Does Hydroxychloroquine Protect against Preeclampsia and Preterm Delivery in Systemic Lupus Erythematosus Pregnancies?

OBJECTIVE: Systemic lupus erythematosus (SLE) increases the risk of complications in pregnancy. Hydroxychloroquine (HCQ) decreases flares and neonatal lupus syndrome. Limited evidence suggests that HCQ also reduces preeclampsia and preterm birth in SLE pregnancies. We studied whether HCQ was associated with lower odds of preeclampsia and preterm delivery in SLE pregnancies. STUDY DESIGN: We conducted a retrospective cohort study of 129 deliveries of 110 patients with SLE delivered at a single institution (2000-2017). HCQ exposure and preeclampsia, along with other clinical data, were extracted from chart review. Crude and multivariable-adjusted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 41% were exposed to HCQ, of whom 13.5% were complicated by preeclampsia versus 26.3% unexposed to HCQ (adjusted OR = 0.5; 95% CI: 0.2-1.4). The difference was pronounced for first pregnancies (7 vs. 44%), but power was limited. The difference in preterm deliveries was less pronounced comparing HCQ-exposed pregnancies with HCQ-unexposed pregnancies (34 vs. 40.8%; OR = 0.3; 95% CI: 0.3-1.5). CONCLUSION: Pregnant SLE patients trended toward less preeclampsia and preterm delivery when treated with HCQ. Future larger studies are needed to increase the statistical power, account for additional potential confounders, and more fully account for parity.

Systemic lupus erythematosus in pregnancy: high risk, high reward.

PURPOSE OF REVIEW: The aim of this study was to describe risks of systemic lupus erythematosus (SLE) in pregnancy and the importance of preconception counselling, medication optimization and close surveillance. RECENT FINDINGS: Advances in care for pregnant patients with SLE have led to improved obstetric outcomes, but maternal and foetal risks continue to be elevated. Conception during periods of disease quiescence and continuation of most medications decrease adverse pregnancy outcomes. Hydroxychloroquine (HCQ) appears protective against flares in pregnancy, neonatal congenital heart block and preterm birth. SUMMARY: SLE in pregnancy confers increased maternal and foetal risks, including disease flares, preeclampsia, preterm birth, foetal growth restriction, neonatal lupus erythematosus (NLE) and congenital heart block. Disease control on an effective medication regimen mitigates many of these risks, but pregnancy in women with SLE remains a high-risk condition requiring multidisciplinary care and an individualized approach to each patient.

Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach.

BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital. OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease. STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum. RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum. Compared with the cardiac cohort, by 8 weeks postpartum, the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17). The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71). CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine.

OBJECTIVE: To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol. METHODS: This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity. RESULTS: Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99). CONCLUSION: Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

Fast synaptic transmission in the goldfish CNS mediated by multiple nicotinic receptors.

Usually nicotinic receptors in the central nervous system only influence the strength of a signal between neurons. At a few critical connections, for instance some of those involved in the flight response, nicotinic receptors not only modulate the signal, they actually determine whether a signal is conveyed or not. We show at one of the few such connections accessible for study, up to three different nicotinic receptor subtypes mediate the signal. The subtypes appear to be clustered in separate locations. Depending on the number and combination of the subtypes present the signal can range from short to long duration and from low to high amplitude. This provides a critical connection with a built-in plasticity and may enable it to adapt to a changing environment.

Lactate and procalcitonin levels in peripartum women with intraamniotic infection.

BACKGROUND: Pregnant women are vulnerable to infection as their immune response is modulated. OBJECTIVE: Serum biomarkers are used to diagnose and manage severe infections, but data on their utility during labor are limited. We compared lactate and procalcitonin levels in women with and without an intraamniotic infection to determine whether they are useful biomarkers for infection during labor. STUDY DESIGN: We performed a prospective, observational cohort study of term, singleton pregnancies admitted with planned vaginal delivery in 2019 at a university medical center. The lactate and procalcitonin levels were determined during early labor, within 2 hours following delivery, and on postpartum day 1. Women with an intraamniotic infection in addition had their lactate and procalcitonin levels determined following an intraamniotic infection diagnosis. Samples were processed immediately in the hospital clinical laboratory. The primary outcome was the mean lactate level following delivery. The secondary outcomes were the lactate and procalcitonin levels at other time points. Comparisons based on infection status were performed using multivariate linear regressions. RESULTS: A total of 22 women with intraamniotic infection and 29 uninfected women were included. The mean early labor lactate level (1.47 vs 1.49 mmol/L) and mean procalcitonin level (0.048 vs 0.039 ng/mL) did not differ and were normal in the uninfected and intraamniotic infection groups. The mean lactate level was highest following delivery for women in both the uninfected and intraamniotic infection groups (2.00 vs 2.33 mmol/L; adjusted P=.08; 95% confidence interval, 0.98-1.53). The lactate level returned to normal by postpartum day 1 and did not differ significantly based on the infection status at any time point in the adjusted models. The procalcitonin level following delivery was higher among women with vs without an intraamniotic infection (0.142 vs 0.091 ng/mL; adjusted P=.03). The procalcitonin level rose further in both the intraamniotic infection and uninfected groups on postpartum day 1 (0.737 vs 0.408 ng/mL; adjusted P=.05). CONCLUSION: The lactate level is not significantly elevated in pregnant women with an intraamniotic infection above the physiological increase that is observed in women without infection at delivery. The procalcitonin level is elevated at delivery in women with an intraamniotic infection and warrants further investigation as a peripartum infection marker.

Correlation of C-start behaviors with neural activity recorded from the hindbrain in free-swimming goldfish (Carassius auratus).

Startle behaviors in teleost fishes are well suited for investigations of mechanisms of sensorimotor integration because the behavior is quantifiable and much of the underlying circuitry has been identified. The teleost C-start is triggered by an action potential in one of the two Mauthner (M) cells. To correlate C-start behavior with electrophysiology, extracellular recordings were obtained from the surface of the medulla oblongata in the hindbrain, close to the M-axons, in freely swimming goldfish monitored using high-speed video. The recordings included action potentials generated by the two M-axons, as well as neighboring axons in the dorsal medial longitudinal fasciculus. Axonal backfills indicated that the latter originate from identifiable reticulospinal somata in rhombomeres 2-8 and local interneurons. Diverse auditory and visual stimuli evoked behaviors with kinematics characteristic of the C-start, and the amplitude of the first component of the hindbrain field potential correlated with the C-start direction. The onset of the field potential preceded that of the simultaneously recorded trunk EMG and movement initiation by 1.08+/-0.04 and 8.13+/-0.17 ms, respectively. A subsequent longer latency field potential was predictive of a counterturn. These results indicate that characteristic features of the C-start can be extracted from the neural activity of the M-cell and a population of other reticulospinal neurons in free-swimming goldfish.