Pregnancy and Iron Deficiency: Unresolved Issues

Iron deficiency and iron deficiency anemia are prevalent among pregnant women. The extent to which iron deficiency affects maternal and neonatal health is uncertain. Existing data suggest that maternal iron deficiency anemia may be associated with adverse outcomes, including preterm delivery and higher maternal mortality. Further research is needed on the maternal and neonatal benefits of iron supplementation during pregnancy.     

母亲孕期缺铁性贫血与子代孤独症发生风险的关联分析

目的 探究孕期母亲缺铁性贫血与子代孤独症谱系障碍(ASD)结局的关联,为ASD的早期预防及干预提供思路。方法 于2018-2020年采用病例对照研究,选取ASD儿童145名(病例组)与 正常儿童251名(对照组)纳入研究。采用调查问卷收集儿童及母亲一般情况及母亲孕期缺铁性贫血暴露等情况,采用单因素及多因素Logistic回归分析母亲孕期缺铁性贫血暴露与子代ASD发病的风险。进一步采用中介分析探索产儿科不良结局如剖宫产、早产、低出生体重在母亲孕期缺铁性贫血与子代ASD风险关联中的中介作用。结果 ASD 组母亲孕期缺铁性贫血发生率高于对照组(21.31% vs. 7.56%,P<0.001)。单因素Logistic 回归分析显示母亲孕期缺铁性贫血是子代发生ASD 的危险因素(OR=3.31,95%CI:1.73~6.32)。在校正了儿童性别、母亲学历、母亲被动吸烟及孕早期营养素补充后,多因素Logistic回归分析结果趋势未发生改变(OR=3.44,95%CI:1.53~7.71)。本研究未见剖宫产(间接效应 OR=0.99,95%CI:0.94~1.05)、早产(间接效应OR=1.00,95%CI:0.95~1.08)、低出生体重(间接效应 OR=0.99,95%CI:0.94~1.04)在母亲缺铁性贫血和子代ASD发生风险中存在中介作用。结论 母亲孕期缺铁性贫血是子代发生ASD的独立危险因素。孕期缺铁性贫血的早期筛查、早期干预十分必要,可减少子代ASD的发生风险。     

Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth

A negative association between anemia and duration of gestation and low birth weight has been reported in the majority of studies, although a causal link remains to be proven. This paper explores potential biological mechanisms that might explain how anemia, iron deficiency or both could cause low birth weight and preterm delivery. The risk factors for preterm delivery and intrauterine growth retardation are quite similar, although relatively little is understood about the influence of maternal nutritional status on risk of preterm delivery. Several potential biological mechanisms were identified through which anemia or iron deficiency could affect pregnancy outcome. Anemia (by causing hypoxia) and iron deficiency (by increasing serum norepinephrine concentrations) can induce maternal and fetal stress, which stimulates the synthesis of corticotropin-releasing hormone (CRH). Elevated CRH concentrations are a major risk factor for preterm labor, pregnancy-induced hypertension and eclampsia, and premature rupture of the membranes. CRH also increases fetal cortisol production, and cortisol may inhibit longitudinal growth of the fetus. An alternative mechanism could be that iron deficiency increases oxidative damage to erythrocytes and the fetoplacental unit. Iron deficiency may also increase the risk of maternal infections, which can stimulate the production of CRH and are a major risk factor for preterm delivery. It would be useful to explore these potential biological mechanisms in randomized, controlled iron supplementation trials in anemic and iron-deficient pregnant women.     

Iron deficiency anemia: Pregnancy outcomes with or without iron supplementation

Objective

To estimate the efficacy of iron supplementation in anemic pregnant women on the basis of occurrence of pregnancy complications and birth outcomes.

Methods

Comparison of the occurrence of medically recorded pregnancy complications and birth outcomes in pregnant women affected with medically recorded iron deficiency anemia and iron supplementation who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities.

Results

Of 22 843 cases with congenital abnormalities, 3242 (14.2%), while of 38 151 controls, 6358 (16.7%) had mothers with anemia. There was no higher rate of preterm births and low birth weight in the newborns of anemic pregnant women supplemented by iron. However, anemic pregnant women without iron treatment had a significantly shorter gestational age at delivery with a somewhat higher rate of preterm births but these adverse birth outcomes were prevented with iron supplementation. The rate of total and some congenital abnormalities was lower than expected and explained mainly by the healthier lifestyle and folic acid supplements. The secondary findings of the study showed a higher risk of constipation-related hemorrhoids and hypotension in anemic pregnant women with iron supplementation.

Conclusion

A higher rate of preterm birth was found in anemic pregnant women without iron treatment but this adverse birth outcome was prevented with iron supplementation. There was no higher rate of congenital abnormalities in the offspring of anemic pregnant women supplemented with iron and/or folic acid supplements.     

Micronutrients in pregnancy

Vitamins and minerals, referred to collectively as micronutrients, have important influences on the health of pregnant women and the growing fetus. Iron deficiency results in anemia which may increase the risk of death from hemorrhage during delivery, but its effects on fetal development and birth outcomes is still unclear. Folic acid deficiency can lead to hematological consequences, pregnancy complications and congenital malformations, but again the association with other birth outcomes is equivocal. Zinc deficiency has been associated in some, but not all studies with complications of pregnancy and delivery, as well as with growth retardation, congenital abnormalities and retarded neurobehavioral and immunological development in the fetus. Iodine deficiency during pregnancy results in cretinism and possible fetal wastage and preterm delivery. Deficiency of other minerals such as magnesium, selenium, copper, and calcium have also been associated with complications of pregnancy, childbirth or fetal development. Deficiencies of vitamins other than folate may likewise be related to such complications; and vitamin A or beta-carotene supplements in pregnancy reduced maternal mortality by 50 % in a controlled trial in Nepal. Additional research is need on the prevalence of such deficiencies and their consequences and on cost-effective public health interventions for their control.     

Anemia vs iron deficiency: increased risk of preterm delivery in a prospective study.

Using criteria from the Centers for Disease Control, anemia and iron-deficiency anemia (anemia with serum ferritin concentrations less than 12 micrograms/L) were assessed in greater than 800 inner-city gravidas at entry to prenatal care. Iron-deficiency anemia was associated with significantly lower energy and iron intakes early in pregnancy and a lower mean corpuscular volume. The odds of low birth weight were tripled and of preterm delivery more than doubled with iron deficiency, but were not increased with anemia from other causes. When vaginal bleeding at or before entry to care accompanied anemia, the odds of a preterm delivery were increased fivefold for iron-deficiency anemia and doubled for other anemias. Inadequate pregnancy weight gain was more prevalent among those with iron-deficiency anemia and in those with anemias of other etiologies. The prevalence of iron-deficiency anemia (3.5%), however, was lower than anticipated for an inner-city, minority population in whom most anemias had been attributed clinically to iron deficiency.     

Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential

This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron-rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants.     

A national survey of iron and folate status in pregnant women in Switzerland.

Women often do not meet the increased iron and folate needs of pregnancy. Maternal iron-deficiency anemia is associated with poor maternal and infant outcomes, including preterm delivery and low birth weight. Poor folate status increases risk for maternal anemia, spontaneous abortion, and congenital defects. Because of this, supplemental iron and folate are often recommended during pregnancy. There are few data on iron and folate status in pregnant women in Switzerland. We measured iron and folate status in a national sample of Swiss pregnant women, estimated the prevalence of anemia, and determined if supplement use is associated with iron and/or folate status in this group. A 3-stage probability to size cluster sampling method was used to obtain a representative national sample of pregnant women (n = 381) in the second and third trimester. We measured hemoglobin, hematocrit, mean corpuscular volume, and serum folate and ferritin concentrations. Serum transferrin receptor concentration was determined in anemic subjects. The use of iron and folate supplements was evaluated by questionnaire. Mean hemoglobin (+/- SD) in the sample was 123 g/L (+/- 1.0). The prevalence of anemia was 6%. Of the 21 anemic women, 11 were iron-deficient, giving an iron-deficiency anemia prevalence of 3%. Nineteen percent of women had low serum ferritin concentrations (< 12 micrograms/L) and 4% had low serum folate concentration (< 2.5 micrograms/L). Supplements containing iron were taken by 65% of women, and 63% were taking folate-containing supplements. Women in the second and third trimester taking folate-containing supplements had significantly higher serum folate concentrations compared to those not taking a folate supplement (p < 0.001). In the third trimester, women taking iron-containing supplements had significantly higher serum ferritin concentrations compared to those not taking an iron-containing supplement (p < 0.01). Our findings indicate that iron and folate status appears to be adequate in the majority of pregnant women in Switzerland, and that use of iron and folate supplements may have a positive impact on status.     

Is There a Causal Relationship between Iron Deficiency or Iron-Deficiency Anemia and Weight at Birth, Length of Gestation and Perinatal Mortality?

An extensive literature review was conducted to identify whether iron deficiency, iron-deficiency anemia and anemia from any cause are causally related to low birth weight, preterm birth or perinatal mortality. Strong evidence exists for an association between maternal hemoglobin concentration and birth weight as well as between maternal hemoglobin concentration and preterm birth. It was not possible to determine how much of this association is attributable to iron-deficiency anemia in particular. Minimal values for both low birth weight and preterm birth occurred at maternal hemoglobin concentrations below the current cut-off value for anemia during pregnancy (110 g/L) in a number of studies, particularly those in which maternal hemoglobin values were not controlled for the duration of gestation. Supplementation of anemic or nonanemic pregnant women with iron, folic acid or both does not appear to increase either birth weight or the duration of gestation. However, these studies must be interpreted cautiously because most are subject to a bias toward false-negative findings. Thus, although there may be other reasons to offer women supplemental iron during pregnancy, the currently available evidence from studies with designs appropriate to establish a causal relationship is insufficient to support or reject this practice for the specific purposes of raising birth weight or lowering the rate of preterm birth.     

Evidence-Based Recommendations for an Optimal Prenatal Supplement for Women in the U.S., Part Two: Minerals

The levels of many essential minerals decrease during pregnancy if un-supplemented, including calcium, iron, magnesium, selenium, zinc, and possibly chromium and iodine. Sub-optimal intake of minerals from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of minerals is often below the Recommended Dietary Allowance (RDA), especially for iodine and magnesium, and 28% of women develop iron deficiency anemia during their third trimester. The goal of this paper is to propose evidence-based recommendations for the optimal level of prenatal supplementation for each mineral for most women in the United States. Overall, the evidence suggests that optimal mineral supplementation can significantly reduce a wide range of pregnancy complications (including anemia, gestational hypertension, gestational diabetes, hyperthyroidism, miscarriage, and pre-eclampsia) and infant health problems (including anemia, asthma/wheeze, autism, cerebral palsy, hypothyroidism, intellectual disability, low birth weight, neural tube defects, preterm birth, rickets, and wheeze). An evaluation of 180 commercial prenatal supplements found that they varied widely in mineral content, often contained only a subset of essential minerals, and the levels were often below our recommendations. Therefore, there is a need to establish recommendations on the optimal level of mineral supplementation during pregnancy.     

Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial

BACKGROUND: Iron deficiency anemia (IDA) is common in pregnant women, but previous trials aimed at preventing IDA used high-dose iron supplements that are known to cause gastrointestinal side effects. OBJECTIVE: The objective was to assess the effect on maternal IDA and iron deficiency (ID, without anemia) of supplementing pregnant women with a low dosage (20 mg/d) of iron. Effects on iron status were assessed at the time of delivery and at 6 mo postpartum. Gastrointestinal side effects were assessed at 24 and 36 wk of gestation. DESIGN: This was a randomized, double-blind, placebo-controlled trial of a 20-mg daily iron supplement (ferrous sulfate) given from 20 wk of gestation until delivery. RESULTS: A total of 430 women were enrolled, and 386 (89.7%) completed the follow-up to 6 mo postpartum. At delivery, fewer women from the iron-supplemented group than from the placebo group had IDA [6/198, or 3%, compared with 20/185, or 11%; relative risk (RR): 0.28; 95% CI: 0.12, 0.68; P < 0.005], and fewer women from the iron-supplemented group had ID (65/186, or 35%, compared with 102/176, or 58%; RR: 0.60; 95% CI: 0.48, 0.76; P < 0.001). There was no significant difference in gastrointestinal side effects between groups. At 6 mo postpartum, fewer women from the iron-supplemented group had ID (31/190, or 16%, compared with 51/177, or 29%; RR: 0.57; 95% CI: 0.38, 0.84; P < 0.005). The rate of IDA between the groups did not differ significantly at 6 mo postpartum. CONCLUSION: Supplementing the diet of women with 20 mg Fe/d from week 20 of pregnancy until delivery is an effective strategy for preventing IDA and ID without side effects.     

Iron status is an important cause of anemia in HIV-infected Tanzanian women but is not related to accelerated HIV disease progression

In HIV-infected populations from developing countries, it is unclear what proportion of anemia is attributable to iron deficiency (ID) and whether high body iron stores worsen HIV disease progression. We therefore evaluated these research questions in 584 HIV-infected Tanzanian women. Hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and C-reactive protein (CRP) concentrations were evaluated between 13 and 43 wk after women gave birth. ID was defined as SF or sTfR outside normal ranges, and ID anemia (IDA) as ID plus low Hb. In multivariate Cox regression models, the association between SF and HIV disease progression was assessed. Participants received iron + folate supplements during pregnancy. Hb (r = -0.159; P = 0.0001), SF (r = 0.355; P < 0.0001), and sTfR/log SF index (r = -0.119; P = 0.004) were related to CRP, whereas sTfR (r = 0.029; P = 0.48) was not. Prevalence estimates were 39.7% for ID and 23.6% for IDA. ID was associated with 48.9% of anemia cases. Categories of SF were not significantly associated with HIV-related mortality or progression to stage 4. Nevertheless, SF > 150.0 microg/L was related to a nonsignificantly elevated risk of progression to stage 4 (rate ratio = 1.78; 95% CI = 0.68-4.64; P = 0.24) compared with SF < 12.0 microg/L. In HIV-infected, parous women from sub-Saharan Africa, ID is of moderately high prevalence and is an important underlying cause of anemia. High storage iron does not appear to be related to HIV disease progression in this population, but more research on the role of iron during HIV disease is needed.     

2 325例学龄期儿童缺铁性贫血患病状况及影响因素分析

目的探究2 325例学龄前儿童缺铁性贫血患病情况并分析其影响因素。方法选取2016年6月—2018年6月在河西学院附属张掖人民医院进行体检的2 325例儿童为研究对象,筛选出其中缺铁性贫血患儿,患儿及家属接受问卷调查,分析接受体检学龄前儿童缺铁性贫血患病情况,影响学龄前儿童缺铁性贫血患病单因素以及多因素logistic回归分析。结果接受体检2 325例儿童中检出缺铁性贫血儿童198例,其中轻度、中度以及重度贫血分别60例、81例和57例,缺铁性贫血儿童患病率为8.52%;单因素分析结果显示,影响学龄前儿童缺铁性贫血因素有年龄、出生时体质量指数、母亲妊娠期是否有贫血、是否早产、患儿肠胃消化能力是否正常、喂养形式、进辅食时间、父母学历、是否正常补充铁元素、家庭饮食习惯以及父母月收入(P0.05);多因素logistic回归分析结果显示,年龄小、母亲妊娠期贫血、早产、患儿肠胃消化能力不佳、进辅食时间晚、未补充铁元素以及家庭饮食习惯不佳等为导致患儿缺铁性贫血发生的危险因素(P0.05)。结论预防学龄期儿童缺铁性贫血工作关键在于关注孕妇以及胎儿营养情况,调整儿童饮食结构,养成合适饮食习惯。     

Issues in prevention of iron deficiency anemia in India

Iron deficiency anemia (IDA) continues to be major public health problem in India. It is estimated that about 20% of maternal deaths are directly related to anemia and another 50% of maternal deaths are associated with it. The question, therefore, is why, despite being the first country to launch the National Nutritional Anemia Prophylaxis Programme in 1970, the problem of IDA remains so widespread. As is to be expected, the economic implications of IDA are also massive. The issues of control of IDA in India are multiple. Inadequate dietary intake of iron, defective iron absorption, increased iron requirements due to repeated pregnancies and lactation, poor iron reserves at birth, timing of umbilical cord clamping, timing and type of complementary food introduction, frequency of infections in children, and excessive physiological blood loss during adolescence and pregnancy are some of the causes responsible for the high prevalence of anemia in India. In addition, there are other multiple programmatic and organizational issues. This review, therefore, is an attempt to examine the current burden of anemia in India, its epidemiology, and the various issues regarding its prevention and control, as well as to offer some innovative approaches to deal with this major health problem.     

妊娠期缺铁性贫血的预防

对３９名健康孕妇从妊中期开始进行血红蛋白（Ｈｂ）、血清铁蛋白（ＳＦ）、血铁饱和度（ＴＳ）、红细胞内游离原卟啉（ＦＥＰ）与Ｈｂ比值动态观察。对照组：孕期未服铁剂。铁剂组：妊中期取血后每日服用硫酸亚铁３００ｍｇ。各观察对象于１８－２２周、２８－３２周、３８－４０周取静脉血。结果显示：妊娠期Ｈｂ、ＳＦ、ＴＳ下降，ＦＥＰ／Ｈｂ上升，缺铁症发生率增高，妊中期开始补铁对预防贫血有效。     

Community Mobilization and Social Marketing to Promote Weekly Iron-Folic Acid Supplementation in Women of Reproductive Age in Vietnam: Impact on Anemia and Iron Status

The community mobilization and social marketing program promoting a preventive approach of weekly iron-folic acid supplementation in women of reproductive age improved iron status of non-pregnant women in Vietnam. Three to six months of weekly pre-pregnancy supplementation and regular weekly intake of supplements during pregnancy allowed women to achieve good iron and hemoglobin status during the two first trimesters of pregnancy. In the third trimester, iron deficiency and anemia were notably present but low birth weight prevalence was low. This demonstrates the effectiveness and safety of the preventive approach as implemented here to prevent and control iron deficiency and anemia in women of reproductive age before and during pregnancy.     

Maternal zinc supplementation does not affect size at birth or pregnancy duration in Peru.

To estimate the effect of maternal zinc deficiency on pregnancy outcomes, we conducted a zinc supplementation trial in an urban shantytown in Lima, Peru, a population with habitual low zinc intakes. Beginning at 10-24 wk gestation, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg iron and 250 (g folate, with or without 15 mg zinc. Women were followed up monthly during pregnancy. At birth, newborn weight was recorded, and crownheel length, head circumference and other circumferences and skinfold thicknesses were assessed on d 1. At delivery, 1016 remained in the study; duration of pregnancy was known for all women, and birth weight information was available for 957 newborns. No differences were noted in duration of pregnancy (39.4 +/- 2.2 vs. 39. 5 +/- 2.0 wk) or birth weight (3267 +/- 461 vs. 3300 +/- 498 g) by prenatal supplement type (iron + folate + zinc vs. iron + folate; P > 0.05), and there were no differences in the rates of preterm (<37 wk) or post-term (>42 wk) delivery, low birth weight (<2500 g) or high birth weight (>4000 g). Finally, there were no differences by prenatal supplement type in newborn head circumference, crownheel length, chest circumference, mid-upper arm circumference, calf circumference or skinfold thickness at any of three sites. Adjustment for covariates and confounding factors did not alter these results. Adding zinc to prenatal iron and folate tablets did not affect duration of pregnancy or size at birth in this population.     

A micronutrient-fortified beverage prevents iron deficiency,reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women

Maternal malnutrition continues to be a major contributor to adverse reproductive outcomes in developing countries, despite longstanding efforts to fortify foods or to distribute medicinal supplements to pregnant women. The objective of this study was to test the effect of a micronutrient-fortified beverage containing 11 micronutrients (iron, iodine, zinc, vitamin A, vitamin C, niacin, riboflavin, folate, vitamin B-12, vitamin B-6 and vitamin E) on the hemoglobin, iron and vitamin A status of pregnant women in Tanzania. A group of 259 pregnant women with gestational ages of 8 to 34 wk were enrolled in a randomized double-blind controlled trial in which study women received 8 wk of supplementation. Hemoglobin, ferritin and dried blood spot retinol were measured at baseline and at the end of the supplementation period. The supplement resulted in a 4.16 g/L increase in hemoglobin concentration and a 3 micro g/L increase in ferritin and reduced the risk of anemia and iron deficiency anemia by 51 and 56%, respectively. The risk of iron deficiency was reduced by 70% among those who had iron deficiency at baseline and by 92% among those who had adequate stores. The micronutrient-fortified beverage may be a useful and convenient preventative measure, one that could help improve the nutritional status of women both before and during pregnancy and thereby help avoid some of the potential maternal and fetal consequences of micronutrient deficiencies.     

Preconception maternal iron status is a risk factor for iron deficiency in infant rhesus monkeys (Macaca mulatta)

Iron deficiency is the most common micronutrient deficiency during pregnancy, and maternal anemia has been associated with poor pregnancy outcomes. However, it is still not clear how directly maternal iron status is linked to the infant's iron status postpartum. We investigated the impact of maternal iron deficiency on the hematological status of infant rhesus monkeys. Two groups of females, 8 iron deficient and 8 iron sufficient were assessed through pregnancy and for 6 mo postpartum. At conception, 4 females in each group were provided an iron-enriched diet. Iron status of the infant at birth reflected the preconception status of the mother, regardless of diet. Serum ferritin (Ft) concentrations were significantly higher in infants born to iron-sufficient mothers and were correlated with maternal transferrin saturation at entrance to the study (r = 0.52, P < 0.04). Infant iron status continued to reflect prenatal conditions through 6 mo of age. Our study confirmed the importance of iron sufficiency in gravid female monkeys for ensuring their infants' normal hematological development postpartum. A dietary intervention during pregnancy with only a moderate addition of iron was not sufficient to prevent the offspring from developing iron deficiency. These findings stress the importance of improving iron nutriture prior to conception.     

围孕期叶酸补充情况及其对妊娠结局影响

  目的  了解单胎妊娠围孕期叶酸补充情况和补充剂量, 探讨围孕期叶酸补充与妊娠结局的关系。  方法  以2017年10月-2019年6月期间在广州市花都区妇幼保健院分娩的6 536例单胎活产的孕妇作为研究对象。在分娩前或分娩后回顾性的调查孕妇一般人口学特征、围孕期增补叶酸情况及妊娠结局等信息。  结果  孕前半年服用叶酸坚持1个月以上的孕妇1 345人(20.18%); 围孕期每日叶酸服用剂量正常的孕妇764人(11.69%)。与未补充叶酸相比, 孕前补充叶酸可使新生儿增加74.68 g出生体重, 孕后补充增加55.05 g(P＜0.05)。在控制孕妇年龄、文化水平、孕前BMI、被动吸烟时间等相关因素后, 孕前补充叶酸可以使小于胎龄儿(small for gestational age, SGA)的发生风险降低(aOR=0.66, 95% CI: 0.46~0.95)。低出生体重(low birth weight, LBW)和自发早产与叶酸补充类型无关。围孕期高剂量补充叶酸可能增加自发早产的发生风险(aOR=1.75, 95% CI: 1.02~3.01)。SGA和LBW与叶酸补充剂量无关。  结论  围孕期补充叶酸可以促进胎儿生长, 降低SGA的发生风险。