Vitamin D supplementation during pregnancy to prevent vitamin D deficiency in newborns: a systematic review and meta-analysis / Suplementação de vitamina D durante a gravidez para a prevenção da deficiência de vitamina D em recém-nascidos: uma revisão sistemática e meta-análise

Abstract Objectives: to assess the effects of vitamin D supplementation during pregnancy on the outcomes of vitamin D concentration in newborns, length at birth, overall health (Apgar), birth weight and maternal vitamin D concentration after childbirth. Methods: this research was conducted in the electronic databases of MEDLINE, LILACS, EMBASE and Cochrane Library until December 2020, using the terms "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" and their synonyms. Randomized controlled trials were searched by evaluating the effects of maternal vitamin D supplementation in neonates. The data was analyzed on RevMan 5.4 software and the quality of evidence on GRADE. Results: the newborn's overall health condition was presented as Apgar, with a mean difference (MD) of 0.15 (CI95%=0.06-0.25; p=0.002; I2=0%, two studies, 648 participants, moderate quality evidence) at the first minute and 0.11 (CI95%=0.04-0.17; p=0.001; I2=0%, two studies, 648 participants, moderate quality evidence) at the fifth minute. Significant effects were also presented at the length at birth considering any supplemented dose (MD=0.19; CI95%=0.08-0.30; p=0.0010; I2=0%, 1452 participants, low quality evidence) and birth weight in doses higher than 4000IU/day (MD=257.05 (CI95%=137.81-376.29; p<0.0001; I2=14%, 176 participants, moderate quality evidence). Conclusion: vitamin D supplementation during pregnancy improves serum 25 (OH) D concentration and suggests positive effects on overall health condition, length at birth and birth weight. PROSPERO CRD42017073292.

Resumo Objetivos: avaliar os efeitos da suplementação materna de vitamina D durante a gravidez nos desfechos concentração de vitamina D no recém-nascido, comprimento ao nascer, estado geral de saúde (Apgar), peso ao nascer e concentração de vitamina D materna após o nascimento. Métodos: a pesquisa foi conduzida nas bases de dados eletrônicas MEDLINE, LILACS, EMBASE e Cochrane Library até dezembro de 2020, utilizando os termos "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" e seus sinônimos. Pesquisou-se por ensaios clínicos randomizados avaliando os efeitos da suplementação materna de vitamina D no neonato. Os dados foram analisados pelo software RevMan 5.4 e a avaliação da qualidade das evidências pelo GRADE. Resultados: o estado geral de saúde do recém-nascido foi apresentado como Apgar, com uma diferença de média (DM) de 0,15 (IC95%=0,06-0,25; p=0,002; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para o teste no primeiro minuto e 0,11 (IC95%=0,04-0,17; p=0,001; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para quinto minuto. Efeitos significativos também foram apresentados para o comprimento ao nascer em qualquer dose suplementada (DM=0,19 (IC95%=0,08-0,30; p=0,0010; I2=0%, 1452 participantes, evidência de baixa qualidade) e peso ao nascer em doses maiores que 4000UI/dia (DM=257,05 (IC95%=137,81-376,29; p<0,0001; I2=14%, 176 participantes, evidência de qualidade moderada). Conclusão: a suplementação de vitamina D durante a gravidez melhora a concentração sérica de 25 (OH)D e sugere apresentar efeitos positivos no estado geral de saúde, comprimento ao nascer e peso ao nascer. PROSPERO CRD42017073292.

Prenatal metal mixture concentrations and reward motivation in children.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Safety of English ivy (Hedera helix) leaf extract during pregnancy: retrospective cohort study.

BACKGROUND: English ivy (Hedera helix) is commonly used to reduce productive cough symptoms by acting as expectorant therapy. The safety of Hedera helix extract during pregnancy was not established yet. This study aims to determine the safety of English ivy leaf extract on newborns. OBJECTIVES: To determine the weight, APGAR (Activity-Pulse-Grimace-Appearance-Respiration) score, and health status of the newborns among the studied groups. METHODS: A retrospective multicenter cohort study was conducted during the fourth quarter of 2020 on 245 pregnant women and their newborns in two hospitals located in Riyadh, Saudi Arabia. The women were divided into an exposed group (N = 165) who used English ivy leaf extract syrup during pregnancy, and a control group (N = 80) who were not using any natural-pharmaceutical product for cough. RESULTS: The mean weight of the newborns in the exposed group was 3 kg compared to 2.8 kg in the control group (p-value < 0.05). The median APGAR score of the newborns in the exposed group was 8.5/10 compared to 8.0/10 in the control group (p-value > 0.05). There were no significant differences regarding the percentages of full-term and preterm newborns in the exposed and control groups (78.8% vs. 76.3%, and 21.0% vs. 24.0%, respectively, odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.45-1.63, p-value > 0.05). Regarding the newborns' health complications reported, there was no statistical difference in the percentages of full-term newborns diagnosed with at least one health complication between the exposed and control groups (0.6 vs. 3.8, OR = 0.15, 95% CI = 0.01-1.47, p-value > 0.05). CONCLUSION: Hedera helix (English ivy) leaf extract syrup was safe to be used in short term during pregnancy for the fetus.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (ß' = 0.078 (0.024-0.133); p = 0.005), head circumference (ß' = 0.060 (0.012-0.107); p = 0.02), body mass index (ß' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (ß' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

Comparison of birth weights of neonates of mothers receiving vs. not receiving zinc supplement at pregnancy.

BACKGROUND: Zinc is an essential element for normal embryogenesis and embryonic and neonatal development. Therefore, we compared the birth weights of neonates born to mothers who consumed zinc supplement during pregnancy with that of neonates born to mothers who did not. METHODS: In a cross-sectional study, we divided 200 pregnant mothers into two groups: case group (mothers receiving zinc supplement during pregnancy) and control group (mothers not receiving zinc supplement during pregnancy) Then, the neonate's cord zinc level and mother's serum level were measured and neonate's growth charts (weight, height and head circumference)were completed. RESULTS: In this study, both groups of mothers were observed to have zinc deficiency; 35% of the mothers who consumed zinc supplements and 81% of the mothers who did not consume zinc supplements (P < 0.001). Based on the results, maternal serum of zinc (P < 0.001), neonatal birth weight (P = 0.008), maternal age (P < 0.001) and parity (P < 0.01) in zinc-supplemented group were higher. Neonatal birth weight was associated moderately with mother's zinc serum levels and poorly with neonatal serum zinc levels. CONCLUSION: Zinc consumption during pregnancy increases serum zinc level of mother and neonatal weight. Neonatal weight has a higher correlation to maternal serum zinc level.

Maternal Dietary Selenium Intake during Pregnancy Is Associated with Higher Birth Weight and Lower Risk of Small for Gestational Age Births in the Norwegian Mother, Father and Child Cohort Study.

Selenium is an essential trace element involved in the body's redox reactions. Low selenium intake during pregnancy has been associated with low birth weight and an increased risk of children being born small for gestational age (SGA). Based on data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN), we studied the association of maternal selenium intake from diet and supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with birth weight and SGA status, according to population-based, ultrasound-based and customized growth standards. An increase of one standard deviation of maternal dietary selenium intake was associated with increased birth weight z-scores (ß = 0.027, 95% CI: 0.007, 0.041) and lower SGA risk (OR = 0.91, 95% CI 0.86, 0.97) after adjusting for confounders. Maternal organic and inorganic selenium intake from supplements as well as whole blood selenium concentration were not associated with birth weight or SGA. Our results suggest that a maternal diet rich in selenium during pregnancy may be beneficial for foetal growth. However, the effect estimates were small and further studies are needed to elucidate the potential impact of selenium on foetal growth.

Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis.

Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life. We performed a systematic review and meta-analysis combining human and animal studies to assess whether prenatal amino acid (AA) supplementation could be a promising approach to promote healthy fetal growth. PubMed, Embase and Cochrane libraries were searched to identify studies orally supplementing the following AA groups during gestation: (1) arginine family; (2) branched chain (BCAA); (3) methyl donors. Primary outcome was fetal/birth weight. 22 human and 89 animal studies were included in the systematic review. The arginine family, and especially arginine itself, was studied most. Our meta-analysis showed beneficial effects of arginine and (N-Carbamyl) glutamate (NCG), but not aspartic acid and citrulline on fetal/birth weight. However, no effects were reported when isonitrogenous control diet was included. BCAA and methyl donor supplementation did not affect fetal/birth weight. Arginine family supplementation, in particular arginine and NCG, improves fetal growth in complicated pregnancies. BCAA and methyl donor supplementation do not seem to be as promising to target fetal growth. Well controlled research in complicated pregnancies is needed before ruling out AA supplements or preferring arginine above other AAs.

Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study.

BACKGROUND: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AIM: The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. STUDY DESIGN: Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. SUBJECTS: Nulliparous women with singleton pregnancies. OUTCOME MEASURES: SGA (<10th customised birthweight centile). RESULTS: 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67-01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (ß 2.56 (95% CI: 0.87-4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. CONCLUSIONS: In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

A pilot study on investigating the role of Salvia miltiorrhiza in fetal growth restriction.

To date there is no effective treatment for pregnancies complicated by fetal growth restriction (FGR). Salvia miltiorrhiza, a traditional Chinese herb has been shown to promote blood flow and improve microcirculatory disturbance. In this pilot study, we evaluated whether S. miltiorrhiza can potentially become a possible therapy for FGR. Nineteen pregnant women with FGR were treated with S. miltiorrhiza and ATP supplementation for an average of 7 days, and 17 cases received ATP supplementation as controls. The estimated fetal weights (EFWs) were measured by ultrasound after treatment, and the birthweights were recorded after birth. After treatment with S. miltiorrhiza, 7 (37%) FGR cases showed an increase in EFW to above the 10th percentile, compared with 4 (23%) FGR cases in controls (odds ratio: 1.896, 95% confidence limits (CLs): 0.44-8.144). At delivery, 10 (53%) FGR cases in the treatment group delivered babies with a birthweight above the 10th percentile, compared with 6 (35%) FGR cases in the control group (odds ratio: 2.037, 95% CL: 0.532-7.793); 80 or 64% FGR cases in the treatment group showed an increase in fetal abdominal circumference (AC) or biparietal diameter (BPD) above the 10th percentile before delivery. While 44 or 30% FGR cases in the control group showed an increase in AC or BPD. No improvement of head circumference (HC) or femur length (FL) was seen. These pilot data suggest the need for multicenter randomized clinical trials on the potential of S. miltiorrhiza to improve perinatal outcome in pregnant women complicated by FGR.

Effect of a nutrient-rich, food-based supplement given to rural Vietnamese mothers prior to and/or during pregnancy on birth outcomes: A randomized controlled trial.

Obtaining a nutrient-rich diet during pregnancy is a challenge for pregnant women living in low-income countries. This randomized, controlled trial was designed to determine if a freshly prepared food supplement from local animal-source foods and dark-green leafy vegetables given prior to and/or during pregnancy improved birth outcomes in rural Vietnamese women. Primiparous women, 18 to 30 years of age, who participated in the study were assigned to one of three groups: PC-T women received the supplement from pre-conception to term, MG-T women received the supplement from mid-gestation to term, and the RPC women received routine prenatal care. Supplement intake was observed and quantified. Infant anthropometry was measured at birth and/or within seven days of delivery. The effect of the intervention on maternal and birth outcomes was determined using linear regression modeling. Of the 460 women enrolled in the study, 317 women completed the study. Those not completing the study had either moved from the area, did not conceive within 12 months of study enrollment, or miscarried. The food-based supplement increased protein, iron, zinc, folate, vitamin A and B12 intakes in the PC-T and the MG-T groups. However, it failed to alter infant anthropometric measurements at birth. In the entire cohort, maternal gestational weight gain was greater in women with a low pre-pregnancy BMI (<18.5) and in women with a higher educational attainment. Working as a farmer reduced gestational weight gain but it did not affect birth weight or length. In summary, a nutrient-rich, food-based supplement given to rural Vietnamese women from pre-conception to term or mid-gestation to term did not affect maternal or infant outcomes. The low weight gains, possibly due to demanding farm work done throughout the reproductive cycle, may have obviated any effects of the low energy, nutrient-rich food supplement on birth outcomes. Trial registration : Registered Clinical Trials.gov: NCT01235767.

Dietary supplementation with N-carbamylglycinate (CGly) improved feed source proline absorption and reproductive performance in sows.

Nutrient requirements are increased in the late-gestation period due to the faster growth of the foetal-placental unit and maternal erythrocyte mass. Glycine, proline and arginine are important amino acids that could improve foetal growth and development. The present study aims to investigate the effects of a derivative of glycine (N-carbamylglycinate, CGly) on the amino acid profiles and reproductive performances of late gestation sows. Thirty-two multiparous gestating sows (∼d 80) were selected, and randomly assigned into two groups: (1) control and (2) treatment (CGly, 800 mg kg-1) from day 85 of gestation to parturition. The serum amino acid profiles at day 110 of gestation and reproductive performance were investigated. The results showed that dietary supplementation of CGly in the late gestation period significantly improved the levels of glycine (p < 0.05) and proline (p < 0.01) in the serum of the perinatal sows, and thereafter improved the litter birth weights (p < 0.05) and number born alive (p < 0.1). Based on the in vitro studies, the improvement of proline levels is probably due to the induced expression of SLC6A20 and SLC38A2. Further studies should focus on the details of amino acid absorption, especially the competitive and cooperative absorption processes for different amino acids and derivatives.

Effects of Maternal Vitamin D3 Supplementation on Offspring Epigenetic Clock of Gestational Age at Birth: A Post-hoc Analysis of a Randomized Controlled Trial.

Vitamin D could be beneficial for healthy ageing in humans. We previously found that vitamin D supplementation may slow down epigenetic ageing in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that maternal vitamin D supplementation would slow down the epigenetic gestational age acceleration (GAA) in newborn babies. Ninety-two pregnant women (aged 29.6 ± 4.8 y; 21% African Americans, 28% Hispanics) were randomized to receive 4000 IU/day vitamin D3 or placebo, plus prenatal vitamins containing 400 IU vitamin D3 during pregnancy in a randomized controlled trial (RCT). Cord blood genome-wide methylation analysis was performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age was calculated based on two calculations developed by Knight and Bohlin. DNA methylation gestational ages calculated by Knight's clock and Bohlin' clock were highly correlated with the gestational age in the placebo group (correlation coefficients = 0.88, p s< 0.001, respectively). GAA was associated with higher birth weight (p = 0.039). In the entire cohort, vitamin D3 supplementation was not associated with GAA (p > 0.05). However, vitamin D3 supplementation decreased GAA by both Knight's clock (ß = -0.89, p = 0.047) and Bohlin's clock (ß = -0.71, p = 0.005) in the African American participants. Maternal vitamin D3 supplementation may slow down the epigenetic gestational ageing process in African American neonates. Long-term follow-up studies are warranted to determine the role of epigenetic age acceleration in the growth and development of offspring.

Glucosamine Supplementation in Premating Drinking Water Improves Within-Litter Birth Weight Uniformity of Rats Partly through Modulating Hormone Metabolism and Genes Involved in Implantation.

Within-litter birth weight variation in multiparous animals has become a big issue due to high incidence of low birth weight neonates, which gives rise to high preweaning mortality and morbidity. Foetus with various birth weights is the outcome of diverse embryos competence which is affected by oocyte quality. Glucosamine (GlcN) has been reported to be involved in oocyte maturation; however, its effect on pregnant outcomes remains unknown. The present study was conducted to investigate the effects of premating GlcN supplementation via drinking water on within-litter birth weight variation and its underlying mechanism. Fifty eight Sprague-Dawley female rats were randomly assigned to one of two groups with normal drinking water or drinking water supplemented with 0.5 mM GlcN from six to eight weeks old. Variation of within-litter birth weight in the GlcN group was 5.55%, significantly lower compared with 8.17% in the control group. Birth weight was significantly increased in the GlcN group (2.27 ± 0.06) compared with the control group (2.08 ± 0.04). Both absolute and relative weights of the ovary at the end of GlcN treatment were higher in the GlcN group than in the control group (P < 0.05). In the GlcN group, there were more successfully implanted blastocysts (13.38 ± 0.63 and 15.75 ± 0.59 in the control and treatment group, respectively) with more uniform distribution along the two uterine horns compared with the control group. Besides, gene expressions of Alk3 and Bmp2 were increased in the implantation sites, while IGF-1 and Mucin-1 were decreased significantly in rats administrated with GlcN. Maternal progesterone, estradiol, and IGF-1 concentrations on D 19.5 were significantly increased, while insulin and total cholesterol levels were significantly decreased in contrast with control dams. In summary, the administration of 0.5 mM GlcN solution before mating reduced within-litter birth weight variation, accompanied with increased fetal weight. Further investigation indicated that the improved outcome of pregnancy results at least partly from the increased ovary weights of the rats, the homogeneous embryo developmental competence, the enhanced receptivity of the uterine environment, and the adjusted maternal hormone levels.

L-arginine supplementation during the final third of gestation improves litter uniformity and physical characteristics of neonatal piglet thermoregulation.

The study assessed the effects of dietary L-arginine supplementation from days 85 to 115 of gestation on sow performance, litter quality, piglet physiology and survival variables in the first 24 hr of life. Twenty multiparous sows, with a history of hyperprolificacy (more than 14 piglets per litter), were used. A completely randomized experimental design was used, consisting of two treatments: feed supplemented or not with 1% L-arginine from days 85 to 115 of gestation. The experimental unit consisted of the sow and its respective litter, using 10 replicates per treatment. The sows were distributed into the treatments based on body condition and parity. Supplementation with L-arginine reduced the within-litter standard deviation and the within-litter coefficient of variation of piglet weight at 24 hr by 54 g and 4.14 percentage points respectively (p = .029; p = .035). Supplementation with 1.0% L-arginine decreased the percentages of piglets weighing less than 800 g by 5.60 and 5.08 points at birth and at 24 hr of life respectively. Piglets from sows supplemented with L-arginine had higher (p = .088) average rectal temperatures at birth and lower (p = .030) rectal temperature at 24 hr of life in comparison with control piglets. No significant differences in placental weight or estimated colostrum production and intake were observed in the first 24 hr of life. At 24 hr of life, piglets weighing less than 1,000 g and from supplemented sows had lower (p = .048) surface/mass ratios and higher body mass index (p = .070). Piglets from supplemented sows and who weighed 1601 to 1,800 g had lower body mass index and ponderal index (p = .002; p = .003). Supplementation with L-arginine during the final third of gestation reduces the incidence of unviable piglets (<800 g) and improved litter uniformity and piglets' body conformation within the first 24 hr of life.

Maternal folic acid supplementation and infant birthweight in low- and middle-income countries: A systematic review.

The relationship between maternal folic acid supplementation in pregnancy and infant birthweight has not been well described in low- and middle-income countries. We conducted a systematic review and meta-analysis of the current evidence of the association between folic acid supplementation in pregnancy on three primary outcomes: the incidence of low birthweight, small for gestational age, and mean birthweight. Seventeen studies were identified, which satisfied the inclusion criteria, covering a total of 275,421 women from 13 cohort studies and four randomized controlled trials. For the primary outcome of mean birthweight (n = 9), the pooled mean difference between folic acid and control groups was 0.37 kg (95% confidence interval [CI]: 0.24 to 0.50), and this effect was larger in the randomized controlled trials (0.56, 95% CI: 0.15 to 0.97, n = 3). The pooled odds ratio was 0.59 for low birthweight (95% CI: 0.47 to 0.74, n = 10) among folic acid supplementation versus control. The pooled odds ratio for the association with small for gestational age was 0.63 (95% CI: 0.39 to 1.01, n = 5). Maternal folic acid supplementation in low- and middle-income countries was associated with an increased mean birthweight of infants and decreases in the incidence of low birthweight and small for gestational age.

The impact of dietary supplementation of arginine during gestation in a commercial swine herd: II. Offspring performance.

Arginine (Arg) is an important amino acid of pig fetal development; however, whether Arg improves postnatal performance is ill-defined. Therefore, the influence of Arg supplementation at different gestational stages on offspring performance was evaluated in a commercial swine herd. Sows (n = 548) were allocated into 4, diet by stage of gestation treatments: Control (n = 143; 0% suppl. Arg), or dietary treatments supplemented with 1% L-Arg (free-base; Ajinomoto Animal Nutrition North America, Inc., Chicago, IL): from 15 to 45 d of gestation (n = 138; Early-Arg); 15 d of gestation to farrowing (n = 139; Full-Arg); and from day 85 of gestation to farrowing (n = 128; Late-Arg). All offspring were individually identified and weighed at birth; at weaning, a subset was selected for evaluation of carcass performance at market. All data were analyzed using birth weight (BiWt) and age as covariates. Wean weights (WW) and prewean (PW) ADG tended to increase (P = 0.06) in progeny from sows supplemented with Arg, as compared to progeny from Control sows. Preplanned contrast comparisons revealed an increased (P = 0.03) BiWt for pigs from sows receiving 1% L-Arg prior to day 45 of gestation (Early-Arg and Full-Arg; 1.38 kg/pig), as compared to pigs from sows not supplemented prior to day 45 of gestation (Control and Late-Arg; 1.34 kg/pig). No difference in BiWt was observed (1.36 kg/pig; P = 0.68) for Arg supplementation after day 85 of gestation (Full-Arg and Late-Arg), as compared to those not receiving Arg supplementation after day 85 (Control and Early-Arg); although WW and PW ADG were greater (P = 0.02), respectively. A 3.6% decrease (P = 0.05) in peak lean accretion ADG occurred when dams received 1% L-Arg prior to day 45 of gestation (Early-Arg and Full-Arg), however, no other significant differences were detected in finishing growth parameters or carcass characteristics (P ≥ 0.1). Pig mortality rates tended (P = 0.07) to decrease in progeny of dams supplemented Arg after day 85 (3.6%) compared to dams not provided additional Arg during late gestation (4.9%). Collectively, these data suggest that Arg provided during late gestation may improve WW and PW ADG, however, finishing performance was not affected. While Arg supplementation provided some moderate production benefits, further investigation is warranted to comprehensively understand the gestational timing and biological role of Arg supplementation during fetal and postnatal development in commercial production systems.

Effect of l-carnitine supplementation and sugar beet pulp inclusion in gilt gestation diets on gilt live weight, lactation feed intake, and offspring growth from birth to slaughter1.

This study evaluated the effects of l-carnitine (CAR) and sugar beet pulp (SBP) inclusion in gilt gestation diets on gilt live weight, cortisol concentration, lactation feed intake, and lifetime growth of progeny. Eighty-four pregnant gilts (Large White × Landrace) were randomly assigned to a treatment at day 38 of gestation until parturition; Control (0% SBP, 0 g CAR), CAR (0.125 g/d CAR), SBP (40% SBP), and SBP plus CAR (40% SBP, 0.125 g/d CAR). Gilts were weighed and back-fat depth was recorded on day 38, day 90, and day 108 of gestation and at weaning. Gilt saliva samples were collected pre-farrowing and fecal consistency was scored from entry to the farrowing room until day 5 post-partum. The number of piglets born (total, live, and stillborn) and individual birth weight was recorded. Piglet blood glucose concentration was measured 24 h post-partum and pigs were weighed on day 1, day 6, day 14, day 26, day 76, day 110, and day 147 of life. Carcass data were collected at slaughter. There was no interaction between CAR and SBP for any variable measured. The SBP-fed gilts were heavier on day 90 and day 108 of gestation (P < 0.05) and lost more weight during lactation (P < 0.05) than control gilts. They also had a greater fecal consistency score (P < 0.01). Total farrowing duration, piglet birth interval, and lactation feed intakes were similar between treatments (P > 0.05). The number of piglets born (total, live, and stillborn) and piglet birth weight was likewise similar between treatments (P > 0.05). Piglets from CAR-fed gilts had lower blood glucose concentrations (P < 0.01), while piglets from SBP-fed gilts had greater blood glucose concentrations (P < 0.01). Piglets from CAR gilts had a lower average daily gain between day 1 and day 6 (P < 0.05) and day 14 and day 26 post-partum (P < 0.05) compared to piglets from control gilts. However, CAR gilts weaned a greater number of pigs (P = 0.07). Live weight and carcass weight at slaughter were heavier for pigs from CAR gilts (P < 0.05) and from SBP gilts (P < 0.05). Pigs from CAR gilts (P < 0.01) and SBP gilts (P < 0.05) had increased carcass muscle depth. In conclusion, no benefit was found from the combined feeding of CAR and SBP. Fed separately, CAR increased the live weight, carcass weight, and muscle depth of progeny at slaughter. Feeding a high SBP diet increased fecal consistency in gilts pre-farrowing and increased live weight and carcass muscle depth of progeny.

The impact of dietary supplementation of arginine during gestation in a commercial swine herd: I. Gilt reproductive performance.

Supplemental arginine (Arg) during gestation purportedly benefits fetal development. However, the benefits of a gestational Arg dietary strategy in commercial production are unclear. Therefore, the objectives of this study examined Arg supplementation during different gestational stages and the effects on gilt reproductive performance. Pubertal gilts (n = 548) were allocated into 4 treatment groups: Control (n = 143; 0% supplemental Arg) or 1 of 3 supplemental Arg (1% as fed) treatments: from 15 to 45 d of gestation (n = 138; Early-Arg); from 15 d of gestation until farrowing (n = 139; Full-Arg); or from 85 d of gestation until farrowing (n = 128; Late-Arg). At farrowing, the number of total born (TB), born alive (BA), stillborn piglets (SB), mummified fetuses (MM), and individual piglet birth weights (BiWt) were recorded. The wean-to-estrus interval (WEI) and subsequent sow reproductive performance (to third parity) were also monitored. No significant effect of supplemental Arg during any part of P0 gestation was observed for TB, BA, SB, or MM (P ≥ 0.29). Offspring BiWt and variation among individual piglet birth weights did not differ (P = 0.42 and 0.89, respectively) among treatment groups. Following weaning, the WEI was similar among treatments (average of 8.0 ± 0.8 d; P = 0.88). Litter performance over 3 parities revealed a decrease (P = 0.02) in BA for Early-Arg fed gilts compared with all other treatments, whereas TB and WEI were similar among treatments over 3 parities (P > 0.05). There was an increased proportion of sows with average size litters (12 to 16 TB) from the Full-Arg treatment sows (76.8% ± 3.7%) when compared with Control (58.7% ± 4.2%; P = 0.01); however, the proportion of sows with high (>16 TB) and low (<12 TB) litters was not different among treatments (P = 0.20). These results suggest that gestational Arg supplementation had a minimal impact on reproductive performance in first parity sows. These data underscore the complexity of AA supplementation and the need for continued research into understanding how and when utilizing a gestational dietary Arg strategy can optimize fetal development and sow performance.

Effect of live yeast supplementation to gestating sows and nursery piglets on postweaning growth performance and nutrient digestibility.

The objectives of the present study were to determine the effects of live yeast (LY) supplementation of sows during gestation and lactation and to determine the effects of supplementation of their offspring after weaning on growth performance and nutrient digestibility. A total of 40 sows were assigned to 2 dietary treatments (control vs. LY) based on parity and expected farrowing date. Birth weight, weaning weight, litter size, and mortality were measured. After weaning, 128 mixed-sex piglets (64 from each sow treatment) were selected based on their source litter and initial BW, and randomly assigned to 2 treatments (control or LY) at 4 pigs per pen (total of 32 pigs per treatment) for a 6-wk growth performance study. At the end of the growth performance trial, 2 barrows from each pen were moved to metabolism crates for total fecal collection for a digestibility trial. Addition of LY to the sow diets had no effects on birth weight, weaning weight, litter size at birth, and mortality. Piglets had greater BW on days 21 and 42 post-weaning when sows were fed diets supplemented with LY, and overall ADG was greater in piglets from sows that received LY (P < 0.05). There was no effect of sow and nursery diets on overall ADFI and G:F intake. Supplementing diets with LY during the nursery phase increased apparent total tract digestibility (ATTD) of DM, GE, and phosphorus (P) during this phase. The ATTD of GE was also greater in piglets from sows that received LY. In conclusion, LY supplementation of diets during gestation and lactation and during the nursery phase could increase ADG and ATTD of DM, GE, and P in the offspring, and this may lead to a greater lifetime growth performance in the offspring.

Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso.

BACKGROUND: Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women. METHODS: A double-blind, randomized controlled trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat. RESULTS: 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39-3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by trial arm. Half of placentae had evidence of past malaria infection. C-reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04-4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14). CONCLUSION: Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy. Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.