Decline in stillbirths and perinatal mortality after implementation of a more aggressive induction policy in post-date pregnancies: a nationwide register study.

INTRODUCTION: In 2011 Danish national guidelines were changed towards a more aggressive induction and fetal surveillance policy from (1) induction of labor at gestational age (GA) of 42+0  weeks and (2) no fetal surveillance after 40+0  weeks to (1) induction of labor between 41+2 and 41+6  weeks, (2) earlier induction at 41+0  weeks in the case of maternal age >40 years or body mass index (BMI) >35 kg/m2 and (3) fetal surveillance at GA 41+0  weeks. MATERIAL AND METHODS: This national cohort study included all pregnancies that reached 41+0  weeks of gestation in 2008-2014 (n = 102 167). Multivariate logistic regression analyses were used to estimate risks in the years after (2012-2014) vs. before (2008-2010) new national guidelines, adjusted for maternal age, BMI, and parity. RESULTS: We observed a decline in stillbirths from 0.9‰ to 0.5‰ [odds ratio (OR)adjusted 0.50, 95% CI 0.29-0.89, p = 0.018]. Furthermore, a decline in perinatal deaths from 1.3‰ to 0.8‰ (ORadjusted 0.62, 95% CI 0.39-0.96, p = 0.033) and vacuum extraction (ORadjusted 0.86, 95% CI 0.82-0.90, p = 0.007) was observed. The risk of cesarean section (ORadjusted 0.98, 95% CI 0.94-1.02, p = 0.251), Apgar score below 7 at five minutes (ORadjusted 0.96, 95% CI 0.81-1.14, p = 0.0.678) and admissions to the neonatal department (ORadjusted 1.04, 95% CI 1.00-1.14, p = 0.064) did not change, whereas induction of labor increased from 28.2 to 42.6% (ORadjusted 1.89, 95% CI 1.84-1.95, p < 0.001). CONCLUSIONS: This study showed a decline in stillbirths and perinatal mortality after implementation of new Danish guidelines for post-date pregnancies. The risk of interventions as cesarean section and vacuum extraction remained stable despite an increase in labor inductions.

The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study.

INTRODUCTION: Fetal cells in maternal blood may be used for noninvasive prenatal diagnostics, although their low number is a challenge. This study's objectives were to evaluate whether physical activity, transabdominal and transvaginal ultrasound scans of the uterus, as well as overnight or day-to-day variation affect the number of isolated fetal cells, more specifically the presumed endovascular trophoblast (pEVT). MATERIAL AND METHODS: In each of 3 different experiments, 10 normal singleton pregnant women (gestational age 10+4-14+4 weeks) participated. The number of pEVTs was assessed in 30-36 ml blood using specific markers for enrichment and identification. RESULTS: The number of pEVTs increased overnight (p = 0.001) from a median of 1.5 to 3.5 and even further to a median of 6.0 after 30 min of physical activity (p = 0.04) but was not affected by transabdominal and transvaginal ultrasound scans. Repeated sampling showed that the interindividual variation of pEVTs was higher than the intraindividual variation (p < 0.001). However, even in pregnant women with a consistently low number of pEVTs, isolation of the pEVTs for prenatal diagnoses was possible in all cases by doing 2 separate blood samplings a few days apart. DISCUSSION: The number of pEVTs identified in maternal blood can be increased by presampling conditions or repeated sampling.

The cell-free fetal DNA fraction in maternal blood decreases after physical activity.

OBJECTIVE: If noninvasive prenatal testing using next generation sequencing is to be effective for pregnant women, a cell-free fetal DNA (cffDNA) fraction above 4% is essential unless the depth of sequencing is increased. This study's objective is to determine whether physical activity has an effect on the proportion of cell-free DNA (cfDNA) arising from the fetus (fetal fraction). METHODS: Nine pregnant women carrying male fetuses at gestational age 12(+0) weeks to 14(+6) weeks were included. Plasma from nine pregnant women was drawn prior to, immediately after, and 30 min after 30 min of cycling with a pulse-rate of 150 beats per minute. The concentrations of cffDNA (DYS14) and cfDNA (RASSF1A) were assessed using quantitative real-time polymerase chain reaction. RESULTS: The fetal fraction decreased significantly in all participants after physical activity (p < 0.01), a decrease varying from 1-17 percentage points. This was due to a significant increase in the concentration of cfDNA (p < 0.01), whereas the concentration of cffDNA remained the same. This alteration of the fetal fraction was not present 30 min after physical activity. CONCLUSION: When planning the timing of noninvasive prenatal diagnosis based on the fetal fraction, physical activity prior to sampling should be avoided.

Autocorrelation and cross-correlation between hCGß and PAPP-A in repeated sampling during first trimester of pregnancy.

BACKGROUND: Theoretically, repeated sampling of free ß-human chorionic gonadotropin (hCGß) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester of pregnancy might improve performance of risk assessment of trisomy 21 (T21). To assess the performance of a screening test involving repeated measures of biochemical markers, correlations between markers must be estimated. The aims of this study were to calculate the autocorrelation and cross-correlation between hCGß and PAPP-A in the first trimester of pregnancy and to investigate the possible impact of gestational age at the first sample and time between sampling on the correlation. METHODS: A prospective study was conducted including 3891 unaffected singleton pregnancies. Two measurements of hCGß and PAPP-A were obtained during the first trimester in each pregnancy. Correlations between the four parameters, hCGß first, hCGß second, PAPP-A first and PAPP-A second, were estimated and presented in terms of Pearson's r coefficients. Furthermore, the correlation between paired samples as a function of time between samples was investigated. RESULTS: The study demonstrated high correlation between first and second samples of hCGß and PAPP-A with a correlation coefficient of 0.80 and 0.79, respectively. By contrast, the correlations between hCGß and PAPP-A were low. In addition, the study demonstrated that the correlation between paired samples of hCGß and PAPP-A decreases with earlier gestational age at the first sample and with increasing time between samples. CONCLUSIONS: We have developed a parameter set in terms of correlations between biochemical markers, which can be incorporated into a T21 screening algorithm based on repeated measures within the first trimester.

Pregnancy-associated plasma protein A levels and neonatal complications in post-date pregnancies.

OBJECTIVES: To assess the association between serum pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotropin (free ß-hCG) in the first trimester and perinatal complications in post-date pregnancies. METHODS: A total of 4948 women, who delivered after 40 gestational weeks, were included. Labour was not induced routinely until 42 weeks. Serum levels of PAPP-A and free ß-hCG were determined at the first-trimester screening for Down syndrome. Neonatal complications were obtained from specific registration forms filled out by senior neonatologists. RESULTS: In post-date pregnancies, PAPP-A < 0.4 multiples of the median was associated with Apgar score of less than 7 at 5 min (ORadj 5.4, 95% CI 2.0-14.3), admission to the neonatal intensive care unit (ORadj 1.5, 95% CI 1.0-2.3) and newborn hypoglycaemia (ORadj 3.4, 95% CI 1.8-6.4). In small for gestation (SGA) neonates, the risk of hypoglycaemia was further increased (OR 14.6, 95% CI 3.4-58.0). Similar analyses were made with free ß-hCG, but no statistically significant associations were found. CONCLUSIONS: Low first-trimester serum PAPP-A was associated with increased neonatal morbidity in post-date pregnancies, particularly in newborns with SGA. Thus, PAPP-A may qualify the timing of induction of labour in these pregnancies.

Towards better reliability in fetal heart rate variability using time domain and spectral domain analyses. A new method for assessing fetal neurological state?

OBJECTIVES: Fetal heart rate variability (FHRV) has shown potential in fetal surveillance. Therefore, we aimed to evaluate the reliability of time domain and spectral domain parameters based on non-invasive fetal electrocardiography (NI-FECG). METHOD: NI-FECG, with a sampling frequency of 1 kHz, was obtained in 75 healthy, singleton pregnant women between gestational age (GA) 20+0 to 41+0. The recording was divided into a) heart rate pattern (HRP) and b) periods fulfilling certain criteria of stationarity of RR-intervals, termed stationary heart rate pattern (SHRP). Within each recording, the first and the last time series from each HRP with less than 5% artifact correction were analyzed and compared. Standard deviation of normal-to-normal RR-intervals (SDNN), root mean square of successive differences (RMSSD), high frequency power (HF-power), low frequency power (LF-power), and LF-power/HF-power were performed. A multivariate mixed model was used and acceptable reliability was defined as intraclass correlation coefficient (ICC) ≥ 0.80 and a coefficient of variation (CV) ≤ 15%. Based on these results, the CV and ICC were computed if the average of two to six time series was used. RESULTS: For GA 28+0 to 34+6, SDNN and RMSSD exhibited acceptable reliability (CV < 15%; ICC > 90%), whereas GA 35+0 to 41+0and 20+0 to 27+6 showed higher CVs. Spectral domain parameters also showed high CVs However, by using the mean value of two to six time series, acceptable reliability in SDNN, RMSSD and HF-power from GA 28+0 was achieved. Stationarity of RR-intervals showed high influence on reliability and SHRP was superior to HRP, whereas the length of the time series showed minor influence. CONCLUSION: Acceptable reliability seems achievable in SDNN, RMSSD and HF-power from gestational week 28. However, stationarity of RR-intervals should be considered when selecting time series for analyses.

Fetal respiratory movements improve reliability of heart rate variability and suggest a coupling between fetal respiratory arrhythmia and vagal activity.

Fetal heart rate variability (FHRV) reflects autonomic cardiac regulation. The autonomic nervous system constantly adjusts the heart rate to maintain homeostasis. By providing insight into the fetal autonomic state, FHRV has the potential to become an investigational and clinical instrument. However, the method needs standardization and the influence of fetal movements, including fetal respiratory movements, is not well explored. Therefore, in a highly standardized setting, the aim was to evaluate the association between fetal movements and fetal heart rate variability (FHRV) including their impact on reliability. Fetal heart rate was obtained by noninvasive fetal electrocardiography (NI-FECG) and fetal movements by simultaneous ultrasound scanning in 30 healthy singleton pregnant women on two occasions with a maximum interval of 7 days. The standard deviation of normal-to-normal RR-intervals (SDNN), root mean square of successive RR-interval differences (RMDDS), high-frequency power (HF-power), low-frequency power (LF-power), and LF/HF were measured. A multivariate mixed model was used and reliability was defined as acceptable by a coefficient of variance (CV) ≤15% and an intraclass correlation coefficient (ICC) ≥0.80. During time periods with fetal respiratory movements, the highest reliability was achieved. Intra- and inter-observer reliability measurements were very high (CV: 0-9%; ICC â‰§ 0.86). Within the same recording, SDNN and RMSSD achieved acceptable reliability (CV: 14-15%; ICC â‰§ 0.80). However, day-to-day reliability displayed high CV's. In time periods with fetal respiratory movements, as compared to periods with quiescence RMSSD and HF-power were higher (Ratio: 1.33-2.03) and LF/HF power lower (Ratio: 0.54). In periods with fetal body movements SDNN, RMSSD and HF-power were higher (Ratio: 1.27-1.65). In conclusion, time periods with fetal respiratory movements were associated with high reliability of FHRV analyses and the highest values of parameters supposed to represent vagal activity.

Growth-restricted human fetuses have preserved respiratory sinus arrhythmia but reduced heart rate variability estimates of vagal activity during quiescence.

The aim was to assess the association between fetal growth restriction (FGR) and fetal heart rate variability (FHRV) in relation to fetal movements. A prospective observational cohort study was performed. Non-invasive fetal electrocardiography (NI-FECG) allowed beat-to-beat assessments with <5% corrections of RR intervals. FHRV analyses included: Root mean square of successive RR interval differences (RMSSD), high frequency power (HF power), and low frequency power (LF power). Fetal movements were categorized by continuous ultrasound scanning. We enrolled 36 singleton pregnant women expecting a small fetus (< the 2.3 percentile of mean weight for gestational age) diagnosed by ultrasound, of whom 25 presented with a birthweight < the 2.3 percentile. Among these, 11 were excluded due to low quality NI-FECG recordings, leaving 14 women with 28 recordings eligible for inclusion in the analyses. The control group consisted of 22 healthy fetuses with birthweights between the 10th and the 90th percentile (average for gestational age [AGA]). In FGR fetuses the HRV response to respiratory activity was comparable to that of AGA fetuses. RMSSD (Ratio 1.54 [95% CI: 1.33; 1.79]) and HF power (Ratio 2.88 [95% CI: 2.12; 3.91]) increased, whereas LF/HF power (Ratio: 0.44 [95% CI: 0.31;0.63]) decreased. However, during fetal quiescence, FGR fetuses differed significantly from AGA fetuses. Compared to AGA fetuses, FGR fetuses displayed lower RMSSD (Ratio 0.77 (95% CI: 0.58; 1.02)) and HF power (Ratio 0.56 (95% CI:0.32; 0.98)). This reduction was associated with the severity of the FGR. In conclusion, FGR fetuses displayed a respiratory sinus arrhythmia (RSA) comparable to AGA fetuses; however, more important, parameters representing cardiac vagal activity were impaired in FGR fetuses during quiescence. RSA may constitute an intrinsic function of the cardiovascular system, which is unaffected by fetal compromise. However, the basic cardiac outflow assessed during fetal quiescence indicates a suppressed cardiac vagal activity in the FGR fetuses.

PAPP-A and free ß-hCG in relation to admission to neonatal intensive care unit and neonatal disease.

OBJECTIVE: To evaluate pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotrophin (ß-hCG) in relation to admission to a neonatal intensive care unit (NICU) and neonatal disease. METHODS: A total of 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital between January 2005 and December 2007 were included. PAPP-A and free ß-hCG were measured between gestational weeks 8 and 13 and converted into multiples of the median (MoM) values. Information about neonatal outcome was obtained from specific registration forms completed by senior neonatologists at the time of admission to and discharge from the NICU. RESULTS: Both PAPP-A and free ß-hCG < 0.4 MoM were associated with admission to NICU (odds ratio 1.6; 95% confidence interval, 1.2-2.0 and odds ratio 1.5; 95% confidence interval, 1.1-2.1). The results could not be explained by preterm delivery or low birth weight, because adjusting for these factors did not affect the results. Low PAPP-A was also significantly associated with neonatal hypoglycemia, jaundice, and low Apgar score and low free ß-hCG with jaundice. CONCLUSION: Low PAPP-A and free ß-hCG were significantly associated with admission to NICU and neonatal disease, independently from what could be expected because of preterm delivery or low birth weight.

PAPP-A and free ß-hCG measured prior to 10 weeks is associated with preterm delivery and small-for-gestational-age infants.

OBJECTIVE: To evaluate whether measuring pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotrophin (ß-hCG) before 10 weeks of gestation affect the association between these biomarkers and adverse pregnancy outcomes. METHODS: Singleton pregnant women (9450) who attended the prenatal screening program, Aarhus University Hospital, Denmark, were included. Maternal serum levels of PAPP-A and free ß-hCG were measured between week 8 and 13 weeks and 6 days. The risk of preterm delivery (<37 weeks) and small for gestational age (SGA) (

Low serum interleukin-17 is associated with preterm delivery.

OBJECTIVE: To study maternal serum interleukin-17 (IL-17) during normal pregnancy and evaluate the association with preterm delivery. DESIGN: Prospective study. SETTING: Aarhus University Hospital, Denmark. POPULATION: Three cohorts: (a) low-risk cohort of 1,069 women who had serum drawn in weeks 12 and 19, (b) subgroup of the low-risk cohort, consisting of 40 women, who had serum drawn at 12, 19, 26, 33 and 39 weeks of gestation and (c) a symptomatic cohort of 93 women admitted with symptoms of preterm delivery at a gestational age of 24(+ 0) weeks to 33(+ 6) weeks. METHODS: Serum IL-17 determined by an in-house developed multiplex sandwich immunoassay. MAIN OUTCOME MEASURES: Preterm delivery <37(+0) weeks gestation. RESULTS: Serum IL-17 did not change during normal pregnancy. At admission to hospital, women with preterm contractions had significantly decreased serum IL-17 as compared with normal pregnancies (median <4 [interquartile ranges, IQR, <4-10 pg/ml] vs. 174 pg/ml [IQR, 92 - 485 pg/ml]); this difference was enhanced and highly significant for women delivering preterm versus term (median <4 [IQR, <4-7.9 pg/ml] vs. median 6.0 [IQR, <4-221 pg/ml]; p-value 0.03). Serum IL-17 was also lower in women with preterm prelabor rupture of membranes. A slightly, but not statistically significant decrease was found in weeks 12 and 19 in low-risk women who subsequently delivered preterm. CONCLUSION: Maternal serum IL-17 may be involved in preterm delivery.

PAPP-A, free ß-hCG, and early fetal growth identify two pathways leading to preterm delivery.

OBJECTIVE: To evaluate early fetal growth and the biomarkers, pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotrophin (ß-hCG), in relation to preterm delivery. METHODS: A cohort study of 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital between January 2005 and December 2007, was conducted. PAPP-A and free ß-hCG were measured in the first trimester. Early fetal growth was estimated by (GA(20)- GA(12))/Days(calendar), where GA(12) reflects the gestational age in days calculated from the crown-rump length at a 12-week scan, GA(20) reflects the gestational age in days calculated from the biparietal diameter at a 20-week scan, and Days(calendar) is the number of calendar days between the two scans. RESULTS: Low PAPP-A and low free ß-hCG were significantly associated with preterm delivery (<37 weeks). The association was even stronger when low PAPP-A and slow early fetal growth were combined, resulting in an adjusted odds ratio of 3.8 (95% CI, 1.6-8.7). Fast early fetal growth, but neither high PAPP-A nor high free ß-hCG, was significantly associated with preterm delivery. CONCLUSION: Two different biological pathways leading to spontaneous preterm delivery are suggested: fast early fetal growth and the combination of low PAPP-A and slow early fetal growth.

Biology of pregnancy-associated plasma protein-A in relation to prenatal diagnostics: an overview.

Pregnancy-associated plasma protein-A (PAPP-A) is highly efficient as a serum marker in first-trimester screening for chromosomal abnormalities. Furthermore, there is increasing evidence that low levels of PAPP-A in the first trimester are associated with adverse pregnancy outcomes such as preterm delivery, intrauterine growth retardation, preeclampsia, and stillbirth. PAPP-A is a glycoprotein, produced in the placenta, and it is present in the maternal circulation in increasing concentrations during pregnancy. By means of its proteolytic activity, PAPP-A functions as a regulatory protein in the insulin-like growth factor system, known to be important for placental formation and regulation of fetal growth. This overview describes aspects of biochemistry, synthesis, and biological functions of PAPP-A, with a focus on information of importance to clinicians. The clinical applications of PAPP-A are summarized, and new insights regarding the analyses of PAPP-A discussed.

Fetal Heart Rate Variability Is Affected by Fetal Movements: A Systematic Review.

Introduction: Fetal heart rate variability (FHRV) evaluates the fetal neurological state, which is poorly assessed by conventional prenatal surveillance including cardiotocography (CTG). Accurate FHRV on a beat-to-beat basis, assessed by time domain and spectral domain analyses, has shown promising results in the scope of fetal surveillance. However, accepted standards for these techniques are lacking, and the influence of fetal breathing movements and gross movements may be especially challenging. Thus, current standards for equivalent assessments in adults prescribe rest and controlled respiration. The aim of this review is to clarify the importance of fetal movements on FHRV. Methods: A systematic review in accordance with the PRISMA guidelines based on publications in the EMBASE, the MEDLINE, and the Cochrane Library databases was performed. Studies describing the impact of fetal movements on time domain, spectral domain and entropy analyses in healthy human fetuses were reviewed. Only studies based on fetal electrocardiography or fetal magnetocardiography were included. PROSPERO registration number: CRD42018068806. Results: In total, 14 observational studies were included. Fetal movement detection, signal processing, length, and selection of appropriate time series varied across studies. Despite these divergences, all studies showed an increase in overall FHRV in the moving fetus compared to the resting fetus. Especially short-term, vagal mediated indexes showed an increase during fetal breathing movements including an increase in Root Mean Square of the Successive Differences (RMSSD) and High Frequency power (HF) and a decrease in Low Frequency power/High Frequency power (LF/HF). These findings were present even in analyses restricted to one specific fetal behavioral state defined by Nijhuis. On the other hand, fetal body movements seemed to increase parameters supposed to represent the sympathetic response [LF and Standard Deviation of RR-intervals from normal sinus beats (SDNN)] proportionally more than parameters representing the parasympathetic response (RMSSD, HF). Results regarding entropy analyses were inconclusive. Conclusion: Time domain analyses as well as spectral domain analyses are affected by fetal movements. Fetal movements and especially breathing movements should be considered in these analyses of FHRV.

Performance of first-trimester combined screening for trisomy 13 and 18 with the double test taken at a gestational age of 8 + 0 to 13 + 6.

OBJECTIVE: To evaluate the performance of the combined test for first-trimester screening for trisomy 18 and 13, when the double test is scheduled weeks before the nuchal translucency scanning. METHODS: The study included all 40 cases of trisomy 18 and 13 from April 2004 to October 2008 in a screening programme, where the double test was measured in gestational weeks 8 + 0 to 13 + 6 and the nuchal translucency in weeks 11 + 2 to 13 + 6. RESULTS: Twenty-eight among the 40 cases had complete information on all variables in the first-trimester screening test. Among 19 cases having the double test taken before 10 + 0 weeks, 10 cases were detected (detection rate (DR) = 53%) and among 9 cases having the double test taken after 10 + 0 weeks, 6 cases were detected (DR 67%). There was no significant difference in the DRs (p = 0.48). A total of 29 cases were detected at the first-trimester screening, resulting in an overall DR for trisomy 18 and 13 at 73%. CONCLUSION: This study showed no significant differences in the trisomy 18/13 DRs when grouped according to having the double test taken before or after 10 + 0 weeks. The DR was 73% at the first-trimester screening.

Fetal growth in pregnancies conceived after gastric bypass surgery in relation to surgery-to-conception interval: a Danish national cohort study.

OBJECTIVE: To describe early and late fetal growth in pregnancies conceived after gastric bypass surgery in relation to time from surgery to conception of pregnancy. METHODS: National cohort study on 387 Danish women, who had laparoscopic or open gastric bypass surgery prior to a singleton pregnancy in which first trimester screening was performed between January 2008 and June 2011. Data were derived from national registers (Danish National Registry of Patients and Danish National Birth Registry, Pregnancy Complications and Abortion-clinical quality database (PreCAb) and the Danish Fetal Medicine Database). Main outcome measures were early and late fetal growth in relation to time from bariatric surgery to conception of the pregnancy. Early fetal growth was expressed as "Fetal Growth Index": the ratio between the estimated number of days from first trimester ultrasound to second trimester ultrasound biometries and the actual calender time elapsed in days. Late fetal growth was expressed as the observed versus expected birthweight according to gestational age (GA). RESULTS: The surgery-to-conception interval ranged from 3 to 1851 days with a mean value of 502 (SD, 351) days. The mean "fetal growth index" was 0.99 (SD, 0.02) days/day and thus significantly lower than in the background population (mean, 1.04 (SD, 0.09) days/day, p<0.0001). The proportion of infants being small for gestational age was 18.8% and the proportion of large for gestational age infants was 6.7%. The correlation coefficients between surgery-to-conception time and "fetal growth index" and birthweight according to GA were 0.01 (p = 0.8) and 0.04 (p = 0.4), respectively. CONCLUSION: Fetal growth index was lower than reported in the background population. No correlation was found between the surgery-to-conception interval and early or late fetal growth in pregnancies conceived after gastric bypass surgery.

Fetal gender and several cytokines are associated with the number of fetal cells in maternal blood--an observational study.

OBJECTIVE: To identify factors influencing the number of fetal cells in maternal blood. METHODS: A total of 57 pregnant women at a gestational age of weeks 11-14 were included. The number of fetal cells in maternal blood was assessed in 30 ml of blood using specific markers for both enrichment and subsequent identification. RESULTS: Participants carrying male fetuses had a higher median number of fetal cells in maternal blood than those carrying female fetuses (5 vs. 3, p = 0.04). Certain cytokines (RANTES, IL-2 and IL-5) were significantly associated with the number of fetal cells in maternal blood. CONCLUSION: The number of fetal cells in maternal blood is associated with certain cytokines and fetal gender.

[Bilateral tubal pregnancy]. / Bilateral ekstrauterin graviditet.

Bilateral tubal pregnancies are extremely rare and they are usually found after assisted reproductive techniques have been applied. A rare case of bilateral tubal pregnancy after natural conception, occurring in a woman without any predisposing factors for ectopic pregnancy, is presented. The condition was diagnosed during laparoscopic surgery, and she was optimally treated with conservative tubal surgery. A short review of the literature is provided and discussed along with the clinical features, diagnostic difficulties and treatment options of bilateral tubal pregnancy.

Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks.

OBJECTIVE: To evaluate if there is a performance difference in the combined screening for trisomy 21 between the double tests performed before and after 10 + 0 weeks of gestation. METHODS: The study included all 97 trisomy 21 cases from January 2004 to December 2007, in a screening program where the double test was measured in week 8 + 0 to 13 + 6 and the nuchal translucency in week 11 + 3 to 13 + 6. RESULTS: As many as 87 of the 97 cases were diagnosed in the screening program (detection rate = 90%). Among the 53 cases having the double test taken before 10 + 0 weeks, no cases were missed [detection rate (DR) = 100%, CI = 0.94-1.00] and among the 44 having the double test taken after 10 + 0 weeks, 10 cases were missed (DR = 77%, CI = 0.65-0.90). This difference in DR was highly significant (P = 0.0009). No difference was observed between false positive rates or median maternal age of the two groups. CONCLUSION: A significantly higher DR was obtained when the double test was taken early in pregnancy (<10 + 0 weeks), than when it was taken later (>or=10 + 0 weeks). The results could not be explained by a difference in either the false positive rate or the maternal age between the two groups.