Incarceration of the Gravid Uterus - a Rare Condition not to be Missed.

BACKGROUND: Incarceration of a gravid uterus (IGU) is a rare manifestation in obstetrics that may be associated with serious complications. CASE: We report on a 29-year-old patient at 34+2 weeks' gestation who presented with HELLP syndrome. IGU had been initially diagnosed in our department at 23+6 weeks' gestation. Urgent cesarean section was performed taking into account the specific characteristics of IGU. A healthy premature child was born. With the prior knowledge of IGU no complications during delivery occurred and mother and child had favorable outcomes. CONCLUSION: IGU is a rare condition in pregnancy that should not be overlooked. Early diagnosis and treatment of IGU can prevent serious complications to the mother and child during pregnancy and delivery. In this report, we discuss the specific peculiarities of an incarcerated uterus that need to be considered in this regard. HINTERGRUND: Ein Uterus incarceratus ist eine seltene Manifestation in der Geburtshilfe, welche mit schwerwiegenden Komplikationen einhergehen kann. FALL: Wir berichten über eine 29-jährige Patientin, die sich mit 34+2 Schwangerschaftswochen (SSW) mit einem HELLP-Syndrom in unserer Klinik vorgestellt hat. Die Erstdiagnose des inkarzerierten Uterus wurde in unserer Klinik mit 23+6 SSW gestellt. Aufgrund unserer Vorkenntnis über diese Diagnose konnte nun die dringend indizierte Sectio caesarea unter Berücksichtigung der spezifischen Merkmale in modifizierter Technik durchgeführt werden. Es wurde ein gesundes Frühgeborenes geboren. Es traten während der Geburt keine Komplikationen auf und Mutter und Kind hatten einen günstigen Verlauf. SCHLUSSFOLGERUNG: Ein Uterus incarceratus ist eine seltene Manifestation in der Schwangerschaft, welche nicht übersehen werden sollte. Eine frühzeitige Diagnose und Behandlung kann schwerwiegende Komplikationen für Mutter und Kind während der Schwangerschaft und unter der Geburt verhindern. Wir diskutieren die spezifischen Besonderheiten eines Uterus incarceratus, die hierbei zu berücksichtigen sind.

Percent error of ultrasound examination to estimate fetal weight at term in different categories of birth weight with focus on maternal diabetes and obesity.

BACKGROUND: Sonography based estimate of fetal weight is a considerable issue for delivery planning. The study evaluated the influence of diabetes, obesity, excess weight gain, fetal and neonatal anthropometrics on accuracy of estimated fetal weight with respect to the extent of the percent error of estimated fetal weight to birth weight for different categories. METHODS: Multicenter retrospective analysis from 11,049 term deliveries and fetal ultrasound biometry performed within 14 days to delivery. Estimated fetal weight was calculated by Hadlock IV. Percent error from birth weight was determined for categories in 250 g increments between 2500 g and 4500 g. Estimated fetal weight accuracy was categorized as accurate ≤ 10% of birth weight, under- and overestimated by > ± 10% - ± 20% and > 20%. RESULTS: Diabetes was diagnosed in 12.5%, obesity in 12.6% and weight gain exceeding IOM recommendation in 49.1% of the women. The percentage of accurate estimated fetal weight was not significantly different in the presence of maternal diabetes (70.0% vs. 71.8%, p = 0.17), obesity (69.6% vs. 71.9%, p = 0.08) or excess weight gain (71.2% vs. 72%, p = 0.352) but of preexisting diabetes (61.1% vs. 71.7%; p = 0.007) that was associated with the highest macrosomia rate (26.9%). Mean percent error of estimated fetal weight from birth weight was 2.39% ± 9.13%. The extent of percent error varied with birth weight with the lowest numbers for 3000 g-3249 g and increasing with the extent of birth weight variation: 5% ± 11% overestimation in the lowest and 12% ± 8% underestimation in the highest ranges. CONCLUSION: Diabetes, obesity and excess weight gain are not necessarily confounders of estimated fetal weight accuracy. Percent error of estimated fetal weight is closely related to birth weight with clinically relevant over- and underestimation at both extremes. This work provides detailed data regarding the extent of percent error for different birth weight categories and may therefore improve delivery planning.

Influence of Sonographic Fetal Weight Estimation Inaccuracies in Macrosomia on Perinatal Outcome.

OBJECTIVE: To evaluate the influence of inaccurate sonographic fetal weight estimation in macrosomia on the mode of delivery and neonatal outcome (NO). METHODS: In 14 633 pregnancies between 2002 and 2016, this retrospective study evaluated the association between sonographic fetal weight estimation, true birth weight (BW), mode of delivery (primary cesarean section [pCS], secondary cesarean section, vaginal delivery, and operative vaginal delivery rates) and NO parameters (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit [NICU] admission, shoulder dystocia). Singleton pregnancies > 37 + 0 weeks with ultrasound-estimated fetal weight (EFW) within 7 days before delivery were included. The study population was divided into four groups: Group 1 (false-negative): EFW < 4000 g/BW ≥ 4000 g; Group 2 (true-positive): EFW ≥ 4000 g/BW ≥ 4000 g; Group 3 (false-positive): EFW ≥ 4000 g/BW < 4000 g; and Group 4 (true-negative): EFW < 4000 g/BW < 4000 g. RESULTS: As expected, the highest secondary cesarean section (sCS) rate was found in Group 2 (true-positive) (30.62 %), compared with only 17.68 % in Group 4 (true-negative). The sCS rate in the false-positive Group 3 was significantly higher (28.48 %) in comparison with the false-negative Group 1 (21.22 %; OR 1.48; 95 % CI, 1.16 to 1.89; P = 0.002). In comparison with the true-negative Group 4, univariate analyses showed significantly higher rates for sCS in all other groups: odds ratio (OR) 2.06 for Group 2 (95 % CI, 1.74 to 2.42; P < 0.001), 1.85 for Group 3 (95 % CI, 1.54 to 2.22, P < 0.001), and 1.25 for Group 1 (95 % CI, 1.05 to 1.49; P < 0.01). No significant differences were found for NO between Groups 1 and 3 for the parameters 5-min Apgar < 7 (P = 0.75), pH < 7.1 (P = 0.28), or NICU admission (P = 0.54). However, there was a significantly higher chance for shoulder dystocia in Group 1 compared with Group 3 (OR 4.58; 95 % CI, 1.34 to 24.30; P = 0.008). CONCLUSION: Sonographic EFW inaccuracies in fetal macrosomia appear to have a greater impact on the mode of delivery than birth weight itself. Underestimation of fetal weight may be associated with a higher probability of shoulder dystocia.

[COVID-19 in Pregnancy - a Risk for the Unborn Child?] / COVID-19 in der Schwangerschaft: Ursache für eine intrakranielle Blutung bei einem Frühgeborenen?

Geburtskliniken werden zunehmend mit an Covid-19 erkrankten Schwangeren konfrontiert. Dies stellt Geburtshelfer vor große Herausforderungen, da einige Fragestellungen noch nicht ausreichend wissenschaftlich erforscht sind. Über Covid-19 während der Schwangerschaft und seine Auswirkungen auf das ungeborene und neugeborene Kind ist nicht viel bekannt.

The cumulative impact of parity on the body mass index (BMI) in a non-selected Lower Saxony population.

OBJECTIVES: During the last decade obesity has been continuously rising in adults in industrial countries. The increased occurrence of perinatal complications caused by maternal obesity poses a major challenge for obstetricians during pregnancy and childbirth. This study aims to examine the association between parity, pregnancy, birth risks, and body mass index (BMI) of women from Lower Saxony, Germany. METHODS: This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony's statewide quality assurance initiative. Mothers were categorized according to BMI as normal weight (18.5 to <25 kg/m2) or obese (≥30 kg/m2). RESULTS: Most of the mothers in this study population were either in their first (33.9%) or second pregnancy (43.4%). The mean age of women giving birth for the first time was 28.3 years. Maternal age increased with increasing parity. The proportion of pregnant women with a BMI over 30 was 11% in primiparous women, 14.3% in second para, 17.3% in third para and 24.1% in fourth para or more women. Increasing parity was positively correlated with the incidence of classical diseases related to obesity, namely diabetes mellitus, gestational diabetes, hypertension, pregnancy-related hypertension and urinary protein excretion. An increased risk of primary or secondary cesarean section was observed in the obese women, particularly during the first deliveries. CONCLUSIONS: There is a positive and significant correlation between parity and increased maternal BMI. The highest weight gain happens during the first pregnancy. The rate of operative deliveries and complications during delivery is increased in obese pregnant women.

Ultrasound Fetal Weight Estimation in Diabetic Pregnancies.

OBJECTIVES: To evaluate different formulas for estimating fetal weight in diabetic pregnancies. METHODS: This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight. RESULTS: Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small. CONCLUSIONS: Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range.

Fetal Weight Estimation Using Automated Fractional Limb Volume With 2-Dimensional Size Parameters: A Multicenter Study.

OBJECTIVES: To develop new fetal weight prediction models using automated fractional limb volume (FLV). METHODS: A prospective multicenter study measured fetal biometry within 4 to 7 days of delivery. Three-dimensional data acquisition included the automated FLV that was based on 50% of the humerus diaphysis (fractional arm volume [AVol]) or 50% of the femur diaphysis (fractional thigh volume [TVol]) length. A regression analysis provided population sample-specific coefficients to develop 4 weight estimation models. Estimated and actual birth weights (BWs) were compared for the mean percent difference ± standard deviation of the percent differences. Systematic errors were analyzed by the Student t test, and random errors were compared by the Pitman test. RESULTS: A total of 328 pregnancies were scanned before delivery (BW range, 825-5470 g). Only 71.3% to 72.6% of weight estimations were within 10% of actual BW using original published models by Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337) and INTERGROWTH-21st (Ultrasound Obstet Gynecol 2017; 49:478-486). All predictions were accurate by using sample-specific model coefficients to minimize bias in making these comparisons (Hadlock, 0.4% ± 8.7%; INTERGROWTH-21st, 0.5% ± 10.0%; AVol, 0.3% ± 7.4%; and TVol, 0.3% ± 8.0%). Both AVol- and TVol-based models improved the percentage of correctly classified BW ±10% in 83.2% and 83.9% of cases, respectively, compared to the INTERGROWTH-21st model (73.8%; P < .01). For BW of less than 2500 g, all models slightly overestimated BW (+2.0% to +3.1%). For BW of greater than 4000 g, AVol (-2.4% ± 6.5%) and TVol (-2.3% ± 6.9%) models) had weight predictions with small systematic errors that were not different from zero (P > .05). For these larger fetuses, both AVol and TVol models correctly classified BW (±10%) in 83.3% and 87.5% of cases compared to the others (Hadlock, 79.2%; INTERGROWTH-21st, 70.8%) although these differences did not reach statistical significance. CONCLUSIONS: In this cohort, the inclusion of automated FLV measurements with conventional 2-dimensional biometry was generally associated with improved weight predictions.

Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses.

PURPOSE: To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses. MATERIALS AND METHODS: In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated. RESULTS: 41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor. CONCLUSION: Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery.

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term.

OBJECTIVE: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term. METHODS: This was a retrospective study of 1008 appropriate-for-gestational age (AGA) term fetuses. Doppler measurements [umbilical artery (UA), middle cerebral artery (MCA), and cerebroplacental ratio (CPR)] and computerized CTG (cCTG) with STV analysis were performed prior to active labor (≤ 4 cm cervical dilatation) within 72 h of delivery. The association between Doppler indices and STV values with adverse perinatal outcome was analyzed using univariate regression analysis. RESULTS: No significant association between Doppler parameters and the need for secondary cesarean delivery (CD) or operative vaginal delivery (OVD) was shown. Regarding fetuses delivered by CD due to fetal distress, regression analyzes revealed significantly higher UA PI MoM. However, the differences in MCA PI MoM and CPR MoM were not statistically significant. Fetuses with the need for emergency CD showed significantly higher UA PI MoM, lower MCA PI MoM and lower CPR MoM. Neonates with a 5-min Apgar score < 7 had significantly lower MCA PI MoM and neonatal acidosis (UA pH ≤ 7.10) showed a significant association with UA PI MoM. None of the assessed outcome parameters were significantly associated to STV. CONCLUSION: Doppler indices assessed close to delivery in low-risk fetuses at term show a moderate association with adverse outcome parameters, whereas STV does not appear to predict poor perinatal outcome in this group of fetuses.

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in small-for-gestational age fetuses at term.

OBJECTIVE: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term. METHODS: In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0 weeks' gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72 h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis. RESULTS: There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV. CONCLUSION: STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.

Can Sonographic Fetal Biometry Predict Adverse Perinatal Outcome?

OBJECTIVE: To evaluate the association of sonographic fetal biometry (sonographic head circumference (soHC), sonographic abdominal circumference (soAC), estimated fetal weight (EFW)) with mode of delivery and adverse perinatal outcome. METHODS: Singleton pregnancies with a gestational age ≥ 37 weeks and an ultrasound examination with complete biometric parameters within 7 days before delivery were retrospectively included. The association between soHC, soAC, EFW and fetal (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit (NICU) admission, shoulder dystocia (ShD)) and maternal (obstetric intervention (OI): caesarean or vaginal operative delivery, obstetric anal sphincter injury syndrome (OASIS), postpartum hemorrhage (pph)) adverse outcomes were analyzed using univariate and multivariate logistic regression analyses. RESULTS: 12 396 women were included and 3479 (28.07 %) needed an OI. Multivariate analyses demonstrated significant contributions for the prediction of OI by soHC and soAC, whereas EFW did not reach significance. The highest OR was shown for soHC (1087, p < 0.001). ShD occurred in 73 (0.59 %) of the deliveries. Multivariate analyses showed that significant contributions for the prediction of ShD were provided only by soAC (OR 1460, p = 0.007). For the other maternal and neonatal adverse outcome parameters, no significant association with the biometric measurements could be demonstrated in the multivariate analyses. The overall detection rates for the prediction of adverse perinatal outcome by the different biometric parameters and EFW were poor. CONCLUSION: Obstetric management decisions should not be based solely on measurements of biometric parameters or EFW.

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB-related skeletal disorders in three fetuses and a 106-year-old exhibit.

The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. These characteristics allowed the diagnosis of Piepkorn type of osteochondrodysplasia in four new cases, three fetuses of 15 to 22 weeks and one 106-year-old museum exhibit. Piepkorn type of osteochondrodysplasia has been assigned to the giant cell chondrodysplasias such as atelosteogenesis type 1 (AO1) and boomerang dysplasia (BD). Analysis of the Filamin B gene in 3p14.3, which is associated with these disorders, allowed the identification of the first FLNB mutations in Piepkorn type of osteochondrodysplasia. The heterozygous missense mutations, found in the three fetuses, were located in exons 28 and 29, encoding the immunoglobulin-like repeat region R15, one of three mutational hot spots in dominant FLNB-related skeletal disorders. Direct preparations and alcian blue staining revealed single upper and lower arm and leg bone primordia, preaxial oligodactyly, and polysyndactyly with complete fusion and doubling of the middle and end phalanges II-V to produce eight distal finger rays. Considering the unique clinical features and the extent of underossification, Piepkorn type of osteochondrodysplasia can be regarded as a distinct entity within the AO1-BD-POCD continuum.

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth.

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

Longitudinal z Score Distribution in Sonographic Fetal Biometry: Influence of Examiner and Experience.

OBJECTIVES: To analyze the influence of examiners and their experience on the quality of biometric measurements via the evolution of z scores in a longitudinal multicenter study. METHODS: This retrospective study included 4607 sonographic fetal biometric examinations performed by 18 examiners at the beginning of their sonography training. To analyze the quality of biometric measurements, z scores comparing the individual measurements with the expected values from a standard population were computed. To investigate the effect of examiners and their experience, we applied a multivariable regression analysis via generalized additive mixed models. RESULTS: Mean z scores for biparietal diameter, abdominal circumference, and femur length were statistically different from the expected value of 0 (P < .001); no significant differences were found for head circumference measurements. Regression analyses showed a significant effect of the number of examinations on the distribution of z scores for each type of measurement. This effect yielded z score values close to the expected value of 0 at 100 to 200 examinations for all biometric measurements, indicating good consistency with the distribution of values in the reference population. Near the end of the study period, an increasing tendency toward either overestimation (head circumference) or underestimation (biparietal diameter, abdominal circumference, and femur length) was observed. CONCLUSIONS: A longitudinal analysis of the z score distribution for quality control of biometry is feasible. A prospective and automatized use of this technique could help identify potential systematic errors and therefore improve the detection rate for high-risk pregnancies.

Longitudinal Assessment of Examiner Experience and the Accuracy of Sonographic Fetal Weight Estimation at Term.

OBJECTIVES: To evaluate the influence of examiner experience on the accuracy of sonographic weight estimation and to further analyze examiners' individual learning curves. METHODS: In this multicenter study, 4613 sonographic weight estimations performed by 18 examiners at the beginning of their ultrasound training were included. To assess the effect of experience on the accuracy of weight estimation, a multivariable mixed regression model analysis was performed, with percentage error and absolute percentage error as outcome variables and the examiner, the examiner's experience (number of examinations), birth weight, gestational age, scan-to-delivery interval, and maternal body mass index as fixed effects and the perinatal center as random intercepts. To further analyze the individual learning curves of the examiners, the cumulative summation technique was used. RESULTS: Regression analyses showed a significant influence of the number of examinations on the accuracy of sonographic weight estimation after adjustment for the above-mentioned parameters (P < .001). A typical learning curve with improving accuracy was found until approximately 200 examinations. Between 200 and 300 examinations, the diagnostic performance started to deteriorate again, with a continuous decrease until the end of the study period. Cumulative summation charts representing individual learning curves varied greatly between different examiners. CONCLUSIONS: These findings indicate the great importance of continuous quality control systems in sonographic weight estimation.

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome.

BACKGROUND: In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. OBJECTIVES: To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. STUDY DESIGN: In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. RESULTS: Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response group compared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively. CONCLUSION: The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis.

A New Sonographic Weight Estimation Formula for Small-for-Gestational-Age Fetuses.

OBJECTIVES: The purpose of this study was to develop a new specific weight estimation formula for small-for-gestational-age (SGA) fetuses that differentiated between symmetric and asymmetric growth patterns. METHODS: A statistical estimation technique known as component-wise gradient boosting was applied to a group of 898 SGA fetuses (symmetric, n = 750; asymmetric, n = 148). A new formula was derived from the data obtained and was then compared to other commonly used equations. RESULTS: The new formula derived is as follows: estimated fetal weight = e^[1.3734627 + 0.0057133 × biparietal diameter + 0.0011282 × head circumference + 0.0201147 × abdominal circumference + 0.0183081 × femur length - 0.0000177 × biparietal diameter(2) - 0.0000018 × head circumference(2) - 0.0000297 × abdominal circumference(2) -0.0001007 × femur length(2) + 0.0397563 × I(sex = male) + 0.0064505 × gestational age (days) + 0.0096528 × I(SGA = asymmetric)], where the function I denotes an indicator function, which is 1 if the expression is fulfilled (sex = male; SGA type = asymmetric) and otherwise 0. In the whole study group and the 2 subgroups, the new formula showed the lowest median absolute percentage error, mean percentage error, and random error and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSIONS: The new formula substantially improves weight estimation in SGA fetuses.

Differential effects of low birthweight and intrauterine growth restriction on umbilical cord blood insulin-like growth factor concentrations.

OBJECTIVE: Alterations in the growth hormone-insulin-like growth factor (IGF) axis have been considered as a causal factor for intrauterine growth restriction (IUGR) and for the increased risk of metabolic disease in later life. We compared members of the IGF axis in umbilical cord blood between IUGR neonates, small for gestational age without foetal restriction (SGA) and appropriate for gestational age (AGA) neonates. DESIGN: Prospective controlled multicenter study. PATIENTS: Sixteen ultrasound-proven IUGR, 8 SGA and 40 AGA neonates. MEASUREMENTS: Concentrations of total IGF-I and total IGF-II by immunoassays, bioactive IGF by cell-based bioassay and IGFBP-I in mixed venous and arterial umbilical cord blood samples at birth. Auxological parameters at birth. RESULTS: IGF-I concentrations in IUGR [17·7 µg/l (CI 13·8;21·6)] were clearly below those in AGA [48·3 µg/l (CI 43·7;52·9)] and SGA neonates [36·0 µg/l (CI 26·6;45·4)]. IGF-II levels were significantly reduced in IUGR [201·4 µg/l (CI 190·2;212·6)] compared to AGA neonates [231·2 µg/l (CI 220·6;241·9)]. A trend for lower IGF-II concentrations was observed in IUGR when compared to SGA neonates [232·0 µg/l (CI 207·2;256·8)]. These differences could not be explained by confounding. For IGFBP-1, a trend towards higher values in IUGR was observed. CONCLUSIONS: Low IGF-I cord blood concentrations in hypotrophic neonates after IUGR might not only result from low birthweight per se, but also reflect prenatal placental environment. Alterations of the IGF axis could be in the causal pathway of IUGR and thus constitute a potential surrogate marker for IUGR in the assessment of foetal programming.

Interinstitutional variations in mode of birth after a previous caesarean section: a cross-sectional study in six German hospitals.

AIMS: Regional and interinstitutional variations have been recognized in the increasing incidence of caesarean section. Modes of birth after previous caesarean section vary widely, ranging from elective repeat caesarean section (ERCS) and unplanned repeat caesarean section (URCS) after trial of labour to vaginal birth after caesarean section (VBAC). This study describes interinstitutional variations in mode of birth after previous caesarean section in relation to regional indicators in Germany. MATERIAL AND METHODS: A cross-sectional study using the birth registers of six maternity units (n=12,060) in five different German states (n=370,209). Indicators were tested by χ2 and relative deviations from regional values were expressed as relative risks and 95% confidence intervals. RESULTS: The percentages of women in the six units with previous caesarean section ranged from 11.9% to 15.9% (P=0.002). VBAC was planned for 36.0% to 49.8% (P=0.003) of these women, but actually completed in only 26.2% to 32.8% (P=0.66). Depending on the indicator, the units studied deviated from the regional data by up to 32% [relative risk 0.68 (0.47-0.97)] in respect of completed VBAC among all initiated VBAC. CONCLUSIONS: There is substantial interinstitutional variation in mode of birth following previous caesarean section. This variation is in addition to regional patterns.

DNA methylation of the p66Shc promoter is decreased in placental tissue from women delivering intrauterine growth restricted neonates.

OBJECTIVE: The adaptor protein p66Shc generates mitochondrial reactive oxygen species and translates oxidative signals into apoptosis. We aimed to analyze potential alterations in total methylation and in p66Shc activation in placental tissues from women delivering intrauterine growth restricted neonates (IUGR) versus appropriate for gestational age (AGA) and small for gestational age (SGA) neonates. METHOD: DNA methylation of the p66Shc promoter and of long interspersed nuclear elements (LINE-1), as a marker for total methylation, was quantified by automatic pyrosequencing in 15 IUGR, 25 AGA and 15 SGA placentas. Placental gene expression of p66Shc was determined by TaqMan real-time polymerase chain reaction. RESULTS: No significant difference was found for LINE-1 methylation between IUGR, AGA and SGA newborns. DNA methylation of the p66Shc promoter was significantly decreased in the IUGR compared with the AGA group (p < 0.0001) and the SGA group (p < 0.0001). However, analysis of placental p66Shc gene expression did not show a significant difference between the three groups. CONCLUSION: It remains speculative if the decreased p66Shc promoter methylation might play a role in the pathophysiology of endothelial dysfunction and cardiovascular disease after IUGR.