Fetal-maternal complications and their association with gestational thrombocytopenia.

OBJECTIVES: Thrombocytopenia is defined as a platelet count of < 150 × 109/L. It is a common hematologic abnormality during pregnancy. Evaluation and treatment of gestational thrombocytopenia can be both, expensive and invasive, and may result in an adverse outcome. The aim of our study was to investigate the incidence of perinatal complications in pregnancies complicated with gestational thrombocytopenia and to determine if the severity of maternal gestational thrombocytopenia implicates unfavorable perinatal outcome. MATERIAL AND METHODS: Over a period of three years, we identified 50 patients with gestational thrombocytopenia: 38 with platelet count between 50-100 × 109/L - classified as moderate thrombocytopenia, and 12 with platelet count of < 50 × 109/L - classified as severe thrombocytopenia. Fifty women with normal platelet count constituted the control group. Maternal complications and neonatal outcomes were compared. RESULTS: Neonatal thrombocytopenia occurred more often in pregnancies complicated with gestational thrombocytopenia (p = 0.041). Thrombocytopenia in previous pregnancy seems to be an important predicting factor for disease severity in the current pregnancy (p = 0.01). CONCLUSIONS: Gestational thrombocytopenia, even if severe, is not associated with adverse maternal or neonatal outcome. Moderate neonatal thrombocytopenia is more common in pregnancies complicated with severe gestational thrombocytopenia. The incidence of severe gestational thrombocytopenia is higher in patients with thrombocytopenia in previous pregnancy.

Fetal brain magnetic resonance imaging and long-term neurodevelopmental impairment.

OBJECTIVE: To determine the incidence of fetal brain injury by fetal brain magnetic resonance imaging (MRI) in pregnancies complicated with preterm labor (PL), preterm premature rupture of the membranes (PPROM), and intrauterine growth restriction (IUGR), and to compare fetal brain MRI with prenatal surveillance methods, and with immediate and long-term neurodevelopmental outcome. METHODS: Between February 2007 and January 2009, high-risk pregnancies were analyzed by MRI at 1.5 Tesla after 24 weeks of gestation at the Clinical Hospital Center Zagreb, Croatia. Long-term outcome was defined as neurodevelopmental outcome at 24 months. RESULTS: Among 70 pregnancies analyzed, 40.0% had abnormal fetal brain MRI. The highest incidence occurred in the PL group. There was no correlation between abnormal MRI and fetal surveillance methods (ultrasound, Doppler blood flow analysis, cardiotocography, biophysical profile) or immediate neonatal outcome (1-minute Apgar score, umbilical cord pH). Via MRI, fetal brain injury would have been diagnosed for 45.7% of fetuses with a long-term neurodevelopmental handicap. Binary logistic regression showed that, as compared with other surveillance methods, fetal brain MRI was the best predictor of long-term neurodevelopmental disability. CONCLUSION: PL, IUGR, and PPROM were associated with an early intrauterine CNS insult that was not accurately detected by existing prenatal testing options.

Postasphyxial renal injury in newborns as a prognostic factor of neurological outcome.

OBJECTIVE: To estimate if an acute postasphyxial renal injury in newborns could indicate a neurological outcome. METHODS: We conducted a prospective clinical trial on 50 full-term newborns with 5-minute Apgar score <7 (asphyxiated group) and a control group of 50 full-term newborns with 5-min Apgar score ≥ 7 (non-asphyxiated group). Renal function was assessed on the third day of life by serum values of creatinine, cystatin C and ß2-microglobulin (ß2M) and glomerular filtration rate (GFR). All newborns had brain and renal ultrasonography at early stages and were followed by Amiel-Tison Neurological Assassment (ATNA) throughout the first year of life. RESULTS: Mean GFR was significantly lower in asphyxiated than in non-asphyxiated group (22.08 ± 6.66 ml/min/1, 73 m(2) versus 35.42 ± 2.26 ml/min/1, 73 m(2); p < 0.001) and serum values of creatinine, cystatin C and ß2M were significantly higher (1.13 versus 0.66 mg/dl; 3.92 versus 1.52 mg/l; 1.53 versus 0.99 mg/l; p < 0.001). In asphyxiated group ATNA results throughout the first year of life significantly correlated with renal function (p < 0.01). A correlation of ATNA with Apgar score at 5 min, Sarnat and Sarnat staging of hypoxic ischemic encephalopathy and brain and renal ultrasonography has also been significant (p < 0.01). CONCLUSIONS: Our study showed a significant correlation between early impairment of renal function due to neonatal asphyxia with neurological outcome at the end of the first year of life.

Oxidative stress in small-for-gestational age (SGA) term newborns and their mothers.

This study used malondialdehyde (MDA) determination by HPLC and enzymatic assays for total serum peroxides and antioxidant capacity to evaluate oxidative stress in 47 healthy full-term small-for-gestational age (SGA) newborns vs 67 appropriate-for-gestational age (AGA) newborns. Blood samples were collected at delivery from umbilical cord artery and vein and from peripheral blood of the babies on the third day after birth. Blood samples of mothers were also collected and compared with blood of 29 normal non-pregnant women (NPW). Serum peroxide values were significantly higher in both groups of mothers than in NPW, decreasing towards the third day in AGA mothers, while persisting in SGA mothers. Antioxidant capacity of sera of both groups of mothers was lower than NPW. Both SGA mothers and babies had increased MDA at delivery, unlike AGA counterparts. MDA levels in umbilical vein were higher than in umbilical arteries, while immunohistochemistry revealed abundant presence of 4-hydroxynonenal (HNE)-protein adducts only in stroma of the SGA placenta. These results show that both mothers and babies are exposed to oxidative stress during and after delivery, which is more pronounced and persistent in the perinatal period of the SGA group, while lipid peroxidation in placenta could play a role in SGA pathophysiology.

Perinatal factors associated with the neurologic impairment of children born preterm.

OBJECTIVE: To determine the perinatal risk factors of long-term neurologic impairment for preterm infants. METHODS: A case-control study was conducted with 60 neurologically impaired and 60 healthy children, all born prematurely. RESULTS: There was no relation between neurologic impairment and maternal pregnancy complications or prenatal steroid administration, bacteriologic content of cervical smear, fetal presentation, fetal heart rate, or mode of delivery. Cerebral palsy was associated with early neurologic signs, perinatal asphyxia, neonatal septicemia, abnormal brain ultrasound findings, prolonged interval between rupture of membranes and delivery, and multiple placental lesions. Children with minimal cerebral dysfunction were more frequently first born. Multiple placental lesions, neonatal septicemia, abnormal brain ultrasound findings, and perinatal asphyxia were independently correlated with long-term neurologic impairment. CONCLUSION: Perinatal infection, perinatal asphyxia, and abnormal brain ultrasound findings seem to be risk factors for cerebral palsy whereas primigravidity seems to be correlated with minimal cerebral dysfunction.

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.

Long-term neurodevelopmental outcome of triplets.

OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in triplets and to find out possible connection between the outcome and perinatal events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24-144 months of age correlated with gestational age, birth weight, pregnancy complications, early neonatal period, neonatal cranial ultrasound, period of birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low birth weight and maternal age. In multivariate analysis, both cerebral palsy and minor disabilities correlate significantly with early neonatal complications, neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture of membranes (p=0.047). Children conceived spontaneously do worse than those born after assisted reproduction (p=0.004), those born in the time period 1996-2000 do better than those born before (p=0.021). Seventy-seven percent (77%) of newborns delivered in the time period 1996-2000 and after level 1 antenatal care was introduced, compared with 54% being delivered in the time period before 1996 and with less meticulous types of antenatal care, remain healthy (p=0.015). CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental complications. Stringent perinatal care might appear important determinant of their long-term outcome.

[Magnetic resonance imaging in fetal medicine]. / Uloga magnetske rezonancije u fetalnoj medicini.

Fast magnetic resonance imaging (MRI) has revolutionized our ability to image the fetus by using fast scanning techniques. Individual images are obtained in 300-400 s allowing fetal imaging without sedation due to reduced fetal movement artifacts. MRI is most useful for evaluation of the anomalies of fetal nervous and urinary system which are not fully clarified by ultrasound. The influence of magnetic resonance depending on gestational age on perinatal management nowadays is certain. This review discusses its current application and future developments.

[Why are collagenoses dangerous for pregnancy?]. / Zasto kolagenoze remete trudnocu?

It is well known that certain autoimmune disorders are associated with pregnancy loss. Increased perinatal and maternal mortality as well as increased incidence of disease deterioration during pregnancy are correlated to preconceptual disease regulation, incidence of super-imposed gestosis and renal failure and, recently, with some sorts of antiphospholipid antibodies. Indeed, investigators have attempted to establish an association between recurrent pregnancy loss and the presence of specific antibodies, irrespective of the presence of other clinical signs or complications of collagenosis. The most serious appears to be the presence of anticardiolipin antibodies and lupus anticoagulant while the significance of other autoantibodies that can be found appears to be much less defined. In the present paper pregnancy complicated by various collagenoses and therapeutic modalities are discussed.

Second trimester total human chorionic gonadotropin, alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy.

OBJECTIVE: To assess the value of alpha-fetoprotein (AFP), total human chorionic gonadotropin (ThCG) and unconjugated estriol in predicting certain complications of pregnancy other than fetal aneuploidy. STUDY DESIGN: Among 2384 women that underwent biochemical screening between 15 and 22 weeks of gestation, pregnancy outcome was evaluated in 677 women under 35 years of age according to serum marker levels by using cut-off points discriminative for Down syndrome or neural tube defect (NTD). RESULTS: High alpha-fetoprotein levels (MoM>/=2.0) were found to be significantly more frequent (P<0.05) in cases of fetal growth restriction (odds ratio=2.7), miscarriage (odds ratio=4.4) and intrauterine fetal death (odds ratio=5.8). High chorionic gonadotropin levels (MoM>/=2.02) were associated with intrauterine growth restriction (odds ratio=2.1; P<0.05), miscarriage (odds ratio=4; P<0.01), preterm birth (odds ratio=2.5; P<0.05), and intrauterine fetal death (odds ratio=4.2; P<0.01). Among pregnancies with intrauterine growth restriction and threatening preterm delivery, low unconjugated estriol levels (MoM

[Screening for Down syndrome using triple marker testing in the second trimester of pregnancy]. / Probir Downova sindroma trostrukim testom u drugom tromjesecju trudnoce.

The aim of this study was to check the validity of the biochemical screening of pregnancies with Down's syndrome during the second trimester of pregnancy, in order to reduce the incidence of invasive diagnostic procedures. We used the optimal balance between sensitivity and specificity to determine the "cut off" values to estimate the results of the biochemical screening. Between January 1995 and December 2000, 2000 pregnancies were checked by double (determining hCG and AFP serum levels) and triple test, (determining hCG, AFP and uE3 serum levels). Competitive radioimmunochemical procedures (2nd trimester Amerlax-M, Ortho Clinical Diagnostics, USA) were used. The risk of Down's syndrome was calculated by Prenata program (Ortho Clinical Diagnostics, USA). The "cut off" median MoM values in pregnancies with Down's syndrome were 0.73 (AFP); 2.02 (hCG) and 0.74 (nE3). The calculated risk was compared with possibility 1:300 to estimate the results of biochemical screening. Our results were checked in the cytogenetic laboratory where samples of amniotic fluid, that we also took, were sent. We observed lower AFP levels (0.96 +/- 0.09 MoM), uE3 levels (0.65 +/- 0.1 MoM) and higher levels of hCG (1.57 +/- 0.27 MoM) in pregnancies with Down's syndrome, in comparison with euploid pregnancies of the corresponding gestational age. With 1:200 risk, the sensitivity of triple test is 80%, with acceptable number of false-positive results. This cut-off value showed to be acceptable for separating positive from negative results. Invasive procedures should be performed in pregnancies with positive screening result, with the aim of getting the tissue sample of the fetus for further cytogenetic analysis.

Perinatal care improves the outcome of triplets.

OBJECTIVE: To compare pregnancy complications and neonatal outcome of 85 triplet gestations cared for during the 15 years in a single perinatal unit. METHODS: Pregnancies were divided in two groups according to the differences in the management plan and their outcomes were compared. Group I (N = 44) consisted of pregnancies cared from 1986 to 1995, using standard model of care: preventive hospitalization from the early second trimester or home bed rest with routine hospitalization after 28-32 weeks of pregnancy, routine clinical and ultrasound examinations, biophysical profile and non-stress tests starting at 28 weeks, expert neonatal care without free access to surfactant or to parenteral nutrition. Group II (N = 41) consisted of pregnancies cared for from 1986 to 2000 using modified care: preventive hospitalization from early second trimester or home bed rest with routine hospitalization after 32 weeks of pregnancy, biophysical profile, non-stress tests and pulsed doppler analysis of fetal umbilical artery, fetal aorta and middle cerebral artery blood flow from as early as 26 weeks, and neonatal care improved by free access to surfactant and parenteral nutrition. RESULTS: The mean gestational age, mean birth weight, the proportion of growth-retarded infants, the incidence of various maternal complications and immediate neonatal conditions as judged by APGAR scores did not differ between the groups. The incidence of deliveries up to 28 weeks was lower in the group II in comparison to group I, but the proportion of term and near term deliveries was lower. The incidence of cesarean sections was high (91.8%), but significantly increased cesarean delivery rate because of fetal distress was observed in the group II (P = 0.014). Infants in the group II had less frequently uneventful early neonatal period, mainly due to significantly increased conatal infection (P = 0.007) and neonatal encephalopathy rate (P = 0.001). However, perinatal mortality was decreased from 235% in the group I to 142% in the group II for newborns that reached 24 weeks of gestation or more. The decrease of perinatal mortality was observed also in the newborns born after 28 weeks of gestation (123% in the group I and 99% in the group II). None of the children weighing <1000 g died in utero in the group II. Early neonatal death of infants weighing >1500 g was significantly reduced in the group II (P = 0.048). CONCLUSION: Advances in neonatal care, but also the delivery of infants in better overall condition must be the explanation for improved outcome of triplet gestations managed by modified care. A higher cesarean section rate because of imminent fetal jeopardy as judged by not only fetal heart rate tracings, but also umbilical, aortic and middle cerebral artery flow analysis, could be the explanation for lowered perinatal mortality and significantly improved outcome in very preterm infants from triplet gestations.

[Endocrine, paracrine and electrophysiologic regulation of human labor]. / Endokrina, parakrina i elektrofizioloska regulacija radanja u ljudi.

The problem of labor and delivery, either at term or occurring prematurely, are among the greatest problems facing physicians nowadays. The understanding of the process of preparation and initiation of active labor is of utmost importance. Currently, the clinical methods to assess the changes of the uterus and cervix are still subjective, inaccurate and crude. Fortunately, a noninvasive method of transabdominal uterine muscle electrical activity analysis (electromiography, EMG) is digitalized and standardized in recognizing uterine contractility, and biochemical changes, as well as ultrasound and fluorescent methods, are emerging to estimate cervical preparation prior to active labor. Studies in humans indicate that uterine and cervical function an be accurately monitored during pregnancy and during the preparation for labor. In the review article all aspects of uterine muscle and uterine cervix architecture, preparation for labor and control of these processes are presented. The development of new methods of diagnosis for the patient in labor will improve our ability to diagnose preterm labor early enough to undertake all kinds of scientifically based methods and strategies specifically for the management of this condition.