Maternal and neonatal complications following Kielland's rotational forceps delivery: A systematic review and meta‐analysis

Background There is conflicting evidence regarding the safety of Kielland's rotational forceps delivery (KRFD) in comparison with other modes of delivery for the management of persistent fetal malposition in the second stage of labour. Objectives To derive estimates of risks of maternal and neonatal complications following KRFD, compared with rotational ventouse delivery (RVD), non-rotational forceps delivery (NRFD) or a second-stage caesarean section (CS), from a systematic review and meta-analysis of the literature. Search Strategy Standard search methodology, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. Selection Criteria Case series, prospective or retrospective cohort studies and population-based studies. Data Collection and Analysis A meta-analysis using a random-effects model was used to derive weighted pooled estimates of maternal and neonatal complications. Main Results Thirteen studies were included. For postpartum haemorrhage there was no significant difference between Kielland's and ventouse delivery; the rate was lower in Kielland's delivery compared with non-rotational forceps (RR 0.79, 95% CI 0.65–0.95) and second-stage CS (RR 0.45, 95% CI 0.36–0.58). There were no differences in the rates of anal sphincter injuries or admission to neonatal intensive care. Rates of shoulder dystocia were higher with Kielland's delivery compared with ventouse delivery (RR 1.79, 95% CI 1.08–2.98), but rates of neonatal birth trauma were lower (RR 0.49, 95% CI 0.26–0.91). There were no differences seen in the rates of 5-min APGAR score < 7 between Kielland's delivery and other instrumental births, but they were lower when compared with second-stage CS (RR 0.47, 95% CI 0.23–0.97). Conclusions Kielland's rotational forceps delivery is a safe option for the management of fetal malposition in the second stage of labour

Risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review of the literature

Objectives: To estimate the risk of miscarriage after amniocentesis or chorionic villus sampling (CVS) based on a systematic review of the literature. Methods: A search of MEDLINE, EMBASE, and The Cochrane Library (2000-2017) was carried out to identify studies reporting complications following CVS or amniocentesis. The inclusion criteria for the systematic review were studies reporting results from large controlled studies (n1,000 invasive procedures) and those reporting data for pregnancy loss prior to 24 weeks’ gestation. Data for cases that had invasive procedure and controls were inputted in contingency tables and risk of miscarriage was estimated for each study. Summary statistics were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Results: The electronic search from the databases yielded 2,465 potential citations of which 2,431 were excluded, leaving 34 studies for full-text review. The final review included 10 studies for amniocentesis and 6 studies for CVS, which were used to estimate risk of miscarriage in pregnancies that had an invasive procedure and the control pregnancies that did not. The procedure-related risk of miscarriage following amniocentesis was 0.35% (95% confidence interval [CI]: 0.07 to 0.63) and that following CVS was 0.35% (95%C CI: -0.31 to 1.00). Conclusion: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks

Objective: To assess the additive value of fetal growth velocity between 32 and 36 weeks’ gestation on the performance of ultrasonographic estimated fetal weight (EFW) at 35+0 - 36+6 weeks’ gestation for prediction of small for gestational age (SGA) neonates and adverse perinatal outcome. Methods: This was a prospective study of 14,497 singleton pregnancies that had undergone routine ultrasound examination at 28+0 - 34+6 and at 35+0 - 36+6 weeks’ gestation. Multivariable logistic regression analysis was used to determine whether addition of growth velocity, defined by a difference in EFW and abdominal circumference (AC) Z-scores between the early and late third trimester scans divided by the time interval between them, improved the performance of EFW at 35+0 - 36+6 weeks in the prediction of first, delivery of SGA neonates with birthweight <10th and <3rd percentiles within two weeks and at any stage after assessment and second, composite of adverse perinatal outcome defined as stillbirth, neonatal death or admission to the neonatal unit for ≥48 hours. Results Multivariable logistic regression analysis demonstrated that significant contributors to prediction of SGA neonates were EFW Z-score at 35+0 - 36+6 weeks’ gestation, fetal growth velocity by either AC or EFW Z-scores and maternal risk factors. The area under the receiver operating characteristic curves (AUROC) and detection rate (DR) with 95% confidence interval, at 10% screen positive rate, for prediction of SGA neonates <10th percentile born within two weeks of assessment achieved by EFW Z-score at 35+0 - 36+6 weeks (AUROC 0.938, 0.928 - 0.947; DR 80.7, 77.6 - 83.9) were not significantly improved by addition of EFW growth velocity and maternal risk factors (AUROC 0.941, 0.932 - 0.950; p=0.061; DR 82.5, 79.4 - 85.3). Similar results were obtained when growth velocity was defined by AC rather than EFW growth velocity. Similarly, there was no significant improvement in AUROC and DR, at 10% screen positive rate, for prediction of SGA neonates <10th percentile born at any stage after assessment or SGA neonates <3rd percentile born within two weeks or at any stage after assessment achieved by EFW Z-score at 35+0 - 36+6 weeks by addition of maternal factors and either EFW growth velocity of AC growth velocity. Multivariable logistic regression analysis demonstrated that the only significant contributor to adverse perinatal outcome was maternal risk factors. Multivariable logistic regression analysis in the group with EFW <10th percentile demonstrated that significant contribution to prediction of birth of neonates with birthweight <10th and <3rd percentiles and adverse perinatal outcome was provided by EFW Z-score at 35+0 - 36+6 weeks, but not by AC growth velocity <1st decile. Conclusion: The predictive performance of EFW at 35+0 - 36+6 weeks’ gestation for birth of SGA neonates and adverse perinatal outcome is not improved by addition of estimated growth velocity between 32 and 36 weeks’ gestation

Prediction of adverse perinatal outcome by cerebroplacental ratio in women undergoing induction of labor

Objective: To investigate the performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured within 24 hours of induction of labor. Methods: This was a prospective observational study in 1,902 singleton pregnancies undergoing induction of labor at ≥ 37 weeks’ gestation. Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) before induction of labor. The measured UA PI and MCA PI and their ratio were converted to multiples of the median (MoM) after adjustment for gestational age. Univariate and multivariate logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for cesarean section for presumed fetal distress and neonatal adverse outcome, which included umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score 24 hours, or hypoxic ischemic encephalopathy. Results: A combination of maternal and pregnancy characteristics, including age, weight, racial origin, previous obstetric history, preeclampsia, gestational age at delivery and amniotic fluid volume, identified 39% of pregnancies requiring cesarean section for fetal distress at FPR of 10%; addition of CPR did not improve the performance of screening. In screening for adverse neonatal outcome by a combination of parity and CPR the DR was 17% at FPR of 10%. Conclusion: Low CPR, measured within 24 hours of induction of labor, is associated with increased risk of cesarean section for fetal distress and adverse neonatal outcome, but the performance of CPR for such surrogates of adverse perinatal outcome is poor

Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test

Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 contingent on the results of the first-trimester combined test in twin pregnancies. Methods: Screening for trisomies 21, 18 and 13 was carried out by a combination of maternal age, fetal nuchal translucency (NT) thickness, and serum free ß-hCG and PAPP-A at 11-13 weeks’ gestation in 959 twin pregnancies in two UK NHS hospitals. Women in the high-risk group (risk >1 in 100) were offered options of invasive testing, cfDNA testing or no further testing and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates. Results: In 42 (4.4%) of the 959 pregnancies there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow up. The 917 pregnancies with known trisomic status of both twins, included 6 that were discordant for trisomy 21, 4 discordant for trisomy 18 and 896 with no trisomies 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.2%) and 667 (72.7%) of the pregnancies were classified as high-risk, intermediate-risk and low-risk, respectively. The high-risk group included 5 (83.3%) cases of trisomy 21 and 3 (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included 6 with trisomy 21, 3 with trisomy 18 and 206 with no trisomies 21, 18 or 13. The cfDNA test correctly classified as screen positive all 6 cases of trisomy 21 and 2 of the 3 with trisomy 18 and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening, led to prenatal detection of all cases of trisomy 21 and 3 of 4 with trisomy 18. Conclusions: The study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies

Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome

Background: Third trimester studies in selected high-risk pregnancies have reported that low cerebroplacental ratio (CPR), due to high pulsatility index (PI) in the umbilical artery (UA), and or decreased PI in the fetal middle cerebral artery (MCA), is associated with increased risk of adverse perinatal outcomes. Objective: To investigate the predictive performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured routinely at 35+6 - 36+6 weeks’ gestation. Methods: This was a prospective observational study in 47,211 women with singleton pregnancies undergoing routine ultrasound examination at 35+6 - 36+6 weeks’ gestation, including measurement of UA-PI and MCA-PI. The measured UA-PI and MCA-PI and their ratio were converted to multiples of the median (MoM) after adjustment for gestational age. Multivariable logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history and obstetric factors. The following outcome measures were considered: first, adverse perinatal outcome consisting of stillbirth, neonatal death or hypoxic ischemic encephalopathy grades 2 and 3, second, presence of surrogate markers of perinatal hypoxia consisting of umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score 24 hours, third, cesarean section for presumed fetal distress in labor, and fourth, neonatal birthweight <3rd percentile for gestational age. Results: Low CPR was associated with increased risk of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, cesarean section for presumed fetal distress in labor and birth of neonates with birthweight <3rd percentile. However, multivariable regression analysis demonstrated that the prediction of these adverse outcomes by maternal demographic characteristics and medical history was only marginally improved by the addition of CPR. The performance of low CPR in the prediction of each adverse outcome was poor, with detection rates of 13–26% and false positive rate of about 10%. In appropriate for gestational age (AGA) neonates with birthweight ≥10th percentile the predictive accuracy of CPR was low with positive and negative likelihood ratios (LRs) ranging from 1.21 to 1.82, and 0.92 to 0.98, respectively; although the accuracy was better in small for gestational age (SGA) neonates this was also low with positive LRs of 1.31 to 2.26 and negative LRs of 0.69 to 0.92. Similar values were obtained in fetuses classified as SGA and AGA according to the estimated fetal weight. In the prediction of adverse outcomes within two weeks, rather than at any stage, after assessment the detection rate was higher but this was achieved at higher false positive rate and therefore similar positive and negative LRs. Conclusion: In pregnancies undergoing routine antenatal assessment at 35+0 - 36+6 weeks’ gestation measurement of CPR provides poor prediction of adverse perinatal outcome in both SGA and AGA fetuses. Consequently, there is no justification in a shift of the focus of prenatal care from identification of pregnancies with low estimated fetal weight to that of pregnancies with low CPR

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks

Objective: To evaluate the performance of ultrasonographic estimated fetal weight (EFW) at 35+0 - 36+6 weeks’ gestation in the prediction of small for gestational age (SGA) neonates and assess the additive value of first, maternal risk factors and second, fetal growth velocity between 20 and 36 weeks’ gestation in improving such prediction. Methods: This was a prospective study of 44,043 singleton pregnancies that had undergone routine ultrasound examination at 19+0 - 23+6 and at 35+0 - 36+6 weeks’ gestation. Multivariable logistic regression analysis was used to determine whether addition of maternal risk factors and growth velocity, defined by a difference in EFW Z-scores or fetal abdominal circumference (AC) Z-scores between the third and second trimester scans divided by the time interval between them, improved the performance of EFW at 35+0 - 36+6 weeks in the prediction of delivery of SGA neonates with birthweight <10th and <3rd percentiles within two weeks and at any stage after assessment. Results: Screening by EFW at 35+0 - 36+6 weeks’ gestation <10th percentile predicted 63.4% (95% CI 62.0, 64.7) of neonates with birthweight <10th percentile and 74.2% (95% CI 72.2, 76.1) of neonates with birthweight <3rd percentile born at any stage after assessment, at screen positive rate of 10%. The respective values for SGA neonates born within two weeks of assessment were 76.8% (95% CI 74.4, 79.0) and 81.3% (95% CI 78.2, 84.0). In the group of fetuses with EFW <10th percentile, 43.7% were born with birthweight ≥10th percentile. For a desired 90% detection rate of SGA neonates delivering at any stage after assessment the necessary screen positive rate would be 33.7% for SGA <10th percentile and 24.4% for SGA <3rd percentile. Multivariable logistic regression analysis demonstrated that in the prediction of SGA neonates with birthweight <10th and <3rd percentiles there was a significant contribution from EFW Z-score at 35+0 - 36+6 weeks’ gestation, maternal risk factors and AC growth velocity, but not EFW growth velocity. However, the area under the receiver operating characteristic curves for SGA neonates in screening by maternal risk factors and EFW Z-score was not improved by addition of AC growth velocity. Conclusion: Screening for SGA neonates by EFW at 35+0 - 36+6 weeks’ gestation and use of a cut-off of the 10th percentile predicts 63% of affected neonates. Prediction of 90% of SGA neonates necessitates classification of about 35% of the population as being screen positive use of the 35th percentile cut-off in EFW. The predictive performance of EFW is not improved by addition of estimated growth velocity between the second and third trimesters of pregnancy

Impaired placental perfusion and major fetal cardiac defects

Objectives: To investigate the relationship between fetal congenital heart defects (CHD) and placental perfusion assessed by uterine artery pulsatility index (UtA-PI) in relation to development of preeclampsia (PE). Methods: This was a prospective screening study in singleton pregnancies at 19-24 weeks’ gestation. Transvaginal ultrasound was used to measure the UtA-PI and the values were converted into multiples of the normal median (MoM). Median MoM values in pregnancies with fetuses with isolated major CHD were compared to those without CHD in relation to development of PE. Results: The 91,407 singleton pregnancies fulfilling the entry criteria included 206 (0.23%) with isolated major fetal CHD and 91,201 without CHD. The prevalence of PE was 4.4% in those with CHD and 2.7% in those without CHD (RR 1.6, 95% CI 0.84-3.04; p=0.150); the respective values for preterm-PE, with delivery at <37 weeks’ gestation, were 2.4% and 0.7%, (RR 3.4, 95% CI 1.42-8.09; p=0.006). In the total population, the median UtA-PI MoM was significantly higher in those that developed PE compared to those without PE (1.22, IQR 0.94-1.57 vs. 1.00, IQR 0.84-1.19; p<0.0001) and in the PE group the median UtA-PI MoM was inversely related to gestational age at delivery (r=-0.458; p<0.0001). The same pattern of inverse relationship between UtA-PI MoM and gestational age at delivery with PE was observed in pregnancies with and without CHD, but in the CHD group, compared to those without CHD, UtA-PI was significantly higher both in pregnancies with and in those without PE. Conclusions: In both pregnancies with and without fetal CHD that develop PE impedance to flow in the uterine arteries is increased and this increase is particularly marked in those with preterm-PE. The prevalence of preterm-PE is more than 3 times higher in pregnancies with than without fetal major CHD and the prevalence of major CHD in pregnancies with preterm-PE is also more than 3 times higher than in those without PE. However, >97% of pregnancies with fetal CHD do not develop preterm-PE and >99% of pregnancies with preterm-PE are not associated with fetal CHD

Comparison of screening for pre-eclampsia at 31-34 weeks' gestation by sFlt-1/PlGF ratio and a method combining maternal factors with sFlt-1 and PlGF

Objective: To estimate the patient-specific risk of preeclampsia (PE) at 31-34 weeks’ gestation by a combination of maternal characteristics and medical history with multiple of the median (MoM) values of serum placental growth factor (PLGF) and serum soluble fms-like tyrosine kinase-1 (sFLT-1) and compare the performance of screening to that achieved by the sFLT-1 to PLGF ratio. Methods: This was a prospective observational study in women attending for a third-trimester ultrasound scan at 31-34 weeks as part of routine pregnancy care. We estimated the performance of screening of PE with delivery within four weeks of assessment (PE at <4 weeks) and PE from four weeks after assessment and up to 40 weeks’ gestation (PE at 4w-40GW) in screening by the sFLT-1 to PLGF ratio and by a to PLGF ratio and by a method utilizing Bayes theorem to combine maternal factors and MoM values of sFLT-1 and PLGF. The significance of difference in performance of screening between the method utilising Bayes theorem and that of the sFLT-1 to PLGF ratio was assessed by comparison of the areas under the receiver operating characteristic curves (AUROC). Results: The study population of 8,063 singleton pregnancies included 231 (2.9%) that subsequently developed PE. In the prediction of delivery with PE at <4 weeks the performance of the method utilising Bayes theorem was similar to that of the sFLT-1 to PLGF (AUROC: 0.987, 95%CI 0.979-0.995 vs. 0.988, 95%CI: 0.981-0.994; p=0.961). and at fixed fixed screen positive rate (SPR) of 3.9% the detection rate (DR) was 87.1% for both methods. In contrast, the performance of screening for delivery with PE at 4w-40GW was better with the method utilising Bayes theorem than with the sFLT-1 to PLGF ratio (AUROC: 0.884, 95%CI 0.854-0.914 vs. 0.818, 95%CI: 0.775--0.860 ; p<0.0001) and at total fixed SPR of 25.7% the DRs were 84.4% vs. 73.0%. Conclusion: At 31-34 weeks’ gestation the performance of screening for PE at <4 weeks from assessment by the method utilising Bayes theorem is similar to that of the sFLT-1 to PLGF ratio, but the former is superior to the latter in prediction of PE >>4 weeks

Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis

Objective: The objective of our study was to estimate the procedure-related risks of miscarriage following CVS and amniocentesis in a large unselected screened and to determine whether these risks are consistent with those reported in systematic reviews and meta-analysis. Methods: This was a retrospective cohort study undertaken at a large Fetal Medicine Unit in the United Kingdom during the period of January 2009 to May 2018. We included all singleton pregnancies that booked at our unit before 20 weeks after excluding those with multiple pregnancies, major fetal defects, terminations and lost to follow-up. We estimated the risk of miscarriage in those that had a CVS or amniocentesis as well as those that did not have any invasive procedure, to estimate the procedure-related risk as a risk-difference (95% confidence interval [CI]). Univariate and multivariate regression analysis was used to derive odds ratios (OR) (95%CI) and determine which maternal and pregnancy characteristics provided a significant contribution in prediction of miscarriage and whether CVS or amniocentesis provided a significant independent. Results: During the study period, there were 45,120 singleton pregnancies, including 1,546 that had an invasive procedure. We excluded 1,429 pregnancies (3.2%), due to fetal defects, termination of pregnancy or those with missing outcomes. In pregnancies that underwent CVS, the risk of miscarriage was 1.5% (13/861), compared to 1.2% (476/39,152) in pregnancies that did not have a procedure (p=0.437). In pregnancies that underwent an amniocentesis, the risk of miscarriage was 0.8% (3/375), compared to 1.2% (491/42,463) in those that did not (p=0.520). Univariate and multivariate regression analysis demonstrated that there was no significant prediction to the risk of miscarriage from CVS (p=0.399; p=0.592, respectively) or amniocentesis (p=0.543; p=0.550, respectively). The risk of procedure-related loss attributed to CVS was 0.29% (95%CI: -0.53-1.12) and that following amniocentesis was -0.36% (95%CI: -1.26-0.55), which was not significantly different from those that did not have any procedure. Conclusion: The procedure-related risks of miscarriage following CVS and amniocentesis are considerably lower than currently quoted. The estimates of risks based on our study are 0.29% for CVS and -0.36 for amniocentesis