Maddalena Massari

Maternal blood mitochondrial DNA content during normal and intrauterine growth restricted (IUGR) pregnancy.

OBJECTIVE We investigated mitochondrial DNA (mtDNA) content in the maternal circulation of normal pregnancies of different gestational ages and in pregnancies complicated by intrauterine growth restriction (IUGR). STUDY DESIGN We examined 70 maternal blood samples: 13 nonpregnant women; 45 normal pregnancies, divided into the 3 trimesters; and 12 pregnancies complicated by IUGR. MtDNA content was determined by real-time quantitative polymerase chain reaction, using a genomic control and a target gene. RESULTS A highly significant progressive reduction in circulating mtDNA was observed in pregnant women of first, second, and third trimesters and compared to nonpregnant women (mean value: 237, 188, 144, and 283, respectively; P < .001). Moreover, mtDNA was significantly increased in women carrying IUGR fetuses compared to women with normal pregnancies (430 vs 144; P < .001). CONCLUSION MtDNA could provide new insight into the mechanisms that occur during physiological gestation. Furthermore, mtDNA content may help recognize the IUGR disease in pregnancy.

Folate Intake and Markers of Folate Status in Women of Reproductive Age, Pregnant and Lactating Women: A Meta-Analysis

Background. Pregnant and breastfeeding women are at risk for folate deficiency. Folate supplementation has been shown to be associated with enhanced markers of folate status. However, dose-response analyses for adult women are still lacking. Objective. To assess the dose-response relationship between total folate intake (folic acid plus dietary folate) and markers of folate status (plasma/serum folate, red blood cell folate, and plasma homocysteine); to evaluate potential differences between women in childbearing age, pregnant and lactating women. Methods. Electronic literature searches were carried out on three databases until February 2010. The overall pooled regression coefficient (β) and SE(β) were calculated using meta-analysis on a double-log scale. Results. The majority of data was based on nonpregnant, nonlactating women in childbearingage. The pooled estimate of the relationship between folate intake and serum/plasma folate was 0.56 (95% CI = 0.40–0.72, P < 0.00001); that is, the doubling of folate intake increases the folate level in serum/plasma by 47%. For red blood cell folate, the pooled-effect estimate was 0.30 (95% CI = 0.22–0.38, P < 0.00001), that is, +23% for doubling intake. For plasma-homocysteine it was –0.10 (95% = –0.17 to –0.04, P = 0.001), that is, –7% for doubling the intake. Associations tended to be weaker in pregnant and lactating women. Conclusion. Significant relationships between folate intake and serum/plasma folate, red blood cell folate, and plasma homocysteine were quantified. This dose-response methodology may be applied for setting requirements for women in childbearing age, as well as for pregnant and lactating women.

Breastfeeding during Pregnancy Position Paper of the Italian Society of Perinatal Medicine and the Task Force on Breastfeeding, Ministry of Health, Italy

As more women breastfeed for longer, it is increasingly likely that women may be still breastfeeding when they become pregnant again. The Italian Society of Perinatal Medicine (SIMP) Working Group on Breastfeeding has reviewed the literature to determine the medical compatibility of pregnancy and breastfeeding. We found no evidence indicating that healthy women are at higher risk of miscarriage or preterm delivery if they breastfeed while pregnant. No evidence indicates that the pregnancy–breastfeeding overlap might cause intrauterine growth restriction, particularly in women from developed countries. Little information is available on the composition of human milk of pregnant women, and we found no data on the growth of infants nursed by a pregnant woman. However, both the composition of postpartum breast milk and the growth of the subsequent newborn appear to be partly affected, at least in developing countries. SIMP supports breastfeeding during pregnancy in the first 2 trimesters, and we believe it to be sustainable in the third trimester. Based on the hypothetical risk, caution may be warranted for women at risk of premature delivery, although no evidence exists that breastfeeding could trigger labor inducing uterine contractions. In conclusion, currently available data do not support routine discouragement of breastfeeding during pregnancy. Further studies are certainly needed to explore the consequences of breastfeeding during pregnancy on maternal health, on the breastfed infant, on the embryo/fetus, and, subsequently, on the growth of the newborn.

Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension, preeclampsia, intrauterine growth restricted and normal pregnancies

Abstract Objective: Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the association between both maternal and fetal HLA-G 14 bp insertion/deletion polymorphism and obstetrical complications. Methods: Clinical and genetic data of 282 women/fetuses (31 severe PE, 8 mild PE, 46 IUGR, 42 PIH and 155 controls) were analyzed both individually and jointly under a codominant, a dominant and a recessive model. Results: HLA-G 14 bp polymorphism was not associated with obstetrical complications, considering the mother and fetus genotypes both jointly and individually. Conclusions: With this study we filled several gaps occurring in previous studies: we analyzed a very well-defined population of PE, PIH and IUGR pregnancies, considering both fetal and maternal HLA-G 14 bp polymorphism, individually and jointly. Our findings showed that fetal and maternal HLA-G 14 bp genotypes are not associated with increased risk for the development of obstetrical complications, suggesting that this polymorphism has no immuno-modulatory role in the development of PE, PIH or IUGR.

Inflammatory and Oxidative Responses in Pregnancies With Obesity and Periodontal Disease

Background: Maternal obesity is related to immunologic and inflammatory systemic modifications that may worsen the pregnancy inflammatory status. Hormonal changes during pregnancy can adversely affect oral biofilms and oral health initiating or worsening periodontal diseases, with enhanced local and systemic oxidative stress and inflammation. Objective: The aim of this study was to examine the relationship between local salivary and systemic parameters of oxidative stress and inflammation in relation to obesity and periodontal diseases. Study Design: Sixty-two women with singleton pregnancies were enrolled. Twenty-seven women were normal weight (NW; 18.5< body mass index [BMI] <25 kg/m2) and 35 obese (BMI ≥30 kg/m2). Seventeen of the obese had gestational diabetes mellitus (GDM). During third trimester, periodontal status was evaluated, saliva (s) was collected to assess total antioxidant capacity (s-TAC) and C-reactive protein (s-CRP) levels, and venous plasma (p) was used to measure CRP levels (p-CRP). Maternal, fetal, and placental data were registered at delivery. Results: Levels of s-TAC, s-CRP, and p-CRP were significantly higher in obese, particularly in the presence of GDM, compared to NW and related to each other (P = .000; r > 0.59), to maternal BMI (P = .000; r > 0.52), and fasting glycemia (P < .002; r > 0.47). Periodontal disease was more frequent in obese groups (80%) versus NW (52%; P = .04), particularly when GDM was diagnosed (P = .009). A significant interaction effect between maternal BMI and oral condition was found for s-TAC levels. Obese with periodontitis showed significant increase in local and systemic parameters versus NW. Conclusion: Obesity and periodontal disease could synergistically amplify the inflammatory and oxidative status, resulting in increased local and systemic biomarkers particularly when GDM is diagnosed.

Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians

Vitamin D plays a pivotal role in the regulation of calcium-phosphorus metabolism, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur.Besides its historical skeletal functions, in the last years it has been demonstrated that vitamin D directly or indirectly regulates up to 1250 genes, playing so-called extraskeletal actions. Indeed, recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious, allergic and autoimmune diseases. Thus, vitamin D deficiency may affect not only musculoskeletal health but also a potentially wide range of acute and chronic conditions. At present, the prevalence of vitamin D deficiency is high in Italian children and adolescents, and national recommendations on vitamin D supplementation during pediatric age are lacking. An expert panel of the Italian Society of Preventive and Social Pediatrics reviewed available literature focusing on randomized controlled trials of vitamin D supplementation to provide a practical approach to vitamin D supplementation for infants, children and adolescents.

Impact of Obesity and Hyperglycemia on Placental Mitochondria

A lipotoxic placental environment is recognized in maternal obesity, with increased inflammation and oxidative stress. These changes might alter mitochondrial function, with excessive production of reactive oxygen species, in a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes. Here, we hypothesize that maternal pregestational body mass index (BMI) and glycemic levels can alter placental mitochondria. We measured mitochondrial DNA (mtDNA, real-time PCR) and morphology (electron microscopy) in placentas of forty-seven singleton pregnancies at elective cesarean section. Thirty-seven women were normoglycemic: twenty-one normal-weight women, NW, and sixteen obese women, OB/GDM(−). Ten obese women had gestational diabetes mellitus, OB/GDM(+). OB/GDM(−) presented higher mtDNA levels versus NW, suggesting increased mitochondrial biogenesis in the normoglycemic obese group. These mitochondria showed similar morphology to NW. On the contrary, in OB/GDM(+), mtDNA was not significantly increased versus NW. Nevertheless, mitochondria showed morphological abnormalities, indicating impaired functionality. The metabolic response of the placenta to impairment in obese pregnancies can possibly vary depending on several parameters, resulting in opposite strains acting when insulin resistance of GDM occurs in the obese environment, characterized by inflammation and oxidative stress. Therefore, mitochondrial alterations represent a feature of obese pregnancies with changes in placental energetics that possibly can affect pregnancy outcomes.

Micronutrients and the Obstetrical Syndromes

Knowledge about the role of micronutrients in the great obstetrical syndromes is steadily increasing in recent years. Evidence about the influence of a “prudent” or “Mediterranean” diets on preterm delivery and preeclampsia, coming from great databases, points out to the role of fruit and vegetables, i.e., micronutrients, during pregnancy.