Efficacy and effectiveness of artemether-lumefantrine after initial and repeated treatment in children <5 years of age with acute uncomplicated Plasmodium falciparum malaria in rural Tanzania: a randomized trial.

BACKGROUND: We assessed the efficacy, effectiveness and safety of artemether-lumefantrine, which is the most widely used artemisinin-based combination therapy in Africa, against Plasmodium falciparum malaria during an extended follow-up period after initial and repeated treatment. METHODS: We performed an open-label randomized trial of artemether-lumefantrine with supervised (n=180) and unsupervised intake (n=179) in children <5 years of age with uncomplicated falciparum malaria in rural Tanzania. Recurrent infections between day 14 and day 56 were retreated within the same study arm. Main end points were polymerase chain reaction (PCR)-corrected cure rates by day 56 and day 42 after initial and repeated treatment, respectively, as estimated by survival analysis. RESULTS: The PCR-corrected cure rate after initial treatment was 98.1% (95% confidence interval [CI], 94.2%-99.4%) after supervised and 95.1% (95% CI, 90.7%-98.1%) after unsupervised intake (P=.29). After retreatment of recurrent infections, the cure rates were 92.9% (95% CI, 81.8%-97.3%) and 97.6% (95% CI, 89.3%-98.8%), respectively (P=.58). Reinfections occurred in 46.9% (82 of 175) versus 50.9 % of the patients (relative risk [RR], 0.92 [95% CI, 0.74-1.14]; P=.46) after initial therapy and 32.4% (24 of 74) versus 39.0% (32 of 82) (RR, 0.83 [95% CI, 0.54-1.27]; P=.39) after retreatment. Median blood lumefantrine concentrations in supervised and unsupervised patients on day 7 were 304 versus 194 ng/mL (P<.001) after initial treatment and 253 versus 164 ng/mL (P=.001) after retreatment. Vomiting was the most commonly reported drug-related adverse event (in 1% of patients) after both initial and repeated treatment. CONCLUSIONS: Artemether-lumefantrine was highly efficacious even after unsupervised administration, despite significantly lower lumefantrine concentrations, compared with concentration achieved with supervised intake, and was well-tolerated and safe after initial and repeated treatment. CLINICAL TRIAL REGISTRATION: ISRCTN69189899.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study.

BACKGROUND: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. METHODS: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. RESULTS: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046). CONCLUSIONS: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Impact of training in clinical and microscopy diagnosis of childhood malaria on antimalarial drug prescription and health outcome at primary health care level in Tanzania: a randomized controlled trial.

BACKGROUND: Prescribing antimalarial medicines based on parasite confirmed diagnosis of malaria is critical to rational drug use and optimal outcome of febrile illness. The impact of microscopy-based versus clinical-based diagnosis of childhood malaria was assessed at primary health care (PHC) facilities using a cluster randomized controlled training intervention trial. METHODS: Sixteen PHC facilities in rural Tanzania were randomly allocated to training of health staff in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children presenting at these facilities were assessed, treated and scheduled for follow up visit after 7 days. Blood smears on day 0 were only done in Arm-I but on Day 7 in all arms. Primary outcome was antimalarial drug prescription. Other outcomes included antibiotic prescription and health outcome. Multilevel regression models were applied with PHC as level of clustering to compare outcomes in the three study arms. RESULTS: A total of 973, 1,058 and 1,100 children were enrolled in arms I, II and III, respectively, during the study period. Antimalarial prescriptions were significantly reduced in Arm-I (61.3%) compared to Arms-II (95.3%) and III (99.5%) (both P < 0.001), whereas antibiotic prescriptions did not vary significantly between the arms (49.9%, 54.8% and 34.2%, respectively). In Arm-I, 99.1% of children with positive blood smear readings received antimalarial prescriptions and so did 11.3% of children with negative readings. Those with positive readings were less likely to be prescribed antibiotics than those with negative (relative risk = 0.66, 95% confidence interval: 0.55, 0.72). On day 7 follow-up, more children reported symptoms in Arm-I compared to Arm-III, but fewer children had malaria parasitaemia (p = 0.049). The overall sensitivity of microscopy reading at PHC compared to reference level was 74.5% and the specificity was 59.0% but both varied widely between PHCs. CONCLUSION: Microscopy based diagnosis of malaria at PHC facilities reduces prescription of antimalarial drugs, and appears to improve appropriate management of non-malaria fevers, but major variation in accuracy of the microscopy readings was found. Lack of qualified laboratory technicians at PHC facilities and the relatively short training period may have contributed to the shortcomings. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov with the identifier NCT00687895.

Influence of mandatory generic substitution on pharmaceutical sales patterns: a national study over five years.

BACKGROUND: Mandatory generic substitution was introduced in Sweden in October 2002 in order to try to curb escalating pharmaceutical expenditure. The aim of this study was to investigate how sales patterns for substitutable and non-substitutable pharmaceuticals have developed since the introduction of mandatory generic substitution; furthermore, to compare sales patterns in different groups of the population, based on patients' age and gender. METHODS: Five therapeutic groups comprising both substitutable and non-substitutable pharmaceuticals were included. The study period was from January 2000 to June 2005. National sales data were used, covering volumes of dispensed prescription medicines (expressed in defined daily doses per 1000 inhabitants and day) of each pharmacological substance in the therapeutic groups for each age and gender group. Sales patterns for substitutable and non-substitutable pharmaceuticals were compared using a descriptive approach. RESULTS: In most therapeutic groups there has been an increase in the volumes of substitutable pharmaceuticals sold since the introduction of the reform, ranging from one third to three times the initial volume; whereas the volumes of non-substitutable pharmaceuticals have levelled out or declined. There were few gender differences in sales patterns of substitutable and non-substitutable drugs. In three therapeutic groups, sales patterns differed across different age groups, and there was a tendency for volumes of recently introduced non-substitutable pharmaceuticals to be proportionally higher in the youngest age groups. CONCLUSION: Since the introduction of the reform, there has been a proportionally larger increase in sales of substitutable pharmaceuticals compared with sales of non-substitutable pharmaceuticals. This indicates that the reform might have contributed to larger sales of less expensive pharmaceuticals.

Home-based management of fever and malaria treatment practices in Uganda.

The Home-Based Management of Fever/Malaria (HBMF) strategy in rural Uganda was evaluated in a quasi-experimental study. The intervention consisted of volunteers educating mothers and providing a 3-day course of pre-packaged chloroquine plus sulfadoxine/pyrimethamine tablets (HOMAPAK), free of charge, for the treatment of under-five fevers. Using a structured questionnaire, information was obtained on care-seeking and treatment practices before (n=498) and 18 months after the introduction of HBMF (n=587). Assessment of the intervention effect indicated 13.5% improvement in the accumulated proportion of patients (1) treated, (2) treated within 24h of illness onset, (3) treated with the recommended antimalarials, (4) treated at an adequate dosage and (5) treated for the correct duration. Combining this with the antimalarial drug efficacy resulted in a 10.4% improvement in the community effectiveness of malaria treatment. HOMAPAK use was reported in 25% of 156 febrile children; 23% in the most poor compared with 50% in the least poor. Using HOMAPAK instead of other allopathic antimalarials increased the likelihood of completing all steps (odds ratio 37, 95% CI 4.8-286). Similar to other large-scale public health interventions, this study demonstrates modest practice changes at the population level. However, practices improved markedly among HOMAPAK users, suggesting that intensifying implementation efforts to increase HOMAPAK use, especially among the poorest, would be beneficial.

Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects.

The aim of this study was to investigate which principal human cytochrome P450 (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin derivatives differ with respect to their respective induction and inhibition capacity. Seventy-five healthy adults were randomized to receive therapeutic oral doses of artemisinin, dihydroartemisinin, arteether, artemether or artesunate for 5 days (days 1-5). A six-drug cocktail consisting of caffeine, coumarin, mephenytoin, metoprolol, chlorzoxazone and midazolam was administered orally on days -6, 1, 5 and 10 to assess the activities of CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Four-hour plasma concentrations of parent drugs and corresponding metabolites and 7-hydroxycoumarin urine concentrations were quantified by liquid chromatography-tandem mass spectrometry. The 1-hydroxymidazolam/midazolam 4-h plasma concentration ratio (CYP3A) was increased on day 5 by artemisinin [2.66-fold (98.75% CI: 2.10-3.36)], artemether [1.54 (1.14-2.09)] and dihydroartemisinin [1.25 (1.06-1.47)] compared with day -6. The S-4'-hydroxymephenytoin/S-mephenytoin ratio (CYP2C19) was increased on day 5 by artemisinin [1.69 (1.47-1.94)] and arteether [1.33 (1.15-1.55)] compared with day -6. The paraxanthine/caffeine ratio (CYP1A2) was decreased on day 1 after administration of artemisinin [0.27 (0.18-0.39)], arteether [0.70 (0.55-0.89)] and dihydroartemisinin [0.73 (0.59-0.90)] compared with day -6. The alpha-hydroxymetoprolol/metoprolol ratio (CYP2D6) was lower on day 1 compared with day -6 in the artemisinin [0.82 (0.70-0.96)] and dihydroartemisinin [0.83 (0.71-0.96)] groups, respectively. In the artemisinin-treated subjects this decrease was followed by a 1.34-fold (1.14-1.58) increase from day 1 to day 5. These results show that intake of artemisinin antimalarials affect the activities of several principal human drug metabolizing CYP450 enzymes. Even though not significant in all treatment groups, changes in the individual metrics were of the same direction for all the artemisinin drugs, suggesting a class effect that needs to be considered in the development of new artemisinin derivatives and combination treatments of malaria.

Impact of a generic substitution reform on patients' and society's expenditure for pharmaceuticals.

Sweden's pharmaceutical expenditure has increased during the last decades. On 1 October 2002 mandatory generic substitution was introduced in Sweden with the purpose to reduce the growth in pharmaceutical expenditure. The aim of the present study was to investigate if the implementation of generic substitution was associated with changes in patients' expenses and reimbursed cost for prescribed pharmaceuticals included in the Swedish Pharmaceutical Benefits Scheme (PBS). Monthly pharmacy sales data was obtained from the National Corporation of Swedish Pharmacies (Apoteket AB). The study period ranged between 1 January 2000 and 31 December 2004. Changes in pharmaceutical expenditure associated with the introduction of generic substitution were analysed with a linear segmented regression. The study comprised outpatient prescription pharmaceuticals encompassed by PBS for Sweden in total and each county council. Two different data sets were analysed. The first comprised all prescribed pharmaceuticals. The second contained only pharmaceuticals on regular prescriptions (i.e. exclusion of multidose dispensed drugs). Changes in patient co-payment per 1000 inhabitants and working day and subsidised cost per 1000 inhabitants and working day associated with the introduction of generic substitution were analysed. Expenditure was expressed in Swedish krona, SEK (SEK 1=US$ 0.14/euro 0.11, 7 July 2006). The Swedish Consumer Price Index was used to inflation-adjust expenditures with 2004 as base. The introduction of generic substitution was associated with a significant change in slope for patient co-payment in both all prescribed pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.005) for Sweden in total. The slope shifted direction from a slight increase before the reform into a decline after the reform was implemented. This was also found for the average slope of patient co-payment for all county councils (p<0.0001). The introduction of generic substitution was associated with a statistically significant shift in slope for subsidised cost for Sweden in total (p<0.001). The slope shifted from a monthly increase before October 2002 to a monthly decline for all prescribed pharmaceuticals afterwards. Similar results were found for the average slope of subsidised cost for all county councils both for all prescribed pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.0001). The introduction of generic substitution was associated with a shift in trend from an increase into a decrease both for patients' and society's expenditures. This suggests that generic substitution has contributed to a reduction in the growth of pharmaceutical expenditure.

Sexual autonomy and contraceptive use among women in Nigeria: findings from the Demographic and Health Survey data.

CONTEXT: The persistent low contraceptive use and high fertility in Nigeria despite improvements in educational achievements calls for an examination of the role of factors, which may moderate the use of modern contraception. This article explores the influence of sexual autonomy on the use of modern contraceptive methods among women and its relative importance compared with other, more traditional, indicators of women's autonomy such as education and occupation. DATA AND METHODS: Data from two Demographic and Health Surveys (DHS), 2008 and 2013, were used in this study. An index of sexual autonomy was constructed by combining related DHS variables, and its association with current use of modern contraception was examined at each time point as well as over time using multivariate regression analysis. RESULTS: The observed prevalence for use of modern contraception was 2.8 and 2.6 times higher among women who had high sexual autonomy in 2008 and 2013, respectively. The corresponding figures for women with secondary or higher education were 8.2 and 11.8 times higher, respectively, compared with women with no education. But after controlling for wealth index, religion, place of residence, autonomy and experience of intimate partner violence (IPV), the likelihood of use of modern contraception was lowered to about 2.5 (from 8.2) and 2.8 (from 11.8) times during 2008 and 2013, respectively, among women with secondary or higher education. The likelihood of use of modern contraception lowered only to 1.6 (from 2.8) and 1.8 (from 2.6) times among women with high sexual autonomy after controlling for other covariates, respectively, during the same period. CONCLUSION: Sexual autonomy seems to play an important role in women's use of modern contraceptive methods independent of education and a number of other factors related to women's status. Sexual autonomy needs to be simultaneously promoted alongside increasing educational opportunities to enhance women's ability to use modern contraception.

Alarm Variables for Dengue Outbreaks: A Multi-Centre Study in Asia and Latin America.

BACKGROUND: Worldwide, dengue is an unrelenting economic and health burden. Dengue outbreaks have become increasingly common, which place great strain on health infrastructure and services. Early warning models could allow health systems and vector control programmes to respond more cost-effectively and efficiently. METHODOLOGY/PRINCIPAL FINDINGS: The Shewhart method and Endemic Channel were used to identify alarm variables that may predict dengue outbreaks. Five country datasets were compiled by epidemiological week over the years 2007-2013. These data were split between the years 2007-2011 (historic period) and 2012-2013 (evaluation period). Associations between alarm/ outbreak variables were analysed using logistic regression during the historic period while alarm and outbreak signals were captured during the evaluation period. These signals were combined to form alarm/ outbreak periods, where 2 signals were equal to 1 period. Alarm periods were quantified and used to predict subsequent outbreak periods. Across Mexico and Dominican Republic, an increase in probable cases predicted outbreaks of hospitalised cases with sensitivities and positive predictive values (PPV) of 93%/ 83% and 97%/ 86% respectively, at a lag of 1-12 weeks. An increase in mean temperature ably predicted outbreaks of hospitalised cases in Mexico and Brazil, with sensitivities and PPVs of 79%/ 73% and 81%/ 46% respectively, also at a lag of 1-12 weeks. Mean age was predictive of hospitalised cases at sensitivities and PPVs of 72%/ 74% and 96%/ 45% in Mexico and Malaysia respectively, at a lag of 4-16 weeks. CONCLUSIONS/SIGNIFICANCE: An increase in probable cases was predictive of outbreaks, while meteorological variables, particularly mean temperature, demonstrated predictive potential in some countries, but not all. While it is difficult to define uniform variables applicable in every country context, the use of probable cases and meteorological variables in tailored early warning systems could be used to highlight the occurrence of dengue outbreaks or indicate increased risk of dengue transmission.

Malaria rapid testing by community health workers is effective and safe for targeting malaria treatment: randomised cross-over trial in Tanzania.

BACKGROUND: Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients. CONCLUSIONS/SIGNIFICANCE: RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00301015.

Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis.

OBJECTIVE: A systematic review of the nonsurgical treatment of patients with appendiceal abscess or phlegmon, with emphasis on the success rate, need for drainage of abscesses, risk of undetected serious disease, and need for interval appendectomy to prevent recurrence. SUMMARY BACKGROUND DATA: Patients with appendiceal abscess or phlegmon are traditionally managed by nonsurgical treatment and interval appendectomy. This practice is controversial with proponents of immediate surgery and others questioning the need for interval appendectomy. METHODS: A Medline search identified 61 studies published between January 1964 and December 2005 reporting on the results of nonsurgical treatment of appendiceal abscess or phlegmon. The results were pooled taking the potential clustering on the study-level into account. A meta-analysis of the morbidity after immediate surgery compared with that after nonsurgical treatment was performed. RESULTS: Appendiceal abscess or phlegmon is found in 3.8% (95% confidence interval (CI), 2.6-4.9) of patients with appendicitis. Nonsurgical treatment fails in 7.2% (CI: 4.0-10.5). The need for drainage of an abscess is 19.7% (CI: 11.0-28.3). Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3; CI: 1.9-5.6; P < 0.001). After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6-1.7) and an important benign disease in 0.7% (CI: 0.2-11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7-11.1). CONCLUSIONS: The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon.

Diarrhoea case management in low- and middle-income countries--an unfinished agenda.

OBJECTIVE: To ascertain whether diarrhoea management improved during 1986-2003, a period when significant efforts were made to promote effective case management in children. METHODS: We analysed household data from 107 Demographic and Health Surveys in 40 low- and middle-income countries from 1986 to 2003 and assessed trends in indicators of rehydration, fluid quantity and food intake in children with diarrhoea. A statistical analysis was made of the overall trend for each indicator. FINDINGS: Modest progress was made with regard to the use of oral rehydration therapy (ORT) (0.39% per year) and increased fluid intake (1.02% per year), and use rates remained low in 2003, when compared with desired full coverage. Although use rates improved in the majority of countries, no progress was made in several countries. We estimate that, annually, 307 million children in low- and middle-income countries did not receive ORT, 356 million did not get increased amounts of fluids, and at the beginning of the 21st century, 227 million children got neither ORT nor increased amounts of fluids. CONCLUSION: The finding that many children in low- and middle-income countries do not receive proper treatment for diarrhoea points to the urgency in addressing this unfinished agenda in child survival. The effectiveness of diarrhoea control needs to be improved after critical review of established approaches and activities to reach caregivers of children at risk of dying from diarrhoeal diseases. Significant efforts must be made to scale up activities to improve case management and reduce childhood deaths from diarrhoea.

Overweight and obesity at school entry as predictor of overweight in adolescence in an Arctic child population.

BACKGROUND: The aim of this study was to analyse the changes in the prevalence of overweight, obesity, and in mean body mass index (BMI) among school children, and to analyse the predictive value of overweight and obesity at school entry to overweight and obesity in adolescence in an Arctic child population. METHODS: Retrospective cohort study. A database was created on the basis of files from health examinations. Data on children aged 5-7 years and 13-17 years and the subsample of children followed from school entry to adolescence was analysed. RESULTS: During the years 1972-2002 the prevalence of overweight and obesity increased significantly, and mean BMI rose by 5.6% at school entry and by 4.7% in adolescence. Sensitivity and specificity: Of the children being obese in adolescence, 56.3% were already obese at school entry; for the overweight children, 50.6% were also overweight or obese at school entry. Of the children with normal weight in adolescence, 91.9% were also normal weight at school entry. The positive predictive value of being overweight or obese combined at school entry was 59.5%, i.e. more than every second retained their overweight or obesity in adolescence. Only 10% of the obese school entry children had gained normal weight in adolescence. The negative predictive value for normal weight children at school entry was 91.3%. CONCLUSION: The study showed that during 30 years from 1972, overweight and obesity among school children in Greenland have increased dramatically. Overweight and obesity at school entry were shown to be a good predictor of overweight or obesity in adolescence.

Symphysis-fundus measurements for detection of small for gestational age pregnancies.

BACKGROUND: In Sweden measurements of the symphysis-fundus (SF) distance are used to detect small for gestational age (SGA) pregnancies. The aim of this study was to evaluate the efficiency of Swedish ultrasound-based SF reference curves in detecting SGA pregnancies. METHODS: To assess the sensitivity for detection of SGA pregnancies we performed a case-control study. Through the Swedish Medical Birth Register we identified all singleton SGA infants born in Uppsala in 1993-1997 and randomly recruited non-SGA singleton infants as controls. We included 169 term and 73 preterm SGA cases and 296 controls, all born at term. The reference curves constructed by Steingrimsdottir (S curve) and Kieler (K curve) were evaluated. Gestational age at the first alarm in the preterm SGA group was recorded. RESULTS: In term pregnancies the S curve showed a sensitivity of 32% and specificity of 90% at a cut-off of -2 SDs. The corresponding values for the K curve were 51% and 83%, respectively. In preterm SGA pregnancies the sensitivity of the S curve was 49% and of the K curve 58%. The first alarm below 2 SDs was noted before 32 weeks in 37% with the S curve and 43% with the K curve for preterm SGA pregnancies. CONCLUSIONS: Both tested Swedish SF reference curves had low sensitivities for term SGA pregnancies. Sensitivity was higher for the preterm group and SF measurements seem to be better for detecting the most severe cases of SGA.