The Yin and Yang of Maternal Calcium & Magnesium: How Chronic Magnesium Insufficiency and an Unbalanced Calcium to Magnesium Ratio Impact Fetal Development and Maternal Health

1. Introduction

Calcium & Magnesium – Two Major Mineral Nutrients

Calcium (Ca²⁺) and magnesium (Mg²⁺) are both essential minerals that play vital roles in many physiologic processes. Mg²⁺ and Ca²⁺ work together to support each other’s absorption and utilization. Maintaining a proper ratio (i.e., balance) between these minerals is necessary for each of them to carry out their individual roles, which are discussed below.

Ca²⁺ is the most abundant mineral in the human body with nearly all (99%) of it contained as insoluble calcium phosphates within the skeleton and teeth. The remainder, which is found as ionized Ca²⁺ in the circulatory system, intra- and extracellular fluids, and various tissues, is vital to maintaining the skeleton, transmitting nerve impulses, and regulating hormone secretion, vascular tone, cellular signaling, blood clotting, and cardiac and skeletal muscle function [1]. Ca²⁺ participates in the structural stabilization of biomolecules and membranes and controls the catalytic activity of hundreds of enzymes [2,3]. With respect to pregnancy and lactation, Ca²⁺ triggers new life at fertilization, controls several developmental processes, and may also regulate diverse cellular processes during differentiation including metabolism, proliferation, secretion, contraction, synaptic transmission, learning and memory [4].

Mg²⁺ is the fourth most abundant mineral in the human body, behind Ca²⁺, sodium (Na), and potassium (K), and the second most abundant intracellular cation following K [5,6,7,8]. Like Ca²⁺, most of the body’s Mg²⁺ is found in the skeleton (50-60%) with the remainder contained in the muscles and tissues (40-50%). Less than 1% is found in the circulatory system, with the largest fraction of this 1% contained in erythrocytes. Mg²⁺ plays crucial roles in diverse physiological processes [5,6,7,8]. It is critical to the stability of all polyphosphate compounds and their roles in many enzymatic reactions. These reactions facilitate the hydrolysis of phosphate esters (ATPases), and the transfer of phosphoryl groups (kinases and phosphatases) in virtually every metabolic pathway [7]. Mg²⁺ serves as a cofactor in over 600 enzyme systems that govern a variety of physiological activities, including glucose metabolism, protein synthesis, muscle and nerve transmission, neuromuscular conduction, blood glucose management, and blood pressure regulation [5,6,7,8]. It also plays an important role in signal transduction, most likely as a second messenger [11], and is required for the active transport of Ca²⁺ and K ions across cell membranes, making it essential for proper immune responses, antioxidant synthesis, vitamin D synthesis and activation, nerve impulse transmission, muscular contraction, vasomotor tone, and proper heart rhythm [7,9,10].

In this review we evaluated how maternal levels of Ca²⁺ and Mg²⁺ during pregnancy affect health outcomes of the fetus. We focused on these two minerals because they are critical for proper fetal growth and development, and disruptions to their maternal levels are strongly associated with poor outcomes. The goal of this literature analysis was to determine if a cutoff concentration of Mg²⁺, which may reflect chronic latent Mg²⁺ deficiency, could potentially inform on adverse health risks to mother and/or baby early in pregnancy (first and second trimester). Conditions that occur late in pregnancy (third trimester) have been widely reported on and therefore were not the focus of this review.

2. Materials and Methods

The PRISMA-S search protocol was used to search scientific and clinical databases, as well as private collections, to identify and analyze almost 2,000 publications [108]. Searches included terms such as “pregnancy,” “lactation,” “calcium,” “magnesium,” “fetus,” “maternal,” “serum,” and related search terms. Results were published on or before May 1, 2025. We screened over 1,500 results and selected 107 core articles after removing duplicates, as well as secondary, non-English, and irrelevant studies.

3. Results

Reported levels of serum Ca²⁺ and Mg²⁺ during pregnancy and lactation

Pregnancy and lactation are times of high Ca²⁺ and Mg²⁺ demand [12,13]. Approximately 25-30 g of Ca²⁺ and 0.8 to 1 g of Mg²⁺ are transferred from mother to the fetal skeleton by the end of a normal pregnancy. Typically, the fetus accumulates 2-3 mg Ca²⁺/day during the first trimester [12]. During the second and third trimesters the rate of accumulation increases to 250 mg Ca²⁺/day and over 300 mg Ca²⁺/day, respectively.

Less is known about the rates of Mg²⁺ accumulation by the fetus. Historical data suggest that about 80% of fetal mineral content is accumulated during the third trimester, as Ziegler’s 1976 study reported that the rate of Mg²⁺ transfer increases from 1.8 mg/day to 5-7.5 mg/day over the last five weeks of pregnancy [13]. However, more recent clinical data from Larsson et al. clearly show that maternal Mg²⁺ transfer to the placenta and fetus takes place in parallel with Ca²⁺ transfer and begins early in the first trimester (Table 1) [14]. It is our stance that Larson’s tabulated data is particularly important because they were gathered from a defined population in a single laboratory over time, and thus less susceptible to the variability introduced by inter-laboratory analyses of diverse populations [15]. The question then, of whether these data could be applicable to the population at large, can be answered by other reports by Cai et al. (China) and Hansu and Cikim (Turkey), which suggest the trends summarized in Table 1 are pregnancy in women around the world [16,17].

Some have asserted that the changes in Mg²⁺ levels reported by Larsson et.al. reflect its dilution caused by increases in plasma volume during pregnancy. This idea is not supported by data published by De Jorge et al., which shows Mg²⁺ concentrations show a similar pattern of changes throughout pregnancy (Table 2) [19].

In another study, Rigo et al. confirm that Larsson’s findings on the mineral levels in the mother also inform Mg²⁺ levels in the fetus [20]. Here, a systematic literature review and meta-analysis of serum Mg²⁺ levels in newborns was conducted with the goal of quantifying normal and tolerable concentration ranges during the neonatal period. In this review they also highlighted factors that influence Mg²⁺ levels and how maternal Mg²⁺ levels during pregnancy relate to serum Mg²⁺ in the neonate at birth. Their literature review showed that mothers who did not receive dietary Mg²⁺ supplementation during pregnancy gave birth to neonates with Mg²⁺ levels (0.76 (95% CI: 0.52, 0.99) mmol/L) similar to those of their mother during pregnancy (0.74 (95% CI: 0.43, 1.04) mmol/L). However, neonate levels increased during the first week of life (0.91 (95% CI: 0.55, 1.26) mmol/L) before returning to their baseline levels (0.74 (95% CI: 0.43, 1.04) mmoL/L). This pattern was also seen in mothers who received dietary Mg²⁺ supplementation during pregnancy. In this group the average neonatal serum Mg²⁺ concentration was higher at 1.29 mmol/L (95% CI: 0.50, 2.08), which rose to 1.44 mmol/L (95% CI: 0.61, 2.27) during the first week of life. It should be noted that despite the low average Mg²⁺ levels in mothers who did not receive dietary supplements, some individuals in this group gave birth to newborns with Mg²⁺ levels as high as 2.0 mmol/L. Serum Mg²⁺ levels > 2.5 mmol/L have been linked to an increased risk of mortality, admission into intensive care, hypotonia, hypotension, and respiratory depression [21,22,23]. However, in Rigo’s study, serum Mg²⁺ levels of 2.0 mmol/L were shown to be well tolerated by neonates.

Maternal transfer of minerals continues during lactation [24]. Breastmilk contains higher levels of Ca²⁺ and Mg²⁺ at the start of lactation, which start to decline after approximately 6 months (Table 3) [25,26,27]. Assuming a daily neonatal intake of about 800 mL of breast milk, this fluid provides 225-240 mg Ca²⁺/day early in lactation and 200-210 mg Ca²⁺/day later in lactation to support continuing neonatal growth and development. Likewise, Mg²⁺ content in this volume of breast milk is 27 mg/day early in lactation and decreases to 18 mg/day later in lactation.

The data generated by Gates et. al. (Table 3) also reveal insight into how mineral deficiencies in mothers of preterm infants are reflected in the quality of their breastmilk [27]. Their preterm children had an average gestational age of 28.2 ± 2.8 weeks and average birth weight of 1,098 g (vs. normal term birth weight of about 3,200 g). The volumes of breast milk each day increased from an average of 171.8 mL (day 7) to 224.2 mL (day 21) and then decreased slightly to 210.3 mL. In addition to the shortfall in milk supply by these mothers as compared to mothers who carry to term, the Ca²⁺ content in their breastmilk was initially low and decreased during lactation. In contrast, both the Mg²⁺ and phosphorus content of their breastmilk paralleled the contents of breastmilk provided by mothers of full term babies.

Another Perspective: The Molar Ratio of Serum Ca²⁺ to Serum Mg²⁺ and Impacts on Fetal and Maternal Outcomes

Larsson’s data on Ca²⁺ and Mg²⁺ levels from pregnancy to postpartum (Table 1) may also be considered from another perspective: the molar ratio of serum Ca²⁺ to serum Mg²⁺ (Table 4).

Both clinical guidelines and published data show that the risk of adverse effects on mother and/or fetus is minimal when both serum Ca²⁺ and serum Mg²⁺ are high in the reference ranges (Table 4, HiCa:HiMg column).2 In contrast, these same documents raise minor concerns when serum Ca²⁺ is low in the reference ranges. For example, Tsakiridis et al. reviewed the most recently published guidelines for antenatal nutrition issued by five international regulatory or medical authorities [28]. They found that most of these authorities recommended Ca²⁺ supplementation in populations with low dietary Ca²⁺ intake. Clinical data suggested that supplementation benefitted women at risk for preeclampsia and reduced the risk of gestational hypertension, neonatal mortality, and preterm birth in women with low dietary Ca²⁺ intake. The data were sufficient to prompt the recommendation that Ca²⁺ consumption be highly encouraged during pregnancy, especially during the second and third trimester.

Likewise, Adams et al. summarized evidence for the benefits associated with supplementation of Ca²⁺ and Mg²⁺ [29]. They identified clear associations between low serum Ca²⁺ and risk of preeclampsia, eclampsia, and pregnancy-induced hypertension, supporting the benefits of supplementation. Less definitive correlations between the effects of supplementation and preterm birth or maternal mortality were identified. Maternal Ca²⁺ supplementation was also related to reductions in neonatal hypertension, low birth weight, and neonatal intensive care unit admission. The authors concluded that Ca²⁺ supplementation of 550 mg of elemental Ca²⁺ daily should be recommended for U.S. women, with a need for higher levels of supplementation if the woman had a low intake of milk, vegetables, or milk-based foods or was at high risk of preeclampsia, preterm birth, and/or gestational hypertension. It was speculated that supplementation could help reduce the risk of other conditions associated with low Ca²⁺ intake including preterm birth, low birth weight, neonatal mortality, and Autism Spectrum Disorder.

Despite the value of Ca²⁺ in maintaining skeletal integrity [30,31], neither Adams nor other recent reviewers identified a relationship between low serum Ca²⁺ and maternal bone health. For example, Tihtonen et al. screened 3,555 records in 11 databases and analyzed data from seven randomized controlled trials (RCTs) including 1,566 pregnant women [32]. No advantage of Ca²⁺ supplementation was found on maternal bone mineral density after delivery or during breast-feeding, even when dietary Ca²⁺ intake was low. Further, the conclusion was not modified even when the dose of Ca²⁺ or concomitant vitamin D administration was considered. Similarly, Cai et al. screened supplementation reports in multiple databases and analyzed five randomized controlled trials including 567 lactating women [33]. Their meta-analysis indicated that Ca²⁺ supplementation does not provide clinically important benefits for bone mineral density in lactating women. However, both groups of investigators noted confounding elements, in that there was adequate dietary intake before supplementation in some studies, and others did not measure baseline Ca²⁺ intake. These findings suggested that advising lactating women to meet the current recommended Ca²⁺ intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available.

Conversely, when the serum Mg²⁺ concentration is low (Table 4, LoCa:LoMg and HiCa:LoMg columns), the published literature is rife with adverse consequences.

Adverse Effects Associated with Maternal Chronic Mg²⁺ Insufficiency Early in Pregnancy

Instead of describing reduced Mg²⁺ as a “deficiency,” we will use the term “chronic insufficiency” to define a metabolic state where the serum mineral concentration is in the lowest quartile of its normal range (Table 1) for a period of at least 3 months. Recent reports suggest that chronic Mg²⁺ insufficiency enhances the risks of adverse events for mother and child (Table 5). We will focus our attention on examples of adverse events that occur early in pregnancy (Table 6), because adverse effects that occur late in pregnancy are widely recognized.

4. Interim Summary & Action Steps

Pregnancy and lactation are stressful periods of increased metabolic demands associated with changes in the mother’s physiology and social environment and developmental requirements of the child. Clinicians recognize that many women fail to consume adequate vitamins and minerals necessary to support a healthy pregnancy. When this is the case, supplementation of key vitamins and minerals may be required. Optimizing endometrial wellbeing may also help to prevent common pregnancy complications, including adverse effects on both early and late fetal development, as well as compromised mineral and complex oligosaccharide levels in breast milk.

For a mineral such as iron, the U.S. Food and Drug Administration has provided specific recommendations for provision with folate. In contrast, no specific recommendations for prenatal Ca²⁺ or Mg²⁺ supplementation have been established. This is a significant shortcoming, since inadequate stores or intake of these two essential mineral nutrients can have adverse effects on the mother, such as hypertension, complications of labor, and extended disability and recovery time after delivery. Furthermore, the fetus can be affected, resulting in abnormal organ and tissue development, intrauterine growth retardation, congenital malformations, reduced immunocompetence, preterm delivery, and lifelong, increased risk of metabolic disturbances such as type 2 diabetes, metabolic syndrome/obesity, hypertension, and chronic kidney disease.

5. What Constitutes the Reference Range for These Minerals?

Serum Ca²⁺ is routinely monitored, and the reference range for Ca²⁺ (2.2-2.7 mmol/L) is relatively consistent around the world [1]. Consequently, Ca²⁺ levels are readily available to clinicians, providing guidance in patient care. In contrast, Mg²⁺ is often viewed as a micromineral that has little significance until serious adverse events (e.g., preeclampsia, eclampsia, high risk of premature birth) prompt administration of tocolytics such as intravenous magnesium sulfate. Also, the interpretation of serum Mg²⁺ levels presents a number of practical problems. First, serum Mg²⁺ may not be routinely monitored, although clinical instruments for such monitoring are readily available [56]. Interlaboratory variability further complicates interpretation of existing data [57,58]. Equally problematic is the observation that there is little consensus on reference values and the units in which they are reported. Serum Mg²⁺ values are reported in mg/dL, mmol/L, or mEq/L. In addition, serum Mg²⁺ values may be determined as total Mg²⁺ or ionized Mg²⁺. As a result of these differences, no standardized reference range for serum Mg²⁺ has been established, which has led to a wide variety of reference ranges being reported (Table 7).

Serum Mg²⁺ concentration shows little variation as a consequence of tight physiological regulation, and clinicians have concluded that its serum concentration may not provide the most informative picture of Mg²⁺ status in an individual [73,74]. Nonetheless, if chronically low serum Mg²⁺ is a concern, defining ranges of serum Mg²⁺ concentrations that will support the health of both normal subjects and patients remains a challenge that merits attention [75,76]. Indeed, the German Society for Magnesium Research e.V. recently proposed a value of 0.85 mmol/L to define the lower limit of serum Mg²⁺ concentration associated with lower risks to good health [77,78].

Are the dietary requirements for calcium and magnesium adequately met?

The recommended daily Ca²⁺ intake in the general adult population ranges between 500 and 1,300 mg daily [1,79]. Surprisingly, the Recommended Daily Allowances (RDAs) for pregnant and lactating women (1,000-1,300 mg Ca daily) fall within the same range. Maternal sources of both Ca²⁺ and Mg²⁺ include increased uptake from the diet, increased renal uptake and recirculation, and bone resorption. In fact, bone resorption is so extensive that the loss of Ca²⁺ during pregnancy and 6 months of lactation is equivalent to 4-5% of the mother’s total skeletal calcium content (about 1,200 g Ca²⁺) [1]. (Bone loss is expected to be more extensive if a mother bears twins or triplets.)

As Weaver, Heaney and others have noted, most of the Ca²⁺ in the American diet comes from dairy products [80]. (N.B. Dairy products do not include oat, soy or other plant-derived “milk.”) Changes in the Western diet indicate that diet alone may not be sufficient to meet maternal needs for Ca²⁺ during pregnancy and lactation. As a result, in 2020, the World Health Organization issued an updated guideline for Ca²⁺ supplementation before and during pregnancy [81]. The committee concluded that low-certainty evidence suggests that starting Ca²⁺ supplementation before and/or early in pregnancy (compared to placebo or no treatment) may include the possibility of a risk reduction for preeclampsia and eclampsia, particularly for those women with greater than 80% compliance with calcium supplementation. They also noted “that the acceptability of Ca²⁺ supplementation by women may vary – while women may value nutritional interventions that can lead to a healthy baby and a positive pregnancy experience, Ca²⁺ tablets can be large, have a powdery texture and be unpalatable to consume. Feasibility may also be limited in settings where Ca²⁺ is not always available due to logistical or staff constraints or cost. In addition, limited access to pre-conception healthcare services may be a barrier to the provision of Ca²⁺ supplements prior to pregnancy.”

The recommended daily Mg²⁺ intake in the general adult population ranges between 310 and 420 mg, whereas pregnant women have a recommended daily Mg²⁺ intake of 350–400 mg [82]. Maternal sources of Mg²⁺ include uptake from the diet, renal uptake and recirculation, and bone resorption. In addition, some evidence suggests altered tissue distribution and an increased renal output of Mg²⁺ during pregnancy [83]. Unlike Ca²⁺, Mg²⁺ uptake is not significantly affected by vitamin D. Dietary surveys confirm that dietary Mg²⁺ remains below recommended levels in Europe and the United States. According to several recent reports, these diets include between 30% and 50% less Mg²⁺ than the daily recommended dosage [84,85]. Many authorities state, however, “magnesium deficiency is extremely rare [87].”

Likewise, both the Australian Government Department of Health and World Health Organization guidelines state that there is insufficient evidence to conclude whether dietary Mg²⁺ supplementation during pregnancy is beneficial, even for leg cramps [28]. Other government authorities are silent about Mg²⁺. Adams et al. and other investigators provide weak recommendations for Mg²⁺ supplementation [29]. “Overall, because U.S. women have average magnesium intake that is 22% less than the RDA, and because levels decrease during pregnancy, we recommend supplementing with 350 mg because 345 mg was found be sufficient to keep magnesium levels stable, and supplementation studies with doses of 345–500 mg were found to be beneficial. This recommendation appears likely to reduce the rate of pregnancy-induced hypertension, maternal hospitalization, preterm birth, low birth weight, and low Apgar scores, and could possibly help with other conditions as well [29].”

Defining an Action Range for Mg²⁺

By considering all this information together with recent reports by Čabarkapa et al., Liebscher and Liebscher, Escobedo-Monge et al., and Rosanoff et al., an action range for Mg²⁺ (i.e., a concentration range that may prompt clinical intervention) can be reasonably defined as 0.7 to 0.85 mmol serum mg/L [87,88,89]. Čabarkapa’s prospective study, which included 403 pregnant women > 18 years old, with singleton pregnancies, provides particularly relevant data [87]. Between 11- and 14-weeks’ gestation, a single blood sample was collected from every study participant and concentrations of urea, creatinine, uric acid, Mg²⁺, free beta subunit of human chorionic gonadotrophin, plasma protein A related to pregnancy, and C-reactive protein were measured. All subjects were followed through the rest of pregnancy. 61 of the study participants developed pre-eclampsia and were retrospectively compared to a group of 342 participants who experienced uncomplicated pregnancies and normal outcomes. Serum Mg²⁺ levels were significantly lower in PEKT mothers compared to the TNT group (0.69 ± 0.18 vs. 0.85 ± 0.08 mmol/L; p < 0.001). The level of serum Mg²⁺ had the strongest significant positive correlation (p < 0.05) with the week of gestational outcomes (R = 0.442), weight (R = 0.416), and Apgar score (R = 0.343) of the newborns, and the strongest significant negative correlation with the number of miscarriages (R = −0.413), serum creatinine levels (R = −0.471), and the number of pregnancies (R = −0.326). The week of gestational outcome was predicted with the greatest reliability by the serum Mg²⁺. A serum Mg²⁺ level ≤ 0.81 mmol/L in the first trimester predicted preeclampsia with a sensitivity of 77.0% and specificity of 71.6%. When serum creatinine levels were considered in conjunction with serum Mg²⁺, it was found that creatinine levels > 53 µmol/L detected preeclampsia with a sensitivity of 93% (preeclampsia 62.3 µmol/L vs. normal 49.2 µmol/L; p < 0.001). Thus, in late first trimester, Ca²⁺, Mg²⁺ and creatinine levels appear to be biomarkers associated with risk of preeclampsia later in pregnancy.3

6. Potential for Reducing Risks

If our working hypothesis has validity, high Ca²⁺: Mg²⁺ molar ratios (i.e., values in the range > 3, see Table 4) and serum Mg²⁺ concentration in the lowest quartile of the reference range (0.7 - 0.85 mmol/L) may present increased risk for complications during pregnancy and lactation (Figure 1). “Moving the needle” by increasing maternal serum Mg²⁺ concentration to ≥ 0.85 mmol/L is a potential action step. How can this be accomplished? Actions such as the following may reduce the risks associated with chronic Mg²⁺ insufficiency.

Diet and education

As a first action step, let us echo the words of Murphy et al. [90]. “Adequate consumption of nutrients that support infant neurodevelopment is critical among pregnant women and women of childbearing age.” Their review of the potential effects of socioeconomic inequalities on nutrient gaps in these life stages is particularly informative. They analyzed data from 2007–2018 NHANES related to usual intake (foods and dietary supplements) of neurodevelopment-related nutrients among women of childbearing age and pregnant women (20–44 years). Usual intake was compared across household food security, poverty-to-income ratio (PIR), and household participation in federal food and nutrition assistance programs. Women in households that participated in the Supplemental Nutrition Assistance Program had a significantly lower intake of multiple nutrients relative to those who did not participate. For example, 50% had intakes below the estimated average requirement (EAR) for vitamin A (versus 32%), 42% were below the EAR for calcium (versus 33%) and 65% were below the EAR for magnesium (versus 42%). Similar gradients were observed by PIR and household food security, and among pregnant women wherein gaps were more evident in those experiencing socioeconomic inequalities. The use of dietary supplements attenuated shortfalls for most nutrients. These findings highlight a critical need to support the nutritional requirements for women of childbearing age and pregnant women.

As Henriksen and others have pointed out, a mixed diet including whole grain cereals, milk and dairy products, vegetables, starchy roots, berries, meat and fish constitutes the best sources of Mg²⁺ [80,91]. Magnesium concentrations are especially high in dark chocolate, and nuts. “Hard” water contains more Mg²⁺ than “soft” water and drinking either “hard” or mineral water can contribute 10–20 mg/day to the total Mg²⁺ intake.

Supplementation

Numerous clinical trials have tested whether the risk the pregnancy complications mentioned herein can be mitigated by supplementing the diet with Mg²⁺ alone or with a combination of Mg²⁺ and Ca²⁺. Unfortunately, the results are conflicting and have often been judged to be of low evidentiary value [92,93,94,95,96,97,98,99]. When statistical analyses fail to establish causal relationships, authors may conclude that serum mineral levels were “adequate” [99].

On the other hand, since Mg²⁺ is involved in roughly 80% of physiological processes, establishing causal relationships between serum Mg²⁺ and risks associated with chronic Mg²⁺ insufficiency through statistical analyses of data from large clinical trials may be an unrealistic expectation. For example, well-designed trials typically include large cohorts of women having a wide range of serum Mg²⁺ levels. Mechanistically, those with sufficient Mg²⁺ will not benefit from supplementation, since absorption will be limited naturally; their lack of responsiveness will skew subsequent statistical analyses unless the data are stratified. Some of the trial designs include supplementation that is started during pregnancy and is of short duration. This may be “too little and too late,” since some studies suggest twelve weeks or more of supplementation may be needed to restore intracellular Mg²⁺. Moreover, Larsson’s data (Table 1) show that Mg²⁺ is utilized from start to finish of pregnancy [14]. Finally, the course of supplementation may be inadequate.

This last comment is illustrated by comparison of the outcomes of two randomized clinical trials in which nominal supplemental doses of 300 mg of magnesium citrate were administered daily to pregnant women at risk for adverse events [100,101]. The BRAMAG study was carried out at three centers in Brazil [100]. Over 800 women were enrolled, each with a singleton pregnancy and at least one risk factor for adverse events. The 407 women in the treatment group received a tablet containing 300 mg of magnesium citrate daily from the 12^th to the 20^th week of gestation.4 Preeclampsia or eclampsia, severe hypertension, placental abruption, and stroke or death were monitored in the mothers. Preterm birth, stillbirth, neonatal death or NICU admission after birth, and small for gestational age birthweights were monitored in the offspring. Data from the 407 study participants who received magnesium citrate compared to data from 422 participants who were given placebo. 75 neonates (18.4%) in the magnesium supplement arm and 76 neonates (18.0%) in the placebo arm developed at least one of the adverse effects listed above – an adjusted odds ratio (aOR) of 1.10 (95% CI 0.72–1.68). The most common outcome among neonates was preterm birth (9.3%). 49 (12.0%) women in the magnesium arm and 41 women (9.7%) in the placebo arm developed at least one of the pregnancy complications listed above – an aOR of 1.29 (95% CI 0.83–2.00). The most common complication was pre-eclampsia prior to 37 weeks’ gestation (9.3%) and severe gestational hypertension prior to 37 weeks’ gestation (4.9%). Of note, the risk of placental abruption was lower in the magnesium group (9 events [2.2%]) compared to the placebo arm (21 events [5.0%]), equivalent to an adjusted OR of 0.43 (95% CI 0.20 to 0.95). The authors concluded, “Oral magnesium citrate supplementation did not appear to reduce adverse perinatal or maternal outcomes in high-risk singleton pregnancies.”

Conversely, in a separate study that was carried out in Turkey, the effects of Mg²⁺ supplementation in women with serum Mg²⁺ concentrations in the lowest quartile of the normal range were evaluated [101]. The study included 120 pregnant women at 12-14 weeks’ gestation. Participants had an average age of 29 years and normal weight. Most study participants had a history of gestational diabetes mellitus, preeclampsia, preterm birth, and stillbirth. Participants with Mg²⁺ serum levels higher than 1.9 mg/dl were considered a control group (Group A, n = 60). Participants with Mg²⁺ levels lower than this were considered to have hypomagnesemia and were divided into Groups B and C (n = 60 for both). Each participant received a daily multimineral tablet containing 100 mg Mg²⁺ until delivery. Group A had an average serum Mg²⁺ level of 0.86 mmol/L. Groups B and C had an average serum Mg²⁺ level of 0.71 mmol/L. Group C received an additional tablet daily for one month during pregnancy that contained 200 mg Mg²⁺ as magnesium citrate in an effervescent formulation. The data showed that supplemental Mg²⁺ significantly reduced maternal preeclampsia (P = 0.018), preterm birth (P = 0.044), gestational diabetes (P = 0.003), and leg cramps (P < 0.001) for the mother, as well as a reduced risk of intrauterine growth restriction (IUGR) (P < 0.001), low birth weight (P = 0.002), and Apgar score under 7 (P = 0.006) for the child. The investigators concluded, “Mg²⁺ supplement during pregnancy likely decreases the probability of occurrence of many complications of pregnancy.”

7. Discussion

In summary, available data affirm the importance of maintaining adequate maternal mineral nutrition before and during pregnancy and during lactation. Adequate Ca²⁺ and Mg²⁺ may be particularly important to both mother and child, given the broad spectrum of physiological roles of these two key minerals.

Taken together, a growing body of data suggests that maternal counseling about risks associated with serum Mg²⁺ of 0.70 to 0.85 mmol/L and serum Ca²⁺ in the reference range should be considered prior to and early in pregnancy. Straightforward actions such as counseling to improve a mother’s diet, adding necessary supplements both before, during and after pregnancy, have proven valuable and cost-effective in the past and will continue to do so [102,103,104].

Although these actionable insights could potentially mitigate a wide variety of birth defects and complications, we acknowledge this review’s limitations. Randomized controlled trial outcomes reported heterogeneous findings, which highlight the need for additional high-quality prospective studies aimed at evaluating the clinical outcomes of chronic Ca²⁺ and Mg²⁺ insufficiency, defining the optimal serum Mg²⁺ levels, and testing supplementation strategies.

Based on the information available in the scientific literature, we conclude that nutritional supplementation at all stages of pregnancy may be a safe and cost-effective way to reduce the risk of pregnancy complications and adverse outcomes for mother and child [105,106,107]. Future large-scale studies, including randomized trials, will be required to confirm this working hypothesis.