Intravenous Immunoglobulin in the Management of Severe Early Onset Red Blood Cell Alloimmunization

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed < 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on 'Statistical Package for Social Science Version 16.0' (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple "top-up" transfusion, and six (35%) phototherapy. CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Burden and risk factors associated with low birth weight among newborns in a tertiary care hospital Karachi, Pakistan

Background: Birth weight is one of the significant determinants of perinatal survival and infant morbidity and illnesses during early childhood. The burden of LBW neonates in the developed world is around 7%, whereas it is more than double at around 16.5% in developing countries.Methods: The retrospective cross-sectional study was conducted at the Indus Hospital and Health Network, Karachi, Pakistan. Data was extracted through the electronic medical record (EMR) with specific coding related to LBW from 1st January 2019 to 31st December 2020.Results: Our study showed LBW disease burden of 7.61% equated to 7% in the developed world while, in contrast with LBW prevalence in the developing countries, 16.5%. Gestational diabetes, pregnancy-induced hypertension, and primigravida are the major risk factors associated with LBW.Conclusions: Our study concludes that antenatal care is one of the major aspects to decrease the incidence of LBW, especially in primigravida. By estimating LBW, we can plan early detection and prompt interventions against this problem, reducing the burden of morbidity and mortality in neonates.

Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice

The hormone erythroferrone (ERFE) is produced by erythroid cells in response to hemorrhage, hypoxia or other erythropoietic stimuli, and suppresses the hepatic production of the iron-regulatory hormone hepcidin, thereby mobilizing iron for erythropoiesis. Suppression of hepcidin by ERFE is thought to be mediated by interference with paracrine BMP signaling that regulates hepcidin transcription in hepatocytes. In anemias with ineffective erythropoiesis, ERFE is pathologically overproduced but its contribution to the clinical manifestations of these anemias is not well understood. We generated three lines of transgenic mice with graded erythroid overexpression of ERFE and showed that they developed dose-dependent iron overload, impaired hepatic BMP signaling and relative hepcidin deficiency. These findings add to the evidence that ERFE is a mediator of iron overload in conditions where ERFE is overproduced, including anemias with ineffective erythropoiesis. At the highest levels of ERFE overexpression the mice manifested decreased perinatal survival, impaired growth, small hypofunctional kidneys, decreased gonadal fat depots and neurobehavioral abnormalities, all consistent with impaired organ-specific BMP signaling during development. Neutralizing excessive ERFE in congenital anemias with ineffective erythropoiesis may not only prevent iron overload but may have additional benefits for growth and development.

Do Serial Sonographic Assessments of Fetuses with Isolated Congenital Diaphragmatic Hernia Help Us Predict Survival?

<b><i>Objective:</i></b> The aim of this study was to assess the ability of serial prenatal sonographic measurements, and specifically changes in the observed-to-expected lung-to-head ratio (O/E LHR) throughout gestation and to predict survival in congenital diaphragmatic hernia (CDH). <b><i>Methods:</i></b> Retrospective study of CDH fetuses evaluated prenatally and treated postnatally in a single tertiary center, 2008–2020. Sonographic evaluations included side of herniation, liver involvement, and O/E LHR. All data were calculated to assess ability to predict survival. <b><i>Results:</i></b> Overall, 94 fetuses were evaluated prenatally and delivered in our medical center. Among them, 75 had isolated CDH and 19 nonisolated. CDH was categorized as left (<i>n</i> = 76; 80.8%), right (<i>n</i> = 16; 17.0%), or bilateral (<i>n</i> = 2; 2.2%). Overall perinatal survival rate was 57% for all live-born infants, 68% in isolated CDH, and 40% in nonisolated (excluding 2 cases that underwent fetoscopic endoluminal tracheal occlusion and did not survive). The O/E LHR was lower in cases with perinatal death compared to survivors. In cases with multiple evaluations, the minimal O/E LHR was the most accurate predictor of survival and need for perinatal extracorporeal membrane oxygenation (ECMO) support. This remained significant when excluding twin pregnancies or when evaluating only isolated left CDH. In addition to disease severity, the side of herniation and liver position was associated with preoperative mortality. <b><i>Conclusion:</i></b> O/E LHR is associated with perinatal survival. In cases with multiple evaluations, the minimal O/E LHR is the most accurate and significant predictor of perinatal mortality and need for ECMO support.

Frequent refresher training on newborn resuscitation and potential impact on perinatal outcome over time in a rural Tanzanian hospital: an observational study

ObjectivesGlobally, perinatal mortality remains high, especially in sub-Saharan countries, mainly because of inadequate obstetric and newborn care. Helping Babies Breathe (HBB) resuscitation training as part of a continuous quality improvement (CQI) programme may improve outcomes. The aim of this study was to describe observed changes in perinatal survival during a 6-year period, while adjusting for relevant perinatal risk factors.SettingDelivery rooms and operating theatre in a rural referral hospital in northern-central Tanzania providing comprehensive obstetric and basic newborn care 24 hours a day. The hospital serves approximately 2 million people comprising low social-economic status.ParticipantsAll newborns (n=31 122) born in the hospital from February 2010 through January 2017; 4893 were born in the 1-year baseline period (February 2010 through January 2011), 26 229 in the following CQI period.InterventionsThe HBB CQI project, including frequent HBB training, was implemented from February 2011. This is a quality assessment analysis of prospectively collected observational data including patient, process and outcome measures of every delivery. Logistic regression modelling was used to construct risk-adjusted variable life adjusted display (VLAD) and cumulative sum (CUSUM) plots to monitor changes in perinatal survival (primary outcome).ResultsDuring the 6-year CQI period, the unadjusted number of extra lives saved according to the VLAD plot was 150 despite more women admitted with pregnancy and labour complications and more caesarean deliveries. After adjusting for these risk factors, the risk-adjusted VLAD plot indicated that an estimated 250 extra lives were saved. The risk-adjusted CUSUM plot confirmed a persistent and steady increase in perinatal survival.ConclusionsThe risk-adjusted statistical process control methods indicate significant improvement in perinatal survival after initiation of the HBB CQI project with continuous focus on newborn resuscitation training during the period, despite a concomitant increase in high-risk deliveries. Risk-adjusted VLAD and CUSUM are useful methods to quantify, illustrate and demonstrate persistent changes in outcome over time.