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The editorial in "Frontiers in Pharmacology" discusses recent advancements in perinatal and neonatal clinical pharmacology, emphasizing the importance of pharmaceutical interventions during the perinatal period. The complexity of drug therapy during pregnancy and neonatal care is highlighted, with a call for more research to establish optimal drug choices and dosing regimens. Various studies included in the research topic showcase different methodologies to understand drug effects in perinatal and neonatal pharmacology, emphasizing the need for a multifaceted approach and collaboration to improve health outcomes for these populations. [Extracted from the article]

Purpose: Recent studies suggest increased birth defect risk associated with maternal use of specific oral antifungals. We estimated associations between first‐trimester antifungal use and selected non‐cardiac birth defects using National Birth Defects Prevention Study (NBDPS) data. Methods: Participants with a pregnancy affected by a study‐eligible birth defect ("cases") were ascertained from 10 birth defect surveillance programs; participants who delivered livebirths without a major birth defect ("controls") were randomly selected from birth records or hospital discharge lists. First‐trimester antifungal use was self‐reported via maternal interview. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects with ≥5 exposed cases using logistic regression. We estimated crude ORs and exact 95% CIs for birth defects with 3–4 exposed cases. Additionally, we conducted a probabilistic bias analysis of exposure misclassification. Results: Our analysis included 19 624 cases and 11 427 controls; 257 (1.3%) cases and 123 (1.1%) controls reported first‐trimester antifungal use. Of those who reported antifungals, 62.6% of cases and 64.2% of controls reported topical antifungals; 10.1% of cases and 4.9% of controls reported oral antifungals. We observed the strongest associations for encephalocele and Dandy‐Walker malformation and modestly elevated estimates for several other defects. Bias‐adjusted estimates were similar to the main analysis. Conclusion: First‐trimester antifungal use was positively associated with several birth defects in our analysis, although CIs were imprecise. Further study is warranted to investigate associations between antifungal use and birth defects, including potential bias due to confounding by indication. [ABSTRACT FROM AUTHOR]

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease‐ and/or target organ‐specific examples. Identifying and testing PD targets and effects in special populations, and application of age‐ and/or population‐specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD‐related as well as drug safety‐related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development. [ABSTRACT FROM AUTHOR]

The reserve of primordial follicles, which serves all oocytes for the female reproductive lifespan, is established a few days after birth in mice. During this process, more than half of the oocytes are primarily eliminated by apoptosis. Autophagy, the conserved intracellular process maintaining cellular homeostasis, serves as a protective mechanism for oocyte survival. In the current study, we speculate a new role for autophagy during primordial folliculogenesis. Active autophagy was observed in perinatal ovaries from 16.5 days post coitus to 3 days post parturition. The inhibition of autophagy by 3‐methyladenine (3‐MA) increased the number of cyst oocytes and delayed follicle formation in vivo and in organ cultures. Furthermore, the reactive oxygen species (ROS) level was elevated in ovaries treated with 3‐MA, while N‐acetylcysteine, an oxidant, alleviated the inhibitory effect of 3‐MA on primordial folliculogenesis. Additionally, the expression of growth differentiation factor 9 and transforming growth factor β1, which regulates follicle activation, was decreased after 3‐MA treatment. These data suggest that the physiological level of autophagy in perinatal ovaries regulates germ cell cyst breakdown and primordial follicle assembly by ROS clearance and exerts extensive effects on further follicular development. Active autophagy was observed in perinatal ovaries from 16.5 dpc to 3 dpp, and the physiological level of autophagy in perinatal ovaries regulates germ cell cyst breakdown and primordial follicle assembly by ROS clearance and exerts extensive effects on further follicular development. [ABSTRACT FROM AUTHOR]

Background: The growth of fetal organs is a dynamic process involving considerable changes in the anatomical and physiological parameters that can alter fetal exposure to xenobiotics in utero. Physiologically based pharmacokinetic models can be used to predict the fetal exposure as time-varying parameters can easily be incorporated.Objective: The objective of this study was to collate, analyse and integrate the available time-varying parameters needed for the physiologically based pharmacokinetic modelling of xenobiotic kinetics in a fetal population.Methods: We performed a comprehensive literature search on the physiological development of fetal organs. Data were carefully assessed, integrated and a meta-analysis was performed to establish growth trends with fetal age and weight. Algorithms and models were generated to describe the growth of these parameter values as functions of age and/or weight.Results: Fetal physiologically based pharmacokinetic parameters, including the size of the heart, liver, brain, kidneys, lungs, spleen, muscles, pancreas, skin, bones, adrenal and thyroid glands, thymus, gut and gonads were quantified as a function of fetal age and weight. Variability around the means of these parameters at different fetal ages was also reported. The growth of the investigated parameters was not consistent (with respect to direction and monotonicity).Conclusion: Despite the limitations identified in the availability of some values, the data presented in this article provide a unique resource for age-dependent organ size and composition parameters needed for fetal physiologically based pharmacokinetic modelling. This will facilitate the application of physiologically based pharmacokinetic models during drug development and in the risk assessment of environmental chemicals and following maternally administered drugs or unintended exposure to environmental toxicants in this population. [ABSTRACT FROM AUTHOR]

The management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and fetus. MG often affects women in second and third decades of life during the childbearing age. Exacerbations of MG are likely to occur during the first trimester and postpartum period. The treatment of MG during pregnancy needs to be individualized depending on the severity of MG as well as the efficacy of various treatment modalities and their possible harmful effects on pregnancy. In addition, special attention has to be given to avoid drugs and other factors (such as urinary tract infections) which may worsen MG. The key to successful outcome during pregnancy in myasthenic women lies in multidisciplinary care involving obstetricians, neurologists, anesthetist as well as neonatologist. In this review, we discuss various therapeutic options available for the management of MG during pregnancy and provide recommendations based on the current best evidence. [ABSTRACT FROM AUTHOR]

Neonatal abstinence syndrome (NAS) due to in‐utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ‐opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid‐exposed mother‐infant dyads is associated with differences in NAS severity in an independent cohort. Full‐term opioid‐exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next‐generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the −18 (11.4% vs 4.4%, P = .0001), −14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the −169 (R = 0.43, P = .008), −152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point‐wise with longer infant length of stay. Maternal associations remained significant point‐wise for −169 (β = 0.07, P = .007) and on an experiment‐wise level for +84 (β = −0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS. [ABSTRACT FROM AUTHOR]

A focused reflection on rational medicines use in neonates is valuable and relevant, because indicators to assess rational medicines use are difficult to apply to neonates. Polypharmacy and exposure to antibiotics are common, while dosing regimens or clinical guidelines are only rarely supported by robust evidence in neonates. This is at least in part due to the extensive variability in pharmacokinetics and subsequent effects of medicines in neonates. Medicines utilization research informs us on trends, on between unit variability and on the impact of guideline implementation. We illustrate these aspects using data on drugs for gastroesophageal reflux, analgesics or anti-epileptic drugs. Areas for additional research are drug-related exposure during breastfeeding (exposure prediction) and how to assess safety (tools to assess seriousness, causality, and severity tailored to neonates) since both efficacy and safety determine rational drug use. To further improve rational medicines use, we need more data and tools to assess efficacy and safety in neonates. Moreover, we should facilitate access to such data, and explore strategies for effective implementation. This is because prescription practices are not only rational decisions, but also have psychosocial aspects that may guide clinicians to irrational practices, in part influenced by the psychosocial characteristics of this population. [ABSTRACT FROM AUTHOR]

Background: Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs. Methods: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included. Results: The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19–0.83) or twice (OR = 0.43, 95% CrI: 0.21–0.68) was associated with significantly reduced risk of MTCT. Conclusions: Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether early folic acid or multivitamin supplementation during pregnancy prevents diagnosis of hyperkinetic disorders (HKD), treatment for attention deficit hyperactivity disorder (ADHD), and ADHD-like behaviors reported by parents participating in the DNBC for children at age 7. Methods: HKD diagnosis and ADHD medication use data were obtained from the Danish National Hospital, Central Psychiatric and Pharmaceutical registers. We estimated hazard ratios (HRs) for HKD diagnosis and ADHD medication use and risk ratios (RRs) for parent-reported ADHD behavior collected with the Strength and Difficulties Questionnaire (SDQ), comparing children whose mothers took folic acid or multivitamin supplements early in pregnancy defined as starting periconceptionally (4 weeks prior to their last menstrual period (LMP)) through 8 weeks after their LMP (4-8 weeks), to children whose mothers indicated no supplement use for the same entire period. Results: We identified 384 children (1.1%) with a hospital diagnosis for HKD and 642 children (1.8%) treated with ADHD medication. We found no association between risk of HKD diagnosis or intake of ADHD medication and early maternal folic acid use. However, early multivitamin use was associated with an approximately 30% reduction in risk for HKD diagnosis (aHR: 0.70, 95% CI: 0.52-0.96) and 21% reduction in treatment with ADHD medication (aHR: 0.79, 95% CI: 0.62-0.98). We observed a reduced risk in parent-reported ADHD behaviors, but these results were attenuated after adjustment. Conclusion: Our data suggest that multivitamin use in early pregnancy may reduce risk for HKD diagnosis and treatment for ADHD in the offspring. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials (ENM) are widely used in commercial, domestic, and more recently biomedical applications. While the majority of exposures to ENM are unintentional, biomedical platforms are being evaluated for use in individualized and/or tissue-targeted therapies. Treatments are often avoided during prenatal periods to reduce adverse effects on the developing fetus. The placenta is central to maternal-fetal medicine. Perturbation of placental functions can limit transfer of necessary nutrients, alter production of hormones needed during pregnancy, or allow undesired passage of xenobiotics to the developing fetus. The development of therapeutics to target specific maternal, placental, or fetal tissues would be especially important to reduce or circumvent toxicities. Therefore, this review will discuss the potential use of ENM in perinatal medicine, the applicable physiochemical properties of ENM in therapeutic use, and current methodologies of ENM testing in perinatal medicine, and identify maternal, fetal, and offspring concerns associated with ENM exposure during gestation. As potential nanoparticle-based therapies continue to develop, so does the need for thorough consideration and evaluation for use in perinatal medicine. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are exposed to a wide range of medications, including antibiotics. Although antibiotics are many times absolutely important to prevent and treat infections as well as prevent premature labor, their overuse poses a threat to the growing fetus as well as the mother. The ill-effects of antibiotic over-use and having them without prescription can cause developmental abnormalities in the fetus, known as teratogenicity. They could also cause maternal allergic reactions, as well as long term effects on the child's immunity and growth in future. Aim: In this study we aim to study the knowledge and attitude of pregnant women toward usage of antibiotics and risk of preterm baby. Methodology: We conducted a cross-sectional study, of 2470 women who presented in king Abdulaziz University, Jeddah, Saudi Arabia from April 2017 to December. Conclusion: We noted that most mothers were aware of that they must not take antibiotics without prescription while pregnant, especially for ailments such as common cold and abdominal pain. However, the pharmacists must be regulated for unnecessary over-dispatching of antibiotics, especially without confirming the pregnancy status of the costumers. [ABSTRACT FROM AUTHOR]

The authors discuss pharmacological mechanisms associated with free and total drug concentrations during pregnancy. Topics explored include the drug protein binding process in pregnancy, pharmacokinetic studies which focused on total and free antiretroviral drug concentrations in the third trimester and in postpartum, and the pregnancy-related alteration of protein concentrations.

Objective: To evaluate perinatal outcomes and congenital heart defect (CHD) prognosis in a non-selected population. Methods: The population-based surveillance data used in this assessment of CHDs were based on birth defect surveillance data collected from 2010–2012 in Liuyang City, China. Infants living with CHDs were followed up for 5 years to determine their prognosis. Prevalence, prenatal diagnosis, perinatal outcomes, and total and type-specific prognosis data were assessed using SPSS 18.0. Results: In total, 190 CHD cases were identified among the 53313 included perinatal infants (PIs), indicating a CHD prevalence of 35.64 per 10000 PIs in this non-selected population. The five most frequently identified types of CHDs were ventricular septal defects (VSDs, 38.95%), atrial septal defects (ASDs, 15.79%), cardiomegaly (7.89%), tetralogy of Fallot (TOF, 5.79%), and atrioventricular septal defects (AVSDs, 5.26%). Of the 190 CHD cases, 110 (57.89%) were diagnosed prenatally, 30 (15.79%) were diagnosed with associated malformations, and 69 (36.32%) resulted in termination of pregnancy (TOP). Moreover, 15 (7.89%) PIs died within 7 days after delivery, and 42 (22.10%) died within 1 year. In contrast, 79 (41.58%) were still alive after 5 years. When TOP cases were included, the 5-year survival rate of PIs with prenatally detected CHDs was lower than that of PIs with postnatally detected CHDs (25.45% vs. 63.75%). The CHD subtype associated with the highest rate of infant (less than 1 year old) mortality was transposition of the great arteries (100%). The subtypes associated with higher 5-year survival rates were patent ductus arteriosus (80%), ASD (63.33%), VSD (52.70%) and AVSD (50%). Conclusions: The rates of prenatal CHD detection and TOP were high in this study population, and the 5-year survival rate of PIs with CHDs was low. The government should strengthen efforts to educate pediatricians regarding this issue and provide financial assistance to improve the prognosis of infants living with CHDs, especially during the first year of life. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate drug use before and during pregnancy in Japan. Methods: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study. We analyzed data from JECS involving cases where drugs were used for 12 months before pregnancy was diagnosed, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy. Results: We analyzed data from 97,464 pregnant women. The percentages of pregnant women who had taken one or more drugs and supplements before diagnosis of pregnancy, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy, were 78.4%, 57.1%, and 68.8% respectively. Excluding iron supplements, folic acid, and other vitamins and minerals, the percentages of women taking supplements were 75.3%, 36.0%, and 51.7% at each respective time point. The following drugs and supplements were frequently used for 12 months before pregnancy diagnosis: Commercially available antipyretics, analgesics, and/or medicine for treating common cold (34.7%), antipyretics, analgesics, and/or medicine for treating common colds, which were prescribed in hospitals (29.8%), antimicrobial drugs (14.0%), and anti-allergy drugs (12.5%). The following drugs and supplements were frequently used from the time of pregnancy diagnosis until week 12 of pregnancy, and after week 12 of pregnancy: folic acid (28.9% and 26.2%), antipyretics, analgesics and/or medicines for treating common cold, that were prescribed in hospitals (7.8% and 13.3%), Chinese herbal medicines (6.0% and 9.4%, and uterine relaxants (5.1% and 15.2%). Conclusions: The analysis of a nationwide cohort study showed that a high percentage of Japanese pregnant women were taking medicinal drugs. Further research is required to elucidate the relationship between drug use during pregnancy and birth defects in Japan. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review evaluates maternal tolerance and obstetric and perinatal outcomes following sildenafil citrate (SC) use in human pregnancy.Data Sources: Scopus, PubMed, Cochrane Library, Web of Science, Embase, and Google Scholar were searched. Relevant full-text studies including case series and reports in English were included. Publications were excluded if the pregnancy was terminated or if SC was used only at conception.Results: Sixteen studies were included (n = 165). Indications for use and outcomes were variably reported. Maternal outcomes reported were headache (45.8%, 49/107), visual disturbances (17.3%, 14/81), dyspepsia/epigastric pain (15.8%, 15/95), and hypotension (0%, 0/39). There were more caesarean (83.3%, 55/66) than vaginal deliveries (16.7%, 11/66) and postpartum haemorrhage occurred in 3.9% (3/76) of women exposed to SC. Neonatal outcomes including nursery admission (67.3%, 35/52), Apgar scores <7 at 5 min (7.1%, 4/56), and cord arterial pH <7.1 (0%, 0/17) were reported. Stillbirths (4.3%, 3/69) and neonatal deaths (3.9%, 5/129) were comparable to SC-naïve groups. There were no congenital malformations (0%, 0/35).Conclusions: Despite limited data, overall there does not appear to be any severe adverse maternal side effects nor any increase in the rate of stillbirths, neonatal deaths, or congenital anomalies attributed to SC. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire.Material and Methods: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: <75th percentile, 75th-90th percentile and >90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins.Results: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery <34 weeks [odds ratio 1.71 (95% confidence interval 1.11-2.65) and odds ratio 2.83 (95% confidence interval 1.73-4.64), respectively]. Discordance >75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term.Conclusion: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months. [ABSTRACT FROM AUTHOR]

While there is strong evidence from rodent and human studies that a reduction in serotonin transporter (5-HTT) function in early-life can increase the risk for several neuropsychiatric disorders in adulthood, the effects of reduced 5-HTT function on behavior across developmental stages are underinvestigated. To elucidate how perinatal pharmacological and lifelong genetic inactivation of the 5-HTT affects behavior across development, we conducted a battery of behavioral tests in rats perinatally exposed to fluoxetine or vehicle and in 5-HTT −/− versus 5-HTT +/+ rats. We measured motor-related behavior, olfactory function, grooming behavior, sensorimotor gating, object directed behavior and novel object recognition in the first three postnatal weeks and if possible the tests were repeated in adolescence and adulthood. We also measured developmental milestones such as eye opening, reflex development and body weight. We observed that both pharmacological and genetic inactivation of 5-HTT resulted in a developmental delay. Except for hypo-locomotion, most of the observed early-life effects were normalized later in life. In adolescence and adulthood we observed object directed behavior and decreased novel object recognition in the 5-HTT −/− rats, which might be related to the lifelong inactivation of 5-HTT. Together, these data provide an important contribution to the understanding of the effects of perinatal and lifelong 5-HTT inactivation on behavior across developmental stages. [ABSTRACT FROM AUTHOR]

Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life. [ABSTRACT FROM AUTHOR]

Objective: Although there is an established link between parenting stress, postnatal depression, and anxiety, no study has yet investigated this link in first-time parental couples. The specific aims of this study were 1) to investigate whether there were any differences between first-time fathers' and mothers' postnatal parenting stress, anxiety, and depression symptoms and to see their evolution between three and 6 months after their child's birth; and 2) to explore how each parent's parenting stress and anxiety levels and the anxiety levels and depressive symptoms of their partners contributed to parental postnatal depression. Method: The sample included 362 parents (181 couples; mothers' MAge D 35.03, SD D 4.7; fathers' MAge D 37.9, SD D 5.6) of healthy babies. At three (T1) and 6 months (T2) postpartum, both parents filled out, in a counterbalanced order, the Parenting Stress Index-Short Form, the Edinburgh Postnatal Depression Scale, and the State- Trait Anxiety Inventory. Results: The analyses showed that compared to fathers, mothers reported higher scores on postpartum anxiety, depression, and parenting stress. The scores for all measures for both mothers and fathers decreased from T1 to T2. However, a path analysis suggested that the persistence of both maternal and paternal postnatal depression was directly influenced by the parent's own levels of anxiety and parenting stress and by the presence of depression in his/her partner. Discussion: This study highlights the relevant impact and effects of both maternal and paternal stress, anxiety, and depression symptoms during the transition to parenthood. Therefore, to provide efficacious, targeted, early interventions, perinatal screening should be directed at both parents. [ABSTRACT FROM AUTHOR]

Attempting to look past these limitations, at a minimum the evidence does not allow us to assume that risks of the medications in pregnancy is always just the sum of the risk associated individual drugs. Importantly, based on the vast observational literature on medication in pregnancy, the patients can be reassured that pharmacological treatment in pregnancy is mostly safe. However, it is important to be aware of the individual variations in pharmacokinetics and placental transfer associated with pregnancy physiology during different stages of gestation, the potential risk of teratogenicity, and drug-drug interactions when using multiple medications. [Extracted from the article]

The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. [ABSTRACT FROM AUTHOR]

Atherosclerosis, in turn preceded by endothelial dysfunction, underlies a series of important cardiovascular diseases. Reduced bioavailability of endothelial nitric oxide, by increasing vascular tone and promoting platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, plays a key role in the onset of the majority of cardiovascular diseases. In addition, high blood levels of asymmetric dimethylarginine, a potent inhibitor of nitric oxide synthesis, are associated with future development of adverse cardiovascular events and cardiac death. Recent reports have demonstrated that another methylarginine, i.e., symmetric dimethylarginine, is also involved in the onset of endothelial dysfunction and hypertension. Almost a decade ago, prematurity at birth and intrauterine growth retardation were first associated with a potential negative influence on the cardiovascular apparatus, thus constituting risk factors or leading to early onset of cardiovascular diseases. This condition is referred to as cardiovascular perinatal programming. Accordingly, cardiovascular morbidity and mortality are higher among former preterm adults than in those born at term. The aim of this paper was to undertake a comprehensive literature review focusing on cellular and biochemical mechanisms resulting in both reduced nitric oxide bioavailability and increased methylarginine levels in subjects born preterm. Evidence of the involvement of these compounds in the perinatal programming of cardiovascular risk are also discussed. [ABSTRACT FROM AUTHOR]

Introduction: We analyzed the association between different acculturation measures and smoking among pregnant immigrant women from Turkey and compared smoking rates between Turkish and German women. Methods: Perinatal data from a project on the influence of migration and acculturation on pregnancy and birth in Berlin was analyzed. An acculturation index (FRAKK) and two proxy measures (German language proficiency, length of stay in Germany) were used. We performed logistic regression models and calculated age-standardized prevalence ratios (SPR). Results: Smoking prevalence was 19.8% among pregnant Turkish women (n = 702) and 17.8% among German women (n = 2,999). The chance of being a smoker was significantly higher among Turkish women with a length of stay of ≥20 years compared to 0-4 years (OR = 3.63, 95% CI = 1.64- 8.05); with good/very good language skills compared to none/minor skills; with high levels of acculturation compared to low levels (the latter only among 18-29-year-old women). Compared to German women, Turkish women with a short length of stay, low acculturation scores and none/minor language skills had lower smoking rates. This finding inverts with long length of stay, high acculturation scores and good/very good language skills (≥20 years: SPR = 2.14, 95% CI = 1.56-2.94). Conclusions: Smoking among pregnant Turkish women increases with increasing acculturation. Additionally, immigrant women with a low acculturation level are less often smokers and women with a high level are more often smokers than German women. Prevention measures have to prevent women with a low acculturation from starting to smoke and to induce those with a high acculturation to quit. As smoking and acculturation are group phenomena, it is necessary to involve immigrant communities. [ABSTRACT FROM AUTHOR]

Probiotic supplementation to a mother during the perinatal period can have a positive impact on the breast milk composition. The aim of our study was to evaluate the effect of oral supplementation with the probiotic VSL#3, during late pregnancy and lactation, on breast milk levels of beneficial bacteria and some functional components (oligosaccharides and lactoferrin) potentially able to have a positive influence on the microbiota. Breast milk microbiota was analyzed by conventional and quantitative real-time PCR. In a double-blind, placebo-controlled, randomized trial, 66 women took daily either the probiotic ( n = 33) or a placebo ( n = 33). Intergroup analysis demonstrated that the amounts of both lactobacilli and bifidobacteria were significantly higher in the colostrum and mature milk of the mothers taking VSL#3 in comparison to those taking placebo. The analysis of bacterial strains and species present in breast milk of VSL#3 supplemented mothers indicated that the administered probiotic microorganisms did not pass from maternal gut to mammary gland. In women with vaginal delivery, significantly higher amounts of lactobacilli and bifidobacteria were detected in colostrum and mature milk of probiotic treated group in comparison to placebo group, whereas no significant difference was observed between groups in women who had caesarean section, neither in colostrum nor in mature milk. Milk levels of oligosaccharides and lactoferrin were similar in placebo and probiotic supplemented groups at all timepoints and regardless of the mode of delivery. Our results indicate a probiotic-dependent modulation of breast milk microbiota in vaginally delivering women, possibly exerted through a systemic effect. [ABSTRACT FROM AUTHOR]

Background: Globally, India contributes the largest share in sheer numbers to the burden of maternal and infant under-nutrition, morbidity and mortality. A major gap in our knowledge is how socio-cultural practices and beliefs influence the perinatal period and thus perinatal outcomes, particularly in the rapidly growing urban setting. Methods and Findings: Using data from a qualitative study in urban south India, including in-depth interviews with 36 women who had recently been through childbirth as well as observations of family life and clinic encounters, we explored the territory of familial, cultural and traditional practices and beliefs influencing women and their families through pregnancy, childbirth and infancy. We found that while there were some similarities in cultural practices to those described before in studies from low resource village settings, there are changing practices and ideas. Fertility concerns dominate women’s experience of married life; notions of gender preference and ideal family size are changing rapidly in response to the urban context; however inter-generational family pressures are still considerable. While a rich repertoire of cultural practices persists throughout the perinatal continuum, their existence is normalised and even underplayed. In terms of diet and nutrition, traditional messages including notions of ‘hot’ and ‘cold’ foods, are stronger than health messages; however breastfeeding is the cultural norm and the practice of delayed breastfeeding appears to be disappearing in this urban setting. Marriage, pregnancy and childbirth are so much part of the norm for women, that there is little expectation of individual choice in any of these major life events. Conclusions: A greater understanding is needed of the dynamic factors shaping the perinatal period in urban India, including an acknowledgment of the health promoting as well as potentially harmful cultural practices and the critical role of the family. This will help plan culturally appropriate integrated perinatal health care. [ABSTRACT FROM AUTHOR]

Objective Twin pregnancy is associated with increased obstetric and perinatal risk. There are conflicting reports on whether assisted conception (ART) further increases these risks. The aim of this study is to assess the obstetric and perinatal outcomes of twin pregnancies according to mode of conception. Study design A retrospective study of all viable dichorionic-diamniotic (DCDA) twin pregnancies ( n = 539) delivered at Cork University Maternity Hospital, Ireland between 2009 and 2012, divided according to spontaneous conception (SC) and ART conception, specifically IVF or ICSI. Results The ART conceived group were on average 4 years older (36.8 ± 4.23 vs 32.3 ± 4.93 years) and more frequently nulliparous (73.7%; n = 126 vs 36.1%; n = 133) than their SC counterparts ( p < 0.001). There was no significant difference in maternal antenatal complications. ART twins were twice as likely to be delivered by caesarean section (CS) (OR 2.35; 95% CI 1.76–3.14). There was no significant difference in the rates of preterm birth or NICU admission according to mode of conception. ART conceived twins were almost twice as likely to be delivered moderately preterm (32–33 +6 ) (OR 1.98, 95% CI 1.21–3.23) and were more likely to have RDS and neonatal hypoglycaemia Conclusions Twin pregnancy, irrespective of mode of conception, carries an increased risk of morbidity and mortality for both mother and babies and therefore couples should be counselled regarding the increased risk of iatrogenic twinning associated with double embryo transfer. However, for those that do conceive twins, they can be advised that assisted conception conveys no significant disadvantage over naturally conceived twin pregnancies. [ABSTRACT FROM AUTHOR]

Literature is scarce regarding the use of clopidogrel during pregnancy and the potential hazard to maternal and fetal health. We report a 33-year-old female, who presented to our clinic at 40 weeks gestation with a history of multiple prior ischemic strokes and transient ischemic attacks. The patient was placed on clopidogrel for secondary stroke prophylaxis prior to conception and maintained therapy throughout pregnancy without interruption or complication. Clopidogrel was discontinued 7 days prior to induction of labor, and a healthy baby was vaginally delivered without bleeding complications or congenital anomalies. Clopidogrel was restarted 12 hours postpartum without an incident. To our knowledge, this is the first report of clopidogrel use in pregnancy for secondary stroke prophylaxis. We also provide a current review of the literature of the use of clopidogrel in pregnancy. Based on the limited data available, clopidogrel use in pregnancy has not demonstrated significant toxicity to either the mother or the newborn. However, additional studies are needed to further assess the efficacy and safety of this medication in this patient population. [ABSTRACT FROM AUTHOR]

Highlights: [•] Perinatal exposure to ethinyl estradiol (EE2) altered endocrine sensitive endpoints in Wistar rats. [•] Gestation length and weight gain were altered in dams. [•] Anogenital distance, urethral slit length and number of nipples were altered in female offspring. [•] Prostate and ovary weights were reduced in male offspring at PD 22. [Copyright &y& Elsevier]

Aim(s) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Methods Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Results Mean (± SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml−1) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml−1). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml−1) and unbound drug concentrations (0.003 ± 0.001 ng ml−1) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Conclusions Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant. [ABSTRACT FROM AUTHOR]

Highlights: [•] Caffeine metabolism is highly dependent on development. [•] Behavioral parameters are affected by caffeine exposure during early periods of brain development. [•] Perinatal and postnatal exposure to caffeine causes modifications in the adenosine A1 receptors. [•] Neurotransmitters systems are affected by caffeine consumption. [•] Recent epidemiological studies reinforce the lack of consensus on the caffeine effects during pregnancy. [ABSTRACT FROM AUTHOR]

Highlights: [•] High doses of a dietary relevant mixture of phytoestrogens induced endocrine disruption in rats. [•] Mammary gland histology was altered in adult males after perinatal exposure. [•] Anti-androgenic effects on anogenital distance were present in newborn males. [•] An excessive human intake of phytoestrogens from dietary supplements or special dietary habits may contribute to endocrine disruption following exposure during fetal life. [Copyright &y& Elsevier]

Highlights: [•] Low-dose, prolonged exposure, as might occur with environmental contaminants. [•] Contributes to the understanding of reduced estrogen responsiveness of the uterus from androgenized rats. [•] Correlates androgen excess and progesterone and androgen receptors in the uterus. [•] Evaluates the dynamics of uterine growth/regression after androgen exposure. [Copyright &y& Elsevier]

Abstract: Perinatal infection aggravates neonatal hypoxic–ischemic (HI) brain injury and may interfere with therapeutic hypothermia. While the NF-κB signaling pathway has been implicated in microglia activation in infection-sensitized HI, the current therapeutic strategies rely on systemic intervention, which could impair neonatal immunity and increase the risk of severe infection. To devise a brain-targeted anti-NF-κB strategy, we examined the effects of intranasal delivery of tat-NBD peptides in two animal models of neonatal infection-sensitized HI. Kinetic experiments showed that tat-NBD peptides entered the olfactory bulbs rapidly (10–30min) and peaked in the cerebral cortex around 60min after intranasal application in P7 rats. Further, intranasal delivery of 1.4mg/kg tat-NBD, which is only 7% of the intravenous dose in past studies, markedly attenuated NF-κB signaling, microglia activation, and brain damage triggered by HI with 4 or 72h pre-exposure to the bacterial endotoxin lipopolysaccharide (LPS). In contrast, intranasal delivery of mutant tat-NBD peptides or systemic application of minocycline failed to block LPS-sensitized HI injury. Yet, intranasal delivery of up to 5.6mg/kg tat-NBD peptides immediately after pure-HI insult showed little protection, likely due to its rapid clearance from the brain and inability to inhibit parenchymal plasminogen activators. Together, these results suggest a novel therapy of infection-sensitized HI brain injury in newborns. [Copyright &y& Elsevier]

Highlights: [•] Perinatal exposure of DBP induced neurotoxicity in neonatal and immature rats. [•] DBP exposure induced cell apoptosis in hippocampal neurons of these animals. [•] DBP exposure decreased the expression of synaptophysin in the hippocampus. [•] DBP exposure reduced both the slope and amplitude of fEPSPs. [•] Perinatal exposure of DBP had no influence on mature animals after DBP withdrawal. [ABSTRACT FROM AUTHOR]