Hypocalcemia is common in the first 48 h of life in ELBW infants

BACKGROUND: The incidence of early hypocalcemia in extremely low birthweight (ELBW) infants is unknown because the distribution of serum calcium values in this population is not defined. OBJECTIVE: To determine the range of serum calcium values in ELBW infants during the first 48 h of life and the risks associated with low values. DESIGN/METHODS: Retrospective analysis of all ELBW infants admitted on day 1 of life from April 2004 to October 2006. Demographic variables, therapy, serum calcium (Ca), pH, albumin, and blood ionized Ca were recorded. RESULTS: There were 381 Ca levels obtained from 111 patients. Mean Ca was 6.90 mg/dL (1.73 mmol/L) (5(th)-95(th) percentile: 5.16-8.80). Ca levels rose after 24 h of life. Almost one quarter (23.1%) of the Ca levels were low by current standards. The majority of subjects (59.9%) had at least one hypocalcemic value. CONCLUSIONS: Serum Ca values are lower in ELBW infants and inconsequential. Thus, hypocalcemia should be re-defined for ELBW infants.     

Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study

Prematurity, neonatal asphyxia, hypomagnesemia, and advanced maternal diabetes are traditional risk factors for hypocalcemia in infants of diabetic mothers (IDMs). The aim of this study was to determine the relative contribution of these factors separately and combined in a cohort of diabetic pregnancies managed prospectively in the recent 9 years and to find accurate predictors of neonatal hypocalcemia in infants of diabetic mothers. We hypothesized that these factors plus low cord blood calcium (Ca) concentration allow prediction of IDMs who develop neonatal hypocalcemia. We studied 186 IDMs (White class B-RT); gestational age (GA, weeks) was by last menstrual period, confirmed +/- 2 weeks by Ballard score. The goals of glycemic control were: preprandial blood glucose less than 100 mg/dl and 90-minute postprandial blood glucose less than 140 mg/dl. Apgar scores, and cord, 24-, 48- and 72-hour serum calcium (Ca) (mg/dl) and magnesium (Mg; mg/dl) were determined. In univariate analysis, lowest serum Ca correlated with cord blood Ca (r = 0.48, p less than 0.001), GA (r = 0.37, p less than 0.001), and 1-minute Apgar score (r = 0.18, p = 0.09), but did not correlate with cord Mg or with advanced White class. In multiple regression, cord Ca and GA were dominant effects and other variables became insignificant. Lowest Ca (mg/dl) was predicted as follows: lowest Ca = 34.05 - 3.22 (Ca cord) - 0.84 (GA) + 0.10 (GA) (Ca cord). This equation predicts neonatal hypocalcemia (lowest Ca less than 8 mg/dl) with a sensitivity of 72% and a specificity of 75%. Thus, GA and cord Ca allow determination of IDMs at risk for neonatal hypocalcemia.     

Increasing amniotic fluid magnesium concentrations with stable maternal serum levels: a prospective clinical trial

OBJECTIVE: To compare the effect of prolonged maternal intravenous MgSO4 administration on amniotic fluid and serum concentrations of magnesium over time in preterm labor patients. STUDY DESIGN: Patients at 24-34 weeks of singleton gestation who presented with contractions (> 8 in 60 minutes) underwent amniocentesis to rule out intrauterine infection after signing an informed consent form. Some of these women who were clinically judged to have preterm labor received intravenous MgSO4: a 4-g loading dose followed by a 2 g/h maintenance dose. For technical reasons some patients had amniocentesis performed before initiation of MgSO4 (controls), while others had the procedure during tocolytic therapy (study subjects). Duration of treatment until amniocentesis was recorded, and blood samples were drawn at the time of amniocentesis. Maternal serum and amniotic fluid magnesium levels were measured using a colorimetric end point method. Data were evaluated using the Student t test and linear regression analysis. RESULTS: Mean magnesium levels in maternal serum rose from 1.74 +/- 0.2 mg/dL in controls to 4.01 +/- 0.4 mg/dL in the study group. Mean magnesium levels in Mean magnesium levels in amniotic fluid were 1.41 +/- 0.18 mg/dL in the controls versus 2.28 +/- 0.53 mg/dL in the treatment group. Duration of MgSO4 treatment ranged from 3 to 22 hours. Amniotic fluid magnesium concentrations increased significantly during therapy (correlation coefficient = 0.89; p < 0.001), while maternal serum levels remained stable over time (correlation coefficient between maternal serum levels and time = -0.39; p=0.34). CONCLUSION: Although maternal serum magnesium levels remained stable with intravenous MgSO4 therapy, concentrations continued to rise in amniotic fluid over time. However, amniotic fluid magnesium levels never exceeded maternal serum concentrations during the study period.     

Evaluation of creatine kinase level during long-term tocolysis

OBJECTIVE: This study was performed to evaluate serum creatine kinase (CK) levels during tocolytic therapy. METHODS: A retrospective study was performed in 27 patients who were treated with intravenous tocolytic agents for more than one week. The first-line tocolytic agent was ritodrine hydrochloride, followed by concomitant magnesium sulfate (MgSO4). The serum CK level was measured on admission and every week thereafter. The patients were divided into the normal CK (group 1) and abnormal CK (> 150 IU/L) (group 2) groups. RESULTS: Seventeen patients received both ritodrine hydrochloride and MgSO4. The CK levels in all patients rose significantly from 58.4 +/- 30.8 IU/L on admission to 116.0 +/- 68.7 IU/L on day 7 (p = 0.002). Abnormal elevation of CK occurred in 7 (25.9%) of the 27 patients. Significant differences were found between groups 1 and 2 in the total doses of ritodrine and MgSO4 (p = 0.046 and p = 0.0028, respectively). All patients in group 2 received ritodrine in combination with MgSO4 (p = 0.018). CONCLUSION: When tocolytic therapy continued for more than 1 week, nearly one-fourth of patients showed an increase in CK level above the normal range.     

Calcium metabolism in pre-eclampsia.

OBJECTIVES: To study calcium metabolism in pre-eclampsia and normotensive gravid women. METHOD: Ten milliliters of heparinized blood samples and 24-h urine samples were collected from 50 pre-eclamptic and 50 normotensive primigravidae. Blood samples were studied for calcium uptake, intracellular calcium level and calcium-dependent adenosine triphosphatase activity of red blood cell ghost. Urinary calcium excretion was estimated from the 24-h urine samples. These values were compared in the two groups. RESULTS: The mean gestational age at recruitment was similar in both the groups. The mean maternal age was 24.28 +/- 2.41 years in pre-eclamptic and 23.48 +/- 4.16 years in normotensive women. In pre-eclampsia 24-h urinary calcium excretion (71.20 +/- 22.95 mg/day) and calcium-dependent ATPase activity (10.78 +/- 2.40 nmol/Pi/mg protein/min) was significantly lower compared to normotensive primigravidae (calcium excretion = 189.24 +/- 57.06 mg/day; Ca2+-dependent ATPase = 12.64 +/- 2.42 nmolPi/mg /protein per min; P < 0.001). Intracellular calcium levels and calcium uptake at 10 min by red blood cells were significantly higher in pre-eclampsia (P < 0.05). Calcium uptake by red blood cells at 20 and 30 min was similar in both groups. CONCLUSION: Pre-eclampsia is associated with increased levels of intracellular calcium, decreased calcium-dependent ATPase activity of erythrocytes and hypocalciuria.     

Disorders of maternal calcium metabolism implicated by abnormal calcium metabolism in the neonate

Normal fetal and neonatal calcium homeostasis is dependent upon an adequate supply of calcium from maternal sources. Both maternal hypercalcemia and hypocalcemia can cause metabolic bone disease or disorders of calcium homeostasis in neonates. Maternal hypercalcemia can suppress fetal parathyroid function and cause neonatal hypocalcemia. Conversely, maternal hypocalcemia can stimulate fetal parathyroid tissue causing bone demineralization. We report two asymptomatic women, one with previously unrecognized hypoparathyroidism and the other with unrecognized familial benign hypercalcemia, who were diagnosed when their newborn infants presented with abnormalities of calcium metabolism. J.B. was born at 34 weeks' gestation with transient hyperbilirubinemia and thrombocytopenia. At 1 month of age he had severe bone demineralization, cortical irregularities, widening and cupping of the metaphyses, and lucent bands in the scapulae. The total serum calcium and phosphorus were normal with an ionized calcium of 5.4 mg/dL (4.6-5.4). His alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were all increased. P.B., mother of J.B., had no symptoms of hypocalcemia either prior to, or during this pregnancy. She had severe hypocalcemia and hyperphosphatemia, laboratory values typical of hypoparathyroidism. J.N. presented at 6 weeks of age with new onset of seizures and tetany secondary to severe hypocalcemia. The serum phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone levels were normal. At 15 weeks of age his calcium was slightly elevated with a low fractional excretion of calcium. P.N., mother of J.N., had no symptoms of hypercalcemia either prior to, or during this pregnancy. Her serum calcium was 12.7 mg/dL and urine calcium was 66.5 mg/24 hr, with a low fractional excretion of calcium ranging from 0.0064 to 0.0073. P.N. has a brother who previously had parathyroid surgery. Both J.N. and P.N. meet the diagnostic criteria for familial benign hypercalcemia. These cases illustrate the important relationships between maternal serum calcium levels and neonatal calcium homeostasis. They emphasize the need to assess maternal calcium levels when infants are born with abnormal serum calcium levels or metabolic bone disease.     

Tocolytic magnesium sulfate toxicity and unexpected neonatal death.

A 31-year-old primigravida with twins had spontaneous rupture of the membranes at 32 weeks' gestation. On admission, because of contractions, the mother was started on tocolytic magnesium sulfate (MgSO4) along with betamethasone and prophylactic antibiotics. About a day later, she was found to have magnesium toxicity. Her serum total magnesium level was 9.0 mg/dl. Tocolysis was immediately discontinued. At cesarean delivery the following day, twin A, a female, died at 30 minutes of age despite a vigorous resuscitation. Although the preceding fetal heart rate patterns had been reassuring and the umbilical blood gases were normal, quite unexpectedly, the Apgar scores were 1/1/0. An autopsy revealed no anatomic abnormalities. Twin B, a female who survived, was also intubated at delivery. During her stay in the Neonatal Intensive Care Unit, she was found to have modestly elevated levels of serum cardiotroponin T. In our opinion, it is probable that the death of twin A can be directly attributed to magnesium sulfate toxicity. Neonatologists who attend deliveries should be aware that unexpected death may occur in babies who were exposed to high doses of tocolytic MgSO4.     

Maternal magnesium level effect on preterm labor treatment

Abstract

Objective: To compare the initial serum magnesium levels between preterm labor (PL) and control groups and to evaluate MgSO4 treatment response in preterm labor group according to their initial serum magnesium levels.

Methods: Hundred women diagnosed as preterm labor between 28 and 33 weeks of gestation and 100 non-complicated pregnant women were enrolled in this prospective study. Total basal serum magnesium levels were measured in both the groups. After a 6?g intravenous bolus of MgSO4, a dose of 2?g/h was given as an infusion in the preterm labor group.

Results: Serum magnesium levels were significantly lower in preterm labor group (p?<?0.001). The active contractions stopped in 69 (73,4%) preterm patients. The basal Mg level was significantly lower in this preterm group (1.6 versus 1.9, respectively, p?<?0.001). Predictive value of basal magnesium level measurement for magnesium tocolysis response was calculated by receiver operating characteristic analyses with 95% confidence interval. Positive predictive and negative predictive values were found as 64.5% and 92.5%, respectively, with 83% accuracy, when cut-off magnesium value was taken as a <1.75?mg/dl (sensitivity?=?80%, specificity?=?84,1%).

Conclusions: Basal magnesium levels in preterm labor had a predictive value in evaluating MgSO4 tocolysis response. It may help to select patients who are appropriate for MgSO4 tocolysis.     

Effects of short-time (3 months) tibolone treatment on bone turnover in postmenopausal women

This study was planned to elucidate the effects of tibolone on bone biochemistry parameters in postmenopausal women at 3 month intervals. There were 56 healthy postmenopausal women enrolled in the study. The women had not received hormone replacement therapy (HRT) previously. Tibolone (2.5 mg/day) was prescribed for 3 months. Serum osteocalcin, calcium, phosphorus, alkaline phosphatase, creatinine and urine calcium, phosphorus creatinine, deoxypyridinoline were measured, and physical examinations were performed at the onset and at the end of the study. The mean serum osteocalcin level and deoxypyridinoline/creatinine (DPD/cr) ratio both decreased significantly (50.3% and 22.9%; P=0.012 and P=0.001, respectively). The slight decreases in serum alkaline phosphatase (4.5%) and urine calcium (13.6%) levels were not statistically significant. There was a positive correlation between DPD/cr and urine calcium ( r=0.66, P=0.001). We conclude that bone formation may be increased early by tibolone after short-term administration.     

Predictors of methotrexate treatment failure in ectopic pregnancy

OBJECTIVE: To determine the possible predictors of methotrexate treatment failure in ectopic pregnancy. STUDY DESIGN: Fifty-eight patients diagnosed with ectopic pregnancy were treated with methotrexate (50 mg/m2). Selected variables in the history of the patients, the signs and symptoms at the time of admission, transvaginal ultrasound findings and serum beta-human chorionic gonadotropin (beta-hCG) levels on day 1 and 3 were evaluated in a logistic regression model to predict treatmentfailure, defined as tubal rupture. RESULTS: Methotrexate treatment failed in 9 cases (15.5 %). Another 9 cases (15.5%) required a second dose of methotrexate, and no treatment failures were observed in these cases. The presence of subchorionic tubal hematoma in the ectopic gestation (OR = 22.9, CI = 2.7-194.7, p = 0.004), the presence of an embryo (OR = 24, CI = 2.1-269, p = 0.01) and day 1 serum beta-hCG level > or = 3,000 mIU/mL (OR = 27.1, CI = 2.1-342.5, p = 0.01) were the main predictors of treatment failure. Follow-up serum beta-hCG levels > or =3,500 mIU/mL (OR = 42.9, CI = 4.3-421) on day 3 were significant predictors of treatment failure. Follow-up risk score was calculated as > 4 on day 3 by adding day 3 serum beta-hCG level to the admission score. Only 1 treatment failure (2.4%) occurred in 42 patients with an admission score of nil. No treatment failure occurred in 39 patients whose follow-up score was nil. The increase in admission risk (OR = 32.1, CI = 3.8-270, p = 0.001) and follow-up risk (OR = 9.2, CI = 2.4-35.2) were significant predictors of treatment failure. CONCLUSION: Transvaginal ultrasound findings are as important as serum beta-hCG level on the first day of methotrexate treatment. In unruptured cases, day 3 serum beta-hCG level is important to reevaluate the decision to continuefollow-up or perform early surgery for increased risk of treatment failure.     

Prostacyclin and thromboxane levels in women with severe preeclampsia undergoing magnesium sulfate therapy during antepartum and postpartum periods.

OBJECTIVE: To study effects of magnesium sulfate (MgSO(4)) on prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)) levels in women with severe preeclampsia during antepartum and postpartum periods. METHODS: Women with severe preeclampsia were randomized into two groups. Patients in Group A were continuously infused with MgSO(4) for 24 hours postpartum. In Group B, MgSO(4) administration was discontinued when urinary output was of > or =100 ml/hr for 2 consecutive hours. Patient demographic data were collected. Venous blood was drawn at time of MgSO(4) administration and 24 hours after delivery. Plasma levels of 6-keto-PGF1alpha and TXB(2), stable metabolites of PGI(2) and TXA(2), were measured by enzyme-linked immunosorbent assay (ELISA). Data are presented as mean +/- SE, and analyzed by paired t-test. RESULTS: A total of 50 patients were recruited, with 27 in Group A and 23 in Group B. There were no statistical differences for demographic data between the two groups with regards to maternal age; gestational age; systolic and diastolic blood pressures at admission, 12 hours postpartum, and 24 hours postpartum; and mode of delivery. Platelet counts were all within the normal range at the time of enrollment. MgSO(4) was administered for an average of 10 hours postpartum in Group B. Maternal blood pressures returned to normal or close to normal levels in both groups at 24 hours postpartum. 6-keto PGF1alpha levels were significantly decreased 24 hours after delivery compared with the levels at enrollment in both groups, (Group A: 98 +/- 13 vs. 180 +/- 28 pg/mL; Group B: 142 + 17 vs. 194 +/- 31 pg/mL, p < 0.05, respectively). However, there was no difference detected between the two groups. TXB(2) levels were not different between group A and Group B at the time of enrollment, 38 +/- 9 vs. 33 +/- 8 pg/mL, and 24 hours postpartum, 26 +/- 5 vs. 25 +/- 3 pg/mL, respectively. CONCLUSIONS: Administration of MgSO(4) does not affect prostacyclin and thromboxane levels in the maternal circulation in women with preeclampsia during antepartum and postpartum periods. We speculate that a higher level of prostacyclin before delivery may reflect compensatory effects of this vasodilator to offset increased maternal blood pressure during pregnancy.     

Behavior the lipid spectrum following complete ovariectomy and subsequent substitution with estradiol valerate or norethisterone acetate

In a prospective trial the effects of oophorectomy and following administration of estradiol valerate (2,0 mg/day) or norethisterone acetate (5,0 mg/day) on the blood lipids were investigated during the late postoophorectomy time. After complete ovarectomy 52 women (42-49 years old) were randomized in two groups and substituted with these steroids from the 7. to 12. month after operation. Before total estrogen excretion/24 h urine, serum levels of estradiol and testosterone and the maturation value were studied. The blood levels of total-, HDL- nnd LDL cholesterol and triglycerides were markedly higher 2 and 6 months after castration than before. Norethisterone acetate depressed transitorily the total cholesterol and longer the HDL cholesterol, the triglycerides were increased 6 months after administration. A long lasting norethisterone acetate substitution in postmenopausal women should be below 5 mg/day.     

Calcium sensing receptor in pregnancies complicated by gestational diabetes mellitus

Introduction

Infants born from mothers with Gestational diabetes mellitus (GDM) experience several complications, including a higher rate of postnatal hypocalcemia. In this study, we investigated the association between calcium sensing receptor (CaSR) and neonatal hypocalcemia observed in GDM pregnancies.

Methods

Our study consisted of 58 pregnant women with GDM and 40 healthy women and their neonates. CaSR placental expression was evaluated with immunohistochemistry and Western Blot. Three CaSR single nucleotide polymorphisms, A986S, R990G, Q1011E, were evaluated in neonate's genomic DNA. Serum Ca, P, Mg, 25(OH)D and PTH were measured in cord blood and at 2nd day of life.

Results

GDM neonates had lower mean cord blood Ca levels than controls (2.47 ± 0.21 mmol/l vs 2.59 ± 0.13 mmol/l, p = 0.001) while 15.5% developed postnatal hypocalcemia. CaSR expression was lower in GDM than in healthy placentas (p < 0.001). In the GDM group, reduced CaSR immunostaining in the syncytiotrophoblast (p = 0.042) and extravillous cytotrophoblasts (p = 0.002) was associated with lower Ca cord blood levels. Moreover, the absence of the S allele of the A986S polymorphism was associated with lower serum Ca levels both at birth (AA:2.41 ± 0.23 mmol/l, AS + SS: 2.57 ± 0.12 mmol/l, p = 0.002) and at 2nd day of life (AA:2.05 ± 0.22 mmol/l, AS + SS: 2.20 ± 0.18 mmol/l, p = 0.019).

Conclusions

Our results showed that CaSR is under-expressed in GDM compared with healthy placentas and this alteration may be associated with the lower Ca levels measured in cord blood of GDM infants. Placental CaSR seems to exert a local effect in fetal Ca homeostasis, which is dissociated from its contribution to the regulation of Ca homeostasis in postnatal life.     

What is the appropriate intravenous dose of vitamin E for very-low-birth-weight infants?

The Committee on Fetus and Newborn of the American Academy of Pediatrics (AAP) has endorsed 1 to 2 mg/dl as the normal range of serum tocopherol level. Our Cochrane review has shown that vitamin E supplementation resulting in levels >3.5 mg/dl, but not < or =3.5 mg/dl, significantly reduces the risk for severe retinopathy among very-low-birth-weight (VLBW) infants examined but increases the risks of sepsis and of necrotizing enterocolitis among infants treated for >1 week. As a fixed daily intravenous dose of vitamin E results in an inverse relationship between serum level and birth weight and is a risk for both low and high serum tocopherol levels, a dose adjusted for current weight appears more judicious than a fixed dose per day. Based on currently available data the AAP and the American Society for Clinical Nutrition currently recommend a routine intake of 2 ml/kg/day of MVI Pediatric (2.8 IU/kg/day) in VLBW infants (maximum of 5 ml/day or 7 IU/day).     

Etiology of third-trimester maternal hyperuricemia in nonpreeclamptic twin gestations

OBJECTIVE: To determine whether the higher maternal serum uric acid levels observed in the third trimester of nonpreeclamptic twin gestations result from increased uric acid production or decreased renal excretion. METHODS: Thirty-four nonpreeclamptic subjects with twin gestations were analyzed, along with 34 singleton controls matched for age, ethnicity, prepregnancy weight, height, and gestational age. For each subject, a serum sample and 24-hour urine specimen were obtained in the third trimester. Serum and urine uric acid and creatinine levels were determined, as well as total 24-hour urine uric acid, uric acid clearance, creatinine clearance, fractional uric acid clearance, and net tubular uric acid absorption. RESULTS: The twin gestation group had significantly higher maternal serum uric acid levels (5.2 +/- 1.2 compared with 4.0 +/- 1.0 mg/dL, P <.001) and maternal serum creatinine levels (0.7 +/- 0.2 compared with 0.5 +/- 0.1 mg/dL, P <.001) than the paired singleton group. This was associated with greater 24-hour urine uric acid excretion (688.7 +/- 167.0 compared with 597.7 +/- 164.2 mg, P =.04) and 24-hour urine creatinine excretion (1268.4 +/- 249.9 compared with 1161.2 +/- 277.1 mg, P =.03) in the twin group. No differences were seen between the groups in uric acid clearance, creatinine clearance, fractional uric acid clearance, filtered uric acid load, or net uric acid absorption. CONCLUSION: The higher maternal serum uric acid levels observed in the third trimester of nonpreeclamptic twin gestations result in part from increased uric acid production, as reflected in the increased daily uric acid excretion.     

高频振荡通气及联合硫酸镁治疗新生猪重症胎粪吸入综合征的实验研究

目的　探讨高频振荡通气 (HFOV)及联合硫酸镁 (Mg SO4 )治疗合并持续肺动脉高压(PPH)的重症胎粪吸入综合征 (MAS)模型氧合、循环功能 ,血镁浓度及肺组织病理改变。　方法　以2 0 %胎粪混悬液制备重症 MAS模型 ,健康新生猪随机分为 3组 ,即模型 HFOV治疗组 (HFOV组 ,n= 6 ) ,HFOV+Mg SO4 治疗组 (HFOV+Mg SO4 组 ,n=7) ,HFOV对照组 (对照组 ,n=5 ) ,HFOV+Mg SO4 组同时静脉持续泵入 Mg SO4 。监测生命体征、血气、血镁浓度。　结果　 (1) HFOV和 HFOV+Mg SO4 治疗均使 MAS模型动脉血氧分压 (Pa O2 )、动脉血氧 /肺泡血氧分压比 (a/ APO2 )增加 ,肺泡-动脉血氧分压差 (A- a DO2 )、肺内分流 (Qs/ Qt)降低 ,治疗 30 min与治疗前比差异有非常显著性 (P<0 .0 1)。HFOV组各时间点 Pa O2 、a/ APO2 低于对照组 ,A- a DO2 、Qs/ Qt高于对照组 (P<0 .0 5 )。HFOV+Mg SO4 组治疗 12 0 m in后上述指标与对照组差异无显著性 (P>0 .0 5 )。 (2 )尽管氧合功能改善 ,单独 HFOV对重症 MAS的 PPH无降低作用 ,联合 Mg SO4 治疗 30 min即可有效降低 PPH(P<0 .0 5 ) ,并保持疗效。(3) HFOV组较 HFOV+Mg SO4 组有明显肺出血 ,出血沿肺段、小叶分布 ,两组病理评分差异有显著性 (P<0 .0 5 )。 (4) HFOV+Mg SO4 组血镁浓度较治疗     

Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: a 2-year, double-blind, placebo-controlled study

OBJECTIVE: To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio. DESIGN: A 2-year randomized, double-blind, placebo-controlled study. SETTING: Endocrinology outpatient department. PATIENT(S): Fifty-six postmenopausal, hysterectomized women. INTERVENTION(S): Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years. MAIN OUTCOME MEASURE(S): At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated. RESULT(S): Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was -32.5% (95% CI: -20.1; -44.8%) for CEE; -16.4% (95% CI: -3.6; -29.2%) for raloxifene at 150 mg/day; and -15.4% (95% CI: -1.0; -29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point. CONCLUSION(S): Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.     

Hypocalciuria in women with preeclampsia]

To assess the significance of hypocalciuria in pregnant women, 24-hour urinary calcium excretion and the calcium/creatinine ratio (mg/g) in random urine samples were measured with a Toshiba TDA-30R autoanalyzer in the following 4 groups: 3 mild preeclamptic patients, 5 severe preeclamptic patients, 4 patients with intrauterine growth retardation (IUGR), and 10 healthy pregnant women. The mean 24-hour urinary calcium excretion in the 4 groups was 44.3 +/- 21.3 mg/day, 11.6 +/- 2.7 mg/day, 161.4 +/- 80.4 mg/day and 145.0 +/- 45.0 mg/day, respectively. Calcium excretion was significantly lower in the mild and severe preeclamptic patients than in the women with IUGR and the normal pregnant women. There was also a significant difference between the value in the mild and severe preeclamptic patients. The mean calcium/creatinine ratio in random urine samples was 53 +/- 30 mg/g, 18 +/- 5.6 mg/g, 192 +/- 85 mg/g and 169 +/- 70 mg/g, respectively. Also, such significant as 24-hour urinary calcium excretion were found in the mean calcium/creatinine ratio. From these results we conclude that determination of the 24-hour urinary calcium excretion or the calcium/creatinine ratio in random urine samples is a reliable index of preeclampsia.     

Maternal serum cytokine levels in pregnancies complicated by PROM

OBJECTIVE: The aim of the study was to evaluate the maternal serum cytokines levels in pregnancies complicated by premature rupture of membranes (PROM). MATERIALS AND METHODS: Maternal serum of IL-1 beta, IL-4, IL-6, IL-8 and TNF-alfa levels were assessed in patients with PROM between 24-34 weeks of pregnancy (n = 45). Control group consisted of healthy pregnant women (n = 41) at 24-34 weeks of gestation. Serum cytokines concentrations were measured by commercial available enzyme-linked immunosorbent assays. C-reactive protein level and WBC were estimated in both groups. RESULTS: Compared to healthy pregnant, the group of patients with PROM had significantly higher serum levels of IL-1 beta (0.76 pg/ml vs 0.41 pg/ml, p = 0.022), TNF-alfa (1332.46 pg/ml vs 58.01 pg/ml, p < 0.00001) and IL-8 (15.79 pg/ml vs 0 pg/ml, p < 0.00001). CRP concentration and WBC were also significantly higher in serum of pregnant women with PROM then in healthy ones (CRP: 10 mg/l vs 0 mg/l, p = 0.043; WBC: 13,188 +/- 3625/mm3 vs 9132 +/- 1913/mm3, p < 0.00001). No significant differences in IL-6 and IL-4 levels were found between groups. CONCLUSION: Differences in serum maternal levels of cytokines between patients with premature ruptures of membranes and healthy pregnant women suggest that reasons and/or consequences of PROM results in changes in immunological system.     

Calcium-phosphorus-magnesium homeostasis in pregnant women after renal transplantation.

OBJECTIVE: The aim of the study was the assessment of calcium-phosphorus-magnesium homeostasis in pregnant women after renal transplantation. METHODS: The study covered 64 pregnant women in the third trimester of gestation including: 33 women after renal transplantation (the study group) and 31 healthy pregnant women (the control group). Women from both groups were at the similar age: 30.8+/-4.7 vs. 31.3+/-5.0 years (NS) and at the same gestational age 34.8+/-2.4 vs. 35.3+/-2.6 weeks (NS). The mean body mass index (BMI) in the women from the study group before pregnancy was 21.49+/-2.81 vs. 22.1+/-3.02 in the control group (NS), BMI before delivery was 25.43+/-3.05 vs. 26.0+/-3.35 (NS), the percentage of the BMI increase during pregnancy was 18.7+/-7.68 vs. 17.65+/-7.13 (NS) and BMI increase during gestation was 3.93+/-1.56 vs. 3.90+/-1.54, respectively (NS). Arterial blood pressure at the time of blood samples collection for biochemical tests was 151.4+/-26.8/92.5+/-16.9 in women from the study group comparing to 115.0+/-6.0/68.0+/-7.0 mmHg (P<0.001) in the patients from the control group. The maximal blood pressure during pregnancy was 169.2+/-20.7/102.7+/-14.0 vs. 118.0+/-7.0/70.0+/-8.0 mmHg (P<0.001), respectively. We estimated serum levels of: total Ca, ionized Ca(2+), inorganic phosphorus (P(i)), Mg, total protein, albumin and blood morphology. Moreover, urine levels of Ca, P(i), Mg and protein were assessed. RESULTS: The pregnant women after renal transplantation presented increases in serum concentrations of total Ca (2.54+/-0.20 vs. 2.16+/-0.10 mmol/l; P<0.001) and ionized Ca(2+) (1.322+/-0.104 vs. 1.12+/-0.07 mmol/l; P<0.001) and the decrease in P(i) level (1.013+/-0.211 vs. 1.10+/-0.16 mmol/l; P<0.05), total protein (59.3+/-7.0 vs. 65+/-5 g/l; P<0.001) and albumin (461.6+/-65.65 vs. 493.2+/-59 micromol/l; P<0.05). Moreover, in the study group drop in red blood cells count to 3.71+/-0.56 vs. 4.01+/-0.35 x 10(12)/l (P<0.02) in the control group was detected. Despite increased volume of 24-h urine collection in the kidney recipients we observed significantly decreased urine 24-h calcium excretion 2.47+/-0.92 vs. 6.72+/-3.49 mmol (P<0.001) and simultaneous increase in urine Mg excretion 3.422+/-1.025 vs. 2.18+/-0.52 mmol/24 h (P<0.001). There was no difference in urine 24-h P(i) excretion between the study and the control group. The pregnant renal transplant recipients presented proteinuria of 1.19+/-1.9 g/24 h. CONCLUSIONS: Women after kidney grafting present vital aberrations in calcium-phosphorus-magnesium homeostasis during pregnancy. The most significant changes are associated with calcium metabolism (high increase in serum Ca levels and impairment of renal elimination of calcium). The observed changes may be influenced by the doses of immunosuppressive agents and disturbed renal function.