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Adverse infant outcomes often rise in the aftermath of disaster, but few studies have assessed the effects of disaster on maternal health. 1091 southern Louisiana women were interviewed about their pregnancy history, including pregnancy complications. Associations between oil spill exposures and gestational diabetes, hypertensive disorders, and nausea/vomiting were assessed for all reported pregnancies. 631 women had a pregnancy both before and after the oil spill. Generalized estimating equations (logistic regression) with adjustment for confounders were used. To assess possible unmeasured confounding, instead of considering oil spill exposure as a time-varying exposure, women were defined as oil spill-exposed or not. If oil spill-exposed women were equally prone to complications in pregnancies that occurred prior to the oil spill as after it, it was considered that any associations were likely due to selection or reporting issues. Women who reported oil spill exposure, particularly loss of use of the coast, were more likely to report gestational diabetes; however, the level of association was similar for pregnancies before and after the spill (p for interaction >0.10 and odds ratios (ORs) for pregnancies prior to the spill > than those after the spill). No associations were found between oil spill exposure and hypertensive disorders. This analysis does not suggest an increased risk of pregnancy complications associated with exposure to the oil spill; however, future studies should assess exposure and outcomes prospectively and clinically instead of relying on self-report. Full article

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis. Full article

Vitamin C (vitC) is essential for normal pregnancy and fetal development and poor vitC status has been related to complications of pregnancy. We have previously shown lower vitC status in diabetic women throughout pregnancy compared to that of non-diabetic controls. Here, we evaluate the relationship between vitC status late in diabetic pregnancy in relation to fetal outcome, complications of pregnancy, diabetic characteristics, and glycemic control based on data of 47 women from the same cohort. We found a significant relationship between the maternal vitC level > or ≤ the 50% percentile of 26.6 μmol/L, respectively, and the umbilical cord blood vitC level (mean (SD)): 101.0 μmol/L (16.6) versus 78.5 μmol/L (27.8), p = 0.02; n = 12/16), while no relation to birth weight or Apgar score was observed. Diabetic women with complications of pregnancy had significantly lower vitC levels compared to the women without complications (mean (SD): 24.2 μmol/L (10.6) vs. 34.6 μmol/L (14.4), p = 0.01; n = 19 and 28, respectively) and the subgroup of women (about 28%) characterized by hypovitaminosis C (<23 μmol/L) had an increased relative risk of complications of pregnancy that was 2.4 fold higher than the one found in the group of women with a vitC status above this level (p = 0.02, 95% confidence interval 1.2–4.4). No correlation between diabetic characteristics of the pregnant women and vitC status was observed, while a negative association of maternal vitC with HbA1c at delivery was found at regression analysis (r = −0.39, p < 0.01, n = 46). In conclusion, our results may suggest that hypovitaminosis C in diabetic women is associated with increased risk of complications of pregnancy. Full article

Adequate zinc stores in the body are extremely important during periods of accelerated growth. However, zinc deficiency is common in developing countries and low maternal circulating zinc concentrations have previously been associated with pregnancy complications. We reviewed current literature assessing circulating zinc and dietary zinc intake during pregnancy and the associations with preeclampsia (PE); spontaneous preterm birth (sPTB); low birthweight (LBW); and gestational diabetes (GDM). Searches of MEDLINE; CINAHL and Scopus databases identified 639 articles and 64 studies were reviewed. In 10 out of 16 studies a difference was reported with respect to circulating zinc between women who gave birth to a LBW infant (≤2500 g) and those who gave birth to an infant of adequate weight (>2500 g), particularly in populations where inadequate zinc intake is prevalent. In 16 of our 33 studies an association was found between hypertensive disorders of pregnancy and circulating zinc; particularly in women with severe PE (blood pressure ≥160/110 mmHg). No association between maternal zinc status and sPTB or GDM was seen; however; direct comparisons between the studies was difficult. Furthermore; only a small number of studies were based on women from populations where there is a high risk of zinc deficiency. Therefore; the link between maternal zinc status and pregnancy success in these populations cannot be established. Future studies should focus on those vulnerable to zinc deficiency and include dietary zinc intake as a measure of zinc status. Full article

Background: An association between the level of vitamin D and the risk of pregnancy-related complications remains unclear. The aim of this study was to examine concentrations of 25(OH) vitamin D in Polish women with normal pregnancies and pregnancies complicated by gestational hypertension, preeclampsia or gestational diabetes mellitus (GDM). Moreover, we analyzed an association between maternal serum 25(OH)D and the risk of gestational hypertension, preeclampsia and GDM. Material and Methods: The study included 207 pregnant women, among them 171 with pregnancy-related complications: gestational hypertension (n = 45), preeclampsia (n = 23) or GDM (n = 103). The control group consisted of 36 women with normal pregnancies. Concentrations of serum 25(OH)D were measured at admission to the hospital prior to delivery Results: Patients with hypertension did not differ significantly from the controls in terms of their serum 25(OH)D concentrations (18.20 vs. 22.10 ng/mL, p = 0.15). Highly significant differences were found in 25(OH)D concentrations of women with preeclampsia and the controls (14.75 vs. 22.10 ng/mL, p = 0.0021). GDM was not associated with significant differences in 25(OH)D concentration. A low level of 25(OH)D turned out to be associated with an increased risk of preeclampsia during pregnancy on both univariate and multivariate regression analysis, and was a significant predictor of this condition on ROC (receiver operating characteristic) analysis (AUC = 0.70, p < 0.01). Conclusions: 25(OH)D deficiency is common among pregnant Polish women. Low concentrations of 25(OH)D may play a role in the etiopathogenesis of preeclampsia. Routine assessment of the 25(OH)D level during pregnancy may be crucial for the identification of women at increased risk of preeclampsia. Full article

Anti-beta 2 glycoprotein 1 (anti-β₂GP1) antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although they are a subtype of anti-phospholipid (APL) antibody, anti-β₂GP1 antibodies form complexes with β₂GP1 before binding to different receptors associated with anionic phospholipids on structures such as platelets and endothelial cells. β₂GP1 consists of five short consensus repeat termed “sushi” domains. It has three interchangeable conformations with a cryptic epitope at domain 1 within the molecule. Anti-β₂GP1 antibodies against this cryptic epitope are referred to as ‘type A’ antibodies, and have been suggested to be more strongly associated with both vascular and obstetric complications. In contrast, ‘type B’ antibodies, directed against other domains of β₂GP1, are more likely to be benign antibodies found in asymptomatic patients and healthy individuals. Although the interactions between anti-β₂GP1 antibodies, β₂GP1, and platelets have been investigated, the actual targeted metabolic pathway(s) and/or receptor(s) involved remain to be clearly elucidated. This review will discuss the current understanding of the interaction between anti-β₂GP1 antibodies and β₂GP1, with platelet receptors and associated signalling pathways. Full article

A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of delivering preterm may allow for targeted interventions to prevent or delay preterm birth (PTB). In addition to identifying those at increased risk for preterm birth, biomarkers may be able to distinguish neonates at particular risk for future complications due to modifiable environmental factors, such as maternal smoking or alcohol use during pregnancy. Currently, there are no such biomarkers available, though candidate gene and epigenome-wide association studies have identified DNA methylation differences associated with PTB, its risk factors and its long-term outcomes. Further biomarker development is crucial to reducing the health burden associated with adverse intrauterine conditions and preterm birth, and the results of recent DNA methylation studies may advance that goal. Full article

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated. Full article

Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection and commonly associated with sensorineural deficit. At present, there is neither prophylaxis nor treatment during pregnancy. The objective of this study was to evaluate the level of awareness regarding CMV infection and its consequences in women delivering at the University of Geneva Hospitals (Geneva, Switzerland). Methods: The study consisted of a validated questionnaire completed by women in the immediate postpartum period. Results: The questionnaire was completed by 59% (314/528) of delivering women. Only 39% (123/314) knew about CMV and 19.7% (62/314) had received information about preventive measures. Women were more aware about other congenital diseases, such as toxoplasmosis (87%); human immunodeficiency virus (99%); syphilis (85.5%); rubella (92.3%); and group B Streptococcus (63%). Factors associated with CMV awareness were Swiss nationality, high education level, employment in health care or with children, and being followed by an obstetrician. Regarding quality of information, few were aware of the main CMV complications (deafness, 25.2%; mental retardation, 34.5%). Among those informed about CMV, most (74.6%) knew about preventive measures. Among these, 82.5% thought that these were easily applicable. Conclusions: Most women were unaware of CMV infection and its potential risks during pregnancy. It is crucial to improve CMV information given to pregnant women to prevent the risks for the fetus/newborn. Full article

There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question. Full article

Pregnancy causes significant metabolic and hemodynamic changes in a woman’s physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up. Full article

The health behaviours of pregnant women with very severe obesity are not known, though these women are at high risk of pregnancy complications. We carried out a prospective case-control study including 148 very severely obese (BMI >40 kg/m²) and 93 lean (BMI <25 kg/m²) pregnant women. Diet, physical activity, smoking, alcohol and folic acid consumption were assessed by questionnaire in early and late (16 and 28 weeks gestation) pregnancy. Circulating levels of iron, vitamin B12 and folate and other essential trace elements and minerals were measured in a subset at each time point. The findings biochemically confirmed that very severely obese women consumed diets that were energy-rich but poor in essential micronutrients. A third of all women met physical activity recommendations for pregnancy. A third of very severely obese women and two thirds of lean women took folic acid supplements prior to pregnancy. Very severely obese women were more likely to smoke but less likely to drink alcohol than lean women (all p < 0.05). Women with very severe obesity have low self-reported intakes and circulating levels of essential micronutrients in pregnancy and few follow current recommendations for pregnancy nutrition and lifestyle. These high-risk women represent a group to target for education about health behaviours prior to and during pregnancy. Full article

Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. Full article

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. Full article

Objective: To evaluate the outcome of 80 pregnant women with systemic lupus erythematosus (SLE) and explore the risk factors for lupus flare, obstetric complications and fetal loss. Methods: 83 pregnancies in 80 women were divided into three groups. Group A: patients in remission for > 6 months before pregnancy, proteinuria < 0.5 g per day, without renal failure and discontinuation of cytotoxic drugs for > one year; Group B: patients with SLE disease activity in the six months before pregnancy; Group C: patients with new onset SLE during pregnancy. Results: In group A, 76.47% pregnancies achieved full-term deliveries and 80.39% achieved live born infants. In group B and C, the outcome was poor. Among 62 patients (64 pregnancies) diagnosed as SLE before pregnancy, SLE flares occurred in 27 (42.19%) pregnancies. SLE disease activity in the six months before pregnancy was significantly associated with lupus flare (OR 5.00, 95% CI 1.14–21.87, p = 0.03) and fetal loss. New onset lupus during pregnancy was independently associated with obstetric complications (OR 7.22, 95% CI 2.14–24.38, p = 0.001). Conclusions: The current study confirmed the previous report that SLE should be considered a high risk of pregnancy. If pregnancy is planned after remission for > 6 months, the favorable outcome can be achieved. Full article

Hypertensive disorders of pregnancy are a major cause of poor outcome, including placental abruption, organ failure, cerebrovascular accident and disseminated intravascular coagulation. These disorders are associated with increased fetal risk of intrauterine growth restriction, intrauterine death and prematurity. Electrocardiography (ECG) recently emerged as a useful tool to evaluate cardiovascular complications during pregnancy. Specifically, left atrial abnormalities detected by standard ECG are associated with a fourfold increased risk of developing hypertensive disorders during pregnancy. The mechanisms linking left atrial abnormality on ECG with hypertensive disorders are still elusive. Several mechanisms, possibly reflected by abnormal left atrial activation on ECG, has been suggested. These include increased reactivity to angiotensin II and up-regulation of angiotensin type 1 receptors, with activation of autoantibodies targeting these receptors. Full article

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. Full article

Complications of pregnancy represent a significant disease burden, with both immediate and lasting consequences for mother and baby. Two key pregnancy complications, fetal growth restriction (FGR) and preeclampsia (PE), together affect around 10%–15% of all pregnancies worldwide. Despite this high incidence, there are currently no therapies available to treat these pregnancy disorders. Early delivery remains the only intervention to reduce the risk of severe maternal complications and/or stillbirth of the baby; however early delivery itself is associated with increased risk of neonatal mortality and morbidity. As such, there is a pressing need to develop new and effective treatments that can prevent or treat FGR and PE. Animal models have been essential in identifying and screening potential new therapies in this field. In this review, we address recent progress that has been made in developing therapeutic strategies for pregnancy disorders, some of which are now entering clinical trials. Full article

Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. Full article

Type 2 Diabetes Mellitus (T2DM) and Gestational Diabetes (GDM) are important and escalating problems worldwide. GDM increases the risk of complications in pregnancy and birth, as well as a 1 in 2 chance of developing T2DM later in life. The burden of GDM extends to offspring, who have an increased risk of obesity and diabetes—further perpetuating the cycle of diabetes within families. Clinical trial evidence demonstrates T2DM incidence reduced by up to 50% for women with GDM with nutrition and physical activity changes and the economic modeling suggests cost effectiveness. The key diet-related changes to reduce T2DM risk are reviewed, in addition to breastfeeding. The difficulties associated with the delivery of dietary and lifestyle behaviour change to women after GDM are discussed and focus on: complex healthcare system interactions needed for care delivery; women finding postpartum self-care challenging; and low levels of awareness being present across the board. In addition, studies currently underway to improve care provision in this important area will be examined. Full article

Although pregnancy is considered as a physiological state, most pregnant women in developed countries receive multiple medications to prevent maternal or neonatal complications, with antibiotics among the most frequently prescribed. During pregnancy, antibiotics are often prescribed in the context of preterm labor, intrapartum fever, prevention of neonatal Group B Streptococcus fever, and cesarean section. Outside this period, they are commonly prescribed in the community setting for respiratory, urinary, and ear, nose and throat infection symptoms. Whereas some of the current indications have insightful reasons to justify their use, potential risks related to overuse and misuse may surpass the benefits. Of note, the recent 2014 World Health Assembly expressed serious concern regarding antibiotic resistance due to antibiotic overuse and misuse and urged immediate action to combat antibiotic resistance on a global scale. Most studies in the obstetrics field have focused on the benefits of antibiotics for short-term maternal and neonatal complications, but with very little (if any) interest in long-term consequences. Full article

There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. Full article

Maternal markers are widely used to screen for fetal neural tube defects (NTDs), chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening. Full article

Polyunsaturated fatty acids (PUFAs) are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA) are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM) and preterm-PROM (pPROM), are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health. Full article

Prolonged oligohydramnios following extreme preterm prelabour rupture of membranes (EPPROM) is traditionally associated with a high morbidity and mortality to both the mother and the baby. The clinical maternal evaluation and fetal ultrasound assessment may provide important prognostic information for the clinicians and should be taken into account when counselling the patients so as to provide them with enough information to make decision of continuing or interrupting the pregnancy. Current financial constraints on the National Healthcare Service (NHS) resources make it imperative for clinical decision-makers and budgetary planners to make the right decision of continuing or terminating a second trimester pre-viability amniorrhexis for desperate parents. To assess the economic consequences following EPPROM, the risk of infection to both baby and mother, psychological impact on the parents and associated complications and further disability after delivery on this fragile group of patients to the NHS resources. We review the clinical course, outcome, and the challenges to parents and health care professionals on three pregnancies complicated by EPPROM, occurring before 24 weeks’ gestation with a membrane rupture to delivery interval (latent period) of 14 days or more. The anticipated birth of an extremely premature infant poses many challenges for parents and health care professionals. As parents are faced with difficult decisions that can have a long-term impact on the infant, family and country’s resources, it is critical to provide the type of information and support that is needed by them. Taking all these into consideration with the period of ventilation and respiratory assistance in Neonatal Intensive Care Unit (NICU) is essential to provide maximum chances for survival, minimizing the risk for long term sequelae of the neonate and provides the parents enough time to decide on making the right decision with the associated guidance of the healthcare provider. Full article

Background: Smoking is considered the most important preventable risk factor in relation to the development of complications during pregnancy and delivery. The aim of this study was to evaluate the effectiveness of an intensive 6-week gold standard programme (GSP) on pregnant women in real life. Methods: This was a prospective cohort study based on data from a national Danish registry on smoking cessation interventions. The study population included 10,682 women of a fertile age. The pregnancy status of the study population was identified using the National Patient Registry. Results: The response rate to follow up was 76%. The continuous abstinence rate for both pregnant and non-pregnant smokers was 24–32%. The following prognostic factors for continuous abstinence were identified: programme format (individual/group), older age, heavy smoking, compliance with the programme, health professional recommendation, and being a disadvantaged smoker. Conclusions: The GSP seems to be as effective among pregnant smokers as among non-pregnant smoking women. Due to the relatively high effect and clinical significance, the GSP would be an attractive element in smoking cessation intervention among pregnant women. Full article

MicroRNAs (miRNAs) are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies. Full article

Objectives: To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth. Patients and Methods: The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates. Results: The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group. Conclusions: The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth. Full article

Epidemiologic evidence provides some support for a causal association between maternal secondhand smoke (SHS) exposure during pregnancy and reduction in infant birth weight. The purpose of this cross-sectional study is to examine the magnitude of this association in China, where both prevalence and dose of SHS exposure are thought to be higher than in U.S. populations. Women who gave birth in Beijing and Changchun September 2000–November 2001 were interviewed to quantify self-reported prenatal SHS exposure. Their medical records were reviewed for data on pregnancy complications and birth outcomes. Non-smoking women who delivered term babies (≥37 weeks gestation) were included in the study (N = 2,770). Nearly a quarter of the women (24%) reported daily SHS exposure, 47% reported no prenatal exposure, and 75% denied any SHS exposure from the husband smoking at home. Overall, no deficit in mean birth weight was observed with exposure from all sources of SHS combined (+11 grams, 95% CI: +2, +21). Infants had higher mean birth weights among the exposed than the unexposed for all measures of SHS exposure. Future studies on SHS exposure and infant birth weight in China should emphasize more objective measures of exposure to quantify and account for any exposure misclassification. Full article

The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS. Full article

This review summarizes progress in treating severe and complicated malaria, which are global problems, claiming at least one million lives annually, and have been accompanied by advances in our understanding of the pathogenesis of severe malaria complications. New drugs such as intravenous artesunate (AS) and intramuscular artemether (AM) are improving outcomes and decreasing malaria deaths. Trials comparing AM to the traditional parenteral drug, quinine, have not demonstrated however convincing evidence of a mortality advantage for AM. The South East Asian Quinine Artesunate Malaria Trials (SEAQUAMAT), a multicenter, randomized, open-label study comparing AS with quinine showed that parenteral AS was shown to be associated with a 35% reduction in the risk of mortality compare to quinine, and is now the recommended treatment by the WHO for severe and complicated malaria in low-transmission areas and in the second and third trimesters of pregnancy, with almost all the benefit reported in those with high parasite counts. Artesunate is a semisynthetic derivative of artemisinin whose water solubility facilitates absorption and provides an advantage over other artemisinins because it can be formulated as oral, rectal, intramuscular, and intravenous preparations. Artesunate is rapidly hydrolyzed to dihydroartemisinin, which is the most active schizonticidal metabolite. Injectable AS results in a more rapid systemic availability of AS compared with intramuscular AM. This pharmacokinetic advantage may provide a clinical advantage in the treatments of severe and complicated malaria. Full article