Dataset Information

Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.

ABSTRACT: OBJECTIVE:Pregnancies in women with active rheumatic disease often result in poor neonatal outcomes. Hydroxychloroquine (HCQ) reduces disease activity and flares; however, pregnancy causes significant physiologic changes that may alter HCQ levels and lead to therapeutic failure. Therefore, our objective was to evaluate HCQ concentrations during pregnancy and relate levels to outcomes. METHODS:We performed an observational study of pregnant patients with rheumatic disease who were taking HCQ from a single center during 2013-2016. Serum samples were analyzed using high-performance liquid chromatography/mass spectrometry. Primary HCQ exposure was categorized as nontherapeutic (? 100 ng/ml) or therapeutic (> 100 ng/ml). Categorical outcomes were analyzed using Fisher's exact test and continuous outcomes using linear regression models, Wilcoxon signed-rank test, Kruskal-Wallis test, t test, and ANOVA. RESULTS:We analyzed 145 samples from 50 patients with rheumatic disease, 56% of whom had systemic lupus erythematosus (SLE). HCQ concentration varied widely among individuals at each trimester. Mean physician's global assessment scores in patients with SLE were significantly higher in those with average drug levels ? 100 ng/ml compared to > 100 ng/ml (0.93 vs 0.32, p = 0.01). Of patients with SLE, 83% with average drug levels ? 100 ng/ml delivered prematurely (n = 6), compared to only 21% with average levels > 100 ng/ml (n = 19; p = 0.01). HCQ levels were not associated with prematurity or disease activity in non-SLE patients. CONCLUSION:With both high and low HCQ levels associated with preterm birth and disease activity in SLE, further study is necessary to understand HCQ disposition throughout pregnancy and to clarify the relationship between drug levels and outcomes.

SUBMITTER: Balevic SJ

PROVIDER: S-EPMC6314916 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.

Balevic Stephen J SJ Cohen-Wolkowiez Michael M Eudy Amanda M AM Green Thomas P TP Schanberg Laura E LE Clowse Megan E B MEB

The Journal of rheumatology 20181001 1

<h4>Objective</h4>Pregnancies in women with active rheumatic disease often result in poor neonatal outcomes. Hydroxychloroquine (HCQ) reduces disease activity and flares; however, pregnancy causes significant physiologic changes that may alter HCQ levels and lead to therapeutic failure. Therefore, our objective was to evaluate HCQ concentrations during pregnancy and relate levels to outcomes.<h4>Methods</h4>We performed an observational study of pregnant patients with rheumatic disease who were ...[more]

PMID: 30275257

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Project description:BackgroundMaternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear.ObjectiveThis study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity.Study designThis study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, ≥50 kg/m2) patients were compared. Patients in the reference group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, previous cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was composite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventilator use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associations with neonatal outcomes.ResultsOverall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64).ConclusionCompared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.

Project description:BACKGROUND:Hydroxychloroquine is an oral drug prescribed to pregnant women with rheumatic disease to reduce disease activity and prevent flares. Physiologic changes during pregnancy may substantially alter drug pharmacokinetics. However, the effect of pregnancy on hydroxychloroquine disposition and the potential need for dose adjustment remains virtually unknown. METHODS:We performed a population-pharmacokinetic analysis using samples from the Duke Autoimmunity in Pregnancy Registry from 2013 to 2016. We measured hydroxychloroquine concentration using high-performance liquid chromatography/tandem mass spectrometry and analyzed data using non-linear mixed-effect modeling. We calculated differences between pregnancy and postpartum empirical Bayesian estimates using paired t tests. We computed steady-state concentration profiles for hydroxychloroquine during pregnancy and postpartum using individual clinical data and empirical Bayesian estimates developed from the final pharmacokinetic model. RESULTS:We obtained 145 serum samples from 50 patients, 25 of whom had paired pregnancy and postpartum specimens. Five subjects had average concentrations (pregnancy and postpartum) <?100 ng/mL, consistent with medication non-adherence, and were excluded. The population estimated apparent volume of distribution was 1850 L/70 kg and estimated apparent clearance was 51 L/h. Compared with postpartum, median apparent volume of distribution increased significantly during pregnancy (p?<?0.001), whereas apparent clearance and 24-h area under the curve did not change. CONCLUSIONS:We developed a one-compartment population-pharmacokinetic model for hydroxychloroquine in pregnant women with rheumatic disease. Estimates for serum CL were within the expected range for plasma in non-pregnant adults. Because CL and 24-h area under the curve did not change during pregnancy compared with postpartum, our modeling in this small cohort does not support adjusting hydroxychloroquine dose during pregnancy.

Project description:BackgroundThe effect of SARS-CoV-2 infection in pregnant women and newborns is incompletely understood. Preliminary data shows a rather fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. However, it is not clear whether the disease increases the risk of pregnancy-related complications. The aim of the study is to describe the maternal and neonatal clinical characteristics and outcome of pregnancies with SARS-CoV-2 infection.MethodsIn this retrospective national-based study, we analyzed the medical records of all pregnant women infected with SARS-CoV-2 and their neonates who were admitted to New-Jahra Hospital (NJH), Kuwait, between March 15th 2020 and May 31st 2020. During the study period and as part of the public health measures, a total of 185 pregnant women infected with SARS-CoV-2, regardless of symptoms, were hospitalized at NJH, and were included. Maternal and neonatal clinical manifestations, laboratory tests and treatments were collected. The outcomes of pregnancies included miscarriage, intrauterine fetal death (IUFD), preterm birth and live birth were assessed until the end date of the outcomes follow-up (November 10th 2020).ResultsA total of 185 pregnant women infected with SARS-CoV-2 were enrolled with a median age of 31 years (interquartile range, IQR: 27.5-34), and median gestational age at diagnosis of SARS-CoV2 infection was 29 weeks (IQR: 18-34). The majority (88%) of these women had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). At the time of the analysis, out of the 185, 3 (1.6%) of the pregnant women had a miscarriage, 1 (0.54%) had IUFD which was not related to COVID-19, 16 (8.6%) had ongoing pregnancies and 165 (89%) had a live birth. Only 2 (1.1%) of these women developed severe pneumonia and required intensive care. A total of 167 neonates with two sets of twins were born with median gestational age at birth was 38 (IQR: 36-39) weeks. Most of the neonates were asymptomatic, and only 2 of them tested positive on day 5 by nasopharyngeal swab testing.ConclusionsIn this national-based study, most of the pregnant women infected with SARS-CoV-2 showed mild symptoms. Although mother-to-child vertical transmission of SARS-CoV-2 is possible, COVID-19 infection during pregnancy may not lead to unfavorable maternal and neonatal outcomes.

Project description:BACKGROUND:Preterm premature rupture of membranes (PPROM) is associated with high neonatal morbidity and mortality. However, the influences of cesarean section (CS) on neonatal outcomes in preterm pregnancies complicated with PPROM are not well elucidated. The aim of this study was to investigate the influence of delivery modes on neonatal outcomes among pregnant women with PPROM. METHODS:A retrospective cross-sectional study was conducted in 39 public hospitals in 14 cities in the mainland of China from January 1st, 2011 to December 31st, 2011. A total of 2756 singleton pregnancies complicated with PPROM were included. Adverse neonatal outcomes including early neonatal death, birth asphyxia, respiratory distress syndrome (RDS), pneumonia, infection, birth trauma, and 5-min/10-min Apgar scores were obtained from the hospital records. Binary variables and ordinal variables were respectively calculated by binary logistic regressions and ordinal regression. Numerical variables were compared by multiple linear regressions. RESULTS:In total, 2756 newborns were involved in the analysis. Among them, 1166 newborns (42.31%) were delivered by CS and 1590 newborns belonged to vaginal delivery (VD) group. The CS proportion of PPROM obviously increased with the increase of gestational age (??=?5.014, P?=?0.025). Compared with CS group, VD was associated with a higher risk of total newborns mortality (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.102-5.118; P?=?0.027), and a lower level of pneumonia (OR, 0.32; 95% CI, 0.126-0.811; P?=?0.016). However, after multivariable adjustment and stratification for gestational age, only pneumonia was significantly related with CS in 28 to 34 weeks group (OR, 0.34; 95% CI, 0.120-0.940; P?=?0.038). There were no differences regarding to other adverse outcomes in the two groups, including neonatal mortality, birth asphyxia, Apgar scores, RDS, pneumonia, and sepsis. CONCLUSIONS:The proportion of CS of pregnant women with PPROM was very high in China. The mode of delivery does not affect neonatal outcomes of pregnancies complicated with PPROM.

Project description:IntroductionThe prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease.Material and methodsIn a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs).ResultsAmong 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD.ConclusionsModerate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Dataset Information

Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.

Publications

Hydroxychloroquine Levels throughout Pregnancies Complicated by Rheumatic Disease: Implications for Maternal and Neonatal Outcomes.

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