Supplementary calcium in prevention of pre-eclampsia. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. 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. Calcium supplementation in mild preeclampsia remote from term: a randomized double-blind clinical trial. Trial of calcium to prevent preeclampsia. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers. Calcium supplementation to prevent hypertensive disorders of pregnancy. Calcium supplementation and prevention of pregnancy induced hypertension. Randomized, placebo-controlled, calcium supplementation study in pregnant Gambian women: effects on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion in the first year of life. The effect of calcium supplementation on bone density in premenarcheal females: a co-twin approach. Improved bone mineralization and growth in premature infants fed fortified own mother's milk. Vitamins C and E and the risks of preeclampsia and perinatal complications. Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the bone density of the neonates. Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.
To study the effect of calcium supplementation on reduction of pre-eclampsia in Iranian women at high risk of pre-eclampsia.
                Thirty pregnant women at high risk of developing pre-eclampsia were randomized to 2 g of daily calcium and placebo. Subjects and investigators were blinded to treatment allocation. The inclusion criteria were positive rollover test, having at least one risk factor for pre-eclampsia, between 28 and 32 weeks of pregnancy, and blood pressure less than 140/90 (mm Hg). Exclusion criteria were having any chronic condition. Pre-eclampsia was defined as systolic/diastolic blood pressure over 140/90 plus proteinuria. All the subjects were followed up to delivery.
                A sevenfold reduction in the occurrence of pre-eclamsia were seen among the calcium group compared with the placebo group (7 out of 15 developed pre-eclampsia in control group vs. 1 out of 15 in calcium group, P=0.014). No major effect on pregnancy induced hypertension was seen (66% in placebo and 76% in calcium group developed hypertension) but the onset of hypertension was delayed 3 weeks in the calcium group. A longer duration of pregnancy was seen in calcium than placebo (mean+/-S.D.=37+/-2 for calcium and 34+/-2 for placebo, P<0.05). Infants born to the calcium group, on average, were 552 g heavier than infants born to the placebo group, P<0.05.
                Calcium supplementation is beneficial for preventing pre-eclampsia among Iranian women at high risk of developing pre-eclampsia. The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery.
                Randomized placebo-controlled, double-blinded trial in nulliparous normotensive women from populations with dietary calcium < 600 mg/d. Women who were recruited before gestational week 20 received supplements (1.5 g calcium/d or placebo) throughout pregnancy. Primary outcomes were preeclampsia and preterm delivery; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates.
                The groups comprised 8325 women who were assigned randomly. Both groups had similar gestational ages, demographic characteristics, and blood pressure levels at entry. Compliance were both 85% and follow-up losses (calcium, 3.4%; placebo, 3.7%). Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia (4.1% vs 4.5%) that was evident by 35 weeks of gestation (1.2% vs 2.8%; P = .04). Eclampsia (risk ratio, 0.68: 95% CI, 0.48-0.97) and severe gestational hypertension (risk ratio, 0.71; 95% CI, 0.61-0.82) were significantly lower in the calcium group. Overall, there was a reduction in the severe preeclamptic complications index (risk ratio, 0.76; 95% CI, 0.66-0.89; life-table analysis, log rank test; P = .04). The severe maternal morbidity and mortality index was also reduced in the supplementation group (risk ratio, 0.80; 95% CI, 0.70-0.91). Preterm delivery (the neonatal primary outcome) and early preterm delivery tended to be reduced among women who were < or = 20 years of age (risk ratio, 0.82; 95% CI, 0.67-1.01; risk ratio, 0.64; 95% CI, 0.42-0.98, respectively). The neonatal mortality rate was lower (risk ratio, 0.70; 95% CI, 0.56-0.88) in the calcium group.
                A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity, maternal morbidity, and neonatal mortality, albeit these were secondary outcomes. 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. To determine whether calcium supplementation prevents progression to severe disease in preterm nulliparous women with mild preeclampsia.
                Seventy-five women hospitalized at 24-36 weeks' gestation because of mild preeclampsia were randomized to receive either 2 g/day of elemental calcium (36 women) or placebo (39). Both groups had similar demographic characteristics, initial blood pressure measurements, and amount of proteinuria. Diagnostic criteria and clinical management for severe preeclampsia were applied consistently.
                Eighteen of 36 calcium-treated subjects (50%, 95% confidence interval [CI] 33-67) developed severe preeclampsia, compared with 19 of 39 (48.7%, 95% CI 32-65) in the placebo group (relative risk 1.03, 95% CI 0.64-1.03; P = 1.00). Blood pressure values, gestational age at delivery, newborn weights, incidence of low Apgar scores, and umbilical arterial blood gases were similar for the two groups.
                Calcium supplementation does not prevent severe preeclampsia in preterm patients with mild disease. Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data.
                We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations.
                Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy.
                Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women. Results are presented of a randomized, double-blinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/- 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/- 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Life-table analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (log-rank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in high-risk populations. To determine whether increased calcium intake (2 g/day) in pregnancy is effective in reducing the risk of preeclampsia in pregnant teenagers.
                The present study was a prospective, randomized, double-blind, controlled clinical trial. Two hundred sixty teenaged pregnant girls attending the Hospital Gíneco-Obstétrico Isidro Ayora in Quito, Ecuador, were included. Selection criteria were age less than 17.5 years, nulliparity, first prenatal visit before 20 weeks' gestation, and residency in Quito (2800-m altitude). We used a table of random numbers to assign 125 girls to receive 2000 mg of elemental calcium daily, beginning at 20 weeks of gestation and continuing until delivery; 135 women in the control group received a placebo. Blood pressure (BP) was measured twice every 4 weeks until delivery and at 48 hours after delivery. The diagnosis of preeclampsia was defined as BP greater than 140/90 mmHg on at least two occasions more than 6 hours apart and proteinuria greater than 30 mg/dL (over one cross by dipstick on two occasions 4-24 hours apart).
                The average daily calcium intake in this population was approximately 51% of the Recommended Dietary Allowance. Calcium supplementation was associated with a significantly decreased risk of preeclampsia (risk reduction 12.35%; P < .001), with 3.2% (n = 4) developing preeclampsia in the treatment group versus 15.5% (n = 21) in the placebo group. Moreover, calcium supplementation led to a reduction in systolic BP of 9.1 mmHg and in diastolic BP of 6.0 mmHg.
                These results suggest that calcium supplementation during pregnancy in populations with low calcium intake is a safe, effective, and inexpensive preventive measure that significantly reduces the risk of preeclampsia. Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response.
                We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined.
                The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller.
                Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy. In a randomized controlled trial 201 healthy nulliparous women were randomly allocated by means of a computer generated randomization list. From 20 weeks of gestation until delivery they received either 2 g of oral elemental calcium (n = 103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to follow-up after randomization. The study groups were very similar at the time of randomization; with respect to several clinical and demographic variables. Treatment compliance was very similar in both groups as was determined by pill count. The rate of pregnancy induced hypertension was lower in the calcium group than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The incidence of gestational hypertension was 6.18% in the calcium group and 17.20% in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR = 0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy to nulliparous women reduces the incidence of pregnancy induced hypertension. Growth and bone mineral accretion in Gambian infants are poorer than those in Western populations. The calcium intake of Gambian women is low, typically 300-400 mg Ca/d, and they have low breast-milk calcium concentrations, which result in low calcium intakes for their breastfed infants. A low maternal calcium supply in pregnancy may limit fetal mineral accretion and breast-milk calcium concentrations and thereby affect infant growth and bone mineral accretion.
                We investigated the effects of calcium supplementation in Gambian women during pregnancy on breast-milk calcium concentrations and infant birth weight, growth, and bone mineral accretion.
                A randomized, double-blind, placebo-controlled supplementation study was conducted in 125 Gambian women who received 1500 mg Ca/d (as calcium carbonate) or placebo from 20 wk of gestation until delivery. Infant birth weight and gestational age were recorded. Breast milk was collected, and infant anthropometric and bone measurements were performed at 2, 13, and 52 wk after delivery. Infant bone mineral status was assessed by using single-photon absorptiometry of the radius and whole-body dual-energy X-ray absorptiometry.
                Compliance with the supplement was high. No significant differences were detected between the groups in breast-milk calcium concentration, infant birth weight, or growth or bone mineral status during the first year of life. A slower rate of increase in infant whole-body bone mineral content and bone area was found in the supplement group than in the placebo group (group x time interaction: P = 0.03 and 0.02, respectively).
                Calcium supplementation of pregnant Gambian women had no significant benefit for breast-milk calcium concentrations or infant birth weight, growth, or bone mineral status in the first year of life. The age and developmental stage at which calcium supplementation produces the greatest bone effects remain controversial. We tested the hypothesis that calcium supplementation may improve bone accrual in premenarcheal females. Fifty-one pairs of premenarcheal female twins (27 monozygotic and 24 dizygotic; mean +/- sd age, 10.3 +/- 1.5 yr) participated in a randomized, single-blind, placebo-controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate (Caltrate) supplement. Areal bone mineral density (aBMD) was measured at baseline and 6, 12, 18 and 24 months. There were no within-pair differences in height, weight, or calcium intake at baseline. Calcium supplementation was associated (P < 0.05) with increased aBMD compared with placebo, adjusted for age, height, and weight at the following time points from baseline: total hip, 6 months (1.9%), 12 months (1.6%), and 18 months (2.4%); lumbar spine, 12 months (1.0%); femoral neck, 6 months (1.9%). Adjusted total body bone mineral content was higher in the calcium group at 6 months (2.0%), 12 months (2.5%), 18 months (4.6%), and 24 months (3.7%), respectively (all P < 0.001). Calcium supplementation was effective in increasing aBMD at regional sites over the first 12-18 months, but these gains were not maintained to 24 months. "Preterm" human milk fortified with protein (0.85 gm/dL), calcium (90 mg/dL), and phosphorus (45 mg/dL) was compared with unfortified preterm human milk as a feeding for low birth weight infants. Additionally, a special formula for low birth weight infants (Similac Special Care (SC), 20 cal/oz), was compared with a standard 20 cal/oz formula (Similac). Bone mineral content (BMC), as measured by photon absorptiometry, improved in the study groups fed fortified human milk and Similac SC formula during the first 6 weeks of full oral feedings. Even though the intakes of calcium in the groups fed fortified human milk and Similac SC formula approached the intrauterine requirement for Ca during the third trimester of pregnancy (150 mg/kg/d), the values for BMC in these two groups (37 to 39 mg/cm) at the completion of the study were still considerably less than the intrauterine values for radial BMC at 36 to 37 weeks gestational age (72.6 +/- 14.1 mg/cm). Furthermore, the relative phosphorus deficiency (as determined by increased urinary Ca excretion and increased renal tubular reabsorption of phosphate) in the human milk groups occurred with or without supplements of Ca and P. Rate of weight gain in the fortified human milk group was greater than that of the unfortified human milk group and was comparable to that of infants fed Similac SC formula. Rate of weight gain for the unfortified human milk group was similar to that of infants fed Similac formula containing 20 cal/oz. However, none of the four feeding groups exceeded the 50th percentile for weight at the time of discharge (36 to 37 weeks postconceptional age). The results suggest that fortifying preterm human milk with Ca, P, and protein for low birth weight infants will improve bone mineralization and rate of growth to levels comparable to those achieved with a special formula containing high amounts of protein, Ca, and P. Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.
                We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.
                Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).
                Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).
                Copyright 2006 Massachusetts Medical Society. Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls.
                The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner.
                In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae.
                At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size.
                In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation. Eighty seven pregnant women belonging to poor socioeconomic groups of population were investigated to find out the effect of calcium supplementation during pregnancy on the bone density of the mother as well as of the neonate. Supplements of 300 and 600 mg of elemental calcium administered daily from the 20th week of gestation onward until term, brought about a significant increase in the bone density of the neonates born of such mothers compared to that of the neonates born to unsupplemented mothers. Although no significant difference was observed between the initial and final values for bone densities among the mothers, there was a tendency for an increase in the bone density of the mothers who received 600 mg of calcium supplements. Individual variation of different neonatal bones in their response to maternal calcium supplements was observed. Bone density of the neonate was not related to the birth weight, crown-heel, or crown-rump lengths. Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone. Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.
Calcium supplementation is associated with a significant protective benefit in the prevention of pre-eclampsia, and should be used for this indication according to a previous review. This review indicates that there are no additional benefits for calcium supplementation in prevention of preterm birth or low infant birth weight. While there was a statistically significant difference of 80 g identified in mean infant birth weight, there was significant heterogeneity identified, and the clinical significance of this difference is uncertain.