Preterm Labor and Birth: A Clinical Review.

When caring for women experiencing preterm labor and birth, nurses play a significant role as bedside experts, advocates, patient educators, and key members of the maternity care team. Enhanced expertise on clinical and professional knowledge of preterm labor and birth is crucial in prevention and treatment. As preterm birth rates continue to rise, perinatal nurses as well-informed clinical experts have the opportunity to offer innovative education, holistic assessments, and communication through shared decision-making models. Educating pregnant women about early recognition of preterm labor warning signs and symptoms allows for timely diagnosis, interventions, and treatment. Informed and collaborative nursing practice improves quality of clinical care based on individualized interactions. A clinical review of preterm labor and preterm birth is presented for perinatal nurses.

AhR and IDO1 in pathogenesis of Covid-19 and the "Systemic AhR Activation Syndrome:" a translational review and therapeutic perspectives.

Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a "Systemic AhR Activation Syndrome" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.

Does Compression of the Fourth Ventricle Cause Preterm Labor? Analysis of Data From the PROMOTE Study.

BACKGROUND: The technique for the compression of the fourth ventricle (CV4) in the brain has been described as a method of reaching the physiologic centers that reside in its floor and of restoring optimal flow of the cerebrospinal fluid. However, a study published as an abstract in 1992 questioned whether CV4, when applied to pregnant women, could induce uterine contractions and possibly labor. OBJECTIVE: To further examine whether CV4 could induce uterine contractions and labor as part of the osteopathic manipulative treatment (OMT) protocol used in the Pregnancy Research in Osteopathic Manipulation Optimizing Treatment Effects (PROMOTE) study. METHODS: Labor and delivery data collected during the PROMOTE study from 2007-2011 were analyzed. The PROMOTE study was funded by the National Institutes of Health and was a randomized controlled clinical trial that measured the primary outcomes of back-specific functioning and pain in pregnant women aged 18 to 34 years. Participants were randomly divided into 3 groups-usual obstetric care only, placebo ultrasound treatment plus usual obstetric care, and OMT plus usual obstetric care. Study participants were scheduled for 7 treatment visits. Presented data were gathered from labor and delivery records. RESULTS: Four hundred participants were included. No significant differences were identified between treatment groups for the development of high-risk status (P=.293) or preterm delivery (P=.673). Evaluation of high-risk status by preterm delivery for the groups also showed no significant differences between groups (P=.455). CONCLUSION: The application of CV4 as part of an OMT protocol during the third trimester caused neither a higher incidence of preterm labor nor the development of high-risk status.

Harms of cervical cancer screening in the United States and the Netherlands.

We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilized data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding and discharge) and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21-65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births and over 8 million health problems. Under the Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%) and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared to the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to threefold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations.

Magnesium in pregnancy.

Magnesium deficiency is prevalent in women of childbearing age in both developing and developed countries. The need for magnesium increases during pregnancy, and the majority of pregnant women likely do not meet this increased need. Magnesium deficiency or insufficiency during pregnancy may pose a health risk for both the mother and the newborn, with implications that may extend into adulthood of the offspring. The measurement of serum magnesium is the most widely used method for determining magnesium levels, but it has significant limitations that have both hindered the assessment of deficiency and affected the reliability of studies in pregnant women. Thus far, limited studies have suggested links between magnesium inadequacy and certain conditions in pregnancy associated with high mortality and morbidity, such as gestational diabetes, preterm labor, preeclampsia, and small for gestational age or intrauterine growth restriction. This review provides recommendations for further study and improved testing using measurement of red cell magnesium. Pregnant women should be counseled to increase their intake of magnesium-rich foods such as nuts, seeds, beans, and leafy greens and/or to supplement with magnesium at a safe level.

A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth.

PURPOSE OF REVIEW: The aim of this review was to evaluate recently published review articles which examine the use of nutritional supplements to prevent preterm birth (PTB) by modifying vaginal bacteria. RECENT FINDINGS: Probiotics, vitamin D and vitamin C were all identified as nutritional supplements that have the potential to alter bacterial flora and consequently reduce PTB and treat or prevent genital infections. Evidence shows that probiotics may reduce the incidence of PTB as well as being effective at treating bacterial vaginosis, a known cause for PTB. Low vitamin D levels may be associated with bacterial vaginosis, although no evidence was identified which demonstrated that vitamin D supplementation reduced the risk of having bacterial vaginosis or PTB.There is little evidence regarding vitamin C supplementation, although it does suggest a possible benefit with regard to preterm rupture of membranes; however, this did not appear to reduce rates of PTB. SUMMARY: Although there is evidence that taking probiotics in pregnancy may reduce the incidence of PTB, it is mainly derived from small, poor quality studies. Vitamin D and vitamin C may have potential benefits, but these remain to be proven. Large randomized controlled trials are needed to more accurately evaluate the potential benefits of these low-cost interventions for reducing PTB and its consequences.

[Vitamin D and pregnancy]. / Vitamine D et grossesse.

Vitamin D insufficiency is characterized, since 2005, by 25(OH)D concentration less than 75 nmol/L (or 30 ng/mL). Vitamin D could interfere with many mechanisms involved in preeclampsia's pathogenesis including trophoblastic invasion and immunomodulation as well as blood pressure control and proteinuria. Occurrence of preeclampsia and gestational diabetes seems to be linked to vitamin D deficiency but recent data in the literature are contradictory. Vitamin D supplementation during pregnancy is controversial. Some societies consider it unnecessary and others recommend up to 2000 UI/d. There is no reported case of teratogenicity linked with vitamin D intake.

Use of herbal products among 392 Italian pregnant women: focus on pregnancy outcome.

PURPOSE: The present study aimed to explore the use of herbal products among a sample of Italian pregnant women and the possible influence of herbal consumption on pregnancy outcome. METHODS: The study was conducted over a 10-month period (2 days a week, from January to October 2009) at the Maternity wards of Padua and Rovereto Hospital. Data were collected through a face-to-face interview on the basis of a prestructured questionnaire including socio-demographic characteristics of the enrolled subjects, specific questions on herbal use, information about pregnancy and newborn. RESULTS: In total, 392 interviews were considered. One hundred and nine out of 392 women (27.8%) reported to have been taking one or more herbal products during pregnancy, in the 36.7% of cases throughout all pregnancy. The most frequently herbs taken by interviewees were chamomile, licorice, fennel, aloe, valerian, echinacea, almond oil, propolis, and cranberry. Four out of 109 women (3.7%) reported side-effects: constipation after a tisane containing a mix of herbs, rash and itching after local application of aloe or almond oil. The decision to use herbal products was mainly based on personal judgement and on the conviction that these natural substances would be safer than traditional medicines. Users were more often affected by morbidities pregnancy-related and their neonates were more frequently small for their gestational age. An higher incidence of threatening miscarriages and preterm labours was observed among regular users of chamomile and licorice. CONCLUSIONS: This research underlines that the use of herbal products during pregnancy is common among Italian women, not always appropriate and in some cases potentially harmful.

[Treatment of preterm delivery with calcium channel blockers--Nifedipine].

AIM: To assess the feasibility of the calcium antagonist Nifedipine as an oral tocolytic for the treatment of preterm labor. METHODS: Thirty-seven pregnant women in preterm labor participated in a prospective longitudinal study. Inclusion criteria were: gestational age between 24 and 32 weeks gestation; uterine contractions in 30 min interval; lack of cervical dilatation and lack of contraindications for tocolysis. In all cases the calcium antagonist Nifedipine was used in dosage 4 x 10 mg per os. The clinical response to tocolysis, gestational age at delivery and potential side effects were analyzed. RESULTS: Forty-one pregnant women participated in the study. Two were lost for follow up and another two cases were excluded because myoma uteri was diagnosed. Thirty-seven pregnancies were finally analyzed. In five of them maternal contractions persisted despite of treatment which necessitated parenteral tocolysis. In two of these five cases the pregnancy was terminated (1--spontalneous abortion in 26 w.g., 1--preterm delivery at 32 w.g.). The other 32 pregnancies were delivered at term without any side effects attributed the treatment. CONCLUSION: Nifedipine is an effective oral tocolytic and a rational alternative to other tocolytic agents in the management of preterm labour.

[Etiologic factors of prematurity in Ziguinchor maternity hospital center (Senegal)]. / Facteurs étiologiques de la prématurité au centre hospitalier régional de Ziguinchor, Sénégal.

A case-control study was conducted between September 2003 and January 2004. Fifty four newborn babies born before 37 weeks of gestation resulting from 47 pregnancies including 7 multiple pregnancies were compared to 105 newborn babies born between 37 and the 42 weeks of gestation. Parturient geographical origin, marital status, age, alcohol or tea consumption and height were not significantly associated to premature birth (p > 0.05). On the other hand, a higher parity or equal to 3, a number of antenatal care lower than 3 were significantly associated with the risk of premature birth (p < 0.05). But a gestity and a parity lower than 3 and a number of antenatal consultations higher or equal to 3 had a protective effect (OR < 1; p < 0.05). We recommend a reinforcement of malarial prevention during pregnancy according to WHO recommendations and the improvement of the quality of the antenatal care in the Ziguinchor medical district.

World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women.

OBJECTIVE: The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Polyunsaturated fatty acids and risk of preterm delivery.

Preterm delivery (PD) is characterized both by increased neonatal morbidity and mortality and by important late pathologic sequelae. From a clinical stand-point, PD may results from a medical condition where the continuation of pregnancy could bring about a marked risk for the foetus and/or for the mother, or from an adverse event where the pregnancy is going to end spontaneously before 37 weeks of gestation. In the past few years some epidemiological studies have shown that diet may interfere with complex multifactorial processes contributing to the preterm triggering of labour. The attention has been focused on polyunsaturated fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and linoleic acid, precursor Omega-6 series. Their importance in modulating Prostaglandin concentrations at different levels is already known. Moreover, it has been reported that in clinical situation, such as PD, the endogenous levels of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational and clinical studies suggest that dietary intake of Omega-3 fatty acids is capable of significantly prolonging the duration of gestation in the range of 4-7 days; such prolongation would possibly occur through the inhibition of prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3 appears to be marginal, and recommended assumption could be reached only by a ten-fold increase in blue fish ingestion. The recommended intake of EPA + DHA should be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in light of controlled clinical studies and of the actual categories of risk for preterm delivery, the dietary supplementation of Omega-3, in addition to other pharmacological measures (17alpha-hydroxyprogesterone caproate), could be implemented for the secondary and/or tertiary prophylaxis of preterm delivery.

[Severe maternal anemia and pregnancy outcome]. / Anémies maternelles sévères et issues de grossesse.

OBJECTIVES: The aim of this study was to determine the effects of severe antenatal maternal anemia on pregnancy outcome. MATERIAL: and methods. A retrospective study comparing 2 groups of pregnant women: 111 (pregnant women) with anemia (Hb < 8 g/dl), 111 non- anemic pregnant women (Hb >10 g/dl). Clinical and biological characteristics for both groups were compared. Data on the newborn babies were collected. RESULTS: In the anemic group: iron deficiency was the most common cause of anemia (92.7%). There was no significant difference between the 2 groups with respect to age or parity. Maternal anemia was found to be significantly associated with more frequent preterm birth (29.2% vs 9.2%) and increased low birth weight (2933 g vs 3159 g). DISCUSSION: The literature is not conclusive on the influence of anemia in pregnant women. More frequent preterm birth and low birth weight have been reported in the majority of studies considering mild to moderate maternal anemia (in contrast to our study where the mothers had severe anemia). Many studies indicated that routine iron supplementation during pregnancy may have beneficial effects on pregnancy outcome. Severe anemia in pregnancy may have adverse effects for the newborn and should be treated or prevented early in pregnancy.

Multivitamin use and the risk of preterm birth.

Previous research suggests that multivitamin use before and during pregnancy can diminish diet-related deficiencies of certain micronutrients and potentially prevent preterm birth. To assess this association, the authors performed an analysis by using data from the Pregnancy, Infection, and Nutrition Study (n = 2,010). Women were recruited at 24-29 weeks of pregnancy from four prenatal care clinics in North Carolina from August 1995 to June 2000. For women who took multivitamins prior to pregnancy, compared with nonusers, the adjusted risk ratio was 0.50 (95% confidence interval: 0.20, 1.25) for delivering preterm (<37 weeks). In contrast, prenatal and periconceptional use, compared with nonuse, were not related to preterm birth, with adjusted risk ratios of 1.1. Preconceptional multivitamin use was inversely associated with both early (<35 weeks; adjusted odds ratio = 0.59, 95% confidence interval: 0.12, 2.76) and late (35-36 weeks; adjusted odds ratio = 0.40, 95% confidence interval: 0.12, 1.40) preterm birth; findings were based on only two and three exposed cases, respectively. These results suggest that, compared with nonusers, women who take multivitamin supplements prior to conception may have a reduced risk of preterm birth, but further studies are needed with a larger sample of preconceptional users.

Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort.

Previous studies, mainly among populations with high consumption of seafood, have suggested that increased marine n-3 polyunsaturated fatty acid (PUFA) intake during pregnancy promotes longer gestation and higher birth weight. Few studies have isolated the contribution of fetal growth to birth weight. Using data from 2,109 pregnant women in Massachusetts enrolled in Project Viva from 1999 to 2002, the authors examined associations of marine n-3 PUFA and seafood intake with birth weight and birth-weight-for-gestational-age z value (fetal growth) using linear regression; length of gestation using median regression; and low birth weight, preterm delivery, and being small for gestational age using logistic regression. After adjustment for maternal and child factors, birth weight was 94 (95% confidence interval: 23, 166) g lower and fetal growth z value 0.19 (95% confidence interval: 0.08, 0.31) units lower in the highest compared with the lowest quartile of first-trimester n-3 PUFA intake. Results for the second and third trimesters were similar, and findings for seafood paralleled those for n-3 PUFA. Elongated n-3 PUFA intake and seafood intake were not associated with length of gestation or risk of preterm birth. Results from this US cohort support the conclusion that seafood intake during pregnancy is associated with reduced fetal growth.

Women and omega-3 Fatty acids.

Omega-3 fatty acids (omega-3 FA) are constituents of the membranes of all cells in the body and are precursors of locally produced hormones, eicosanoids, which are important in the prevention and treatment of various diseases, especially in women. Omega-3 FA are of interest in some of the most common conditions affecting women. One mechanism underlying dysmenorrhea is a disturbed balance between antiinflammatory, vasodilator eicosanoids derived from omega-3 FA and proinflammatory, vasoconstrictor eicosanoids derived from omega-6 FA. Increased intake of omega-3 FA can reverse the symptoms in this condition by decreasing the amount of omega-6 FA in cell membranes. An increased prostacyclin/thromboxane ratio induced by omega-3 FA can facilitate pregnancy in women with infertility problems by increasing uterine blood flow. Supplementation with omega-3 FA during pregnancy lowers the risk of premature birth and can increase the length of pregnancy and birth weight by altering the balance of eicosanoids involved in labor and promote fetal growth by improving placental blood flow. Intake of omega-3 FA during pregnancy and breast feeding may facilitate the child's brain development. There is also some evidence that supplementation with omega-3 FA might help to prevent preeclampsia, postpartum depression, menopausal problems, postmenopausal osteoporosis, and breast cancer. Furthermore, because elevated triglyceride levels are associated with cardiovascular disease, especially in women; and because omega-3 FA have powerful effects on triglycerides, women in particular gain from an increased intake of these fatty acids. This is especially important in women receiving hormone therapy, which can increase triglyceride levels. The quality of the omega-3 FA preparation is important. It should have an appropriate antioxidant content not to induce lipid peroxidation, and its content of dioxin and polychlorinated biphenyls (PCBs) should be well below the established safe limit.

Rapidly polymerizing hydrogel prevents balloon dislodgement in a model of fetal tracheal occlusion.

BACKGROUND/PURPOSE: This study examined whether an injectable hydrogel could buttress the balloon used in fetal tracheal occlusion, thus preventing its displacement. METHODS: Fetal lambs (n = 11) underwent tracheal occlusion through local delivery of a detachable silicone balloon and were divided in 2 groups: group I had no further manipulations, and group II received an intratracheal injection of a rapidly polymerizing hydrogel, cranially to the balloon. Near term, balloon placement was examined, the lung volume-to-body weight ratio (LV:BW) was determined, and tracheal histology was performed. Statistical analysis was by the Fisher's Exact test, with significance set at P <.05. RESULTS: Complete tracheal occlusion was achieved in all fetuses intraoperatively. The rate of balloon dislodgement was significantly higher in group I (4 of 7, or 57.1%) than in group II (0 of 4). In group II, balloons were recovered in situ with a column of residual hydrogel reinforcing their cephalad position. Animals in which balloon occlusion was maintained had significantly higher LV:BW, with no evidence of tracheal damage. CONCLUSIONS: Intratracheal delivery of a rapidly polymerizing hydrogel cephalad to detachable silicone balloons results in improved fetal tracheal occlusion, with no harmful effects to the trachea. This adjuvant principle may enhance minimally invasive balloon tracheal occlusion for treatment of severe fetal pulmonary hypoplasia.

New data on the importance of gestational Mg deficiency.

Chronic primary Mg deficiency is frequent. About 20% of the population consumes less than two-thirds of the RDA for Mg. Women, particularly, have low intakes. For example, in France, 23% of women and 18% of men have inadequate intakes. Mg deficiency during pregnancy can induce maternal, fetal, and pediatric consequences that might last throughout life. Studies of gestational Mg deficiency in animals show that Mg deficiency may have marked effects on parturition and postuterine involution. It has interfered with fetal growth and development, and caused morbidity from hematological effects and disturbances in temperature regulation, to teratogenic effects. Emphasis, here, is on effects of chronic clinical gestational Mg deficiency as it affects the infant. Premature labor, contributed to by uterine hyperexcitability caused by chronic maternal Mg deficiency, that can be intensified by stress, gives rise to preterm birth. If the only cause of uterine overactivity is Mg deficiency, its supplementation constitutes nontoxic tocolytic treatment, as an adjuvant treatment, that is devoid of toxicity and enhances efficacy and safety of tocolytic drugs such as beta-2 mimetics. Evidence is considered that Mg deficiency or Mg depletion can contribute to the Sudden Infant Death Syndrome (SIDS). SIDS may be a fetal consequence of maternal Mg deficiency through impaired control of Brown Adipose Tissue (BAT) thermoregulation mechanisms leading to a modified temperature set point. SIDS can result from dysthermias: hypo- or hyperthermic forms. Possibly, simple nutritional Mg supplements might be preventive. Various stresses in an infant can transform simple Mg deficiency into Mg depletion. For example, lying prone can be stressful for the baby, as can parental smoking. The role of chronopathological stress appears to be often neglected, as it constitutes a clinical form of primary hypofunction of the biological clock [with its anatomical and clinical stigma such as reduced production of melatonin (MT) and of its urinary metabolite: 6 Sulfatoxy-Melatonin (6 SMT)]. SIDS might be linked to impaired maturation of both the photoneuroendocrine system and BAT. Prophylaxis of this form of SIDS should include atoxic nutritional Mg therapy for pregnant women with total light deprivation at night for the infant. Consequences of maternal primary Mg deficiency have been inadequately studied. To determine ultimate outcomes of gestational Mg deficiency in infants, a long-term multicenter placebo-controlled prospective study should undertaken on effects of maternal nutritional Mg supplementation on lethality/morbidity in fetus, neonates, infants, children and adults, not only during pregnancy and the baby's first year, but throughout life.