Neonatal activin A was correlated (P<0.0001) with Hyp (r=0.95), Xan (r=0.90), and NRBC count (r=0.90) in newborns without later IVH and in those who developed IVH (Hyp, r=0.89, P=0.0002; Xan, r=0.95, P<0.0001; NRBC count, r=0.90, P=0.0002). At a cutoff of 0.8 microg/L activin A, the sensitivity and specificity were 100% [11 of 11; 95% confidence interval (CI), 71%-100%] and 93% (39 of 42; 95% CI, 81%-98%), and positive and negative predictive values were 79% (95% CI, 61%-100%) and 0% (95% CI, 0%-2%), respectively. The area under the ROC curve was 0.98. CONCLUSIONS: Activin A concentrations at birth are increased in preterm newborns who later develop IVH and may be useful for early identification of infants with hypoxic-ischemic brain insults who are at high risk for IVH.     

S100B protein is increased in asphyxiated term infants developing intraventricular hemorrhage

OBJECTIVE: To establish whether S100B protein may be useful in the early detection of intraventricular hemorrhage in asphyxiated term infants. DESIGN: Case-control study. PATIENTS: Twenty full-term newborns with intraventricular hemorrhage, 20 asphyxiated infants without intraventricular hemorrhage, and 80 normal newborns. INTERVENTIONS: Routine laboratory variables and neurologic patterns were assessed at birth after 12 and 72 hrs. Ultrasound imaging and middle cerebral artery Doppler velocimetry pulsatility index were recorded at 12 and 72 hrs after birth. S100B protein blood concentrations were determined at 12 hrs. MEASUREMENTS AND MAIN RESULTS: S100B protein levels were significantly higher in samples collected from newborns who developed intraventricular hemorrhage (1.87 +/- 0.60 microg/L) than from those who did not develop intraventricular hemorrhage (0.72 +/- 0.39 microg/L) or from normal infants (0.66 +/- 0.31 microg/L). Multiple logistic regression analysis showed a significant correlation between circulating S100B protein concentrations and the occurrence of intraventricular hemorrhage. CONCLUSIONS: This study suggests that elevated S100B protein represents a useful tool for the early detection of intraventricular hemorrhage in the postasphyxia period when clinical examination and cerebral ultrasound might still be silent.     

Urinary S100B protein measurements: A tool for the early identification of hypoxic-ischemic encephalopathy in asphyxiated full-term infants

OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect which infants will develop brain damage after asphyxia insult. DESIGN AND SETTING: Prospective study conducted in three tertiary departments of neonatology from December 1999 to July 2002. PARTICIPANTS: A total of 44 infants with perinatal asphyxia and 68 control infants. INTERVENTION: Routine laboratory variables, neurologic patterns, ultrasound imaging, and urine concentrations of S100B protein were determined at nine time points. MAIN OUTCOME MEASURES: The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, and 72 hrs after birth. The results were correlated with the presence or absence of hypoxic-ischemic encephalopathy. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling. RESULTS: S100B protein levels were significantly higher in samples collected at all monitoring time points from newborns with perinatal asphyxia with or without hypoxic-ischemic encephalopathy than in samples from normal infants (all p <.001). When asphyxiated infants were subdivided according to the presence of mild or absence of hypoxic-ischemic encephalopathy (group A) and of moderate or severe hypoxic-ischemic encephalopathy (group B), S100B levels were significantly higher at all the predetermined monitoring time points in group B infants than group A or control infants (all p <.001). An S100B concentration cutoff of 0.41 microg/L at first urination had a sensitivity of 91.3% and a specificity of 94.6% for predicting the development of hypoxic-ischemic encephalopathy. The sensitivity and specificity of measurements obtained from 4 to 72 hrs after birth were up to 100% and 98.8%, respectively. CONCLUSIONS: Longitudinal S100B protein measurements in urine soon after birth are a useful tool to identify which asphyxiated infants are at risk of hypoxic-ischemic encephalopathy and its possible neurologic sequelae.     

Lung fractional moving blood volume in normally grown and growth restricted foetuses

OBJECTIVE: To examine foetal lung blood perfusion using power Doppler ultrasound (PDU) and to compare fractional moving blood volume (FMBV) and mean pixel intensity (MPI) estimations in the lungs of normally grown (NG) foetuses and foetuses with intrauterine growth restriction (IUGR) and also to correlate foetal lung FMBV and MPI with respiratory complications after birth. METHODS: Lungs of 47 NG and 25 IUGR foetuses after 32 weeks of gestation were examined with PDU. FMBV and MPI were estimated in a defined region in the posterior part of the foetal lung closest to maternal abdominal wall. FMBV and MPI were correlated to foetal weight deviation and gestational age. Perinatal outcome and respiratory complications after birth were recorded in both groups. RESULTS: There were significantly lower FMBV and MPI values in IUGR than in NG foetuses. The overall variation was lower for FMBV than for MPI. There was a slightly higher correlation between FMBV and foetal weight deviation [r = 0.33, 95% confidence intervals (CI) 0.11-0.52] than between MPI and foetal weight deviation (r = 0.26, 95% CI 0.03-0.46). There was no significant correlation between FMBV or MPI and gestational age. No differences between the groups were found in the rate of respiratory complications, and they were not correlated either to the FMBV or MPI. CONCLUSION: FMBV and MPI, estimated from the PDU signals of foetal lung circulation, showed lower values in third-trimester pregnancies complicated by IUGR. The frequency of neonatal respiratory complications was not increased in cases with low pulmonary FMBV and MPI values.     

Maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction.

OBJECTIVE: To investigate maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Maternal echocardiography and ambulatory blood pressure monitoring were performed in pregnancies complicated by IUGR (n = 12) and controls (n = 12), all of whom were normotensive at enrollment. RESULTS: Compared to controls, maternal blood pressure (P = 0.016) and total vascular resistance (P = 0.008) were higher in IUGR pregnancies. Heart rate was lower (P = 0.003), as was systolic function expressed by midwall fractional shortening (P = 0.04). No significant differences between the two groups were observed for left atrial or left ventricular dimensions, nor for left ventricular geometry. Assessment of diastolic function by means of transmitral Doppler flow measurements revealed a significantly longer isovolumetric relaxation time in pregnancies with IUGR (P = 0.006). CONCLUSIONS: In normotensive pregnancies complicated by IUGR, as compared to controls, there is decreased diastolic and systolic maternal cardiac function, and a higher blood pressure.     

Circadian rhythm of maternal blood pressure and fetal growth

This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 ± 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1–2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0–1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5–1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier.     

Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males.

BACKGROUND: Severe traumatic brain injury (TBI) is associated with a 30%-70% mortality rate. S100B has been proposed as a biomarker for indicating outcome after TBI. Nevertheless, controversy has arisen concerning the predictive value of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to determine whether S100B serum levels correlate with primary outcome following isolated severe TBI or multitrauma in males. METHODS: Twenty-three consecutive male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS) 3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting of eight healthy volunteers were enrolled in this prospective study. Clinical outcome variables of severe TBI comprised: survival, time to intensive care unit (ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU discharge]. Venous blood samples were taken at admission in the ICU (study entry), 24 h later, and 7 days later. Serum S100B concentration was measured by an immunoluminometric assay. RESULTS: At study entry (mean time 10.9 h after injury), mean S100B concentrations were significantly increased in the patient with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations when compared with survivors (0.85 microg/L). In fact, there was a significant correlation between higher initial S100B concentrations and fatal outcome (Spearman's =0.485, p=0.019). However, there was no correlation between higher S100B concentrations and the presence of multitrauma. The specificity of S100B in predicting mortality according to the cut-off of 0.79 microg/L was 73% at study entry. Conclusions: Increased serum S100B levels constitute a valid predictor of unfavourable outcome in severe TBI, regardless of the presence of associated multitrauma.     

Maternal and fetal hemodynamic effects induced by nitric oxide donors and plasma volume expansion in pregnancies with gestational hypertension complicated by intrauterine growth restriction with absent end-diastolic flow in the umbilical artery.

OBJECTIVE: To evaluate the effect of plasma volume expansion (PVE) and nitric oxide (NO) donors, in addition to antihypertensive therapy for gestational hypertensive pregnancies complicated by intrauterine growth restriction (IUGR) with absent end-diastolic flow (AEDF) in the umbilical artery (UA). METHODS: This was a case-control study into which 32 gestational hypertensive pregnancies with IUGR and AEDF were enrolled. Sixteen of these were treated with antihypertensive drugs, NO donors and PVE (Group A), and 16, matched for maternal age, gestational age and fetal conditions, were treated with antihypertensive drugs only (Group B). All patients underwent fetal and uteroplacental assessment and maternal echocardiography to evaluate total vascular resistance (TVR) and cardiac output before and 5-14 days after initiation of treatment. RESULTS: After 5-14 days of treatment, the maternal TVR in Group A fell from 2170 +/- 248 to 1377 +/- 110 dynes.s.cm(-5) (P < 0.01), and that in Group B fell from 2090 +/- 260 to 1824 +/- 126 dynes.s.cm(-5) (P < 0.01), with the reduction being greater in Group A than in Group B (P < 0.01). There was a significant increase in cardiac output in Group A after 5-14 days of treatment vs. baseline (6.19 +/- 0.77 vs. 4.32 +/- 0.66, P < 0.001), and, after treatment, cardiac output was significantly greater in Group A than it was in Group B (6.19 +/- 0.77 vs. 4.70 +/- 0.44, P < 0.001). Reappearance of end-diastolic flow in the UA occurred in 14/16 patients in Group A but in no patients in Group B (87.5% vs. 0%, P < 0.05). The interval between detection of UA-AEDF and delivery was 28 +/- 16 days in Group A and 11 +/- 6 days in Group B (P < 0.05). CONCLUSION: Administration of NO donors and PVE in gestational hypertensive pregnancies affected by IUGR and UA-AEDF appears to improve both maternal and fetal hemodynamics, inducing prolongation of gestation.     

Effects of mode of delivery on maternal-neonatal plasma antioxidant status and on protein S100B serum concentrations

OBJECTIVE: To investigate the effect of the mode of labour and delivery on total antioxidant status (TAS) and on the protein S100B serum concentrations in mothers and their newborns. MATERIAL AND METHODS: Sixty women with normal pregnancies were divided into three groups: Group A (n = 20) with normal labour and vaginal delivery (VG), group B (n = 18) with prolonged labour+VG and group C (n = 22) with scheduled caesarean section (CS). Blood was obtained at the beginning of the labour process and immediately after delivery (pre- and post-delivery) as well as from the umbilical cord (CB). TAS and creatine kinase (CK) were measured using commercial kits. Serum S100B levels were evaluated with the electrochemiluminescence immunoassay "ECLIA" on the ROCHE ELECSYS 2010 immunoassay analyser. RESULTS: Post-delivery, TAS levels were significantly decreased in group A and especially in group B. S100B levels were increased in group B (0.0712+/-0.02 microg/L) as compared with those of group A (0.0567+/-0.03 microg/L, p<0.01) and group C (0.038+/-0.03 microg/L, p<0.01), the levels in group C remaining practically unaltered (pre- versus post-delivery). In the newborns, S100B levels were almost 2-fold higher in group B (0.67+/-0.18 microg/L) than those in group A (0.40+/-0.05 microg/L p<0.001) and group C (0.31+/-0.04 microg/L p<0.001). A negative correlation was found between TAS and S100B protein (r = -0.61, p<0.001), the latter positively correlated to CK (r = 0.48, p<0.01). CONCLUSIONS: The increased S100B serum levels in the mothers of group B, post-delivery, may have been due to the long-lasting, oxidative and/or psychogenic stress. The observed remarkably high levels of S100B in the group B newborns may have been due to compressive conditions on the foetus brain during this mode of delivery.     

Effect of the pretest probability of intrauterine growth retardation on the predictiveness of sonographic estimated fetal weight in detecting IUGR: a clinical application of Bayes' theorem

Four hundred and five women with singleton pregnancies and fetal age determination by crown-rump length were classified on the basis of their prenatal clinical findings into four risk categories for intrauterine growth retardation (IUGR), defined as a neonatal weight below the 10th percentile of age-dependent birth weight distribution curve. The incidence of IUGR in these four groups were 3.5% (very low risk), 20.6% (low risk), 49.6% (intermediate risk), and 88.0% (high risk). Severe growth retardation (birth weight less than 2.5th percentile) increased from 0% to 76.0% as the incidence of IUGR increased throughout the risk groups. The effect of these pretest risks on the prediction of severe IUGR by sonographic estimated fetal weight (EFW) was evaluated. The positive predictive value of the test, as well as the probability of having a growth-retarded infant after a normal EFW was obtained were considerably higher when the pretest probability of IUGR increased. In the very low risk group, the probability of severe IUGR was negligible regardless of the EFW. When the EFW was less than 10th percentile of our age-dependent EFW curve, the probability of severe IUGR in the other risk groups was high enough to warrant fetal well-being surveillance and/or timely interruption of gestation as appropriate. However, when the pretest probability was high, the risk of severe IUGR in spite of an EFW within the 10th percentile to 90th percentile remained sufficient to require fetal well-being surveillance as well. The study shows that placing ultrasound results in the context of the pretest risk of IUGR may improve clinical decision making in pregnancies complicated by fetal growth retardation.     

Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.

OBJECTIVES: To correlate levels of angiogenic growth factors with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). METHODS: In 16 women with pre-eclampsia and 15 women with isolated IUGR, pulsatility indices (PI) in the umbilical and uterine arteries were measured by Doppler ultrasonography. At delivery, maternal and fetal blood (umbilical vein and artery separately) was sampled and angiogenic growth factors measured by means of enzyme linked immunosorbent assay (ELISA). RESULTS: Umbilical artery PI was significantly higher in women with IUGR than in those with pre-eclampsia, whereas uterine artery PI was not statistically significantly different. Maternal soluble fms-like tyrosine kinase-1 (sFlt-1) levels were higher in women with pre-eclampsia than in those with IUGR (P < 0.0001). Umbilical vein basic fibroblast growth factor (bFGF) levels were lower in women with pre-eclampsia than in those with IUGR (P < 0.05). Placental growth factor (PlGF) levels in the umbilical vein were below the detection limit in nearly all samples of IUGR fetuses and lower than in those with pre-eclampsia (P < 0.001). Maternal PlGF levels were inversely correlated with PI values of both vessels. In the umbilical vein sFlt-1 was positively and soluble kinase insert domain receptor (sKDR) negatively correlated with umbilical artery PI. No correlation could be found in the serum of the umbilical artery for all growth factors and for vascular endothelial growth factor (VEGF) in all compartments. CONCLUSIONS: The correlations between maternal and fetal angiogenic growth factor serum levels and Doppler ultrasound indices of uterine and umbilical arteries in pre-eclampsia and IUGR reflect the severity of the disorders especially for the fetus. A combination of both measurements may be useful in future screening for early prediction of pregnancy complications. Published by John Wiley & Sons, Ltd.     

彩色多谱勒对IUGR脐动脉血流的检测

目的：应用彩色多谱勒检测正常妊娠和胎儿宫内发育迟缓（以简称ＩＵＧＲ）的脐动脉血流指标ＰＩ、ＲＩ、Ｓ／Ｄ值。材料和方法：应用彩色多谱勒检测了２００例正常妊娠和１１１例ＩＵＧＲ的脐动脉血流,孕周从２６－４１周。结果：正常妊娠组及ＩＵＧＲ组的脐动脉血流指标均随妊娠周数的增高而降低,但ＩＵＧＲ组的脐动脉血流ＰＩ、ＲＩ、Ｓ／Ｄ值明显高于正常妊娠组（Ｐ〈０．０１）。孕３０周后,脐动脉血流Ｓ／Ｄ值〉４,揭示胎儿预后不良。结论：脐动脉血流检测不仅是胎儿监护的一种方法,而且可作为诊断ＩＵＧＲ的一个指标及对估计胎儿预后有一定的临床价值。     

Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications

Placental insufficiency-related complications are one of the leading causes of maternal and perinatal morbidity and mortality. This study investigated the quantification of placenta-specific microRNAs (miRNAs) in the maternal circulation during gestation in a cohort of women with normally progressing pregnancies, the differentiation between placental insufficiency-related complications and normally progressing pregnancies, and the differentiation between placental insufficiency and normally progressing pregnancies during the early stages of gestation. Both absolute and relative quantification of placenta-specific miRNAs (ie, miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) was determined in 50 women with normally progressing pregnancies, 32 with complicated pregnancies [21 with preeclampsia with or without intrauterine growth retardation (IUGR) and 11 with IUGR], and 7 women with pregnancies at various gestational stages who later developed preeclampsia and/or IUGR using real-time PCR and a comparative C(T) method relative to normalization factor (ie, geometric mean of ubiquitous miR-16 and let-7d). Both quantification approaches revealed significant increases in extracellular placenta-specific miRNA levels over time in women with normally progressing pregnancies; however, they were not able to differentiate between normally progressing and complicated pregnancies at the time of preeclampsia and/or IUGR onset. Nevertheless, significant elevation of extracellular miRNA levels was observed during early gestation (ie, within the 12th to 16th weeks) in pregnancies with later onset of preeclampsia and/or IUGR. Early gestation extracellular miRNA screening can differentiate between women with normally progressing pregnancies and those who may later develop placental insufficiency-related complications.     

Increased levels of serum S100B protein in critically ill patients without brain injury

There is increasing evidence that the release of S100B protein, which is an acknowledged marker of brain injury, is also induced by other causes including hemorrhagic shock. The aim of this study was to investigate the serum concentration of S100B in critically ill mechanically ventilated patients with various degrees of organ dysfunction but without evidence of brain injury or any other neurological disorder and its possible association with tissue perfusion indices. Forty-six critically ill mechanically ventilated patients were studied on intensive care unit admission and until 6 days later. Measurement of serum S100B protein was obtained daily at the time of laboratory sampling and blood gas and lactate analysis. All patients exhibited increased levels of serum S100B levels at least once (median, 0.31 microg/L; interquartile range 25%-75%, 0.17-0.68 microg/L; range 0.04-18 microg/L). There was a significant correlation between S100B and arterial lactate (r, 0.66; P < 0.001), mean arterial pressure (MAP) (r, -0.41; P < 0.001), and pH (r, -0.37; P < 0.001). Serum concentrations of S100B were significantly higher in the presence of hemoglobin (Hb) level of less than 7 mg/dL compared with those measured when Hb level was greater than 7 mg/dL (median, 1.61 mg/dL; interquartile range 25%-75%, 0.66-3.57, vs. median, 0.29; interquartile range 25%-75%, 0.15-0.56, respectively; P < 0.001). Multiple regression analysis with dependent variable S100B and independent variables lactate, Hb, pH, and MAP showed that the only independent variable was the lactate (r, 0.79; r2, 0.62; P < 0.001). Sequential organ failure assessment score was positively associated with S100B values (P < 0.05). In conclusion, serum levels of S100B protein are elevated in critically ill patients, in the absence of an apparent brain damage. Increased S100B values correlated positively with lactate levels and negatively with MAP and pH. Low Hb level is associated with increased S100B levels. These results indicate that serum S100B protein concentration may be related to tissue hypoperfusion.     

Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome.

OBJECTIVE: To describe sequential changes in uterine artery waveform between the first and second trimesters of gestation and to analyze their association with the subsequent risk of hypertensive disorders and fetal growth restriction (IUGR). METHODS: Sequential uterine artery Doppler recordings were obtained in a final cohort of 870 singleton pregnancies over two gestational age intervals: 11-14 weeks and 19-22 weeks. The left and right uterine arteries were examined by color and pulsed Doppler and the mean pulsatility index (PI) as well as the presence of a bilateral protodiastolic notch were recorded during both intervals. Pregnancies were followed for occurrence of hypertensive disorders and IUGR. RESULTS: Mean uterine artery PI showed a significant linear decrease within each of the two intervals considered, while the prevalence of a bilateral notch showed decreasing values only throughout 11-14 weeks of gestation. Sixty-four (7.3%) pregnancies developed a hypertensive disorder and/or IUGR, including three (0.34%) cases of gestational hypertension, 24 cases of pre-eclampsia (2.75%) and 37 (4.25%) of IUGR. Compared with pregnancies with a normal outcome, complicated pregnancies showed a significantly higher prevalence of a bilateral notch and a higher mean PI in each of the two intervals studied. Compared with normal pregnancies, complicated pregnancies had a significantly higher persistence of a bilateral notch (30% vs. 8%), a higher proportion of women with an abnormal first-trimester uterine artery PI shifting to normal in the second trimester (14% vs. 4%) and a higher incidence of a normal first-trimester mean PI that shifted to abnormal in the second trimester (13% vs. 4%). Persistence of an abnormal mean PI from the first to the second trimester identified the group with the greatest risk for adverse perinatal outcome (OR, 10.7; 95% CI, 3.7-30.9). In addition, women in whom the uterine artery mean PI shifted from abnormal to normal between the two trimesters and women in whom the reverse shift occurred showed a similar intermediate risk (OR, 5; 95% CI, 2.1-10.6), comparable to that in women with persistence of a bilateral notch (OR, 5.6; 95% CI, 2.9-10.7). CONCLUSIONS: The sequence of changes in uterine flow between the first and second trimesters correlates with the subsequent development of hypertensive disorders and IUGR. Women with a persistent abnormal mean PI represent the group with the greatest risk for adverse perinatal outcome.     

Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction

The present study was performed to compare serum concentrations of maternal and fetal angiogenic growth factors in IUGR (intrauterine growth restriction) and normal pregnancy at the time of delivery. VEGF (vascular endothelial growth factor), PlGF (placental growth factor), sFlt-1 (soluble fms-like tyrosine kinase 1), sKDR (soluble kinase domain receptor) and bFGF (basic fibroblast growth factor) were measured by ELISA in serum from a maternal peripheral vein, the umbilical vein and the umbilical arteries in 15 women with pregnancies complicated by IUGR and 16 controls (women with normal pregnancies). In IUGR, sFlt-1 was increased, and PlGF and sKDR were decreased, in both maternal serum and serum from the umbilical vein. Additionally, bFGF was increased in serum from the umbilical vein of women with pregnancies complicated by IUGR. No significant differences in growth factor concentrations between the groups were found in serum from the umbilical artery. In both groups, levels of VEGF were higher and levels of sFlt-1 were lower in serum from the umbilical vein and umbilical artery compared with maternal serum. PlGF levels were found to be lower in serum from the umbilical vein compared with maternal serum in both groups, whereas PlGF levels in serum from the umbilical artery were significantly lower only in the control group. These findings suggest an imbalance of angiogenic and anti-angiogenic factors in IUGR, with formation of an anti-angiogenic state in maternal and, to a lesser extent, umbilical vein blood. The placenta appears to play a central role in the release of sFlt-1 into maternal and umbilical blood. Umbilical artery blood was unaffected in IUGR, indicating that the fetus does not contribute to changes in angiogenic growth factor concentrations.     

Serum S100 protein could predict altered consciousness in glyphosate or glufosinate poisoning patients

Background: Central nervous system (CNS) complications such as seizures and reduced consciousness are important in glufosinate and may occur in severe glyphosate poisoning. The aim of this study was to assess the possible role of serum S100B protein as a biochemical marker of CNS complications associated with glyphosate or glufosinate poisoning.

Methods: The study enrolled 40 patients (23 glyphosate poisoning and 17 glufosinate poisoning). Altered consciousness and seizure were observed during hospitalization. S100B level was measured with fully automated modular analytic E170 system using electrochemoluminometric immunoassay.

Results: Among 40 patients, neurologic features were observed in 12 patients with a median time to onset of 21.5 (IQR 8.25–24.75) h. Serum S100B concentrations measured on admission were higher in the group with neurologic features than in the group without neurologic features [0.148?μg/L (IQR 0.128–0.248) vs. 0.072?μg/L (IQR 0.047–0.084), p?Conclusions: In our pilot study, S100B was a significant predictor of neurologic complications in patients with glyphosate and glufosinate poisoning. Large prospective cohorts are needed to confirm this finding.     

Uterine and umbilical artery flow velocity waveform analysis in pregnancies complicated by chronic hypertension or preeclampsia

Using continuous wave Doppler ultrasound, we studied the umbilical and uterine flow velocity waveforms in 68 pregnant women who had chronic hypertension and/or preeclampsia. The systolic-diastolic (S/D) ratio was considered an expression of vascular resistance peripheral to the point of insonation. Abnormal umbilical artery S/D ratio (greater than 95th percentile) alone or with abnormal uterine artery S/D ratio was associated with poor pregnancy outcome as judged by incidence of intrauterine growth retardation (IUGR), cesarean section rate, birth weight, perinatal morbidity and mortality, and prematurity. In patients with preeclampsia and abnormal Doppler values, pregnancy outcome was poor, whereas in those with normal Doppler values, pregnancy outcome approached normal. The same relationship was also found in patients with chronic hypertension. The sensitivity and specificity for the prediction of IUGR by the umbilical artery S/D ratio alone was 71% and 93%, respectively. The uterine artery S/D ratio alone yielded a 66% sensitivity and 64% specificity, and when both tests were taken into account, the sensitivity increased to 75% and the specificity to 100%. Abnormal umbilical and uterine artery S/D ratios were associated with 100% IUGR and 25% perinatal mortality. We conclude that in pregnant women with hypertensive disorders there is a significant difference in pregnancy outcome between those with normal and those with abnormal Doppler values. Umbilical artery S/D ratio alone is a better predictor of IUGR and poor pregnancy outcome than the uterine artery S/D ratio.     

Diabetes in pregnancy and cesarean delivery.

OBJECTIVE: To evaluate the effect of diabetes during pregnancy on cesarean delivery and to determine whether the association between diabetes during pregnancy and cesarean delivery is mediated by birth weight. RESEARCH DESIGN AND METHODS: South Carolina 1993 birth certificates were matched through a unique identifier with infant and maternal hospital discharge records for the same year, yielding a total study population of 42,071 singleton births. Adjusted odds ratios (ORs) and 95% CIs were determined for the association between diabetes in pregnancy and cesarean delivery through multiple logistic regression, controlling for maternal age, race, education, number of prenatal care visits, length of gestation, birth weight, and a number of medical indications. RESULTS: Of the study population, 0.7% were pregnancies complicated by preexisting diabetes, 2.9% were pregnancies complicated by gestational diabetes, and 23.4% were cesarean deliveries. After controlling for confounders, including birth weight, cesarean delivery was strongly associated with both preexisting diabetes (OR [95% CI] 6.20 [4.47-8.61]) and gestational diabetes (1.71 [1.41-2.07]). The estimates remained essentially unchanged without birth weight in the model, and were substantially higher in analyses restricted to deliveries without common medical indications for cesarean delivery. CONCLUSIONS: Both preexisting and gestational diabetes increase the risk for cesarean delivery, independent of the effect of birth weight. The association is markedly greater among women without other medical indications for cesarean delivery. The increased risk of cesarean delivery for women with diabetes is mediated through other factors, which may include practice patterns and physician referrals to high-risk care.