First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes-a single center cohort study.

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

Hepatic arterial buffer response: activation in donor fetuses and the effect of laser ablation of intertwin anastomosis.

OBJECTIVES: Hepatic arterial buffer response (HABR) is an important defence mechanism for maintaining liver blood flow. It is suspected that HABR is active in monochorionic diamniotic twins (MCDA) with twin-to-twin transfusion syndrome (TTTS) where donor compensates a setting of volume depletion and the recipient an overload. The present study investigates whether in TTTS, HABR is active in donor and/or recipient individually and try to determine if the activation of HABR is a direct response to TTTS. METHODS: Hepatic artery (HA) peak systolic velocity (PSV) was measured in normal MCDA fetuses and TTTS. Correlation with relevant fetal Dopplers and characteristics were determined. Z-scores for HA-PSV (HAV-Z) were calculated and its association with TTTS in donors and recipients were determined as well as changes in HAV-Z after laser treatment. RESULTS: In this study 118 MCDA were included, 61.9 % normal and 38.1 % TTTS. Of the TTTS 22 required laser treatment. A total of 382 scans were performed in normal group and 155 in TTTS. Our data demonstrates that in donors HAV-Z was 2.4 Z-scores higher compared to normal fetuses (ß=2.429 95 % CI 1.887, 2.971; p<0.001) and after laser treatment HAV-Z reduced (ß=-1.829 95 % CI -2.593, -1.064; p<0.001). There was no significant difference between recipients and normal (ß=-0.092 95 % CI -0.633, 0.449; p=0.738). CONCLUSIONS: HABR is active in TTTS, promoting an increased hepatic blood flow in donors. The activation is direct response to TTTS as shown by the reduction in HAV-Z after laser. This finding provides important insights into the pathophysiology of TTTS.

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.

Fetal Megacystis in the first trimester: Comparing management and outcomes between longitudinal bladder length groups.

Fetal megacystis is a sonographic sign, defined in first trimester as a longitudinal bladder length (LBD)>7 mm. Different causes may be associated with megacystis and outcomes vary with many factors. There are no international guidelines on how to manage megacystis cases, and invasive testing is controversial when no other abnormalities are found. The main objective of this study is to compare etiologies, management and outcomes of fetuses with first trimester megacystis, specifically between groups of LBD≤15 mm and >15 mm. This is a retrospective cohort study of megacystis cases managed in a Prenatal Diagnosis Center, between January 2009 and September 2020. Descriptive and bivariate analysis were performed. We studied 43 fetuses: 67.4% with LBD≤15 mm and 32.6% with LBD>15 mm. We found an association between LBD and isolated Low Urinary Tract Obstruction (LUTO) (3.4% vs 64.3%; p<0.001) and with isolated megacystis (44.8% vs 0.0%; p = 0.001). No differences were seen regarding the presence of aneuploidies (31.0% vs 14.3%; p = 0.213). Invasive testing was performed in 93.0% of cases. Overall, we report 41.9% of live births, 39.5% of pregnancy termination and 18.6% of intrauterine fetal demise. We found a higher rate of live births in fetuses with LBD≤15 mm (55.2% vs 14.3%; p = 0.011). For a mean follow-up time of 20.6 months, we report one neonatal death and one case of renal insufficiency. In conclusion, isolated LUTO is more frequent if LBD>15 mm whereas isolated megacystis is more frequently found if LBD≤15 mm. If LBD≤15 mm, live birth rates and long-term outcomes seem to be enhanced.

Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

OBJECTIVE: The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. STUDY DESIGN: A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. RESULTS: In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05; p = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02; p = 0.066, respectively). CONCLUSION: Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. KEY POINTS: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..

Nasal bone in fetal aneuploidy risk assessment: are they independent markers in the first and second trimesters?

OBJECTIVES: In the mid-trimester ultrasound, nasal bone (NB) length can be used to correct the a priori risk for trisomy 21. Our study aims to evaluate if there is a correlation between an absent NB in the first trimester and a hypoplastic NB in the second trimester. METHODS: Our two year retrospective analysis of data derived from routine clinical practice. Single euploid fetuses were included. The NB was assessed in both trimesters according to international guidelines and transformed into categorical variables. Logistic regression was performed in order to accomplish our main objective. RESULTS: From the 759 normal pregnancies included, 45 (5.93%) had abnormal NB in the first trimester and 23 (3%) in the second trimester. Eleven cases (47.8%) of the abnormal NB in the second trimester were abnormal in the 11-14 weeks scan. After the diagnosis of an absent NB in the first trimester the odds ratio (OR) for a hypoplastic NB in the second trimester is 18.926 (7.791-45.977; p-value <0.01). CONCLUSIONS: Our data suggest a strong association between the NB in the first and in the second trimester in normal euploid fetuses. This is important information to consider when counseling patients on the basis of this ultrasound marker.

Chorionic villus sampling: 10 years of experience in a University referral center.

OBJECTIVES: The purpose of this study was to estimate our center-specific CVS-related miscarriage rate. METHODS: This is an observational retrospective study of women submitted to a CVS in our hospital, between January 1st, 2007 and December 31st, 2016. Maternal and pregnancy characteristics, procedure details, genetic results and pregnancy outcomes of all patients were collected. The FMF miscarriage risk algorithm was used to estimate our population expected risk of miscarriage. To establish the procedure-related risk of miscarriage, we compared the observed with the expected miscarriage rate. RESULTS: We had a total number of 1523 women with a singleton pregnancy who did a CVS over the 10-year period. The mean maternal age was 34 years old; the majority of the women was Caucasian, multiparous and had a spontaneous pregnancy. The most common indication for CVS was a high-risk result in the 1st trimester combined screening test. The karyotype was normal in 72,7% of cases, 11,1% were T21 and 7,2% were T13 or T18. In the study group, 33 women were diagnosed with a fetal demise, 435 had a TOP and there were 4 intrauterine deaths and 34 miscarriages. The rate of miscarriage in our population was 3,2% and the expected patient specific risk for miscarriage was 3,0%. There was no statistical significance between the two miscarriage rates p = 0,705. CONCLUSION: In our study the risk of miscarriage in the CVS group was not significantly different from that the expected patient specific risk (3.2 % vs 3%, p = 0.7). The procedure-related risk of miscarriage was 0,2%, similar to the rates describe in the literature. An accurate risk of pregnancy loss should be used when counseling women for CVS to allow an informed decision.

Prediction of birth weight discordance from fetal weight estimations at 21-24 weeks' scans in monochorionic and dichorionic twins.

OBJECTIVE: To evaluate if inter-twin estimated fetal weight (EFW) differences at 21-24 weeks' scans predict birth weight discordance in monochorionic and dichorionic twins born at three gestational age periods. METHODS: We counted the number of pairs with discordant EFWs (EFWs greater than the mean + 1SD; i.e. a difference above 12% in dichorionic and 21% in monochorionic twins) derived during a 21-24 weeks' scan as compared to actual discordant birth weight (>25%) in monochorionic and dichorionic pairs born at ≤32, 33-36 and >36 weeks. RESULTS: We studied 416 dichorionic and 244 monochorionic twins. The frequency of EFWs discordance at 21-24 weeks was the same for dichorionic and monochorionic twins but the total number of birth weight discordant pairs was significantly smaller among dichorionic twins (OR 0.2, 95% CI 0.1, 0.6). Generally, the positive predictive values for birth weight discordance by using the EFWs difference were quite poor, but always better in monochorionic than in dichorionic twins. Whereas the negative predictive value and hence the sensitivity for monochorionic twins was 100% irrespective of gestational age at birth, it was much lower in the dichorionic pairs. CONCLUSION: Concordant EFWs at 21-24 weeks exclude discordant birth weight in monochorionic twins whereas discordant EFWs are poor predictors of birth weight discordance especially in dichorionic twins irrespective when the twins were born.

Abdominal circumference ratio for the diagnosis of intertwin birth weight discordance.

OBJECTIVES: We assessed the accuracy of predicting severe twin birth weight discordance (>25%) using the estimated fetal weights (EFW) and abdominal circumference (AC) ratio. METHOD: A cohort of twin gestations underwent ultrasound examinations within two weeks from birth. We focused on the accuracy of EFW and on the diagnosis of severe birth weight discordance by the difference in EFWs and the AC ratio. RESULTS: The 661 eligible twin pairs included 51 (7.7%) severely discordant pairs. The accuracy of an EFW to predict the actual birth weight was quite poor, with an acceptable specificity (96.4%), but low sensitivity (28.6-40.5%), to detect severely discordant pairs, whereas an AC ratio of 1.3 detected these discordant pairs with sensitivity and specificity of 97.3-100% and 99.6-99.7%, respectively. CONCLUSION: By comparing EFWs, 59.5-71.4% of discordant pairs >25% are missed, whereas an AC ratio >1.3 would identify almost all cases.

Selective intrauterine growth restriction and vascular abnormalities of monochorionic placentation / Restrição seletiva do crescimento intrauterino e patologia vascular das placentas monocoriônicas

It is reported the clinical case of a biamnionic monochorionic twin gestation, with selective intrauterine growth restriction diagnosed at 18 weeks in the second twin and significant weight discordance, with intermittently absent end-diastolic umbilical artery flow. Possible etiology, diagnosis, classification, clinical outcome and prognosis are discussed. This is not a situation of wide acceptance yet, but in recent studies it seems to identify a subgroup with a high risk of death in the smaller twin and neurological damage in the other one.

Relata um caso clínico de gestação biamniótica monocoriónica, com restrição de crescimento intrauterino seletivo diagnosticada com 18 semanas no segundo gêmeo e grande discrepância ponderal, com fluxos diastólicos finais intermitentemente ausentes na artéria umbilical. Discute-se a possível etiologia, diagnóstico, classificação, evolução clínica e prognóstico desta entidade. É uma situação ainda não muito valorizada, que em estudos recentes parece identificar um subgrupo com risco aumentado de morte no gêmeo menor e de lesão neurológica no maior.