Time-to-delivery and delivery outcomes comparing three methods of labor induction in 7551 nulliparous women: a population-based cohort study.

OBJECTIVE: Determine time-to-delivery and mode-of-delivery in labor induction among women with unripe cervix. STUDY DESIGN: 7551 nulliparous women with singleton deliveries, ⩾37 weeks, Bishop Score ⩽6, induced with dinoprostone, misoprostol or transcervical single balloon catheter. Linear regression analysis was used to estimate mean time-to-delivery with ß-estimates and 95% confidence intervals with adjustments. Multivariable logistic regression analysis was used to calculate odds of cesarean delivery, instrumental vaginal delivery, maternal and neonatal outcomes. RESULTS: Adjusted mean time-to-delivery was 6.9 and 1.5 h shorter, respectively, when inducing labor with balloon catheter (mean 18.3 h, ß -6.9, 95% confidence intervals; -7.6 to -6.3) or misoprostol (mean 23.7 h, ß -1.5, 95% confidence intervals; -2.3 to -0.8) compared with dinoprostone (mean 25.2 h). There were no significant differences in adverse maternal or infant outcomes between induction methods. CONCLUSIONS: Balloon catheter is the most effective induction method with respect to time-to-delivery in nulliparous women at term compared with prostaglandin methods.

Prenatal ultrasound and childhood autism: long-term follow-up after a randomized controlled trial of first- vs second-trimester ultrasound.

OBJECTIVE: To analyze whether the frequency of autism spectrum disorder (ASD) in a cohort of Swedish children differs between those exposed to ultrasound in the 12(th) week and those exposed to ultrasound in the 18(th) week of gestation. METHODS: The study cohort consisted of approximately 30 000 children born between 1999 and 2003 to mothers who had been randomized to a prenatal ultrasound examination at either 12 or 18 weeks' gestation as part of the framework for a study on nuchal translucency screening. The outcome measure in the present study was the rate of ASD diagnoses among the children. Information on ASD diagnoses was based on data from the Swedish social insurance agency concerning childcare allowance granted for ASD. RESULTS: Between 1999 and 2003, a total of 14 726 children were born to women who underwent a 12-week ultrasound examination and 14 596 to women who underwent an 18-week ultrasound examination. Of these, 181 (1.2%) and 176 (1.2%) children, respectively, had been diagnosed with ASD. There was no difference in ASD frequency between the early and late ultrasound groups. CONCLUSIONS: Women subjected to at least one prenatal ultrasound examination at either 12 or 18 weeks' gestation had children with similar rates of ASD. However, this result reflects routine care 10-15 years ago in Sweden. Today, higher intensity ultrasound scans are performed more frequently, at earlier stages during pregnancy and for non-medical purposes, implying longer exposure time for the fetus. This change in the use of ultrasound necessitates further follow-up study of the possible effects that high exposure to ultrasound during the gestational period has on the developing brain. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study.

OBJECTIVE: To evaluate whether defective placentation disorders, i.e. pre-eclampsia, stillbirth, small for gestational age (SGA), and spontaneous preterm birth, are associated with risk of retained placenta. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Primiparous women in Sweden with singleton vaginal deliveries between 1997 and 2009 at 32-41 weeks of gestation (n = 386,607), without placental abruption or infants with congenital malformations. METHODS: Risks were calculated as odds ratios (ORs) by unconditional logistic regression with 95% confidence intervals (95% CIs) after adjustments for maternal, delivery, and infant characteristics. MAIN OUTCOME MEASURE: Retained placenta, defined by the presence of both a diagnostic code (of retained placenta) and a procedure code (for the manual removal of the placenta). RESULTS: The overall rate of retained placenta was 2.17%. The risk of retained placenta was increased for women with pre-eclampsia (adjusted OR, aOR, 1.37, 95% CI 1.21-1.54), stillbirth (aOR 1.71, 95% CI 1.28-2.29), SGA birth (aOR 1.47, 95% CI 1.28-1.70), and spontaneous preterm birth (32-34 weeks of gestation, aOR 2.35, 95% CI 1.97-2.81; 35-36 weeks of gestation, aOR 1.55, 95% CI 1.37-1.75). The risk was further increased for women with preterm pre-eclampsia (aOR 1.69, 95% CI 1.25-2.28) and preterm SGA birth (aOR 2.19, 95% CI 1.42-3.38). There was no association between preterm stillbirth (aOR 1.10, 95% CI 0.63-1.92) and retained placenta, but the exposed group comprised only 15 cases. CONCLUSIONS: Defective placentation disorders are associated with an increased risk of retained placenta. Whether these relationships indicate a common pathophysiology remains to be investigated.

Miscarriage after a normal scan at 12-14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening.

OBJECTIVES: To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. METHODS: The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. RESULTS: The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). CONCLUSION: In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

By how much does increased nuchal translucency increase the risk of adverse pregnancy outcome in chromosomally normal fetuses? A study of 16,260 fetuses derived from an unselected pregnant population.

OBJECTIVE: In this study we aimed to estimate the magnitude of a possible increase in risk of adverse outcome in fetuses with normal karyotype and increased nuchal translucency (NT), and to determine how well NT measurements can distinguish between fetuses with normal and adverse outcome. METHODS: We studied 16,260 consecutive fetuses with normal karyotype derived from an unselected pregnant population. The following cut-offs for increased risk of adverse outcome were chosen a priori: NT > or = 95th percentile, > or = 3 mm, > or = 3.5 mm, and > or = 4.5 mm. The positive and negative likelihood ratios (+LR, - LR) of the risk cut-offs with regard to fetal malformation, miscarriage, perinatal death, termination of pregnancy and total adverse outcome were calculated, and receiver-operating characteristics (ROC) curves were drawn. RESULTS: The total rate of adverse outcome was 2.7%. + LR and - LR of NT > or = 3.0 mm were: for lethal or severe malformation, + LR 15.0 (95% CI 7.0-28.6), - LR 0.89 (95% CI 0.81-0.95); for malformation of at least intermediate severity, + LR 8.1 (95% CI 4.3-14.0), - LR 0.95 (95% CI 0.92-0.97); for termination of pregnancy, + LR 41.6 (95% CI 17.1-86.6), - LR 0.67 (95% CI 0.41-0.85); for any adverse outcome, + LR 6.4 (95% CI 3.4-11), - LR 0.96 (95% CI 0.94-0.98). The odds for these adverse outcomes increased with increasing NT. NT > or = 3 mm did not significantly increase the risk of miscarriage or perinatal death. Areas under ROC curves for NT were small, with 95% CI below or only slightly above 0.5. CONCLUSION: Our likelihood ratios can be used to calculate the individual risk of unfavorable outcome, but NT screening cannot reliably distinguish between normal and adverse outcome in fetuses with normal karyotype.

Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation-a randomised controlled trial in 39,572 pregnancies.

OBJECTIVE: To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws. DESIGN: Randomised controlled trial. SETTING: Multicentre trial including eight hospitals. POPULATION: A total of 39,572 unselected pregnant women. METHODS: Women were randomised either to one routine ultrasound scan at 12 (12-14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15-22) gws. Anomaly screening was performed in both groups following a check-list. A repeat scan was offered in the 12-week scan group if the fetal anatomy could not be adequately seen at 12-14 gws or if NT was >or=3.5 mm in a fetus with normal or unknown chromosomes. MAIN OUTCOME MEASURES: Antenatal detection rate of malformed fetuses. RESULTS: The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12-week scan group and 47% (72/152) in the 18-week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12-week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12-14 gws. CONCLUSIONS: None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12-week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18-week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.

Routine ultrasound examination at 12 or 18 gestational weeks for prenatal detection of major congenital heart malformations? A randomised controlled trial comprising 36,299 fetuses.

OBJECTIVE: To compare the rate of prenatal diagnosis of heart malformations between two policies of screening for heart malformations. DESIGN: Randomised controlled trial. SETTING: Six university hospitals, two district general hospitals. SAMPLE: A total of 39 572 unselected pregnancies randomised to either policy. METHODS: The 12-week policy implied one routine scan at 12 weeks including measurement of nuchal translucency (NT), and the 18-week policy implied one routine scan at 18 weeks. Fetal anatomy was scrutinised using the same check-list in both groups, and in both groups, indications for fetal echocardiography were ultrasound findings of any fetal anomaly, including abnormal four-chamber view, or other risk factors for heart malformation. In the 12-week scan group, NT >or=3.5 mm was also an indication for fetal echocardiography. MAIN OUTCOME MEASURE: Prenatal diagnosis of major congenital heart malformation. RESULTS: In the 12-week scan group, 7 (11%) of 61 major heart malformations were prenatally diagnosed versus 9 (15%) of 60 in the 18-week scan group (P= 0.60). In four (6.6%) women in the 12-week scan group, the routine scan was the starting point for investigations resulting in a prenatal diagnosis versus in 9 (15%) women in the 18-week scan group (P=0.15). The diagnosis was made

Is measurement of nuchal translucency thickness a useful screening tool for heart defects? A study of 16,383 fetuses.

OBJECTIVE: To determine the performance of nuchal translucency thickness (NT) measurement as a screening method for congenital heart defects (CHD) among fetuses with normal karyotype. METHODS: An NT measurement was made in 16 383 consecutive euploid fetuses derived from an unselected pregnant population. The cut-offs for increased risk of heart defects, chosen a priori and tested prospectively, were: NT >or= 95th centile for crown-rump length, NT >or= 3 mm, and NT >or= 3.5 mm. The sensitivity and false-positive rate (FPR; 1 minus specificity) of the risk cut-offs and their positive and negative likelihood ratios (+LR and -LR) with regard to CHD were calculated. RESULTS: Among the 16 383 fetuses with an NT measurement there were 127 cases with a diagnosis of heart defect confirmed by cardiac investigations after birth or at autopsy. Of these, 55 defects were defined as major, of which 52 were isolated (no other defects or chromosomal aberrations), corresponding to a prevalence of major heart defects in chromosomally normal fetuses/newborns of 3.3/1000. The sensitivity, FPR, +LR and -LR for NT >or= 95th centile with regard to an isolated major heart defect were: 13.5%, 2.6%, 5.2 and 0.9, respectively. For NT >or= 3.0 mm these values were: 9.6%, 0.8%, 12.0 and 0.9, and for NT >or= 3.5 mm they were: 5.8%, 0.3%, 19.3 and 0.9. CONCLUSIONS: NT measurement is a poor screening method for isolated major CHD. A method with a much higher detection rate and with a reasonably low FPR is needed. However, increased NT indicates increased risk of fetal heart defect, and women carrying fetuses with increased NT should be offered fetal echocardiography in the second trimester.

Ultrasound dating at 12-14 weeks of gestation. A prospective cross-validation of established dating formulae in in-vitro fertilized pregnancies.

OBJECTIVES: To determine the accuracy of established ultrasound dating formulae when used at 12-14 weeks of gestation. METHODS: One-hundred and sixty-seven singleton pregnancies conceived after in-vitro fertilization (IVF) underwent a dating scan at 12-14 weeks of gestation. Gestational age at the dating scan was calculated by adding 14 days to the number of days between the date of oocyte retrieval and the date of the ultrasound scan. Gestational age according to oocyte retrieval was regarded as the true gestational age. True gestational age was compared to gestational age calculated on the basis of 21 dating formulae based on fetal crown-rump length (CRL) measurements and to three dating formulae based on fetal biparietal diameter (BPD) measurements. In a previous study the three BPD formulae tested here had been shown to be superior to four other BPD formulae when used at 12-14 weeks of gestation. The mean of the differences between estimated and true gestational age and their standard deviation (SD) were calculated for each formula. The SD of the differences was assumed to reflect random measurement error. Systematic measurement error was assumed to exist if zero lay outside the mean difference+/-2SE (SE: standard error of the mean). RESULTS: The three best CRL formulae were associated with mean (non-systematic) measurement errors of -0.0, -0.1 and -0.3 days, and the SD of the measurement errors of these formulae varied from 2.37 to 2.45. All but two of the remaining CRL formulae were associated with systematic over- or under-estimation of gestational age, and the SDs of their measurement error varied between 2.25 and 4.86 days. Dating formulae using BPD systematically underestimated gestational age by -0.4 to -0.7 days, and the SDs of their measurement errors varied from 1.86 to 2.09. CONCLUSIONS: We have identified three BPD formulae that are suitable for dating at 12-14 weeks of gestation. They are superior to all 21 CRL formulae tested here, because their random measurement errors were much smaller than those of the three best CRL formulae. The small systematic negative measurement errors associated with the BPD formulae are likely to be clinically unimportant.

Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39,572 pregnancies.

OBJECTIVES: Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age-based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS. METHODS: A total of 39,572 pregnant women were randomized to a scan at 12-14 gestational weeks including NT screening for DS (12-week group) or to a scan at 15-20 weeks with screening for DS based on maternal age (18-week group). Fetal karyotyping was offered if risk according to NT was > or = 1:250 in the 12-week group and if maternal age was > or = 35 years in the 18-week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared. RESULTS: Ten babies with DS were born alive with the 12-week policy vs. 16 with the 18-week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12-week group (45/19,796) than in the 18-week group (27/19 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12-week group vs. 89 in the 18-week group. NT screening detected 71% of cases of DS for a 3.5% test-positive rate whereas maternal age had the potential of detecting 58% for a test-positive rate of 18%. CONCLUSIONS: The number of newborns with DS differed less than expected between pregnancies that had been screened at 12-14 weeks' gestation by NT compared with those screened at 15-20 weeks by maternal age. One explanation could be that NT screening--because it is performed early in pregnancy--results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18-week scan. The major advantage of the 12-week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS.

Ultrasound dating at 12-14 or 15-20 weeks of gestation? A prospective cross-validation of established dating formulae in a population of in-vitro fertilized pregnancies randomized to early or late dating scan.

OBJECTIVES: To determine the accuracy of established ultrasound dating formulae when used at 12-14 and 15-20 gestational weeks. METHODS: A total of 363 singleton pregnancies conceived after in-vitro fertilization (IVF) and randomized to a dating scan at 12-14 or 15-20 gestational weeks were studied. 'True' gestational age was calculated on the basis of the day of oocyte retrieval and was compared to gestational age calculated on the basis of seven dating formulae including the fetal biparietal diameter (BPD) and three dating formulae including BPD and fetal femur length (FL). The mean of the differences between estimated and true gestational age (systematic measurement error) and their SD (random measurement error) were calculated for each formula. RESULTS: Three formulae showed systematic errors of less than -0.7 days at both early and late scanning. Two formulae overestimated gestational age at both early and late scanning by 5.7 and 3.1 vs. 2.3 and 2.8 days, respectively, while five formulae manifested very different systematic errors at early and late scanning. The formulae used for clinical management underestimated gestational age by a mean of 3 days when dating was performed at 12-14 weeks, and by a mean of 0.8 days when dating was done at 15-20 weeks. The random error was on average 1 day less when the scan was carried out early (2 vs. 3 days; P < 0.0005). Mean true gestational age at delivery in IVF pregnancies with spontaneous start of labor was 279 days (SD 12.9); excluding preterm deliveries it was 281 days (SD 8.1). CONCLUSIONS: Ultrasound dating formulae originally intended for use in the middle of the second trimester do not necessarily perform well when used for dating earlier in gestation. The systematic and random error of any dating formula must be assessed for the gestational age interval in which the formula is intended to be used.

Fetal loss rate after second trimester amniocentesis at different gestational age.

BACKGROUND: Recent studies have debated the safety of early amniocentesis, one of which reported a significant increase in spontaneous fetal losses following amniocentesis performed at 10-13 weeks of gestation. The aim of this study was to determine the fetal loss rate following amniocentesis performed at different stages in the second trimester. METHODS: One thousand six hundred and fifty-one consecutive amniocenteses undertaken in a low risk population between 13 weeks+0 days and 20 weeks+6 days were evaluated. In 87% of the women the reason for testing was maternal age (mean 37.1 years). Data concerning patients, procedure details and pregnancy outcome were recorded. RESULTS: Spontaneous abortion before 28 weeks of gestation occurred in 1.1%, one third of which were within two weeks and the remaining within seven weeks after the procedure. The fetal loss rate was higher when the amniocentesis was performed earlier in pregnancy, at 13 weeks+0 days exceeding 3%. Abnormal color of the amniotic fluid and leakage of amniotic fluid were strong predictors of fetal loss. Transplacental needle insertion did not increase the risk of pregnancy loss. CONCLUSION: Amniocentesis performed very early in the second trimester is followed by an increased fetal loss rate that cannot be explained solely by a higher risk of spontaneous abortion at this time of gestation.