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.

Characterizing the process of urgent referrals and transfers to a large tertiary care apheresis centre in Ontario: A retrospective database review.

BACKGROUND: Therapeutic plasma exchange (TPE) and red blood cell exchange (RBCX) are life-saving apheresis procedures offered in 7 Ontario hospitals. Most referrals are directed by CritiCall Ontario (CritiCall), a 24/7 service funded by the Ontario Ministry of Health and Long-Term Care. We used CritiCall data to examine referral requests, acceptances, and transfers for urgent apheresis to our centre. METHODS: Retrospective CritiCall referral and transfer data for urgent apheresis between October 2013 and December 2018 were included. Continuous variables were analyzed by linear regression. Categorical variables were analyzed using nonparametric tests. RESULTS: Eighty-five cases (52 TPE, 33 RBCX) were identified. Median patient age was 52 years (interquartile range [IQR] 32) for TPE, 29 years (IQR 18) for RBCX. Most patients (58%) were female. Total time from referral to arrival at our centre was 243 (IQR 166) minutes. The greatest proportion of this total was from patient acceptance to arrival (169 [IQR 112] minutes). Median distance between referring and accepting centres was 39 (IQR 30) kilometres, with ground transportation used most often. Multiple linear regression examining factors that contribute to total time demonstrated that the number of physicians contacted prior to patient acceptance and inter-hospital distance were independently associated (p = 0.007 and p = 0.048, respectively). INTERPRETATION: Addressing modifiable factors to reduce time is important given that time to initiate treatment is associated with better outcomes. Quality improvement strategies should be aimed at coordinated provincial resource sharing, pairing referrals with nearest available apheresis centres, and creating efficiency in the interval between patient acceptance and arrival.

Clinical and laboratory predictors of fetal and neonatal alloimmune thrombocytopenia.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of intracranial hemorrhage (ICH) in thrombocytopenic term infants. We investigated clinical and laboratory predictors of severe FNAIT in a tertiary care referral center. STUDY DESIGN AND METHODS: Retrospective cohort study over a 30-year period. We defined FNAIT as recurrence of neonatal thrombocytopenia in a subsequent pregnancy; and severe outcomes as any of: (1) a birth platelet count below 20 × 109 /L; (2) ICH or (3) fetal death. We used a generalized estimating equations analysis and classification tree analysis to identify risk factors for severe FNAIT in a subsequent pregnancy. RESULTS: During index pregnancies (n = 135 in 131 mothers), 71 infants (52.6%) had severe outcomes including a platelet count <20 × 109 /L (n = 45), fetal or neonatal ICH (n = 32), or fetal death (n = 4). During subsequent pregnancies (n = 72), 15 infants (20.8%) had severe outcomes including birth platelets <20 × 109 /L (n = 10), ICH (n = 2), or death (n = 3). Forty-two women (58.3%) received antenatal intravenous immune globulin (IVIG) during subsequent pregnancies. Eight mothers (n = 9 infants) had severe FNAIT outcomes despite receiving antenatal IVIG. Maternal antibodies to human platelet antigens (HPA) was the only independent predictor of severe FNAIT in a subsequent pregnancy (OR = 25.3, p = .004). Nevertheless, one of 43 infants from antibody-negative mothers had a severe outcome. CONCLUSIONS: The presence of anti-HPA is highly indicative of the diagnosis of severe FNAIT; however, we observed one infant who had severe FNAIT recurrence, defined using strict clinical criteria, without a maternal antibody. Improved diagnostic and therapeutic strategies are needed to prevent severe FNAIT in high-risk mothers.

Lower limb-localized vascular phenomena explain initial orthostatic hypotension upon standing from squat.

The cause(s) of initial orthostatic hypotension (transient fall in blood pressure within 15 s upon active rising) have not been established. We tested the hypothesis that this hypotension is due to local vascular phenomena in contracting leg muscles from the brief effort of standing up. Seventeen young healthy subjects (2 male and 15 female, 22.5 ± 1.0 years) performed an active rise from resting squat after a 10-s squat, a 1-min squat, or a 5-min squat. Beat-by-beat arterial blood pressure, cardiac output, heart rate, and stroke volume (Finometer finger photoplethysmography) and right common femoral artery blood flow (Doppler and Echo ultrasound) were recorded. Data are means ± SE. Quiet standing before squat represented baseline. Peak increases in lower limb and total vascular conductance (ml·min(-1)·mmHg(-1)) upon standing were not different within squat conditions (10-s squat, 50.0 ± 12.4 vs. 44.3 ± 5.0; 1-min squat, 54.7 ± 9.2 vs. 50.5 ± 4.5; 5-min squat, 67.4 ± 13.7 vs. 58.8 ± 3.9; all P > 0.574). Mean arterial blood pressure (in mmHg) fell to a nadir well below standing baseline in all conditions despite increases in cardiac output. The hypotension predicted by the increase in leg vascular conductance accounted for this hypotension [observed vs. predicted (in mmHg): 10-s squat, -17.1 ± 2.1 vs. -18.3 ± 5.5; 1-min squat, -22.0 ± 3.8 vs. -25.3 ± 4.9; 5-min squat, -28.3 ± 4.0 vs. -29.2 ± 6.7]. We conclude that rapid contraction induced dilation in leg muscles with the effort of standing, along with a minor potential contribution of elevated lower limb arterio-venous pressure gradient, outstrips compensatory cardiac output responses and is the cause of initial orthostatic hypotension upon standing from squat.

Self-reported periconception weight loss attempts do not alter infant body composition.

OBJECTIVES: Maternal obesity increases the risk for adverse infant outcomes; therefore, achieving an optimal body mass index before conception is recommended. Periconceptional maternal weight loss, however, has been associated with adverse outcomes for the fetus, including altered body composition in animal studies. It is not clear whether periconception weight loss alters infant body composition in humans. The aim of this study was to compare body composition in offspring of women who attempted to lose or maintain weight in the periconception period. METHODS: Women who delivered a healthy term infant were grouped according to attempt to lose weight. Infant body composition was determined by air displacement plethysmography and anthropometric measurements. RESULTS: In a cohort of 73 women, 27 attempted to lose weight and 46 maintained weight in the periconception period. Infant birth weight, percent body fat, and head and arm circumference were not altered by maternal attempts to lose weight. Infant abdominal circumference was increased in the offspring of women who attempted to lose weight in the periconception period. Infant percent body fat was increased in overweight and obese mothers and in female infants. CONCLUSION: The results of this study showed that attempts to lose weight in the periconception period do not significantly alter infant body composition. The increase in abdominal circumference may indicate a difference in fat distribution in offspring of women who attempted to lose weight, which may increase their risk for future metabolic and cardiovascular disease.

Periconception weight loss: common sense for mothers, but what about for babies?

Obesity in the childbearing population is increasingly common. Obesity is associated with increased risk for a number of maternal and neonatal pregnancy complications. Some of these complications, such as gestational diabetes, are risk factors for long-term disease in both mother and baby. While clinical practice guidelines advocate for healthy weight prior to pregnancy, there is not a clear directive for achieving healthy weight before conception. There are known benefits to even moderate weight loss prior to pregnancy, but there are potential adverse effects of restricted nutrition during the periconceptional period. Epidemiological and animal studies point to differences in offspring conceived during a time of maternal nutritional restriction. These include changes in hypothalamic-pituitary-adrenal axis function, body composition, glucose metabolism, and cardiovascular function. The periconceptional period is therefore believed to play an important role in programming offspring physiological function and is sensitive to nutritional insult. This review summarizes the evidence to date for offspring programming as a result of maternal periconception weight loss. Further research is needed in humans to clearly identify benefits and potential risks of losing weight in the months before conceiving. This may then inform us of clinical practice guidelines for optimal approaches to achieving a healthy weight before pregnancy.