Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Clinical consequences of gestational diabetes mellitus and maternal obesity as defined by asian BMI thresholds in Viet Nam: a prospective, hospital-based, cohort study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) is common in South East Asia, occurring at relatively lean Body Mass Index (BMI). Outside pregnancy, cardiometabolic risks increase at lower BMI in Asian populations, justifying Asian-specific thresholds for overweight and obesity. We aimed to explore the effects of GDM and obesity on perinatal outcomes using a WHO expert consultation-recommended Asian-specific definition of obesity. METHODS: This is a secondary analysis of a prospective, hospital-based, cohort study in Ho Chi Minh City. Participants were recruited from antenatal clinics between 19+ 0-22+ 6 weeks gestation and followed until delivery. GDM screening occurred between 24 and 28 weeks using WHO criteria. Obesity was defined as BMI ≥ 27.5 kg/m2, based on weight and height at recruitment. We assessed associations between GDM (singly, and in combination with obesity) and perinatal outcomes. Participants were categorised into four groups: no GDM/non-obese (reference group), GDM/non-obese, no GDM/obese and GDM/obese. Outcomes included primary caesarean section, hypertensive disorders of pregnancy (HDP), large-for-gestational-age (LGA), birth weight, preterm birth, and composite adverse neonatal outcome. Logistic and linear regressions were performed with adjustment for differences in baseline characteristics. RESULTS: Among 4,970 participants, 908 (18%) developed GDM. Compared to women without GDM, GDM increased risks for preterm birth (OR: 1.40, 95% CI: 1.09-1.78), higher birthweight (birthweight z-score 0.16 versus 0.09, p = 0.027), and LGA (OR 1.14, 0.89-1.46). GDM without obesity was associated with an increased risk of preterm birth (OR 1.35, 1.04-1.74). Obese women without GDM were more likely to deliver by caesarean section and have an LGA baby (1.80, 1.33-2.44 and 2.75, 1.88-4.03). The highest risks were observed amongst women with both GDM and obesity: caesarean Sect. (2.43, 1.49-3.96), LGA (3.36, 1.94-5.80) and preterm birth (2.42, 1.32-4.44). CONCLUSIONS: GDM was associated with an increased risk of preterm birth and larger newborn size. Using an Asian-specific definition of obesity, we demonstrate obese women with GDM are at the highest risk of adverse outcomes. Using a BMI threshold in pregnancy of 27.5 kg/m2 (between 19 and 22 weeks gestation) for Asian women can identify women who will benefit from intensified diabetes, nutritional, and obstetric care. This has relevance for obstetric service delivery within Asia, and other health systems providing pregnancy care for Asian expatriate women.

Effects of higher protein formula with improved fat blend on growth, feeding tolerance and nutritional biomarkers in preterm infants: A double-blind, randomized, controlled clinical trial.

BACKGROUND: Preterm formulas containing greater protein:energy ratio are beneficial for non-breastfed infants, since protein is critical for promoting catch-up growth and synthesis of lean body mass. Additionally, formulas containing enriched sn-2 palmitate (sn-2) and reduced medium chain triglycerides (MCTs) may support better feeding tolerance and nutrient utilization. METHODS: The objective of this randomized, controlled, double-blinded clinical trial is to evaluate growth, feeding tolerance and nutritional biomarkers of preterm infants with birth weight ≤2000g and gestational age ≤33wks from one neonatal unit in Vietnam receiving experimental formula (EF, n = 80) containing higher protein level of 3.4 g/100 kcal and improved fat blend with enriched sn-2 and modified level of MCTs or isocaloric control formula (CF, n = 80) containing protein level of 2.9 g/100 kcal and standard fat blend. The differences in weight gain (g/d; primary endpoint) from day 1 (D1) of full enteral feeding (FEF) until D21 between groups was evaluated for non-inferiority (margin = -2.5  g/d) and superiority (margin = 0  g/d). RESULTS: Mean weight gain was 3.09  g/d greater in EF than CF; the lower limit of 95% CI (0.31  g/d) exceeded both non-inferiority and superiority margins. There was no significant difference in length-for-age and head circumference-for-age z-score. By D79, the mean change in weight-for-age z-scores from D1 in EF group (+0.76 SDs) surpassed the criteria for catch-up growth (+0.67 SDs). Infants in the EF group (vs. CF) tended to have softer stools (EF = 3.2 ± 0.59 vs. CF = 3.4 ± 0.58; P = 0.07) based on 5-point scale (1 = watery, 5 = hard). Difference in blood urea nitrogen and biomarkers for bone mineral status (i.e., plasma phosphorus, alkaline phosphatase and urinary calcium/phosphorus ratio) between EF and CF on FEF Day 21 reached statistical significance (P < 0.05) but all mean values stayed within normal clinical ranges for both groups. CONCLUSION: Preterm formula with greater protein:energy ratio and new fat blend is safe, nutritionally suitable, well-tolerated, and improves catch-up weight gain of preterm infants. Clinical trial registry identifier is NCT03055052 (ClinicalTrials.gov).

Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses.

Background: Preterm infants are highly vulnerable to infectious disease. While many factors are likely to contribute to this enhanced susceptibility, the immature nature of the preterm immune system is postulated as one key factor. Methods: In our study, we used high-dimensional flow cytometry and cytokine assays to characterise the immune profiles in 25 preterm (range: 30.4-34.1 weeks gestational age) and 25 term infant (range: 37-40 weeks gestational age) cord blood samples. Results: We found that preterm infants exhibit reduced frequencies of monocytes, CD56bright NK cells, CD8+ T-cells, γδ T-cells and an increased frequency of intermediate monocytes, CD4+ T-cells, central memory CD4+ and CD8+ T-cells, Tregs and transitional B-cells compared to term infants. Pro-inflammatory cytokines IL-1ß, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1ß. However, IL-15 and MCP-1 were higher in preterm infants. Conclusion: Overall, we identify key differences in pro-inflammatory immune profiles between preterm and term infants. These findings may help to explain why preterm infants are more susceptible to infectious disease during early life and facilitate the development of targeted interventions to protect this highly vulnerable group.

Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.

BACKGROUND: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. METHODS: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. RESULTS: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. CONCLUSION: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
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Clinical pregnancy following GnRH agonist administration in the luteal phase of fresh or frozen assisted reproductive technology (ART) cycles: Systematic review and meta-analysis.

OBJECTIVES: To study if the GnRH agonist administration in luteal phase improves clinical pregnancy rate of fresh and frozen embryo transfer. Also, this meta-analysis compares the treatment effect of luteal GnRH agonist administration between long agonist and antagonist protocols of fresh cycles, and between two types of treatment: fresh and frozen embryo transfers. STUDY DESIGN: Systematic review and meta-analysis (registration number CRD42017059152). RESULTS: For the overall 20 studies (5497 patients), clinical pregnancy rate significantly increased in group of GnRH agonist administration compared to control group (RR 1.24, 95% CI 1.14-1.34, p < 0.0001). Regarding the treatment effect of luteal GnRH agonist administration between long agonist and antagonist protocol fresh cycles, no significant difference was observed (RR = 1.28, 95% CI 0.98-1.67, p = 0.07). Also, in comparison between fresh and frozen embryo transfer, similar effect of GnRH agonist administration was found (RR = 0.93, 95% CI 0.74-1.16, p = 0.49). CONCLUSIONS: There is evidence that GnRH agonist administration in luteal phase improve clinical pregnancy rate in both fresh and frozen cycles. Within fresh cycles, no significant difference of clinical pregnancy rate is found between two protocols. In frozen cycles, the effect of GnRH agonist administration in enhancing clinical pregnancy rate is similar to fresh cycles.