Prenatal features of aneurysm of the posterior cerebral artery: a case report.

BACKGROUND: Fetal cerebral aneurysm other than aneurysm of vein of Galen aneurysmal malformation (VGAM) is extremely rare. This report describes prenatal features of aneurysm of the posterior cerebral artery (APCA) with rapid progression and its natural intrauterine course of the disease, which has never been reported. CASE PRESENTATION: This is the first report of prenatal features of APCA, detected at 34-36 weeks of gestation, simulating choroid plexus cyst or arachnoid cyst. The diagnosis was based on color flow ultrasound with tracing along the course of cerebral arteries. Also, rendered 3D color flow ultrasound was helpful in demonstrating course of the vessels feeding the aneurysm and supporting the diagnosis. The aneurysm showed nature of rapidly progressive changes, leading to leakage resulting in intracerebral and intraventricular hemorrhage as well as high output state associated with anemia. Prenatal diagnosis and management are very challenging. This case ended up with planned delivery at 37 weeks, giving birth to a surviving male newborn, weighing 2600 g. The neonatal CT brain scans and CTA confirmed the prenatal findings. The prognosis was relatively poor because of extensive intracerebral hemorrhage with severe hydrocephalus and brain midline shift. The couple opted for neonatal palliative care without neurosurgical correction. CONCLUSION: This study demonstrate that the most important tool for prenatal diagnosis is color Doppler ultrasound, which will demonstrate turbulent blood flow. Three-dimension color Doppler ultrasound is helpful in supporting the diagnosis. The case presented here suggests that the disease has a natural course of rapid progression and massive brain destruction or high output congestive heart failure can be expected.

Prenatal Detection of Rapid Progressive Changes in Massive Lymphangioma from Flank to the Lower Extremity.

Lymphangioma is a congenital anomaly in which abnormal lymphatic drainages localize to form a benign mass, but it has the tendency to grow in size and the potential to infiltrate surrounding structures, causing devastating effects and leading to severe morbidity. The most common site of lymphangioma is the neck region (cystic hygroma colli), whereas lymphangioma in the lower limbs is very rare, accounting for only 2% of cases. Accordingly, the prenatal diagnosis of lymphangioma of the lower limbs has been scarcely reported. This study describes two cases of lymphangioma of the lower limbs, focusing on unique sonographic features and the natural course of rapidly progressive changes, which is different from nuchal lymphangioma. Based on previous isolated case reports together with our two cases, lymphangioma of the lower limbs usually develops in the second trimester, tends to have rapidly progressive changes, and is unlikely to be associated with aneuploidy and structural anomalies. Diagnoses can be made by using sonographic findings pertaining to the subcutaneous complex and multi-septate anechoic cystic lesions in the lower limbs, the latter of which can infiltrate visceral structures. Prenatal detection can be helpful in laying the groundwork for providing counseling to the parents and the planning of management strategies, i.e., opting to terminate the pregnancy, revising delivery plans, and looking towards the postnatal management of the infant.

Comparison of fetal and neonatal cardiac morphology between the infants of mothers with well-controlled gestational diabetes mellitus and normal controls.

OBJECTIVE: To compare fetal and neonatal cardiac morphology in fetuses of mothers with gestational diabetes mellitus (GDM) with the controls. PATIENTS AND METHODS: Pregnant women at average risk of GDM underwent 100-g, 3-h-OGTT at 24-28 weeks of gestation for diagnosis of GDM. Both GDM group and the control group underwent fetal echocardiography at 32-36 weeks to assess cardiac dimensions. The neonates underwent echocardiography within 48 h after birth to assess cardiac morphology. RESULTS: A total of 154 pregnant women were recruited, including 60 in the GDM group and 94 in the control group. All of the study group were well controlled for GDM. Most baseline characteristics of both groups were comparable. All obstetric outcomes were not significantly different between the two groups. Morphological cardiac dimensions in the fetuses and newborns of both groups were also not significant different. Subgroup analysis in the study group showed no significantly different in cardiac morphology between the group with diet control and that of insulin control. CONCLUSION: Fetal and neonatal cardiac morphologic changes among mothers with well-controlled GDM are not significantly different from those in the controls. It is possible that good control of maternal blood glucose can prevent fetal and neonatal cardiac abnormalities.

Trends in the Prevalence of Diabetes Mellitus in Pregnancy during the Past Two Decades in Northern Thailand.

Background: The prevalence of gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PDM) has increased dramatically in the past decade in all ethnic groups. The prevalence also varies markedly among different ethnic groups. Each ethnic group must have its own data about GDM/PDM for improvement in women's health care. We conducted this study with the main objective of assessing recent trends in the prevalence of PDM/GDM among pregnant women in the northern part of Thailand during the past two decades. The secondary objective is to identify the risk factors influencing the prevalence of DM in pregnancies. Patients and Methods: The maternal-fetal medicine database was accessed to retrieve consecutive obstetric records of women who gave birth in Chiang Mai University Hospital, Thailand, from January 2003 to December 2022. This is a 20-year study period of the same protocol of GDM screening policy, using the 50 g glucose challenge test as a screening test for the average risk group and the 100 g OGTT as a diagnostic test. The women were categorized into GDM, PDM and non-DM groups. Trends or percentage changes in the prevalence of GDM/PDM during the study period were evaluated. Risk factors related to GDM/PDM were identified. Results: Among 37,027 women who gave birth during the study period, the prevalence of DM in pregnancy was 11.4% (4223 cases), including 214 cases of PDM (0.6%) and 4009 cases of GDM (10.8%). The prevalence of PDM significantly increased from 0.3% in 2003 to 1.5% in 2022; also, the prevalence of GDM significantly increased, dramatically, from 3.4% in 2003 to 22.0% in 2022. The prevalence of GDM increased in recent years in all age groups (adolescent, reproductive and elderly groups), while that of PDM did not significantly change in the adolescent group during the study period. Maternal age and pre-pregnancy BMI significantly increased in the more recent years. Independent factors significantly associated with the prevalence of PDM/GDM include maternal age, pre-pregnancy BMI, higher socio-economic status, and urban areas of residence. Recent time is still an independent risk factor after adjustment for other known factors. Conclusions: Relatively, GDM and PDM are highly prevalent in the northern part of Thailand, and their prevalence continuously increased during the past two decades. The trend of increased prevalence was evident in all age groups. Increasing maternal age and pre-pregnancy BMI mainly contributed to the increase in the prevalence of GDM and PDM in recent years. Recent time is still an independent risk factor after adjustment for other known factors, indicating that some other unexplained risk factors are associated with the increase in prevalence of DM in recent years, possibly the increase in sedentary lifestyle. Modification of lifestyle, especially reducing pre-pregnancy BMI among reproductive women, may reduce the prevalence of DM in pregnancy.

Performance of Serum Quad Test in Screening for Fetal Down Syndrome in a Large-Scale Unselected Population in a Developing Country.

Objective: To assess the effectiveness of Quad test in the detection of Down syndrome (DS) in routine practice among a large-scale population and to compare the effectiveness of Quad test based on the Western reference model (WM) and that based on Thai reference model (TM). Methods: Quad test was performed on 42,769 pregnancies at 14-21 weeks. The fetal risk of DS derived from Quad test was automatically computed based on WM and used in evaluating the effectiveness. Also, the fetal risk was calculated based on the TM. Results: Of 39,740 women with complete follow-ups including 74 fetuses with DS, with WM, the detection and false positive rates were 81.1% and 7.2%, respectively, whereas the detection and false positive rates with TM were 87.8%, and 6.8%, respectively. According to ROC curves, the performance of Quad test based on TM was slightly but significantly better than that based on WM (AUC of 0.959 vs. 0.940, p = 0.001). Conclusion: Quad test is highly effective in service settings and suitable for developing countries and the effectiveness is even higher when based on ethnicity-specific reference model.

Fetal Hemodynamic Response to Anemia in Early Gestation: Using Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: To assess fetal hemodynamic changes in response to anemia in early gestation, using fetal Hb Bart's disease as a study model. METHODS: A prospective study was conducted on pregnancies at risk for fetal Hb Bart's disease at 12-14 weeks of gestation. Fetal hemodynamics were comprehensively assessed by 2D ultrasound, Doppler velocity, and cardio-STIC just prior to the invasive procedure for diagnosis. The various hemodynamic parameters of the affected and unaffected fetuses were compared. RESULTS: Of 56 fetuses at risk, 17 had Hb Bart's disease and 39 were unaffected. The right and combined ventricular cardiac outputs (CO) were significantly higher in the affected fetuses (0.993 vs. 1.358; p < 0.001 and 1.010 vs. 1.236; p < 0.001, respectively), whereas the left CO tended to be higher but not significantly (1.027 vs. 1.113; p = 0.058). Cardiac dimensions, middle-cerebral artery peak systolic velocity, Tei index, and isovolemic contraction time were significantly increased, while the global sphericity index was significantly decreased. Interestingly, cardiac preload, ventricular wall thickness, shortening fraction, isovolemic relaxation time, and fetal heart rate were unchanged. Four fetuses had hydropic changes, but all cardiac functions were normal. CONCLUSION: Fetal anemia induces hypervolemia and increases cardiac output to meet the tissue oxygen requirement, resulting in an increase in size without hypertrophy, volume load without pressure load, and a decrease in the globular sphericity index. The heart works very well but works harder, especially systolic ventricular load. Hydrops fetalis due to anemia appears not to be caused by heart failure as previously believed but rather by volume load with high vascular permeability at least in early pregnancy.

Fetal Cardiac Inflow Characteristics in Response to Fetal Anemia: Based on Fetal Hemoglobin Bart's Disease at Mid-Pregnancy.

OBJECTIVES: To identify the inflow (filling time fraction [FTF] and E/A ratio) characteristics of fetuses with anemia, and to evaluate the performance of the inflow markers in predicting the affected fetuses. METHODS: Fetuses at risk of hemoglobin (Hb) Bart's disease at 17-22 weeks were prospectively recruited to undergo echocardiography before diagnostic cordocentesis. Cardiac Doppler images were digitally stored for off-line blinded measurements of FTF and E/A ratio. RESULTS: A total of 428 fetuses at risk of Hb Bart's disease were analyzed, including 88 affected fetuses (20.6%). The mean gestational age at the time of diagnosis was 19.43 ± 1.5 weeks. The FTFs in both sides were significantly lower in the affected fetuses, whereas the E/A ratios of both sides were significantly higher in the affected group. According to the receiver operating characteristic curves, the performance of the FTF of the right side in predicting affected fetuses was slightly better than that of the left side (area under curve: 0.707 versus 0.680, P < .001). Likewise, the performance of the E/A ratio of the tricuspid valve was slightly better than that of the mitral valve. Also, FTF was superior to E/A ratio in predicting the affected fetuses. CONCLUSIONS: New insights leading to a better understanding of the fetal cardiac response to anemia are: 1) the FTFs in both sides were significantly decreased, suggesting some degree of diastolic ventricular dysfunction; 2) the E/A ratios of both sides were significantly increased, indicating volume load; and 3) The inflow parameters may be useful as a new predictor of fetal anemia, especially among pregnancies at risk.

Platelet function in newborns and the women affected by pregnancy-induced hypertension.

BACKGROUND: Platelet dysfunction is one of the serious and common complications associated with pregnancy-induced hypertension (PIH). Nevertheless, the role of platelet dysfunction in the newborns of PIH mothers is unclear. This study aimed to study platelet problems in infants and women affected by PIH. METHODS: A prospective cohort study was conducted on singleton pregnancies who delivered at a gestation age of 32 weeks or more. The women were divided into the PIH group and the normal control group. The blood tests for maternal and neonatal platelet evaluation such as platelet concentration, mean platelet volume (MPV), and clotting time were performed for comparisons between both groups. RESULTS: A total of 106 cases were recruited for the study (55 cases in the PIH group and 51 cases in the control group). Hematologic studies showed a significant increase in the incidence of thrombocytopenia and platelet dysfunction (increased MPV) in women affected with PIH when compared with those in the control group (p = .028 and p = .001). However, the platelet study in newborns was not significantly different between both groups (p = .680 and p = .265). CONCLUSIONS: This study supports the theory that endothelial cell damage and platelet aggregation as indicated by thrombocytopenia together with increased MPV levels in maternal affected with PIH. Importantly, this study provides new insight into that these problems in mothers with PIH do not occur in their neonatal vessels, as indicated by normal platelet counts and MPV levels.

Effect of metformin on reducing platelet dysfunction in gestational diabetes mellitus: a randomized controlled trial.

Objectives: To evaluate the effect of metformin in improving platelet dysfunction in women with gestational diabetes mellitus (GDM). Patients and methods: A randomized controlled trial was conducted on pregnant women diagnosed with GDM. Singleton low-risk pregnancies meeting the inclusion criteria were randomly allocated at 27-31 weeks to receive metformin and placebo through the rest of pregnancy. Thirty-seven and 39 cases were recruited into the metformin group and the placebo group, respectively. MPVs, P-selectin, and 8-isoprostane levels were determined at the time of allocation and 6 weeks after treatment. Obstetric and neonatal outcomes were also assessed. Results: Most baseline characteristics of the two groups were comparable. The levels of P-selectin after 6 weeks of treatment were significantly higher in the metformin group (68.9 ± 14.4 vs 60.6 ± 11.3; P-value = 0.006), indicating more platelet activation. All of the obstetric and neonatal outcomes were comparable except that birth weight was significantly lower in the metformin group (3018 ± 364 g vs 3204 ± 393 g; P-value = 0.037). Conclusion: Metformin, in addition to diet and lifestyle modifications, does not improve or worsen oxidative stress and platelet dysfunction in women with GDM. Nevertheless, metformin significantly reduces fetal weight in women with GDM, theoretically preventing macrosomia.

Fetal heart rate tracing interpretation in cases of fetal heart block: A case series.

Simple assessment of FHR baseline variability can differentiate second-degree heart block (SHB) from complete heart block (CHB). In cases of SHB, antepartum NST can be reliably used for fetal surveillance. Intrapartum assessment of FHR variability and accelerations is useful to select cases for safe vaginal delivery.

Comparisons of serum non-transferrin-bound iron levels and fetal cardiac function between fetuses affected with hemoglobin Bart's disease and normal fetuses.

Objective: To compare the levels of Non-transferrin bound iron (NTBI) in fetuses with anemia, using Hb Bart's disease as a study model, and those in unaffected fetuses and to determine the association between fetal cardiac function and the levels of NTBI. Patients and methods: A prospective study was conducted on pregnancies at risk of fetal Hb Bart's disease. All fetuses underwent standard ultrasound examination at 18-22 weeks of gestation for fetal biometry, anomaly screening and fetal cardiac function. After that, 2 ml of fetal blood was taken by cordocentesis to measure NTBI by Labile Plasma Iron (LPI), serum iron, hemoglobin and hematocrit. The NTBI levels of both groups were compared and the correlation between NTBI and fetal cardiac function was determined. Results: A total of 50 fetuses, including 20 fetuses with Hb Bart's disease and 30 unaffected fetuses were recruited. There was a significant increase in the level of serum iron in the affected group (median: 22.7 vs. 9.7; p-value: 0.013) and also a significant increase in NTBI when compared with those of the unaffected fetuses (median 0.11 vs. 0.07; p-value: 0.046). In comparisons of fetal cardiac function, myocardial performance (Tei) index of both sides was significantly increased in the affected group (left Tei: p = 0.001, Right Tei: p = 0.008). Also, isovolumetric contraction time (ICT) was also significantly prolonged (left ICT: p = 0.00, right ICT: p = 0.000). Fetal LPI levels were significantly correlated inversely with fetal hemoglobin levels (p = 0.030) but not significantly correlated with the fetal serum iron levels (p = 0.138). Fetal LPI levels were also significantly correlated positively with myocardial performance index (Tei) of both sides (right Tei: R = 0.000, left Tei: R = 0.000) and right ICT (R = 0.013), but not significantly correlated with left ICT (R = 0.554). Conclusion: Anemia caused by fetal Hb Bart's disease in pre-hydropic stage is significantly associated with fetal cardiac dysfunction and increased fetal serum NTBI levels which are significantly correlated with worsening cardiac dysfunction. Nevertheless, based on the limitations of the present study, further studies including long-term data are required to support a role of fetal anemia as well as increased fetal serum NTBI levels in development of subsequent heart failure or cardiac compromise among the survivors, possibly predisposing to cardiovascular disease in adult life.

Comparison of the Performances of Middle Cerebral Artery Peak Systolic Velocity and Cardiothoracic Diameter Ratio in Predicting Fetal Anemia: Using Fetal Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: The aim of the study was to compare the performances of cardiothoracic diameter ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV) in predicting fetal hemoglobin (Hb) Bart's disease and identify the best CTR cut-off for each gestational period. METHODS: Pregnancies at risk of fetal Hb Bart's disease (gestational ages of 12-36 weeks) were prospectively recruited to undergo ultrasound examination. The measurements of CTR and MCA-PSV were performed and recorded before invasive diagnosis. RESULTS: During the study period (2005-2019), a total of 1,717 pregnancies at risk of fetal Hb Bart's disease met the inclusion criteria and were available for analysis, including 329 (19.2%) fetuses with Hb Bart's disease. The mean gestational age at the time of diagnosis was 19.30 ± 5.6 weeks, ranging from 12 to 36 weeks. The overall performance of CTR Z-scores is superior to that of MCA-PSV multiple of median (MoM) values; area under curve of 0.866 versus 0.711, p value <0.001. The diagnostic indices of CTR and MCA-PSV are increased with gestational age. Based on receiver operating characteristic curves of CTR Z-scores, the best cut-off points of CTR at 12-14, 15-17, 18-20, 21-23, and ≥24 weeks are 0.48, 0.49, 0.50, 0.51, and 0.54, respectively. The best cut-off of MCA-PSV is 1.3 MoM, giving the best performance at 21-23 weeks with a sensitivity of 91.8% and specificity of 85.5%. CONCLUSION: The performance of CTR is much better than MCA-PSV in predicting fetal anemia caused by Hb Bart's disease. Nevertheless, whether this can be reproduced in anemia due to other causes, like isoimmunization, is yet to be explored.

Prenatal Sonographic and Molecular Genetic Diagnosis of Popliteal Pterygium Syndrome.

Popliteal pterygium syndrome (PPS) is an extremely rare autosomal dominant disorder, characterized by the cleft palate with or without cleft lip, limbs abnormalities with highly characteristic features of popliteal webbing, syndactyly, and genital abnormalities and nail anomalies. Prenatal diagnosis of PPS has been extremely rare. We describe a unique case of fetal PPS at 20 weeks of gestation. The diagnosis of PPS was based on the ultrasound findings of bilateral popliteal webbings, extending from posterior aspects of the upper thighs through the lower legs, resulting in restriction in knee extension, bilateral equinovarus feet with syndactyly, ambiguous genitalia and the grooved lip. Anatomical structures were otherwise normal. Trio whole-exome sequencing revealed a de novo heterozygous IRF6 gene mutation in the fetus, confirming the diagnosis with PPS. In conclusion, popliteal webbing or combination of facial cleft or cleft variants and bilateral abnormal postures of the lower limbs is suggestive of PPS and genetic diagnosis should be warranted.

First trimester genetic sonogram for screening fetal Down syndrome: A population-based study.

OBJECTIVE: To evaluate the performance of first trimester sonomarkers in the detection of fetal Down syndrome among Thai pregnant women. MATERIALS AND METHODS: Pregnant women at 11-13+6 weeks' gestation underwent ultrasound examination for assessment of nuchal translucency (NT), nasal bone (NB), tricuspid regurgitation (TR), and abnormal ductus venosus (aDV) Doppler waveforms. The women were followed up for final outcomes. Fetal abnormalities other than trisomy 21 were excluded. The performances of each sonomarker and their combinations in predicting fetal Down syndrome were calculated. RESULTS: A total of 7820 pregnant women meeting the inclusion criteria were available for analysis, including 20 cases with fetal Down syndrome and 7800 unaffected cases. Of the four sonomarkers, NT, as a single sonomarker, had the highest detection rate (55.0% at a false positive rate of about 5%), whereas the remaining single sonomarkers had low detection rate (15-20%). The combination of all sonomarkers had the highest detection rate of 70% but the false positive rate was as high as 10.8%. The combination of NT and NB had a detection rate of 60% with an acceptable false positive rate of 6.9%, whereas the other combinations yielded relatively high false positive rates. CONCLUSION: The first trimester genetic sonogram in screening for Down syndrome among Asian women is acceptably effective and may be offered to some selected groups of the population. NT is the best sonomarker with a detection rate of 55% at 5% false positive rate and its combination with NB can improve performance with minimal increase in false positive rate.

Fetal Beckwith-Wiedemann syndrome associated with abnormal quad test, placental mesenchymal dysplasia and HELLP syndrome.

We describe a unique case of Beckwith-Wiedemann syndrome (BWS). A 29-year-old woman with ultrasound and clinical findings, specific to BWS is described. Important insights gained from this study are as follows: (1) quad test may be very useful to increase awareness of BWS. This is the first report, which demonstrated that elevated inhibin-A is related to BWS. Unexplained elevation of serum biomarkers, especially all the four markers, should raise awareness of BWS. (2) Early provisional diagnosis in this case was based on the findings of omphalocele, placental mesenchymal dysplasia and abnormal quad test. (3) Follow-up scans are important for late-occurring supportive findings, such as macroglossia, ear abnormalities and visceromegaly. (4) BWS is strongly associated with preeclampsia, which tended to be more severe and of earlier-onset. (5) Molecular genetic analysis is helpful, but not always necessary in cases of fulfilment of clinical criteria like in this case.

Comparison of pregnancy outcomes after second trimester amniocentesis between procedures performed by experts and non-experts.

OBJECTIVES: To compare the rate of fetal loss in pregnancy after second trimester amniocentesis between procedures performed by experts and non-experts and to assess other pregnancy complications as secondary outcomes. METHODS: A retrospective cohort study was performed on singleton pregnancies that underwent mid-trimester amniocenteses in a single institution. The fetal loss rates of procedures performed by experts and non-experts were collected and analyzed. Other adverse pregnancy outcomes were also examined. RESULTS: In total, 14,450 amniocenteses were performed during the study period. These included 11,357 (78.6%) procedures in the group expert operators and 3,093 (21.4%) procedures in the group non-expert operators. In the non-expert group, the fetal loss rate was slightly increased but not significantly (p=0.24).In addition, the higher number of spontaneous abortions was associated with blood-stained amniotic fluid sample (p<0.001; RR=9.28). Multiple needle insertions also increased in the non-expert group significantly. However, no difference in pregnancy outcomes was found between in single and multiple needle insertions. CONCLUSIONS: The amniocentesis procedures performed by the non-experts was not increase the fetal loss rate. However, the other adverse pregnancy outcomes, including preterm birth, low birth weight and fetal growth restriction were significantly increased in the non-expert group.

Fetal Cardiac Cellular Damage Caused by Anemia in Utero in Hb Bart's Disease.

BACKGROUND: Severe fetal anemias can cause high output cardiac failure. Mitochondria are key regulators of cardiac function. However, the effects of an early phase of fetal anemia on the fetal heart and cardiac mitochondrial function are not known. OBJECTIVE: The aim of this study is to compare mitochondrial function and cardiac biochemical alterations in the fetal cardiac tissue between anemic and non-anemic fetuses. MATERIALS AND METHODS: A cross-sectional study was conducted in Fetuses affected by Hb Bart's disease (n=18) and non-anemic fetuses (n=10) at 17-20 weeks. Echocardiograms had been carried out in all cases to assess prenatal cardiac function. Cardiac tissues were collected after pregnancy termination for the determination of cardiac iron accumulation, mitochondrial function, including mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, mitochondrial dynamics, inflammation, and apoptosis. RESULTS: Prenatal cardiac function evaluated by ultrasound was comparable between the Hb Bart's and non-anemic groups. In Bart's group, the levels of cardiac mitochondrial depolarization and swelling, and the TNF-α level were significantly higher, compared to the non-anemic group. On the contrary, anti-inflammatory (IL-10) levels were significantly lower in the Hb Bart's group. Additionally, active caspase-3 and Bcl-2 expression were also significantly higher (P= 0.001, P=0.035) in Bart's group. The mitochondrial fission protein expression, including p-DRP1/total DRP1, was significantly higher in Bart's group. However, there was no difference in cardiac iron accumulation levels between these two groups. CONCLUSION: Despite equivalent prenatal cardiac function and comparable cardiac iron accumulation in the Bart's and non-anemic groups, fetal anemia is significantly associated with cardiac mitochondrial dysfunction, increased mitochondrial fission, and increased inflammation and apoptosis. These findings indicate that an early phase of fetal anemia without cardiac iron overload can lead to cardiac mitochondrial dysfunction in fetuses with Hb Bart's.

A comparison of pregnancy outcomes after second-trimester amniocentesis between cases with penetration of the placenta and nonpenetration.

OBJECTIVE: To compare the fetal loss rate associated with second-trimester amniocentesis between the procedures with penetration and nonpenetration of the placenta, as a primary outcome and to compare the rates of adverse pregnancy outcomes including preterm birth, fetal growth restriction and low birth weight, as secondary outcomes. METHOD: A retrospective cohort study was conducted on women undergoing second-trimester amniocentesis. Our prospective database of amniocentesis, from January 1989 to December 2018, was accessed to retrieve the records meeting the inclusion criteria consisting of singleton pregnancies, gestational age of 16-22 weeks, and known obstetric outcomes. The patients were categorized into two groups: placental penetration and nonpenetration. The rates of fetal loss, including abortion (<24 weeks of gestation) and fetal death in utero (>24 weeks of gestation), and other adverse pregnancy outcomes were compared between the two groups. RESULTS: A total of 21,566 procedures were performed during the study period. Of them, 8601 were excluded due to chromosomal/structural abnormalities, various underlying medical diseases and incomplete data or unavailability of final outcomes. Finally, 12,965 cases were available for analysis including 4692 (36.2%) in the group of placental penetration and 8273 (63.8%) in the group of nonpenetration. The abortion rate after amniocentesis trended to be increased in the placental penetration group (0.6 versus 0.4%, p = .064; RR: 1.60, 95%CI 0.97-2.64). Likewise, the fetal loss rate trended to be increased in the placental penetration group (1.0 versus 0.7%, p = .121; RR: 1.35 95%CI 0.92-1.98). Interestingly, preterm birth rate was significantly increased in the placental penetration group (13.8 versus 12.6%, p = .043; RR: 1.10 95%CI 1.00-1.20). CONCLUSION: Fetal loss rate was slightly increased, but not statistically significant, among the procedures with placental penetration. However, penetration of the placenta was slightly but significantly associated with an increase in rates of preterm birth.

Foetal haemodynamic response to anaemia.

This study aims to update new knowledge regarding foetal cardiovascular response to anaemia, using foetal haemoglobin Bart's disease as a study model. Original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The main foetal cardiovascular changes in response to anaemia are consequences of hypervolaemia and increased cardiac output to meet tissue oxygen requirement. New challenging insights are as follows: (i) the earliest morphological change is an increase in cardiac size and remodelling of the sphericity (an increase in diameter more pronounced than that in long axis) followed by several markers, such as placentomegaly and hepatosplenomegaly. (ii) The earliest functional change is increased peak systolic velocity of the red blood cells because of low viscosity, especially in the middle cerebral artery. (iii) The foetal heart has very high reserve potentials to cope with anaemia: increasing workload without increased central venous pressure and increased myocardial performance without compromising shortening fraction. This hard-working period with good performance lasts long, including most part of the second and third trimester. (iv) At the time cardiomegaly myocardial cellular damage has already occurred, in spite of good cardiac function. (v) Anaemic hydrops foetalis is mainly due to hypervolaemia, hypoalbuminaemia, and high vascular permeability, not heart failure. (vi) Foetal heart failure occurs only when the adaptive mechanism becomes exhausted or long after the development of anaemic hydrops foetalis. Heart failure is a very late result of a longstanding overworked heart. (vii) Ultrasound is highly effective in the detection of foetal response to anaemia. An increase in cardiac size and middle cerebral artery is very helpful in predicting the affected foetuses in pre-hydropic phase. (viii) Theoretically, intrauterine treatment of anaemic hydrops results in satisfactory outcomes as long as cardiac function is normal, but intrauterine intervention should be strongly considered in pre-hydropic phase because myocardial cell damage could have already occurred in this phase or early hydropic phase. Anaemic hydrops foetalis is not primarily caused by heart failure as commonly advocated, but it is rather a consequence of hypervolaemia, hypoalbuminaemia, and high vascular permeability while heart failure is a very late consequence of a longstanding overworked heart. New insights gained from this review may be useful to base clinical practice on which sonographic markers imply significant pathological changes, how ultrasound can be helpful in early detection of anaemic response, when intrauterine transfusion for anaemia due to non-lethal causes should be administered, etc.

Comparisons of pregnancy outcomes between twin pregnancies with and without second-trimester amniocentesis.

OBJECTIVE: To assess the amniocentesis-related pregnancy loss rate and preterm birth rate among twin pregnancies undergoing amniocentesis. METHODS: A retrospective cohort study was conducted at a tertiary center. The study group included twin pregnancies undergoing amniocentesis during 16 to 22 weeks of gestation. The control group was those not undergoing amniocentesis. All amniocenteses were performed by the MFM specialists. The main outcomes were the rate of pregnancy loss (before 24 weeks) and preterm birth. RESULTS: A total of 332 cases in the study group and 1188 controls were analyzed. The percentages of maternal age ≥35 years, high parity, and cases complicated with medical diseases were significantly higher in the study group. The pregnancy loss rate after the procedure tended to be higher, but not significant, in the study group (3.0% vs 2.2% P = .383). Likewise, the rate of preterm birth in the study group was higher, but not significant (70.5% vs 66.0% P = .130). Logistic regression analysis to adjust confounding factors showed no significance of amniocentesis on pregnancy loss and preterm birth. CONCLUSION: Though amniocentesis in twin pregnancies has theoretical risk of pregnancy loss, it is relatively safe when performed by maternal-fetal medicine specialists. This information is useful for counseling, especially when performed by experienced hands.