Natural history of cervical intraepithelial neoplasia in pregnancy: postpartum histo-pathologic outcome and review of the literature.

BACKGROUND: To study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women. METHODS: A retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed. RESULTS: A total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9% of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4%, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5%, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8%, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9%) and no progression to invasive cancer was observed. CONCLUSIONS: CIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.

Abnormal maternal echocardiographic findings in triplet pregnancies presenting with dyspnoea.

OBJECTIVE: The objective of our study was to evaluate the prevalence of abnormal maternal echocardiographic findings in triplet pregnancies presenting with dyspnoea. STUDY DESIGN: Between 2003 and 2013, patients' records of 96 triplet pregnancies at our department were analysed including maternal and fetal outcome, echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After exclusion of triplet pregnancies with fetal demise before 23 + 0 weeks, selective feticide or missing outcome data, the study population consisted of 60 triplet pregnancies. All women with dyspnoea underwent echocardiography and measurement of NT-proBNP. RESULTS: Dyspnoea towards the end of pregnancy was observed in 13.3% (8/60) of all women with triplet pregnancies, and all of these women underwent echocardiography. The prevalence of abnormal echocardiographic findings in women with dyspnoea was 37.5% (3/8) with peripartum cardiomyopathy in one woman. Median serum NT-proBNP was significantly higher in women with abnormal echocardiographic findings compared with those without (1779 ng/ml, range 1045-6076 ng/ml vs 172 ng/ml, range 50-311 ng/ml; p < 0.001 by Mann-Whitney-U Test). CONCLUSION: We conclude that triplet pregnancies presenting with dyspnoea show a high prevalence of abnormal echocardiographic findings. Since dyspnoea is a common sign in triplet pregnancies and is associated with a high rate of cardiac involvement, echocardiography and evaluation of maternal NT-proBNP could be considered to improve early diagnosis and perinatal management.

Low incidence of early developmental dysplasia of the hip in universal ultrasonographic screening of newborns: analysis and evaluation of risk factors.

PURPOSE: Different timing and approaches to screening for developmental dysplasia of the hip (DDH) are used in the orthopaedic community. Thus ultrasonographic screening programs and reports based on clinical examinations produced differing incidence rates of DDH. Furthermore different risk factors and a change of incidence of DDH in the last decades were discussed. The purpose of this study was the evaluation of incidence and risk factors of the very early DDH in a modern cohort based on a universal ultrasound screening program. METHODS: We analysed the results of the screening program performed at our institution: 5,356 consecutive hips of newborns were screened ultrasonographically and clinically according to the system published by R. Graf within the first two postnatal weeks [1]. A set of risk factors was analysed by univariate and multiple linear regression models. RESULTS: Sonographic signs of developmental dysplasia of the hip were found in 0.24 % of the newborns. A significant negative influence of the risk factors birth weight, family history of DDH and female gender on the α-angle was found. Early or pre-term delivery showed a protective potential for DDH. CONCLUSIONS: Our data show a very low incidence of DDH in the first two postnatal weeks. Despite the significance of the risk factors analysed, it has to be considered that these factors only showed low impact on the risk of early DDH. In conclusion we favour universal ultrasound screening for DDH at the age of six to eight weeks.

Cerebral Lesions at Fetal Magnetic Resonance Imaging and Neurologic Outcome After Single Fetal Death in Monochorionic Twins.

BACKGROUND: Single fetal death (sFD) in monochorionic twin pregnancies is associated with substantial morbidity and mortality in the survivor. The aim of our study was to evaluate the rate of cerebral lesions detected at fetal Magnetic Resonance Imaging (MRI) and to correlate the results with the neurologic outcome of the survivors of monochorionic twin pregnancies after sFD. METHODS: Between 2005 and 2012, 11 monochorionic twin pregnancies with sFD and subsequent fetal MRI of the survivor were included. All neonates underwent neurologic assessment after birth and 56% of surviving infants underwent long-term neurologic assessment. MRI findings and neurologic outcome of the survivors were evaluated. RESULTS: Gestational age at sFD was 20.9 (±2.9) weeks; 55% (6/11) of survivors of monochorionic twin pregnancies after sFD showed cerebral lesions at fetal MRI; 72% (8/11) of all survivors had normal neonatal neurologic outcome: all survivors with normal fetal MRI and 50% of survivors with cerebral lesions at fetal MRI. Long-term neurologic assessment was normal in all tested patients with normal fetal MRI and in one of three tested patients with cerebral lesions at fetal MRI. CONCLUSION: Survivors of monochorionic twin pregnancies after sFD show a high rate of cerebral lesions at fetal MRI. The importance of cerebral lesions at fetal MRI in survivors after sFD in monochorionic twin pregnancies is uncertain. All tested survivors with normal fetal MRI showed normal neurologic outcome but only one of three survivors with cerebral lesions at fetal MRI showed normal long-term neurologic outcome.

Isolated Short Fetal Femur Length in the Second Trimester and the Association with Adverse Perinatal Outcome: Experiences from a Tertiary Referral Center.

OBJECTIVE: To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome. METHODS: This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5th percentile in a fetus with an abdominal circumference greater than the 10th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student's t-tests were used where appropriate. RESULTS: Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups. CONCLUSION: Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed.

The Effects of Hemodynamic Alterations on Lung Volumes in Fetuses with Tetralogy of Fallot: An MRI Study.

This study assessed whether the presence of tetralogy of Fallot (TOF) affects fetal lung development and whether these fetuses are at risk of pulmonary hypoplasia (PH). Furthermore, we investigated whether the degree of the concomitant pulmonary valve (PV) stenosis or a stenosis in the branch pulmonary arteries correlates with the fetal lung volume. Lung volumetry was performed in 16 fetuses with TOF who underwent MRI between gestational weeks 21 and 35 and in 22 controls. Fetal biometric data and the diameters of the PVs were evaluated by ultrasound. PV and branch pulmonary artery diameters were standardized (z-scores), and fetal lung volume/fetal body weight (FLV/FBW) ratios (ml/g) were calculated. The mean FLV/FBW ratio (0.031 ± 0.009 ml/g) in the TOF group was statistically significantly lower than in the control group (0.041 ± 0.009 ml/g; P = 0.003). None of the fetuses with TOF met the criterion for PH. FLV did not correlate with the degree of PV stenosis, but rather with the presence of a significant stenosis in at least one branch pulmonary artery. The presence of TOF moderately affects fetal lung growth, which is apparently not dependent on the degree of the PV stenosis. However, only an additional stenosis in at least one branch pulmonary artery was associated with a small FLV, but not with PH. Thus, reduced pulmonary blood flow may be offset by additional factors, such as the ability to establish a sufficient collateral system and to alter structural vascular size and, thus, pulmonary vascular resistance.

Individualized assessment of preterm birth risk using two modified prediction models.

OBJECTIVES: To construct two prediction models for individualized assessment of preterm delivery risk within 48h and before completed 32 weeks of gestation and to test the validity of modified and previously published models. STUDY DESIGN: Data on 617 consecutive women with preterm labor transferred to a tertiary care center for threatened preterm delivery between 22 and 32 weeks of gestation were analysed. Variables predicting the risk of delivery within 48h and before completed 32 weeks of gestation were assessed and applied to previously published prediction models. Multivariate analyses identified variables that were incorporated into two modified models that were subsequently validated. RESULTS: Two modified prediction models were developed and internally validated, incorporating four and six of the following variables to predict the risk of delivery within 48h and before completed 32 weeks of gestation, respectively: presence of preterm premature rupture of membranes and/or vaginal bleeding, sonographic cervical length, week of gestation, fetal fibronectin, and serum C-reactive protein. The correspondence between the actual and the predicted preterm birth rates suggests excellent calibration of the models. Internal validation analyses for the modified 48h and 32 week prediction models revealed considerably high concordance-indices of 0.8 (95%CI: [0.70-0.81]) and 0.85 (95%CI: [0.82-0.90]), respectively. CONCLUSIONS: Two modified prediction models to assess the risk of preterm birth were constructed and validated. The models can be used for individualized prediction of preterm birth and allow more accurate risk assessment than based upon a single risk factor. An online-based risk-calculator was constructed and can be assessed through: http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/clinical-software/prematurebirth/.

Isolated single umbilical artery: evaluating the risk of adverse pregnancy outcome.

OBJECTIVE: To evaluate if isolated single umbilical artery (SUA) diagnosed on second-trimester ultrasound has an independent risk association with adverse pregnancy outcomes. STUDY DESIGN: We compared 136 singleton pregnancies with isolated SUA with 500 consecutive singleton pregnancies with a three-vessel cord (3 VC). Pregnancies complicated by chromosomal abnormalities and other congenital malformations were excluded. The rates of intrauterine growth restriction (IUGR) defined as birth weight less than the 3rd percentile, small for gestational age (SGA) fetuses, defined as a birth weight lower than the 10th percentile and the incidence of very preterm deliveries before 34 weeks of gestation were compared between the two groups. Multivariable logistic regression analysis was performed to evaluate the risk association between SUA and adverse pregnancy outcomes, while controlling for potential confounders. RESULTS: Fetuses with isolated SUA had significantly lower birth weight (2942.5 ± 783.7 vs. 3243.7 ± 585.6 g, p = 0.002), and were delivered at an earlier gestational age (38.7 ± 3.4 vs. 39.5 ± 2.2 weeks, p < 0.001), when compared to fetuses with a 3 VC. Fetuses with isolated SUA were at higher risk for IUGR (15.4% vs. 1.8%, p < 0.001), SGA (20.6% vs. 4.4%, p < 0.001) and very preterm delivery (6.6% vs. 1.4%, p = 0.002). Using a multiple logistic regression model, isolated SUA was shown to be an independent risk factor for IUGR (adjusted OR = 11.3, 95% CI 4.8-25.6; p < 0.001) and very preterm delivery (adjusted OR = 5.0, 95% CI 1.8-13.8; p = 0.002). CONCLUSIONS: The presence of isolated SUA is independently associated with an increased risk for IUGR, SGA and very preterm delivery.

Congenital heart disease in monochorionic twins with and without twin-to-twin transfusion syndrome.

OBJECTIVE: This study aims to evaluate the prevalence of congenital heart disease (CHD) in monochorionic (MC) twin pregnancies with and without twin-to-twin transfusion syndrome (TTTS) in an unselected cohort, which underwent prenatal and postnatal echocardiography. METHOD: This was a retrospective cohort study including 451 MC twin pregnancies between 2002 and 2012. Complete outcome data were available for 381 pregnancies. All patients had prenatal echocardiography, and postnatal echocardiography was performed in all newborns with symptoms or to follow-up on prenatal findings. Data from prenatal and postnatal echocardiography and autopsy were analyzed. The classification of Houyel et al. was used for structural CHD. RESULTS: Structural CHD was diagnosed in 5.5% of all MC twins (42/762). Twins with TTTS showed a significant higher rate of CHD than unaffected twins (9.3% vs 4.7%; p = 0.03). Prenatal detection rate of CHD was 48%. Most common abnormalities were ventricular septal defects (VSD) (2.1%) followed by anomalies of the ventricular outflow tracts (1.3%) in the overall population and VSD (2.9%) and anomalies of the great arteries (2.9%) in the group with TTTS. CONCLUSION: MC twin pregnancies show a high prevalence of structural CHD (5.5%), especially those affected by TTTS. A detailed prenatal and postnatal echocardiography could be considered in these pregnancies.

Are fetuses with isolated echogenic bowel at higher risk for an adverse pregnancy outcome? Experiences from a tertiary referral center.

OBJECTIVE: The purpose of this study was to determine the risk of poor perinatal outcome in normal karyotype second-trimester fetuses with the sonographic finding of isolated echogenic bowel. METHOD: Medical records, ultrasonographic findings and outcome details were reviewed for 97 cases of isolated fetal echogenic bowel, after excluding cases of aneuploidy and major congenital anomalies, and compared with a cohort of 400 fetuses without pathologic intra-abdominal findings. RESULTS: The incidence of echogenic bowel during the 14-year study period was 0.8%. Eighty (82.5%) pregnancies resulted in healthy, live-born infants. Congenital infection and cystic fibrosis was reported in 6.2% and 4.4%, respectively. The incidence of intrauterine growth restriction and intrauterine fetal demise was significantly higher in the group of isolated echogenic bowels compared with the control group (9.9% versus 1.3%, p ≤ 0.001; 8.9% versus 0.5% p ≤ 0.001). CONCLUSION: Echogenic bowel is a risk factor for an adverse pregnancy outcome, even in normal karyotype fetuses without congenital anomalies. This information should be considered when counseling patients after midtrimester echogenic bowel is diagnosed.

Maxillary dental arch biometry: assessment with fetal MR imaging.

OBJECTIVE: To define normal growth of the fetal maxillary dental arch using magnetic resonance imaging. METHOD: Four hundred twenty-four consecutive fetuses (18 to 37 weeks) with a morphologically normal anatomy or only minor malformations, not affecting bone growth and face anatomy were included. On axial T2-weighted images the dental arch length and width were measured. The measurements were correlated with gestational age and the biparietal diameter (BPD) of the fetal head using correlation and regression analysis. RESULTS: A linear growth relationship was observed between the dental arch length and gestational age (r = 0.86; p = < 0.0001; y = -1.85 + 0.75 × gestational age) and the dental arch width and gestational age (r = 0.92; p = < 0.0001; y = -2.19 + 1.05 × gestational age). A significant correlation was found between the dental arch length and the BPD (r = 0.903; p = < 0.0001) and the dental arch width and the BPD (r = 0.927; p = < 0.0001). The interobserver variability showed good agreement for the dental arch length (intraclass coefficient 0.981; r = 0.963) and width (intraclass coefficient 0.987; r = 0.974), respectively. CONCLUSION: We present a nomogram for the in utero assessment of the fetal dental arch. These data may help in the early detection of abnormal dental arch development.

Mean, lowest, and highest pulsatility index of the uterine artery and adverse pregnancy outcome in twin pregnancies.

OBJECTIVE: The objective of the study was to assess the use of mean, lowest, and highest pulsatility index (PI) of the uterine arteries to screen for adverse pregnany outcome in twin pregnancies. STUDY DESIGN: This was a screening study of 423 twin pregnancies. Relationship between PI at 20-22 weeks and adverse pregnancy outcome was evaluated. RESULTS: Mean, lowest, and highest PI above the 95th centile were significant risk factors for preeclampsia and adverse pregnancy outcome in monochorionic and dichorionic twins. We calculated a sensitivity for preeclampsia for mean, highest, and lowest PI of 35%, 29%, and 27%, respectively. CONCLUSION: Increased mean, lowest, and highest PI is associated with a higher risk of preeclampsia and adverse pregnancy outcome in twins. We observed the highest sensitivity and specificity by using highest PI. The high incidence of preeclampsia in twins makes it attractive to use the PI of the uterine artery for risk stratification in twins.

Relevance of gamma-glutamyltransferase--a marker for apoptotic balance--in predicting tumor stage and prognosis in cervical cancer.

INTRODUCTION: Recent large epidemiologic population-based studies identified gamma-glutamyltransferase (GGT) as a marker for increased cervical cancer incidence. Furthermore, high levels of GGT seem to increase the risk of progression of high-grade cervical dysplasia to invasive carcinoma. Therefore, we evaluated the association between pre-therapeutic serum GGT levels, tumor stage and prognosis in patients with cervical cancer. MATERIALS AND METHODS: In this multi-center trial, pre-therapeutic GGT levels were examined in 692 patients with cervical cancer. GGT levels were correlated with clinico-pathological parameters. Patients were assigned to previously described GGT risk groups and uni- and multivariable survival analyses were performed. RESULTS: GGT serum levels were associated with FIGO stage (p<0.0001) and age (r=0.2, p<0.0001) but not with lymph node involvement (p=0.85), and histological type (p=0.98). High-risk GGT group affiliation (p=0.01 and p<0.0001) was associated with poor disease-free and overall survival in a univariate analysis, but not in a multivariable Cox-regression model (p=0.59 and p=0.171). We further investigated the association between prognosis and GGT and observed a linear correlation between GGT and prognosis. Therefore we were not able to identify a clear prognostic cut-off value for GGT in patients with cervical cancer. CONCLUSIONS: High GGT--a marker for apoptosis and cervical cancer risk--is associated with advanced tumor stage in patients with cervical cancer.

Influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies.

OBJECTIVE: To evaluate the influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies. METHODS: 200 twin pregnancies were included in the study. 157 nondiabetic pregnant women with twin gestations and 43 twin pregnancies with gestational diabetes mellitus (GDM) with viable fetuses born after 24 weeks of gestation were enrolled. Influence of maternal age, body-mass-index at the time of the oral glucose tolerance test, parity, smoking, chorionicity, gestational age at delivery and diagnosis of GDM on weight discrepancy of the twins was evaluated. RESULTS: Mean weight discrepancy of all analyzed twin pregnancies was 285 grams (+/- 231), relative weight discrepancy was 11.3% (+/- 8.6). Univariate regression analyses showed that GDM, chorionicity and gestational age at delivery were significantly associated with weight discrepancy. In the multivariate model only diagnosis of GDM was significantly associated with weight discrepancy. CONCLUSION: Twin pregnancies with insulin requiring gestational diabetes seem to have less birth weight discrepancy than twin pregnancies with normal glucose tolerance.

Breech presentation: a retrospective analysis of 12-years' experience at a single center.

OBJECTIVE: To investigate neonatal outcome after breech presentation in term pregnancies. STUDY DESIGN: Data from 1345 term breech deliveries over a 12-year study period were retrospectively reviewed. Neonatal morbidity and mortality were compared by route of delivery. RESULTS: We investigated 1345 term breech deliveries. A total of 1041 patients (77.4%) attempted a vaginal delivery; of these, 808 (60.1%) were delivered vaginally and 233 patients (17.3%) who failed at vaginal birth underwent cesarean section. The other 304 women (22.6%) were delivered by a planned cesarean section. No statistical differences were found in the incidence of low 5-minute Apgar scores and arterial cord blood pH values