Prediction of large-for-gestational-age infant by fetal growth charts and hemoglobin A1c level in pregnancy complicated by pregestational diabetes.

OBJECTIVES: To compare the ability of three fetal growth charts (Fetal Medicine Foundation (FMF), Hadlock and National Institutes of Child Health and Human Development (NICHD) race/ethnicity-specific) to predict large-for-gestational age (LGA) at birth in pregnant individuals with pregestational diabetes, and to determine whether inclusion of hemoglobin A1c (HbA1c) level improves the predictive performance of the growth charts. METHODS: This was a retrospective analysis of individuals with Type-1 or Type-2 diabetes with a singleton pregnancy that resulted in a non-anomalous live birth. Fetal biometry was performed between 28 + 0 and 36 + 6 weeks of gestation. The primary exposure was suspected LGA, defined as estimated fetal weight ≥ 90th percentile using the Hadlock (Formula C), FMF and NICHD growth charts. The primary outcome was LGA at birth, defined as birth weight ≥ 90th percentile, using 2017 USA natality reference data. The performance of the three growth charts to predict LGA at birth, alone and in combination with HbA1c as a continuous measure, was assessed using the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Of 358 assessed pregnant individuals with pregestational diabetes (34% with Type 1 and 66% with Type 2), 147 (41%) had a LGA infant at birth. Suspected LGA was identified in 123 (34.4%) by the Hadlock, 152 (42.5%) by the FMF and 152 (42.5%) by the NICHD growth chart. The FMF growth chart had the highest sensitivity (77% vs 69% (NICHD) vs 63% (Hadlock)) and the Hadlock growth chart had the highest specificity (86% vs 76% (NICHD) and 82% (FMF)) for predicting LGA at birth. The FMF growth chart had a significantly higher AUC (0.79 (95% CI, 0.74-0.84)) for LGA at birth compared with the NICHD (AUC, 0.72 (95% CI, 0.68-0.77); P < 0.001) and Hadlock (AUC, 0.75 (95% CI, 0.70-0.79); P < 0.01) growth charts. Prediction of LGA improved for all three growth charts with the inclusion of HbA1c measurement in comparison to each growth chart alone (P < 0.001 for all); the FMF growth chart remained more predictive of LGA at birth (AUC, 0.85 (95% CI, 0.81-0.90)) compared with the NICHD (AUC, 0.79 (95% CI, 0.73-0.84)) and Hadlock (AUC, 0.81 (95% CI, 0.76-0.86)) growth charts. CONCLUSIONS: The FMF fetal growth chart had the best predictive performance for LGA at birth in comparison with the Hadlock and NICHD race/ethnicity-specific growth charts in pregnant individuals with pregestational diabetes. Inclusion of HbA1c improved further the prediction of LGA for all three charts. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

Frequency and prediction of persistent urinary tract dilation in third trimester and postnatal urinary tract dilation in infants following diagnosis in second trimester.

OBJECTIVE: To determine the frequency, associated characteristics and prognostic value of the current risk stratification system for prenatal urinary tract dilation (UTD) for predicting persistent UTD in the third trimester and subsequent postnatal UTD in the infant, following diagnosis in the second trimester. METHODS: This was a single-institution retrospective cohort study of singleton pregnancies diagnosed with unilateral or bilateral UTD in the second trimester (before 28 weeks' gestation) with follow-up in the third trimester (at or after 28 weeks) between January 2017 and May 2019. In all cases, the prenatal diagnosis and stratification to low-risk (Grade A1) or increased-risk (Grade A2-3) UTD was made using the 2014 UTD consensus classification system. The primary outcomes included persistent prenatal UTD in the third trimester and postnatal UTD up to 6 months of age. We performed multivariable analysis to assess whether patient and second- and third-trimester sonographic characteristics (such as UTD laterality, other renal abnormality (calyceal dilation, abnormal parenchymal appearance, abnormal ureter or bladder) and anteroposterior renal pelvic diameter (AP-RPD)) were associated with the study outcomes. We assessed the predictive value of the current risk stratification system (Grade A1 vs Grade A2-3) in the second and third trimesters for persistent prenatal UTD and postnatal UTD using the area under the receiver-operating-characteristics curve (AUC). RESULTS: Of 26 620 second-trimester ultrasound assessments in the study period, 347 patients were diagnosed with UTD in the second trimester and had third-trimester follow-up, of whom 150/347 (43% (95% CI, 38-49%)) had persistent UTD in the third trimester. Among the 282/347 (81%) patients with postnatal follow-up available, the frequency of postnatal UTD was 49/282 (17% (95% CI, 13-22%)), and among the subset with persistent UTD in the third trimester, the frequency of postnatal UTD was 46/102 (45% (95% CI, 35-55%)). The most frequent postnatal diagnosis was transient UTD (76%), followed by duplicated collecting system (10%). Of infants originally diagnosed with UTD in the second trimester, 2% (7/347) required surgery; stated differently, of the 49 infants with postnatal UTD, 14% (7/49) required surgery. At second-trimester diagnosis, sonographic predictors of both persistent prenatal UTD and postnatal UTD included the presence of other renal abnormality and UTD Grade A2-3. At third-trimester follow-up, predictors of postnatal UTD were larger mean AP-RPD and UTD Grade A2-3, while all cases had other renal abnormality. Second-trimester diagnosis of UTD Grade A2-3 had satisfactory discrimination for predicting persistent prenatal UTD (AUC, 0.64 (95% CI, 0.58-0.70)) and postnatal UTD (AUC, 0.72 (95% CI, 0.63-0.81)), as did third-trimester UTD Grade A2-3 for predicting postnatal UTD (AUC, 0.66 (95% CI, 0.56-0.76)). CONCLUSIONS: The majority of cases of prenatal UTD did not result in postnatal UTD, and of those that did, very few required surgery. Follow-up third-trimester assessment after a second-trimester diagnosis of UTD is warranted. The current risk stratification system by UTD grade, based on the 2014 UTD consensus classification, can be used to predict postnatal UTD with fair accuracy. Further research is needed to determine whether the predictive performance of this system can be improved by incorporating additional risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery: a cohort study.

OBJECTIVE: To investigate the association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery. DESIGN: A retrospective cohort study. SETTING: Data from the Consortium on Safe Labor Study in the USA (2002-2008). POPULATION: Singleton deliveries at ≥23 weeks of gestation (221 274 assessed deliveries, 62 331 by caesarean section). METHODS: The association of chorioamnionitis, and secondarily the duration of chorioamnionitis estimated from intrapartum antibiotic use, with adverse maternal outcomes was analysed using logistic regression with generalised estimating equations, adjusting for age, parity, race, pregestational diabetes, chronic hypertension, gestational age at delivery, study site and delivery year. Analyses were stratified by vaginal versus caesarean delivery. MAIN OUTCOME MEASURES: The composite adverse maternal outcome included: postpartum transfusion, endometritis, wound/perineal infection/separation, venous thromboembolism, hysterectomy, admission to intensive care unit and/or death. RESULTS: Chorioamnionitis was associated with higher odds of the composite adverse maternal outcome with caesarean delivery (adjusted odds ratio 2.31; 95% CI 1.97-2.71); and the association persisted regardless of whether a woman had a trial of labour, preterm delivery or maternal group B streptococcus colonisation. The most common adverse outcomes after caesarean section were postpartum transfusion (56.0%) and wound/perineal infection or endometritis (38.6%). Chorioamnionitis was not associated with adverse maternal outcomes after vaginal delivery. The duration of chorioamnionitis as the exposure did not alter the association between chorioamnionitis and adverse maternal outcomes. CONCLUSIONS: Chorioamnionitis, but not the estimated duration, was associated with increased odds of adverse maternal outcomes with caesarean delivery. This finding has implications for care programmes to prevent maternal morbidity after a caesarean section complicated by chorioamnionitis. TWEETABLE ABSTRACT: Chorioamnionitis, but not its duration, increases the risk of adverse maternal outcomes with caesarean delivery.

Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: an observational cohort study.

OBJECTIVE: To examine the impact of pharmacologic treatment for depression on obstetric outcomes in women treated for depression during the 2 years prior to pregnancy. STUDY DESIGN: Observational cohort study among 2859 women treated for depression during the 2 years prior to pregnancy. The primary exposure was any antidepressant treatment during pregnancy. Secondary analyses examined the impact of treatment by period of antidepressant exposure. Multivariable logistic regression models as well as propensity score analysis was utilized. RESULTS: Among 2859 women, 1648 (58%) were treated with antidepressant medication during pregnancy. Women who received antidepressants had no difference in preterm and early-term deliveries, Apgar scores, and small for gestational age (SGA); they had a lower likelihood of breastfeeding (adjusted odds ratio (AOR) 0.69, (95% confidence interval (CI): 0.51 to 0.94)). In secondary analysis, women who used antidepressants all three trimesters who delivered at term were more likely to deliver early term (AOR 1.36, (95% CI: 1.09 to 1.72)). Women who were treated with antidepressants only during the first and second trimesters had a reduced likelihood of SGA (AOR: 0.51 (95% CI: 0.32 to 0.83)). Generally similar results were observed with propensity score analysis. CONCLUSION: Antidepressant exposure during pregnancy does not confer an increased risk of preterm birth nor growth restriction in women recently treated for depression, but also does not appear to markedly improve these outcomes.

Spectrum of malignancies among HIV-infected patients in South India.

INTRODUCTION: The current study examines the spectrum of malignancies among HIV-infected South Indians enrolled in a clinical care program. MATERIALS AND METHODS: We conducted a nested matched case-control study among 42 HIV-infected cases who developed cancer and 82 HIV-infected controls between 1998 and 2008 at a tertiary care HIV care program in South India. RESULTS: The most common types of cancer included non-Hodgkin's lymphoma (38.1%), Hodgkin's lymphoma (16.7%), squamous cell carcinoma (14.3%), and adenocarcinoma (14.3%). The median duration of time from HIV infection to cancer diagnosis was 549 days [interquartile range (IQR): 58-2013]. The nadir CD4 cell count was significantly lower in cases compared to controls (134 cells/µl vs. 169 cells/µl; P = 0.015). Cancer patients were more likely to have a more advanced HIV disease stage at the time of cancer diagnosis compared to control patients (Stage C: 90.5% vs. 49.4%; P<0.0001). Significantly more cancer patients were receiving antiretroviral treatment relative to control patients at the time of cancer diagnosis (92.9% vs. 66.3%; P=0.001). CONCLUSIONS: HIV-infected patients who developed cancer had more advanced immunodeficiency at the time of cancer diagnosis and a lower nadir CD4 cell count. It is possible that with the continued roll-out of highly active antiretroviral therapy in India, the incidence of HIV-associated malignancies will decrease.

The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study.

We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55-2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77-11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01-15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8-39.3), for incident HSV-2 2.1% (95% CI: 0.6-3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5-5.8). Women's greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.

Couples at risk for HIV infection in Southern India: characteristics of HIV-infected patients in concordant and discordant heterosexual relationships.

The aim of the article is to compare the clinical and behavioural characteristics of HIV-infected South Indian patients in concordant and discordant heterosexual relationships. A cross-sectional analysis of married couples in concordant and discordant relationships was carried out. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV-1 RNA loads were assessed. A total of 839 concordant patients and 996 discordant patients were included in this analysis. Significantly more men were in discordant than concordant relationships (97% versus 59%; P = 0.002). More discordant patients had never initiated highly active antiretroviral treatment (HAART) than concordant patients (14.1% versus 8.5%; P = 0.004). Concordant patients had significantly higher CD4 cell counts than discordant patients at the time of enrolling to care (205 versus 139 cells/microL; P = 0.001). Discordant patients had significantly higher plasma viral loads than concordant patients (100,000 copies/mL versus 89,154 copies/mL; P = 0.002). Discordant patients were more likely to use condoms with their spouses than concordant patients (49% versus 28.8%; P = 0.01). In conclusion, couples-based interventions and the provision of HAART could substantially decrease behavioural and clinical correlates of HIV transmission among discordant South Indian married couples. The spouses of HIV-infected index patients are at increased risk for HIV infection, and further preventive measures are needed.

Risk factors for HIV transmission among heterosexual discordant couples in South India.

OBJECTIVE: To assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care. METHODS: A nested matched case-control study of serodiscordant couples in which the HIV-infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV-1 RNA loads were measured at enrollment and longitudinally over 12 months of follow-up. The study included 70 cases who seroconverted during study follow-up and 167 matched controls who remained persistently serodiscordant. RESULTS: The incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person-years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100,000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1-2.8], non-disclosure of HIV status (OR: 5.5; 95% CI: 4.3-6.2) and not using condoms (OR: 2.8; 95% CI: 2.4-3.6). CONCLUSIONS: Couples-based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.

Gender-related differences in quality of life domains of persons living with HIV/AIDS in South India in the era prior to greater access to antiretroviral therapy.

This study sought to examine gender-based differences in the quality of life of men and women living with HIV in South India in the era prior to greater access to antiretroviral therapy. The participants in this prospective longitudinal study consisted of 215 men and 141 women who were administered a quality of life (QOL) instrument comprising five scales: physical well-being, psychosocial well-being, sexual well-being, satisfaction with health care, and strength of partner relationship. Interviews were conducted at enrollment and at 6 months in clinical care. Men and women reported similar scores in physical well-being, satisfaction with health care, and relationship with partner from the period prior to care, at enrollment, and at 6 months. Women scored significantly lower than men in psychosocial well-being from the period prior to care, at enrollment, and at 6 months (p < 0.05); women reported significantly higher levels of partner satisfaction at 6 months (p < 0.05). In light of the increasing feminization of the HIV epidemic in India, greater emphasis should be placed on examining the long-term experiences of Indian women living with HIV/AIDS, particularly their psychosocial well-being.

Regression of Kaposi's sarcoma lesions following highly active antiretroviral therapy in an HIV-infected patient.

This case report documents that highly active antiretroviral therapy (HAART) can lead to the regression of Kaposi's sarcoma (KS) lesions in the auditory canal of an HIV-infected male from Chennai, India. In resource-limited settings where administering anti-KS chemotherapeutic agents may not be feasible, HAART alone can be an option in HIV-infected individuals with KS.

Gender-based differences in treatment and outcome among HIV patients in South India.

OBJECTIVE: To describe gender-based differences in disease progression, treatment, and outcome among patients receiving highly active antiretroviral therapy (HAART) in South India. METHODS: Therapy-naïve patients initiating HAART between February 1996 and June 2006 at a tertiary HIV referral center in Chennai, South India, were analyzed using the YRG CARE HIV Observational Database. Patients with 1 year of follow-up after initiating HAART were examined to investigate immunological and clinical outcomes, including the development of adverse events to therapy and opportunistic infections. RESULTS: All previously therapy-naïve patients who initiated HAART with at least 1 year of follow-up (n = 1972) were analyzed. At enrollment into care, women had higher CD4 counts, lower hemoglobin, and higher body mass index (BMI) than their male counterparts (p < 0.05). At the time of initiating therapy, women had higher CD4 counts and lower hemoglobin (p < 0.05); women continued to have higher CD4 counts at 12 months (p < 0.05). After 1 year following HAART initiation, significantly more men developed tuberculosis and Pneumocystis jiroveci pneumonia (p < 0.05), more women experienced lactic acidosis and nausea, and more men developed immune reconstitution syndrome (p < 0.05). CONCLUSIONS: Significant physiological, immunological, and clinical differences exist between men and women initiating HAART in a resource-limited setting in South India. Future studies should examine whether clinical management strategies should be different for men and women in resource-limited settings.

Prevalence and incidence of sexually transmitted infections among South Indians at increased risk of HIV infection.

Sexually transmitted infections (STIs) have been identified as cofactors of HIV transmission. Greater understanding of local STI burdens can assist in the development of more effective STI and HIV prevention strategies. The aim of this study is to determine the prevalence and incidence of STIs among South Indian men and women identified to be at increased risk for HIV infection. Individuals at increased risk for HIV infection were enrolled in a prospective longitudinal study in Chennai, India (n = 480) between August 2002 and December 2003. Participants were enrolled from patients seeking services at an sexually transmitted disease (STD) clinic and a confidential HIV testing and counseling program. The most common prevalent STIs were herpes simplex virus (HSV)-2 (50% of women, 29% of men), syphilis (11% of women, 8% of men), and Trichomonas vaginalis (6% of women). At enrollment, women, participants with no schooling, participants with greater than four sex partners, and single participants were found to be at increased risk for HSV-2 infection (p < 0.05). The two most common incident STIs at 12 months were HSV-2 with 12% of men and 8% of women testing positive and hepatitis B with 2% of men and 5% of women testing hepatitis B surface antigen (HBsAg) positive. In this cohort of South Indian men and women with a high background prevalence of HSV-2, suppressive therapy against herpes replication may have a substantial impact in reducing both HSV-2 transmission and HIV acquisition. With the high incidence of STIs, targeted prevention and clinical management strategies among individuals practicing high risk behaviors may help to slow the continued spread of HIV in India.

Financial burden of health services for people with HIV/AIDS in India.

In resource-limited settings, illness can impose a major financial burden on patients and their families. With the advent and increasing accessibility of antiretroviral therapy, HIV/AIDS has now become a fundamentally chronic treatable disease with far reaching economic and social consequences, and hence it is crucial to also examine the long-term financial impact of HIV healthcare. Beyond the direct costs of medications, monitoring, and medical care, additional costs include the long-term lost earnings of HIV-infected individuals as well as of their household members who also provide care. A clearer understanding of the financial burden of healthcare for HIV-infected Indians can allow policy makers and planners to better allocate limited resources. This article reviews the financial consequences of HIV care and treatment on individuals and their households by examining current treatment options, HIV monitoring, the clinical course of HIV disease, and the roles of the private and public sector in providing HIV care in India. Future studies should more thoroughly examine the financial impact of HIV-related costs incurred by households over time and examine household responses to these costs.

Rapid determination of artemisinin and related analogues using high-performance liquid chromatography and an evaporative light scattering detector.

Artemisinin and its analogues are a class of compounds of current interest in the treatment of drug-resistant malaria. These antimalarials are preferentially taken up into malaria infected erythrocytes as compared to uninfected erythrocytes, a fact that may represent an important parameter in drug potency. Numerous methods for the analysis of specific artemisinin analogues have been developed, but most are not widely adaptable to a large range of analogues. In this paper we describe a high-performance liquid chromatographic method developed and validated for artemisinin and several analogues of artemisinin using a readily available evaporative light scattering detector. This quantitation method was found to be straight forward, rapid, inexpensive and reproducible. Standard calibration curves constructed for six artemisinin compounds were linear with the detection limit determined between 6 and 60 ng. The intra- and inter-day accuracy were found to be 2.75% and 4.15%, respectively with less than 3% variation in precision. The validated assay was applied to a mixture of artemisinin derivatives, where they were easily separated and quantitated.