Neural injury markers to predict neonatal complications in intrauterine growth restriction.

We assessed the neural injury markers (NIMs) in maternal and umbilical blood in preterm deliveries with and without intrauterine growth restriction (IUGR), and relationship between NIMs and neonatal complications. Deliveries between 24 and 34 weeks' gestation with (study group) and without (control group) IUGR were included to the study. Three NIMs (s100B, neurone-specific enolase [NSE] and alpha-foetoprotein [AFP]) were investigated in umbilical arterial, umbilical venous and maternal venous serum. Thirty-two IUGR and twenty-nine non-IUGR pregnancies with preterm delivery were included. Maternal and umbilical arterial s100B levels were significantly higher in the study group, whereas there was no relationship among IUGR, AFP and NSE levels. In the study group, umbilical venous s100B and NSE levels were associated with perinatal mortality (p = 0.012, 0.005, respectively), necrotising enterocolitis (NEC) (p = 0.001, 0.04, respectively) and need for intubation (p = 0.001, 0.007, respectively). Negative predictive values for perinatal mortality and NEC were 100% and for need for intubation it was 92.8% when both s100B and NSE were below the cutoff line determined by the receiver-operating characteristic curves. Perinatal mortality, NEC and need for intubation can be predicted by assessment of umbilical venous s100B and NSE measurement during birth in IUGR newborns.

Preterm premature rupture of membranes in singleton vs twin pregnancies: The latency periods and the clinical outcomes revisited.

Our objective was to compare the latency periods after preterm premature rupture of membranes (PPROM) and determine its subsequent impact on maternal and fetal outcomes for singleton and twin gestations > 24 weeks' and ≤ 34 weeks' gestation. Delivery in the first 72 h after the rupture of membranes was observed to be more frequent in the twin group (RR 1.98, 95% CI 1.06-3.73, p = 0.03); whereas the overall median latency periods were comparable (p = 0.06). Singleton pregnancies had shorter latency periods after 28 gestational weeks by comparison to the latency periods before 28 weeks. Gestational age of rupture of membranes and delivery and latency periods were comparable between spontaneous twin pregnancies and twin pregnancies after assisted reproductive technologies (ART). As a conclusion, singleton and twin pregnancies had similar outcomes after PPROM. The first 72 h is especially important for the outcome of twin pregnancies at when the delivery risk is high.

Cyclooxygenase immunohistochemical staining in the human ductus arteriosus after 24 weeks of gestational age.

Cyclooxygenase inhibitors (CI) which contained risks to fetal health were one of the most effective tocolytics. In order to indirectly investigate the effects of CI in human ductus arteriosus, immunohistochemical staining for cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) was evaluated in post-mortem fetuses with gestational ages between 24 and 34 weeks. Neither COX1 nor COX2 staining was related to gestational age. COX1 and COX2 staining in the vessel walls were not related to each other. COX1 staining in the endothelium, inner media and outer media were positively correlated with each other (COX1 endothelium vs IM staining Spearman's rho statistic [rs] = 0.721, p = 0.001; COX1 endothelium vs OM staining [rs] = 0.634, p = 0.004; COX1 IM vs OM staining [rs] = 0.931, p = 0.001). COX2 staining of endothelium was not correlated with either IM or OM staining. In conclusion, COX2 staining in the post-mortem specimens of human ductus arteriosus between 24 and 34 weeks is weak and limited to the endothelium.

Prenatal diagnosis of mosaicism identified in amniotic fluid cell cultures.

Chromosomal mosaicism in prenatal diagnosis is an important problem to be solved immediately and the probable phenotypic reflections should be explained to the family. We report two numerical and two structural mosaicisms detected in amniocyte cultures. The first fetus had a 47,XY,+mar[10]/46,XY[10] karyotype. The marker chromosome was shown to be derived from chromosome 15 by FISH method. The newborn had intrauterine growth retardation and cerebral thrombosis and died at the 29th day of age. The second fetus had a 45,X[4]/46,XX[26] karyotype. The parents refused cordocentesis and decided to terminate pregnancy in the 21st week. The third case, presented with bilateral large choroid plexus cysts, had a 46,XX, dup(1)(q22-q32)[9]/46,XX[21] karyotype. The parents' karyotypes were normal and the pregnancy was aborted in the 23rd week of gestation. The second structural abnormality was reported as 46,XX,t(6;11)(q23; p13)[3]/46,XX[20]. The mosaicism was detected in only one flask. The parents decided to continue pregnancy and cordocentesis could not be performed due to the fetal and placental position. The baby was born at term. Peripheral blood lymphocyte culture resulted in a 46,XX normal karyotype. Information and risks were explained to all families during genetic counseling. Mosaicism in prenatal diagnosis needs both detailed examination and follow up, since clinical findings depend on the type of abnormality.

High frequency of thrombophilic disorders in women with recurrent fetal miscarriage.

OBJECTIVES: Our purpose was to examine whether genetic thrombophilias are etiological factors for recurrent fetal miscarriage or not. STUDY DESIGN: We compared the rate of thrombophilic anomalies in women with unexplained recurrent fetal miscarriages to the rate of age-matched women with successful pregnancies as a case-control study. RESULTS: A total of 101 consecutive patients with 102 age-matched controls were included in the study. The rate of Factor V (FV) Leiden mutation, Factor (F) II mutation, protein S, protein C, antithrombin III deficiencies and overall thrombophilia in patients with recurrent fetal loss was significantly higher than the frequencies in control patients. CONCLUSION: Women with recurrent fetal miscarriages have an increased incidence of thrombophilia. Genetic thrombophilias may be one of the major etiological factors for recurrent abortion and fetal demise.

Acute fatty liver of pregnancy after aspirin intake.

Acute fatty liver is a rare but fatal complication of pregnancy. Here we describe a patient presenting with stupor and jaundice after aspirin intake at 35 weeks of gestation. Supportive management and delivery resulted in uneventful discharge of the patient and the newborn. Differential diagnosis and management of this condition are discussed.

Prenatal diagnosis of ranula at 21 weeks of gestation.

A fetal sublingual cystic lesion was diagnosed by routine prenatal ultrasonography at 21 weeks of gestation and followed up until term in a tertiary care center. Fetal growth was normal as was the amniotic fluid volume. Ex utero intrapartum treatment was performed and the cyst was aspirated to allow breathing and swallowing during planned Cesarean section. The cyst was totally excised when the newborn was 27 days of age and histological examination revealed a mucous cyst of the mouth floor.

Ratio of nuchal thickness to humerus length for Down syndrome detection.

OBJECTIVE: Ultrasonographic biometry markers are now being used clinically to adjust Down syndrome risk. The limitations are that the definitions of "abnormal" measurements used are arbitrary, thus reducing screening performance, and also that patient-specific Down syndrome risks cannot be calculated. We report a new ultrasonographic algorithm that is sensitive for Down syndrome detection and that estimates individual risk. STUDY DESIGN: Overall in fetal populations with Down syndrome the humerus length is decreased, whereas the nuchal thickness is increased relative to that of a normal population. The nuchal thickness/humerus length ratio therefore shows an even greater increase and magnifies the separation between Down syndrome and healthy groups. Prospective data were collected in midtrimester amniocentesis cases. A regression equation for the median nuchal thickness/humerus length ratio based on biparietal partial diameter was generated. The Down syndrome likelihood ratio, or the odds on the basis of the nuchal thickness/humerus length ratio (multiples of the median), was multiplied by the age-related risk to give the posterior Down syndrome risk. Charts for rapid estimation of individual Down syndrome risk on the basis of maternal age and the nuchal thickness/humerus length ratio were constructed. RESULTS: There were 94 cases of Down syndrome and 4700 cases in which the karyotype was normal. The mean (+/-SD) gestational age of the study population was 16.1 +/- 1.6 weeks. Thirty-three fetuses with Down syndrome and 68 karyotypically normal fetuses had gross anomalies. The equation for the expected median nuchal thickness/humerus length ratio was as follows: 10e(1.7163 - 0.0292) x BPD + 0.0003 x BPD2, where BPD is the biparietal diameter. In the overall study population the nuchal thickness/humerus length ratio and maternal age had a 79.8% detection rate at a 22.1% false-positive rate, compared with maternal age plus humerus length (sensitivity, 55.1%) or maternal age plus nuchal thickness (sensitivity, 66.7%) at the same false-positive rate. For women > or =35 years old the values were 80% and 22.0%, respectively. CONCLUSIONS: We report an ultrasonographic biometry algorithm that, in combination with maternal age, detects 79.6% of Down syndrome cases in a high-risk group. Individual Down syndrome risk can be quickly calculated at the bedside and made available to women who desire this information before making a decision on amniocentesis. On the basis of published standards, ultrasonographic biometry as described would be a cost-effective alternative to amniocentesis in this high-risk group.

Renal lymphangiomatosis during pregnancy: management with percutaneous drainage.

We report a unique case of exacerbation of renal lymphangiomatosis during pregnancy which was managed percutaneously until delivery. Renal lymphangiomatosis is a very rare benign disorder that might cause abdominal pain and rarely hypertension and hematuria. Surgical treatment options may result in nephrectomy. Percutaneous drainage of symptomatic renal lymphangiomas should be viewed as an efficient therapeutic option particularly when surgery is contraindicated.

Massive vulvar edema complicating a diabetic pregnancy.

A 29-year-old primiparous diabetic woman was admitted to hospital due to poor glucose control at 23 weeks' gestation. During hospitalization, bilateral vulvar edema developed and progressed within days. The only remarkable finding in relation to the edema was hypoalbuminemia and associated proteinuria. Despite repositioning the patient, and correction of hypoalbuminemia, edema persisted. Mechanical drainage was tried as an alternative, and resulted in complete resolution of the edema with no recurrence.

Middle cerebral artery Doppler velocimetric deceleration angle as a predictor of fetal anemia in Rh-alloimmunized fetuses without hydrops.

OBJECTIVE: The purpose of this study was to evaluate the screening performance of a new middle cerebral artery Doppler velocimetric index for the prediction of fetal anemia. STUDY DESIGN: Doppler velocimetry of the middle cerebral artery was performed before cordocentesis in 24 Rh-alloimmunized fetuses without hydrops on 52 occasions. The angle between the line describing the average slope during the diastolic phase of the cardiac cycle and the vertical, the middle cerebral artery standardized deceleration angle, was measured. The deceleration angle values were expressed in multiples of the median for gestational age. The screening performances of deceleration angle for the prediction of anemia (difference between expected mean hemoglobin level and measured value >/=2 g/dL) and severe anemia (hemoglobin deficit >/=5 g/dL) were determined. RESULTS: The mean (+/-SD) gestational age at cordocentesis was 28.6 +/- 5.7 weeks' gestation. The risk of fetal anemia increased with decreasing deceleration angle values. The sensitivity and false-positive rate for the detection of anemia in cases with no previous transfusions (one measurement per patient) were 72.0% and 13.3%, respectively; among those with one previous transfusion the values were 90.0% and 0.0%, respectively. For severe anemia the corresponding values were 100% and 0%, respectively, among those with no previous transfusions and 100.0% and 16.7%, respectively, among those with one previous transfusion. There was no risk of severe anemia when the angle was >0.9 multiples of the median. The risk of anemia was significantly reduced with an angle greater than the median for gestational age (deceleration angle >1.0 multiples of the median; relative risk, 0.09; 95% confidence interval, 0.02-0.37). The risk was significantly increased with an angle less than the median for gestational age (deceleration angle <1.0 multiples of the median; relative risk, 30.0; 95% confidence interval, 5.9-158.4). CONCLUSION: The risk of fetal hydrops is remote in the absence of severe anemia. With a new Doppler velocimetric index in the middle cerebral artery the risk of severe anemia was found to be low when the deceleration angle was >0.9 multiples of the median. Anemia can also be predicted with this index. The high sensitivities and acceptable false-positive rates support the potential clinical applicability of the method to reduce the reliance on cordocentesis in Rh alloimmunization. Our findings appear to validate the utility of the deceleration angle for the prediction of fetal anemia.

Splenic artery Doppler peak systolic velocity predicts severe fetal anemia in rhesus disease.

OBJECTIVE: We sought to determine whether main splenic artery Doppler peak systolic velocity predicts severe anemia in the rhesus-alloimmunized fetus. STUDY DESIGN: Splenic artery Doppler peak systolic velocity was obtained before cordocentesis in rhesus-alloimmunized fetuses. Normative values for mean peak systolic velocity based on gestational age were obtained cross-sectionally from a separate group of 144 normal fetuses. The peak systolic velocity values in the study group were expressed as multiples of the median for gestation, and threshold values were used as a screening test for severe anemia. The hemoglobin deficit was defined as mean hemoglobin for gestation minus measured hemoglobin. A hemoglobin deficit value of > or =5 g/dL was used to define severe anemia. We used the peak systolic velocity to screen for severe anemia in the overall study group and the subgroups with or without prior transfusions. RESULTS: The study population consisted of 26 singleton nonhydropic fetuses in which cordocentesis and Doppler measurements were performed on a total of 55 occasions. The mean gestational age and standard deviation at cordocentesis was 29.6 +/- 4.0 weeks. Severe anemia was noted in 20% of fetal cord blood specimens obtained. On the basis of a receiver operating characteristic curve, a peak systolic velocity of > or =1.4 multiples of the median had a detection rate of 100%, with a false-positive rate of 20.8% in the subgroup with no prior transfusion (relative risk, 4.8; 95% confidence interval, 2.2-10.5). For peak systolic velocity threshold of > or =1.50 multiples of the median, corresponding values in the group with one prior transfusion were 80% and 12.5%, respectively (relative risk, 2.5; 95% confidence interval, 1.2-5.3). There was no risk of severe anemia with a peak systolic velocity below the median for gestation. CONCLUSION: Fetal hydrops is rare, with a hemoglobin deficit of <5 g/dL. In the first such report the main splenic artery peak systolic velocity was noted to be a strong predictor of severe anemia. For the overall population, all such instances could be diagnosed while cordocentesis was performed 22.7% of the time. There is no risk of severe anemia with Doppler peak systolic velocities below the median for gestational age. The measurement is easily obtained and should be investigated as a clinical tool for minimizing the necessity for cordocentesis.

Perinatal outcome in adolescent pregnancies: a case-control study from a Turkish university hospital.

OBJECTIVE: To determine whether adolescent pregnancy is associated with increased risk for adverse pregnancy outcome. STUDY DESIGN: Retrospective case-control study which enrolled 1460 singleton adolescent pregnancies and 2980 controls, delivered at Hacettepe University Hospital between January 1990 and January 1998. RESULTS: Significantly higher rate of perinatal and severe perinatal complications were noted in adolescents. The presence of historical risks, multiparity, young age and lack of prenatal care were significant predictors of these complications. Exclusion of them except for age, revealed comparable perinatal and severe perinatal complications in both groups. CONCLUSION: Adolescent women who receive adequate prenatal care are at no greater risk of an adverse obstetric outcome than adult women of a similar sociodemographic background.

The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction.

OBJECTIVE: Our purpose was to determine whether the Doppler cerebroplacental ratio predicts perinatal outcome in fetuses at risk for intrauterine growth restriction. STUDY DESIGN: The middle cerebral and umbilical artery pulsatility index values were measured in 203 fetuses at risk for intrauterine growth restriction, of which 123 were delivered <3 weeks after the last Doppler examination. Perinatal outcome was categorized as (1) birth weight <10th percentile, (2) birth weight <5th percentile, (3) perinatal complications (meconium-stained fluid, cesarean section for fetal distress, 5-minute Apgar score <7, perinatal death, neonatal intensive care unit stay >24 hours, hypoglycemia, or polycythemia), (4) birth weight <10th percentile plus complications, and (5) birth weight <5th percentile plus complications. The cerebroplacental ratio (middle cerebral artery pulsatility index divided by umbilical artery pul-satility index) values were expressed as multiples of the normal median. Receiver-operator characteristic curves (sensitivity vs false-positive rates) were plotted for the prediction of each category of perinatal outcome and the areas under the curves were determined. Stepwise logistic regression analyses were used to determine whether the cerebroplacental ratio improved outcome prediction over umbilical artery Doppler imaging alone. RESULTS: There was a statistically significant increase in perinatal morbidity and mortality in cases with an abnormal cerebroplacental ratio. The areas under the receiver-operator curves characteristics for the prediction of perinatal outcome with use of the cerebroplacental ratio were statistically very significant. For birth weight <10th percentile we noted P <.001, with P <.0001 for each of the other 4 outcome categories. As shown by regression analyses, the cerebroplacental ratio appeared to improve the prediction of perinatal outcome compared with umbilical artery velocimetry alone. An interesting finding was that the cerebroplacental ratio did not appear to correlate significantly with outcome in fetuses at >34 weeks. CONCLUSION: Doppler identification of the fetal "brain-sparing" effect strongly predicts outcome in fetuses at risk for intrauterine growth restriction. The brain-sparing effect predicted perinatal problems only in fetuses <34 weeks' gestation at the Doppler examination.

Gestational age standardized nuchal thickness values for estimating mid-trimester Down's syndrome risk.

OBJECTIVE: Our aim was to develop gestational age standardized indices of fetal nuchal thickening. In addition, we wanted to develop a method for combining nuchal thickness data with maternal age for calculating individual Down's syndrome risk. METHODS: Nuchal thickness was measured prospectively in pregnancies undergoing genetic amniocentesis. A regression equation for expected median nuchal thickness based on the biparietal diameter (BPD) was developed. Nuchal thickness values were expressed as multiples of the median (MoM). Additionally, a new parameter, percentage increase in nuchal thickness (PIN) (measured minus expected nuchal thickness) X100/expected nuchal thickness, was used. Receiver operator characteristics curves for Down's syndrome detection based on nuchal thickness values expressed as MoM, PIN, and in mm were compared. Log10 transformation of MoM data resulted in a Gaussian distribution, and the Down's syndrome likelihood ratios were calculated based on the heights of the Gaussian curves. Likelihood ratios were also calculated based on PIN values. The screening efficiency of maternal age alone was compared to age plus MoM, and age plus PIN values by multiplying age-related risk by the likelihood ratio corresponding to the given nuchal thickness MoM or PIN values. RESULTS: There were 3,574 chromosomally normal and 50 Down's syndrome fetuses in the study. Both PIN and MoM values for nuchal thickness were closely correlated (R = 1.00, P<0.001) and each was poorly correlated with gestational age (R = 0.018, P = 0.28). The Down's syndrome screening efficiency of PIN, MoM, and nuchal thickness values in mm were not significantly different. The addition of nuchal thickness data to maternal age-related risk significantly improved the Down's syndrome screening efficiency: Area under the ROC curve for maternal age risk = 0.58, maternal age + PIN area = 0.79 (P<0.001 compared to maternal age alone) and for maternal age + MoM = 0.77 (P<0.005 compared to maternal age alone). CONCLUSIONS: The development of gestational age standardized nuchal thickness indices makes it possible to combine ultrasound and maternal age-related risk to derive individual Down's syndrome odds.

A new splenic artery Doppler velocimetric index for prediction of severe fetal anemia associated with Rh alloimmunization.

OBJECTIVE: We developed a new Doppler index for the noninvasive prediction of severe fetal anemia by means of Doppler velocimetry of the main splenic artery. STUDY DESIGN: Doppler velocimetry of the main splenic artery was performed in 85 healthy fetuses and in 22 nonhydropic study case patients (41 measurements) at risk for anemia from Rh sensitization. The deceleration angle between the line describing the average slope during the diastolic phase of the cycle and the vertical axis was measured and expressed in multiples of the median (MoM) for gestational age. Severe anemia was defined as a hemoglobin deficit (mean hemoglobin for gestational age minus measured hemoglobin) >/=5 g/dL. Anemia overall was defined as a hemoglobin deficit >/=2 g/dL. RESULTS: Mean gestational age at cordocentesis was 28.6 weeks. Severe anemia was noted on 7 occasions (12.6%) and anemia was noted on 21 (51.2%) occasions. There was a significant correlation between deceleration angle and hemoglobin deficit >/=2 g/dL (r = 0.5763, P <.0001) and also with hemoglobin deficit >/=5 g/dL (r = 0.6418, P <.0001). At deceleration angles <0. 90 MoM, a 90.5% sensitivity and a 30% false-positive rate were achieved for anemia detection. At a threshold deceleration angle of <0.60 MoM, the sensitivity for severe anemia was 100%, with an 8.8% false-positive rate. CONCLUSION: We report a new and sensitive Doppler velocimetric technique for predicting severe anemia. By means of splenic artery velocimetry, all cases of severe anemia could be identified before the development of hydrops, with a >91% reduction in the rate of cordocentesis.

New Down syndrome screening algorithm: ultrasonographic biometry and multiple serum markers combined with maternal age.

OBJECTIVE: We compared the Down syndrome screening efficiency of a new algorithm that combines humerus length measurement and serum analytes versus that of the traditional triple-analyte serum screen. STUDY DESIGN: Humerus length measurements were obtained prospectively in 1743 midtrimester (14 to 24 weeks) singleton fetuses before genetic amniocentesis. All patients had triple-marker serum screening before amniocentesis. Data on humerus length were expressed as multiples of the median, and were normalized by log transformation. Backward multiple stepwise logistic regression analysis was performed to determine which combination of biometry and serum markers best predicted fetal Down syndrome. The screening efficiency of the traditional triple-analyte algorithm was compared with that of a new multivariate gaussian algorithm that combined biometry and serum markers. RESULTS: There were 31 (1.8%) fetuses with Down syndrome in the study population. In the regression analysis humerus length, human chorionic gonadotropin, alpha-fetoprotein, and maternal age were significant predictors of Down syndrome, but unconjugated estriol was not. The combined algorithm (humerus length, human chorionic gonadotropin, and alpha-fetoprotein and age) was superior to the traditional triple screen for Down syndrome detection. The sensitivities at fixed false-positive rates were consistently higher in the combination than in the triple-screen protocol. For example, at a 10% false-positive rate the sensitivities were 65.0% and 52.3%, respectively. Similarly, at a 15% false-positive rate the sensitivities were 73.5% and 55.0%, respectively. CONCLUSION: A new screening algorithm combining humerus length and serum analytes was superior to the traditional triple screen. Although we used a high-risk population in this study, it is expected that the observed superiority of the combination screen would persist in a population of younger women. The development of a combined biometric and serum analyte screening algorithm for estimating individual odds could represent an advance in prenatal Down syndrome screening.

Silicone gel sheeting for stabilization of skin grafts.

BACKGROUND: Success of skin grafts depends on sufficient immobilization and early intervention for hematoma, seroma, or infection. OBJECTIVE: To stabilize and cover skin grafts with a tie-over technique using translucent silicone gel sheet. METHODS: Twenty-seven skin defects were resurfaced with skin grafts. A sterile silicone gel sheet was placed over the skin graft. Gel was fixed to the wound edges with skin staplers. RESULTS: All grafts healed without any complication. CONCLUSION: Using silicone gel sheeting on 27 skin grafts, we found that it is an effective method for stabilization and allows direct visualization of the graft in order to inspect hematoma-like complications.

An alternative for women initially declining genetic amniocentesis: individual Down syndrome odds on the basis of maternal age and multiple ultrasonographic markers.

OBJECTIVE: Our purpose was to develop a method of calculating the individual odds of Down syndrome on the basis of a combination of maternal age and multiple ultrasonographic parameters that can be used to counsel women at high risk who initially decline amniocentesis. STUDY DESIGN: Maternal age and ultrasonographic biometry data were collected prospectively on 3254 normal and 30 Down syndrome singleton fetuses between 15 and 24 weeks' gestation. Humerus length data were expressed as multiples of the normal median. Log transformation of the humerus length data permitted their expression in gaussian frequency distributions and the calculation of likelihood ratios for Down syndrome on the basis of humerus length. We also developed likelihood ratios on the basis of the degree of nuchal skinfold thickening and the presence or absence of hyperechoic fetal bowel and hypoplastic fifth digit. RESULTS: The ultrasonographic parameters and maternal age did not significantly correlate with each other and were significant independent predictors of Down syndrome. We therefore calculated the individual odds of Down syndrome by using the product of the age-related risk and the likelihood ratios associated with nuchal thickening, humerus length shortening, and the presence or absence of hyperechoic fetal bowel or fifth digit hypoplasia, respectively. At a Down syndrome risk level of >1:50, a 60.0% detection rate with 4.5% false-positive rate was observed with a screen-positive rate of 5.5%, positive predictive value of 1:10, and odds ratio (95% confidence interval) of 28.4 (12.8 to 64.0). CONCLUSION: This is the first report of individual odds calculation based on multiple midtrimester biometry parameters and maternal age. The screening efficiency is similar to that reported with triple-analyte serum screening. These data are useful for counseling women who are at increased Down syndrome risk and initially decline amniocentesis.