Antenatal management and neonatal outcomes of monochorionic twin pregnancies in a tertiary teaching hospital: a 10-year review.

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p<.001, p=.02 and p=.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact StatementWhat is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications.What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC.What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. CONCLUSIONS: The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Neomorphic effects of the neonatal anemia (Nan-Eklf) mutation contribute to deficits throughout development.

Transcription factor control of cell-specific downstream targets can be significantly altered when the controlling factor is mutated. We show that the semi-dominant neonatal anemia (Nan) mutation in the EKLF/KLF1 transcription factor leads to ectopic expression of proteins that are not normally expressed in the red blood cell, leading to systemic effects that exacerbate the intrinsic anemia in the adult and alter correct development in the early embryo. Even when expressed as a heterozygote, the Nan-EKLF protein accomplishes this by direct binding and aberrant activation of genes encoding secreted factors that exert a negative effect on erythropoiesis and iron use. Our data form the basis for a novel mechanism of physiological deficiency that is relevant to human dyserythropoietic anemia and likely other disease states.

Clinical and research issues in neonatal anemia and thrombocytopenia.

PURPOSE OF REVIEW: Anemia and thrombocytopenia are the most common hematological problems in neonates. Red blood cell (RBC) and platelet transfusions are the mainstays of therapy, but data to guide neonatal transfusion practices have been sparse. Recombinant hematopoietic growth factors represent another therapeutic alternative, but their use in this population requires a solid understanding of the developmental differences between fetal and adult hematopoiesis. RECENT FINDINGS: Recently, follow-up studies from children randomized as neonates to either liberal or restrictive RBC transfusion approaches were published. Results of these studies have so far been contradictory and have generated more questions than answers. New developmental stage-specific problems associated with RBC transfusions were also uncovered, such as the transfusion-associated necrotizing enterocolitis. Finally, two thrombopoietin (Tpo) mimetics were approved by the FDA for the treatment of adults with chronic immune thrombocytopenia, thus offering a novel potential therapeutic alternative for thrombocytopenic neonates. SUMMARY: In this review, we will discuss the currently available data regarding neonatal RBC and platelet transfusion thresholds, as well as the potential limitations, and concerns associated with the use of erythropoietin and Tpo mimetics in this patient population. Finally, we will point out specific areas wherein additional research is critically needed.

Tiempo de alumbramiento con drenaje y sin drenaje de sangre del cordón umbilical en pacientes anémicas y no anémicas en el hospital Vicente Corral Moscoso, Cuenca – Ecuador 2007 / Delivery time with drainage and no drainage of umbilical cord blood in anemic and nonanemic patients in the hospital Vicente Corral Moscoso, Cuenca - Ecuador 2007

Con un diseño experimental se realizó un estudio clínico, controlado, aleatorizado La muestra incluyó 200 pacientes, el grupo experimental comprendió 100 pacientes en las que se drenó la sangre de cordón umbilical 50 anémicas y 50 no anémicas, y el grupo de control con pinzamiento del cordón lo integraron 100 pacientes, 50 anémicas y 50 no anémicas, al comparar la duración del tercer período del parto del grupo con drenaje se obtuvo una media de 4,6 ± 1,4 min y en el grupo con pinzamiento 9,07 ± 2,5 min. La diferencia fue significativa (P = 0,0001), cuando se comparó la duración del tercer período del parto de 1 a 5 min vs 6 a 10 min, la mayoría de las pacientes del grupo con drenaje, estuvo entre 1 a 5 min, con un RR 0.239 (IC 95: 0.188 – 0.358), RRA 70.1%, RRR 76.1%, NNT 1.426, en las anémicas, y un RR 0.250 (IC 95: 0.179 – 0.383), RRA 66.1%, RRR 75%, NNT 1.513 en las no anémicas, el volumen de drenaje en el grupo de estudio, tuvo una media de 60.3 ± 19.5 ml en las anémicas y 56.9 ± 18 ml en las no anémicas (P = 0.369), la hemorragia del tercer período del parto del grupo con drenaje tuvo una media de 197.6 ± 36 ml vs el grupo con pinzamiento 277.4 ± 49 ml con un valor (P = 0,0001) lo cual es estadísticamente significativo a favor del drenaje.

With an experimental design a clinical study was made, controlled, randomized the sample included 200 patients, the experimental group included/understood 100 patients in whom the umbilical cord blood was drained 50 anemic and 50 non anemic ones, and the control group with pinzamiento of the cord integrated 100 patients, 50 anemic and 50 non anemic ones, when comparing the duration of the third period of the childbirth of the group with drainage obtained an average of 4.6 ± 1.4 min and in the group with pinzamiento 9.07 ± 2.5 min. The difference was significant (P = 0.0001). When the duration of the third period of the childbirth from 1 to 5 was compared min versus 6 to 10 min, most of the patients of the group with drainage, min was between 1 to 5, with a RR 0,239 (IC 95: 0,188 - 0,358), RRA 70,1%, RRR 76,1%, NT 1,426, in the anemic ones, and a RR 0,250 (IC 95: 0.179 - 0,383), RRA 66,1%, RRR 75%, NT 1,513 in the non anemic ones. The volume of drainage in the training group, had an average of 60.3 ± 19,5 mililiter in anemic and the 56,9 ± 18 mililiter in the non anemic ones (P = 0,369).the hemorrhage of the third period of the childbirth of the group with drainage had an average of 197.6 mililiter ± 36 SD versus the group with pinzamiento 277,4 mililiter ± 49 SD with a value p 0.0001 which is statistically significant in favor of the drainage.

Management of Kell isoimmunization--evaluation of a Doppler-guided approach.

OBJECTIVE: To assess the role of peak systolic velocity in the middle cerebral artery (MCA-PSV) in the management of pregnancies complicated by Kell isoimmunization. METHODS: Sixteen fetuses were monitored by conventional protocol (Group 1) and eight fetuses by an MCA-PSV-guided protocol (Group 2). The conventional protocol included a weekly ultrasound evaluation and measurement of maternal anti-Kell titers every 4-6 weeks. In Group 2 Doppler assessment of the MCA-PSV was performed at intervals of 4 to 7 days and MCA-PSV>1.5 multiples of the median (MoM) was considered as an indication for fetal blood sampling (FBS). RESULTS: No parameter emerged as a reliable predictor of isoimmunization severity in Group 1. In Group 2, no FBS was necessary in one case since the MCA-PSV values obtained during the follow-up were <1.29 MoM. In two cases the first FBS was already indicated after 1 week of follow-up, but five other fetuses were followed for 3-9 weeks before FBS was indicated. All fetuses with MCA-PSV>1.5 MoM prior to intrauterine transfusion (IUT) had severe fetal anemia on FBS. In fetuses with severe anemia on the first FBS, the MCA-PSV values 7 days before the first FBS were <1.29 MoM (four cases), between 1.29 and 1.5 MoM (two cases) and >1.55 MoM (one case). CONCLUSIONS: In the management of Kell isoimmunization invasive procedures may be avoided by implementing MCA-PSV measurements. Delineation of appropriate intervals between reassessments, the reliability of MCA-PSV following repeated IUTs, and cut-off values for FBS await further study.

The effects of anaemia as a programming agent in the fetal heart.

The intrauterine environment plays a powerful role in determining the life-long risk of cardiovascular disease. A number of stressors are well known to affect the development of the cardiovascular system in utero including over/under maternal nutrition, excess glucocorticoid and chronic hypoxia. Chronic fetal anaemia in sheep is a complex stressor that alters cardiac loading conditions, causes hypoxic stress and stimulates large changes in flow to specific tissues, including large increases in resting coronary blood flow and conductance. Decreased viscosity can account for approximately half of the increased flow. It appears that immature hearts are 'plastic' in that increases in coronary conductance with fetal anaemia persist into adulthood even if the anaemia is corrected before birth. These large changes in conductance are possible only through extensive remodelling of the coronary tree. Adult hearts that were once anaemic in utero are more resistant to hypoxic stress as adults but it is not known whether such an adaptation would be deleterious in later life. These studies indicate the need for investigation into the basic mechanisms of coronary tree remodelling in the immature myocardium. New information on these mechanisms is likely to lead to better prevention of and therapies for adult-onset coronary disease.