How do we perform intrauterine transfusions?

BACKGROUND: Intrauterine transfusion (IUT) is an invasive but critical and potentially life-saving intervention for severe fetal anemia with demonstrated improvement in outcomes. The fetus is vulnerable to hemodynamic alterations and transfusion-related adverse events; therefore, special consideration must be given to blood component selection and modification. There is widespread IUT practice variability, and existing guidance primarily relies on expert opinion and single center experiences. STUDY DESIGN AND METHODS: Experts in Maternal Fetal Medicine, Pediatric Hematology, and Transfusion Medicine from centers across the United States, collectively performing about 120 IUT annually, offer a multidisciplinary perspective on the performance of IUT and preparation of blood components. This perspective includes strategies for identifying an at-risk fetus, communicating between disciplines, determining the necessary blood volume, selecting and processing blood components, documenting the procedure in medical record, and managing the neonate. RESULTS: Identifying an at-risk fetus relies on review of the clinical history, non-invasive monitoring, and laboratory evaluation. We recommend the use of relatively fresh, group O, cytomegalovirus-safe, freshly irradiated, red blood cells (RBC) that are Hemoglobin S negative and antigen-negative for any maternal antibody, if indicated. These RBC units should be concentrated to remove additives and increase the hematocrit thus minimizing fluctuations in fetal volume status. The units intended for IUT should be labeled clearly and the documentation of transfusion differentiated in the maternal medical record. DISCUSSION: An awareness of the technical, logistical, and regulatory considerations for IUT performance will facilitate improved communication and patient care, especially when rare units of RBC are required.

Understanding Preterm Birth in Pregnancies Complicated by Nonimmune Hydrops Fetalis.

OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is associated with poor perinatal outcomes including preterm birth (PTB). However, the frequency and causes of PTB in this population are not well understood. We hypothesized that NIHF frequently results in PTB due to medically indicated delivery for fetal distress. STUDY DESIGN: This was a secondary analysis of a prospectively enrolled cohort of pregnancies with NIHF that underwent exome sequencing if standard testing was nondiagnostic. The primary outcome was frequency of PTB at <37 weeks' gestation. Secondary outcomes were reasons for PTB, fetal predictors of PTB, and frequency of neonatal death following PTB. RESULTS: Fifty-six cases were included, with a median gestational age at delivery of 32.8 weeks (interquartile range [IQR]: 30.3-35.0). Overall, 86% (48/56) were delivered preterm. Among 48 PTBs, 18 (38%) were spontaneous, 9 (19%) were medically indicated for maternal indications (primarily preeclampsia), and 21 (44%) were medically indicated for fetal indications (nonreassuring antenatal testing or worsening effusions). Neither fetal genetic diagnosis nor polyhydramnios was associated with PTB. CONCLUSION: More than four-fifths of pregnancies with NIHF result in PTB, often due to nonreassuring fetal status. These data are informative for counseling patients and for developing strategies to reduce PTB in pregnancies with NIHF. KEY POINTS: · Pregnancies complicated by nonimmune hydrops fetalis often result in preterm birth.. · Preterm birth in these cases is most often medically indicated for fetal benefit.. · Fetal genetic conditions and polyhydramnios may be associated with preterm birth in cases of NIHF..

Survey of intrauterine red blood cell (RBC) transfusion practices in the United States.

BACKGROUND: A paucity of data exists about the current practice of fetal red blood cell (RBC) transfusion in the United States (US). This investigation describes intrauterine transfusion (IUT) RBC product selection and processing practices at different US institutions. METHODS: A transfusion medicine and maternal-fetal medicine (MFM) team designed a survey to interrogate and characterize RBCs utilized for IUT. This survey was distributed to seventy US institutions with fetal treatment centers (October 2020-April 2021) identified through the NAFTNet (North American Fetal Therapy Network). RESULTS: Thirty-seven institutions responded (response rate 53%, 37/70), but five were excluded for not performing IUTs. Most (84%; 27/32) performed 1-24 IUTs annually; two performed >50 IUTs/year. Group O, Rh(D) negative RBC units were always used by 66% (21/32), and 75% (24/32) provided hemoconcentrated RBCs by washing (17/24) or dry packing (6/24). Overall, 66% (21/32) targeted a hematocrit ≥75%. Fifty percent provided both leukocyte-reduced and CMV-negative RBC units. Irradiation of RBC units was performed within 6 h of issue at 63% (20/32) of sites. Most (81%, 26/32) used RBC units at <7 days of age after collection, 56% (18/32) always provided washed RBC units, while 19% (6/32) issued washed RBC only if fresh units are unavailable. Implicated maternal RBC alloantibodies were matched for 78% (25/32) of the time. The transfused volume was universally determined by the MFMs. DISCUSSION: Heterogeneity and lack of standardization exist in RBC product selection and special processing steps for IUTs in the US. Hence, the establishment of a consensus to standardize IUT protocols is needed.

Perinatal outcomes and 2017 ACC/AHA blood pressure categories.

OBJECTIVE: To evaluate the association of blood pressure category < 20 weeks according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) criteria with adverse perinatal outcomes. STUDY DESIGN: A retrospective cohort study of singleton deliveries between 1/2014 and 10/2017 was undertaken. Blood pressure category assigned by 2017 ACC/AHA criteria applied to blood pressures prior to 20 weeks gestation: normal (systolic < 120 and diastolic < 80), elevated blood pressure (systolic 120-129 and diastolic < 80 mmHg), stage 1 hypertension (systolic 130-139 and/or diastolic 80-89), stage 2 hypertension (prior diagnosis of chronic hypertension or systolic ≥ 140 or diastolic ≥ 90 mmHg). MAIN OUTCOME MEASURES: The primary outcome was preeclampsia. Secondary outcomes included preterm birth and postpartum readmission. Chi-square, ANOVA and Kruskal-Wallis tests and multivariable Poisson regression were used for analysis. RESULTS: Of the 6,067 eligible pregnancies, 3,855 (63.5%) had normotensive blood pressure, 1,224 (20.2%) elevated blood pressure, 624 (10.3%) stage 1 hypertension, and 364 (6.0%) stage 2 hypertension. Compared to 4.6% prevalence of preeclampsia among normotensive pregnancies, higher categories were associated with higher preeclampsia prevalence: elevated blood pressure (10.7%, adjusted relative risk (aRR) 2.2, 95% confidence interval (CI) 1.8-2.6), stage 1 hypertension (15.1%, aRR 2.7, 95% CI 2.2-3.4) and stage 2 hypertension (38.7%, aRR 6.2, 95% CI 5.1-7.4). Non-normal categories were also associated with a higher risk of preterm birth and postpartum readmission. CONCLUSION: Patients with elevated blood pressure and stage 1 and 2 hypertension at < 20 weeks are at increased risk of adverse obstetric perinatal outcomes.

Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia.

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia.

Racial/ethnic disparities among women receiving intrauterine transfusions for alloimmunization at a single fetal treatment center.

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This "IUT cohort" was compared to an "Alloimmunization cohort": patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p < .0001), and more non-English speakers (18.6% vs. 4.6%, p = .001). Twenty-one percent (9/43) of patients had immigrated to the United States, all of whom had pregnancies or miscarriages in their country of origin. A third of patients had new antibodies identified on serial screens during the current pregnancy. Significantly more women of Latina ethnicity and non-English speakers required IUTs compared to the cohort of women with alloimmunization. Insufficient access to care prior to arriving in the United States and among racial and ethnic minorities in the United States may contribute to these findings. Providers should be cognizant of potential, racial, and ethnic inequalities among women receiving intrauterine transfusions.

Placental Abruption as a Risk Factor for Heart Failure.

Complications of pregnancy present an opportunity to identify women at high risk of cardiovascular disease (CVD). Placental abruption is a severe and understudied pregnancy complication, and its relationship with CVD is poorly understood. The California Healthcare Cost and Utilization Project database was used to identify women with hospitalized pregnancies in California between 2005 and 2009, with follow-up through 2011. Pregnancies, exposures, covariates, and outcomes were defined by International Classification of Diseases Ninth Revision codes. Cox proportional-hazards regression was used to examine the association between placental abruption and myocardial infarction (MI), stroke, and heart failure (HF). Multivariate models controlling for age, race, medical co-morbidities, pregnancy complications, psychiatric and substance use disorders, and socioeconomic factors were employed. Among over 1.5 million pregnancies, placental abruption occurred in 14,881 women (1%). Median follow-up time from delivery to event or censoring was 4.87 (interquartile range 3.54 to 5.96) years. In unadjusted models, placental abruption was associated with risk of HF, but not MI or stroke. In fully-adjusted models, placental abruption remained significantly associated with HF (Hazard ratio 1.44; 95% confidence interval 1.09 to 1.90). Among women with placental abruptions, hypertensive disorders of pregnancy and preterm birth respectively modified and mediated the association between placental abruption and HF. In conclusion, placental abruption is a risk factor for HF, particularly in women who also experience hypertensive disorders of pregnancy and preterm birth. Placental abruption is a specific adverse pregnancy outcome associated with risk of HF.

Solid pseudopapillary neoplasm of the pancreas head in a pregnant woman: safe pancreaticoduodenectomy postpartum.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare and typically arise in young women. The optimal management of a pregnant woman suspected of having an SPN of the pancreas head is unclear. We report such a case where close monitoring for tumor growth was done during pregnancy and a successful pancreaticoduodenectomy was performed after term delivery.

A study of prevention and regression of cardiac hypertrophy with a prolactin inhibitor in a biological model of ventricular hypertrophy caused by aorto caval fistulae in rat.

BACKGROUND: The possibility of decreasing or reverting left ventricular hypertrophy and, therefore, cardiac hypertrophy (CH) is an important medical issue. The aim of the present study was to evaluate these two possibilities with a 3-week daily dose of captopril, losartan, or bromocriptine in a preventive or corrective model. METHODS: After aorto caval fistulae (ACF) surgery on adult male Wistar rats to induce CH, animals were assigned to the preventive protocol (drug treatment began immediately after surgery) or corrective protocol (hypertrophy was allowed to develop before drug treatment). After treatments, isoproterenol was administered to half of the animals to further induce CH. The groups included the passive control, the sham-operated animals, those with ACF surgery but without drug treatment, and the 3-week treatments with captopril, losartan, or the low or high dose of bromocriptine. RESULTS: Three treatments, with captopril, losartan, or the high dose of bromocriptine, significantly impeded/reverted an increase in CH-related parameters in the preventive/corrective model compared to the surgically treated group without drug treatment. The same effect was found after isoproterenol administration. The present results show an avoidance/reversion of CH with these three treatments. Better results were found with the angiotensin converting enzyme inhibitor (captopril) than with the prolactin inhibitor (bromocriptine). CONCLUSIONS: Treatments with captopril, losartan, and the high dose of bromocriptine were effective in preventing/reversing the manifestation of CH in the preventive/corrective rat models. Further studies are needed to identify the initial mediator, the key component, and the molecular events involved in the pathogenesis of CH.

Evidence against alpha-adrenoceptors mediating relaxation in rat thoracic aortae: alpha-agonists relaxation depends on interaction with alpha-adrenoceptors.

In rat aorta, the presence of functional alpha(2)-adrenoceptors (alpha(2)-AR) was investigated in ring preparations preconstricted with alpha(1)-adrenergic and non- alpha(1)-adrenergic agonists. Particularly, the hypothetical interference of alpha(2)-AR agonists with alpha(1)-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to alpha(2)-AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 x 10(-6) m), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (-log EC(50)) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine-constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective alpha(2)-AR antagonist, rauwolscine (< or =1 x 10(-6) m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F(2alpha) (3 x 10(-7) m). Moreover, clonidine and UK 14304-induced relaxation of endothelium-denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration-contraction curves to clonidine and UK 14304 in endothelium-denuded aortic rings were significantly shifted to the right by the alpha(1D)-AR selective antagonist, BMY 7378, and rauwolscine. The pA(2) and pK(B) values for BMY 7378 and rauwolscine, respectively, against endothelium-independent actions of clonidine and UK 14304 were characteristic of an effect on the alpha(1D)-AR. The other selective alpha(2)-AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional alpha(2)-AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist-dependent active state of the alpha(1)-AR), inhibitory and excitatory, interaction with alpha(1)-ARs.

Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester.

In this study, we aimed to elucidate whether the daily hypertensive dose of long-term N(G)-nitro-l-arginine methyl ester (l-NAME) treatment, could make a difference between endothelial and smooth muscle functions in rat thoracic aorta. We test the hypothesis that high-dose, long-term l-NAME treatment has a depressive effect on vascular smooth muscle contractile activity which is not related with nitric oxide (NO) synthesis inhibition. After 14 days of treatment, isometric tension and (45)Ca(2+) influx were measured in aortic tissues isolated from l-NAME(10) and l-NAME(100) hypertensive (10 and 100 mg/kg/day, systolic blood pressures 167 +/- 7 and 172 +/- 10 mmHg, respectively) and control normotensive rats (132 +/- 7 mmHg). In l-NAME(10)- and l-NAME(100)-treated rats, acetylcholine-induced relaxation in aortic rings was suppressed with no significant difference between the treatments. l-NAME(100) (but not l-NAME(10)) treatment, significantly inhibited contractile responses to phenylephrine, angiotensin II, and K(+) (80 mm) in endothelium-intact tissues. The effect of l-NAME(100) on phenylephrine-induced contractile responses was not observed after 3 days of treatment. In endothelium-denuded aortic tissues of l-NAME(100) (but not l-NAME(10))-treated rats, phenylephrine (1 x 10(-6) m)- and K(+) (80 mm)-induced contractions and (45)Ca(2+) influxes were significantly reduced. In Ca(2+)-free medium (0.1 mm EDTA), on the contrary, the transient contractions obtained by either phenylephrine (1 x 10(-6) m) or caffeine (1 x 10(-2) m), or the sustained contractions induced by 12-o-tetradecanoylphorbol-13-acetate (1 x 10(-6) m; a protein kinase C activator) in endothelium-denuded aortic rings, were not modified by both l-NAME treatments. These results indicate that in aortic rings from l-NAME hypertensive rats, low and high doses, long-term l-NAME administration may be associated with equivalent inhibition in NO-dependent vasodilator tone (corresponding to equivalent hypertension values); whereas only high-dose, long-term l-NAME administration produces an endothelium-independent decrease in vasocontrictor activity, at least partly explained by a reduction in extracellular Ca(2+) influx.