Translating n-3 polyunsaturated fatty acid status from whole blood to plasma and red blood cells during pregnancy: Translating n-3 status across blood fractions in pregnancy.

Women with low n-3 (omega-3) status in pregnancy can reduce their risk of early preterm birth (<34 weeks' gestation) through n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation. As investigators measure fatty acid status in different blood fractions, equations are needed to compare results across studies. Similarly, derived cut-points for defining low and replete n-3 status are needed to assist clinical interpretation during early pregnancy. Our aims were to develop equations to convert the percentage of total n-3 fatty acids, EPA+DHA and DHA between whole blood, plasma and red blood cells (RBC), and to derive cut-points for defining low and replete total n-3 fatty acid status in plasma and RBC from those already established in whole blood. Using blood samples from 457 pregnant women in a multicentre randomised controlled trial, equations for these interconversions were developed using simple linear regression models. Measures of n-3 fatty acid status in whole blood and plasma were strongly related (R2 > 0.85), while more moderate relationships were observed between measures in whole blood and RBC (R2 0.55 - 0.71), or plasma and RBC (R2 0.55 - 0.63). Using the conversion equations, established cut-points for low and replete n-3 status in whole blood (<4.2% and >4.9% of total fatty acids) converted to <3.7% and >4.3% of plasma total fatty acids, and to <7.3% and >8.1% of RBC total fatty acids. Agreement to define low and replete n-3 status was better between whole blood and plasma, rather than between whole blood and RBC. Our data also show that total n-3 fatty acids in plasma and serum are interchangeable. We conclude that either whole blood or plasma total n-3 fatty acids can be used to define low status in pregnancy and identify women who will most benefit from n-3 LCPUFA supplementation to reduce their risk of early birth. Further research is needed to determine the clinical utility of other fatty acid measures in various blood lipid fractions.

Systematic review and meta-analysis of vitamin D deficiency in different pregnancy on preterm birth: Deficiency in middle pregnancy might be at risk.

BACKGROUND: Current studies suggest that vitamin D deficiency during pregnancy can produce a certain effect for preterm birth (PTB), but there is no research showing whether vitamin D deficiency has a consistent effect in different pregnancies; thus, we conducted a systematic review and meta-analysis of 24 observational studies, grouping them according to the gestational age at the time of serum sampling, to investigate whether vitamin D deficiency in different periods of gestation has different effects on PTB and to provide an evidence-based basis for pregnant women to measure and supplement vitamin D. METHODS: The databases PubMed-Medline, EMBASE, the Cochrane Library, Web of Science, EBSCO, CBM, and CNKI were searched until February 2020. Two researchers independently assessed the eligibility and quality of studies, and STATA 12.0 software was used for meta-analysis. RESULT: Seven cohort studies, 13 case-control studies, and 4 cross-sectional studies were included from 2500 articles by inclusion and exclusion criteria. After adjusting for age, race, and other confounding factors, meta-analysis results showed that vitamin D deficiency in the first trimester, the second trimester, and the third trimester did not increase the risk of PTB (odds ratio (OR) = 1.01, 95% confidence interval (CI) (0.88, 1.16), P = .867; OR = 1.12, 95%CI (0.92, 1.37), P = .249; OR = 1.05, 95%CI (0.87, 1.27), P = .602). However, there was moderate heterogeneity in the study of vitamin D deficiency in the second trimester, and subgroup analysis suggested that vitamin D deficiency in the second trimester may increase the risk of PTB (OR = 1.33, 95%CI (1.15, 1.54), P = .000). A sensitivity analysis of the second trimester showed that excluding any 1 study did not significantly change the results. CONCLUSIONS: Vitamin D deficiency in early and late pregnancy may not be associated with PTB, while vitamin D deficiency in middle pregnancy is likely to have an important effect on PTB. Vitamin D levels should be measured in the second trimester of pregnancy, and vitamin D supplements should be provided if necessary.

Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis.

BACKGROUND: There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM. METHODS: This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. REGISTRATION NUMBER: 10.17605/OSF.IO/NSW54.

Plasma long-chain omega-3 fatty acid status and risk of recurrent early spontaneous preterm birth: a prospective observational study.

INTRODUCTION: A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status. However, the contemporary omega-3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. MATERIAL AND METHODS: A total of 283 high-risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39+0  weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at ≥37+0  weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15-22 weeks of gestation. RESULTS: Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth (n = 51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38-2.15, p = 0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA. CONCLUSIONS: In the majority of our participants, levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 "replete"; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.

Gestational iron deficiency anemia is associated with preterm birth, fetal growth restriction, and postpartum infections.

OBJECTIVES: Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. METHODS: We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. RESULTS: Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. CONCLUSIONS: Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system.

Is the erythropoietin-erythroferrone-hepcidin axis intact in human neonates?

In a two-part process, we assessed elements of the principal hormonal pathway regulating iron homeostasis in human neonates. Part 1: Quantifying erythropoietin (Epo), erythroferrone (ERFE), hepcidin, and relevant serum and erythrocytic iron-related metrics in umbilical cord blood from term (n = 13) and preterm (n = 10) neonates, and from neonates born to mothers with diabetes and obesity (n = 13); Part 2: Quantifying serum Epo, ERFE, and hepcidin before and following darbepoetin administration. Part 1: We measured Epo, ERFE and hepcidin in all cord blood samples. Epo and ERFE levels did not differ between the three groups. Preterm neonates had the lowest hepcidin levels, while neonates born to diabetic women with a very high BMI had the lowest ferritin and RET-He levels. Part 2: Following darbepoetin dosing, ERFE levels generally increased (p < 0.05) and hepcidin levels generally fell (p < 0.05). Our observations suggest that the Epo/ERFE/hepcidin axis is intact in the newborn period.

Predictability of transcutaneous bilirubinometry in late preterm and term infants at risk for pathological hyperbilirubinemia.

BACKGROUND: The aim was to assess the predictability of transcutaneous bilirubinometry in late preterm and term neonates at risk for pathological hyperbilirubinemia, and to identify the neonatal population in which transcutaneous bilirubin most accurately predicts serum bilirubin level (SB, mg/dl). METHODS: The correlations between transcutaneous bilirubin (TCB, mg/dl) and SB in different neonatal population subsets; and between ΔTSB (TCB-SB) and relevant neonatal variables and clinical groups were analyzed. RESULTS: TCB correlated with SB (r = 0.82, p < 0.05) in the cohort (n = 350) and in population subsets (r = 0.81-0.9, p < 0.001). Black infants with gestational age (GA) >35 weeks and chronological age (CA) >3 days recorded strongest correlation (r = 0.9, p < 0.001) followed by Blacks, and non-Black infants with CA >3 days and GA >35 weeks. ΔTSB was positive in Blacks, and in infants with CA <3 days, or with no phototherapy. ΔTSB was negative in non-Blacks, in infants with positive direct Coombs test (DC+) or those receiving phototherapy. Black race [beta (SE) = 1.3(0.33), p < 0.001] had positive, while CA [beta (SE) =-1.74 (0.36), p < 0.001], DC + status [beta (SE) =-0.72 (0.25), p = 0.004] and receipt of phototherapy [beta (SE) =-0.84 (0.21), p < 0.001] each had negative correlation with ΔTSB. ΔTSB for Blacks was >Whites, Hispanics and Asians. CONCLUSION: SB is best predicted by TCB in Black infants with CA over 3 days and GA over 35 weeks. Variability in SB estimation by TCB is race, CA and immune mediated hemolysis specific.

Associations of Vitamin D Deficiency, Parathyroid hormone, Calcium, and Phosphorus with Perinatal Adverse Outcomes. A Prospective Cohort Study.

Vitamin D deficiency during pregnancy has been linked to perinatal adverse outcomes. Studies conducted to date have recommended assessing interactions with other vitamin D-related metabolites to clarify this subject. We aimed to evaluate the association of vitamin D deficiency during early pregnancy with preterm birth. Secondary outcomes included low birth weight and small for gestational age. Additionally, we explored the role that parathyroid hormone, calcium and phosphorus could play in the associations. We conducted a prospective cohort study comprising 289 pregnant women in a hospital in Granada, Spain. Participants were followed-up from weeks 10-12 of gestation to postpartum. Serum 25-hydroxyvitamin D, parathyroid hormone, calcium, and phosphorus were measured within the first week after recruitment. Pearson's χ2 test, Mann-Whitney U test, binary and multivariable logistic regression models were used to explore associations between variables and outcomes. 36.3% of the participants were vitamin D deficient (<20 ng/mL). 25-hydroxyvitamin D concentration was inversely correlated with parathyroid hormone (ρ = -0.146, p = 0.013). Preterm birth was associated with vitamin D deficiency in the multivariable model, being this association stronger amongst women with parathyroid hormone serum levels above the 80th percentile (adjusted odds ratio (aOR) = 6.587, 95% CI (2.049, 21.176), p = 0.002). Calcium and phosphorus were not associated with any studied outcome. Combined measurement of 25-hydroxyvitamin D and parathyroid hormone could be a better estimator of preterm birth than vitamin D in isolation.

Effect of omega-3 lcpufa supplementation on maternal fatty acid and oxylipin concentrations during pregnancy.

INTRODUCTION: Omega-3 long chain polyunsaturated fatty acids (LCPUFA) have been associated with a reduction in risk for preterm birth. However, there is limited understanding of how fatty acids and their bioactive derivatives (oxylipins) change over the course of pregnancy. Here we document the changes in concentration of fatty acids and oxylipins during pregnancy and how fatty acid status and oxylipin concentrations are affected by supplementation with omega-3 LCPUFA. We also investigate the degree to which fatty acid and oxylipin changes across pregnancy are influenced by baseline omega-3 status. MATERIALS AND METHODS: We profiled the fatty acids in all lipids in dried blood spots (total blood fatty acids) by gas chromatography and free (unesterified) fatty acids and their associated oxylipins in separate dried blood spot samples by LC-MS-MS collected from a random sample of 1263 women with a singleton pregnancy who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) trial. ORIP is a double-blind, randomized controlled trial involving 5544 participants and designed to determine the effect of supplementing the diets of pregnant women with omega-3 LCPUFA on the incidence of early preterm birth. Maternal whole blood finger prick samples were collected at baseline (~14 weeks gestation) and at completion of the study intervention period (34 weeks gestation). RESULTS: The concentration of most total and free polyunsaturated fatty acids and their associated oxylipins declined over the course of pregnancy. Omega-3 LCPUFA supplementation increased total DHA and 7-HDHA and mitigated the decline in free DHA, 4-HDHA and 14-HDHA. The intervention had minimal or no effect on free EPA, LA, AA and their associated oxylipins. Omega-3 LCPUFA supplementation in women with higher omega-3 status at baseline was associated with a significant increase in 7-HDHA and 4-HDHA between the treatment and control whereas there were no differences between groups in 7-HDHA and 4-HDHA in women with intermediate or lower baseline omega-3 status. CONCLUSION: Our data suggest a differential response with or without omega-3 supplementation for DHA and DHA-derived oxylipins, which may have an important role to play in modulating pregnancy duration. Further work is needed to understand their role, which may allow us to better tailor omega-3 supplementation for preterm birth prevention.

Maternal Anaemia in Pregnancy: A Significantly Greater Risk Factor for Anaemia in Australian Aboriginal Children than Low Birth Weight or Prematurity.

OBJECTIVES: To identify maternal and perinatal risk factors associated with childhood anaemia. METHODS: A retrospective cohort study was conducted in three remote Katherine East Aboriginal communities in Northern Territory, Australia. Children born 2004-2014 in Community A and 2010-2014 in Community B and C, and their respective mothers were recruited into the study. Maternal and child data were linked to provide a longitudinal view of each child for the first 1000 days from conception to 2-years of age. Descriptive analyses were used to calculate mean maternal age, and proportions were used to describe other antenatal and perinatal characteristics of the mother/child dyads. The main outcome was the prevalence of maternal anaemia in pregnancy and risk factors associated with childhood anaemia at age 6 months. RESULTS: Prevalence of maternal anaemia in pregnancy was higher in the third trimester (62%) compared to the first (46%) and second trimesters (48%). There was a strong positive linear association (R2 = 0.46, p < 0.001) between maternal haemoglobin (Hb) in third trimester pregnancy and child Hb at age 6 months. Maternal anaemia in pregnancy (OR 4.42 95% CI 2.08-9.36) and low birth weight (LBW, OR 2.62, 95% CI 1.21-5.70) were associated with an increased risk of childhood anaemia at 6 months of age. CONCLUSIONS FOR PRACTICE: This is the first study to identify the association of maternal anaemia with childhood anaemia in the Australian Aboriginal population. A review of current policies and practices for anaemia screening, prevention and treatment during pregnancy and early childhood would be beneficial to both mother and child. Our findings indicate that administering prophylactic iron supplementation only to children who are born LBW or premature would be of greater benefit if expanded to include children born to anaemic mothers.

A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.

BACKGROUND: Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS: Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS: In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS: Higher preconception antioxidant levels are not associated with better birth outcomes.

Accuracy of the Bilicare™ transcutaneous bilirubinometer as the predischarge screening tool for significant hyperbilirubinemia in healthy term and late preterm neonates.

Background: The Bilicare™ is a new device that measures transcutaneous bilirubin (TcB) level at the ear pinna. There are only few studies which have evaluated its accuracy in clinical practice.Objective: This study aims to determine the accuracy of Bilicare™ as a predischarge screening tool in late preterm and term neonates and to define the optimal cutoff point for determining the need to measure total serum bilirubin (TSB).Methods: The 35 weeks' gestation or more and healthy neonates who underwent predischarge TSB measurement were enrolled. Bilicare™ TcB was measured within 30 minutes of blood sampling. Paired TcB and TSB data were analyzed.Results: We collected 214 paired samples. Mean age (SD) at TcB measurement was 57.17 (7.47) hours. Mean TSB (SD) was 9.79 (2.83) mg/dL. TcB showed a significant correlation with TSB (r = 0.84, r2 = 0.7). The mean difference (SD) between TcB and TSB was 0.7 (0.21) mg/dL (95%CI 0.49-0.91). TcB tended to overestimate TSB level at the TSB values of <12 mg/dL but underestimate at the higher TSB level. The accuracy of using TcB values to detect neonates who required phototherapy was 92.5%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 78.3, 94.2, 62.1, and 97.3%, respectively. If TcB +3 mg/dL was applied as a cutoff point, the sensitivity, specificity, PPV, and NPV were 100, 53.9, 20.7, and 100%, respectively.Conclusions: Bilicare™ TcB and TSB measurements were well correlated. The TcB level +3 mg/dL could detect all neonates who had significant hyperbilirubinemia requiring phototherapy during their birth hospitalization.

Is the Concentration of Cadmium, Lead, Mercury, and Selenium Related to Preterm Birth?

Environmental pollution and exposure of people to heavy metals cause many bad obstetric outcomes. Our aim is to demonstrate the role of cadmium (Cd), lead (Pb), mercury (Hg), and selenium (Se) in preterm labor etiology with a case-control study. In this study, between November 2017 and April 2018, preterm delivery mothers and term delivery mothers were compared in Çorum, Turkey. All deliveries were performed with cesarean sections and there were 30 mothers in the control group and 20 in the study group. The maternal blood, maternal urine, umbilical cord blood, and heavy metal levels in the amnion fluid in both groups were studied. Graphite furnace atomic absorption spectrometry was used to determine the blood concentration of Cd, Pb, Hg, and Se. We found lower levels of selenium in blood and urine of preterm delivery mothers and umbilical cord and amnion fluids of preterm infants (p < 0.01). We found a statistically significant positive correlation at selenium levels between mother's blood and umbilical cord blood (r (50) = 0.896, p < 0.001) and between maternal urine and amniotic fluid (r (50) = 0.841, p < 0.001). We have not found a similar correlation between mother and fetus of other metals (p > 0.05). We found that selenium levels were lower in mothers who were preterm birth in the light of the data in our study. We could not determine the positive or negative correlation of Cd, Pb, and Hg levels in blood, urine, and amniotic fluid samples with preterm birth.

Maternal postpartum plasma folate status and preterm birth in a high-risk US population.

OBJECTIVE: While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB. DESIGN: Observational study. SETTING: Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.ParticipantsMother-infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24-72 h after delivery. RESULTS: Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3-5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB. CONCLUSIONS: If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.

Effect of Milking Maneuver in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To assess the short and medium-term effects of milking maneuver (MM) compared with early cord clamping for infants born before 37 weeks of pregnancy. MATERIAL AND METHODS: 138 infants between 24+0 and 36+6 weeks of gestation were allocated to MM or early cord clamping. Primary outcomes were the requirement of red blood cell transfusions or phototherapy. RESULTS: Initial hemoglobin was significantly higher in the MM group by 1.675 g/dL (p < 0.05) and initial hematocrit by 5.36% (p < 0.05), but no differences in the need of transfusion during the first 30 days after delivery were found (RR 0.8; 95% CI 0.22-2.85). Peak serum bilirubin was similar in both groups (11,097 ± 3.21 vs. 11,247 ± 3.56 mg/dL, p = 0.837). Phototherapy requirements were higher in the MM group (RR 1.62; 95% CI 1.1-2.38). No differences regarding the need of oral iron supplementation, platelet transfusion, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, meconium aspiration syndrome, use of surfactant, days of oxygen supplementation, need of vasopressors, length of stay in the neonatal intensive care unit, or postpartum hemorrhage were found. CONCLUSION: MM does not reduce the need for red blood cell transfusions and increases phototherapy requirements in preterm infants.

Anaemia among females in child-bearing age: Relative contributions, effects and interactions of α- and ß-thalassaemia.

INTRODUCTION: Anaemia in women during pregnancy and child bearing age is one of the most common global health problems. Reasons are numerous, but in many cases only minimal attempts are made to elucidate the underlying causes. In this study we aim to identify aetiology of anaemia in women of child bearing age and to determine the relative contributions, effects and interactions of α- and ß-thalassaemia in a region of the world where thalassaemia is endemic. METHODS: A cross sectional study was conducted at the Colombo North Teaching Hospital of Sri Lanka. The patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened to identify women with anaemia during pregnancy and 253 anaemic females were randomly re-called for the study. Data were collected using an interviewer-administered questionnaire and haematological investigations were done to identify aetiologies. RESULTS: Out of the 253 females who were anaemic during pregnancy and were re-called, 8 were excluded due to being currently pregnant. Of the remaining 245 females, 117(47.8%) remained anaemic and another 22(9.0%) had non-anaemic microcytosis. Of anaemic females, 28(24.8%) were iron deficient, 40(35.4%) had low-normal serum ferritin without fulfilling the criteria for iron deficiency,18(15.3%) had ß-haemoglobinopathy trait and 20(17.0%) had α-thalassaemia trait. Of females who had non-anaemic microcytosis, 14(66.0%) had α-thalassaemia trait. In 4 females, both α- and ß-thalassaemia trait coexist. These females had higher levels of haemoglobin (p = 0.06), MCV (p<0.05) and MCH (p<0.01) compared to individuals with only ß-thalassaemia trait. A significantly higher proportion of premature births (p<0.01) and lower mean birth weights (p<0.05) were observed in patients with α-thalassaemia trait. CONCLUSIONS: Nearly one third of anaemic females in child bearing age had thalassaemia trait of which α-thalassemia contributes to a majority. Both α- and ß-thalassaemia trait can co-exist and have ameliorating effects on red cell indices in heterozygous states. α-Thalassaemia trait was significantly associated with premature births and low birth weight. It is of paramount importance to investigate the causes of anaemia in women of child bearing age and during pregnancy in addition to providing universal iron supplementation.

Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth.

BACKGROUND: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. METHODS: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. FINDINGS: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). INTERPRETATION: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Selenium deficiency and pregnancy outcome in pregnant women with HIV in Lagos, Nigeria.

OBJECTIVE: To investigate the prevalence of maternal selenium deficiency and its effects on pregnancy outcomes in pregnant women with HIV in Lagos, Nigeria. METHODS: The present descriptive cross-sectional study enrolled women aged 15-49 years with HIV who were at 14-26 weeks of a singleton pregnancy and were attending Lagos University Teaching Hospital, Lagos, Nigeria, between August 1, 2016, and April 30, 2017. Participants were selected by consecutive sampling and baseline data were collected through interviews. Venous blood samples were obtained to measure selenium concentrations, and associations between low maternal selenium concentrations (defined as <0.89 µmol/L) and pregnancy outcomes were examined using bivariate and multivariate analysis. RESULTS: The final analysis included 113 patients; selenium deficiency was recorded in 23 (20.4%) patients. Women with selenium deficiency had an approximately eight-fold higher risk of preterm delivery (adjusted odds ratio 7.61, 95% confidence interval 4.37-18.89; P=0.031) and of delivering a term neonate with a low delivery weight (adjusted odds ratio 8.11, 95% confidence interval 3.27-17.22; P=0.012), compared with women with a normal selenium concentration. CONCLUSION: The prevalence of selenium deficiency among pregnant women with HIV in Lagos was relatively high. The significant associations observed between maternal selenium deficiency and adverse pregnancy outcomes could have implications for the future management of HIV in pregnancy.

MOnitored supplementation of VItamin D in preterm infants (MOSVID trial): study protocol for a randomised controlled trial.

BACKGROUND: The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing < 1000 g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. METHODS/DESIGN: Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52 weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40 ±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52 ±2 weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. DISCUSSION: Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40 weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03087149 . Registered on 15 March 2017.