Including Intrauterine Growth Restriction Research Articles

A novel case of 16q22.3 duplication syndrome in a child with overgrowth: case report and literature review

BackgroundDistal chromosome 16 duplication syndrome (also known as 16q partial trisomy) is a very rare genetic disorder recently described in few clinical reports. 16q trisomy is generally associated with a multisystemic phenotype including intrauterine growth restriction (IUGR), brain and cardiac defects, intellectual disability (ID) and an increased risk of both prenatal and postnatal lethality. Smaller copy number variants (CNV) within the 16q region create partial trisomies, which occur less frequently than full trisomy 16q.Case presentationWe present the clinical case of a 12-years-old male with a 16q22.3q24.1 de novo heterozygous duplication whose phenotype was characterized by ID, facial dysmorphisms, stature and weight overgrowth. To date, only five other cases of this syndrome have been reported in scientific literature, and none of them comprised overgrowth.ConclusionsOur case report highlights the great heterogeneity in clinical manifestations and provides new evidence for better defining the phenotypic picture for smaller 16q distal CNVs, suggesting unusual features.

Awareness of Preeclampsia and Its Associated Factors Among Women in Al Baha Region, Saudi Arabia.

Preeclampsia is associated with the incidence of common fetal problems including intra-uterine growth restriction (IUGR), premature delivery oligohydramnios, placental abruption, fetal discomfort, and intrauterine fetal death. Pregnant women are not well-informed about preeclampsia, including its symptoms, risk factors, and consequences. The aim of the current study is to evaluate the awareness of preeclampsia and its associated factors among women in the Al Baha region, Saudi Arabia. An observational cross-sectional design was employed to assess the awareness of preeclampsia and its associated factors among women in the Al Baha region of Saudi Arabia. Data was collected from April 2023 to September2023. A questionnaire was designed to gather information on participants' sociodemographic characteristics (such as age, educational level, and residency) and their awareness of preeclampsia, including knowledge about signs/symptoms, risk factors, and complications. In the current study, we included 485 pregnant women. The majority of participants were aged 40 years or older (37.5%), followed by those aged 35-39 (20.4%). Among the participants, 70.9% confirmed that they had heard about pre-eclampsia before. The most common signs and symptoms were high blood pressure (47.4%), increased protein in urine (40.2%), continuous headache (39.2%), and vomiting/nausea (40.0%). Participants demonstrated awareness of obesity (29.7%), diabetes mellitus (35.5%), chronic hypertension (47.0%), and chronic kidney disease (31.3%) as major risk factors. Participants were aware of potential risks such as kidney disorders (34.6%), heart disorders (23.7%), and preterm delivery (50.9%). The analysis reveals that younger participants below 20 years old (3.3%) and lower educational levels (5.6%) had lower awareness of preeclampsia compared to older age groups. The findings of this study highlight a reasonable level of preeclampsia awareness and knowledge among Saudi Arabian women residing in the Al Baha region. While the majority of participants were familiar with preeclampsia, there were significant knowledge gaps regarding the precise symptoms, risk factors, and consequences of the condition.

Heterozygous rare variants in NR2F2 cause a recognizable multiple congenital anomaly syndrome with developmental delays.

Nuclear receptor subfamily 2 group F member 2 (NR2F2 or COUP-TF2) encodes a transcription factor which is expressed at high levels during mammalian development. Rare heterozygous Mendelian variants in NR2F2 were initially identified in individuals with congenital heart disease (CHD), then subsequently in cohorts of congenital diaphragmatic hernia (CDH) and 46,XX ovotesticular disorders/differences of sexual development (DSD); however, the phenotypic spectrum associated with pathogenic variants in NR2F2 remains poorly characterized. Currently, less than 40 individuals with heterozygous pathogenic variants in NR2F2 have been reported. Here, we review the clinical and molecular details of 17 previously unreported individuals with rare heterozygous NR2F2 variants, the majority of which were de novo. Clinical features were variable, including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations, thus expanding the phenotypic spectrum associated with NR2F2 variants. The variants seen were predicted loss of function, including a nonsense variant inherited from a mildly affected mosaic mother, missense and a large deletion including the NR2F2 gene. Our study presents evidence for rare, heterozygous NR2F2 variants causing a highly variable syndrome of congenital anomalies, commonly associated with heart defects, developmental delays/intellectual disability, dysmorphic features, feeding difficulties, hypotonia, and genital anomalies. Based on the new and previous cases, we provide clinical recommendations for evaluating individuals diagnosed with an NR2F2-associated disorder.

Thymic and extrathymic Aire-expressing cells in maternal-fetal tolerance.

Healthy pregnancy requires maternal immune tolerance to both fetal and placental tissues which contain a range of self- and non-self-antigens. While many of the components and mechanisms of maternal-fetal tolerance have been investigated in detail and previously and thoroughly reviewed (Erlebacher A. Annu Rev Immunol. 2013;31:387-411), the role of autoimmune regulator (Aire), a critical regulator of central tolerance expressed by medullary thymic epithelial cells (mTECs), has been less explored. Aire is known to facilitate the expression of a range of otherwise tissue-specific antigens (TSAs) in mTECs, and here we highlight recent work showing a role for mTEC-mediated thymic selection in maintaining maternal-fetal tolerance. Recently, however, our group and others have identified additional populations of extrathymic Aire-expressing cells (eTACs) in the secondary lymphoid organs. These hematopoietic antigen-presenting cells possess the ability to induce functional inactivation and/or deletion of cognate T cells, and deletion of maternal eTACs during pregnancy increases T-cell activation in the lymph nodes and lymphocytic infiltration of the uterus, leading to pregnancy complications including intrauterine growth restriction (IUGR) and fetal resorption. In this review, we briefly summarize findings related to essential Aire biology, discuss the known roles of Aire-deficiency related to pregnancy complications and infertility, review the newly discovered role for eTACs in the maintenance of maternal-fetal tolerance-as well as recent work defining eTACs at the single-cell level-and postulate potential mechanisms by which eTACs may regulate this process.

Effect of Aspirin Dose on Preeclampsia Prevention and Fetal-maternal Complications: A Randomized Clinical Trial

Background: Preeclampsia (PE) is a disease characterized by abnormalities in the placenta and endothelial cells. The pathogenesis is not fully understood; however, aspirin prescription can be effective to treat the disease and prevent fetal developmental disorders. Methods: This study was performed as a clinical trial in Shahid Akbrabadi Hospital in Tehran city. Eighty patients participated in two groups (n = 40). The first group of patients received the dose of 80 mg, and the second group received the dose of 160 mg aspirin. Then, the fetal-maternal and treatment process complications were examined in the patients. Results: The results showed that the incidence of fetal-maternal complications, including intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) was lower in patients treated with 160 mg aspirin than in the other group, but this difference was not statistically significant (P-value > 0.05). Aspirin complications such as bleeding were more in the second group than in the first one (P-value < 0.05). Conclusions: Although the increasing dose of aspirin reduces fetal-maternal complications in PE patients, the problems such as aspirin-induced bleeding should be considered.

The Effect of the Immunosuppressant Drug, Tacrolimus, on Nitric Oxide Production in the Immortalized First Trimester Extra-Villous Trophoblast Cells

The remodeling of uterine spiral arteries and subsequent placental formation are crucial for normal growth and development of the fetus. These processes are heavily dependent on the functioning of the extra-villous trophoblast cells and their ability to invade into the maternal decidual blood vessels. Reduced trophoblast invasion and shallow spiral artery remodeling can lead to a number of gestational complications including intrauterine growth restriction (IUGR). Therapeutic intervention with low dose immunosuppressant tacrolimus was able to prevent implantation failure and IUGR in obese and diabetic mice. Treatment with tacrolimus successfully aided in spiral artery modification that was conducive to a successful pregnancy. Further, tacrolimus has shown promise in restoring trophoblast cell functioning in the immortalized first trimester HTR8/SVneo extra-villous trophoblast cells cultured under preeclampsia-like conditions in vitro. However, the mode of action of tacrolimus has yet to be elucidated. Here we attempt to uncover the mode of action of tacrolimus by examining its effects on eNOS activity within the trophoblast cells. Cells were treated with tacrolimus (10 ng/mL), L-NAME (40 nM/mL) or a combination of both and subjected to analysis by several functional assays. The data obtained in this study is suggesting that L-NAME treatment has inhibitory effects on the levels of the pPGR, pSTAT3 and NO within the HTR8/SVneo cells. The use of low-dose tacrolimus abrogated the suppressive effect of L-NAME and restored the levels of the pPGR, pSTAT3, and NO within the cells.

Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction†.

Incomplete maternal vascular responses to pregnancy contribute to pregnancy complications including intrauterine growth restriction (IUGR) and preeclampsia. We aimed to characterize maternal vascular dysfunction in a murine model of fetal growth restriction as an approach toward identifying targetable pathways for improving pregnancy outcomes. We utilized a murine model of late-gestation hypoxia-induced IUGR that reduced E18.5 fetal weight by 34%. Contrary to our hypothesis, uterine artery blood flow as measured in vivo by Doppler ultrasound was increased in mice housed under hypobaric hypoxia (385mmHg; 5500m) vs normoxia (760mmHg; 0m). Using wire myography, uterine arteries isolated from hypoxic mice had similar vasodilator responses to the two activators A769662 and acetylcholine as those from normoxic mice, although the contribution of an increase in nitric oxide production to uterine artery vasodilation was reduced in the hypoxic vs normoxic groups. Vasoconstrictor responses to phenylephrine and potassium chloride were unaltered by hypoxia. The levels of activated adenosine monophosphate-activated protein kinase (AMPK) were reduced with hypoxia in both the uterine artery and placenta as measured by western blot and immunohistochemistry. We concluded that the rise in uterine artery blood flow may be compensatory to hypoxia but was not sufficient to prevent fetal growth restriction. Although AMPK signaling was reduced by hypoxia, AMPK was still receptive to pharmacologic activation in the uterine arteries in which it was a potent vasodilator. Thus, AMPK activation may represent a new therapy for pregnancy complications involving reduced uteroplacental perfusion.

Failure of Decidualization and Maternal Immune Tolerance Underlies Uterovascular Resistance in Intra Uterine Growth Restriction.

Failure of uterine vascular transformation is associated with pregnancy complications including Intra Uterine Growth Restriction (IUGR). The decidua and its immune cell populations play a key role in the earliest stages of this process. Here we investigate the hypothesis that abnormal decidualization and failure of maternal immune tolerance in the second trimester may underlie the uteroplacental pathology of IUGR. Placental bed biopsies were obtained from women undergoing elective caesarian delivery of a healthy term pregnancy, an IUGR pregnancy or a pregnancy complicated by both IUGR and preeclampsia. Decidual tissues were also collected from second trimester terminations from women with either normal or high uterine artery Doppler pulsatile index (PI). Immunohistochemical image analysis and flow cytometry were used to quantify vascular remodeling, decidual leukocytes and decidual status in cases vs. controls. Biopsies from pregnancies complicated by severe IUGR with a high uterine artery pulsatile index (PI) displayed a lack of: myometrial vascular transformation, interstitial, and endovascular extravillous trophoblast (EVT) invasion, and a lower number of maternal leukocytes. Apoptotic mural EVT were observed in association with mature dendritic cells and T cells in the IUGR samples. Second trimester pregnancies with high uterine artery PI displayed a higher incidence of small for gestational age fetuses; a skewed decidual immunology with higher numbers of; CD8 T cells, mature CD83 dendritic cells and lymphatic vessels that were packed with decidual leukocytes. The decidual stromal cells (DSCs) failed to differentiate into the large secretory DSC in these cases, remaining small and cuboidal and expressing lower levels of the nuclear progesterone receptor isoform B, and DSC markers Insulin Growth Factor Binding protein-1 (IGFBP-1) and CD10 as compared to controls. This study shows that defective progesterone mediated decidualization and a hostile maternal immune response against the invading endovascular EVT contribute to the failure of uterovascular remodeling in IUGR pregnancies.

Study of mitochondrial function in placental insufficiency

IntroductionIt has been suggested that mitochondria play a crucial role in sustaining pregnancy and foetal growth. The aim of the study was to assess the influence of mitochondrial functions and genetics on placental insufficiency diseases. MethodsA total of 115 patients were recruited, subdivided into 74 placenta samples and 41 maternal blood samples: placental insufficiency diseases including intra uterine growth restriction (IUGR) (n = 35), preeclampsia (PE) (n = 13), IUGR associated to PE (PER) (n = 25); and controls (n = 42). Haplogroups were determined for all patients. Eighty-six placenta samples were studied for quantitative and qualitative analyses of mtDNA: IUGR (n = 25), PE (n = 1), PER (n = 18) and controls (n = 42). Sixteen placenta samples were selected for functional analysis: IUGR (n = 6), PER (n = 2) and controls (n = 8). ResultsMitochondrial DNA copy numbers and rearrangements and haplogroup distribution were not significantly altered in the patient group. Enzyme activity and expression of respiratory chain complexes were also comparable between both groups. DiscussionOur results do not argue in favour of a mitochondrial involvement in placental insufficiency, suggesting that the glycolytic pathway may represent a key energetic source in placental insufficiency diseases.

A multiscale model of placental oxygen exchange: The effect of villous tree structure on exchange efficiency

The placenta is critical to fetal health during pregnancy as it supplies oxygen and nutrients to maintain life. It has a complex structure, and alterations to this structure across spatial scales are associated with several pregnancy complications, including intrauterine growth restriction (IUGR). The relationship between placental structure and its efficiency as an oxygen exchanger is not well understood in normal or pathological pregnancies. Here we present a computational framework that predicts oxygen transport in the placenta which accounts for blood and oxygen transport in the space around a placental functional unit (the villous tree). The model includes the well-defined branching structure of the largest villous tree branches, as well as a smoothed representation of the small terminal villi that comprise the placenta's gas exchange interfaces. The model demonstrates that oxygen exchange is sensitive to villous tree geometry, including the villous branch length and volume, which are seen to change in IUGR. This is because, to be an efficient exchanger, the architecture of the villous tree must provide a balance between maximising the surface area available for exchange, and the opposing condition of allowing sufficient maternal blood flow to penetrate into the space surrounding the tree. The model also predicts an optimum oxygen exchange when the branch angle is 24 °, as villous branches and TBs are spread out sufficiently to channel maternal blood flow deep into the placental tissue for oxygen exchange without being shunted directly into the DVs. Without concurrent change in the branch length and angles, the model predicts that the number of branching generations has a small influence on oxygen exchange. The modelling framework is presented in 2D for simplicity but is extendible to 3D or to incorporate the high-resolution imaging data that is currently evolving to better quantify placental structure.

A study of serum Apo A-1 and Apo B-100 levels in women with preeclampsia.

To investigate Apo A-1 and Apo B-100 levels and Apo B-100/Apo A-1 ratios in preeclamptic (PE) patients. Forty-eight PE and 48 without PE patients (healthy pregnancies) matched for gestational age were included. Maternal age, parity, gestational age at delivery, obstetrical complications including intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM), serum Apo A-1 and Apo B-100 levels, and the Apo B-100/Apo A-1 ratio were compared. Preeclamptic patients had significantly lower Apo A-1 levels (167.07mg/dl±14.61mg/dl vs. 244.37mg/dl±20.84mg/dl, p<0.001), higher Apo B-100/Apo A-1 ratio (0.63±0.07 vs. 0.42±0.05, p<0.001), but similar Apo B-100 levels (104.84mg/dl±7.05mg/dl vs. 102.39mg/dl±8.08mg/dl, p=0.118). Mean Apo A-1 and Apo B-100 levels and the Apo B-100/Apo A-1 ratio were similar in patients with severe PE, HELLP syndrome, IUGR, and patients requiring antihypertensive therapy compared to PE patients who did not have these complications (p>0.05). Apo A-1 levels had the best accuracy followed by the Apo B-100/Apo A-1 ratio in patients with PE. Apo A-1 and the Apo B-100/Apo A-1 ratio may be useful markers in patients with PE. Further studies are required to elucidate this issue.

NF-kB Regulation in T-cells in Pregnancy is Mediated via Fas/FasL Interactions: The Signal for which is Derived from Exosomes Present in Maternal Plasma

Background: Regulated suppression of maternal Th1 immunity is necessary for normal pregnancy since inappropriate Th1 responses results in increased pregnancy loss and complications including intrauterine growth restriction (IUGR). We have shown that suppression of the p65 subunit of NF-κB in maternal T-cells underlies this change in T-cell responses. This study aimed to determine mechanism(s) that control p65 suppression. Methods and findings: Maternal plasma contained particulate factor’s that suppress p65 and induce T-cell apoptosis in Jurkat T-cells and the factor’s was positive for FasL and TRAIL. Both the Fas activating antibody CH11 and recombinant human TRAIL induced Jurkat apoptosis. Specific Fas activation resulted in p65 suppression which was reversed in the presence of the Fas inactivating antibody ZB4. Despite inducing apoptosis, recombinant TRAIL did not suppress p65 expression. Maternal T-cells expressed increased Fas relative to non-pregnant controls. Fas activation in Jurkats resulted in p65 suppression thus limited IL-2 and IFNA¯ÂÂ§ transcription in response to PMA/ionomycin stimulation. In contrast, partial knockdown of Fas in Jurkats prevented suppression of p65 in response to CH11, leading to increased IL-2 and IFNA¯ÂÂ§ production when stimulated with PMA/ionomycin. FasL+ Exosomes isolated from the particulate fraction of maternal plasma specifically induced p65 suppression in Jurkats since suppression was completely reversed with ZB4. In pregnancies complicated with IUGR where Th1 cytokine production is increased, placental expression of FasL was reduced compared to normal controls. Conclusion: Taken together these data suggest that pregnancy derived FasL+ exosomes in maternal plasma regulate p65 levels in circulating T-cells through Fas activation. The expression of Fas on T-cells and FasL on exosomes both dictate the level of p65 suppression and the level of cytokine production in response to stimulation throughout pregnancy. Inappropriate expression of FasL in placental derived exosomes may underlie one mechanism that is abnormal in complications of pregnancy including IUGR.

Placental massive perivillous fibrinoid deposition is associated with adverse pregnancy outcomes: a clinicopathological study of 12 cases

Abstract Introduction: Massive perivillous fibrinoid deposition (MPFD) is a very rare placental condition characterized by abnormally extensive fibrinoid deposition in the placental villous parenchyma. The aim of this study is to document clinical and pathological features with special focus on pregnancy outcomes of this condition in consecutive cases of MPFD in our local population. Methods: This is a retrospective clinico-pathological study of cases affected by MPFD over the period January 2010–July 2014 in our hospital. We document clinical features (including perinatal outcome and subsequent pregnancies) and placental pathological characteristics. Results: Twelve cases of MPFD were identified among 3640 placentas (0.33%). There was no identified recurrence. The affected infants had adverse outcomes, including intrauterine growth restriction (IUGR) (75%), preterm birth (58.3%), and fetal loss (25%). A high frequency of reduced PAPP-A in the first trimester (25%), and concurrent gestational hypertension or pre-eclampsia (25%) was noted. Conclusion: MPFD is associated with adverse perinatal outcomes. Further research to better understand its pathogenesis and to improve clinical diagnosis and management is warranted.

Perinatal outcomes after hypertensive disorders in pregnancy in a low resource setting.

The objective of this study was to evaluate perinatal outcomes of pregnancies complicated by hypertensive disorders in pregnancy in an urban sub-Saharan African setting. A prospective cohort study of 1010 women of less than 17 weeks of gestation was conducted at two antenatal clinics in Accra, Ghana, between July 2012 and March 2014. Information about hypertensive disorders was available for analysis on 789 pregnancies. The main outcomes were pre-term birth, birthweight, Apgar scores, small for gestational age and mortality. Relative risk (RR, 95% confidence interval (CI)) for the association between hypertensive disorders of pregnancy and perinatal outcomes was assessed using logistic regression adjusting for potential confounders. A total of 88.7% of women remained normotensive, 7.5% developed pregnancy-induced hypertension, 2.0% had chronic hypertension, and 1.7% developed (pre-)eclampsia. No adverse effects were observed in women with pregnancy-induced hypertension. Women with chronic hypertension were more likely to have a lower gestational age at delivery (38.0 ± 2.3 weeks vs. 39.0 ± 1.9 weeks, P = 0.04) and higher risk of pre-term delivery (aRR 4.63, 95% CI 1.35-15.91). Women with pre-eclampsia had emergency Caesarean section significantly more often (88.9% vs. 50%, P = 0.04), with a higher risk for low birthweight infants (aRR 7.95, 95% CI 1.41-44.80) and a higher risk of neonatal death (aRR 18.41, 95% CI 1.20-283.22). Comparable to high-income countries, in Accra hypertensive disorders during pregnancy were associated with increased risk of adverse perinatal outcomes necessitating maternal and newborn care.

Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population.

ObjectiveAdverse maternal outcomes and perinatal complications are closely associated with overt maternal hypothyroidism, but whether these complications occur in women with subclinical hypothyroidism (SCH) during pregnancy remains controversial. The aim of this study was to evaluate the effects of SCH on maternal and perinatal outcomes during pregnancy.MethodsA prospective study of data from 8012 pregnant women (371 women with SCH, 7641 euthyroid women) was performed. Maternal serum samples were collected in different trimesters to examine thyroid hormone concentrations. SCH was defined as a thyroid stimulating hormone concentration exceeding the trimester-specific reference value with a normal free thyroxine concentration. The occurrence of maternal outcomes, including gestational hypertension (GH), gestational diabetes mellitus, placenta previa, placental abruption, prelabor rupture of membranes (PROM), and premature delivery; and perinatal outcomes, including intrauterine growth restriction (IUGR), fetal distress, low birth weight (LBW; live birth weight ≤2500 g), stillbirth, and malformation, was recorded. Logistic regression with adjustment for confounding demographic and medical factors was used to determine the risks of adverse outcomes in patients with SCH.ResultsCompared with euthyroid status, SCH was associated with higher rates of GH (1.819% vs. 3.504%, P = 0.020; χ 2 = 7.345; odds ratio (OR), 2.243; 95% confidence interval (CI), 1.251–4.024), PROM (4.973% vs. 8.625%, P = 0.002; χ 2 = 72.102; adjusted OR, 6.014; 95% CI, 3.975–9.099), IUGR (1.008% vs. 2.965%, <0.001; χ 2 = 13.272; adjusted OR, 3.336; 95% CI, 1.745–6.377), and LBW (1.885% vs. 4.582%, P<0.001; χ 2 = 13.558; adjusted OR, 2.919; 95% CI, 1.650–5.163).ConclusionsThe results of this study indicate that pregnant women with SCH had increased risks of GH and PROM, and their fetuses and infants had increased risks of IUGR and LBW. Thus, routine maternal thyroid function testing is necessary to improve maternal and perinatal outcomes.

The relationship between TGFβ, low oxygen and the outgrowth of extravillous trophoblasts from anchoring villi during the first trimester of pregnancy

BackgroundDuring the first trimester of human pregnancy, specialised placental cells called extravillous trophoblasts (EVTs) grow out from anchoring villi, invade the maternal decidua and remodel the uterine spiral arteries. Inadequate EVT invasion is associated with pregnancy complications including intrauterine growth restriction (IUGR) and pre-eclampsia. During early pregnancy, the placenta exists in a physiologically normal low oxygen environment, which may regulate EVT outgrowth. One potential oxygen responsive regulator of EVTs is the transforming growth factor-beta (TGFβ) family of cytokines. This work aimed to determine the role of TGFβ1, β2 and β3 in regulating EVT outgrowth in the low oxygen environment of early pregnancy. ResultsUsing a quantitative high-throughput first trimester villous explant model of EVT outgrowth we demonstrated no significant difference in the frequency of EVT outgrowth between explants treated with TGFβ1, β2 or β3. However, explants treated with TGFβ2, but not β1 or β3, produced EVT outgrowths with a significantly smaller area in comparison to untreated controls (p=0.03). When explants were cultured in 1.5% oxygen, TGFβ2, but not β1 or β3, in the conditioned medium of explants that produced EVT outgrowth was significantly reduced in comparison to 8% oxygen (p<0.05). There was no significant difference in the concentration of TGFβ2 or TGFβ3 from isolated primary EVTs cultured in 1.5% or 8% oxygen. ConclusionsTGFβ2 inhibits EVT outgrowth expansion from first trimester anchoring villi. As TGFβ2 secretion from anchoring villi is down-regulated in low oxygen, these findings suggest that the low oxygen environment in early pregnancy may be important to allow EVT outgrowth expansion and promote adequate placentation.

PP.83 Can We Predict Poor Pregnancy Outcomes in Women Presenting with Reduced Fetal Movements?

ObjectivesReduced fetal movements (RFM) are associated with adverse pregnancy outcomes, including intrauterine growth restriction (IUGR) and stillbirth. The aim was to review risk factors which could predict poor perinatal outcomes...

Biological Mechanisms for Nutritional Regulation of Maternal Health and Fetal Development

This review paper highlights mechanisms for nutritional regulation of maternal health and fetal development. Malnutrition (nutrient deficiencies or obesity) in pregnant women adversely affects their health by causing or exacerbating a plethora of problems, such as anaemia, maternal haemorrhage, insulin resistance, and hypertensive disorders (e.g. pre-eclampsia/eclampsia). Maternal malnutrition during gestation also impairs embryonic and fetal growth and development, resulting in deleterious outcomes, including intrauterine growth restriction (IUGR), low birthweight, preterm birth, and birth defects (e.g. neural tube defects and iodine deficiency disorders). IUGR and preterm birth contribute to high rates of neonatal morbidity and mortality. Major common mechanisms responsible for malnutrition-induced IUGR and preterm birth include: (i) abnormal growth and development of the placenta; (ii) impaired placental transfer of nutrients from mother to fetus; (iii) endocrine disorders; and (iv) disturbances in normal metabolic processes. Activation of a series of physiological responses leading to premature and sustained contraction of the uterine myometrium also results in preterm birth. Recent epidemiologic studies have suggested a link between IUGR and chronic metabolic disease in children and adults, and the effects of IUGR may be carried forward to subsequent generations through epigenetics. While advanced medical therapies, which are generally unavailable in low-income countries, are required to support preterm and IUGR infants, optimal nutrition during pregnancy may help ameliorate many of these problems. Future studies are necessary to develop effective nutritional interventions to enhance fetal growth and development and alleviate the burden of maternal morbidity and mortality in low- and middle-income countries.

Effect of balanced protein energy supplementation during pregnancy on birth outcomes

BackgroundThe nutritional status of the mother prior to and during pregnancy plays a vital role in fetal growth and development, and maternal undernourishment may lead to adverse perinatal outcomes including intrauterine growth restriction (IUGR). Several macronutrient interventions had been proposed for adequate protein and energy supplementation during pregnancy. The objective of this paper was to review the effect of balanced protein energy supplementation during pregnancy on birth outcomes. This paper is a part of a series of reviews undertaken for getting estimates of effectiveness of an intervention for input to Lives Saved Tool (LiST) model.MethodsA literature search was conducted on PubMed, Cochrane Library and WHO regional data bases to identify randomized trials (RCTs) and quasi RCTs that evaluated the impact of balanced protein energy supplementation in pregnancy. Balanced protein energy supplementation was defined as nutritional supplementation during pregnancy in which proteins provided less than 25% of the total energy content. Those studies were excluded in which the main intervention was dietary advice to pregnant women for increase in protein energy intake, high protein supplementation (i.e. supplementation in which protein provides at least 25% of total energy content), isocaloric protein supplementation (where protein replaces an equal quantity of non-protein energy content), or low energy diet to pregnant women who are either overweight or who exhibit high weight gain earlier in gestation. The primary outcomes were incidence of small for gestational age (SGA) birth, mean birth weight and neonatal mortality. Quality of evidence was evaluated according to the Child Health Epidemiology Reference group (CHERG) adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.ResultsThe final number of studies included in our review was eleven comprising of both RCTs and quasi-RCTs. Our meta-analysis indicates that providing pregnant females with balanced protein energy supplementation resulted in a significant reduction of 31 % in the risk of giving birth to small for gestational age infants (Relative risk (RR) =0.69, 95% Confidence interval (CI) 0.56 to 0.85). This estimate had been recommended for LiST as a proxy for reduction in IUGR. Pooled results for mean birth weight showed that balanced protein supplemented group gained more weight compared to control [Mean difference 59.89 g, 95 % CI 33.09-86.68]. This effect was more pronounced in malnourished women compared to adequately nourished women. There was no statistically significant effect of balanced protein energy supplementation on neonatal mortality (RR= 0.63, 95% CI 0.37 to 1.06).ConclusionProviding pregnant females with balanced protein energy supplementation leads to reduction in risk of small for gestational age infants, especially among undernourished pregnant women. Given these findings, we can recommend balanced protein energy supplementation as an intervention among undernourished women for inclusion in the LiST model with a point estimate of 31% [95% CI 15% to 44%] reduction in IUGR.

Genetic, Biochemical, and Environmental Factors Associated with Pregnancy Outcomes in Newborns from the Czech Republic

BackgroundOxidative damage to placental DNA can result in negative pregnancy outcomes, including intrauterine growth restriction (IUGR) and low birth weight (LBW).ObjectiveWe investigated associations between the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in placental DNA, exposure to air pollutants during pregnancy, genetic polymorphisms in 94 selected genes, and pregnancy outcomes.MethodsWe studied 891 newborns who were IUGR- or LBW-affected or normal weight and were born between 1994 and 1999 in the Czech Republic in two districts with different levels of air pollution.ResultsWe found nonsignificantly elevated 8-oxodG levels in the IUGR-affected group compared with the non-IUGR group (p = 0.055). Similarly, slightly elevated 8-oxodG levels were found in the LBW-affected group compared with the non-LBW group (p < 0.050). In univariate analyses, we identified single nucleotide polymorphisms associated with 8-oxodG levels, IUGR, and LBW. Exposure to particulate matter < 2.5 μm was associated with increased 8-oxodG levels in placental DNA and LBW. However, multivariate-adjusted logistic regression revealed that above-median 8-oxodG levels were the only factor significantly associated with IUGR [OR = 1.56; 95% confidence interval (CI), 1.07–2.37; p = 0.022]. Above-median levels of 8-oxodG were associated with LBW (OR = 1.88; 95% CI, 1.15–3.06; p = 0.011). Other variables associated with LBW included sex and gestational age of the newborn, maternal smoking, and haplotypes in the promoter region of the gene encoding mannose-binding lectin 2 (MBL2). The role of air pollutants in the risk of adverse pregnancy outcomes seemed to be less important.ConclusionsLevels of 8-oxodG in placental DNA were associated with the risk of IUGR as well as LBW. Newborn’s sex, gestational age, maternal smoking, and genetic polymorphisms in the promoter region of the MBL2 gene were associated with LBW incidence.