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Effects of iodine supplementation during pregnancy on pregnant women and their offspring: a systematic review and meta-analysis of trials over the past 3 decades.
Nazeri, P, Shariat, M, Azizi, F
European journal of endocrinology. 2021;(1):91-106
Abstract
OBJECTIVE The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant growth parameters and neurocognitive development using meta-analysis. METHODS A systematic review was conducted on trials published from January 1989 to December 2019 by searching MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar. For most maternal and neonatal outcomes, a narrative synthesis of the data was performed. For birth anthropometric measurements and infant neurocognitive outcomes, the pooled standardized mean differences (SMDs) with 95% CIs were estimated using fixed/random effect models. RESULTS Fourteen trials were eligible for inclusion in the systematic review, of which five trials were included in the meta-analysis. Although the findings of different thyroid parameters are inconclusive, more consistent evidence showed that iodine supplementation could prevent the increase in thyroglobulin concentration during pregnancy. In the meta-analysis, no differences were found in weight (-0.11 (95% CI: -0.23 to 0.01)), length (-0.06 (95% CI: -0.21 to 0.09)), and head circumference (0.26 (95% CI: -0.35 to 0.88)) at birth, or in cognitive (0.07 (95% CI: -0.07 to 0.20)), language (0.06 (95% CI: -0.22 to 0.35)), and motor (0.07 (95% CI: -0.06 to 0.21)) development during the first 2 years of life in infants between the iodine-supplemented and control groups. CONCLUSION Iodine supplementation during pregnancy can improve the iodine status in pregnant women and their offspring; however, according to our meta-analysis, there was no evidence of improved growth or neurodevelopmental outcomes in infants of iodine-supplemented mothers.
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Vitamin D Supplementation during Pregnancy: An Evidence Analysis Center Systematic Review and Meta-Analysis.
Gallo, S, McDermid, JM, Al-Nimr, RI, Hakeem, R, Moreschi, JM, Pari-Keener, M, Stahnke, B, Papoutsakis, C, Handu, D, Cheng, FW
Journal of the Academy of Nutrition and Dietetics. 2020;(5):898-924.e4
Abstract
BACKGROUND Given the high rates of vitamin D deficiency among pregnant women and possible effects on offspring health, a systematic review on this topic was conducted to help inform future practice guidelines. OBJECTIVE To evaluate associations between maternal vitamin D supplementation, maternal 25-hydroxyvitamin D (25(OH)D) concentrations, and health outcomes. METHODS A PubMed literature search was conducted to identify studies that examined the health effects of vitamin D supplementation during pregnancy on maternal and infant health outcomes published from 2000 to 2016. Among 976 identified publications, 20 randomized clinical trials met the inclusion criteria. The initial search was extended to include five studies published between July 2016 and September 2018. MAIN OUTCOME MEASURES Maternal and infant 25(OH)D concentrations, gestational diabetes, preeclampsia or gestational hypertension, cesarean section, maternal parathyroid hormone and calcium concentrations, and infant gestational age, birth weight, and birth length. STATISTICAL ANALYSES Mean differences, odds ratios, and 95% CIs were calculated, only for the initial search, using separate random-effects meta-analyses for each outcome. RESULTS Evidence was good or strong that maternal vitamin D supplementation significantly increased maternal (13 studies, n=18, mean difference, 14.1 ng/mL [35.2 nmol/L]; 95% CI=9.6-18.6 ng/mL [24.0-46.4 nmol/L]) and infant (nine studies, n=12; 9.7, 5.2, 14.2 ng/mL [24.2, 12.9, 35.5 nmol/L]) 25(OH)D concentrations, although heterogeneity was significant (I2=95.9% and I2=97.4, respectively, P<0.001). Evidence was fair that vitamin D supplementation significantly decreases maternal homeostatic model assessment-insulin resistance (five studies, n=7; -1.1, -1.5, -0.7) and increases infant birth weight (nine studies, n=11, 114.2, 63.4, 165.1 g), both had insignificant heterogeneity. A null effect of maternal supplementation on other maternal (preeclampsia, cesarean section) and infant (gestational age, birth length) outcomes was found. CONCLUSIONS Results show vitamin D supplementation during pregnancy improves maternal and infant 25(OH)D concentrations and may play a role in maternal insulin resistance and fetal growth. To further inform practice and policies on the amount of vitamin D, which supports a healthy pregnancy, high quality dose-response randomized clinical trials, which assess pregnancy-specific 25(OH)D thresholds, and appropriately powered clinical outcomes are needed.
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The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis.
Jayasinghe, C, Polson, R, van Woerden, HC, Wilson, P
BMC pediatrics. 2018;(1):150
Abstract
BACKGROUND Although antenatal iron supplementation is beneficial to mothers, its impact on the neurodevelopment of offspring is controversial. A systematic review and meta-analysis was undertaken to assess whether routine maternal antenatal iron supplementation confers later neurodevelopmental benefit to offspring. METHODS Electronic databases were searched using MESH terms or key words and identified papers were reviewed by two independent reviewers. The study quality was assessed using the Cochrane risk of bias assessment tool. The review was registered in the PROSPERO CRD data base. RESULTS Seven publications were identified, based on four randomised trials published between 2006 and 2016. Three of the trials were in the Asian sub-continent. A range of tools were used to evaluate neurodevelopment. Meta-analysis of outcomes from the three RCTs meeting our inclusion criteria showed minimal effect of antenatal iron supplementation on the neurodevelopment of offspring, which was not statistically significant: weighted mean difference of 0.54 (95% CI: -0.67 to 1.75); test for overall effect Z = 0.87; p = 0.38; and heterogeneity 48%. Meta-analysis of outcomes of these RCTs at later stages of development produced similar results. CONCLUSIONS The benefit of routine antenatal iron supplementation on neurodevelopment in offspring was not statistically significant in this relatively limited set of trials, and some benefit cannot be excluded in areas with a high prevalence of maternal anaemia. A large randomized controlled trial showing significant benefit would be required to modify our conclusions.
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Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews.
Shepherd, E, Salam, RA, Middleton, P, Makrides, M, McIntyre, S, Badawi, N, Crowther, CA
The Cochrane database of systematic reviews. 2017;(8):CD012077
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BACKGROUND Cerebral palsy is an umbrella term encompassing disorders of movement and posture, attributed to non-progressive disturbances occurring in the developing fetal or infant brain. As there are diverse risk factors and causes, no one strategy will prevent all cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for their contribution to prevention. OBJECTIVES To summarise the evidence from Cochrane reviews regarding the effects of antenatal and intrapartum interventions for preventing cerebral palsy. METHODS We searched the Cochrane Database of Systematic Reviews on 7 August 2016, for reviews of antenatal or intrapartum interventions reporting on cerebral palsy. Two authors assessed reviews for inclusion, extracted data, assessed review quality, using AMSTAR and ROBIS, and quality of the evidence, using the GRADE approach. We organised reviews by topic, and summarised findings in text and tables. We categorised interventions as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm or of lack of effectiveness); probably ineffective (moderate-quality evidence of harm or of lack of effectiveness); and no conclusions possible (low- to very low-quality evidence). MAIN RESULTS We included 15 Cochrane reviews. A further 62 reviews pre-specified the outcome cerebral palsy in their methods, but none of the included randomised controlled trials (RCTs) reported this outcome. The included reviews were high quality and at low risk of bias. They included 279 RCTs; data for cerebral palsy were available from 27 (10%) RCTs, involving 32,490 children. They considered interventions for: treating mild to moderate hypertension (two) and pre-eclampsia (two); diagnosing and preventing fetal compromise in labour (one); preventing preterm birth (four); preterm fetal maturation or neuroprotection (five); and managing preterm fetal compromise (one). Quality of evidence ranged from very low to high. Effective interventions: high-quality evidence of effectiveness There was a reduction in cerebral palsy in children born to women at risk of preterm birth who received magnesium sulphate for neuroprotection of the fetus compared with placebo (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.54 to 0.87; five RCTs; 6145 children). Probably ineffective interventions: moderate-quality evidence of harm There was an increase in cerebral palsy in children born to mothers in preterm labour with intact membranes who received any prophylactic antibiotics versus no antibiotics (RR 1.82, 95% CI 0.99 to 3.34; one RCT; 3173 children). There was an increase in cerebral palsy in children, who as preterm babies with suspected fetal compromise, were born immediately compared with those for whom birth was deferred (RR 5.88, 95% CI 1.33 to 26.02; one RCT; 507 children). Probably ineffective interventions: moderate-quality evidence of lack of effectiveness There was no clear difference in the presence of cerebral palsy in children born to women at risk of preterm birth who received repeat doses of corticosteroids compared with a single course (RR 1.03, 95% CI 0.71 to 1.50; four RCTs; 3800 children). No conclusions possible: low- to very low-quality evidence Low-quality evidence found there was a possible reduction in cerebral palsy for children born to women at risk of preterm birth who received antenatal corticosteroids for accelerating fetal lung maturation compared with placebo (RR 0.60, 95% CI 0.34 to 1.03; five RCTs; 904 children). There was no clear difference in the presence of cerebral palsy with interventionist care for severe pre-eclampsia versus expectant care (RR 6.01, 95% CI 0.75 to 48.14; one RCT; 262 children); magnesium sulphate for pre-eclampsia versus placebo (RR 0.34, 95% CI 0.09 to 1.26; one RCT; 2895 children); continuous cardiotocography for fetal assessment during labour versus intermittent auscultation (average RR 1.75, 95% CI 0.84 to 3.63; two RCTs; 13,252 children); prenatal progesterone for prevention of preterm birth versus placebo (RR 0.14, 95% CI 0.01 to 3.48; one RCT; 274 children); and betamimetics for inhibiting preterm labour versus placebo (RR 0.19, 95% CI 0.02 to 1.63; one RCT; 246 children).Very low-quality found no clear difference for the presence of cerebral palsy with any antihypertensive drug (oral beta-blockers) for treatment of mild to moderate hypertension versus placebo (RR 0.33, 95% CI 0.01 to 8.01; one RCT; 110 children); magnesium sulphate for prevention of preterm birth versus other tocolytic agents (RR 0.13, 95% CI 0.01 to 2.51; one RCT; 106 children); and vitamin K and phenobarbital prior to preterm birth for prevention of neonatal periventricular haemorrhage versus placebo (RR 0.77, 95% CI 0.33 to 1.76; one RCT; 299 children). AUTHORS' CONCLUSIONS This overview summarises evidence from Cochrane reviews on the effects of antenatal and intrapartum interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians and consumers to aid decision-making and evidence translation. We recommend that readers consult the included Cochrane reviews to formally assess other benefits or harms of included interventions, including impacts on risk factors for cerebral palsy (such as the reduction in intraventricular haemorrhage for preterm babies following exposure to antenatal corticosteroids).Magnesium sulphate for women at risk of preterm birth for fetal neuroprotection can prevent cerebral palsy. Prophylactic antibiotics for women in preterm labour with intact membranes, and immediate rather than deferred birth of preterm babies with suspected fetal compromise, may increase the risk of cerebral palsy. Repeat doses compared with a single course of antenatal corticosteroids for women at risk of preterm birth do not clearly impact the risk of cerebral palsy.Cerebral palsy is rarely diagnosed at birth, has diverse risk factors and causes, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane reviews assessing antenatal and intrapartum interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of interventions addressing risk factors for cerebral palsy, and consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design, and aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data, to focus research efforts on prevention.
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What characteristics of nutrition and physical activity interventions are key to effectively reducing weight gain in obese or overweight pregnant women? A systematic review and meta-analysis.
Yeo, S, Walker, JS, Caughey, MC, Ferraro, AM, Asafu-Adjei, JK
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2017;(4):385-399
Abstract
UNLABELLED Lifestyle interventions targeting gestational weight gain (GWG) report varying degrees of success. To better understand factors influencing efficacy, we reviewed randomized trials specifically among obese and overweight pregnant women. METHODS We conducted a systematic review and a meta-analysis of 32 studies with a pooled population of 5,869 overweight or obese pregnant women. Random effects models were fit to compute the weighted mean difference (WMD) in GWG between groups across studies. Subgroup analyses were conducted to compare intervention efficacy in overweight vs. obese pregnant women, and interventions delivered by prenatal care providers (PCPs) vs. non-PCPs during pregnancy. Moderator analyses ensured. RESULTS Nine (28%) of 32 studies reported significant reductions in GWG in response to intervention. Of these, six (66%) of nine were delivered by PCPs. Overall, the WMD in GWG was -1.71 (95% confidence interval [CI]: -2.55, -0.86) kg. However, interventions delivered by PCPs yielded a significantly greater reduction in GWG compared to interventions delivered by non-PCPs (WMD = -3.88 kg; 95% CI: -7.01, -0.75 vs. -0.80 kg; 95% CI: -1.32, -0.28; p for difference = 0.005). CONCLUSION When PCPs counsel nutrition and physical activity, obese and overweight pregnant women have greater success meeting GWG targets and may be more motivated to modify their behaviour than with other modes of intervention deliveries.
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Iodine supplementation for women during the preconception, pregnancy and postpartum period.
Harding, KB, Peña-Rosas, JP, Webster, AC, Yap, CM, Payne, BA, Ota, E, De-Regil, LM
The Cochrane database of systematic reviews. 2017;(3):CD011761
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BACKGROUND Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. OBJECTIVES To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. SELECTION CRITERIA Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. MAIN RESULTS We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. AUTHORS' CONCLUSIONS There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.
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Weighing as a stand-alone intervention does not reduce excessive gestational weight gain compared to routine antenatal care: a systematic review and meta-analysis of randomised controlled trials.
Fealy, SM, Taylor, RM, Foureur, M, Attia, J, Ebert, L, Bisquera, A, Hure, AJ
BMC pregnancy and childbirth. 2017;(1):36
Abstract
BACKGROUND Excessive gestational weight gain is associated with short and long-term adverse maternal and infant health outcomes, independent of pre-pregnancy body mass index. Weighing pregnant women as a stand-alone intervention during antenatal visits is suggested to reduce pregnancy weight gain. In the absence of effective interventions to reduce excessive gestational gain within the real world setting, this study aims to test if routine weighing as a stand-alone intervention can reduce total pregnancy weight gain and, in particular, excessive gestational weight gain. METHODS A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted between November 2014 and January 2016, and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Seven databases were searched. A priori eligibility criteria were applied to published literature by at least two independent reviewers. Studies considered methodologically rigorous, as per the Academy of Nutrition and Dietetics Quality Criteria Checklist for Primary Research, were included. Meta-analysis was conducted using fixed-effects models. RESULTS A total of 5223 (non-duplicated) records were screened, resulting in two RCTs that were pooled for meta-analysis (n = 1068 randomised participants; n = 538 intervention, n = 534 control). No difference in total weight gain per week was observed between intervention and control groups (weighted mean difference (WMD) -0.00 kg/week, 95% confidence interval (CI) -0.03 to 0.02). There was also no reduction in excessive gestational weight gain between intervention and control, according to pre-pregnancy body mass index (BMI). However, total weight gain was lower in underweight women (n = 23, BMI <18.5 kg/m2) in the intervention compared to control group (-0.12 kg/week, 95% CI -0.23 to -0.01). No significant differences were observed for other pregnancy, birth and infant outcomes. CONCLUSION Weighing as a stand-alone intervention is not worse nor better at reducing excessive gestational weight gain than routine antenatal care.
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Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials.
Pérez-López, FR, Pasupuleti, V, Mezones-Holguin, E, Benites-Zapata, VA, Thota, P, Deshpande, A, Hernandez, AV
Fertility and sterility. 2015;(5):1278-88.e4
Abstract
OBJECTIVE To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables. DESIGN Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING Not applicable. PATIENT(S): Pregnant women and neonates. INTERVENTION(S): PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation ± calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy. MAIN OUTCOME MEASURE(S): Measures were: circulating 25-hydroxyvitamin D [25(OH)D] levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs). RESULT(S): Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH)D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2-66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9-155.3 g) and 0.3 cm (95% CI 0.10-0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. CONCLUSION(S): Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion.
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Antenatal dietary education and supplementation to increase energy and protein intake.
Ota, E, Hori, H, Mori, R, Tobe-Gai, R, Farrar, D
The Cochrane database of systematic reviews. 2015;(6):CD000032
Abstract
BACKGROUND Gestational weight gain is positively associated with fetal growth, and observational studies of food supplementation in pregnancy have reported increases in gestational weight gain and fetal growth. OBJECTIVES To assess the effects of education during pregnancy to increase energy and protein intake, or of actual energy and protein supplementation, on energy and protein intake, and the effect on maternal and infant health outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), reference lists of retrieved studies and contacted researchers in the field. SELECTION CRITERIA Randomised controlled trials of dietary education to increase energy and protein intake, or of actual energy and protein supplementation, during pregnancy. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and checked for accuracy. Extracted data were supplemented by additional information from the trialists we contacted. MAIN RESULTS We examined 149 reports corresponding to 65 trials. Of these trials, 17 were included, 46 were excluded, and two are ongoing. Overall, 17 trials involving 9030 women were included. For this update, we assessed methodological quality of the included trials using the standard Cochrane criteria (risk of bias) and the GRADE approach. The overall risk of bias was unclear. Nutritional education (five trials, 1090 women) Women given nutritional education had a lower relative risk of having a preterm birth (two trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98, low-quality evidence), and low birthweight (one trial, 300 women) (RR 0.04, 95% CI 0.01 to 0.14). Head circumference at birth was increased in one trial (389 women) (mean difference (MD) 0.99 cm, 95% CI 0.43 to 1.55), while birthweight was significantly increased among undernourished women in two trials (320 women) (MD 489.76 g, 95% CI 427.93 to 551.59, low-quality evidence), but did not significantly increase for adequately nourished women (MD 15.00, 95% CI -76.30 to 106.30, one trial, 406 women). Protein intake increased significantly (three trials, 632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant differences were observed on any other outcomes such as neonatal death (RR 1.28, 95% CI 0.35 to 4.72, one trial, 448 women, low-quality evidence), stillbirth (RR 0.37, 95% CI 0.07 to 1.90, one trial, 431 women, low-quality evidence), small-for-gestational age (RR 0.97, 95% CI 0.45 to 2.11, one trial, 404 women, low-quality evidence) and total gestational weight gain (MD -0.41, 95% CI -4.41 to 3.59, two trials, 233 women). There were no data on perinatal death. Balanced energy and protein supplementation (12 trials, 6705 women)Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.60, 95% CI 0.39 to 0.94, five trials, 3408 women, moderate-quality evidence), and the mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26, Tau² = 1744, I² = 44%, 11 trials, 5385 women, moderate-quality evidence). There was also a significant reduction in the risk of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I² = 16%, seven trials, 4408 women, moderate-quality evidence). No significant effect was detected for preterm birth (RR 0.96, 95% CI 0.80 to 1.16, five trials, 3384 women, moderate-quality evidence) or neonatal death (RR 0.68, 95% CI 0.43 to 1.07, five trials, 3381 women, low-quality evidence). Weekly gestational weight gain was not significantly increased (MD 18.63, 95% CI -1.81 to 39.07, nine trials, 2391 women, very low quality evidence). There were no data reported on perinatal death and low birthweight. High-protein supplementation (one trial, 1051 women)High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41, moderate-quality evidence). There was no significant effect for stillbirth (RR 0.81, 95% CI 0.31 to 2.15, one trial, 529 women), neonatal death (RR 2.78, 95% CI 0.75 to 10.36, one trial, 529 women), preterm birth (RR 1.14, 95% CI 0.83 to 1.56, one trial, 505 women), birthweight (MD -73.00, 95% CI -171.26 to 25.26, one trial, 504 women) and weekly gestational weight gain (MD 4.50, 95% CI -33.55 to 42.55, one trial, 486 women, low-quality evidence). No data were reported on perinatal death. Isocaloric protein supplementation (two trials, 184 women)Isocaloric protein supplementation (two trials, 184 women) had no significant effect on birthweight (MD 108.25, 95% CI -220.89 to 437.40) and weekly gestational weight gain (MD 110.45, 95% CI -82.87 to 303.76, very low-quality evidence). No data reported on perinatal mortality, stillbirth, neonatal death, small-for-gestational age, and preterm birth. AUTHORS' CONCLUSIONS This review provides encouraging evidence that antenatal nutritional education with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, low birthweight, increasing head circumference at birth, increasing birthweight among undernourished women, and increasing protein intake. There was no evidence of benefit or adverse effect for any other outcome reported.Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.The results of this review should be interpreted with caution. The risk of bias was either unclear or high for at least one category examined in several of the included trials, and the quality of the evidence was low for several important outcomes. Also, as the anthropometric characteristics of the general obstetric population is changing, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well-designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.
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Antenatal dietary advice and supplementation to increase energy and protein intake.
Ota, E, Tobe-Gai, R, Mori, R, Farrar, D
The Cochrane database of systematic reviews. 2012;(9):CD000032
Abstract
BACKGROUND Gestational weight gain is positively associated with fetal growth, and observational studies of food supplementation in pregnancy have reported increases in gestational weight gain and fetal growth. OBJECTIVES To assess the effects of advice during pregnancy to increase energy and protein intake, or of actual energy and protein supplementation, on energy and protein intakes, and the effect on maternal and infant health outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (22 July 2011) and contacted researchers in the field. We updated the search on 12 July 2012 and added the results to the awaiting classification section of the review. SELECTION CRITERIA Randomised controlled trials of dietary advice to increase energy and protein intake, or of actual energy and protein supplementation, during pregnancy. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and checked for accuracy. Extracted data were supplemented by additional information from the trialists we contacted. MAIN RESULTS We examined 110 reports corresponding to 46 trials. Of these trials, 15 were included, 30 were excluded, and one is ongoing. Overall, 15 trials involving 7410 women were included.Nutritional advice (four trials, 790 women)Women given nutritional advice had a lower relative risk of having a preterm birth (two trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98 ), head circumference at birth was increased in one trial (389 women) (mean difference (MD) 0.99 cm, 95% CI 0.43 to 1.55) and protein intake increased (three trials, 632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant differences were observed on any other outcomes.Balanced energy and protein supplementation (11 trials, 5385 women)Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.62, 95% CI 0.40 to 0.98, five trials, 3408 women), mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26 , Tau(2)= 1744, I(2) = 44%, 11 trials, 5385 women). There was also a significant reduction in the risk of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I(2) = 16%, seven trials, 4408 women). No significant effect was detected for preterm birth or neonatal death.High-protein supplementation (one trial, 1051 women)High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41).Isocaloric protein supplementation (two trials, 184 women)Isocaloric protein supplementation (two trials,184 women) had no significant effect on birthweight and weekly gestational weight gain. AUTHORS' CONCLUSIONS This review provides encouraging evidence that antenatal nutritional advice with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, increasing head circumference at birth and increasing protein intake, there was no evidence of benefit or adverse effect for any other outcome reported.Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.The results of this review should be interpreted with caution, the risk of bias was either unclear or high for at least one category examined in several of the included trials and the quality of the evidence was low for several important outcomes. Also the anthropometric characteristics of the general obstetric population is changing, therefore, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.