Association of Eicosapentaenoic and Docosahexaenoic Acid Intake with Low Birth Weight in the Second Trimester: The Japan Pregnancy Eating and Activity Cohort Study.

This study examined the association of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during the second trimester with low birth weight (LBW) in pregnant Japanese women and was conducted in conjunction with the Japan Pregnancy Eating and Activity Cohort (J-PEACH) study. The study included 504 pregnant women from four Japanese sites. During the second trimester (14-27 weeks), the participants filled out a self-administered questionnaire assessing the frequency of DHA and EPA supplement intake in the past month, as well as a brief-type self-administered diet history questionnaire (BDHQ). The analysis involved data from two time points: responses to the BDHQ and infant data at birth. In total, 471 and 33 participants were classified into the normal birth weight and LBW groups, respectively. The participants were divided into high-, medium-, and low-intake groups based on their total dietary and EPA and DHA supplementary intakes. The Cochran-Armitage trend test was used to analyze the data; the prevalence of LBW was higher in the low-intake group (p = 0.04). There was no significant sex-based trend (p = 0.27 and p = 0.35). In Japanese women, low dietary and supplementary EPA and DHA intake until the second trimester were risk factors for LBW.

A practical method for prenatal diagnosis of anal atresia by second trimester ultrasound screening - A retrospective study.

OBJECTIVES: The study aimed to demonstrate the performance of anal atresia ultrasound screening in the second trimester and to describe associated experiences in a primary care fetal medicine clinic. MATERIALS AND METHODS: We retrospectively analyzed the medical records of fetuses who underwent a second-trimester screening at the Taiji clinic between November 2019 and May 2022. Fisher's exact test was conducted to investigate potential risk factors. RESULTS: There were 28 459 fetuses screened in our clinic during the study period; eventually, 6 cases were diagnosed with anal atresia after birth. The incidence of anal atresia in our sample was 2.11 in 10 000. Based on our findings, potential risk factors significantly associated with anal atresia included: multiple pregnancies (p-value = 0.0185) and in-vitro fertilization (p-value = 0.038). Half of the anal atresia cases were associated with abnormalities affecting other organ systems, most frequently the genitourinary system (66.7%) and cardiovascular system (66.7%), especially persistent left superior vena cava (2 cases). CONCLUSION: Anal atresia is a malformation that requires extensive care; the clinical management after the prenatal discovery of its signs should include testing for chromosomal abnormalities and close monitoring of the amniotic fluid volume. Therefore, prenatal ultrasound screening for anal atresia in the second trimester is critical, particularly in the cases of multiple and IVF pregnancies, and multiple abnormalities. The fetuses with ultrasound signs of anal atresia should be followed at a later gestational period and referred to a specialized institution for postnatal management planning and parental counseling.

Spatiotemporal molecular dynamics of the developing human thalamus.

The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially distinct nuclei, but the molecular architecture of thalamic development is poorly understood, especially in humans. To begin to delineate the molecular trajectories of cell fate specification and organization in the developing human thalamus, we used single-cell and multiplexed spatial transcriptomics. We show that molecularly defined thalamic neurons differentiate in the second trimester of human development and that these neurons organize into spatially and molecularly distinct nuclei. We identified major subtypes of glutamatergic neuron subtypes that are differentially enriched in anatomically distinct nuclei and six subtypes of γ-aminobutyric acid-mediated (GABAergic) neurons that are shared and distinct across thalamic nuclei.

Clinical Value of Serum miR-124 and miR-200C Combined with Ultrasound NT in Screening Down Syndrome in Elderly Puerperae in the Second Trimester.

Objective: To evaluate the clinical value of serum miR-124 and miR-200C combined with ultrasound NT in screening Down syndrome (DS) in elderly puerperae during the second trimester. Methods: 84 elderly pregnant women at high risk of DS were included (DS group: 58, non-DS group: 26). Serum markers (uE3, ß-hCG, AFP, miR-124, and miR-200C) were measured. Differences in markers between groups were analyzed, and a prediction model was used for DS evaluation. Results: The DS group showed higher smoking, drinking, and radiation exposure rates (P < .05). MOM values of ß-hCG and AFP were higher, while MOM value of uE3 was lower in the DS group (P < .05). MiR-124 and miR-200C were up-regulated in the DS group (P < .05). The prediction model and ROC curve analysis indicated the diagnostic value of the markers for DS (AUC = 0.779, 0.817, 0.780, 0.884, 0.887, P < .05). MiR-124 had the highest diagnostic specificity. Conclusion: MiR-124 and miR-200C can serve as auxiliary serum markers for early screening of DS in elderly puerperae during the second trimester.

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD). OBJECTIVE: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring. METHODS: We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n = 298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n = 73). RESULTS: High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio  2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group. CONCLUSIONS: Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.

Evaluating women's acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians: a mixed methods study.

BACKGROUND: Studies evaluating task sharing in postabortion care have mainly focused on women in first trimester and many lack a qualitative component. We aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences in Uganda. METHODS: Our mixed methods study combined 1140 structured interview data from a randomized controlled equivalence trial and in-depth interviews (n = 28) among women managed with misoprostol for second trimester incomplete abortion at 14 public health facilities in Uganda. Acceptability, our main outcome, was measured at the 14-day follow-up visit using a structured questionnaire as a composite variable of: 1) treatment experience (as expected/ better than expected/ worse than expected), and 2) satisfaction - if patient would recommend the treatment to a friend or choose the method again. We used generalized mixed effects models to obtain the risk difference in acceptable post abortion care between midwife and physician groups. We used inductive content analysis for qualitative data. RESULTS: From 14th August 2018 to 16th November 2021, we assessed 7190 women for eligibility and randomized 1191 (593 to midwife and 598 to physician). We successfully followed up 1140 women and 1071 (94%) found the treatment acceptable. The adjusted risk difference was 1.2% (95% CI, - 1.2 to 3.6%) between the two groups, and within our predefined equivalence range of - 5 to + 5%. Treatment success and feeling calm and safe after treatment enhanced acceptability while experience of side effects and worrying bleeding patterns reduced satisfaction. CONCLUSIONS: Misoprostol treatment of uncomplicated second trimester incomplete abortion was equally and highly acceptable to women when care was provided by midwives compared with physicians. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to postabortion care services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03622073.

Approximately 9.6% of abortion-related deaths occur in Sub-Saharan Africa. These deaths can be prevented if unintended pregnancies are avoided, women can access safe abortions within the expectations of the country's laws, and post abortion care (PAC) services are provided equitably. Previous research shows that women with abortion complications in the first trimester of pregnancy can be treated with misoprostol by either midwives or physicians. This sharing of tasks between the midwives and physicians is safe, effective, and acceptable. However, there is a gap in evidence on task sharing in the second trimester. To check practicability of task sharing in second trimester, we aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences. Our study therefore combined quantitative and qualitative approaches. Women's acceptability of misoprostol treatment for incomplete second trimester abortion was found to be equally acceptable when provided by midwives compared with physicians. Treatment success, feeling calm and safe after treatment increased acceptability, while experience of side effects and worrying bleeding patterns reduced satisfaction. Counselling of women may address some of these problems since it provides reassurance and reduces anxiety. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to PAC services.

Comparison of the effectiveness and safety of treatment of incomplete second trimester abortion with misoprostol provided by midwives and physicians: a randomised, controlled, equivalence trial in Uganda.

BACKGROUND: To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of treatment for incomplete second trimester abortion with misoprostol, comparing care provision by midwives with that provided by physicians in Uganda. METHODS: Our multicentre, randomised, controlled, equivalence trial undertaken in 14 health facilities in Uganda recruited women with incomplete abortion of uterine size 13-18 weeks. We randomly assigned (1:1) women to clinical assessment and treatment by either midwife or physician. The randomisation sequence was computer generated, in blocks of four to 12, and stratified for study site. Participants received sublingual misoprostol (400 µg once every 3 h for up to five doses). The study was not concealed from the health-care providers and study participants. Primary outcome was complete abortion within 24 h that did not require surgical evacuation. Analysis was per-protocol and intention to treat; the intention-to-treat population consisted of women who were randomised, received at least one dose of misoprostol, and reported primary outcome data, and the per-protocol population excluded women with unexplained discontinuation of treatment. We used generalised mixed-effects models to obtain the risk difference. The predefined equivalence range was -5% to 5%. The trial was registered at ClinicalTrials.gov, NCT03622073. FINDINGS: Between Aug 14, 2018, and Nov 16, 2021, 1191 eligible women were randomly assigned to each group (593 women to the midwife group and 598 to the physician group). 1164 women were included in the per-protocol analysis, and 530 (92%) of 577 women in the midwife group and 553 (94%) of 587 women in the physician group had a complete abortion within 24 h. The model-based risk difference for the midwife versus physician group was -2·3% (95% CI -4·4 to -0·3), and within our predefined equivalence range (-5% to 5%). Two women in the midwife group received blood transfusion. INTERPRETATION: Clinical assessment and treatment of second trimester incomplete abortion with misoprostol provided by midwives was equally effective and safe as when provided by physicians. In low-income settings, inclusion of midwives in the medical management of uncomplicated second trimester incomplete abortion has potential to increase women's access to safe post-abortion care. FUNDING: Swedish Research Council and THRiVE-2.

Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms.

BACKGROUND: We previously showed that continued folic acid (FA) supplementation beyond the first trimester of pregnancy appears to have beneficial effects on neurocognitive performance in children followed for up to 11 years, but the biological mechanism for this effect has remained unclear. Using samples from our randomized controlled trial of folic acid supplementation in second and third trimester (FASSTT), where significant improvements in cognitive and psychosocial performance were demonstrated in children from mothers supplemented in pregnancy with 400 µg/day FA compared with placebo, we examined methylation patterns from cord blood (CB) using the EPIC array which covers approximately 850,000 cytosine-guanine (CG) sites across the genome. Genes showing significant differences were verified using pyrosequencing and mechanistic approaches used in vitro to determine effects on transcription. RESULTS: FA supplementation resulted in significant differences in methylation, particularly at brain-related genes. Further analysis showed these genes split into two groups. In one group, which included the CES1 gene, methylation changes at the promoters were important for regulating transcription. We also identified a second group which had a characteristic bimodal profile, with low promoter and high gene body (GB) methylation. In the latter, loss of methylation in the GB is linked to decreases in transcription: this group included the PRKAR1B/HEATR2 genes and the dopamine receptor regulator PDE4C. Overall, methylation in CB also showed good correlation with methylation profiles seen in a published data set of late gestation foetal brain samples. CONCLUSION: We show here clear alterations in DNA methylation at specific classes of neurodevelopmental genes in the same cohort of children, born to FA-supplemented mothers, who previously showed improved cognitive and psychosocial performance. Our results show measurable differences at neural genes which are important for transcriptional regulation and add to the supporting evidence for continued FA supplementation throughout later gestation. This trial was registered on 15 May 2013 at www.isrctn.com as ISRCTN19917787.

The association between serum selenium level and gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: The relationship between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The purpose is to update and summarize previous studies to understand the relationship in more detail. METHODS: PubMed, The Cochrane Library, EMBASE, Web of science, CNKI, WANFANG DATA and Cqvip were searched for studies published up to 3 September 2021. The random-effects model was used to measure the combined estimation. The overall effect was reported in a standard mean difference (SMD) and 95% confidence interval (95% CI). All data were analysed by Review Manager 5.4. RESULTS: Twenty-seven studies involving 1588 patients with GDM and 2450 healthy pregnant women contributed to this meta-analysis. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.29; 95% CI: -1.60 to -0.97, p < 0.00001). Subgroup analyses showed that such trend was consistent within the non-European population (Asia: SMD = -1.44; 95% CI: -1.79 to -1.08, p < 0.00001; Africa: SMD = -2.62; 95% CI: -4.50 to -0.74, p = 0.006) and in the second and third trimesters (the second trimester: SMD = -1.41; 95% CI: -1.82 to -0.99, p < 0.00001; the third trimester: SMD = -1.54; 95% CI: -2.09 to -0.98, p < 0.00001), but not within the European population (SMD = -0.47; 95% CI: -1.09 to 0.16, p = 0.14) or in the first trimester (SMD = -0.52; 95% CI: -1.13 to 0.10, p = 0.10). CONCLUSIONS: This meta-analysis showed that the serum selenium level of patients with GDM was lower than that in healthy pregnant women, especially within the non-European population and in the second and third trimesters.

Immediate IUD insertion after second trimester abortion: implications for service delivery.

BACKGROUND: The availability of modern contraception including long-acting reversible contraceptives (LARC), is a fundamental component of postabortion care. Findings from a recent randomized controlled trial (RCT) in South Africa comparing immediate to delayed insertion of the copper intrauterine device (IUD) after medical abortion (MA) at 17-20 gestational weeks showed that immediate insertion resulted in higher IUD use at 6 weeks postabortion, but that expulsion rates were significantly higher than for delayed insertion. This study aims to explore barriers, facilitators, and context-specific factors relevant to the implementation of immediate IUD provision after second trimester medical abortion. METHODS: We performed a qualitative study alongside the RCT in which we conducted in-depth interviews with 14 staff providing healthcare to study participants and 24 study participants. Research questions explored barriers and facilitators to implementation of immediate IUD insertion, contraceptive decision-making, and the impact of context and supplementary trial activities on service provision. Interviews were recorded and transcribed, with translation into English if needed. We performed a triangulated thematic analysis at the level of the transcribed interview text. RESULTS: Contraceptive counselling at the abortion facility by a study nurse improved knowledge, corrected misconceptions, and increased demand for the IUD postabortion. Women expressed a clear preference for immediate insertion. Convenience, protection from pregnancy and privacy issues were paramount and women expressed preference for engagement with staff who knew their abortion history, and with whom they had an established connection. Doctors and nurses were generally in favour of immediate insertion and said it could be incorporated into standard care if women wanted this. This contrasted with the need for interventions by the research team to reinforce adherence by staff to provide contraception as allocated during the trial. CONCLUSIONS: Women and staff favour immediate IUD insertion after second trimester medical abortion, but service delivery may require structures that ensure timely insertion postabortion, continuity of care, communication that mitigates loss to follow-up and training of staff to ensure competence.

Development of human white matter pathways in utero over the second and third trimester.

During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.

Effect of Maternal Nutritional Status and Mode of Delivery on Zinc and Iron Stores at Birth.

Zinc and iron deficiencies among infants aged under 6 months may be related with nutrient store at birth. This study aimed to investigate the association between zinc and iron stores at birth with maternal nutritional status and intakes during pregnancy. 117 pregnant women were enrolled at the end of second trimester and followed until delivery. Clinical data during pregnancy, including pre-pregnancy body mass index (BMI) and at parturition were collected from medical record. Zinc and iron intakes were estimated from a food frequency questionnaire. Serum zinc and ferritin were determined in maternal blood at enrollment and cord blood. Mean cord blood zinc and ferritin were 10.8 ± 2.6 µmol/L and 176 ± 75.6 µg/L, respectively. Cord blood zinc was associated with pre-pregnancy BMI (adj. ß 0.150; p = 0.023) and serum zinc (adj. ß 0.115; p = 0.023). Cord blood ferritin was associated with pre-pregnancy BMI (adj. ß -5.231; p = 0.009). Cord blood zinc and ferritin were significantly higher among those having vaginal delivery compared to cesarean delivery (adj. ß 1.376; p = 0.007 and 32.959; p = 0.028, respectively). Maternal nutritional status and mode of delivery were significantly associated with zinc and iron stores at birth. Nutrition during preconception and pregnancy should be ensured to build adequate stores of nutrients for infants.

A "holistic" sonographic view on congenital heart disease: How automatic reconstruction using fetal intelligent navigation echocardiography eases unveiling of abnormal cardiac anatomy part II-Left heart anomalies.

Volume ultrasound has been shown to provide valid complementary information on fetal anatomy. Four-dimensional assessment (4D) of the fetal cardiovascular system using spatial-temporal image correlation (STIC) allows for detailed examination of a highly complex organ from the early second trimester onward. There is compelling evidence that this technique harbors quite a number of diagnostic opportunities, but manual navigation through STIC volume datasets is highly operator dependent. In fact, STIC is not incorporated yet into daily practice. Application of the novel fetal intelligent navigation echocardiography (FINE) considerably simplifies fetal cardiac volumetric examinations. This automatic technique applied on cardiac volume datasets reportedly has both high sensitivity and specificity for the detection of congenital heart defects (CHDs). Part I reviewed current data regarding detection rates of CHDs and illustrated the additional value of an automatic approach in delineating cardiac anatomy exemplified by congenital lesions of the right heart. In part II of this pictorial essay, we focused on left heart anomalies and aimed to tabulate recent findings on the quantification of normal and abnormal cardiac anatomy.

Reversible Wernicke encephalopathy caused by hyperemesis gravidarum in the second trimester of pregnancy: a case report.

Wernicke encephalopathy is a potentially life-threatening neurologic syndrome caused by acute thiamine (vitamin B1) deficiency. It is usually associated with excessive alcohol consumption. Less frequently, this syndrome can be caused by persistent vomiting. This is a case report of a 33-year-old woman diagnosed with Wernicke encephalopathy (WE) during the second trimester of pregnancy. The presence of neurological and ophthalmological symptoms in the context of hyperemesis gravidarum led us to evoke the diagnosis of WE, and it was confirmed when specific lesions were found in the brain magnetic resonance imaging (MRI). Luckily for our patient, WE was diagnosed promptly and the signs were reversible after thiamine supplementation. In conclusion, any first line care taker or midwife must know the symptoms of Wernicke encephalopathy because prompt diagnosis and treatment can lead to recovery.

Prenatal alcohol exposure is a leading cause of interneuronopathy in humans.

Alcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks' gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.e., 34 weeks' gestation. Results were compared with those obtained in 17 control brains aged 14 weeks of gestation to 35 postnatal months. We also focused on interneuron vascular migration along the cortical microvessels by confocal microscopy with double immunolabellings using Glut1, GABA and calretinin. Semi-quantitative and quantitative analyses of GABAergic and calretininergic interneuron density allowed us to identify an insufficient and delayed production of GABAergic interneurons in the ganglionic eminences during the two first trimesters of the pregnancy and a delayed incorporation into the laminar structures of the frontal cortex. Moreover, a mispositioning of GABAergic and calretininergic interneurons persisted throughout the foetal life, these cells being located in the deep layers instead of the superficial layers II and III. Moreover, vascular migration of calretininergic interneurons within the cortical plate was impaired, as reflected by low numbers of interneurons observed close to the cortical perforating vessel walls that may in part explain their abnormal intracortical distribution. Our results are globally concordant with those previously obtained in mouse models, in which alcohol has been shown to induce an interneuronopathy by affecting interneuron density and positioning within the cortical plate, and which could account for the neurological disabilities observed in children with foetal alcohol disorder spectrum.

Nephrotic syndrome due to preeclampsia before 20 weeks of gestation: a case report.

BACKGROUND: Preeclampsia (PE) refers to the development of hypertension and new-onset proteinuria or progressive organ damage (especially kidney) in a previously normotensive pregnant women after 20 weeks of gestation. Thus, new-onset nephrotic syndrome due to PE before 20 weeks of gestation seems to be rare, making its diagnosis difficult in this time period. CASE PRESENTATION: A 28-year-old woman presented with a new-onset nephrotic syndrome at 16 weeks of gestation. A high dose of oral glucocorticoids (prednisolone, 40 mg) was initiated for presumed glomerulonephritis since she presented with severe nephrotic syndrome before 20 weeks of gestation, however, the treatment was not effective. At 21 weeks of gestation, we confirmed that the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high (sFlt-1, 13,400 pg/mL; PlGF, 21.9 pg/mL; serum sFlt-1/PlGF ratio 611.9). Therefore, we diagnosed nephrotic syndrome due to PE, and oral glucocorticoids were discontinued. After she underwent a cesarean section at 24 weeks & 3 days, we performed a kidney biopsy. Focal segmental sclerotic lesions with epithelial cell hyperplasia and foam cells in the tubular poles were seen on light microscopy. On immunofluorescence tests, C4d staining showed linear peripheral patterns in the glomeruli. Electron microscopy revealed diffuse subendothelial edema with focal foot process effacement. The histological diagnosis was severe glomerular endotheliosis with focal segmental glomerulosclerosis. Furthermore, the histology of placenta was consistent with PE. Eight months after delivery, her proteinuria disappeared completely. CONCLUSIONS: We not only confirmed an abnormal serum sFlt-1/PlGF ratio but also presented the histology compatible with pure PE in the kidney and placenta in a case of nephrotic syndrome before 20 weeks of gestation. The serum sFlt-1/PlGF ratio may be useful in determining the treatment strategy for atypical cases of pregnant women with nephrotic syndrome, particularly before 20 weeks of gestation.

Second trimester cervical length measurements with transvaginal ultrasound: A prospective observational agreement and reliability study.

INTRODUCTION: Universal screening for preterm delivery by adding transvaginal ultrasound measurement of cervical length to routine second trimester ultrasound has been proposed. The aim is to estimate inter- and intraobserver agreement and reliability of second trimester transvaginal ultrasound measurements of cervical length performed by specially trained midwife sonographers. MATERIAL AND METHODS: This is a prospective reliability and agreement study performed in seven Swedish ultrasound centers. In total, 18 midwife sonographers specially trained to perform ultrasound measurements of cervical length and 286 women in the second trimester were included. In each center, two midwife sonographers measured cervical length a few minutes apart in the same woman, the number of women examined per examiner pair varying between 24 and 30 (LIVE study). Sixteen midwife sonographers measured cervical length twice ≥2 months apart on 93 video clips (CLIPS study). The main outcome measures were mean difference, limits of agreement, intraclass correlation coefficient, intra-individual standard deviation, repeatability, Cohen's kappa and Fleiss kappa. RESULTS: The limits of agreement and intraclass correlation coefficient of the best examiner pair in the LIVE study were -4.06 to 4.72 mm and 0.91, and those of the poorest were -11.11 to 11.39 mm and 0.31. In the CLIPS study, median (range) intra-individual standard deviation was 2.14 mm (1.40-3.46), repeatability 5.93 mm (3.88-9.58), intraclass correlation coefficient 0.84 (0.66-0.94). Median (range) interobserver agreement for cervical length ≤25 mm in the CLIPS study was 94.6% (84.9%-98.9%) and Cohen's kappa 0.56 (0.12-0.92), median (range) intraobserver agreement was 95.2% (87.1%-98.9%) and Cohen's kappa 0.68 (0.27-0.93). CONCLUSIONS: Agreement and reliability of cervical length measurements differed substantially between examiner pairs and examiners. If cervical length measurements are used to guide management there is potential for both over- and under-treatment. Uniform training and rigorous supervision and quality control are advised.