Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

OBJECTIVES: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97). CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

A new model based on artificial intelligence to screening preterm birth.

OBJECTIVE: The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI). METHODS: This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM. RESULTS: The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001). CONCLUSION: AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.

Hepatic arterial buffer response in monochorionic diamniotic pregnancies with twin-to-twin transfusion syndrome.

OBJECTIVES: Hepatic arterial buffer response (HABR) is an important regulatory process for hepatic blood flow. Its activity has been described in some fetal adverse conditions but in twin-to-twin transfusion syndrome (TTTS) it is unknown if such response is present. The aim of this study is to test the hypothesis that HABR operates in monochorionic diamniotic twins (MCDA) with TTTS. METHODS: Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured prospectively in 64 MCDA pregnancies. 43 without TTTS (group 1) and in 21 pregnancies with TTTS (group 2). We calculated ratios for PI (HAPI-ratio) and PSV (HAV-ratio) between recipient and donor in group 2 or bigger and smaller fetus in group 1 and compared groups. The association of HAV-ratio and HAPI ratio with TTTS, relation with other fetal Dopplers and reliability of measurement by a single operator were investigated. RESULTS: HAV-ratio and HAPI-ratio appears to be independent from fetal Dopplers, estimated weight and gestational age. In group 2, HAV-ratio is lower than group 1 (p<0.001, 95% CI 0.443-0.643). In group 1 the mean HAV-ratio is 1.014 (±0.021) while in group 2 is 0.47 (±0.035). HAPI-ratio is lower in group 2 than in group 1 although this difference was not significant (p=0.066, 95% CI -0.007-0.231). A good reliability of measurements of hepatic artery PSV and PI was demonstrated by intraclass correlation coefficient analysis (ICC 0.971 95% CI 0.963-0.977, p<0.001 and ICC 0.694 95% CI 0.596-0.772, p<0.001, respectively). CONCLUSIONS: Monochorionic pregnancies with TTTS are associated with lower HAV-ratios. This could be explained by an active HABR.

Cervical pessary plus vaginal progesterone in a singleton pregnancy with a short cervix: an experience-based analysis of cervical pessary's efficacy.

BACKGROUND: Several studies were published about cervical pessary, with controversial results. These studies demonstrated that the patient follow-up after pessary insertion is very different between the study centers and the number of pessary insertions per center was often <30 cases. This study aims to determine cervical pessary performance in singleton pregnancies with a short cervix based on a single center learning curve. METHODS: Between 2011 and 2018, 128 singleton pregnancies between 18 and 24 gestational weeks with a short cervix (<25 mm) were referred to our clinic. All cases were treated with progesterone, and when available in our supplies (due to low resources) cervical pessary was also offered. Three groups were created for statistical analysis: Group 1 (n = 33), treated with progesterone-only; Groups 2 and 3, treated with cervical pessary plus progesterone. Group 2 included the first cases (n = 30) of pessary, defined by a learning curve and cumulative sum analysis, while Group 3 included the subsequent 65 cases. The primary outcome was preterm birth (PTB) < 34 gestational weeks. RESULTS: The learning curve was performed with all cases of pessary plus progesterone, and 30 patients were obtained as the number needed for learning, in our study with two operators. The PTB rate < 34 weeks was 27.3, 20, and 4.6% in groups 1, 2, and 3, respectively. There was no significant difference between Group 1 and 2 (OR 1.1; 95% CI 0.066 - 18.45; p = .945). When comparing Groups 1 and 3 there was a significant difference in PTB rates (OR 0.08; CI95% 0.01-0.42; p = .003). Considering Kaplan-Meyer Survival analysis, we can observe that the performance of progesterone alone (Group 1) was similar to Group 2 (progesterone + first 30 cases of pessary) (p = .432), but the performance of Group 3 (progesterone + subsequent 65 cases of pessary) and Group 1 shows a statistically significant difference (p = .011). CONCLUSION: Learning curve and cumulative sum analysis determined that the application and surveillance of at least 30 patients is required to see significant improvements in the primary outcome of PTB < 34 weeks.

Prevalence and outcome of absence of ductus venosus at 11(+0) to 13(+6) weeks.

INTRODUCTION: To examine the prevalence and outcome of absent ductus venosus (DV) diagnosed at 11-13 weeks' gestation. METHOD: Prospective screening study for aneuploidies in 65,840 singleton pregnancies, including measurement of nuchal translucency (NT) thickness and examination of the DV. Prenatal findings and outcome of fetuses with absent DV were examined. RESULTS: Absent DV was diagnosed in 26 cases giving a prevalence of 1 in 2,532. In 15 (57.7%) cases the NT was above the 95th centile for crown-rump length. In 11 (42.3%) cases, there was an aneuploidy, mainly Turner syndrome. The incidence of aneuploidies was 66.7% (10 of 15) for those with NT above the 95th centile and 9.1% (1 of 11) in those with normal NT (p = 0.015). In addition to the aneuploidies, there were 3 cases with other abnormalities, including one case each of Ebstein anomaly, Noonan syndrome and Pierre Robin sequence. In 9 of the 11 (81.8%) fetuses with NT below the 95th centile, absent DV was an isolated finding and the pregnancies resulted in healthy live births. CONCLUSION: The prognosis of fetuses with absent DV depends on the measurement of NT thickness, being poor if the NT is increased and good if the NT is normal.

Screening for trisomies in dichorionic twins by measurement of fetal nuchal translucency thickness according to the mixture model.

OBJECTIVE: To examine the distribution of fetal nuchal translucency (NT) thickness in dichorionic twins and investigate the effect of the correlation between NT measurements in each twin pair on the performance of screening for trisomies. METHODS: The distribution of fetal NT for crown-rump length (CRL) was examined in 5646 dichorionic twin pregnancies, including 103 with fetal trisomies 21, 18 or 13. The correlation in fetal NT in each euploid twin pregnancy was estimated. RESULTS: The distribution of NT in both euploid and trisomic fetuses was consistent with the mixture model in singleton pregnancies. In the euploid pregnancies, there was a correlation in log NT measurements in each twin pair (r = 0.42, 95% CI: 0.39-0.45) and, after removal of the effect of the operator, this correlation was reduced to 0.34. Allowing for this correlation in risk assessment for trisomies had a major impact on the estimated patient-specific risk but had little effect on the overall performance of screening. CONCLUSIONS: In dichorionic twin pregnancies, the mixture model of distributions of NT can be applied as in singletons. In screening for trisomies, the correlation in NT measurements between the fetuses should be taken into account in the estimation of patient-specific risks.

Maternal plasma plasminogen activator inhibitor-2 at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVE: In patients with preeclampsia maternal plasma concentration of plasminogen activator inhibitor-2 (PAI-2) is reduced. The objective of the study was to determine if the altered levels of PAI-2 precede the onset of the disease. METHODS: Plasma PAI-2 was measured at 11-13 weeks of gestation in 119 pregnancies that developed preeclampsia, 85 that developed gestational hypertension and 204 controls. RESULTS: There were no significant differences in PAI-2 between the preeclampsia, gestational hypertension and controls (1.07 MoM, 1.08 MoM and 0.96 MoM). CONCLUSION: The decrease in plasma PAI-2 observed in preeclampsia does not precede the clinical onset of the disease.