Neonatal deaths in rural Karnataka, India 2014-2018: a prospective population-based observational study in a low-resource setting.

BACKGROUND: Neonatal mortality causes a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). METHODS: We undertook a prospective, population-based research study of pregnant women residing in defined geographic areas in the Karnataka State of India, a research site of the Global Network for Women\u27s and Children\u27s Health Research. Study staff collected demographic and health care characteristics on eligible women enrolled with neonatal outcomes obtained at delivery and day 28. Cause of neonatal mortality at day 28 was assigned by algorithm using prospectively defined variables. RESULTS: From 2014 to 2018, the neonatal mortality rate was 24.5 per 1,000 live births. The cause of the 28-day neonatal deaths was attributed to prematurity (27.9%), birth asphyxia (25.1%), infection (23.7%) and congenital anomalies (18.4%). Four or more antenatal care (ANC) visits was associated with a lower risk of neonatal death compared to fewer ANC visits. In the adjusted model, compared to liveborn infants ≥ 2500 g, infants born weighing \u3c 1000 g RR for mortality was 25.6 (95%CI 18.3, 36.0), for 1000-1499 g infants the RR was 19.8 (95% CI 14.2, 27.5) and for 1500-2499 g infants the RR was 3.1 (95% CI 2.7, 3.6). However, more than one-third (36.8%) of the deaths occurred among infants with a birthweight ≥ 2500 g. Infants born preterm (\u3c 37 weeks) were also at higher risk for 28-day mortality (RR 7.9, 95% CI 6.9, 9.0) compared to infants ≥ 37 weeks. A one-week decrease in gestational age at delivery was associated with a higher risk of mortality with a RR of 1.3 (95% CI 1.3, 1.3). More than 70% of all the deliveries occurred at a hospital. Among infants who died, 50.3% of the infants had received bag/mask ventilation, 47.3% received antibiotics, and 55.6% received oxygen. CONCLUSIONS: Consistent with prior research, the study found that infants who were preterm and low-birth weight remained at highest risk for 28-day neonatal mortality in India. Although most of births now occur within health facilities, a substantial proportion are not receiving basic life-saving interventions. Further efforts to understand the impact of care on infant outcomes are needed. Study registration The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475

RAPIDIRON Trial Follow-Up Study - the RAPIDIRON-KIDS Study: Protocol of a Prospective Observational Follow-Up Study

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India\u27s National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes. METHODS: This prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age. DISCUSSION: This RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05504863 , Registered on 17 August 2022. Clinical Trials Registry - India CTRI/2022/05/042933 . Registered on 31 May 2022

Safe infant feeding in healthcare facilities: Assessment of infection prevention and control conditions and behaviors in India, Malawi, and Tanzania

Infants need to receive care in environments that limit their exposure to pathogens. Inadequate water, sanitation, and hygiene (WASH) environments and suboptimal infection prevention and control practices in healthcare settings contribute to the burden of healthcare-associated infections, which are particularly high in low-income settings. Specific research is needed to understand infant feeding preparation in healthcare settings, a task involving multiple behaviors that can introduce pathogens and negatively impact health. To understand feeding preparation practices and potential risks, and to inform strategies for improvement, we assessed facility WASH environments and observed infant feeding preparation practices across 12 facilities in India, Malawi, and Tanzania serving newborn infants. Research was embedded within the Low Birthweight Infant Feeding Exploration (LIFE) observational cohort study, which documented feeding practices and growth patterns to inform feeding interventions. We assessed WASH-related environments and feeding policies of all 12 facilities involved in the LIFE study. Additionally, we used a guidance-informed tool to carry out 27 feeding preparation observations across 9 facilities, enabling assessment of 270 total behaviors. All facilities had ‘improved’ water and sanitation services. Only 50% had written procedures for preparing expressed breastmilk; 50% had written procedures for cleaning, drying, and storage of infant feeding implements; and 33% had written procedures for preparing infant formula. Among 270 behaviors assessed across the 27 feeding preparation observations, 46 (17.0%) practices were carried out sub-optimally, including preparers not handwashing prior to preparation, and cleaning, drying, and storing of feeding implements in ways that do not effectively prevent contamination. While further research is needed to improve assessment tools and to identify specific microbial risks of the suboptimal behaviors identified, the evidence generated is sufficient to justify investment in developing guidance and programing to strengthen infant feeding preparation practices to ensure optimal newborn health

Effect of schistosome infection on hepatic drug metabolising enzymes

Journal article from South African Journal of Science pages 301-302,Schistosomiasis is a parasitic disease that affects over 200 million persons worldwide.' The disease is caused by infection with any one of several species that are known to affect humans. Infected persons are likely to be consuming a wide spectrum of xenobiotics such as drugs and environmental toxins. The drugs consumed would not only include praziquantel and other schistosomicides, but also those used for the treatment of other parasitic diseases such as antimalarials, anthelmintics and antibiotics. Experiments involving humans and experimental animals suggest that infection with schistosomes causes a reduction in the host's ability to metabolise and remove drugs from the body

Hepatic Cytosolic Glutathione S- Transferases of ostrich (struthio camelus): partial characterisation and interaction with xenobiotics.

An article with pictures.,The glutathione S-transferases (GSTs) in affinity purified pools of male and female ostrich liver were studied. The GSTs were purified from crude liver cytosols by S-hexylglutathione sepharose affinity chromatography with yields comparable to those reported for GST from mammalian livers. The K, for both glutathione (GSH) and 1-chloro-2,4-dinitroSenzenzene (CDNB) were determined and found to be within the range of values known for mammalian and invertebrate species. 1- chloro-2,4-dinitrobenzene proved to be the best of nine substrates tested to measure activity. Activity was inhibited by bromosulphophthalein and cibacron blue which are well known inhibitors of the mammalian enzyme. Our results indicate that the ostrich liver enzymes behave similarly to the mammalian liver enzyme in terms of substrate requirements and inhibition characteristics.,Zimban

Recovery Of Choline And Non-Cholinesterase Activity Of The Freshwater Snail Lymnaea Natalensis Following Exposure To Six Pesticides

Presented at the 5th Congress of the Federation of African Societies of Biochemistry and Molecular Biology in November 2006.,Organophosphates and carbamates are the most widely used insecticides mainly because they are readily biodegradable in the environment. We investigated the recovery of esterase activity of an aquatic snail L. natalensis following a 24-hour exposure to 6 different pest.icides. A third of the snails were sacrificed after 24 hours while another third was allowed to recover in clean water for 14 days and the remainder for 28 days. All pesticides caused significant inhibition of esterase activity. Aldicarb caused the highest inhibition in esterase activity 98 % while thiamethoxam caused the least 61 %. Esterase activity improved significantly in the recovery period and 14 days in the recovery period, aldicarb and thiamethoxam exposed snails had recovered to 57 % and 67 % of control. After 28 days of recovery, aldicarb exposed snails had only 62 % esterase activity in comparison to controls. The results show that even after 28 days of recovery, esterase activity was still reduced by up to 38 % depending on the pesticide, an indication that recovery of the snails depends on the pesticide. From the results we suggest that where pesticides need to be applied more than once, a time gap between applications should be allowed to enable non-target organisms in soil and aquatic systems to recover from effects of previous applications thereby ensuring the good health of non-target organisms.,Federation of African Societies of Biochemistry and Molecular Biolog

Molluscan Esterase Activity As a Biomarker of Aquatic Pollution Caused By Monocrotophos.

Presented at the ANCAP(African Network for Chemical Analysis of Pesticides)Conference in August 2004.,There are many analytical protocols for detecting levels of agrochemicals~inaquatic systems. Methods of analytical chemistry can provide information of the exact concentrations in water samples. However they do not provide information on the potentially harmful effects on the organisms in the aquatic environment as biological markers have been shown to. Biomarkers of environmental quality should be tested under field situations if they are to be accepted outside academic circles and become part of national policies in environmental monitoring programs. We have previously shown that exposure of Lymnaea natalensis to organophosphates caused dose and time dependent inhibition of esterase activity. Here we report on the effects of monocrotophos on esterase activity in L. natalensis under field simulated conditions.Juvenile snails reared outdoors were exposed to single dose (5, 12, 15, 20 and 25ppb) of monocrotophos dissolved in either Matopos (pristine) or Umguza (polluted)dam water for 1, 7 or 14 days. Water was not changed for the duration of exposure. Post mitochondrial supernatants of whole snail homogenates were used to measure esterase activity. Cholinesterase activity was measured using acetylcholine iodide while carboxylesterase activity was measured using a-naphthyl acetate and 4nitrophenyl acetate. Esterase activity was significantly reduced in a dose responsive manner for aIr substrates. The degree of inhibitioll. varied depen,ding on the water source. Our results also indicated a decrease with time in degree of inhibition of esterase activity, suggesting a recovery with time of the snails from pesticide poisoning. On comparing data from the two dams higher inhibitions were observed in snails exposed to Matopos dam water than those exposed to Umguza dam water. Umguza dam water is highly contaminated with industrial effluents and therefore expected to have a higher microbial load and increased pesticide decomposition rate when compared to Matopos dam water, which is relatively pristine. Our results have shown that esterase activity is very sensitive to presence of organophosphates with inhibitions of up to 92 % observed within 24 hours of exposure. Altered esterase activity therefore has a potential use as a biomarker for detecting organophosphatepollution in water samples.,African Network for Chemical Analysis of Pesticide

Cytosolic glutathione s-transferases of ostrich liver.

An article with 14 pages.,Chemicals consummumed by the ostrich are likely to be metabolised by liver detoxifying enzymes such as the cytosolic glutathione Stransferases (GST). We have studied the affinity purified GST from male and female ostrich livers. 1-chloro-2, 4-dinitrobenzene (CDNB) proved to be the best of several substrates tested to measme activity. Activity with this substrate was inhibited by sulphobromoptgnalein and cibamon blue which are well established inhibitors for the m ammalian enzyme. A number of pesticides and environmentai pollutants were also found to be strong inhibitors of the enzymes. Our data indicates that ostrich liver enzymes behave similarly to the mammalian liver enzyme in terms of substrate requirements and inhibition characteristics.,ZIMBANK, RK Financial from the University of Zimbabwe and International Programs in the Chemical Sciences (Uppsaia, Sweden

The Role Of Natural Products In Environmental Toxicology And Health.

Presented at the Afassa Regional Symposium on Natural Products in June 2004.,Many of natural products have been studied as crude extracts. Many active ingredients have also been purified and their chemical structures have been elucidated. Yet in most cases there is a paucity of information regarding their biological activity. Natural products have been tested widely in the ceArol of a number of parasitic diseases around the globe. In the control of malaria various chemicals have been tested for controlling the mosquito vector e.g. extracts of neem. Several other natural compounds have also been tested for possible control of the parasite itself e.g. quinine and artemisinin (a sesquiterpene lactone) which have shown tremendous potential in the control of malaria. Aquatic mollusks transmit a number of other parasitic diseases such as schistosomiasis and fascioliasis in the tropics. A number of different compounds belonging to a variety of different chemical classes have been tested for their efficacy as molluscicides e.g. Azadirachta indica, Cedrus deodara, Allium sativum. Natural products have also been shown to affect animals in their natural ecosystems. There are a number of compounds that have been shown to affect reptilian species e.g. cinnamaldehyde and geranyl acetate. Other compounds such as genestitin, naringenin and zearalenone cause physiological systems in animals. Although the compounds have adverse effects in certain organisms they have beneficial effects in others. The mechanisms by which these natural compounds affect organisms are many and diverse. Such mechanisms include alteration of enzyme activities, receptor binding and macromolecular integrity. Altered enzyme activity includes key detoxication enzymes (xenobiotic metabolism) as well as those involved in intermediary metabolism. Altered binding to receptors of the endocrine system is an emerging area of research (endocrine disruption). Damage to DNA is also a possible target of natural compounds. While there is a large body of information on the effects of anthropogenic compounds on the above targets there is much less data available on the effects of natural products. More recently there is an upsurge in the effects of natural compounds on these targets and this paper will provide examples of the currently available information.,Sida, SARE

Biomarkers of Environmental Pollution

Presented at the Biochemistry and Molecular Biology Society Conference held at the University of Zimbabwe in October 2002,The threat to our environment due to human activity continues as the need for increased agricultural and industrial output continues. Agrochemicals currently used include pesticides such as organochlorines, organophosphates (OP's), neonicotinoids and pyrethroids. Industrial activity continues to generate an increasing diversity and volume of chemicals, such as PCB's and dioxins, that find their way into our natural and manmade water bodies. Metals such as lead, chromium and cadmium are either mined or are discharged as by-products of human activity. When used safely or disposed of properly these compounds are not always hazardous. However, their improper disposal or use poses a hazard to the health of humans, wildlife and the ecosystem as a whole. They are known to cause a variety of toxic effects such as genetic damage, organ toxicity and several physiological changes such as endocrine disruption. There is.a need to identify such toxic compounds and also to monitor their presence particularly in water bodies of Southern Africa where freshwater is scarce. Some of the methods, currently available to detect such toxins, include the measurement of parameters such as esterase activity (or its inhibition) for OP's, the extent of DNA damage (using the COMET assay) and induction/inhibition of detoxication enzymes (cytochrome P-450, glutathione S-transferase, antioxidant enzymes etc.) and induction of vitellogin synthesis (in fish). However, all these methods are not reliable or sufficiently sensitive. A summary of the data presented in the literature as well as that generated in our own laboratory will be presented.,Biochemistry and Molecular Biology Societ