Natural history of blood pressure in sickle cell disease pregnancy.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non-SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSß0 group than in the non-SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSß0 group and non-SCD controls, whereas the mean SBP and DBP in the HbSC/HbSß+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSß0 .

Blood pressure thresholds for the diagnosis of hypertensive disorders of pregnancy in sickle cell disease.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared the characteristics of subjects with new or worsening proteinuria (NWP) during pregnancy to those without. We then constructed receiver operating characteristic (ROC) curves to determine the blood pressure (BP) that best identifies those with NWP. The SBP or DBP thresholds which maximized sensitivity and specificity were 120 mmHg SBP (sensitivity: 55.2%, specificity: 73.5%) and 70 mmHg DBP (sensitivity: 27.6%, specificity: 67.7%). The existing BP threshold of 140/90 mmHg lacked sensitivity in both genotype groups (HbSS/HbSß0 : SBP = 21% sensitive, DBP = 5.3% sensitive; HbSS/HbSß+ : SBP = 10% sensitive, DBP = 0% sensitive). Finally, percent change in SBP, DBP and MAP were all poor tests for identifying NWP. Existing BP thresholds used to diagnose hypertensive disorders of pregnancy (HDP) are not sensitive for pregnant people with SCD. For this population, lowering the BP threshold that defines HDP may improve identification of those who need increased observation, consideration of early delivery and eclampsia prophylaxis.

Postpartum Hemorrhage in Women with von Willebrand Disease: Consider Other Etiologies.

OBJECTIVE: Higher rates of postpartum hemorrhage (PPH) have been reported for women with von Willebrand disease (VWD). Comprehensive multidisciplinary care reduces these rates; thus PPH may not be secondary to VWD. METHODS: We conducted a retrospective review for the period of 2009-2018, including all VWD pregnancies at 2 tertiary care academic hospitals to determine rates, etiology, and timing of PPH. RESULTS: A total of 63 women with 80 pregnancies were included. Three women had twin pregnancies. Sixty-six pregnancies (82.5%) involved type 1 VWD; 4 (5.0%), type 2 (unclear subtype); 3 (3.8%) type 2A; 3 (3.8%) type 2B; and 2 (2.5%), type 2M. Median age of patients was 32.9 years (range 19-43 y). Most patients were blood type O (65%), and 33 of 80 pregnancies (41.3%) were nulliparous. The mean bleeding assessment score was 8 (range 0-16). Thirty-seven pregnancies (46.3%) received prophylactic hemostatic treatment prior to delivery. Seventy-four percent of pregnancies were delivered vaginally, and 88% received epidural anaesthesia. The majority of pregnancies (78.8%) had von Willebrand factor (VWF) levels assessed during the third trimester, with most (71.3%) achieving VWF levels above 1.00 IU/mL. Four pregnancies (5.2%) were complicated by primary PPH; uterine atony in 2 and placenta previa in 1. Delayed postpartum bleeding occurred in 5 pregnancies (6.3%). CONCLUSION: Multidisciplinary care of pregnancies with VWD improves outcomes. Rates of primary and delayed PPH in this study are lower than previously described and are similar to those of women without VWD. In women with VWD, uterine etiologies for primary PPH need to be considered, in a manner similar to the assessment of women without VWD, to ensure hemostasis is achieved.

Expecto Patronum! Leveraging the Positive Force of COVID-19 Vaccines for Pregnant and Lactating Individuals.

For over a year, the world has been gripped by the coronavirus disease 2019 (COVID-19) pandemic, which has had far-reaching effects on society. The integrity of national health care systems has also been challenged, owing to shifts in guidance and misinformation. Although initial reports suggested that pregnant people were not at increased risk of severe COVID-19, current data arising from the "third wave" paint a much more concerning picture. In addition, pregnant and lactating people were excluded from vaccine trials, which has hindered the ability of health care professionals to provide evidence-based counselling regarding the safety and efficacy of the available vaccines in these populations. This commentary reviews the current data on the safety of COVID-19 vaccines in pregnancy. The evidence is clear that the risks of hospitalization and severe maternal and potentially fetal morbidity from COVID-19 in pregnancy far outweigh the very minimal risks of COVID-19 vaccination in pregnancy.

Impact of Perinatal Primary Hyperparathyroidism on Maternal and Fetal and Neonatal Outcomes: Retrospective Case Series.

OBJECTIVE: We sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum. METHODS: A retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported. RESULTS: From 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes. CONCLUSION: Rates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work.

Obstetric neuraxial anesthesia at low platelet counts in the context of immune thrombocytopenia: a systematic review and meta-analysis.

PURPOSE: Primary immune thrombocytopenia (ITP) is an autoimmune condition affecting women of childbearing age that is characterized by diminished platelet quantity with preserved function. Although pregnant women with ITP are often denied obstetric neuraxial anesthesia (OBNA) with low platelet counts for fear of neuraxial hematoma, the true magnitude of neuraxial hematoma for ITP parturients is unknown. The aim of this systematic review and meta-analysis was to examine OBNA outcomes in ITP parturients with platelet counts below 100 x 109·L-1. SOURCE: Articles published in MEDLINE, Embase, Web of Science, Scopus, Cochrane, and PubMed in process until May 14, 2018 were searched. Two reviewers independently screened 954 articles by title and abstract, reviewed 62 full-texts, extracted data, and assessed risk of bias for 26 articles. PRINCIPAL FINDINGS: Of 291 pregnant women with ITP and platelet counts below 100 x 109·L-1, 166 received OBNA and 61 of these had platelet counts below 80 x 109·L-1. No neuraxial hematomas were reported. Meta-analysis of six studies showed higher platelet counts in those with OBNA than without (mean difference [MD], 19 x 109·L-1; 95% confidence interval [CI], 11 to 26; P < 0.001), with no difference between epidural and spinal anesthesia (MD, 0.4 x 109·L-1; 95% CI, -4 to 4; P = 0.86). CONCLUSION: Our study highlights continued reluctance to offer OBNA below the commonly quoted 80 x 109·L-1 platelet count, based largely on consensus and theoretical presumption of risk. This further negatively influences the accrual of large-scale data. The evidence of no neuraxial hematoma after OBNA provided herein offers support for considering neuraxial anesthesia at lower platelet count thresholds. Each patient should be afforded individualized discussion of risk and benefit relative to other analgesic measures. TRIAL REGISTRATION: PROSPERO (CRD42018059220); registered 2 August, 2018.

Reported Outcomes in Perinatal Iron Deficiency Anemia Trials: A Systematic Review.

BACKGROUND/AIMS: Iron deficiency (ID) and iron deficiency anemia (IDA) are global health concerns associated with adverse perinatal effects. Despite efforts taken at the international level, there is no consensus on unified prevention/treatment strategies, largely stemming from inconsistencies of outcome reporting. Our objective was to comprehensively assess outcome reporting perinatal iron intervention trials as Phase 1 of core outcome set (COS) development to inform future research. METHODS: Systematic search in MEDLINE, EMBASE, Cochrane Databases, and CINAHL (January 2000 - April 2016), with inclusion of trials involving pregnant or postpartum women with ID/IDA confirmed before recruitment. Articles were independently screened and selected by 2 reviewers; data were extracted in duplicate. Quality was assessed using published scoring systems. Outcome definitions and measurement methods were tabulated. RESULTS: Of 7,046 citations, 33 randomized controlled trials were included. Sixty-nine reported outcomes were categorized into 8 domains. High methodological quality characterized 25 (76%) studies. Reporting quality was low in 16 (49%), moderate in 13 (39%), and high in 4 (12%) studies. Variation was greatest for outcome definition, timing of assessment and measurement methods. CONCLUSION: This review identifies a comprehensive long-list of outcomes reported of perinatal iron interventions for ID/IDA. Beyond highlighting existing variation in outcome reporting, it provides a foundation for development of a COS for future trials.

Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy.

Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 × 10(9)/L vs corticosteroids 77 × 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 × 10(9)/L and 18 (9%) had platelet counts <50 × 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 × 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP.

The Approach to Peripartum Management of Anticoagulation: A Multidisciplinary Survey.

OBJECTIVE: This study sought to determine whether there is practice variation in the treatment and prevention of acute venous thromboembolism (VTE) in pregnant patients, potentially to prioritize future studies. BACKGROUND: The risk of VTE during pregnancy is five-fold that of the non-pregnant state. Guidance is often lacking for the treatment and prophylaxis of VTE because there are few RCTs. METHODS: The study used a cross-sectional study design using a self-administered electronic questionnaire consisting of 11 case scenarios that were sent to hematologists, maternal-fetal medicine specialists, obstetricians and gynaecologists, and internal medicine specialists across Canada. RESULTS: A total of 254 participants responded to the survey and 193 (76%) completed the survey, 158 of whom indicated that they were involved in the decision to anticoagulate these patients. Anticoagulation of patients with superficial venous thrombosis during pregnancy, monitoring of low-molecular-weight heparin antepartum, and discontinuation of this agent at the time of delivery were the scenarios associated with the largest variability of responses. For the management of acute VTE antepartum, most participants favoured a once-daily regimen, although internists more so than obstetrics and gynaecology physicians (94.7% vs. 73.7%). Cesarean section was not perceived to be a procedure with a marked increased risk of thrombosis to warrant thromboprophylaxis because most physicians elected not to offer thromboprophylaxis for this scenario. However, obesity and severe preeclampsia with Cesarean section led to the predominant use of thromboprophylaxis, at 80.0% and 68.4%, respectively. CONCLUSION: Prospective studies addressing peripartum management where significant discrepancies exist are warranted.

Prophylactic transfusion for pregnant women with sickle cell disease: a systematic review and meta-analysis.

Pregnancy in women with sickle cell disease is associated with adverse maternal and neonatal outcomes. Studies assessing the effects of prophylactic red blood cell transfusions on these outcomes have drawn inconsistent conclusions. The objective of this systematic review was to assess the effect of prophylactic compared with on-demand red blood cell transfusions on maternal and neonatal outcomes in women with sickle cell disease. A systematic search of several medical literature databases was conducted. Twelve studies involving 1291 participants met inclusion criteria. The studies had moderate to high risk of bias. Meta-analysis demonstrated that prophylactic transfusion was associated with a reduction in maternal mortality (7 studies, 955 participants; odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.91), vaso-occlusive pain episodes (11 studies, 1219 participants; OR, 0.26; 95% CI, 0.09-0.76), pulmonary complications (9 studies, 1019 participants; OR, 0.25; 95% CI, 0.09-0.72), pulmonary embolism (3 studies, 237 participants; OR, 0.07; 95% CI, 0.01-0.41), pyelonephritis (6 studies, 455 participants; OR, 0.19; 95% CI, 0.07-0.51), perinatal mortality (8 studies, 1140 participants; OR, 0.43; 95% CI, 0.19-0.99), neonatal death (5 studies, 374 participants; OR, 0.26; 95% CI, 0.07-0.93), and preterm birth (9 studies, 1123 participants; OR, 0.59; 95% CI, 0.37-0.96). Event rates for most of the results were low. Prophylactic transfusions may positively impact several adverse maternal and neonatal outcomes in women with sickle cell disease; however, the evidence stems from a relatively small number of studies with methodologic limitations. A prospective, multicenter, randomized trial is needed to determine whether the potential benefits balance the risks of prophylactic transfusions.

Research standardization tools: pregnancy measures in the PhenX Toolkit.

Only through concerted and well-executed research endeavors can we gain the requisite knowledge to advance pregnancy care and have a positive impact on maternal and newborn health. Yet the heterogeneity inherent in individual studies limits our ability to compare and synthesize study results, thus impeding the capacity to draw meaningful conclusions that can be trusted to inform clinical care. The PhenX Toolkit (http://www.phenxtoolkit.org), supported since 2007 by the National Institutes of Health, is a web-based catalog of standardized protocols for measuring phenotypes and exposures relevant for clinical research. In 2016, a working group of pregnancy experts recommended 15 measures for the PhenX Toolkit that are highly relevant to pregnancy research. The working group followed the established PhenX consensus process to recommend protocols that are broadly validated, well established, nonproprietary, and have a relatively low burden for investigators and participants. The working group considered input from the pregnancy experts and the broader research community and included measures addressing the mode of conception, gestational age, fetal growth assessment, prenatal care, the mode of delivery, gestational diabetes, behavioral and mental health, and environmental exposure biomarkers. These pregnancy measures complement the existing measures for other established domains in the PhenX Toolkit, including reproductive health, anthropometrics, demographic characteristics, and alcohol, tobacco, and other substances. The preceding domains influence a woman's health during pregnancy. For each measure, the PhenX Toolkit includes data dictionaries and data collection worksheets that facilitate incorporation of the protocol into new or existing studies. The measures within the pregnancy domain offer a valuable resource to investigators and clinicians and are well poised to facilitate collaborative pregnancy research with the goal to improve patient care. To achieve this aim, investigators whose work includes the perinatal population are encouraged to utilize the PhenX Toolkit in the design and implementation of their studies, thus potentially reducing heterogeneity in data measures across studies. Such an effort will enhance the overall impact of individual studies, increasing the ability to draw more meaningful conclusions that can then be translated into clinical practice.

Venous thromboembolism in obese pregnant women: approach to diagnosis and management.

Venous thromboembolism (VTE) remains among the leading causes of maternal mortality in the developed world, presenting variably as deep vein thrombosis (DVT), pulmonary embolism (PE) or cerebral vein thrombosis (CVT), among others. Obesity in particular has been recognized as the principal contributing factor to the risk of VTE in pregnancy and with the global increase in the rates of obesity affecting reproductive age women, heightened awareness of the risk and consequences of VTE in this population are vital. Thus, prophylaxis, diagnosis and treatment of VTE in the obese gravida are discussed.

Hyperreactio Luteinalis: Maternal and Fetal Effects.

Hyperreactio luteinalis is a rare condition in which there is massive cystic enlargement of the ovaries, mimicking malignancy, during pregnancy. When confronted with this condition, the fear of missing a cancer diagnosis often leads the physician to react with unnecessary surgical intervention, potentially resulting in impaired future fertility. The literature on the subject contains mainly case reports and one small case series. A recent review attempted to summarize what is currently known, but there has not yet been a pervasive change in the approach to the management of this condition. In order to define the natural history of the condition and its maternal and fetal effects, we examined all case reports available in the English literature from 1993 to 2014, in addition to another as yet unpublished case report. Our analysis suggests that, despite its impressive presentation with ovarian enlargement and hyperandrogenism, hyperreactio luteinalis tends to be self-limiting, with spontaneous postpartum resolution and without untoward maternal or fetal sequelae. In particular, fetal virilization is rare, and dependent on the timing of hyperandrogenism. Adverse pregnancy outcomes are likely a consequence of the abnormally high hCG levels observed in many of these gestations, and the subset of women with these abnormal values should be considered for enhanced surveillance. Vaginal delivery is preferred, and strategies to sustain the potential for breastfeeding must be introduced while maternal androgen levels fall, allowing lactation to be established. Considering its benign nature and postpartum resolution, management of HL must be conservative, and continued education of health care professionals who may encounter this entity is vital.

L'hyperreactio luteinalis est un trouble rare qui donne lieu à une hypertrophie kystique des ovaires de grande envergure, laquelle imite la présence d'une tumeur maligne, pendant la grossesse. La présence d'une telle situation mène souvent le médecin à procéder inutilement à une intervention chirurgicale motivée par la crainte de voir un diagnostic de cancer passer inaperçu, ce qui pourrait affecter la fertilité future de la patiente. La littérature sur le sujet consiste principalement en des exposés de cas et en une série de cas de faible envergure. Bien qu'une récente analyse ait tenté de résumer les données connues à ce sujet à l'heure actuelle, aucune modification n'a encore été universellement apportée à la prise en charge de cette pathologie. Afin de définir l'histoire naturelle de cette dernière et d'en déterminer les effets maternels et fœtaux, nous nous sommes penchés sur tous les exposés de cas ayant été publiés en anglais entre 1993 et 2014, ainsi que sur un exposé de cas n'ayant pas encore été publié. Notre analyse laisse entendre que, malgré sa présentation spectaculaire (hypertrophie ovarienne et hyperandrogénie), l'hyperreactio luteinalis a tendance à être spontanément résolutive à la suite de l'accouchement, sans séquelles indésirables pour la mère ou le fœtus. En particulier, la virilisation fœtale est rare et dépend de la chronologie de l'hyperandrogénie. Les issues de grossesse indésirables sont probablement attribuables aux taux anormalement élevés de hCG qui sont constatés dans bon nombre des grossesses affectées; la mise en œuvre d'une surveillance accrue devrait être envisagée pour ce qui est du sous-groupe des femmes qui présentent de telles valeurs anormales. L'accouchement vaginal est à privilégier et des stratégies visant à soutenir le potentiel d'allaitement doivent être mises en œuvre pendant la chute des taux maternels d'androgènes, afin de permettre la lactation. Compte tenu de la nature bénigne de l'hyperreactio luteinalis et de sa résolution postpartum, la prise en charge de ce trouble doit être conservatrice; de plus, la formation continue des professionnels de la santé qui pourraient devoir y faire face est cruciale.

Pregnancy outcomes and iron status in ß-thalassemia major and intermedia: a systematic review and meta-analysis.

ABSTRACT: Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia intermedia (TI). Pregnancy is associated with adverse maternal and neonatal outcomes, frequency of which has not been well delineated. This systematic review aims to provide risk estimates of maternal and fetal outcomes in TM and TI and explore pregnancy's impact on iron homeostasis. Fifteen studies (429 participants, 684 pregnancies) were included. Meta-analysis revealed a higher thrombosis risk in TI (3.7%) compared to TM (0.92%), unchanged from prepregnancy. Heart failure risks in the earlier years appeared similar (TM 1.6% vs TI 1.1%), and maternal mortality in TM was 3.7%, but with current management, these risks are rare. Gestational diabetes and pre-eclampsia occurred in 3.9% and 11.3% of TM pregnancies, respectively. Caesarean section rates were 83.9% in TM and 67% in TI. No significant difference in stillbirth, small for gestational age neonates, or preterm birth incidence between TM and TI was observed. In TM pregnancies, red cell requirements significantly increased (from 102 to 139 ml/kg/year, P = 0.001), and 70% of TI pregnancies required blood transfusions. As expected, increased transfusion alongside chelation cessation led to a significant increase in serum ferritin during pregnancy (TM by 1005 ng/mL; TI by 332 ng/mL, P < 0.0001). Deterioration in iron status was further reflected by an increase in liver iron concentration (from 4.6 to 11.9 mg/g dry weight, P < 0.0001), and myocardial T2-star (T2∗) magnetic resonance imaging decreased (from 36.2 ± 2.5 ms to 31.1 ms) during pregnancy. These findings emphasize the elevated maternal risk of iron-related cardiomyopathy during pregnancy and labor, stressing the importance of cardiac monitoring and postpartum chelation therapy resumption.