Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin-twin transfusion syndrome.

We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic-dizygotic twins (MC/DZ) with the twin-twin-transfusion syndrome (TTTS), presumably caused by the exchange of stem-cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood. Subsequent genotyping of blood and skin confirmed dizygosity, with the affected twin harboring the RB1 pathogenic variant in skin and blood, and the unaffected twin carrying the variant only in blood.

Effect of Chorionicity on Umbilical Cord Blood Acid-Base Analysis of the Second Twin.

Our objective was to determine whether chorionicity affects umbilical cord blood acid-base parameters of the second twin. This was a retrospective cohort of twin pregnancies delivered at ≥23 weeks of gestation at a tertiary hospital from 2010 to 2016. Patients were included if arterial and venous umbilical cord gas results were available for both newborns and chorionicity was confirmed histologically. Exclusion criteria included intrauterine fetal demise of either twin prior to labor, major fetal anomalies, monoamnionicity, uncertain chronicity and twin-to-twin transfusion syndrome. The primary outcome evaluated was the umbilical artery (UA) pH of the second twin. A total of 593 dichorionic (DC) and 86 monochorionic (MC) twin pregnancies were included. No difference in UA pH was observed between MC and DC twins. Among vaginal deliveries (n = 97), the UA pH of the first twin was higher than the second twin (7.26 vs. 7.24; p = .01). Twin-to-twin delivery interval (TTDI) ≥20 min was associated with a higher UA pH in the first twin compared to the second twin (7.25 vs. 7.16, respectively; p = .006). Multivariable logistic regression was used to predict arterial pH < 7.20 for the second twin; the most predictive factors were arterial pH < 7.20 for the first twin, chronic hypertension and prolonged TTDI. Chorionicity was not associated with any acid-base parameter of umbilical cord blood in either the first or second twin. No differences in neonatal outcomes were observed based on chorionicity or birth order. Populations with a lower cesarean delivery rate may yield different findings.

Leukocyte Counts and Other Hematological Values in Twin-Twin Transfusion Syndrome and Twin Anemia-Polycythemia Sequence.

OBJECTIVE: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). METHODS: We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 × 109/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality. RESULTS: We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 × 109/L versus 7.4 × 109/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively. CONCLUSIONS: Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins.

Monozygotic Twins with Birth-Weight Differences: Metabolic Health Influenced more by Genetics or by Environment?

BACKGROUND: Low birth-weight (bw), low birth-length (bl), unfavourable intrauterine conditions and post-natal catch-up growth can have an impact on growth and metabolic health later in life. OBJECTIVE: We studied genetically identical twins with intra-twin bw-differences due to twin-twin transfusion syndrome from birth to adolescence and analysed the long-term impact of bw and catch-up growth on metabolic parameters. SUBJECTS AND METHODS: Forty-three postpubertal monozygotic twin-pairs (mean age 17.4 years) were examined. Twenty-two pairs were discordant (intra-twin bw- and/or bl-difference ≥1 SDS) of which 12 (55%) experienced catch-up growth. Auxological parameters and blood pressure were measured, a fasting blood sample was collected and bio-impedance spectroscopy was carried out. RESULTS: Irrespective of differences in birth parameters and postnatal catch-up growth, a significant intra-twin correlation was found for nearly all measured parameters of body composition (skinfold, waist-hip circumference, relative body fat/lean body mass) and metabolic health (total, and low-density lipoprotein-C/high-density lipoprotein-C, Apolipoprotein A and B, C-peptide). As an exception to this, and only for the former smaller twins who showed postnatal catch-up growth, a significantly higher fasting insulin level was found compared to that of the co-twins (mean insulin level: 8.4 vs. 5.7 µIU/mL; p < 0.01). Auxology remained different until adulthood: even in subjects with catch-up growth the former smaller twins were significantly lighter (mean-body mass index-SDS: -0.42 vs. 0.21; p < 0.05) and shorter (mean height-SDS: -0.07 vs. 0.37; p < 0.05) than their co-twins. CONCLUSION: In this special group of monozygotic twins with intra-twin bw-differences and catch-up growth, we found that the genetic background was a more important factor in determining later metabolic health than bw and/or catch-up growth.

MicroRNA changes in maternal serum from pregnancies complicated by twin-twin transfusion syndrome: A discovery study.

OBJECTIVE: MicroRNAs (miRNAs) are used as biomarkers in cardiovascular disease and cancer. miRNAs are involved in placental development but have not previously been investigated in twin-twin transfusion syndrome (TTTS). Our aim is to explore the miRNA profile of TTTS pregnancies. METHOD: Initial miRNA profiling was performed using a reverse transcription polymerase chain reaction (RT-PCR) panel on maternal serum samples taken from five women prior to fetoscopic laser ablation for TTTS and compared with serum samples from five women with uncomplicated monochorionic diamniotic twin pregnancies. Validation RT-PCR was performed in an additional cohort of eight TTTS pregnancies and eight uncomplicated pregnancies. RESULTS: Median gestational age at sampling in the TTTS and control groups was 20+0  weeks (interquartile range [IQR], 19+4 -20+0 ) and 20+2  weeks (IQR, 20+0 -20+2 ), respectively. All samples passed quality control. One control sample was excluded as a biological outlier. Thirty-one of 752 miRNAs were significantly different: 17 were upregulated and 14 downregulated in the TTTS group, although they did not remain significant following Benjamini-Hochberg correction for multiple testing. The six miRNAs chosen for validation demonstrated no significant difference. CONCLUSION: This is the first study to investigate miRNA changes in TTTS pregnancies. We did not demonstrate a statistically significant difference in miRNAs in TTTS pregnancies, but further investigation is required.

The impact of laser surgery on angiogenic and anti-angiogenic factors in twin-twin transfusion syndrome: a prospective study.

OBJECTIVE: To examine the effect of laser surgery on angiogenic and anti-angiogenic factors in patients with twin-twin transfusion syndrome (TTTS). METHODS: Cases of TTTS and uncomplicated monochorionic diamniotic twin pregnancies between 16 and 26 weeks' gestation were prospectively enrolled into the study. Maternal blood samples were obtained to measure angiogenic factors (vascular endothelial growth factor-A [VEGF], placental-derived growth factor [PlGF], and endothelin) and anti-angiogenic factors (soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sEng), and sFlt-1/PlGF ratio). For cases, these factors were measured at visit 1 (pre-operatively), visit 2 (postoperative day one), and visit 3 (at least 3 weeks after surgery). In controls, the factors were measured at visit 1 (enrollment) and visit 2 (at least 3 weeks later). Levels of angiogenic and anti-angiogenic factors between cases and controls were compared. RESULTS: At enrollment, the TTTS cases demonstrated an anti-angiogenic state with significantly higher sFlt-1, sEng, sFlt-1/PlGF ratio, and lower PlGF. Laser surgery, comparing visit 1-3, had a partial corrective effect on TTTS cases. sFlt-1 significantly decreased several weeks after surgery. The other factors (PlGF, endothelin, sFlt-1, sEng, and sFlt-1/PlGF ratio) were not statistically significantly different by visit 3. CONCLUSION: Laser surgery partially corrected the angiogenic profile in patients with TTTS.

Hematological disorders at birth in complicated monochorionic twins.

INTRODUCTION: Monochorionic twins are at risk of severe complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS) and acute peripartum TTTS. The pathophysiology is based on inter-twin blood transfusion through placental vascular anastomoses. Areas covered: This review focuses on the incidence, management and outcome of neonatal hematological complications at birth in TTTS, TAPS and acute peripartum TTTS. Expert commentary: Hematological disorders are often present at birth in monochorionic twins and include acute or chronic anemia, polycythemia and thrombocytopenia. Routine measurement of complete blood counts in all complicated monochorionic twins is strongly recommended. Increased awareness on these disorders and correct diagnostic tests will lead to prompt and adequate management at birth.

The Placenta in Twin-to-Twin Transfusion Syndrome and Twin Anemia Polycythemia Sequence.

Twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are complications unique to monochorionic twin pregnancies and their shared circulation. Both are the result of the transfusion imbalance in the intertwin circulation. TTTS is characterized by an amniotic fluid discordance, whereas in TAPS, there is a severe discordance in hemoglobin levels. The article gives an overview of the typical features of TTTS and TAPS placentas.

Cardiac Manifestations of Twin-to-Twin Transfusion Syndrome.

This review addresses the physiology of monochorionic diamniotic (MC/DA) twins and the potential for twin-twin transfusion syndrome (TTTS). It focuses on the underlying cardiovascular pathophysiology of TTTS and the cardiovascular impact of TTTS for both the recipient and the donor twin. It explains the principles for assessment and monitoring of these cardiovascular changes and how these may be used to guide pregnancy management. Finally, it describes the effect of treatment on the altered hemodynamics and how this can influence pregnancy and perinatal management, as well as longer-term follow-up.

Short-Term Postnatal Renal Function in Twin Anemia-Polycythemia Sequence.

OBJECTIVE: To evaluate the short-term renal function in neonates with twin anemia-polycythemia sequence (TAPS). METHODS: All consecutive monochorionic twins with TAPS with double survivors admitted to three European centers were included in this retrospective study. Each twin pair was matched for gestational age at birth with a control twin pair unaffected by TAPS or twin-twin transfusion syndrome. Creatinine and urea levels in the first week after birth were recorded. Short-term postnatal renal dysfunction was defined as creatinine >100 µmol/l during the first week after birth. RESULTS: A total of 52 TAPS twin pairs and 52 control twin pairs with a median gestational age of 31 weeks at birth were included in the study. In the TAPS group, donors had higher mean creatinine levels compared to recipients, 85 versus 71 µmol/l, respectively (p = 0.001). Short-term renal dysfunction was detected in 26.0% (13/50) of the donors versus 6.3% (3/48) of the recipients (p = 0.022). In the control group, no inter-twin differences in creatinine levels were found. CONCLUSIONS: Donor twins with TAPS have higher creatinine levels than recipient twins, suggesting that chronic inter-twin transfusion in TAPS may also cause short-term renal dysfunction. Long-term renal consequences in TAPS donors require further investigation.

Middle cerebral artery peak systolic velocity to predict fetal hemoglobin levels in twin anemia-polycythemia sequence.

OBJECTIVE: To evaluate the diagnostic accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) Doppler measurements in prediction of hemoglobin levels in twin anemia-polycythemia sequence (TAPS). METHODS: This study involved a consecutive cohort comprising monochorionic twin pregnancies complicated by TAPS managed at three European fetal medicine centers between 2005 and 2013. The accuracy of MCA-PSV, measured immediately prior to fetal hemoglobin (Hb) measurement by fetal or cord blood sampling, for prediction of anemia and polycythemia was assessed using 2 × 2 tables. RESULTS: A total of 116 measurements (74 recorded in donors and 42 in recipients) from 43 twin pregnancies complicated by TAPS were available for analysis. MCA-PSV multiples of the median (MoM) values correlated well with Hb levels (r = - 0.86; P < 0.001). The sensitivity of MCA-PSV ≥ 1.5 MoM to predict severe anemia (Hb deficit > 5 SD below the mean) in TAPS donors was 94% (95% CI, 85-98%); specificity was 74% (95% CI, 62-83%); positive and negative predictive values were 76% (95% CI, 65-85%) and 94% (95% CI, 83-98%), respectively. The sensitivity of MCA-PSV ≤ 1.0 MoM to predict polycythemia (Hb level > 5 SD above the mean) in TAPS recipients was 97% (95% CI, 87-99%); specificity was 96% (95% CI, 89-99%); positive and negative predictive values were 93% (95% CI, 81-97%) and 99% (95% CI, 93-100%), respectively. CONCLUSION: MCA-PSV measurement has high diagnostic accuracy for predicting abnormal Hb levels in fetuses with TAPS.

Perinatal outcomes of twin anemia-polycythemia sequence: a systematic review.

OBJECTIVE: To analyze outcomes of monochorionic twins with twin anemia-polycythemia sequence (TAPS). DATA SOURCES: PubMed, EMBASE, Medline, and reference list. STUDY SELECTION: We included reports of TAPS defined prenatally with abnormal Doppler studies of middle cerebral artery and normal amniotic fluid volume which reported data as proportional rates. DATA EXTRACTION: Abstracted outcomes were postnatal hemoglobin levels, postnatal procedures, and survival rates. Outcomes were analyzed for gestational age at diagnosis of TAPS (15 to 23 weeks, 24 to 29 weeks, > 29 weeks), in utero therapy, and nature of onset (isolated TAPS, or following twin-to-twin transfusion syndrome). The review was performed using MOOSE guidelines. Differences were significant if P < 0.05. DATA SYNTHESIS: We assessed data on 28 pregnancies with TAPS. Diagnosis at 15 to 23 weeks' gestation and in utero therapy were associated with the highest mean levels of hemoglobin in anemic twins (P = 0.021), the lowest levels in polycythemic twins (P = 0.025), and the lowest frequency of postnatal procedures (P < 0.001). Survival rate was independent of gestational age at diagnosis and in utero therapy. In cases of TAPS following twin-to-twin transfusion, the mean hemoglobin level was higher in donors than in anemic twins with isolated TAPS (P = 0.029) and similar between recipients and polycythemic twins with isolated TAPS (P = 0.135). Twins with TAPS following twin-to-twin transfusion received in utero therapy more frequently than isolated TAPS twins (P = 0.030) and required a postnatal procedure less often (P < 0.001). Survival rates were similar in each group. CONCLUSION: Diagnosis of TAPS at an early gestational age is associated with more favourable outcomes than later diagnosis. In utero therapy improves neonatal hemoglobin levels but does not change survival rates. Previous twin-to-twin transfusion syndrome does not worsen outcomes.

Objectif : Analyser les issues que connaissent les jumeaux monozygotes qui présentent une séquence anémie-polyglobulie gémellaire (twin anemia-polycythemia sequence ou TAPS). Sources de données : PubMed, EMBASE, Medline et liste de références. Sélection des études : Nous avons inclus les études ayant porté sur la TAPS établie avant la naissance (obtention de résultats anormaux aux études Doppler visant l'artère cérébrale moyenne et constatation d'un volume normal de liquide amniotique) qui signalaient leurs données sous forme de taux proportionnels. Extraction des données : Les issues résumées ont été les suivantes : taux postnataux d'hémoglobine, interventions postnatales et taux de survie. Les issues ont été analysées en fonction de l'âge gestationnel au moment du diagnostic de TAPS (15-23 semaines, 24-29 semaines, > 29 semaines), de la présence d'un traitement in utero et de la nature de l'apparition de la TAPS (TAPS isolée ou apparaissant à la suite du syndrome transfuseur-transfusé). L'analyse a été menée au moyen des lignes directrices MOOSE. Les différences ont été considérées significatives lorsque P < 0,05. Synthèse des données : Nous avons évalué des données portant sur 28 grossesses présentant une TAPS. Le diagnostic à 15-23 semaines de gestation et le traitement in utero ont été associés aux taux moyens d'hémoglobine les plus élevés chez les jumeaux anémiques (P = 0,021), aux taux moyens d'hémoglobine les plus bas chez les jumeaux présentant une polyglobulie (P = 0,025) et à la fréquence d'interventions postnatales la plus basse (P < 0,001). Le taux de survie ne dépendait ni de l'âge gestationnel au moment du diagnostic ni de la présence d'un traitement in utero. Dans les cas de TAPS suivant le syndrome transfuseur-transfusé, le taux moyen d'hémoglobine était plus élevé chez les transfuseurs (par comparaison avec la situation constatée chez les jumeaux anémiques dans les cas de TAPS isolée [P = 0,029]) et il était semblable chez les transfusés (par comparaison avec la situation constatée chez les jumeaux présentant une polyglobulie dans les cas de TAPS isolée [P = 0,135]). Les jumeaux présentant une TAPS constatée à la suite du syndrome transfuseur-transfusé ont reçu un traitement in utero plus fréquemment (P = 0,030) et ont nécessité une intervention postnatale moins souvent (P < 0,001) que les jumeaux présentant une TAPS isolée. Les taux de survie étaient semblables d'un groupe à l'autre. Conclusion : L'établissement d'un diagnostic de TAPS à un âge gestationnel précoce est associé à des issues plus favorables que l'établissement d'un diagnostic de TAPS à un âge gestationnel plus tardif. L'administration d'un traitement in utero améliore les taux néonataux d'hémoglobine, mais ne modifie en rien les taux de survie. La présence d'un syndrome transfuseur-transfusé au préalable n'aggrave en rien les issues.

Clinical characteristics of monochorionic twins with large hemoglobin level discordance at birth.

OBJECTIVES: To evaluate neonatal outcomes and clinical characteristics of monochorionic diamniotic (MCDA) twins with a large intertwin hemoglobin (Hb) difference at birth. METHODS: This was a retrospective cohort study of MCDA twin gestations delivered at Osaka Medical Center and Research Institute for Maternal and Child Health between 2003 and 2012. Cases of pregnancy termination, acardiac twins or intrauterine death were excluded. A large intertwin Hb difference at birth was defined as > 8.0 g/dL according to the postnatal criteria for twin anemia-polycythemia sequence (TAPS). The intertwin reticulocyte count ratio (RCR) was calculated by dividing the reticulocyte count of the anemic twin by that of the polycythemic twin. Cases with Hb differences were divided into two groups according to the RCR, TAPS when the RCR was > 1.7 and acute fetofetal hemorrhage (AFFH) when the RCR was ≤ 1.7. Neonatal outcomes were compared between the TAPS and AFFH groups. RESULTS: During the study period, 432 MCDA twin pregnancies of a total of 532 born at our hospital were analyzed. There were 12 (2.8%) cases of a large intertwin Hb difference. The median gestational age at birth of these cases was 34 (range, 23-38) weeks, and all were delivered by Cesarean section. There were seven (1.6%) cases of TAPS and five (1.2%) of AFFH. The neonatal survival rate was 91.7%; in one pair of twins with TAPS neonatal death occurred. All (100%) cases with TAPS and two (40%) with AFFH required blood transfusion or partial-exchange transfusion for at least one infant. CONCLUSIONS: Although the incidence of TAPS and AFFH may be low in MCDA twins, many affected neonates required treatment for hematological abnormalities. Delivery of MCDA twins via Cesarean section does not appear to prevent AFFH, despite the absence of labor.

Circulating angiogenic factors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome and selective intrauterine growth restriction.

OBJECTIVE: To determine maternal plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), placental growth factor (PLGF), and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR). STUDY DESIGN: A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: (1) uncomplicated MC/DA twins (n = 22), (2) TTTS (n = 23), and (3) sIUGR (n = 15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sVEGFR-1, PLGF, and sEng, as well as cord blood levels of sVEGFR-1 were measured by enzyme-linked immunoassay. RESULTS: Maternal plasma levels of sVEGFR-1 and sEng were significantly higher in patients with TTTS at the early and late second trimester compared with normal monochorionic pregnancies (P < .01). In contrast, in the sIUGR group, sVEGFR-1 and sEng levels were significantly higher only at the late second trimester (P < .05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared with controls (P < .01). Plasma concentrations of sVEGFR-1 were significantly higher among TTTS pregnancies compared with sIUGR at the late second trimester (P = .027). Cord blood levels of sVEGFR-1 were significantly higher in the smaller intrauterine growth restricted twin compared with the normal cotwin. CONCLUSION: Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the antiangiogenic state between TTTS and sIUGR suggests that these 2 conditions may represent a continuum.

Predominantly placenta-expressed mRNAs in maternal plasma as predictive markers for twin-twin transfusion syndrome.

OBJECTIVE: This study aimed to identify a set of predominantly placental (PP) mRNAs, which are associated with later-developing twin-to-twin transfusion syndrome (TTTS). METHOD: First, out of 50 PP mRNAs we previously reported, we select target mRNAs that are ordinarily detectable in maternal plasma. Plasma concentrations of these PP mRNAs were measured in monochorionic diamniotic twin (MCDA-T) pregnancies complicated by TTTS later (n = 11) and in uncomplicated MCDA-T pregnancies (n = 17). Finally, the diagnostic values of the PP mRNAs in plasma were evaluated. RESULTS: From 50 PP mRNAs, nine [human placental lactogen (hPL); pregnancy-specific glycoproteins 2 (PSG2); human pregnancy-specific glycoproteins 3 (PSG3); syncytin; syncytin 2; retinoic acid-induced 14; A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12); chorionic glycoprotein hormones, alpha polypeptide; and chorionic glycoprotein hormones, and beta polypeptide] were selected as target mRNAs. Changes in six PP mRNAs [increased hPL, PSG2, and PSG3 and decreased syncytin, syncytin2, and ADAM12] in maternal plasma were detected in MCDA-T pregnant women who subsequently developed TTTS. Finally, mRNA signatures gave elevated AUCs (hPL/PSG2: 0.8717; hPL/PSG3: 0.8449; hPL/ADAM12: 0.8396) compared with single hPL mRNA. CONCLUSION: Quantitative aberration of plural cell-free PP mRNAs in maternal plasma precedes the appearance of clinically apparent TTTS. This suggests that pathophysiological changes in the placenta are associated with morbid conditions of TTTS.

N-terminal pro-brain natriuretic peptide levels in monochorionic diamniotic twins with twin-to-twin transfusion syndrome treated by fetoscopic laser photocoagulation.

Twin-to-twin transfusion syndrome (TTTS) affects 15% of monochorionic diamniotic (MD) twin pregnancies, and is associated with adverse perinatal outcome. Recently, fetoscopic laser photocoagulation (FLP) has been widely accepted as the most definitive therapy to treat TTTS. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a powerful diagnostic marker of cardiac dysfunction in neonates, and is elevated in MD twins with TTTS. However, there are no reports assessing the effect of FLP on neonatal cardiac overload in TTTS by measuring the serum NT-proBNP levels at birth. Here, we aimed to compare serum NT-proBNP levels at birth in MD twins with TTTS treated with FLP or not. Twelve MD twin pairs with TTTS admitted to our center between October 2007 and September 2012 were enrolled in this study. The MD twin pairs were separated into two groups: seven twins (12 newborn infants) with FLP (FLP group) and five twins (nine newborn infants) without FLP (non-FLP group). Gestational age, birthweight, and Apgar scores were significantly higher in the FLP group than that in the non-FLP group. Serum NT-proBNP levels at birth were significantly lower in the FLP group than in the non-FLP group [1425 pg/ml (range, 466-9560) vs. 29900 pg/ml (range, 7300-77900), respectively; p=0.0003]. The serum NT-proBNP levels of larger and smaller co-twins were significantly correlated with each other (r=0.750; p=0.026). In conclusion, serum NT-proBNP levels at birth are lower in MD twins with TTTS after FLP treatment than in those without FLP.

Maternal thyroid function at gestational weeks 11-13 in twin pregnancies.

BACKGROUND: Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyrotropin (TSH) is suppressed because of the increased hormone production induced by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression. The recognition of this phenomenon is important in order to avoid unnecessary concerns and to correctly establish the diagnosis of overt thyroid disease in twin pregnancies. The aim of this study was to establish reference ranges of maternal serum TSH and free thyroxine (FT4) at gestational weeks 11-13 in twin pregnancies. METHODS: This is a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcomes, and 19 monochorionic pregnancies complicated by severe twin-twin transfusion syndrome. Maternal serum concentrations of TSH, FT4, antithyroperoxidase, and antithyroglobulin antibodies were measured at gestational weeks 11-13. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancies and MoM values in the different groups were compared. RESULTS: In the antibody-negative twin pregnancies with normal outcomes, compared to singletons, serum TSH MoM was lower (median 0.62 [interquartile range [IQR 0.16-1.18] vs. 1.01 [IQR 0.61-1.51]; p < 0.0001), FT4 MoM was not significantly different (median 0.98 [IQR 0.91-1.08] vs. 0.99 [IQR 0.91-1.09]; p = 0.975), and free ß-hCG MoM was higher (median 1.91 [IQR 1.33-2.59] vs. 0.98 [IQR 0.66-1.50]; p < 0.0001). In the antibody-positive group (n = 37), compared to the negative group (n = 198), the median TSH was higher, but FT4 and free ß-hCG were not significantly different. In the twin-twin transfusion syndrome group, compared to normal twin pregnancies, TSH, FT4, and free ß-hCG were not significantly different. CONCLUSION: In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These reference ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.

Hypoalbuminemia in donors with twin anemia-polycythemia sequence: a matched case-control study.

OBJECTIVE: To determine the differences in albumin levels between donors and recipients with twin anemia-polycythemia sequence (TAPS). METHODS: We included all consecutive monochorionic twins with TAPS with double survivors. Each twin pair was matched for gestational age at birth with 2 control monochorionic twin pairs unaffected by TAPS or twin-twin transfusion syndrome. We measured levels of albumin, total protein, and hemoglobin on the first day of life in donors and recipients (TAPS group) and the control group. RESULTS: A total of 25 TAPS twin pairs and 50 control twin pairs were included in the study. The median gestational age at birth was 32 weeks in both groups. In the TAPS group, median levels (IQR) of albumin in donor twins were significantly lower than in recipient twins, i.e. 28.0 g/l (24.0-32.0) versus 32.0 g/l (30.0-34.5) (p = 0.008). Median levels (IQR) of total protein in donor twins were also lower than in recipients, i.e. 44.0 g/l (36.5-49.0) versus 49.0 g/l (46.5-51.0), respectively (p = 0.004). The median (IQR) intertwin albumin difference was significantly higher in the TAPS group than in the control group, i.e. 4.0 g/l (2.5-10.5) versus 2.0 g/l (1.0-4.0) (p = 0.003). The rate of hypoalbuminemia (<20 g/l) and hypoproteinemia (<40 g/l) in donor twins with TAPS was 20% (5/25) and 32% (8/25). CONCLUSIONS: In addition to lower hemoglobin levels, donor twins with TAPS also have significantly lower albumin and total protein levels compared to recipient twins.