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Chile, and several Latin American countries, use the Atalah standard to assess nutritional status during pregnancy. However, this standard (underweight: pre-pregnancy body mass index (BMI)

The 14th edition of the Workshop on Recent Issues in Bioanalysis (14th WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14th WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication covers the recommendations on (Part 2A) BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation and (Part 2B) Regulatory Input. Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 3 (Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity) are published in volume 13 of Bioanalysis, issues 4, and 6 (2021), respectively.

Objective To evaluate whether pregestational obesity is associated with the risk of caesarean section in pregnant women living in a country in an advanced stage of the obstetric transition. Methods Retrospective cohort study. Data were collected from prenatal and hospital records. Pregestational obesity was defined as: body mass index, [weight(k)/height (m2)] ≥30, and caesarean sections were categorized as elective, emergency, or non-emergency/medically necessary. Biodemographic and sociodemographic characteristics, obstetric and perinatal pathologies, and maternal anthropometric variables were assessed. Chi-square and t-tests were used to compare qualitative and quantitative variables, respectively. Simple and adjusted generalized linear models were used to evaluate the association between pregestational obesity and caesarean delivery. Finally, population attributable risk was calculated. Data analysis was performed using STATA.v.14.0. Participants 2309 pregnant women with a singleton pregnancy who gave birth at a public hospital in the Metropolitan Region of Santiago, Chile in 2015. Results The prevalence of pregestational obesity was 21.4%, and the incidence of caesarean deliveries was 34.8% (33% of which corresponded to elective, 46% to emergency, and 21% to non-emergency/medically necessary caesarean deliveries). Pregestational obesity increased the risk of caesarean delivery (aRR = 1.46; 95%CI. [1.19–1.79] as well as the risk of elective (aRR = 1.74; 95%CI. [1.23–2.45]) and emergency caesarean delivery (aRR = 1.44; 95%CI. [1.03–2.00]). The population attributable risk of pregestational obesity for caesarean section was 32%. Conclusion Given the significant association between pregestational obesity and caesarean delivery, it is necessary to develop strategies to decrease obesity among women of childbearing age in order to decrease obstetric intervention.

RESUMEN Objetivos: Comparar indicadores materno-perinatales entre gestantes chilenas y peruanas en Santiago de Chile entre enero y julio del 2017. Materiales y métodos: Estudio transversal analítico en 1578 chilenas y 318 peruanas atendidas en un hospital clínico de Santiago. Se realizó un análisis comparativo de las variables materno-perinatales por nacionalidad. Se realizaron modelos logísticos crudos y ajustados con sus intervalos de confianza al 95% (IC 95%). Resultados: Las gestantes peruanas residían en promedio 5,7 años en Chile, tenían más edad (28,1 ± 6,5 vs. 26,6 ± 6,5 años), menos desocupación (52,3% vs. 60,6%), más probabilidad de ingreso tardío al control prenatal (CP) (OR: 2,17, IC 95%: 1,69-2,78) y de tener anemia (OR: 3,45, IC 95%: 2,13-5,56) asociada al ingreso tardío a CP (OR ajustado: 0,43, IC95%: 0,33-0,56). Las gestantes chilenas tuvieron una mayor probabilidad de obesidad al ingreso al CP (OR: 2,48 IC 95%: 1,81-3,41) y al parto (OR: 2,03, 1,57-2,62). Así como, de diabetes gestacional (DG) (OR: 2,12, IC 95%: 1,24-3,61), parto prematuro (OR: 2,82, IC 95%: 1,59-5,01) e hijos con bajo peso al nacer (BPN) (OR: 3,10, IC 95%: 1,51-6,33). En el modelo ajustado la obesidad se asoció en forma independiente a la DG (OR ajustado: 3,8, IC 95%: 2,44-6,18) y al BPN (OR ajustado: 3,34, IC95%: 2,33-4,85. Conclusiones: El efecto del migrante sano se observa en gestantes inmigrantes peruanas, principalmente en resultados perinatales. Es necesario favorecer el ingreso precoz a la atención prenatal, prevenir la anemia y la obesidad, para evitar resultados materno-perinatales adversos en esta población. ABSTRACT Objectives: To compare maternal and perinatal outcomes between Chilean and Peruvian pregnant women in Santiago, Chile, between January and July 2017. Materials and methods: Analytical cross-sectional study of 1,578 Chilean and 318 Peruvian women who attended a clinical hospital in Santiago. We conducted a comparative analysis of maternal and perinatal variables by nationality. Crude and adjusted logistic models were carried out with a 95% confidence interval (95% CI). Results: Peruvian pregnant women resided an average of 5.7 years in Chile, were older (28.1 ± 6.5 vs. 26.6 ± 6.5 years), had less unemployment (52.3% vs. 60.6%), were more likely to enter prenatal care (PC) late (OR: 2.17, 95% CI: 1.69-2.78) and had higher probability of having anemia (OR: 3.45, 95% CI: 2.13-5.56) associated with late entry to PC (adjusted OR: 0.43, 95% CI: 0.33-0.56). On the other hand, Chilean pregnant women were more likely to be obese upon entry to PC (OR: 2.48, 95% CI: 1.81-3.41) and at the time of delivery (OR: 2.03, 95% CI: 1.57-2.62). In addition, Chilean women had higher rates of gestational diabetes (GD) (OR: 2.12, 95% CI: 1.24-3.61), premature delivery (OR: 2.82, 95% CI: 1.59-5.01) and low birth weight (LBW) (OR: 3.10, 95% CI: 1.51-6.33). In the adjusted model, obesity was independently associated with GD (adjusted OR: 3.8, 95% CI: 2.44-6.18) and LBW (adjusted OR: 3.34, 95% CI: 2.33-4.85). Conclusions: The healthy immigrant effect was observed in pregnant Peruvian immigrants, mainly regarding the perinatal outcomes. It is necessary to promote early access to prenatal care and to stablish measures to prevent anemia and obesity, in order to avoid adverse maternal and perinatal outcomes in the studied population.

Objectives One of every four pregnant women in Chile is obese. Gestational obesity is associated with maternal metabolic complications in pregnancy (e.g., gestational diabetes, preeclampsia), but to our knowledge, there is little evidence on relationships with future metabolic risk. The aim of this study was to evaluate the association between prepregnancy obesity (prepregnancy body mass index ≥30 kg/m 2 ) or excessive gestational weight gain (GWG; according to the 2009 recommendations from the Institute of Medicine), and maternal metabolic complications 10 y postpartum in premenopausal Chilean women. Methods A prospective study was conducted. In 2006, 1067 Chilean mothers of children born in 2002—participants of the GOCS (Growth and Obesity Cohort Study)—were recruited. Mothers completed a questionnaire concerning sociodemographic, anthropometric, and pregnancy characteristics. Of the sample, 402 women were randomly selected to participate in a study related to the determinants of breast cancer risk in 2012. At follow-up, anthropometry, blood pressure, and fasting labs were measured. Complete data was available for 366 women. Results Thirty-two percent of mothers had prepregnancy overweight/obesity and 39.1% had excessive GWG. In adjusted models, prepregnancy obesity was positively associated with increased insulin resistance (odds ratio [OR], 18; 95% confidence interval [CI], 5.2–62.7), metabolic syndrome (OR, 3.3; 95% CI, 1.3–8.3), and hyperglycemia (OR, 3; 95% CI, 1.1–8.6). Prepregnancy overweight/obesity was associated with increased risk for insulin resistance, metabolic syndrome, abdominal obesity, low high-density lipoprotein cholesterol, and hypertriglyceridemia ( P Conclusions Gestational obesity was associated with maternal metabolic alterations 10 y postpartum. Prevention strategies for chronic diseases should consider prepregnancy obesity as a modifiable risk factor for future metabolic health.

Some nutritional interventions have shown their efficacy in reducing gestational weight gain (GWG); however, their applicability in routine care is limited.We assessed the effectiveness of a low-intensity and high-coverage nutritional intervention on maternal and offspring outcomes; the intervention enhanced existing nutritional health care standards and practices at the primary health care level in Chile.This study was a cluster-randomized controlled trial of 12 primary health care centers (PHCCs) from Santiago, Chile. PHCCs were randomly allocated to either nutritional intervention [intervention group (IG), n = 5] or routine care [control group (CG), n = 7]. A total of 4631 pregnant women were recruited (IG, n = 2565; and CG, n = 2066). Primary outcomes were adequate GWG and glycemic control in mothers and birth weight, birth length, macrosomia, and large for gestational age in neonates. The intervention consisted of 4 key actions: training of health care professionals on nutritional recommendations, counseling of pregnant women on diet and physical activity recommendations, offering a physical activity program implemented in the participating PHCCs, and adequate referral to dietitians. Women randomly assigned to the CG received routine antenatal care.At baseline, the mean age was 26.1 y; 45% of women were primipara and 24% were obese. No differences were found in the percentage of women achieving adequate GWG (IG: 30.3%, compared with CG: 31.3%; OR: 0.94; 95% CI: 0.81, 1.09), but women in the IG had lower GWG than those in the CG (11.3 compared with 11.9 kg; mean difference: -0.63 kg; 95% CI: -1.19, -0.08). Effects of the intervention were significantly higher in women with obesity at the begining of pregnancy (mean difference: -1.24 kg; 95% CI: -2.18, -0.30; P for interaction 0.05). No differences were found between groups regarding maternal glycemic control or neonatal outcomes.Our findings demonstrate that a low-intensity, high-coverage intervention delivered through the Chilean public health care system under standard operating conditions reduces GWG and has the potential for successful scale-up. This trial was registered at clinicaltrials.gov as NCT01916603.

PEGylated biotherapeutics can elicit anti-PEG (polyethylene glycol) immune responses in patients treated with this category of drugs. While anti-PEG antibody assays for this class of biotherapeutics have become a common element of the clinical immunogenicity testing strategy, the overall antibody incidence induced by the nanoparticle (NP) delivery system (such as ACCURINS®) has not been fully studied to date. To support the immunogenicity assessment of one of Pfizer’s NP-based therapeutics, consisting of gedatolisib (GEDA) encapsulated in ACCURINS® (GEDA-NP), we developed an anti-GEDA-NP antibody (ADA) assay on the MSD platform for the detection of GEDA-NP induced ADA in human serum. The focus of our strategy was on developing a clinically relevant ADA assay and systematically addressing assay interference through rigorous assay optimization. Our efforts led to a fit-for-purpose assay for the detection of anti-GEDA-NP ADA in serum samples obtained from breast cancer patients. Results from method qualification indicated robust assay performance, as highlighted by inter and intra-assay precision within 25% CV for all controls, and reproducible response profiles across multiple runs during the assessment of assay cut points with breast cancer samples. The assay sensitivity was between 4.3 ng/mL and 123 ng/mL for surrogate positive controls of IgG and IgM isotypes, respectively. Additionally, assay interference from nonspecific matrix proteins and circulating drug was addressed, which ensured accurate assessment of ADA incidence that can be attributed to GEDA-NP.

Anti-drug antibody (ADA) assay selectivity is evaluated during assay validation to assess the potential for individual matrices to interfere with detection of ADA. While current EMA and FDA guideline documents suggest comparative analysis with and without matrix, they do not provide specific recommendations on the acceptance criteria such as an acceptable percent positive control (PC) recovery range or positive rate. Industry has adopted an approach where recovery of PC spiked sample is expected to fall within ± 20% (80 to 120%) vs. that for the PC material spiked in negative control matrix or assay buffer. Here, it is proposed that ADA assay selectivity evaluated using a qualitative assessment of PC recovery vs. a PK-like quantitative method may be more appropriate. The PC recovery test should focus on the reliability of the method to detect the low PC level in individual samples and avoid false-negative ADA reporting. Therefore, it is proposed that assessment of high PC level as well as the assessment of quantitative percent recovery (within ± 20%) should not be included in the test. The recovery test may be viewed as acceptable should a pre-selected number of individual samples (for example at least 8 or 9 out of 10) prepared at the low PC concentration of the assay score as ADA positive.

Objective: Evaluate if an intervention based on nutritional counseling decreases total sugars and energy consumption in overweight and obese pregnant women, compared to their previous consumption and compared to women who only received routine counseling. Methods: Randomized study of two groups: dietary counseling (Intervention Group: IG) and routine counseling (Control Group: CG). The intervention consisted of three educational sessions focused on decreasing intake of foods that most contribute to sugars consumption. Changes in sugars and energy consumption were evaluated by a food frequency questionnaire before and after the intervention. Results: We evaluated 433 pregnant women, 272 in IG and 161 in CG, who before intervention had a mean consumption of 140 g total sugars and 2134 kcal energy per day. At the end of the intervention, the IG showed 15 g/day lower consumption of total sugars (95% CI: &minus, 25 and &minus, 5 g/day), 2% less total energy from sugars (95% CI: &minus, 3% and &minus, 1% g/day), and 125 kcal/day less energy than the CG (95% CI: &minus, 239 and &minus, 10 kcal/day). Table sugar, sweets, and soft drinks had the greatest reduction in consumption. Conclusions: The intervention focused on counseling on the decrease in consumption of the foods that most contribute to sugars consumption in overweight and obese pregnant women was effective in decreasing total sugars and energy consumption, mainly in the food groups high in sugars. Future studies should examine if this intervention has an effect on maternal and fetal outcomes.

International migration is an increasing public health concern, particularly regard to maternal and neonatal health.To compare obstetric and neonatal variables among native and immigrant childbearing women in a clinical hospital in Santiago, Chile.A cross-sectional, analytic study with 2598 childbearing women and their newborn examined between January and July 2015. Data were collected from clinical records by students who had previously been trained. Ethical approval was obtained from the local Ethics Committee at the hospital. All participants signed an informed consent form. A descriptive and comparative analysis was performed. For comparison, a Chi-square test was used for categorical variables, and Student t-test was used for quantitative variables.Among the included women, 41.5% (n = 1078) were immigrants. The immigrants' mean age was 28.1 ± 6.4 years, and that of natives was 26.8 ± 6.9 (p 0.001). Among natives, the obesity rate was 38.3%, as compared to 19.3% among immigrants (p 0.001). A significantly higher rate of caesarean section was seen among natives (36.8%) than among immigrants (31.7%). Obstetric morbidity, pre-eclampsia, gestational diabetes and prematurity were significantly higher among natives. There was no difference regarding low birth weights.In general, immigrants present better maternal and neonatal indicators than native women. Controversially, this is known as the 'healthy immigrant' phenomenon in the literature.

Background Lifestyle interventions are the primary prevention strategy for gestational diabetes (GDM) in obese/overweight women; however, these interventions have shown limited effectiveness. Omega-3 polyunsaturated fatty acids (PUFAs) intake has shown beneficial effects on glucose metabolism, lipid fractions and inflammatory factors in women who already have GDM. Combining PUFAs supplementation with a lifestyle intervention could achieve lower increase of glucose levels by improving insulin sensitivity. Our aim is to assess two prenatal nutritional interventions (home-based dietary counseling and/or docosahexaenoic acid (DHA) supplementation) delivered to obese/overweight women during pregnancy for them and their offspring to achieve better metabolic control. Methods/design Randomized controlled trial, 2 × 2 factorial design. Eligible pregnant women will be randomly allocated to one of the four parallel arms: 1) Home-based dietary counseling +800 mg/day DHA supplementation (n = 250); 2) 800 mg/day DHA (n = 250); 3) Home-based dietary counseling +200 mg/day DHA (n = 250); 4) 200 mg/day DHA (n = 250). Primary outcomes are: GDM; macrosomia; and neonatal insulin resistance. Data analyses will be done on an intention-to-treat basis. Discussion We expect the present study to contribute to the understanding of the potential effectiveness of an omega-3 supplementation on the risk of developing GDM in overweight/obese pregnant women. We will also test if the combination of having better dietary habits alongside with omega 3 supplementation will improve insulin sensitivity and as consequence, a lower elevation of glucose levels could be achieved. Trial Registration: NCT02574767

Background: Women in childbearing ages (WCBA) represent a strategic intervention group to reverse the global trend of increasing obesity. Aim: To conduct a review of studies reporting obesity prevalence in WCBA in Chile in the last 25 years. Material and Methods: To describe obesity prevalence, we used three approaches, namely qualitative review of studies describing obesity prevalence in WCBA and a comparative study of the prevalence of obesity, overweight, abdominal and morbid obesity in WCBA from 2003 and 2009-10 National Health Surveys (ENS). Finally, nutrition status trends of pregnant women in the period 1987-2013 were plotted. Results: According to ENS, obesity prevalence exceeded 20% and excess weight 50%, both in 2003 and 2009-10 surveys. We found seven population studies, being difficult to compare them due to the heterogeneity of obesity definitions, design, and populations. Population studies showed that the prevalence of obesity increases along with age. The higher prevalence of obesity in WCBA aged 20 to 43 years was found in the city of San Carlos in 2007 (35.5%). The lowest was found in female university students, ranging from 0% to 5.9%. Obesity in pregnant women increased from 12.9% to 32.2% in the period 1987-2004 and from 20.3% to 26.3% in the period 2005- 2013. Conclusions: There is a high and increasing prevalence of obesity among women in childbearing age, whether pregnant or not-pregnant

DHA is a critical nutrient for pregnant and lactating women, with important functions in brain development and sight acuity of the newborn. In Chile, DHA int...

BACKGROUND: Maternal obesity before and during pregnancy predicts maternal and infant risks of obesity and its associated metabolic conditions. Dietary and physical activity recommendations during pregnancy as well as weight monitoring are currently available in the Chilean primary health care system. However some of these recommendations are not updated and most of them are poorly implemented. We seek to assess the effectiveness of an intervention that enhances the implementation of updated nutrition health care standards (diet, physical activity, and breastfeeding promotion) during pregnancy on maternal weight gain and infant growth. METHODS: DESIGN & SETTING: Cluster randomized controlled trial. The cluster units will be 12 primary health care centers from two counties (La Florida and Puente Alto) from the South-East Area of Santiago randomly allocated to: 1) enhanced nutrition health care standards (intervention group) or 2) routine care (control group). PARTICIPANTS: Women seeking prenatal care before 15 weeks of gestation, residing within a catchment area of selected health centers, and who express that they are not planning to change residence will be invited to participate in the study. Pregnant women classified as high risk according to the Chilean norms (i.e age 40 years, multiple gestation, pre-gestational medical conditions, previous pregnancy-related issues) and/or underweight will be excluded. INTERVENTION: Pregnant women who attend intervened health care centers starting at their first prenatal visit will receive advice regarding optimal weight gain during pregnancy and diet and physical activity counseling-support. Pregnant women who attend control health clinics will receive routine antenatal care according to national guidelines. We plan to recruit 200 women in each health center. Assuming a 20% loss to follow up, we expect to include 960 women per arm. MAIN OUTCOME MEASURES: 1) Achievement of adequate weight gain based on IOM 2009 recommendations and adequate glycaemic control at 24-28 weeks of pregnancy according to ADA 2011, and 2) healthy infant growth during the first year of age based on WHO standards. DISCUSSION: We expect that the intervention will benefit the participants in achieving adequate weight gain & metabolic control during pregnancy as well as adequate infant growth as a result of an increased impact of standard nutrition and health care practices. Gathered information should contribute to a better understanding of how to develop effective interventions to halt the maternal obesity epidemic and its associated co-morbidities in the Chilean population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01916603.