Selection of a Suitable Animal Model to Evaluate Secretion of Drugs in the Human Milk: A Systematic Approach.

Lack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum.Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs.Various factors that are likely to impact milk to plasma ratio were identified. A literature search was performed to gather available data on milk composition, total volume of milk produced per day, milk pH, haematocrit, and renal blood flow and glomerular filtration rate in various animal models.BLAST nucleotide and protein tools were used to evaluate the similarities between humans and animals in the expression and predominance of selected drug transporters, metabolic enzymes, and blood proteins.A multistep analysis of all the potential variables affecting drug secretion was considered to identify most appropriate animal model. The practicality of using the animal in a lab setting was also considered.Donkeys and goats were identified as the most suitable animals for studying drug secretion in milk.

Can Medical Nutrition Therapy Affect Feto-Maternal Outcomes in Gestational Glucose Intolerance: An Open-Label Pilot Randomized Control Trial in World's Diabetes Capital.

Introduction: Gestational diabetes is defined as the carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Gestational glucose intolerance (GGI) is used to indicate pregnant women whose 2-h postprandial glucose is > 120 mg/dl and below 140 mg/dl (Diabetes in Pregnancy Study Group of India, DIPSI criteria). Aim: This study was planned to see whether intervention in GGI group helps to improve feto-maternal outcomes. Methodology: This open-label randomized control trial was conducted in Department of Obstetrics and Gynaecology of King George's Medical University, Lucknow. Inclusion criteria were all the antenatal women attending the antenatal clinic and diagnosed as GGI, and exclusion criteria were overt diabetes. Results: Total of 1866 antenatal women were screened, and among them, 220 (11.8%) women were diagnosed as gestational diabetes; 412 (22.1%) women were diagnosed as GGI. The mean fasting blood sugars in the women with GGI who had medical nutrition therapy were much lower than the women with GGI who did not have any intervention. The present study showed the women with GGI had higher complications like polyhydramnios, PPROM, foetal growth restriction, macrosomia, preeclampsia, preterm labour and vaginal candidiasis more in the women with GGI as compared to euglycaemic women. Conclusion: The present study of nutritional intervention in GGI group has shown trend towards lesser complication if we start medical nutrition therapy reflected by delayed development of GDM and less neonatal hypoglycaemia and hyperbilirubinemia.

Comparing aspirin 75 to 81 mg vs 150 to 162 mg for prevention of preterm preeclampsia: systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare 2 aspirin dosage regimens for the prevention of preterm preeclampsia (PE): 75 to 81 mg vs 150 to 162 mg taken daily starting in the first trimester of pregnancy. DATA SOURCES: A systematic search was performed using PubMed, Embase, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials from January 1985 to April 2023. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were randomized controlled trials that compared the effect of 2 aspirin dosage regimens during pregnancy for the prevention of PE initiated in the first trimester of pregnancy. The intervention was an aspirin dosage between 150 and 162 mg daily, and the control was an aspirin dosage between 75 and 81 mg daily. METHODS: Of note, 2 reviewers independently screened all citations, selected studies, and evaluated the risk of bias. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool. The corresponding authors of the included studies were contacted to validate each of the collected results. The primary outcome was the risk of preterm preeclampsia, and the secondary outcomes included term preeclampsia, any preeclampsia regardless of gestational age, and severe preeclampsia. Relative risks with their 95% confidence interval were calculated for each study and pooled for global analysis. RESULTS: Of note, 4 randomized controlled trials were retrieved involving 552 participants. Moreover, 2 randomized controlled trials were at unclear risk of bias, 1 trial at low risk of bias and 1 trial at high risk of bias, which did not have the information for the primary outcome. The pooled analysis demonstrated that an aspirin dosage of 150 to 162 mg was associated with a significant reduction of preterm preeclampsia, compared with an aspirin dosage of 75 to 81 mg (3 studies; 472 participants; relative risk, 0.34; 95% confidence interval, 0.15-0.79; P=.01; I2=0%). There was no significant effect on the risk of term preeclampsia (3 studies; 472 participants; relative risk, 0.57; 95% confidence interval, 0.12-2.64; P=.48; I2=64%) and all preeclampsia (4 studies; 552 participants; relative risk, 0.42; 95% confidence interval, 0.17-1.05; P=.06; I2=58%), but there was a reduction of severe preeclampsia (3 studies; 472 participantst; RR, 0.23; 95% CI, 0.09-0.62; P=.003; I2=0%). CONCLUSION: When initiated in the first trimester of pregnancy, an aspirin dosage of 150 to 162 mg daily was associated with a lower risk of preterm PE than an aspirin dosage of 75 to 81 mg daily. However, the lack of large, high-quality studies limited the clinical scope of the current results taken alone.

A viral biomolecular condensate coordinates assembly of progeny particles.

Biomolecular condensates formed by phase separation can compartmentalize and regulate cellular processes1,2. Emerging evidence has suggested that membraneless subcellular compartments in virus-infected cells form by phase separation3-8. Although linked to several viral processes3-5,9,10, evidence that phase separation contributes functionally to the assembly of progeny particles in infected cells is lacking. Here we show that phase separation of the human adenovirus 52-kDa protein has a critical role in the coordinated assembly of infectious progeny particles. We demonstrate that the 52-kDa protein is essential for the organization of viral structural proteins into biomolecular condensates. This organization regulates viral assembly such that capsid assembly is coordinated with the provision of viral genomes needed to produce complete packaged particles. We show that this function is governed by the molecular grammar of an intrinsically disordered region of the 52-kDa protein, and that failure to form condensates or to recruit viral factors that are critical for assembly results in failed packaging and assembly of only non-infectious particles. Our findings identify essential requirements for coordinated assembly of progeny particles and demonstrate that phase separation of a viral protein is critical for production of infectious progeny during adenovirus infection.

Correlation of sFlt/PlGF ratio with severity of preeclampsia in an Indian population.

Background: Preeclampsia affects 2% to 8% of pregnant women and significantly increases the risk for maternal and perinatal morbidity, especially in low- and middle-income countries. There is increasing evidence to support the use of biochemical markers such as placental growth factor and soluble fms-like tyrosine kinase-1 in predicting the severity of preeclampsia and to rule out severe disease in clinical conditions masquerading as severe preeclampsia. OBJECTIVE: This study aimed to assess the role of the sFlt-1/PlGF ratio in predicting adverse perinatal and maternal outcomes in women with preeclampsia in a South Asian population with a higher rate of the disease and its associated complications. STUDY DESIGN: This was a prospective cohort study of women diagnosed with preeclampsia or suspected to have preeclampsia who underwent biophysical and biochemical investigations to measure the severity, including determining maternal hemodynamic indices, mean arterial pressure, fetal biometric and Doppler parameters, and soluble fms-like tyrosine kinase-1 and placental growth factor levels. The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver operating characteristic curve analysis. An adverse maternal outcome was defined as 1 or more of severe hypertension; admission to the intensive care unit; eclampsia; placental abruption; hemolysis, elevated liver enzymes, low-platelet count syndrome; disseminated intravascular coagulation; platelets <100×109/L; creatinine >1.1 mg/dL; and alanine aminotransferase >100 U/L. An adverse perinatal outcome was defined as 1 or more of preterm birth ≤34+0 weeks' gestation, neonatal intensive care unit admission for >48 hours, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity, and confirmed fetal infection. RESULTS: We recruited 91 women with preeclampsia with a mean gestational age of 30.63±2.86 weeks. Women who had adverse maternal events had higher median maternal concentrations of soluble fms-like tyrosine kinase (11,500.0 pg/mL vs 3051.0 pg/mL; P<.001), lower concentrations of placental growth factor (44.88 pg/mL vs 148.50 pg/mL; P<.001), and a higher sFlt-1/PlGF ratio (306.22 vs 30.63; P<.001) than women who did not. Pregnancies with an adverse perinatal outcome also had a higher soluble fms-like tyrosine kinase concentration (12,100.0 pg/mL vs 3051.0 pg/mL; P<.001), lower placental growth factor concentration (27.2 pg/mL vs 148.50 pg/mL; P<.001), and higher sFlt-1/PlGF ratio (378.45.4 vs 30.63; P<.001). The area under the receiver operating characteristic curve showed that soluble fms-like tyrosine kinase and placental growth factor were the best biomarkers when compared with other biochemical markers to predict adverse maternal (area under the curve, 0.81; 95% confidence interval, 0.72-0.90) and fetal (area under the curve, 0.88; 95% confidence interval, 0.80-0.96) outcomes in preeclampsia. CONCLUSION: The sFlt-1/PlGF ratio correlates better with adverse maternal and perinatal outcomes than any other biochemical marker in an Indian population. The incorporation of the sFlt-1/PlGF ratio in women with preeclampsia can help in predicting the severity of the condition and the timings of the delivery.

Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE).

Single-molecule characterization of protein-DNA dynamics provides unprecedented mechanistic details about numerous nuclear processes. Here, we describe a new method that rapidly generates single-molecule information with fluorescently tagged proteins isolated from nuclear extracts of human cells. We demonstrated the wide applicability of this novel technique on undamaged DNA and three forms of DNA damage using seven native DNA repair proteins and two structural variants, including: poly(ADP-ribose) polymerase (PARP1), heterodimeric ultraviolet-damaged DNA-binding protein (UV-DDB), and 8-oxoguanine glycosylase 1 (OGG1). We found that PARP1 binding to DNA nicks is altered by tension, and that UV-DDB did not act as an obligate heterodimer of DDB1 and DDB2 on UV-irradiated DNA. UV-DDB bound to UV photoproducts with an average lifetime of 39 seconds (corrected for photobleaching, τc), whereas binding lifetimes to 8-oxoG adducts were < 1 second. Catalytically inactive OGG1 variant K249Q bound oxidative damage 23-fold longer than WT OGG1, at 47 and 2.0 s, respectively. By measuring three fluorescent colors simultaneously, we also characterized the assembly and disassembly kinetics of UV-DDB and OGG1 complexes on DNA. Hence, the SMADNE technique represents a novel, scalable, and universal method to obtain single-molecule mechanistic insights into key protein-DNA interactions in an environment containing physiologically-relevant nuclear proteins.

Cooperative interaction between AAG and UV-DDB in the removal of modified bases.

UV-DDB is a DNA damage recognition protein recently discovered to participate in the removal of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) by stimulating multiple steps of base excision repair (BER). In this study, we examined whether UV-DDB has a wider role in BER besides oxidized bases and found it has specificity for two known DNA substrates of alkyladenine glycosylase (AAG)/N-methylpurine DNA glycosylase (MPG): 1, N6-ethenoadenine (ϵA) and hypoxanthine. Gel mobility shift assays show that UV-DDB recognizes these two lesions 4-5 times better than non-damaged DNA. Biochemical studies indicated that UV-DDB stimulated AAG activity on both substrates by 4- to 5-fold. Native gels indicated UV-DDB forms a transient complex with AAG to help facilitate release of AAG from the abasic site product. Single molecule experiments confirmed the interaction and showed that UV-DDB can act to displace AAG from abasic sites. Cells when treated with methyl methanesulfonate resulted in foci containing AAG and UV-DDB that developed over the course of several hours after treatment. While colocalization did not reach 100%, foci containing AAG and UV-DDB reached a maximum at three hours post treatment. Together these data indicate that UV-DDB plays an important role in facilitating the repair of AAG substrates.

Novel viral splicing events and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts.

Adenovirus is a common human pathogen that relies on host cell processes for transcription and processing of viral RNA and protein production. Although adenoviral promoters, splice junctions, and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not fully capture the complexity of the adenoviral transcriptome. By combining Illumina short-read and nanopore long-read direct RNA sequencing approaches, we mapped transcription start sites and RNA cleavage and polyadenylation sites across the adenovirus genome. In addition to confirming the known canonical viral early and late RNA cassettes, our analysis of splice junctions within long RNA reads revealed an additional 35 novel viral transcripts that meet stringent criteria for expression. These RNAs include fourteen new splice junctions which lead to expression of canonical open reading frames (ORFs), six novel ORF-containing transcripts, and 15 transcripts encoding for messages that could alter protein functions through truncation or fusion of canonical ORFs. In addition, we detect RNAs that bypass canonical cleavage sites and generate potential chimeric proteins by linking distinct gene transcription units. Among these chimeric proteins we detected an evolutionarily conserved protein containing the N-terminus of E4orf6 fused to the downstream DBP/E2A ORF. Loss of this novel protein, E4orf6/DBP, was associated with aberrant viral replication center morphology and poor viral spread. Our work highlights how long-read sequencing technologies combined with mass spectrometry can reveal further complexity within viral transcriptomes and resulting proteomes.

Association of long and short interpregnancy intervals with maternal outcomes.

Background: Interpregnancy interval (IPI) is spacing between live birth and beginning a new pregnancy. Both long and short IPIs have been associated with adverse maternal outcomes. There is paucity in the Indian literature regarding the impact of IPI on maternal outcomes. Materials and Methodology: The cross-sectional study was conducted in the Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, from July 2019 to June 2020. Women with previous abortions, previous stillbirth, nulliparity, or multiple pregnancies were excluded. A pre-structured pro forma was used for demographic details. IPI was categorized as <6 months, 6 to <24 months, 24 to <60 months, and 60 months. Maternal outcomes were studied, and odds ratios were calculated. Results: There were 6984 deliveries in the period. A total of 4812 women were enrolled after following the inclusion and exclusion criteria. Of 4812 women, 142 (2.9%) had IPI <6 months, 3336/4812 women (69.3%) had IPI 6 to <24 months, 1144/4812 women (23.7%) had IPI 24 to <60 months, and 3.9% women (190/4812) had IPI ≥60 months. High risk of fetal malposition (OR 3.84), fetal growth restriction (OR 2.06), and hypertension (OR 1.86) were seen in women with short IPI <6 months. Women with longer IPI (≥ 60 months) had higher chances of preterm labor (OR 3.82), oligoamnios (OR 2.54), gestational diabetes (OR 2.19), and anemia (OR 1.45). Conclusion: Three-fourths of women had IPI less than 24 months recommended as minimum interval by WHO. Efforts are needed to increase awareness and availability of contraceptive choices for postpartum women to ensure adequate spacing.

Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins.

UV-DDB, consisting of subunits DDB1 and DDB2, recognizes UV-induced photoproducts during global genome nucleotide excision repair (GG-NER). We recently demonstrated a noncanonical role of UV-DDB in stimulating base excision repair (BER) which raised several questions about the timing of UV-DDB arrival at 8-oxoguanine (8-oxoG), and the dependency of UV-DDB on the recruitment of downstream BER and NER proteins. Using two different approaches to introduce 8-oxoG in cells, we show that DDB2 is recruited to 8-oxoG immediately after damage and colocalizes with 8-oxoG glycosylase (OGG1) at sites of repair. 8-oxoG removal and OGG1 recruitment is significantly reduced in the absence of DDB2. NER proteins, XPA and XPC, also accumulate at 8-oxoG. While XPC recruitment is dependent on DDB2, XPA recruitment is DDB2-independent and transcription-coupled. Finally, DDB2 accumulation at 8-oxoG induces local chromatin unfolding. We propose that DDB2-mediated chromatin decompaction facilitates the recruitment of downstream BER proteins to 8-oxoG lesions.

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of the membranes.

Preterm birth is a leading cause of perinatal morbidity and mortality and Preterm premature rupture of the membranes (PPROM) is a major risk factor contributing to approximately one third of preterm deliveries. Vaginal infections are often associated with PPROM and are characterised by loss of lactobacillin normal vaginal flora and overgrowth of other pathogenic microorganisms. Probiotics appear to have an emerging role in prolonging pregnancy after PPROM. This trial compared the efficacy of a vaginal probiotic in combination with standard antibiotic prophylaxis versus only antibiotic in prolongation of latency period and on perinatal outcome in cases of PPROM between 24 and 34 weeks. Although no significant difference was observed in the mean latency period (p = 0.937) and mean gestational age at birth (p = 0.863) between the two groups, the overall neonatal outcome was better in the study group. There is need of further large-scale clinical trials to demonstrate effectiveness of probiotics.IMPACT STATEMENTWhat is already known on this subject? PPROM is an important cause of preterm birth. Prematurity leads significant global burden of neonatal morbidity and mortality. Antibiotics in PPROM have a proven benefit to prolong latency period from start of PPROM to birth. Probiotics have a role in improving vaginal flora and reducing infections and have been tried in PPROM.What do the results of this study add? The usefulness of probiotics in prolonging latency period and improving neonatal outcome has been reported in limited trials. In our study it has shown an improvement in neonatal outcome overall but not statistically significant compared to few studies which have reported significant beneficial effects. This might be due to existence of variation in the type of the vaginal microflora in different study population.What are the implications of these findings for clinical practice and/or further research? Preliminary results suggest that use of probiotic may benefit women with PPROM. This also implies need of multicentric larger scales trials with different types of probiotics so as to clarify whether any intervention in vaginal microflora can lead to any benefits in reducing the prematurity and its consequence, both on the neonate and heath care infrastructure.

Correlation of Insulin Resistance in Pregnancy with Obstetric Outcome.

INTRODUCTION: Pregnancy is characterized by a series of metabolic changes that promote insulin resistance. This could be due to increase in the plasma levels of one or more pregnancy-related hormones such as oestrogen, progesterone, prolactin, cortisol, and human placental lactogen (HPL). The increased insulin resistance in pregnancy is associated with development of diabetes which has implications for the future gestations also. AIMS AND OBJECTIVES: To determine status of insulin resistance in pregnant women and correlate the presence of insulin resistance with obstetric outcome. MATERIAL AND METHOD: A prospective cohort study was conducted in the Department of Obstetrics and Gynaecology, KGMU, Lucknow, over a period of one year. Total 150 pregnant women were enrolled from OPD, out of which 136 women were followed up till delivery. Insulin resistance was calculated by HOMA IR index, twice in whole antenatal period (first in early pregnancy and second in late pregnancy). All women were also tested for GDM by DIPSI test (plasma glucose value after 2 h of 75 gm glucose load irrespective of last meal) as per protocol. RESULTS: In our study, we found 71 women out of 136 (52.2%) were GDM. Total 30 women out of 136 (22.05%) were GGI (Gestational Glucose Intolerance), and total 38 out of 136 (27.9%) women were found to have insulin resistance using HOMA IR ≥ 2 as cut off. Significant correlation was found in between BMI and insulin resistance (p = 0.001) and between GDM and insulin resistance (p = 0.001). Relative risk of development of complications like Preeclampsia, neonatal hypoglycemia, and respiratory distress syndrome was higher in women having insulin resistance and GDM. CONCLUSION: Obstetric complications like preeclampsia, neonatal hypoglycemia, and respiratory distress syndrome are more likely to occur in women with insulin resistance, but larger studies are required to delineate whether insulin resistance alone without development of GDM will have the same implication.

Chaperones for dancing on chromatin: Role of post-translational modifications in dynamic damage detection hand-offs during nucleotide excision repair.

We highlight a recent study exploring the hand-off of UV damage to several key nucleotide excision repair (NER) proteins in the cascade: UV-DDB, XPC and TFIIH. The delicate dance of DNA repair proteins is choreographed by the dynamic hand-off of DNA damage from one recognition complex to another damage verification protein or set of proteins. These DNA transactions on chromatin are strictly chaperoned by post-translational modifications (PTM). This new study examines the role that ubiquitylation and subsequent DDB2 degradation has during this process. In total, this study suggests an intricate cellular timer mechanism that under normal conditions DDB2 helps recruit and ubiquitylate XPC, stabilizing XPC at damaged sites. If DDB2 persists at damaged sites too long, it is turned over by auto-ubiquitylation and removed from DNA by the action of VCP/p97 for degradation in the 26S proteosome.

The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage.

The six major mammalian DNA repair pathways were discovered as independent processes, each dedicated to remove specific types of lesions, but the past two decades have brought into focus the significant interplay between these pathways. In particular, several studies have demonstrated that certain proteins of the nucleotide excision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the removal of oxidative lesions. This review focuses on recent data showing how the NER proteins, XPA, XPC, XPG, CSA, CSB and UV-DDB, work to stimulate known glycosylases involved in the removal of certain forms of base damage resulting from oxidative processes, and also discusses how some oxidative lesions are probably directly repaired through NER. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we detail how we believe UV-DDB may be the first responder in altering the structure of damage containing-nucleosomes, allowing access to BER enzymes.

Pregnancy in women with previous two healthy children, associated factors, and acceptability of contraception among these women: A questionnaire-based, cross-sectional KAP study in world's second most populated country advocating two-child norm.

INTRODUCTION: Indian subcontinent carries 17 % of world's population, being the second largest populated country. The maternal mortality rate of the country is still high. The study was aimed to study factors leading to pregnancy in women with previous two living children and their knowledge about limiting family and their practice for use of contraceptives. METHODS: Questionnaire-based study was conducted in the Department of Obstetrics and Gynaecology. RESULTS: 961 pregnant women attending antenatal outpatient department were interrogated and amongst them 167 (17.3 %) multigravida with previous two healthy children were enrolled in study and were asked to document in Questionnaire. Reasons for current pregnancy were gender bias, no desire to limit family, incorrect contraceptive use, contraceptive failure, doctor's mistake and religious belief. Desire for male child emerged as most common reason (37%) followed by improper or no use of contraception. Most significant associated factor was poor education of female partner (p = 0.010). CONCLUSION: This cross-sectional study evaluated the possible reasons of multiparity. We conclude that preference for male gender child is still very much prevalent in India, along with unmet need of family planning. Improving education of women might help to change attitude towards birth spacing and family size.

Expanding molecular roles of UV-DDB: Shining light on genome stability and cancer.

UV-damaged DNA binding protein (UV-DDB) is a heterodimeric complex, composed of DDB1 and DDB2, and is involved in global genome nucleotide excision repair. Mutations in DDB2 are associated with xeroderma pigmentosum complementation group E. UV-DDB forms a ubiquitin E3 ligase complex with cullin-4A and RBX that helps to relax chromatin around UV-induced photoproducts through the ubiquitination of histone H2A. After providing a brief historical perspective on UV-DDB, we review our current knowledge of the structure and function of this intriguing repair protein. Finally, this article discusses emerging data suggesting that UV-DDB may have other non-canonical roles in base excision repair and the etiology of cancer.

Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins.

Base and nucleotide excision repair (BER and NER) pathways are normally associated with removal of specific types of DNA damage: small base modifications (such as those induced by DNA oxidation) and bulky DNA lesions (such as those induced by ultraviolet or chemical carcinogens), respectively. However, growing evidence indicates that this scenario is much more complex and these pathways exchange proteins and cooperate with each other in the repair of specific lesions. In this review, we highlight studies discussing the involvement of NER in the repair of DNA damage induced by oxidative stress, and BER participating in the removal of bulky adducts on DNA. Adding to this complexity, UVA light experiments revealed that oxidative stress also causes protein oxidation, directly affecting proteins involved in both NER and BER. This reduces the cell's ability to repair DNA damage with deleterious implications to the cells, such as mutagenesis and cell death, and to the organisms, such as cancer and aging. Finally, an interactome of NER and BER proteins is presented, showing the strong connection between these pathways, indicating that further investigation may reveal new functions shared by them, and their cooperation in maintaining genome stability.

Pilot Interventional Study Comparing Fetomaternal Outcomes of 150 mg Versus 75 mg Aspirin Starting Between 11 and 14 Weeks of Pregnancy in Patients with High Risk of Preeclampsia: A Randomized Control Trial.

INTRODUCTION: Hypertensive disorders of pregnancies complicate around 5-10% of pregnancies worldwide, and together they are a member of the deadly triad along with haemorrhage and infection that contribute to a significant amount of maternal morbidity and mortality. AIMS AND OBJECTIVES: To compare differences in the fetomaternal outcomes with the use of 150 mg aspirin versus 75 mg aspirin in pregnant women found to be at high risk of PE. METHODOLOGY: This was a two-armed double-blind parallel randomized control trial conducted in the Department of Obstetrics and Gynaecology, King George's Medical University, carried over a period of 1 year. RESULTS: Preeclampsia occurred in 15 of 87 participants (17%) in the 75 mg aspirin group compared with 6 of 91 (6.5%) in the 150 mg aspirin group. There were a significantly higher incidence of PE, its severity and lesser period of gestation at delivery in the group given 75 mg dose compared to the group given 150 mg dose. There were significantly higher values of mean arterial pressure and uterine artery PI in women who developed preeclampsia compared to those who do not in both the groups. Foetal outcomes were observed in both the groups of women, and there was no statistically significant difference between them. CONCLUSION: This randomized trial showed that among women with singleton pregnancies who were identified by means of first-trimester screening as being at high risk of preterm preeclampsia, use of aspirin 150 mg per day started between 11 and 14 weeks till 36 weeks is a potent intervention to reduce the development of both early- and late-onset preeclampsia as compared to a dose of 75 mg per day.