PLoS ONE Alerts: Obstetrics

Periconceptional Maternal Folic Acid Use of 400 µg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child

2009-11-16T08:00:00Z

Background

Countries worldwide recommend women planning pregnancy to use daily 400 µg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic acid use and markers of global DNA methylation potential (S-adenosylmethionine and S-adenosylhomocysteine blood levels) in mothers and children affect methylation of the insulin-like growth factor 2 gene differentially methylation region (IGF2 DMR) in the child. Moreover, we tested whether the methylation of the IGF2 DMR was independently associated with birth weight.

Methodology/Principal Findings

IGF2 DMR methylation in 120 children aged 17 months (SD 0.3) of whom 86 mothers had used and 34 had not used folic acid periconceptionally were studied. Methylation was measured of 5 CpG dinucleotides covering the DMR using a mass spectrometry-based method. Children of mother who used folic acid had a 4.5% higher methylation of the IGF2 DMR than children who were not exposed to folic acid (49.5% vs. 47.4%; p = 0.014). IGF2 DMR methylation of the children also was associated with the S-adenosylmethionine blood level of the mother but not of the child (+1.7% methylation per SD S-adenosylmethionine; p = 0.037). Finally, we observed an inverse independent association between IGF2 DMR methylation and birth weight (−1.7% methylation per SD birthweight; p = 0.034).

Conclusions

Periconceptional folic acid use is associated with epigenetic changes in IGF2 in the child that may affect intrauterine programming of growth and development with consequences for health and disease throughout life. These results indicate plasticity of IGF2 methylation by periconceptional folic acid use.

The Secretion of Areolar (Montgomery's) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates

2009-10-23T07:00:00Z

Background

The communicative meaning of human areolae for newborn infants was examined here in directly exposing 3-day old neonates to the secretion from the areolar glands of Montgomery donated by non related, non familiar lactating women.

Methodology/Principal Findings

The effect of the areolar stimulus on the infants' behavior and autonomic nervous system was compared to that of seven reference stimuli originating either from human or non human mammalian sources, or from an arbitrarily-chosen artificial odorant. The odor of the native areolar secretion intensified more than all other stimuli the infants' inspiratory activity and appetitive oral responses. These responses appeared to develop independently from direct experience with the breast or milk.

Conclusion/Significance

Areolar secretions from lactating women are especially salient to human newborns. Volatile compounds carried in these substrates are thus in a position to play a key role in establishing behavioral and physiological processes pertaining to milk transfer and production, and, hence, to survival and to the early engagement of attachment and bonding.

Angiogenesis in Differentiated Placental Multipotent Mesenchymal Stromal Cells Is Dependent on Integrin α₅β₁

2009-10-22T07:00:00Z

Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated from term placenta, but their angiogenic ability and the regulatory pathways involved are not known. hPMSCs were shown to express integrins α_v, α₄, α₅, β₁, β₃, and β₅ and could be induced to differentiate into cells expressing endothelial markers. Increases in cell surface integrins α₅ and β₁, but not α₄, α_vβ₃, or α_vβ₅, accompanied endothelial differentiation. Vascular endothelial growth factor-A augmented the effect of fibronectin in enhancing adhesion and migration of differentiated hPMSC through integrin α₅β₁, but not α_vβ₃ or α_vβ₅. Formation of capillary-like structures in vitro from differentiated cells was inhibited by pre-treatment with function-blocking antibodies to integrins α₅ and β₁. When hPMSCs were seeded onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive cells were observed to engraft in the chick endothelium. CAMs transplanted with differentiated hPMSCs had a greater number of vessels containing human cells and more incorporated cells per vessel compared to CAMs transplanted with undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the differentiated cells. Function-blocking antibodies to integrins α₅ and β₁ inhibited angiogenesis in the CAM assay. These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin α₅β₁.

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

2009-09-09T07:00:00Z

Background

Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.

Methods

We conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).

Results

Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (−0.35 vs. 0.10 log₁₀ copies/mL, P = 0.03 and 183.8 vs. −70.8 cells/mm³, P = 0.03, respectively) but similar to those initiating HAART before pregnancy (−0.32 log₁₀ copies/mL, P = 0.96 and 155.8 cells/mm³, P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.

Conclusions

HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins

2009-08-28T07:00:00Z

Background

Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years.

Methods

This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner.

Findings

Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5–38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0–1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin.

Conclusions

There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

Pre- and Postnatal Nutritional Histories Influence Reproductive Maturation and Ovarian Function in the Rat

2009-08-25T07:00:00Z

Background

While prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring.

Methods

Pregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses.

Results

We report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal's nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring's nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations.

Conclusions

These observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis.

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

2009-08-10T07:00:00Z

Background

Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor.

Methods/Results

In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS), without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02) and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001). Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001) and percentage of detectable TNF-α (50 vs 4%, p<0.001).

Conclusions

This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines.

Search for an Association between V249I and T280M CX3CR1 Genetic Polymorphisms, Endothelial Injury and Preeclampsia: The ECLAXIR Study

2009-07-09T07:00:00Z

Background

Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an atheroprotective effect and reduced endothelial dysfunction. The aim of this study was to search for an association between V249I and T280M polymorphisms of CX3CR1, preeclampsia and endothelial dysfunction.

Methodology/Principal Findings

We explored these polymorphisms with real-time polymerase chain reaction in a case-control study (184 white women with preeclampsia and 184 matched normotensive pregnant women). Endothelial dysfunction biomarkers including von Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and M280 alleles were associated neither with preeclampsia, nor with its more severe form or with endothelial injury. In contrast, we found a trend toward increased CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia as compared to its level in later-onset- preeclampsia.

Conclusions/Significance

This is the first study to characterize the CX3CR1 gene polymorphisms in patients with preeclampsia. We found no differences in genotype or haplotype frequencies between patients with PE and normal pregnancies, suggesting that maternal CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to preeclampsia. Further studies should be performed to directly evaluate the pathophysiological role of CX3CL1, a molecule abundantly expressed in endometrium, which has been shown to stimulate human trophoblast migration.

Pulse Wave Analysis in Normal Pregnancy: A Prospective Longitudinal Study

2009-07-03T07:00:00Z

Background

Outside pregnancy, arterial pulse wave analysis provides valuable information in hypertension and vascular disease. Studies in pregnancy using this technique show that vascular stiffness is raised in women with established pre-eclampsia. We aimed to establish normal ranges for parameters of pulse wave analysis in normal pregnancy and to compare different ethnic groups.

Methodology/Principal Findings

This prospective study was conducted at The Homerton University Hospital, London between January 2006 and March 2007. Using applanation tonometry, the radial artery pulse waveform was recorded and the aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated.

We recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia (n = 24, 3.6%) or gestational hypertension (n = 36, 5.4%) were excluded. We also excluded 47 women with other pregnancy complications or incomplete follow-up, leaving 541 healthy normotensive pregnant women for subsequent analysis. In the overall group of 541 women, there were no significant changes in AP or AIx-75 as pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell significantly from the first to the second trimester, then rose again in the third (P<0.001). The two main ethnic groups represented were Caucasian (n = 229) and Afrocaribbean (n = 216). There were no significant differences in AP or AIx-75 in any trimester between these two ethnic groups.

Conclusions

This study is the largest to date of pulse wave analysis in normal pregnancy, the first to report on a subset of women studied longitudinally, and the first to investigate the effect of ethnicity. These data provide the foundation for further investigation into the potential role of this technique in vascular disorders in pregnancy.

Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

2009-06-26T07:00:00Z

Background

We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.

Methods

958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.

Results

Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06–6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction = 0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65–9.39) increase in HIV infection or death among infants of mothers with less severe disease.

Conclusion

Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding.

Trial Registration

Clinical trials.gov NCT00310726

Maternal Obesity Induced by Diet in Rats Permanently Influences Central Processes Regulating Food Intake in Offspring

2009-06-11T07:00:00Z

Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.

Placenta-Derived Fetal Specific mRNA Is More Readily Detectable in Maternal Plasma than in Whole Blood

2009-06-10T07:00:00Z

Background

Placental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis.

Methodology

The concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis. Their fetal specificity was investigated by comparing the transcript concentrations in pre- and post-delivery samples and through SNP genotyping by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry. The gene expression profiles of pregnant and non-pregnant whole blood were investigated by microarray analysis. Upregulated genes in pregnant whole blood were selected for further quantitative analysis.

Principal Findings

The concentrations of the four transcripts were significantly higher in third trimester maternal whole blood than corresponding plasma without significant correlations. KISS1, PLAC4 and PLAC1 were detected in non-pregnant whole blood but not plasma. The transcripts remained detectable in some postpartum whole blood samples. The PLAC4 mRNA in maternal plasma showed fetal genotype while that in corresponding whole blood indicated both fetal and maternal contributions. Microarray analysis revealed upregulation of genes involved in neutrophil functions in pregnant whole blood including DEFA4, CEACAM8, OLFM4, ORM1, MMP8 and MPO. Though possibly pregnancy-related, they were not pregnancy-specific as suggested by the lack of post-delivery reduction in concentrations.

Conclusions

Maternal plasma is preferred over maternal whole blood for placenta-derived fetal RNA detection. Most studied ‘placental’ mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as ‘illegitimate transcription’.

Patient Perspectives with Abbreviated versus Standard Pre-Test HIV Counseling in the Prenatal Setting: A Randomized-Controlled, Non-Inferiority Trial

2009-04-15T07:00:00Z

Background

In the US, an unacceptably high percentage of pregnant women do not undergo prenatal HIV testing. Previous studies have found increased uptake of prenatal HIV testing with abbreviated pre-test counseling, however little is known about patient decision making, testing satisfaction and knowledge in this setting.

Methodology/Findings

A randomized-controlled, non-inferiority trial was conducted from October 2006 through February 2008 at San Francisco General Hospital (SFGH), the public teaching hospital of the City and County of San Francisco. A total of 278 English- and Spanish-speaking pregnant women were randomized to receive either abbreviated or standard nurse-performed HIV test counseling at the initial prenatal visit. Patient decision making experience was compared between abbreviated versus standard HIV counseling strategies among a sample of low-income, urban, ethnically diverse prenatal patients. The primary outcome was the decisional conflict score (DCS) using O'Connor low-literacy scale and secondary outcomes included satisfaction with test decision, basic HIV knowledge and HIV testing uptake. We conducted an intention-to-treat analysis of 278 women – 134 (48.2%) in the abbreviated arm (AA) and 144 (51.8%) in the standard arm (SA). There was no significant difference in the proportion of women with low decisional conflict (71.6% in AA vs. 76.4% in SA, p = .37), and the observed mean difference between the groups of 3.88 (95% CI: −0.65, 8.41) did not exceed the non-inferiority margin. HIV testing uptake was very high (97. 8%) and did not differ significantly between the 2 groups (99.3% in AA vs. 96.5% in SA, p = .12). Likewise, there was no difference in satisfaction with testing decision (97.8% in AA vs. 99.3% in SA, p = .36). However, women in AA had significantly lower mean HIV knowledge scores (78.4%) compared to women in SA (83.7%, p<0.01).

Conclusions/Significance

This study suggests that streamlining the pre-test counseling process, while associated with slightly lower knowledge, does not compromise patient decision making or satisfaction regarding HIV testing.

Trial Registration

ClinicalTrials.gov NCT00503308

Neonatal Handling Affects Durably Bonding and Social Development

2009-04-08T07:00:00Z

The neonatal period in humans and in most mammals is characterized by intense mother-young interactions favoring pair bonding and the adaptation of neonates to their new environment. However, in many post-delivery procedures, human babies commonly experience combined maternal separation and intense handling for about one hour post-birth. Currently, the effects of such disturbances on later attachment and on the development of newborns are still debated: clearly, further investigations are required. As animals present good models for controlled experimentation, we chose domestic horses to investigate this issue. Horses, like humans, are characterized by single births, long lactating periods and selective mother-infant bonds. Routine postnatal procedures for foals, as for human babies, also involve intense handling and maternal separation. In the present study, we monitored the behavior of foals from early stages of development to “adolescence”, in a normal ecological context (social groups with adults and peers). Experimental foals, separated from their mothers and handled for only 1 hour post-birth, were compared to control foals, left undisturbed after birth. Our results revealed short- and long-term effects of this unique neonatal experience on attachment and subsequent social competences. Thus, experimental foals presented patterns of insecure attachment to their mothers (strong dependence on their mothers, little play) and impaired social competences (social withdrawal, aggressiveness) at all ages. We discuss these results in terms of mother-young interactions, timing of interactions and relationships between bonding and subsequent social competences. Our results indicate that this ungulate species could become an interesting animal model. To our knowledge, this is the first clear demonstration that intervention just after birth affects bonding and subsequent social competences (at least until “adolescence”). It opens new research directions for studies on both humans and other animals.

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

2009-03-24T07:00:00Z

Background

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.

Methodology and Principal Findings

Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1β, and IL-10), chemokines (IL-8, MCP-1, MIP1α, MIP1β) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.

Conclusions and Significance

These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function.

PLoS ONE Alerts: Obstetrics

Periconceptional Maternal Folic Acid Use of 400 µg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child

The Secretion of Areolar (Montgomery's) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates

Angiogenesis in Differentiated Placental Multipotent Mesenchymal Stromal Cells Is Dependent on Integrin α5β1

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

Long-Term Neurodevelopmental Outcome of Monochorionic and Matched Dichorionic Twins

Pre- and Postnatal Nutritional Histories Influence Reproductive Maturation and Ovarian Function in the Rat

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

Search for an Association between V249I and T280M CX3CR1 Genetic Polymorphisms, Endothelial Injury and Preeclampsia: The ECLAXIR Study

Pulse Wave Analysis in Normal Pregnancy: A Prospective Longitudinal Study

Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

Maternal Obesity Induced by Diet in Rats Permanently Influences Central Processes Regulating Food Intake in Offspring

Placenta-Derived Fetal Specific mRNA Is More Readily Detectable in Maternal Plasma than in Whole Blood

Patient Perspectives with Abbreviated versus Standard Pre-Test HIV Counseling in the Prenatal Setting: A Randomized-Controlled, Non-Inferiority Trial

Neonatal Handling Affects Durably Bonding and Social Development

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Angiogenesis in Differentiated Placental Multipotent Mesenchymal Stromal Cells Is Dependent on Integrin α₅β₁