Improved method robustness and ruggedness in liquid chromatography-mass spectrometry by increasing the acid content of the mobile phase.

A routine multiresidue method developed for the detection and quantification of veterinary drug residues in animal-based food was used to analyze sheep (ovine) liver. Unlike when working with previously validated matrices (e.g., bovine liver), some of the analytes of interest chromatographed in the form of split- or even fully baseline separated peaks. In other cases a significantly longer retention times (tR) was observed. A detailed investigation led to the elucidation of taurocholic acid as the causative agent. This compound is present in sheep liver at significantly higher concentrations than in most other animal tissues. Taurocholic acid is a zwitterionic compound and likely acts as an ion pairing agent, which modifies the selectivity of the stationary phase in a highly spatial and dynamic way. Injecting smaller volumes of matrix extract or the use of a significantly higher formic acid concentration in the mobile phase reduced or even completely eliminated the peak splitting. A more detailed examination led to the observation that the problem is not restricted to this particular matrix and extraction procedure or the used stationary phase. In fact, a higher formic acid concentration (e.g., 1.0 % versus 0.1 %) significantly improves the peak shape of many analytes present in fortified matrix samples as well as in pure standard solutions. In addition, analytical column aging was observed as being slower with a higher formic acid concentration. Finally the peak shape of analytes interacting with the metallic parts along the flow path of the liquid chromatograph was also significantly improved. Use of 0.1 % acid in mobile phases is often taken for granted in LC-MS. Regardless of the stationary phase, a higher ionic strength better stabilizes the pH and reduces unwanted interactions, which ultimately improves the method robustness. Flow injection experiments often show that 0.1 % acid concentrations produce the highest analyte signals. Yet, the use of 1 % acid in the mobile phase often leads to narrower and therefore taller chromatographic peaks, which may lead to lower detection limits for many analytes and to an improved separation efficiency.

Effectiveness of uterine tamponade devices for refractory postpartum haemorrhage after vaginal birth: a systematic review.

OBJECTIVES: To evaluate uterine tamponade devices' effectiveness for atonic refractory postpartum haemorrhage (PPH) after vaginal birth and the effect of including them in institutional protocols. SEARCH STRATEGY: PubMed, EMBASE, CINAHL, LILACS, POPLINE, from inception to January 2021. STUDY SELECTION: Randomised and non-randomised comparative studies. OUTCOMES: Composite outcome including surgical interventions (artery ligations, compressive sutures or hysterectomy) or maternal death, and hysterectomy. RESULTS: All included studies were at high risk of bias. The certainty of the evidence was rated as very low to low. One randomised study measured the effect of the condom-catheter balloon compared with standard care and found unclear results for the composite outcome (relative risk [RR] 2.33, 95% CI 0.76-7.14) and hysterectomy (RR 4.14, 95% CI 0.48-35.93). Three comparative studies assessed the effect of including uterine balloon tamponade in institutional protocols. A stepped wedge cluster randomised controlled trial suggested an increase in the composite outcome (RR 4.08, 95% CI 1.07-15.58) and unclear results for hysterectomy (RR 4.38, 95% CI 0.47-41.09) with the use of the condom-catheter or surgical glove balloon. One non-randomised study showed unclear effects on the composite outcome (RR 0.33, 95% CI 0.11-1.03) and hysterectomy (RR 0.49, 95% CI 0.04-5.38) after the inclusion of the Bakri balloon. The second non-randomised study found unclear effects on the composite outcome (RR 0.95, 95% CI 0.32-2.81) and hysterectomy (RR 1.84, 95% CI 0.44-7.69) after the inclusion of Ebb or Bakri balloon. CONCLUSIONS: The effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting. TWEETABLE ABSTRACT: Unclear effects of uterine tamponade devices and their inclusion in institutional protocols for atonic refractory PPH after vaginal delivery.

Optimized multimatrix calibration concept for liquid chromatography mass spectrometry-based bioanalysis methods.

In this paper, a calibration procedure for LC/MS-based bioanalysis methods, termed "A/B fortification", is proposed. The concept relies on the post-extraction fortification (B-spike) of an aliquot of the injection-ready sample extract for the determination and compensation of specific signal suppression or enhancement effects compared to matrix-free extract prepared in buffer or mobile phase. Conventional analyte recovery, observed due to the incomplete extraction of analytes from the sample or losses during a cleanup, is determined by the conventional pre-extraction fortification (A-spike) of a blank sample that belongs to the same type of matrix as the sample with the unknown analyte concentration. This approach permits a higher throughput than conventional sample fortification strategies. The results obtained by utilizing the A/B fortification concept were extensively compared against conventional methods (representative bank matrix fortification, sample fortification and internal standard). The proposed concept (based on the pre-fortification of a reference matrix and post-fortification of the sample) was found to be significantly less biased than internal standard-based techniques. The A/B fortification indicated a better accuracy than the sample fortification or representative blank matrix fortification approach and, most importantly, produced significantly fewer outliers. This was linked to the fact that in the case of the A/B fortification, the uncertainty of the subtraction of two peak areas (fortified minus unfortified sample) is reduced, because fortifications are not made prior to the extraction step but are made into the final injection-ready sample extract. Fortification into an injection-ready aliquot eliminates all sample processing-related differences (procedural errors), which can affect conventional sample fortification-based quantifications.

A scalable high-performance magnetic shield for very long baseline atom interferometry.

We report on the design, construction, and characterization of a 10 m-long high-performance magnetic shield for very long baseline atom interferometry. We achieve residual fields below 4 nT and longitudinal inhomogeneities below 2.5 nT/m over 8 m along the longitudinal direction. Our modular design can be extended to longer baselines without compromising the shielding performance. Such a setup constrains biases associated with magnetic field gradients to the sub-pm/s2 level in atomic matterwave accelerometry with rubidium atoms and paves the way toward tests of the universality of free fall with atomic test masses beyond the 10-13 level.

Does the ion mobility resolving power as provided by commercially available ion mobility quadrupole time-of-flight mass spectrometry instruments permit the unambiguous identification of small molecules in complex matrices?

Quadrupole based mass spectrometry based detection has experienced enormous improvements in terms of sensitivity over the last centuries. This development has not been equally matched with improvements in selectivity. Hence, the use of unit mass based MS/MS transitions or high resolution (HRMS) based extracted ion chromatograms is gradually becoming insufficient in the field of high sensitivity multi-residue analysis (e.g. pesticides in food). As a consequence, commercial instruments hyphenating ion mobility (IMS) with low or high resolution mass spectrometry based detection have appeared. The use of such an additional (frequently claimed to be orthogonal) dimension is intended to increase selectivity. In addition, IMS derived collision cross section (CCS) has been proposed to be used as an additional identification point for the unambiguous identification of trace compounds in complex matrices. It is the topic of this paper to investigate the benefit of using such a hyphenated technique for trace analysis of small molecules in complex matrices. The potential of CCS to serve as additional identification point has been critically evaluated. Discussed are the effect of CCS data on false detects and missing detects of analytes present at trace levels. This involves the investigation of the physical resolving power provided by HRMS, IMS and chromatography as well as the correlation among these parameters (orthogonality). It is the conclusion that currently commercially available travelling wave and linear drift tube based IMS devices with a resolving power of up to 50 permit a reduction of false detects, yet this comes at the price of a higher likelihood of missing detects. The reduction of missing detects and the use of CCS as potential confirmatory information would require IMS resolving powers above 100.

Maternal characteristics and causes associated with refractory postpartum haemorrhage after vaginal birth: a secondary analysis of the WHO CHAMPION trial data.

OBJECTIVE: To assess the maternal characteristics and causes associated with refractory postpartum haemorrhage (PPH). DESIGN: Secondary analysis of the WHO CHAMPION trial data. SETTING: Twenty-three hospitals in ten countries. POPULATION: Women from the CHAMPION trial who received uterotonics as first-line treatment of PPH. METHODS: We assessed the association between sociodemographic, pregnancy and childbirth factors and refractory PPH, and compared the causes of PPH between women with refractory PPH and women responsive to first-line PPH treatment. MAIN OUTCOME MEASURES: Maternal characteristics; causes of PPH. RESULTS: Women with labour induced or augmented with uterotonics (adjusted odds ratio [aOR] 1.35; 95% CI 1.07-1.72), with episiotomy or tears requiring suturing (aOR 1.82; 95% CI 1.34-2.48) and who had babies with birthweights ≥3500 g (aOR 1.33; 95% CI 1.04-1.69) showed significantly higher odds of refractory PPH compared with the reference categories in the multivariate analysis adjusted by centre and trial arm. While atony was the sole PPH cause in 53.2% (116/218) of the women in the responsive PPH group, it accounted for only 31.5% (45/143) of the causes in the refractory PPH group. Conversely, tears were the sole cause in 12.8% (28/218) and 28% (40/143) of the responsive PPH and refractory PPH groups, respectively. Placental problems were the sole cause in 11 and 5.6% in the responsive and refractory PPH groups, respectively. CONCLUSION: Women with refractory PPH showed a different pattern of maternal characteristics and PPH causes compared with those with first-line treatment responsive PPH. TWEETABLE ABSTRACT: Women with refractory postpartum haemorrhage are different from those with first-line treatment responsive PPH.

High-resolution mass spectrometry-based multi-residue method covering relevant steroids, stilbenes and resorcylic acid lactones in a variety of animal-based matrices.

A new, relatively simple sample processing and detection workflow has been developed for the quantification and confirmation of banned growth-promoting substances in a wide variety of animal-based food products. The method covers all required compounds (belonging to the so-called A1, A3, A4 and B2f groups as termed by the relevant EU legislation) which are currently monitored by the official European community surveillance programs. The sample processing includes a thermal sample denaturation step, intended to prevent undesirable side-reactions during the following enzymatic deconjugation of covalently bound analytes. A pH-adjusted dual liquid/liquid-extraction produces sufficient clean extracts for a wide range of matrices (urine, muscle, liver, serum, full blood). The method has been validated using two hybrid quadrupole high-resolution mass spectrometers (Orbitrap and time-of-flight technology-based instruments). Full-scan data acquisition, interlaced with targeted modes (unit mass isolation of the precursors, followed by collision-induced fragmentation), produces sufficiently sensitive and selective detection of the analytes within all the validated matrices. The proposed method is an alternative to currently used methods that are restricted to a limited set of analytes and matrices.

Structure and Nanomechanics of Dry and Hydrated Intermediate Filament Films and Fibers Produced from Hagfish Slime Fibers.

Intermediate filaments (IFs) are known for their extensibility, flexibility, toughness, and their ability to hydrate. Using keratin-like IFs obtained from slime fibers from the invertebrate Atlantic hagfish ( Myxine glutinosa), films were produced by drop-casting and coagulation on the surface of a MgCl2 buffer. Drop-casting produced self-supporting, smooth, and dense films rich in ß-sheets (61%), whereas coagulation formed thin, porous films with a nanorough surface and a lower ß-sheet content (51%). The films hydrated and swelled immediately when immersed in water and did not dissolve. X-ray diffraction showed that the ß-crystallites remained stable upon hydration, that swelling presumably happens in the amorphous C-terminal tail-domains of the IFs, and that high salt conditions caused a denser network mesh size, suggesting polyelectrolyte behavior. Hydration resulted in a roughly 1000-fold decrease in apparent Young's modulus from 109 to 106 Pa as revealed by atomic force microscopy nanoindentation. Nanoindentation-based power-law rheology and stress-relaxation measurements indicated viscoelasticity and a soft-solid hydrogel character for hydrated films, where roughly 80% of energy is elastically stored and 20% is dissipated. By pulling coagulation films from the buffer interface, macroscopic fibers with highly aligned IF ß-crystals similar to natural hagfish fibers were produced. We propose that viscoelasticity and strong hydrogen bonding interactions with the buffer interface are crucial for the production of such long biomimetic fibers with aligned ß-sheets. This study demonstrates that hagfish fiber IFs can be reconstituted into functional biomimetic materials that are stiff when dry and retain the ability to hydrate to become soft and viscoelastic when in water.

Hagfish slime exudate stabilization and its effect on slime formation and functionality.

Hagfish produce vast amounts of slime when under attack. The slime is the most dilute hydrogel known to date, and is a highly interesting material for biomaterial research. It forms from a glandular secrete, called exudate, which deploys upon contact with seawater. To study slime formation ex vivo and to characterize its material properties, stabilization of the sensitive slime exudate is crucial. In this study, we compared the two main stabilization methods, dispersion in high osmolarity citrate/PIPES (CP) buffer and immersion in oil, and tested the influence of time, temperature and pH on the stability of the exudate and functionality of the slime. Using water retention measurements to assess slime functionality, we found that CP buffer and oil preserved the exudate within the first 5 hours without loss of functionality. For longer storage times, slime functionality decreased for both stabilization methods, for which the breakdown mechanisms differed. Stabilization in oil likely favored temperature-sensitive osmotic-driven swelling and rupture of the mucin vesicles, causing the exudate to gel and clump. Extended storage in CP buffer resulted in an inhibited unraveling of skeins. We suggest that a water soluble protein glue, which mediates skein unraveling in functional skeins, denatures and gradually becomes insoluble during storage in CP buffer. The breakdown was accentuated when the pH of the CP buffer was raised from pH 6.7 to pH 8.5, probably caused by increased denaturation of the protein glue or by inferior vesicle stabilization. However, when fresh exudate was mixed into seawater or phosphate buffer at pH 6-9, slime functionality was not affected, showing pH insensitivity of the slime formation around a neutral pH. These insights on hagfish exudate stabilization mechanisms will support hagfish slime research at a fundamental level, and contribute to resolve the complex mechanisms of skein unraveling and slime formation.

Rewarding feedback promotes motor skill consolidation via striatal activity.

Knowledge of performance can activate the striatum, a key region of the reward system and highly relevant for motivated behavior. Using functional magnetic resonance imaging, striatal activity linked to knowledge of performance was measured during the training of a repetitive arc-tracking task. Knowledge of performance was given after a random selection of trials or after good performance. The third group received knowledge of performance after good performance plus a monetary reward. Skill learning was measured from pre- to post- (acquisition) and from post- to 24h posttraining (consolidation). Our results demonstrate an influence of feedback on motor skill learning. Adding a monetary reward after good performance leads to better consolidation and higher ventral striatal activation than knowledge of performance alone. In turn, rewarding strategies that increase ventral striatal response during training of a motor skill may be utilized to improve skill consolidation.

Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature.

BACKGROUND: Oxytocin is the drug of choice for preventing and treating postpartum haemorrhage, an important cause of maternal death. Oxytocin is widely available in low and middle-income countries (LMIC) but there are concerns about its quality. OBJECTIVE: To identify, critically appraise and synthesise the findings of studies on the quality of oxytocin available in LMIC. SEARCH STRATEGY: We searched seven electronic databases, without language restriction. SELECTION CRITERIA: Studies reporting results of tests to assess quality of oxytocin samples from LMIC. DATA COLLECTION AND ANALYSIS: Study selection, data extraction and quality assessment were performed in duplicate. Results are presented descriptively. MAIN RESULTS: The search identified 2611 unique citations; eight studies, assessing 559 samples from 15 different countries were included. Most samples were collected from facility level settings (n = 509) and from the private sector (n = 321). The median prevalence of oxytocin samples that failed quality tests was 45.6% (range 0-80%), mostly due to insufficient amounts of active pharmacological ingredient. Over one-third of the samples (n = 204) had low (<90%) oxytocin content indicating substandard medicine; two samples had no active ingredient, suggesting possible counterfeit drugs. The proportion of low fails was higher in samples collected in Africa than in Asia or Latin America (57.5% versus 22.3% versus 0%, respectively, P < 0.0001), in private than in public sectors (34.0% versus 25.3%, P = 0.032) and in facilities than in central distributors (37.9% versus 22.0%, P = 0.030). CONCLUSION: There is a high prevalence of poor-quality oxytocin samples in LMIC countries, mainly due to inadequate amounts of active ingredient. TWEETABLE ABSTRACT: Systematic review points to problems with quality of oxytocin samples from low- and middle-income countries.

Determination of nitrofuran and chloramphenicol residues by high resolution mass spectrometry versus tandem quadrupole mass spectrometry.

An ultra-high performance liquid chromatography based method, coupled to high resolution mass spectrometry (UHPLC-HRMS), was developed to permit the detection and quantification of various nitrofuran and chloramphenicol residues in a number of animal based food products. This method is based on the hydrolysis of covalently bound metabolites and derivatization with 2-nitrobenzaldehyde. Clean-up is achieved by a liquid/liquid and a reversed phase/solid phase extraction. Not only are the four conventional nitrofurans (nitrofurantoin, furazolidone, nitrofurazone and furaltadone) detected, but also nifursol, nitrovin and nifuroxazide. Furthermore, an underivatizable nitrofuran (nifurpirinol) and another banned drug (chloramphenicol) can be quantified as well. The compounds are detected in the form of their precursor ions, [M+H](+) and [M-H](-), respectively. The mass resolving power of 70,000 FWHM, and the applied mass window ensure sufficient selectivity and sensitivity. Confirmation is obtained by monitoring the HRMS resolved product ions which were derived from the unit-mass resolved precursor ions. The multiplexing capability of the utilized Orbitrap instrument provides not only highly selective, but also sensitive confirmatory signals. This method has been validated according to the CD 2002/657/EC for the following matrices: muscle, liver, kidney, fish, honey, eggs and milk.

Reliability of veterinary drug residue confirmation: high resolution mass spectrometry versus tandem mass spectrometry.

Confirmation of suspected residues has been a long time domain of tandem triple quadrupole mass spectrometry (QqQ). The currently most widely used confirmation strategy relies on the use of two selected reaction monitoring signals (SRM). The details of this confirmation procedure are described in detail in the Commission Decision 93/256/EC (CD). On the other hand, high resolution mass spectrometry (HRMS) is nowadays increasingly used for trace analysis. Yet its utility for confirmatory purposes has not been well explored and utilized, since established confirmation strategies like the CD do not yet include rules for modern HRMS technologies. It is the focus of this paper to evaluate the likelihood of false positive and false negative confirmation results, when using a variety of HRMS based measurement modes as compared to conventional QqQ mass spectrometry. The experimental strategy relies on the chromatographic separation of a complex blank sample (bovine liver extract) and the subsequent monitoring of a number of dummy transitions respectively dummy accurate masses. The term "dummy" refers to precursor and derived product ions (based on a realistic neutral loss) whose elemental compositions (CxHyNzOdCle) were produced by a random number generator. Monitoring a large number of such hypothetical SRM's, or accurate masses inevitably produces a number of mass traces containing chromatographic peaks (false detects) which are caused by eluting matrix compounds. The number and intensity of these peaks were recorded and standardized to permit a comparison among the two employed MS technologies. QqQ performance (compounds which happen to produce a response in two SRM traces at identical retention time) was compared with a number of different HRMS(1) and HRMS(2) detection based modes. A HRMS confirmation criterion based on two full scans (an unfragmented and an all ion fragmented) was proposed. Compared to the CD criteria, a significantly lower probability of false positive and false negative findings is obtained by utilizing this criterion.

Multi-residue quantification of veterinary drugs in milk with a novel extraction and cleanup technique: salting out supported liquid extraction (SOSLE).

A quantitative liquid chromatography coupled with high-resolution mass spectrometry method was developed for the determination of more than one hundred compounds belonging to a variety of veterinary drug classes in bovine milk. Salting out supported liquid extraction (SOSLE), a novel extraction and cleanup technique, was introduced to ensure high extraction efficiency and good sample cleanup. The high salt (ammonium sulfate) concentration in the aqueous donor phase permits supported liquid/liquid extraction (SLE) with a relative polar organic acceptor phase (acetonitrile). This is different from traditional SLE, in which the need for phase separation results in the selection of organic solvents with intermediate polarities (e.g., ethyl acetate or dichloromethane). Hence, SOSLE is more efficient in recovering polar analytes than conventional SLE. SOSLE was also compared to classical approaches like solid phase extraction, QuEChERS and ultra-filtration. The proposed technique resulted in extracts of equal or superior cleanliness and with higher average recoveries than those obtained with QuEChERS or SPE. The recovery (median for all compounds) was 73% for QuEChERS, 83% for SPE and 91% for SOSLE. The most significant improvements were observed for polar analytes (penicillines, quinolones and tetracyclines) which are hardly recovered by QuEChERS. The chromatographic separation and detection was based on an ultra-high-performance liquid chromatography Q-Orbitrap system (Q-Exactive plus). The developed analytical method has been validated (based on the commission decision 2002/957/EC) as required for quantitative veterinary drug methods.

Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. DESIGN: Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. SETTING: Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. POPULATION: All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. METHODS: We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. RESULTS: Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. CONCLUSIONS: The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation.

Quantitative analysis of polypeptide antibiotic residues in a variety of food matrices by liquid chromatography coupled to tandem mass spectrometry.

A quantitative LC-MS/MS method was developed for the determination of five polypeptide antibiotics (bacitracin, colistin A, colistin B, polymyxin B1 and polymyxin B2) in a variety of food matrices (muscle, liver, kidney, egg and milk). The described method is sufficiently sensitive, selective and provides acceptable recoveries for all compounds. The extraction is based on acidified methanolic solvent. This is followed by a reversed phase solid phase extraction step to clean-up and concentrate the extracts. The use of a modern core shell column in combination with an eluent consisting of trifluoroacetic acid, formic acid and acetonitrile provides chromatographically well resolved analyte peaks The single-step clean-up is fast and produces a sufficiently clean extract in order to control matrix-related signal suppression in the electrospray interface.

Determination of microbial transglutaminase in meat and meat products.

Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.

OS029. Severe anemia, sickle cell disease, and thalassemia as riskfactors for preeclampsia in developing countries.

INTRODUCTION: Hypertensive disorders during pregnancy contribute greatly to maternal and perinatal morbidity and mortality in developing countries. The pathogenesis of such conditions may be illuminated by exploring their relationship to anemia. OBJECTIVES: To determine whether several types of anemia are risk factors for hypertensive disorders during pregnancy in developing countries. METHODS: Using data from the World Health Organization Global Survey for Maternal and Perinatal Health, collected in hospitals in six African and six Latin American countries from 2007 to 2008 and in four Asian countries from 2004 to 2005, we examined the associations between severe anemia, sickle cell disease and thalassemia and gestational hypertension or preeclampsia/eclampsia. After exclusions for comorbidities (chronic hypertension, diabetes, HIV infection) and missing data, the severe anemia, sickle cell disease, and thalassemia groups consisted of 219,627,117,383, and 9376 women, respectively. RESULTS: Multiparous women with severe anemia were at an increased risk of gestational hypertension (adjusted odds ratio (OR): 1.58; 95% confidence interval (CI): 1.15-2.19). Severe anemia had a significant association with preeclampsia/eclampsia for nulliparous (OR: 3.55; 95% CI: 2.87-4.41) and multiparous (OR: 3.94; 95% CI: 3.05-5.09) women. Sickle cell disease exhibited a significant association with gestational hypertension among nulliparous (OR: 2.49; 95% CI: 1.46-4.25) and multiparous (OR: 3.27; 95% CI: 2.33-4.58) women. No significant associations were found between sickle cell disease and preeclampsia/eclampsia, or between thalassemia and either gestational hypertension or preeclampsia/eclampsia. CONCLUSION: Severe anemia appears to be a risk factor for preeclampsia/eclampsia, while sickle cell disease appears to be a risk factor for gestational hypertension among women seeking hospital care in developing countries.