Prediction of spontaneous preterm birth in women with previous full dilatation cesarean delivery.

BACKGROUND: A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth. OBJECTIVE: This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth. STUDY DESIGN: This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed. RESULTS: Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035). CONCLUSION: In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.

First trimester screening for pre-eclampsia and targeted aspirin prophylaxis: a cost-effectiveness cohort study.

OBJECTIVE: Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. DESIGN: Retrospective observational study. SETTING: London tertiary hospital. POPULATION: 5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method. METHODS: Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal-Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. MAIN OUTCOME MEASURES: Incremental healthcare costs and QALY gained per pregnancy screened. RESULTS: Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. CONCLUSIONS: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving.

Training in Obstetric Ultrasound Biometry: Results from a Multicenter Reproducibility Study.

OBJECTIVES: To assess the intra- and interobserver reproducibility of fetal biometry measurements obtained by trainee (junior) and experienced sonographers (senior) in the contest of two training programs in obstetric ultrasound. METHODS: This was a prospective study on 192 women recruited ensuring an even distribution throughout gestation (18-41 weeks), at University College London Hospital (UCLH), England (87 cases), and at Maternité Regionale Universitaire de Nancy (MRUN), France (105 cases). The training took place in two training centers with experience in ultrasound training and subspecialist training in fetal medicine. Measurements for head circumference (HC), abdominal circumference (AC), and femur length (FL) were obtained twice by junior and senior sonographers, blind to their own and each other's measurements. Differences between and within sonographers were expressed in millimeters and as a percentage of fetal dimensions. Reproducibility was assessed using Bland-Altman plots. RESULTS: Reproducibility was overall high with 95% confidence intervals (CI) within <6% for intraobserver and <8% for interobserver reproducibility. Intraobserver reproducibility was lower within junior than within senior sonographers' measurements for HC (95% CI: <4% versus <3%) and FL (95% CI: <6% and < 5%). Intraobserver reproducibility was similar between the two centers/training programs (AC 95% CI: <6%). Cumulative interobserver reproducibility in both centers was similar to the reproducibility within a single site (95% CI: <5%, <8%, and <7% for HC, AC, and FL, respectively). CONCLUSIONS: Reproducibility of fetal biometry measurement was high in centers with structured training programs regardless of sonographers' experience. Reproducibility was higher in sonographers who completed the training.

Factors associated with preterm birth in women undergoing cervical cerclage.

OBJECTIVES: Cervical cerclage is used to manage women at high risk of late miscarriage (LM) and spontaneous preterm birth (PTB) due to factors such as history of cervical insufficiency (CI), uterine anomaly, cervical surgery and ultrasound (US) diagnosed cervical shortening. Urinary tract infection (UTI) and subsequent pyelonephritis, and bacterial infection are associated with PTB, but their role in PTB after cervical cerclage is unknown. We examined the relationship between UTI and bacterial vaginosis (BV), fetal fibronectin (fFN) test and PTB in women undergoing elective- or US-indicated cervical cerclage. We also investigated whether fetal fibronectin (fFN) test were useful to predict PTB. STUDY DESIGN: This is a single center, retrospective study of singleton pregnant women at PTB clinic, University College London Hospital (UCLH, 2005-2015) who underwent elective or US-indicated cervical cerclage. Women were tested for UTI and BV before cerclage placement and received mid-gestation fFN testing. Patient data were extracted from the PTB clinic database and electronic records. Statistical analyses used Pearson's chi-square and Mann-Whitney U tests. P values were corrected by Bonferroni method as required. RESULTS: 267 singleton pregnant women attended our clinic with completed birth outcome. Of those, 32.2% (86/267) delivered prematurely. All women with UTI or BV received antibiotic treatment. Women with a UTI before cerclage placement were more likely to deliver preterm when compared to those with negative MSU culture (OR 3.39, 95%CI 1.24-9.27, p = 0.04). Their gestational age at delivery were also lower than those with negative MSU result (36+6, IQR 31+4-38+2week vs 38+1, IQR 36+1-39+5-week, p = 0.05). However, UTI after cerclage placement or BV either before or after cerclage placement were not associated with PTB. Women who had a positive fFN result were more likely to deliver preterm (OR 3.85, 95% CI 1.81-8.41, p = 0.0007). CONCLUSIONS: The presence of a UTI before cervical cerclage is associated with a higher rate of PTB in women who receive a cervical cerclage, even when treated. We did not find an association between pre or post-cerclage BV or post-cerclage UTI and PTB. Further research is needed to elucidate the link between UTI and PTB in women undergoing cervical cerclage.

Maternal plasma pentraxin 3 at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVE: To investigate whether in pregnancies that subsequently develop preeclampsia (PE), the maternal plasma concentration of the inflammatory factor pentraxin 3 (PTX3) at 11-13 weeks of gestation is increased and whether such a possible increase is associated with uterine artery pulsatility index (PI). METHODS: The concentration of plasma PTX3 at 11-13 weeks was measured in a case-control study from 120 pregnancies that developed PE, including 27 who required delivery before 34 weeks (early PE), 87 cases of gestational hypertension (GH) and 207 normal controls. The median PTX3 multiple of the median (MoM) in the control and hypertensive groups were compared. Regression analysis was used to determine the significance of the association between plasma PTX3 and uterine artery PI. RESULTS: Plasma PTX3 was significantly higher in the early PE group (1.44 MoM; p < 0.0083) but not in late PE (1.11 MoM) or GH (1.10 MoM) compared to the controls (0.97 MoM). There was no significant association between plasma PTX3 levels and uterine artery PI in either the PE group (p = 0.693) or in the controls (p = 0.209). CONCLUSION: Increase in maternal plasma PTX3 in pregnancies that subsequently develop early PE is evident from 11-13 weeks but the underlying mechanism for such an increase remains uncertain.

Maternal serum angiopoietin-2 at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVE: In women with preeclampsia (PE), the serum concentration of the growth factor angiopoietin-2 (Ang-2) is significantly lower than in unaffected controls. The objective of this study is to determine if the decrease in serum Ang-2 is evident from the first trimester of pregnancy before the clinical onset of PE. METHODS: Serum Ang-2 and uterine artery pulsatility index (PI) were measured at 11 to 13 weeks in 126 pregnancies that subsequently developed PE, 88 cases that developed gestational hypertension (GH) and 214 unaffected controls. RESULTS: Maternal serum Ang-2 in the PE group [0.96 multiple of the median (MoM)] and in GH (1.12 MoM) was not significantly different from the unaffected group (1.07 MoM). Uterine artery PI was significantly higher in the PE group (1.32 MoM) but not in GH (1.11 MoM) compared to the unaffected group (1.05 MoM). CONCLUSION: In pregnancies that develop PE there is Doppler evidence of impaired placentation from the first trimester of pregnancy. However, the impaired placentation is not reflected in altered maternal serum levels of Ang-2.