Early Preterm Period Research Articles

Combined Cesarean Section and Splenectomy in a Patient with Massive Splenomegaly

Background To date, there is limited knowledge of patients with idiopathic splenomegaly in pregnancy, and the literature lacks cases of a combined cesarean section with splenectomy. The documented cases of splenomegaly in pregnancy often have infectious etiology such as that of malarial infection or an autoimmune component such as idiopathic thrombocytopenic purpura. This condition is life-threatening and complicates medical management, but its rarity has led to a paucity of management guidelines for patients with idiopathic splenomegaly in pregnancy. Objective The aim of this case is to provide novel insight into the management and outcomes of patients with idiopathic massive splenomegaly in pregnancy. Study Design This study is a case report with a review of the current literature on the reported cases of splenomegaly in pregnancy, splenectomy in pregnancy, and cesarean section with splenectomy. This case describes a history of pancytopenia and massive splenomegaly in a pregnant patient who underwent extensive workup with no clear etiology. This case additionally describes the course of care for this patient, including a combined cesarean section with splenectomy. We searched PubMed for all English language articles from 2000 to 2023, with search terms including “splenomegaly in pregnancy,” “splenectomy in pregnancy,” and “cesarean section and splenectomy.” Results In this patient’s case, despite an exhaustive infectious disease workup and evaluation for hematologic, inflammatory, and neoplastic causes, no clear etiology was identified. Delivery was deemed necessary at 34 weeks and 2 days gestation due to the patient’s severe, persistent pain, her worsening pancytopenia, and the risk of spontaneous splenic rupture during labor and delivery; our multidisciplinary team concluded that it was safer for both mother and baby to proceed with cesarean delivery and splenectomy in the early pre-term period. This patient’s pancytopenia improved within hours of spleen removal and has remained stable to date in outpatient follow-up. Baby Boy completed a NICU course of 22 days after requiring surfactant and respiratory support due to prematurity as well as monitoring due to maternal splenomegaly and thrombocytopenia. Conclusion This case offers valuable insights into managing patients with idiopathic splenomegaly during pregnancy and underscores the need for further investigation. Establishing clear delivery indications for these patients remains crucial, and prospective studies should evaluate the long-term impacts on both mother and child following combined splenectomy and cesarean delivery in the context of pancytopenia.

Role of fetal cardiac assessment in predicting adverse perinatal outcomes in preterm dichorionic twins

Aim: To investigate the role of the fetal modified myocardial performance index (Mod-MPI) and fetal cardiac output index measurement in predicting adverse perinatal outcomes among preterm dichorionic twins. Materials and Method: This prospective cohort study was conducted at the X Clinic and included 34 dichorionic twin fetuses born early preterm and 40 dichorionic twin fetuses born late preterm. The early preterm group was divided into two according to whether they were admitted to the neonatal intensive care unit (NICU). The groups' cardiac function and Mod-MPI measurements were compared regarding their predictive ability for adverse perinatal outcomes. Results: The Mod-MPI values were similar between the early and late preterm groups (p=0.144). The left ventricular cardiac output Z-score was lower in the preterm group (p=0.014). The Mod-MPI and left ventricular outflow tract-isovolumetric contraction and isovolumetric relaxation times were significantly higher among the newborns admitted to the NICU in the early preterm group (p=0.002, p=0.003, and p=0.001, respectively). Conclusion: Our study suggests that the Mod-MPI measurement can be used to predict adverse perinatal outcomes in dichorionic twin fetuses born in the early preterm period.

Rescue Antenatal Corticosteroids in Late Preterm Birth after Completion of the Initial Cycle of Antenatal Corticosteroids during the Early Preterm Period

Rescue Antenatal Corticosteroids in Late Preterm Birth after Completion of the Initial Cycle of Antenatal Corticosteroids during the Early Preterm Period

Development of associational fiber tracts in fetal human brain: a cadaveric laboratory investigation.

The advent of diffusion tensor imaging (DTI) in addition to cadaveric brain dissection allowed a comprehensive description of an adult human brain. Nonetheless, the knowledge of the development of the internal architecture of the brain is mostly incomplete. Our study aimed to provide a description of the anatomical variations of the major associational bundles, among fetal and early post-natal periods. Seventeen formalin-fixed fetal human brains were enrolled for sulci analysis, and 13 specimens were dissected under the operating microscope, using Klingler's technique. Although fronto-temporal connections could be observed in all stages of development, a distinction between the uncinate fascicle, and the inferior fronto-occipital fascicle was clear starting from the early preterm period (25-35 post-conceptional week). Similarly, we were consistently able to isolate the periatrial white matter that forms the sagittal stratum (SS), with no clear distinction among SS layers. Arcuate fascicle and superior longitudinal fascicle were isolated only at the late stage of development without a reliable description of their entire course. The results of our study demonstrated that, although white matter is mostly unmyelinated among fetal human brains, cadaveric dissection can be performed with consistent results. Furthermore, the stepwise development of the associational fiber tracts strengthens the hypothesis that anatomy and function run in parallel, and higher is the cognitive functions subserved by an anatomical structure, later the development of the fascicle. Further histological-anatomical-DWI investigations are required to appraise and explore this topic.

Lamellar body count: Marker for foetal lung maturation promoted by intra-amniotic infection and/or inflammation

ObjectiveThere is evidence indicating that the risk of respiratory distress syndrome is reduced in preterm neonates exposed to intra-amniotic infection and/or inflammation. We hypothesised that foetal lung maturation promoted by intra-amniotic infection and/or inflammation results in elevated lamellar body count (LBC) in amniotic fluid (AF). This study aimed to determine the relationship between LBC in AF and intra-amniotic infection and/or inflammation in patients with threatened preterm birth. Study designThis was a retrospective cohort study of patients with threatened preterm birth. A total of 104 consecutive pregnant women underwent amniocentesis in the early preterm period [gestational age < 34 weeks] to evaluate intra-amniotic infection and/or inflammation and foetal lung maturity. Intra-amniotic infection was confirmed by positive AF culture results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma. Intra-amniotic inflammation was defined as a positive AF matrix metalloproteinase-8 rapid test. Outcomes of the study population were compared according to LBC in AF using a cut-off of 15,000/mm3. ResultsThe rates of elevated LBC and intra-amniotic infection and/or inflammation were 23% (24/104) and 52% (54/104), respectively. The median LBC was significantly higher in patients with intra-amniotic infection and/or inflammation than in those without [median LBC, 9,000/mm3 (interquartile range, IQR: 3,000–39,000) vs. 3,000/mm3 (IQR: 2,750–5,000), p < 0.001]. Intra-amniotic infection and/or inflammation was observed in 96% (23/24) of patients with elevated LBC and 39% (31/80) of patients without elevated LBC (p < 0.001). On multivariable analysis, the presence of intra-amniotic infection and/or inflammation was significantly associated with elevated LBC with an odds ratio (OR) of 66.0 [95% confidence interval (CI) 6.6–664.4, p < 0.001], even after accounting for gestational age at amniocentesis being a significantly related factor for predicting elevated LBC with an OR of 1.5 (95% CI 1.1–2.0, p = 0.004). ConclusionLBC elevation was independently associated with the presence of intra-amniotic infection and/or inflammation in women with early threatened preterm birth (gestational age < 34 weeks). This finding may support the view that an intra-amniotic inflammatory response promotes foetal lung maturation that can be detected by elevated LBC in AF.

Ethical challenges in management of critically ill pregnant patients with coronavirus disease 2019 (COVID-19).

Despite the overwhelming number of coronavirus disease 2019 (COVID-19) cases worldwide, data regarding the optimal clinical guidance in pregnant patients is not uniform or well established. As a result, clinical decisions to optimize maternal and fetal benefit, particularly in patients with critical COVID-19 in the early preterm period, continue to be a challenge for obstetricians. There is often uncertainty in clinical judgment about fetal monitoring, timing of delivery, and mode of delivery because of the challenge in balancing maternal and fetal interests in reducing morbidity and mortality. The obstetrician and critical care team should empower pregnant patients or their surrogate decision maker to make informed decisions in response to the team's clinical evaluation. A clinically grounded ethical framework, based on the concepts of the moral management of medical uncertainty, beneficence-based obligations, and preventive ethics, should guide the decision-making process.

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

912 Optimal timing of corticosteroids in growth restricted pregnancies delivered in the late preterm period

To evaluate the rate of optimally timed antenatal corticosteroid administration among newborns with fetal growth restriction delivered in the late preterm period and if antenatal corticosteroids given in the early preterm period decreases a neonatal composite respiratory outcome as compared to women who received corticosteroids in the late preterm period. This was a retrospective cohort study including singleton gestations delivered in the late preterm period (34.0 - 36.6 weeks gestation) with growth restriction. We compared women receiving corticosteroids in the early preterm period (22.0 - 34.0 weeks gestation) to those who received corticosteroids in the late preterm period. The primary outcomes included the rate of optimally timed corticosteroid administration (between 24 hours - 7 days of delivery) and neonatal composite respiratory outcome consisting of continuous positive airway pressure or high flow nasal cannula requirement, oxygen requirement with FiO2 ≥ 30%, mechanical ventilation, or neonatal death. Bivariate and multivariate analyses was performed. Among 182 women who met all inclusion criteria, 50 (27.4%) received early preterm steroids and 132 (72.6%) received late preterm steroids. The rate of optimally timed steroid administration was 38.4% (70/182, early preterm 30 % vs late preterm 41.7%, p= 0.15). The primary composite respiratory outcome occurred in 34 pregnancies (18.7%). Neonates exposed to early preterm steroids required more respiratory support at delivery (early preterm 36% vs late preterm 12.1%, p<0.001); multivariable modeling controlling for gestational age demonstrated that the composite respiratory outcome was higher in newborns who received early preterm steroids (AOR 2.7, p =0.023). Administration of antenatal corticosteroids for growth restricted pregnancies delivered in the late preterm period is not often appropriately timed for optimal effect. Antenatal corticosteroids given in the early preterm period may be less beneficial than those given in the late preterm period for pregnancies delivered in the late preterm period.

Earlier preterm birth is associated with a worse neurocognitive outcome in a rabbit model.

Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB. Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age. PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits. In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

Clinical Implications of SARS-CoV-2 Infection in the Viable Preterm Period.

Objective This study aimed to determine the rate of preterm birth (PTB) during hospitalization among women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 23 and 37 weeks of gestation and whether this rate differs by gestational age at diagnosis of infection. Study Design Retrospective, cross-sectional study of all women diagnosed with SARS-CoV-2 infection between 23 and 37 weeks of gestation within a large integrated health system from March 13 to April 24, 2020. Cases with severe fetal structural malformations detected prior to infection were excluded. Women were stratified into two groups based on gestational age at diagnosis: early preterm (23 0/7 to 33 6/7 weeks) versus late preterm (34 to 36 6/7 weeks). We compared the rate of PTB during hospitalization with infection between the two groups. Statistical analysis included use of Wilcoxon rank sum and Fisher exact tests, as well as a multivariable logistic regression. Statistical significance was defined as a p -value <0.05. Results Of the 65 patients included, 36 (53.7%) were diagnosed in the early preterm period and 29 (46.3%) were diagnosed in the late preterm period. Baseline demographics were similar between groups. The rate of PTB during hospitalization with infection was significantly lower among women diagnosed in the early preterm period compared with late preterm (7/36 [19.4%] vs. 18/29 [62%], p -value = 0.001). Of the 25 patients who delivered during hospitalization with infection, the majority were indicated deliveries (64%, 16/25). There were no deliveries <33 weeks of gestation for worsening coronavirus disease 2019 and severity of disease did not alter the likelihood of delivery during hospitalization with SARS-CoV-2 infection (adjusted odds ratio [aOR]: 0.64; 95% confidence interval [CI]: 0.24–1.59). Increased maternal age was associated with a lower likelihood of delivery during hospitalization with SARS-CoV-2 infection (aOR: 0.77; 95% CI: 0.58–0.96), while later gestational age at diagnosis of infection was associated with a higher likelihood of delivery during hospitalization (aOR: 2.9; 95% CI: 1.67–8.09). Conclusion The likelihood of PTB during hospitalization with SARS-CoV-2 infection is significantly lower among women diagnosed in the early preterm period compared with late preterm. Most women with SARS-CoV-2 infection in the early preterm period recovered and were discharged home. The majority of PTB were indicated and not due to spontaneous preterm labor. Key Points Preterm delivery is less likely among women diagnosed in the early preterm compared with late preterm.Most women infected in the early preterm period recovered and were discharged home undelivered.The majority of preterm birth were indicated and not due to spontaneous preterm labor.

The World Health Organization ACTION-I (Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries

BackgroundAntenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries.Methods/designThe trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up).DiscussionFindings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization’s global recommendations on ACS use.Trial registrationACTRN12617000476336. Registered on 31 March 2017.

The association between gestational age at delivery, closure type and perinatal outcomes in neonates with isolated gastroschisis

Objective: The objective of this study was to examine the association between gestational age at delivery and closure type for neonates with gastroschisis. In addition, we compared perinatal outcomes among the cases of gastroschisis based on the following two factors: gestational age at delivery and abdominal wall closure technique.Methods: This was a retrospective cohort study of all fetuses with isolated gastroschisis that were diagnosed prenatally and delivered between September 2000 and January 2017, in a single tertiary care center. Neonates were compared based on the gestational age at the time of delivery: early preterm (less than 350/7 weeks), late preterm (350/7 – 366/7 weeks), and early term (370/6 – 386/7 weeks), using bivariate and multivariate analyses. The primary outcome was the type of abdominal wall closure: primary surgical closure or delayed closure using spring-loaded silo. Secondary outcomes included length of ventilatory support, length of parenteral nutrition, and length of hospital stay.Results: The analysis included 206 pregnancies complicated by gastroschisis. In univariate analysis, no differences were detected in primary closure rates of gastroschisis among the gestational age at delivery groups (67.4%, at <35 weeks, 70.8% at 350/7–366/7 weeks, 73.7% at 370/6–386/7 weeks, p = .865). However, for every additional 100 grams of neonatal live birth weight there was an associated 9% increased odds of primary closure (OR 1.09, 95% CI 1.14–1.19, p = .04). Delivery in the early preterm period compared to the other two groups, was associated with longer duration of ventilation support and longer dependence on the parenteral nutrition. Neonates who underwent primary closure had shorter ventilation support, shorter time to initiation of enteral feeds and to discontinue parenteral nutrition, and shorter length of stay. In multivariate analyses, controlling for gestational age at delivery and presence of bowel atresia, primary closure continued to be associated with the shorter duration of ventilation (by 5 days), earlier initiation of enteral feeds (by 7 days), shorter hospital stay (by 17 days) and lower odds of wound infection (OR = 0.37, 95% CI 0.15–0.97).Conclusions: Our study did not find an association between gestational age at delivery and the rates of primary closure of the abdominal wall defect; however later gestational age at delivery was associated with shorter duration of ventilatory support and parenteral nutrition dependence. In addition, we found that primary closure of gastroschisis, compared with delayed closure technique, was associated with improved neonatal outcomes, including shorter time to initiate enteral feeds and discontinue parenteral nutrition, shorter hospital stay, and lower risk of surgical wound infection. Therefore, postponing delivery of fetuses with gastroschisis until 37 weeks may be considered. Other factors besides the gestational age at delivery should be explored as predictors of primary closure in neonates with gastroschisis.

Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of spontaneous preterm delivery in twins: a retrospective cohort study.

To evaluate the association between the concentrations of immune-related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of spontaneous preterm delivery in twins. The study population consisted of consecutive women with a twin pregnancy who underwent clinically indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon-γ, tumor necrosis factor-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin) using multiplex immunoassay kits. The association between AF protein levels and subsequent early preterm birth were examined. A total of 96 sets of twins were enrolled, including 17 early preterm birth cases and 79 term controls. AF concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were significantly higher in cases than controls. Among these analytes, the combination of AF IL-8 and MMP-9 values had the highest predictive value for early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml(-1) and MMP-9<1000 pg ml(-1), 30% (15/50) for IL-8>1200 pg ml(-1) or MMP-9>1000 pg ml(-1), and 90% (9/10) for IL-8>1200 pg ml(-1) and MMP-9>1000 pg ml(-1) (P<0.001). High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins predicted well the risk of early preterm birth.

Cerebral maturation in the early preterm period—A magnetization transfer and diffusion tensor imaging study using voxel-based analysis

The magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) correlates of early brain development were examined in cohort of 18 very preterm neonates (27–31 gestational weeks) presenting with normal radiological findings scanned within 2weeks after birth (28–32 gestational weeks). A combination of non-linear image registration, tissue segmentation, and voxel-wise regression was used to map the age dependent changes in MTR and DTI-derived parameters in 3D across the brain based on the cross-sectional in vivo preterm data. The regression coefficient maps obtained differed between brain regions and between the different quantitative MRI indices. Significant linear increases as well as decreases in MTR and DTI-derived parameters were observed throughout the preterm brain. In particular, the lamination pattern in the cerebral wall was evident on parametric and regression coefficient maps. The frontal white matter area (subplate and intermediate zone) demonstrated a linear decrease in MTR. While the intermediate zone showed an unexpected decrease in fractional anisotropy (FA) with age, with this decrease (and the increase in mean diffusivity (MD)) driven primarily by an increase in radial diffusivity (RD) values, the subplate showed no change in FA (and an increase in MD). The latter was the result of a concomitant similar increase in axial diffusivity (AD) and RD values. Interpreting the in vivo results in terms of available histological data, we present a biophysical model that describes the relation between various microstructural changes measured by complementary quantitative methods available on clinical scanners and a range of maturational processes in brain tissue.

Automatic whole brain MRI segmentation of the developing neonatal brain.

Magnetic resonance (MR) imaging is increasingly being used to assess brain growth and development in infants. Such studies are often based on quantitative analysis of anatomical segmentations of brain MR images. However, the large changes in brain shape and appearance associated with development, the lower signal to noise ratio and partial volume effects in the neonatal brain present challenges for automatic segmentation of neonatal MR imaging data. In this study, we propose a framework for accurate intensity-based segmentation of the developing neonatal brain, from the early preterm period to term-equivalent age, into 50 brain regions. We present a novel segmentation algorithm that models the intensities across the whole brain by introducing a structural hierarchy and anatomical constraints. The proposed method is compared to standard atlas-based techniques and improves label overlaps with respect to manual reference segmentations. We demonstrate that the proposed technique achieves highly accurate results and is very robust across a wide range of gestational ages, from 24 weeks gestational age to term-equivalent age.

Balancing the risks of stillbirth and neonatal death in the early preterm small-for-gestational-age fetus

Timing of delivery for the early preterm small-for-gestational-age (SGA) fetus remains unknown. Our aim was to estimate the risk of stillbirth in the early preterm SGA fetus compared with the risk of neonatal death. We performed a retrospective cohort study of singleton pregnancies that underwent second-trimester anatomy ultrasound (excluding fetal anomalies, aneuploidy, and pregnancies with incomplete neonatal follow-up data). SGA was defined as birthweight <10th percentile by the Alexander standard. Life-table analysis was used to calculate the cumulative risks of stillbirth per 10,000 ongoing SGA pregnancies and of neonatal death per 10,000 SGA live births for 2-week gestational age strata in the early preterm period (24-33 weeks 6 days of gestation). We further examined the composite risk of expectant management and then compared the risk of expectant management with the risk of immediate delivery. Of 76,453 singleton pregnancies, 7036 SGA pregnancies that met inclusion criteria were ongoing at 24 weeks of gestation; there were 64 stillbirths, 226 live births, and 18 neonatal deaths from 24-33 weeks 6 days of gestation. As the risk of stillbirth increases with advancing gestational age, the risk of neonatal death falls, until the 32-33 weeks 6 days of gestation stratum. The relative risk of expectant management compared with immediate delivery remains <1 for each gestational age strata. Our findings suggest that the balance between the competing risks of stillbirth and neonatal death for the early preterm SGA fetus occurs at 32-33 weeks 6 days of gestation. These data can be useful when delivery timing remains uncertain.

Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum

Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major site of vulnerability in hypoxic-ischaemic perinatal brain injury.

An Easy and Practical Method for Routine, Bedside Testing of Somatosensory Systems in Extremely Low Birth Weight Infants

This study was set out to develop and describe a novel, simple, and safe method for routine bedside testing of somatosensory system in very early preterm infants. We recorded electroencephalogram (EEG) activity after tactile stimulation of hand (palm) and foot (sole) by a soft hairbrush stimulator in extremely low birth weight infants (n = 10; GA, 24-28, recording at conceptional age 30-32 wk) and compared with the raw EEG responses to those seen by one- or two-channel brain monitors. In every subject, single tactile stimuli produced prominent (100-350 microV) somatosensory evoked responses (SERs) that were readily identified in the ongoing EEG signal. The maximal SER was in the contralateral hemisphere at around the corresponding somatosensory representation areas. Conventional EEG filtering did significantly reduce the SERs, but they could still be identified in the routine brain monitor setting widely available in NICUs. The method described here is directly applicable to assessment of integrity of somatosensory system in the early preterm period. It needs minimal training and requires an EEG system or a brain monitor device that is available in most units. Thus, the technique is likely to open a novel window to neurologic assessment of these babies.

Uterine artery Doppler in the prediction of adverse pregnancy outcome

To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high-risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers.

Cell proliferation in the growing human heart: MIB-1 immunostaining in preterm and term infants at autopsy

Few studies of human cardiac myocyte proliferation in the perinatal period have been conducted. We measured the proliferative activity of left ventricular myocytes in tissue obtained at autopsy in three surgically induced abortuses, 20 preterm infants with gestational ages ranging from 12 to 35 weeks, eight term infants with ages ranging from 1 day to 11 months, and five adults. The preterm infants lived less than 24 h, thus simulating the in utero condition of developing hearts. To assess the proliferative activity of the myocytes, we measured immunoreactivity using the monoclonal antibody MIB-1 against the recombinant Ki-67 nuclear antigen. Immunostained sections were examined by light microscopy, and the results expressed as a staining index (SI) of 0–3, according to the percentage of positively stained myocyte nuclei. Myocyte proliferative activity remained constant during the early preterm period and decreased in the late preterm and early postterm periods. Adult myocytes, regardless of cardiac weight, did not reveal proliferative activity as assessed by immunostaining. This proliferation pattern is consistent with findings in most earlier studies in animal models.