Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group

A multicentre, randomized controlled double-blind trial in 5 maternity hospitals in Australia assessed the effect of a daily supplement of calcium (1.8g oral calcium or an oral placebo) taken daily until delivery, from less than 24 weeks' gestation, on the frequency of pregnancy-induced hypertension, preeclampsia and preterm birth (< 37 weeks' gestation) in 456 nulliparas with a singleton pregnancy. Treatment with calcium reduced the risk of preeclampsia (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02) and the risk of preterm birth (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02). No significant differences were seen between the 2 groups in the frequency of pregnancy-induced hypertension, although the study only had statistical power to detect large differences in this outcome. An updated systematic review of the 9 randomized trials of calcium supplementation in pregnancy shows a significant reduction in the risk of hypertension and preeclampsia although no effect on preterm birth. Calcium supplementation during pregnancy reduced the risk of preeclampsia and preterm birth in this nulliparous population. The available evidence for systematic review of all the randomized trials of calcium supplementation shows benefit in reducing the risk of hypertension and preeclampsia.     

Effect of milk and calcium supplementation on bone density and bone turnover in pregnant Chinese women: a randomized controlled trail

Objective  

Calcium demand is increased during pregnancy. However, few randomized controlled trials examined the effects of calcium supplementation on bone mass during pregnancy. This study determined effects of calcium and milk supplementation on maternal bone mineral density (BMD) and bone turnover in pregnant Chinese women with habitual low calcium intake.     

Calcium supplementation during pregnancy and lactation: effects on the mother and the fetus

Calcium consumption is essential for bone development and maintenance throughout life, yet more than one half of the female population in the United States does not consume the recommended amount of calcium. Calcium intake is especially crucial during pregnancy and lactation because of the potential adverse effect on maternal bone health if maternal calcium stores are depleted. There is often a transient lowered bone mineral density and increased rate of bone resorption, with the greatest consequence during the third trimester and throughout lactation. Studies indicate that calcium consumption should be encouraged, especially during pregnancy and lactation, to replace maternal skeletal calcium stores that are depleted during these periods. Because the fetus in utero and the neonate through breast-feeding are dependent on maternal sources for the total calcium load, adequate maternal calcium intake also can affect fetal bone health positively. Proper calcium consumption can be attained through the diet by the consumption of dairy products or leafy greens (such as kale), the consumption of fortified foods, or by supplementation with widely available calcium-containing supplement products. Because many women experience heartburn during pregnancy, calcium-based antacids are ideal for providing heartburn relief, and they offer a calcium supplement to ensure maternal and fetal bone health, without the danger of adverse effects on the neonate.     

The effect of calcium supplementation during pregnancy on fetal and infant growth: a nested randomized controlled trial within WHO calcium supplementation trial

Objective. To evaluate whether prenatal calcium supplementation affects fetal and infant growth during the first year of life.

Methods. Ninety-one pregnant women and 159 mothers and their infants enrolled beginning before 20 weeks gestation, and women received daily supplements containing either 1.5 g calcium or placebo. Women were examined by ultrasound at 20, 24, 28, 32 and 36 weeks to evaluate fetal biometry. During the first year after delivery, sub-groups of infants born from mothers participating in the trial were examined to assess infant growth. Anthropometric measurements of the infants were assessed. Mothers were enquired about lactation patterns, morbidities of the infants, separation from the mother, and admission to hospital.

Results. Ultrasound measurements of fetal biometry did not show any differences between fetuses whose mothers received calcium supplementation during pregnancy and those who received placebo. Concerning infant growth, the mean weight and head circumference of infants born to calcium-supplemented mothers were similar to those born to placebo-supplemented mothers during the first year of life. The mean mid-arm circumference and mean length were significantly higher in the infants of the calcium group at sixth and ninth month, respectively. But, at 12 months, there were no significant differences in any of the anthropometric measurements.

Conclusion. Calcium supplementation during pregnancy of women with low calcium intake does not have a noticeable impact on fetal and infant growth during the first year of life.     

Calcium plus linoleic acid therapy for pregnancy-induced hypertension.

OBJECTIVE: To determine the effect of dietary supplementation of calcium plus conjugated linoleic acid (calcium-CLA) in reducing the incidence of vascular endothelial dysfunction in pregnant women at high risk of developing pregnancy-induced hypertension (PIH). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial conducted at 4 outpatient clinics in 2 developing countries recruited 48 healthy primigravidas younger than 19 years or older than 35 years who had a family history of pre-eclampsia and diastolic notch. Twenty-four participants received daily elemental calcium (600 mg) plus CLA (450 mg) and 24 received placebo from week 18 to 22 of pregnancy until delivery. RESULTS: Calcium-CLA supplementation reduced significantly the incidence of PIH (2 cases [8%] in the study group vs. 10 cases [42%] in the placebo group; relative risk, 0.20; 95% confidence interval, 0.05-0.82; P=.01). Endothelial dysfunction was also significantly reduced after calcium-CLA supplementation (in 18 women [75%] vs. 4 women [17%]; P<.001), compared with the placebo group (in 15 [63%] vs. 9 women [38%]; P=.08). CONCLUSION: In pregnant women at high risk for PIH, calcium-CLA supplementation decreases the incidence of PIH and improves endothelial function.     

妊娠期补充钙剂的临床观察

目的观察孕期补充钙剂的效果以及对妊娠的影响。方法将186例20～34周的孕妇随机分为补钙组(98例，服用乐力氨基酸螫合钙)和对照组(98例)，分别于服药前查血钙、尿蛋白。观察期间每4周复查1次血钙及尿蛋白，每周复查1次血压、宫高，腹围。结果妊娠期血钙低于正常非孕期，随妊娠进展下降更明显(P＜0．05)，补充钙组血钙较对照组明显升高(P＜0．05)，补钙组的临床缺钙症状明显低于对照组且妊高征、胎儿宫内发育迟缓发生率明显低于对照组(P＜0．01)。结论，孕期补充乐力钙有益于降低缺钙症状的发生，降低妊高征、胎儿宫内发育迟缓发生率，对母婴都是非常有益的。     

Calcium, nitric oxide, and preeclampsia

A relationship between calcium dietary intake and incidence of preeclampsia was proposed. In the Andean Ecuadorian population, the average calcium intake, evaluated by a 24 hours dietary recall range between 52.3% of the US RDA to 77%. The calcium intake in women with preeclampsia was significantly lower in relation with normal pregnant women. Three prospective, randomized, double-blind, placebo-controlled clinical trials to investigate the effect of calcium supplementation (2 g/day of elemental calcium) in the incidence of pregnancy-induced hypertension and preeclampsia were conduced between 1984 and 1995. All the subjects included were nulliparous, younger that 25 years old, first prenatal visit before 24 weeks' gestation, residency in Quito, and normotensives. These clinical trials showed a risk reduction in pregnancy induced hypertension and preeclampsia in the calcium group. Calcium supplementation was associated with an increase in the serum ionized calcium concentrations. Moreover, women with preeclampsia showed a significant decrease in the levels of the serum ionized calcium. Ionic calcium is crucial for the synthesis of vasoactive substances in the endothelium as prostacyclin and nitric oxide. Recent results suggest that an alteration in the action of NO may be related to a high inactivation by free radical superoxide, secondary to an inflammatory process.     

Serum calcium and parathormone during normal pregnancy in malay women

Objective: To ascertain the calcium status in normal pregnant Malay women.

Methods: In a cross-sectional study, serum parathormone (PTH) and calcium concentrations, and 24-h urinary calcium excretion were estimated in age-matched normotensive pregnant women, over the 3 trimesters.

Results: No statistically significant differences were evident in serum ionised calcium concentrations between the pregnant women in the 3 trimesters. Serum total calcium however, was significantly lower in women in the 3rd trimester of pregnancy (2.29 ± 0.16, 2.26 ± 0.13, and 2.16 ± 0.12 mmol l^–1 in the 1st, 2nd, and 3rd trimesters, respectively; P < 0.001). Serum parathyroid hormone concentration was significantly higher in the 3rd trimester of pregnancy (3.37 ± 3.31, 4.36 ± 4.55, and 7.17 ± 6.6 pg ml^–1 in the 1st, 2nd, and 3rd trimesters, respectively; P < 0.05). No significant differences were evident in serum sodium and potassium concentrations between the 3 groups. Urinary calcium excretion was significantly lower in women in the 3rd trimester of pregnancy (3.41 ± 1.80, 3.56 ± 3.31, and 2.46 ± 1.71 mmol day^–1 in the 1st, 2nd, and in the 3rd trimesters, respectively; P < 0.05). No significant differences were evident in urine output, creatinine clearance, or in the excretion of sodium and potassium between the 3 groups.

Conclusions: It appears that a significant fall in serum total calcium occurs in the 2nd half of normal human pregnancy when there is also an increased fetal demand and perhaps also a relatively insufficient maternal intake and/or intestinal absorption. The lower urinary calcium excretion probably occurs secondary to this and may suggest a fall in total body calcium and an attempt by the body to conserve calcium. While under normal circumstances, this level of fall in total calcium may not be significant, the coincidence of occurrence of hypertensive disorders of pregnancy during this stage of pregnancy, and the evident link between low calcium intake and pregnancy-induced hypertension (PIH) and its possible amelioration with calcium supplementation, suggests a need to assess calcium status in pregnant women with a view to providing calcium supplementation during pregnancy.     

First Antenatal Visit Haematocrit and Pregnancy Induced Hypertension

First antenatal visit haematocrit values during the first and second trimesters were retrospectively collected from 546 nulliparas with singleton pregnancies. The results were analysed for correlation with development of pregnancy induced hypertension (PIH) later in pregnancy. It was found that women with higher haematocrit values, especially over 0.40, had an increased risk of developing PIH. However, there appeared to be no absolute level of haematocrit which had sufficient discriminative value to be useful in clinical practice.     

Zinc and pregnancy

Zinc, an essential trace element, plays a critical role in normal growth and development, cellular integrity and many biological functions, including protein synthesis and nucleic acid metabolism. Since all these are involved in cell division and growth, zinc is believed to be important for foetal growth and development. Zinc requirement is increased during pregnancy but the lack of a valid indicator precludes a true estimate of zinc deficiency in pregnancy even in developed countries. This review examines the possibility that a gestational deficiency of zinc can adversely affect the pregnancy outcome. Preliminary human data suggest a beneficial effect of prenatal zinc supplementation trials in particular on infant's neurobehavioral development. In the light of the currently available information, zinc supplementation at therapeutic load (30 mg/day) as it is proposed for the treatment of hormonal skin disorders to adolescents, cannot be toxic.     

Iron supplementation in pregnancy

Iron deficiency is the most common nutritional disorder in the world. Pregnant women are at especially high risk for iron deficiency and iron deficiency anemia. A considerable proportion of pregnant women in both developing and industrialized countries become anemic during pregnancy. The prevalence of anemia in pregnant women has remained unacceptably high worldwide despite the fact that routine iron supplementation during pregnancy has been almost universally recommended to prevent maternal anemia, especially in developing countries over the past 30 years. The major problem with iron supplementation during pregnancy is compliance. Despite many studies, the relationship between maternal anemia and adverse pregnancy outcome is unclear. However, there is now sufficient evidence that iron supplements increase hemoglobin and serum ferritin levels during pregnancy and also improve the maternal iron status in the puerperium, even in women who enter pregnancy with adequate iron stores. Recent information also suggests an association between maternal iron status in pregnancy and the iron status of infants postpartum. The necessity of routine iron supplementation during pregnancy has been debated in industrialized countries and routine supplementation is not universally practiced in all these countries. In view of existing data, however, routine iron supplementation during pregnancy seems to be a safe strategy to prevent maternal anemia in developing countries, where traditional diets provide inadequate iron and where malaria and other infections causing increased losses are endemic.     

Supplementation during pregnancy: beliefs and science

Pregnancy represents a challenge from a nutritional perspective, because micronutrient intake during the periconceptional period and in pregnancy affects fetal organ development and the mother’s health. Inappropriate diet/nutrition in pregnancy can lead to numerous deficiencies including iron deficiency and may impair placental function and play a role in miscarriage, intrauterine growth restriction, preterm delivery, and preeclampsia. This article reviews the risks associated with nutrient deficiencies in pregnant women and presents an overview of recommendations for dietary supplementation in pregnancy, focusing on oral iron supplementation. Risk factor detection, including dietary patterns and comorbidities, is paramount in optimal pregnancy management. Dietary habits, which can lead to deficiencies (e.g., iron, folate, vitamin D, and calcium) and result in negative health consequences for the mother and fetus/newborn, need to be investigated. Prenatal care should be personalized, accounting for ethnicity, culture, education, information level about pregnancy, and dietary and physical habits. Clinicians should make a plan for appropriate supplementation and prophylaxis/treatment of nutritional and other needs, and consider adequate intake of calcium, iodine, vitamin D, folate, and iron. Among the available oral iron supplements, prolonged-released ferrous sulfate (ferrous sulfate–polymeric complex) presents the lowest incidence of overall and gastrointestinal adverse events, with positive implications for compliance.     

Prevention of hypertensive disorders of pregnancy.

A prospective randomised clinical trial comprising 510 pregnant patients was performed to determine whether supplementation with calcium, low-dose aspirin or a combination of calcium and low-dose aspirin can lower the incidence of hypertension in pregnancy. Greatest benefits were obtained with calcium. Perinatal mortality was lowest in the aspirin group.     

妊高征患者硫酸镁治疗前后血浆与红细胞内钙镁含量的变化

目的探讨妊高征患者钙镁含量变化及硫酸镁的治疗机理。方法采用全自动生化分析仪测定３６例妊高征患者（妊高征组）外周血血浆和红细胞内的钙镁含量及硫酸镁治疗４小时时钙镁含量的变化,并以１４例正常妊娠妇女作对照（正常妊娠组）。结果中、重度妊高征患者血浆钙含量较对照组明显下降;红细胞内钙含量较对照组明显升高而镁含量明显下降。硫酸镁治疗４小时后,血浆、红细胞内镁值均较治疗前明显升高;血浆钙含量明显升高,而红细胞内钙含量明显降低。结论镁缺乏是妊高征患者体内离子紊乱的基础,硫酸镁能够改善这种紊乱,起到积极的治疗作用。     

Calcium supplementation and prevention of preeclampsia: a meta-analysis

Background: Since the early 1980s, epidemiological evidence has suggested a connection between low calcium intake and preeclampsia The purpose of this meta-analysis is to summarize current evidence regarding calcium supplementation during pregnancy in predicting preeclampsia and associated maternal–fetal complications. Methods: Literature revision of all RCT (random allocation of calcium versus placebo) available in MEDLINE/PUBMED up to 2/29/2012 regarding calcium supplementation during pregnancy for preventing preeclampsia. We used the Mantel-Haenszel’s Method for four subgroup of patients: Adequate calcium intake; Low calcium intake; Low risk of preeclampsia; High risk of preeclampsia. We considered p < 0.05 as significant. Results: There is no consensus in Literature about: (1) the efficacy of calcium supplementation in the prevention of preeclampsia, (2) other/adverse/long-term effects of calcium supplementation in pregnancy. Conclusions: Preeclampsia is likely to be a multifactorial disease. However, inadequate calcium intake represents a factor associated with an increased incidence of hypertensive disease. The results of our meta-analysis demonstrate that the additional intake of calcium during pregnancy is an effective measure to reduce the incidence of preeclampsia, especially in populations at high risk of preeclampsia due to ethnicity, gender, age, high BMI and in those with low baseline calcium intake.     

Calcium, magnesium, and zinc supplementation and perinatal outcome

The overall importance of nutrition to favorable perinatal outcome is only beginning to be fully appreciated. Although nutritional status can be linked to such things as socioeconomic class and education, it is nutrition directly that exerts a biologic effect. This review has attempted to look at three elements and their relationship to maternal and fetal outcome. At the present time, there does not seem to be a role for routine magnesium supplementation during pregnancy. Magnesium deficiency, as an isolated nutritional deficiency, is rare, and the evidence is, at best, weak that magnesium supplementation reduces the risk of poor perinatal outcome. Zinc deficiency is also a very rare isolated nutritional finding. Our ability to measure zinc accurately, be it in leukocytes or serum, is improving, but the routine use of zinc supplements during pregnancy cannot be recommended at this time. It may be that zinc will be a useful diagnostic marker, rather than a therapeutic intervention. There is substantial evidence that the average American diet does not contain sufficient calcium. An expansive literature continues to grow in the areas of calcium and colon cancer, calcium and breast cancer, calcium and hypertension, and calcium and osteoporosis. Is it possible that our susceptibilities to these problems begin in utero? Obviously, the answer is unknown. What is known is that supplemental calcium to some degree is needed in the diets of most Americans and in about two thirds of pregnant women. Calcium supplementation seems to affect blood pressure favorably and, pending confirmation with larger trials, may significantly reduce prematurity and preeclampsia risk, thus improving perinatal outcome for a large number of our high-risk patients.     

The management of hypoparathyroidism in pregnancy

The management of hypoparathyroidism in pregnancy is reviewed, and previously reported cases are discussed. Two new cases are described. Hypoparathyroidism can be successfully managed in pregnancy. With adequate vitamin D supplementation throughout and elevation of calcium intake in the third trimester, this condition constitutes no threat to the mother or fetus.     

Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis

Objective: To evaluate the effect of folic acid supplementation during pregnancy on the risk of gestational hypertension/preeclampsia. Methods: A systematic review and meta-analysis were conducted. Medline, Embase, Scopus, and the Web of Science were searched from inception to December 2014. Results: Out of 1224 potentially relevant studies, 13 studies met our inclusion criteria (2 randomized controlled trials (RCTs), 10 cohort studies, and 1 case–control study). The pooled relative risk (RR) and 95% confidence interval (CI) of the two RCTs were 0.62 (0.45–0.87) in the trial arm as compared with the placebo arm. The pooled RR was 0.92 (95% CI: 0.79–1.08) for nine cohort studies with available data on folic acid supplementation in pregnancy and gestational hypertension/preeclampsia. Pooled RR was 0.88 (95% CI: 0.76–1.02) for eight cohort studies with available data on folic acid supplementation and preeclampsia. Conclusion: Whether folic acid supplementation in pregnancy can prevent the occurrence of gestational hypertension/preeclampsia remains uncertain.     

A "conservative" approach to iron supplementation during pregnancy

A review of current knowledge about iron metabolism during pregnancy and the evidence from various studies on the effects of iron supplementation in pregnancy on maternal, fetal, and infant outcomes suggest that the implicit goal of current recommendations regarding iron supplementation may be to achieve the highest hemoglobin concentration possible. This goal is only weakly related to improved maternal and infant outcomes in the current pregnancy or to improved maternal iron stores long-term. Indeed, the claim that iron supplementation is universally innocuous is shown to be controversial. For women in developed countries who are generally clinically healthy and have access to adequate nutrition, the benefits of iron supplementation are unclear, and there may be risks. Thus, a better "conservative" approach may be that such women do not require routine iron supplementation during pregnancy. The midwifery philosophy of individualizing care based on a woman's history and health status is one that should be taken in approaching the issue of iron supplementation in pregnancy.     

Calcium supplementation for the prevention of pre-eclampsia

OBJECTIVE: To study the effect of calcium supplementation during pregnancy on blood pressure and maternal and neonatal outcomes. METHOD: A total of 524 healthy primigravidas with a blood pressure less than 140/90 mm Hg were randomly assigned between the 12th and 25th weeks to receive 2 g of elemental calcium or placebo and were followed-up until delivery. RESULTS: The incidence of pre-eclampsia was significantly less in the calcium than in the placebo group (4.0% vs 12.0%; odds ratio [OR], 0.31; 95% confidence interval [CI], 0.15-0.63); the mean systolic and diastolic blood pressures at study completion were different in the calcium and placebo group (P=0.007 and P=0.02). The risk for preterm delivery was less in the calcium (7.0%) than in the placebo (12.7%) group (OR, 0.51; 95% CI, 0.28-0.93). The mean baseline calcium intake was 313.83+/-203.25 mg/day (range, 85.71-910.71 mg/day), which is lower than the recommended dietary intake of 1000 mg, and the 24-hour urinary calcium excretion was 130.82+/-67.44 mg/dL (range, 40.5-387 mg/dL). CONCLUSION: Calcium supplementation appears to reduce the occurrence of pre-eclampsia and preterm delivery in primigravidas who have a daily dietary calcium intake less than the recommended dietary allowances.