Prevention and Management of Iron Deficiency/Iron-Deficiency Anemia in Women: An Asian Expert Consensus.

The lack of standardized clinical practice impeding the optimal management of iron deficiency (ID) and iron deficiency anemia (IDA) in women is a global concern, particularly in the Asia-Pacific region. The aim of this study was to determine best practices through a Delphi consensus process. In Round 1, panelists were asked to rate their level of agreement with 99 statements across four domains: identification, diagnosis and assessment, prevention, and treatment of ID/IDA in women. In Round 2, panelists reappraised their ratings in view of the collective feedback and responses to Round 1. After two rounds, consensus (≥85% agreement) was reached for 84% of the Delphi statements. Experts agreed on the role of presenting symptoms and risk factors in prompting assessments of anemia and iron status in women. Experts repeatedly called for prevention, recommending preventive iron supplementation for pregnant women irrespective of anemia prevalence levels, and for non-pregnant adult women, adolescent girls, and perimenopausal women living in areas with a high prevalence of anemia. Experts unanimously agreed to prescribing oral ferrous iron as first-line therapy for uncomplicated ID/IDA. The recommendations and clinical pathway algorithms generated should be used to inform clinical practice and standardize the care of women at risk or presenting with ID/IDA in the Asia-Pacific region.

Perimortem caesarean section in COVID-19 era.

Cardiac arrest in pregnancy is very rare. Various methods have been proposed to return spontaneous circulation and prevent mortality, such as Perimortem Caesarean Section (PMCS). Since 2019, the COVID-19 pandemic has added to the difficulty in decision making and performing PMCS. Infection prevention being a priority due to the rapid spreading of the virus could cause hesitation upon initiating an emergency procedure, especially PMCS. We have reviewed the issues impacting on basic and advanced life support in adults with suspected or confirmed COVID-19.

Determining laboratory parameters in pregnant women with severe COVID-19.

Objective: Coronavirus disease causes a wide spectrum of clinical picture in pregnant women. There are still a few studies concerning laboratory parameters to differentiate the severity of coronavirus disease-19 in pregnant patients. This article aims to identify the cut-off on laboratory parameters between pregnant women with asymptomatic/mild/moderate and severe/critical coronavirus disease-19 illness. Methods: All coronavirus disease-19 pregnant women coming to Dr. Cipto Mangunkusumo hospital between January and August 2021 were recruited into this cross-sectional study. All data extracted from medical records were classified into demographic characteristics and laboratory parameters. We defined demographic characteristics as age, parity, systolic, and diastolic blood pressure, heart rate, temperature, respiratory rate, and oxygen saturation. Laboratory parameters measured in this study consisted of complete blood count, renal function test including urea, creatinine, liver function test including aspartate transferase, alanine transferase, infection marker test including procalcitonin, C-reactive protein, interleukin-6, cycle threshold values, ferritin, coagulation test including d-dimer, fibrinogen, random blood glucose, albumin, electrolytes. Data analysis was performed using SPSS statistics. Results: There were 159 cases assessed in this study consisting of 130 (81.8%) patients with asymptomatic/mild/moderate illness and 29 (18.2%) patients with severe/critical illness of coronavirus disease-19. Of 28 laboratory parameters, 12 of them were significant statistically; thus, it resulted to make a cut-off using receiver operating characteristic curve and show relative risk, and 95% confidence interval. In multivariate analysis that aspartate transferase, D-dimer, and albumin were laboratory parameters impacted to the severity of coronavirus disease-19 in pregnant women. The area under receiver operating characteristic curve was 0.834 (95% CI 0.736-0.932). Conclusion: Of all laboratory parameters, urea, aspartate transferase, alanine transferase, procalcitonin, C-reactive protein, lactate dehydrogenase (LDH), ferritin, D-dimer, random blood glucose, cycle threshold values, albumin, and chloride differs between asymptomatic/mild/moderate, and severe/critical illness coronavirus disease-19 in pregnant women; aspartate transferase, D-dimer, and albumin were laboratory parameters impacted the most to the severity of coronavirus disease-19 in pregnant women.

Decidual dendritic cells 10 and CD4+CD25+FOXP3 regulatory T cell in preeclampsia and their correlation with nutritional factors in pathomechanism of immune rejection in pregnancy.

BACKGROUND: Immune intolerance is thought to be the underlying cause of immune rejection to fetus in preeclampsia. Decidual dendritic cell-10 (DC-10) and T regulator cell (Treg) play important role to create tolerogenic environment during pregnancy. However, their roles on the specific pathomechanism of preeclampsia along with various nutritional factors have not been widely studied. AIM: To determine the number of DC-10 and Treg in preeclampsia and their correlations with decidual nutritional factors. METHOD: This was a cross-sectional study among early onset preeclampsia (EOPE), late onset preeclampsia (LOPE), and normotensive (NT) pregnancies. Decidual specimens were obtained by curettage after caesarean section. The number of DC-10 and Treg cells were counted using flow cytometry. The levels of nutritional factors (zinc, retinol, all-trans retinoic acid, vitamin D) were determined using ICP-MS and LC-MS method. RESULT: A total of 14 subjects for each group were included in the study. The DC-10 was significantly lower in both EOPE and LOPE compared to NT (p < 0.001). Treg cells were significantly higher in EOPE compare to NT (p = 0.015). There was a moderate correlation between zinc level and DC-10 (p = 0.011) and a strong correlation between retinol level and DC-10 (p = 0.002) in the NT group. A moderate correlation was found between vitamin D level and Treg cells in the NT group (p = 0.026). CONCLUSION: There was a lower number of DC-10 and higher number of Treg cells in early preeclampsia. There was no correlation between DC-10 and Treg number with decidual nutritional factors in preeclampsia.

Relationship of Placental Vascular Indices with Macroscopic, Histopathologic, and Intraoperative Blood Loss in Placenta Accreta Spectrum Disorders.

Introduction: Placenta accreta spectrum is an obstetrical complication with a high level of morbidity. The 3-dimensional (3D) power Doppler method has been widely used to improve the diagnosis. Therefore, this study aims to elucidate better the relationship of quantitative placental vascular indices towards macroscopic findings, histopathological grading, and intraoperative blood loss in the disorder. Methods: A preliminary study using a cross-sectional design was conducted on 34 clinically diagnosed women with PAS. The 3D power Doppler with the VOCAL II software was used to measure the level of vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Gross anatomical appearance and histopathology results were categorized as accreta, increta, and percreta. In addition, the intraoperative blood loss level was measured, and 1500 mL was the cutoff for massive hemorrhage. Results: The vascularity indexes were VI = 44.2 (23.7-74.9), FI = 35.4 (24.9-57), and VFI = 15.3 (8.5-41.7). The FI value was significant in comparing gross pathological stages (p=0.015) and had a moderate positive correlation in relation to blood loss (r = 0.449). VI, FI, and VFI above the cutoff values were shown to be strongly associated with blood loss ≥ 1500 cc with aOR 7.00 (95% CI 1.23-39.56), aOR 10.00 (95% CI 1.58-63.09), and aOR 9.16 (95% CI 1.53-54.59), respectively. Conclusion: This preliminary study demonstrated an initial potential of the FI value from 3D USG power Doppler to predict the depth of PAS invasion before surgery and intraoperative blood loss level.

Vitamin D supplementation higher than 2000 IU/day compared to lower dose on maternal-fetal outcome: Systematic review and meta-analysis.

INTRODUCTION: Although vitamin D is widely known as an essential micronutrient during pregnancy, the exact supplementation dose to prevent maternal-fetal outcomes remains a question. This study aims to provide a systematic review and a meta-analysis of data from randomized controlled trial on > 2000 IU/day vitamin D supplementation compared to ⩽ 2000 IU/day; and ⩽ 2000 IU/day compared to placebo, on their effects on the incidence of preeclampsia, gestational diabetes mellitus, preterm birth, and differences on birth weight. METHODS: A systematic literature search on PubMed, EBSCO-MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate randomized controlled trial studies on the effects of oral vitamin D > 2000 IU/day versus ⩽ 2000 IU/day; and ⩽ 2000 IU/day versus placebo, on preeclampsia, gestational diabetes mellitus, preterm birth and birth weight. Risk ratio, mean difference, and 95% confidence interval were calculated. RESULTS: There were a total of 27 randomized controlled trials selected. Maternal vitamin D supplementation > 2000 IU/day had a positive effect only on gestational diabetes mellitus (seven randomized controlled trials; risk ratio = 0.70, 95% confidence interval: 0.51-0.95, I2 = 0). Vitamin D supplementation ⩽ 2000 IU/day has reduced the risk of preeclampsia (three randomized controlled trials; risk ratio = 0.29, 95% confidence interval: 0.09-0.95, I2 = 0), with no significant difference when compared to > 2000 IU/day (eight randomized controlled trials; risk ratio = 0.80, 95% confidence interval: 0.51-1.24, I2 = 31). No difference in preterm birth risk and birth weight after vitamin D supplementation. The quality of evidence varies from moderate to very low certainty. The risk of preeclampsia and gestational diabetes mellitus after high-dose versus low-dose vitamin D supplementation was the ones with moderate certainty. CONCLUSION: Vitamin D supplementation > 2000 IU/day might be important to reduce the risk of gestational diabetes mellitus. Lower dose vitamin D supplementation (⩽ 2000 IU/day) seemed adequate to reduce the risk of preeclampsia, with no significant difference compared to the higher dose.

Maternal Amino Acid Status in Severe Preeclampsia: A Cross-Sectional Study.

INTRODUCTION: Preeclampsia has been one of the leading causes of maternal death in Indonesia. It is postulated that its relationship with oxidative stress may be the underlying pathology of the disease. Nutrients and amino acids have been suggested as a scavenger for oxygen-free radicals. No previous study regarding the amino acid status in preeclampsia has been conducted in women in Indonesia. METHODS: This was a cross-sectional study of a total of 64 pregnant women, 30 with normal pregnancy and 34 with severe preeclampsia. Data were obtained in Cipto Mangunkusumo National Referral Hospital in Jakarta from July to December 2020. Maternal blood samples were taken during or soon after delivery. Amino acid levels were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bivariate analysis was then performed. RESULTS: We identified 19 different levels of amino acids in this study. Four amino acids that were elevated in the preeclampsia group were phenylalanine, serine, glycine, and glutamate. Serine (331.55 vs. 287.43; p = 0.03), glycine (183.3 vs. 234.35, p = 0.03), and glutamate levels (102.23 vs. 160.70, p = 0.000) were higher in preeclamptic patients. While in the essential amino acids group, phenylalanine levels (71.5 vs. 85.5, p = 0.023) were higher, and methionine levels (16.3 vs. 12.9, p = 0.022) were lower in preeclamptic patients. CONCLUSIONS: These findings suggest that severe preeclampsia had differences in concentration of some amino acids compared to normal pregnancy. Glutamate and methionine were associated with preeclampsia. Furthermore, a more detailed study regarding amino acids in the pathomechanism of preeclampsia is suggested.

Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition.

Preeclampsia is one of the most common obstetrical complications worldwide. The pathomechanism of this disease begins with abnormal placentation in early pregnancy, which is associated with inappropriate decidualization, vasculogenesis, angiogenesis, and spiral artery remodeling, leading to endothelial dysfunction. In these processes, appropriate cellular deaths have been proposed to play a pivotal role, including apoptosis and autophagy. The proper functioning of these physiological cell deaths for placentation depends on the wellbeing of the trophoblasts, affected by the structural and functional integrity of each cellular component including the cell membrane, mitochondria, endoplasmic reticulum, genetics, and epigenetics. This cellular wellness, which includes optimal cellular integrity and function, is heavily influenced by nutritional adequacy. In contrast, nutritional deficiencies may result in the alteration of plasma membrane, mitochondrial dysfunction, endoplasmic reticulum stress, and changes in gene expression, DNA methylation, and miRNA expression, as well as weakened defense against environmental contaminants, hence inducing a series of inappropriate cellular deaths such as abnormal apoptosis and necrosis, and autophagy dysfunction and resulting in abnormal trophoblast invasion. Despite their inherent connection, the currently available studies examined the functions of each organelle, the cellular death mechanisms and the nutrition involved, both physiologically in the placenta and in preeclampsia, separately. Therefore, this review aims to comprehensively discuss the relationship between each organelle in maintaining the physiological cell death mechanisms and the nutrition involved, and the interconnection between the disruptions in the cellular organelles and inappropriate cell death mechanisms, resulting in poor trophoblast invasion and differentiation, as seen in preeclampsia.

Maternal and fetal characteristics to predict c-section delivery: A scoring system for pregnant women.

INTRODUCTION: Cesarean section is one of the most common obstetrical interventions that has been performed at an increasing rate globally, due to both medical and non-medical reasons. This study aims to develop a prediction tool for pregnant women potentially needing c-section, such that necessary preparations from the mothers, families, and health providers can be made. METHODS: A total of 603 pregnant women were recruited in the first phase of c-section prediction tool development. The association between the maternal and fetal factors on the risk of c-section were analyzed, followed by a stepwise multivariate regression analysis. In the next phase, 61 pregnant women were enrolled for external validation. Discrimination was assessed using area under the curve. The calibration plot was then made and assessed using the Hosmer-Lemeshow test. RESULTS: There were 251 (41.6%) cases of vaginal delivery and 352 (58.4%) of c-section assessed. Multivariate analysis showed that gestational age < 37 wg (OR: 1.66, 95% CI: 1.10-2.51), pre-pregnancy body mass index (underweight) (OR: 0.40, 95% CI: 0.22-0.76), no history of vaginal delivery (OR: 2.66, 95% CI: 1.76-4.02), history of uterine surgery (OR: 8.34, 95% CI: 4.54-15.30), obstetrical complications (OR: 5.61, 95% CI: 3.53-8.90), birthweight ⩾ 3500 g (OR: 4.28, 95% CI: 2.16-8.47), and non-cephalic presentation (OR: 2.74, 95% CI: 1.53-4.89) were independently associated with c-section delivery. Those parameters were included in a 7-item scoring tool, with consecutive predictive scores of 1,-1,2,3,3,2,2,1. The area under the curve result was 0.813 (95% CI: 0.779-0.847), indicating a good predictive ability. The external validation showed AUC: 0.806, 95% CI: 0.694-0.917, Hosmer-Lemeshow test p = 0.666 and calibration plot coefficient of r = 0.939. CONCLUSION: A total of 7 maternal-fetal factors were found to be strongly associated with c-section delivery, including gestational age < 37, maternal underweight body mass index, previous uterine surgery, obstetrical complications, birthweight ⩾ 3500, history of vaginal delivery, and non-cephalic presentation. Using these factors, a prediction tool was developed and validated with good quality.

Cytokines storm in COVID-19 with dengue co-infection in pregnancy: Fatal maternal and fetal outcome.

We report a 23-year-old pregnant woman who presented with acute high-grade fever, vomiting, and diarrhea for 5 days. She was first hospitalized in RSUD Tangerang-a secondary hospital based in Tangerang and were referred to Cipto Mangunkusumo General Hospital as a tertiary hospital. Initial laboratory results from previous hospital revealed leukopenia, low platelet, elevated aspartate transaminase, and alanine transaminase. Chest radiograph showed no pulmonary infiltration. Reverse transcriptase-PCR (RT-PCR) of the nasopharyngeal swab detected SARS-CoV-2, and NS1 antigen or IgM dengue-specific antibodies were positive. COVID-19 with dengue fever co-infection was diagnosed. Hemorrhagic manifestations were seen in both the mother (gum and gastrointestinal bleeding) and pregnancy (placental abruption). Patient was put on ventilator and was unfortunately lead to her death that were caused by multiorgan dysfunction failure due to co-infection of dengue and COVID-19. Both dengue and COVID-19 had similar manifestation, as it is a warning sign in pregnant patient experienced both that can lead to fatal result in mother and baby. Early diagnosis and management of co-infection is high clinical importance, especially in endemic area of dengue like Indonesia.

Oxidative Stress Induced Damage and Early Senescence in Preterm Placenta.

INTRODUCTION: Senescent cells have been demonstrated to release High Mobility Group Box 1 (HMGB1) which induces labor through an inflammatory pathway. This research is aimed at demonstrating whether telomere shortening, proinflammatory HMGB1, and oxidative damage marker 8-OHdG play a role in the placenta of preterm birth in comparison to term birth. METHOD: A cross-sectional study on 67 full thickness of the placenta obtained from mothers with term and preterm birth. Mothers with clinical signs of infection (fever > 38°C, leukocytosis > 18000/µL, or abnormal vaginal discharge) and other pregnancy complications were excluded. Real-time polymerase chain reaction was performed to measure T/S ratio and ELISA quantification to measure the amount of HMGB1 and 8-OHdG. RESULT: A total of 34 placentas from preterm and 33 placentas from term birth were examined. Maternal characteristics were comparable between the two groups. There were no statistical difference of T/S ratio (p = 0.181), HMGB1 (p = 0.119), and 8-OHdG (p = 0.144) between the preterm and term groups. HMGB1 was moderately correlated with 8-OHdG (r = 0.314). Telomere T/S ratio of the placenta did not differ between preterm and term labor despite difference in gestational age, suggesting earlier shortening in the preterm group. It is possible that critical telomere length has been achieved in both term and preterm placenta that warrants labor through senescence process. The result of our study also showed that HMGB1 was not correlated to telomere length, due to the fact that HMGB1 is not upregulated until the critical length of telomere for senescence is exhibited. CONCLUSION: Similar telomere length might be exhibited due to early telomere shortening in preterm birth that mimics the term placenta. The relationship between placental telomere shortening and HMGB1 release remains to be uncovered. Further research is needed to discover the factors leading to early telomere shortening in the placenta of preterm birth.

Long-chain polyunsaturated fatty acid (LC-PUFA) status in severe preeclampsia and preterm birth: a cross sectional study.

Long-Chain Polyunsaturated Fatty Acid (LCPUFA) is essential throughout pregnancy, since deficiency of LPUFA may linked to obstetrical complications. This study aimed to investigate LCPUFA status in severe preeclampsia and preterm birth. A cross sectional study was conducted in 104 pregnant women, which divided into normal pregnancy, severe preeclampsia and preterm birth groups. Serum percentage and concentration of total LCPUFA, omega-3, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), and arachidonic acid (AA) were measured using gas chromatography/mass spectrometry. Receiver operating characteristic (ROC), bivariate and multivariate analysis were performed. Severe preeclampsia showed the highest concentration of total PUFA and the lowest DHA percentage, with significantly higher Omega-6/Omega-3 ratio (p = 0.004) and lower omega-3 index (p < 0.002) compared to control. Preterm birth showed the least omega-3 concentrations, with significantly low omega-6 derivates (LA (p = 0.014) and AA (p = 0.025)) compared to control. LCPUFA parameters have shown to increase the risk in both conditions, particularly ALA ≤ 53 µmol/L in preeclampsia with OR 5.44, 95%CI 1.16-25.42 and preterm birth with OR 4.68, 95%CI 1.52-14.38. These findings suggest that severe preeclampsia and preterm birth have an imbalance in LCPUFA status.

The Concentration of Micronutrients and Heavy Metals in Maternal Serum, Placenta, and Cord Blood: A Cross-Sectional Study in Preterm Birth.

BACKGROUND: Preterm birth is still a global burden particularly in Indonesia. The suboptimal concentration of certain micronutrients and heavy metals is hypothesized to play a role in the mechanism of preterm birth. OBJECTIVE: This study aimed to analyze the micronutrients and heavy metals concentrations between subjects with term and preterm birth. DESIGN: A cross-sectional study was conducted during January-June 2017 in Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital, Jakarta, Indonesia. Subjects were divided into term and preterm birth groups. The measured outcomes were maternal serum, placental, and blood cord concentration of zinc, copper, iron, selenium, manganese, mercury, lead, AtRA, and 25(OH)D. RESULTS: A total of 51 pregnant women participated in this study. Term group had higher concentration of maternal serum AtRA (0.22 ± 0.07 ng/mL versus 0.12 ± 0.03 ng/mL, p <0.001), higher placental concentration of manganese {0.99 (0.38 - 1.78) µg/g versus 0.42 ± 0.18 µg/g, p <0.001}, iron (252.16 ± 170.61 µg/g versus 78.45 ± 51.73 µg/g, p <0.001), copper {2.96 ± 1.80 µg/g versus 1.62 (0.70 - 3.88) µg/g, p 0.019}, zinc {58.34 (27.88 - 124.05) µg/g versus 28.41 (1.46 - 137.69) µg/g, p 0.011}, selenium (0.31 ± 0.31 ng/g versus 0.14 ± 0.20 ng/g, p 0.024), AtRA {21.7 ± 10.69 ng/g versus 0.7 (0.42 - 5.10) ng/g, p <0.001}, and 25(OH)D {75.84 ± 45.12 ng/g versus 18.00 (5 - 88) ng/g, p <0.001}, lower placental concentration of mercury (0.20 ± 0.17 ng/g versus 20.47 ± 41.35 ng/g, p 0.019) and lead (0.02 ± 0.01 ng/g versus 0.81 ± 1.43 ng/g, p 0.009), and higher cord blood concentration of copper {32.20 (16.30 - 69.60) µg/dL versus 20.60 (5.80 - 53.30) µg/dL, p 0.006} and AtRA (0.16 ± 0.04 versus 0.07 ± 0.01, p <0.001). CONCLUSION: Preterm birth is associated with lower concentrations of micronutrients which play a role in antioxidant mechanism, as well as higher concentration of mercury and lead.

Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

BACKGROUND: Preeclampsia and intra-uterine growth restriction (IUGR) are major health problems during pregnancy affecting both mother and child. Defective placental development and failure of trophoblast differentiation during pregnancy are important aspects in the pathogenesis of both syndromes. Recent studies have shown that autophagy is involved in the trophoblast survival capacity. As vitamin D has a central role in many cellular processes, we studied the relation of vitamin D and autophagy in those processes of preeclampsia and IUGR. METHODS: Serum and placental samples from four groups of cases; normal term, IUGR, early-onset and late-onset preeclampsia, were analyzed for 25(OH)D vitamin D, sFLT1, PGF, LGALS13 in serum and vitamin D receptor (VDR), MAP1LC3B and BECN1 in placental tissues. RESULTS: There was a significant difference in the sFLT1/PGF ratio in preeclamptic cases compared to controls and IUGR. There was a significant difference between these groups in the MAP1LC3B/BECN1 ratio as marker of the trophoblast survival capacity with a significantly reduced ratio in villous trophoblast of early-onset preeclampsia. Maternal vitamin D deficiency was found in all pathological pregnancies combined with significantly reduced staining levels of placental VDR in IUGR. Finally, there was a strong and significant negative correlation between the survival capacity (MAP1LC3B/BECN1) and both maternal vitamin D and placental VDR in the preeclampsia groups. CONCLUSION: Vitamin D and intracellular VDR are strongly related to the trophoblast survival capacity in preeclampsia.

The trophoblast survival capacity in preeclampsia.

BACKGROUND: Preeclampsia has become the world's major maternal health problem putting a huge burden on mothers, newborns and also on the health systems. The pathogenesis of preeclampsia seems to include events in very early pregnancy affecting differentiation of placental villous trophoblast. The arising changes of the cell death spectrum from apoptosis via increased autophagy and aponecrosis to necrosis in turn induce systemic inflammation of the mother. METHODS: Placental tissue samples and maternal serum samples from 40 pregnant women were collected from normal pregnancy, IUGR, early-onset and late-onset preeclampsia. Immunohistochemistry for LC3B and Beclin-1 was quantified using systematic random sampling techniques. Serum levels of LDH and other markers were assessed in serum. RESULTS: Expression of the autophagy markers LC3B and Beclin-1 was significantly different between groups as was the LC3B/Beclin-1 ratio. Early-onset preeclampsia and IUGR had the highest autophagy protein expression levels, while normal pregnancy and late-onset preeclampsia had the highest LC3B/Beclin-1 ratio. Early-onset preeclampsia had the highest negative correlation with free LDH as cell defect marker. CONCLUSIONS: Autophagy plays a critical role in the cell death spectrum and cellular survival capacity of villous trophoblast. Alterations in autophagic protein expression are involved in pathological pregnancies such as preeclampsia.

Maternal and cord blood cyclophilin A in severe preeclampsia and normal pregnancy and its correlation with vitamin D and zinc.

OBJECTIVE: To investigate maternal and cord blood cyclophilin A level in severe preeclampsia compared with normal pregnancy and its correlation with vitamin D and zinc level. METHODS: We conducted a cross-sectional observational study of pregnant women who gave birth in Cipto Mangunkusumo Hospital between January and April 2014. RESULTS: Thirty-nine subjects were included. Subjects with severe preeclampsia have higher serum cyclophilin A levels compared with normotensive pregnancy (1299.60 vs. 1039.50; p 0.017). Maternal cyclophilin A, vitamin D, and zinc correlation were not statistically significant (p 0.189 & p 0.853). CONCLUSION: Cyclophilin A levels in severe preeclampsia is higher compared to normal pregnancy. There is no correlation between cyclophilin A, zinc, and vitamin D.

Effects of Bifidobacterium animalis lactis HN019 (DR10TM), inulin, and micronutrient fortified milk on faecal DR10TM, immune markers, and maternal micronutrients among Indonesian pregnant women.

BACKGROUND AND OBJECTIVES: Maternal nutrition affects fetal growth and development. This study evaluates the effects of milk powder fortified with micronutrients, docosahexaenoic acid (DHA), a prebiotic, and probiotic Bifidobacterium animalis subsp. lactis HN019 DR10TM on the micronutrient status, as well as the presence of faecal probiotic and immune markers in pregnant women. METHODS AND STUDY DESIGN: This randomised, double- blind, placebo-controlled trial was conducted at Budi Kemuliaan and Cipto Mangunkusumo Hospital in Jakarta from 2013 to 2014. A total of 104 participants were randomly allocated to receive either completely enriched milk powder (intervention group) or iron- and vitamin folic-acid-enriched milk powder (control group). Data were collected using standardised measures and were statistically analysed using the independent t or Mann-Whitney test. RESULTS: At the baseline, the micronutrient status of the participants was acceptable, except for 25-OH-vitamin D, in both the intervention and control groups. Vitamin B-1, zinc, total free fatty acid, linoleic acid, arachidonic acid, and DHA were significantly higher in the intervention group in the second trimester (p=0.014, 0.028, 0.023, 0.014, 0.001, and 0.032, respectively). Interleukin-6 and tumor necrosis factor-α levels did not significantly vary during pregnancy. B. animalis subsp. lactis DR10TM was present in the faeces of the intervention group but not the control group (61.1% vs 0%). CONCLUSION: Milk fortified with a prebiotic, probiotic, DHA and micronutrients increases the faecal concentration of the organism used for fortification in Indonesian pregnant women. This may represent an improvement in intra-partum maternal gut health.

Effect of ethnicity on first trimester biomarkers for combined trisomy 21 screening: results from a multicenter study in six Asian countries.

OBJECTIVE: To assess differences between first trimester trisomy 21 screening markers free beta chain of the human chorionic gonadotrophin (ßhCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women of six different Asian countries (China, Indonesia, Korea, Taiwan, Thailand, and Vietnam) and compare serum levels with those in women of European countries. METHODS: Median and multiple of median (MoM) values of free ßhCG and PAPP-A were determined in more than 3000 pregnant women from the Asian countries during their first trimester of pregnancy. Differences in MoM values between a European reference group from a previous multicenter evaluation and the Asian population were evaluated. Two different types of population correction factors for T21 risk estimation were assessed. RESULTS: An at least 10% difference of median MoMs between European and Asian PAPP-A values was found to be statistically significant (p < 0.0001). The specificity of the screening did not show a big difference in individual countries, when using the country-specific correction factor compared with the overall Asian correction factor (<1.4%). CONCLUSIONS: The use of a correction factor is recommended based on the differences in European and Asian MoM values. Developing country-specific medians in larger study populations can help identify clinical relevant differences and give the opportunity to explore a more accurate risk calculation.

Antioxidant supplementation in pregnant women with low antioxidant status.

AIM: The aim of this study was to investigate the benefit of antioxidant supplementation in a cohort of women with low antioxidant status and determine the changes in cell-free mRNA. MATERIAL AND METHODS: This study was a randomized, placebo-controlled trial of 8-12 weeks' pregnant women who had low antioxidant status treated with either antioxidants or control diets daily until 2 weeks' postpartum. The primary end-point was the risk of pre-eclampsia and the secondary end-point was the changes of angiogenic and anti-oxidant mRNA markers related to the outcome (ClinicalTrial.gov, number NCT01232205). RESULTS: There were 110 women enrolled in the study, randomly assigned to the supplementation (n = 52) and control group (n = 58). The overall rate of pre-eclampsia was 8.7% (nine subjects). There were significant differences (P = 0.034) between the supplementation and control group in the incidence of pre-eclampsia (2.0% [one case] and 14.5% [eight cases], respectively) and mRNA level of superoxide-dismutase, heme oxygenase-1, vascular endothelial growth factor receptor-1, endoglin and placental growth factor after supplementation. CONCLUSION: Supplementation of women with low antioxidant status with micronutrients containing antioxidants during early gestation might reduce the risk of pre-eclampsia.

Vitamin B6 supplementation in pregnant women with nausea and vomiting.

OBJECTIVE: To determine whether supplementation with vitamin B(6) improves nausea and/or vomiting in pregnancy. METHODS: This experimental study was conducted with 60 pregnant women experiencing nausea and/or vomiting prior to the 12th gestational week. Of these women, 30 were treated daily with 10mg and the remaining 30 with 1.28 mg of pyridoxine hydrochloride for 2 weeks. The primary outcome was the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score in each group at the end of treatment. RESULTS: The women experiencing nausea and/or vomiting in pregnancy had significantly lower levels of circulating vitamin B(6) (P=0.007) compared with those without this symptom. Vitamin B(6) supplementation significantly increased plasma vitamin B(6) concentration (P<0.05 in both groups). There were no significant differences in PUQE score or in plasma concentration levels of protein, dopamine, serotonin, unconjugated estriol, and ghrelin after supplementation between the 2 groups at baseline, but there was a significantly lesser decrease in PUQE score and a greater increase in vitamin B(6) level and vitamin B(6) concentration to plasma protein concentration ratios in group 1 than in group 2 after supplementation (P<0.05 for all). CONCLUSION: Although the high-supplementation group had a greater decrease in PUQE score in comparison to the low-supplementation group, the difference is unlikely to affect the severity of symptoms.