A Consistent Endoscopic Landmark to Identify the Anterior Ethmoidal Artery.

OBJECTIVE: The anterior ethmoidal artery (AEA) is an important structure to identify during endoscopic sinus surgery. Although identification on imaging is easily taught, a consistent endoscopic landmark for the AEA, independent of anatomic ethmoid cell variation, is lacking, leaving many surgeons unclear about the exact location without dependence on navigation. Here, we describe a consistent endoscopic landmark, regardless of anatomical ethmoid variation. METHODS: We prospectively enrolled adult patients undergoing endoscopic surgery involving frontal and ethmoid sinuses in this observational study. The AEA landmark was defined simply as the septation or ridge one step back along the ethmoid skull base from the posterior table of the frontal sinus. The gold standard to calculate the sensitivity of our endoscopic landmark was an image-navigation system, registered to within 1.5 mm accuracy, locating the AEA within three planes. Both endoscopic and computerized tomography (CT) images of the pointer at the landmark were taken simultaneously. The concordance of endoscopic to navigation images was independently assessed by three blinded rhinologists. RESULTS: Forty patients were included in our study with 73 sides analyzed. Diagnoses included chronic rhinosinusitis without polyps (52.5%), with polyps (22.5%), recurrent acute sinusitis (15%), sinonasal tumors (7.5%), and odontogenic sinusitis (2.5%). The AEA was accurately identified using our endoscopic landmark in 97.3% of the cases (71/73). Of the two cases in which the AEA was not found within the landmark, the artery was located ≤1 mm posteriorly. CONCLUSION: We describe a consistent endoscopic landmark to identify the AEA, conserved across various clinical diagnoses and anatomic variations in sinus structure. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1096-1099, 2024.

A Rare Case of Neurosyphilis with Calvaria Osteitis Presenting in Pregnancy.

Background: The incidence of syphilis throughout the world is increasing. Rates in pregnancy are similarly rising, presenting risks of an untreated syphilis infection that can be detrimental to the mother and fetus. Although routine screening for syphilis infections is recommended at the initial prenatal visit, there is a lack of universal agreement on rescreening pregnant people and approximately 50% of syphilis cases are asymptomatic in the general population. Furthermore, some symptoms of syphilis can overlap with nonspecific pregnancy-related symptoms. Meanwhile, Treponema pallidum can spread to various maternal and fetoplacental tissues quickly after infection and occur at any stage of syphilis. Case: A 26-year-old gravida 5 para 2 presented with a new onset headache and visual and auditory changes at 23 weeks of gestation. A computerized tomography scan revealed numerous ill-defined lytic lesions throughout the calvarium, suspicious for syphilitic osteitis. She tested positive for syphilis antibodies with a rapid plasma reagin (RPR) titer of 1 : 32. Cerebrospinal fluid evaluation from a lumbar puncture resulted in reactive fluorescent treponemal antibody (FTA) testing. She was diagnosed with secondary syphilis with osteitis and neuro and otic components. She completed 14 days of intravenous aqueous crystalline penicillin G with additional benzathine penicillin G 2.4 million units intramuscular weekly for two weeks. There was no evidence of congenital syphilis on neonatal examination. Conclusion: Syphilitic osteitis and neuro, otic, or ocular syphilis infections occur rarely in the nonpregnant population, and therefore, little data in pregnancy is available to inform outcomes in these specific disease states. It is of paramount importance to complete appropriate syphilis screening, recognize symptoms, and consider utilizing rescreen protocols to ensure prompt infection identification and treatment. For neuro, otic, and ocular syphilis, aqueous crystalline penicillin G (as opposed to benzathine penicillin G) is required to achieve treponemicidal concentrations in those physiologic compartments. There is no agreement as to the appropriate treatment regimen for the rare finding of syphilitic osteitis.

In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up In Vivo.

PURPOSE: We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals. METHOD: Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry. The corneas were evaluated for the presence of beta-tubulin, cytokeratin 3, zonula occludens-1, and alpha smooth muscle actin (SMA) markers. Gene expression of aldehyde dehydrogenase 3A1 (ALDH3A1), cluster of differentiation 31, CD163, alpha-SMA, hepatocyte growth factor, and fibroblast growth factor 2 (FGF-2) and protein expression of CD44 and collagen VI were evaluated. RESULTS: Intraocular pressure, corneal thickness, and hysteresis for the corneas treated with collagen-PEG gels did not significantly change compared with the saline group. However, placido disk topography revealed greater regularity of the central cornea in the gel-treated group compared to the saline group. The gel-treated group exhibited a lower degree of epithelial hyperplasia than the saline group. Immunohistochemical and gene expression analysis showed that the gel-treated corneas exhibited lower alpha-SMA expression compared with the saline group. CD163 and CD44 were found to be elevated in the saline-treated group compared with normal corneas. CONCLUSIONS: The in situ-forming collagen-PEG gel promoted epithelialization that improved central corneal topography, epithelial layer morphology, and reduced expression of fibrotic and inflammatory biomarkers after 60 days compared to the saline group.

In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair.

Purpose: Millions worldwide suffer vision impairment or blindness from corneal injury, and there remains an urgent need for a more effective and accessible way to treat corneal defects. We have designed and characterized an in situ-forming semi-interpenetrating polymer network (SIPN) hydrogel using biomaterials widely used in ophthalmology and medicine. Methods: The SIPN was formed by cross-linking collagen type I with bifunctional polyethylene glycol using N-hydroxysuccinimide ester chemistry in the presence of linear hyaluronic acid (HA). Gelation time and the mechanical, optical, swelling, and degradation properties of the SIPN were assessed. Cytocompatibility with human corneal epithelial cells and corneal stromal stem cells (CSSCs) was determined in vitro, as was the spatial distribution of encapsulated CSSCs within the SIPN. In vivo wound healing was evaluated by multimodal imaging in an anterior lamellar keratectomy injury model in rabbits, followed by immunohistochemical analysis of treated and untreated tissues. Results: The collagen-hyaluronate SIPN formed in situ without an external energy source and demonstrated mechanical and optical properties similar to the cornea. It was biocompatible with human corneal cells, enhancing CSSC viability when compared with collagen gel controls and preventing encapsulated CSSC sedimentation. In vivo application of the SIPN significantly reduced stromal defect size compared with controls after 7 days and promoted multilayered epithelial regeneration. Conclusions: This in situ-forming SIPN hydrogel may be a promising alternative to keratoplasty and represents a step toward expanding treatment options for patients suffering from corneal injury. Translational Relevance: We detail the synthesis and initial characterization of an SIPN hydrogel as a potential alternative to lamellar keratoplasty and a tunable platform for further development in corneal tissue engineering and therapeutic cell delivery.

Supramolecular host-guest hyaluronic acid hydrogels enhance corneal wound healing through dynamic spatiotemporal effects.

Severe corneal wounds can lead to ulceration and scarring if not promptly and adequately treated. Hyaluronic acid (HA) has been investigated for the treatment of corneal wounds due to its remarkable biocompatibility, transparency and mucoadhesive properties. However, linear HA has low retention time on the cornea while many chemical moieties used to crosslink HA can cause toxicity, which limits their clinical ocular applications. Here, we used supramolecular non-covalent host-guest interactions between HA-cyclodextrin and HA-adamantane to form shear-thinning HA hydrogels and evaluated their impact on corneal wound healing. Supramolecular HA hydrogels facilitated adhesion and spreading of encapsulated human corneal epithelial cells ex vivo and improved corneal wound healing in vivo as an in situ-formed, acellular therapeutic membrane. The HA hydrogels were absorbed within the corneal stroma over time, modulated mesenchymal cornea stromal cell secretome production, reduced cellularity and inflammation of the anterior stroma, and significantly mitigated corneal edema compared to treatment with linear HA and untreated control eyes. Taken together, our results demonstrate supramolecular HA hydrogels as a promising and versatile biomaterial platform for corneal wound healing.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

3D Printable, Modified Trephine Designs for Consistent Anterior Lamellar Keratectomy Wounds in Rabbits.

PURPOSE: Our goal is to develop a low-cost tool that can be used to create consistent, partial-thickness defects in rabbit and other large animals with minimal surgical training and that can facilitate pre-clinical testing of lamellar and in situ-forming biosynthetic matrix materials for corneal repair. MATERIALS & METHODS: In this study, three modified trephines were designed to create deep corneal wound defects with consistent depth in large animals. The modified trephines incorporated either 3D-printed parts made from photopolymerizable resins, or custom-cut commercially available Teflon sheets. Wound defects were imaged with optical coherence tomography (OCT), and the depth was analyzed based on the OCT images. RESULTS: The results revealed that an inner-stopper guard trephine had the best performance in creating consistent and precise wound defect depth compared to modified vacuum trephine and custom guard vacuum trephine. A 75% ± 10% cut of the cornea was achieved with the inner-stopper guard trephine. The wound defect depth by created by the inner-stopper guard trephine was independent of the corneal thickness or size of the globes. Although the cut depth of the inner-stopper guard trephine differed by the experience-level of its users, the consistency (standard deviation) of the depth was independent of experience. CONCLUSIONS: Our studies provided three cost-efficient animal trephines that can create corneal wounds of consistent depth by lab researchers without extensive training in keratectomy.

The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study.

BACKGROUND: Olfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia. METHODS: Seven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months. RESULTS: All patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI < 16) did not improve significantly. Five patients with hyposmia (TDI > 16 but <30) showed an improvement with 60% achieving normosmia (TDI > 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections. CONCLUSION: PRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.

Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma.

Objective In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged as a fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Understanding the mechanisms by which HNSCC evades immune-mediated control will aid in the development of new therapies to augment an antitumor immune response. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on malignant cells and lymphocytes such as natural killer (NK) cells. We sought to determine whether tumor-derived CEACAM1 inhibits NK cell cytotoxicity and whether blockade of CEACAM1 restores antitumor immunity. Study Design In vitro HNSCC cell line study. Setting Research laboratory. Subject and Methods We utilized a real-time cell analyzer to assess NK cell cytotoxicity against an oral squamous cell carcinoma cell line after modulating CEACAM1 expression by cytokines and shRNA knockdown of CEACAM1 expression. Results NK cells and HNSCC cells both demonstrated cytokine-inducible expression of CEACAM1. Coincubation of NK cells and HNSCC cells resulted in the upregulation of CEACAM1 on the tumor cells. When compared with CEACAM1- cells, CEACAM1+ tumor cells exhibited increased cell growth and increased size and number of organoids in 3-dimensional culture. Notably, CEACAM1+ HNSCC cells were more resistant to NK cell-mediated killing, but the inhibited expression of CEACAM1 by an shRNA construct restored NK cell cytotoxicity. Conclusion Together, these data indicate that CEACAM1 acts as an inducible checkpoint molecule, and they support the idea that targeting CEACAM1 could serve as a novel immunotherapy approach in HNSCC.

The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells.

Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions. We found that AhR mRNA is highly expressed in peripheral CD56bright NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56bright NK cells were highly sensitive to AhR ligands. Specifically, AhR ligands modulated their activation and their expression of NK cell receptors, as well as cytokine secretion which is the major function of these cells. As CD56bright NK cells are highly enriched in tissues and in tumors, our observations point to a possible effect of local AhR ligands in the regulation of the function of CD56bright tissue-resident or intratumoral NK cells.

Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial.

OBJECTIVE: Despite known racial disparities in obstetrics, as well as differences in magnesium pharmacodynamics according to race, the effect of race/ethnicity in magnesium sulfate (MgSO4) use during pregnancy has not been studied. Whether some mothers are at increased risk of side effects, or infants at decreased neuroprotective effects is unknown. We analyze the effect of race/ethnicity in maternal/infant outcomes after MgSO4 neuroprotection. STUDY DESIGN: Subgroup analysis of a multicenter clinical trial (BEAM trial) where pregnant women at risk of preterm birth were randomized to either MgSO4 or placebo. For this study, nonanomalous singleton pregnancies were studied. The effect of race in maternal/neonatal outcomes after MgSO4 was analyzed with Breslow-Day and multifactorial ANOVA. Logistic regression was used to calculate odds ratios (OR) of complications according to race. RESULTS: 922 MgSO4 and 972 placebo cases were included (45.0% African-American, 36.2% Caucasian, 17.8% Hispanics, and 1.0% Asians). Interaction analysis showed a significant effect of race/ethnicity (p = .043). Hispanics presented the highest frequency (88.3%, p < .001), as well as the highest odds of MgSO4 side effects [OR(95%CI) = 6.6 (1.3-33.8)]. CONCLUSION: Hispanics present increased risk of magnesium toxicity compared to other racial/ethnic groups. Whether specific racial/ethnic groups require closer surveillance for early signs of magnesium toxicity needs to be further explored.

Fetoplacental regional variations in the expression of angiopoietin-1, angiopoietin-2, and Tie2 in normal-term and near-term pregnancies.

BACKGROUND: Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) are known to be involved in fetoplacental angiogenesis adequacy, which is a primary determinant of fetal growth. Regional variations in Ang1, Ang2, and Tie2 remain unknown, although fetoplacental vascularity and gene expressions differ between the placental center and the periphery. OBJECTIVE: The aim of this study was to test the hypothesis that there are regional variations in the expression of these angiopoietins in human placentas from uncomplicated term and near term pregnancies. STUDY DESIGN: In this prospective study, central and peripheral samples were collected from fresh placentas from normal-term and near-term pregnancies delivered by Cesarean section (n = 7, 36-41 week gestation) prior to the onset of labor. Regional differences in Ang1, Ang2, and Tie2 protein expressions were measured by Western blot and densitometric analyses with b-actin normalization, and their fetoplacental regional localization assessed by immunohistochemistry. The Ang1 and Ang2 ratios at central and peripheral sites were determined. Statistical analysis was performed using Student's t-test. RESULTS: Ang1 protein expression was higher in the placental periphery than in the center (2.48 ± 0.42 versus 1.74 ± 0.27, p = 0.01). In contrast, Ang2 protein expression was greater in the placental center than in the periphery (10.10 ± 1.82 versus 7.15 ± 1.12, respectively, p = 0.03). The Ang1-Ang2 ratio reflected these differential expressions. Tie2 protein expression was higher in the placental periphery than in the center (0.21 ± 0.02 versus 0.16 ± 0.02, p = 0.003). The immunoreactivity of Ang1 and Tie2 was stronger in the periphery than in the center, and that of Ang2 was stronger in the center than in the periphery. CONCLUSIONS: Ang1, Ang2, and Tie2 are differentially expressed in placental center and periphery. Ang1/Ang2 ratio reflects this regional variation in the angiogenic balance that has implications for fetoplacental villous angiogenesis. The results also demonstrate the importance of considering the location of placental sampling sites for any future investigations of fetoplacental villous angiogenesis.

Down-regulation of placental neuropilin-1 in fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental origin. Information, however, on the role of specific proangiogenic and antiangiogenic mechanisms operating at the placental level remains limited. Elucidation of these placenta-specific angiogenic mechanisms will not only extend our understanding of the causal pathway for restricted fetal growth but may also lead to the development of biomarkers that may allow early recognition of FGR. OBJECTIVE: We sought to test the hypothesis that fetoplacental angiogenic gene expression is altered in pregnancies complicated with FGR and umbilical artery Doppler AEDF. STUDY DESIGN: Placental samples were collected from FGR pregnancies complicated with umbilical artery Doppler AEDF (study group, n = 7), and from uncomplicated pregnancies (control group, n = 7), all delivered by cesarean during the last trimester of pregnancy. Angiogenic oligonucleotide microarray analysis was performed and was corroborated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The Student t test with Bonferroni correction was used with P < .05 considered statistically significant. Independent groups t test was used to analyze the immunostain intensity scores with a P < .05 considered statistically significant. RESULTS: Our microarray results showed that among several differentially expressed angiogenic genes in the growth-restricted group, only the down-regulation of neuropilin (NRP)-1 was most significant (P < .0007). Quantitative real-time polymerase chain reaction confirmed a significantly lower NRP-1 gene expression in the FGR group than in the control group (mean ± SD (ˆ)cycle threshold: 0.624 ± 0.55 and 1.325 ± 0.84, respectively, P = .04). Western blot validated significantly lower NRP-1 protein expression in the FGR group than in the control group (mean ± SD NRP-1/ß-actin ratio: 0.13 ± 0.04 and 0.34 ± 0.05, respectively, P < .001). Finally, immunohistochemistry of placental villi further corroborated a significantly decreased expression of NRP-1 in the FGR group (P = .006). CONCLUSION: The study demonstrated significant down-regulation of placental NRP-1 expression in FGR pregnancies complicated with AEDF in umbilical artery. As NRP-1 is known to promote sprouting angiogenesis, its down-regulation may be involved in the deficient vascular branching observed in FGR placentas suggesting the presence of an antiangiogenic state. Further studies may elucidate such a causal role and may lead to the development of novel diagnostic and therapeutic tools.

DHA supplementation and pregnancy outcomes.

BACKGROUND: Observational studies associate higher intakes of n-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy with higher gestation duration and birth size. The results of randomized supplementation trials using various n-3 LCPUFA sources and amounts are mixed. OBJECTIVE: We tested the hypothesis that 600 mg/d of the n-3 LCPUFA docosahexaenoic acid (DHA) can increase maternal and newborn DHA status, gestation duration, birth weight, and length. Safety was assessed. DESIGN: This phase III, double-blind, randomized controlled trial was conducted between January 2006 and October 2011. Women (n = 350) consumed capsules (placebo, DHA) from <20 wk of gestation to birth. Blood (enrollment, birth, and cord) was analyzed for red blood cell (RBC) phospholipid DHA. The statistical analysis was intent-to-treat. RESULTS: Most of the capsules were consumed (76% placebo; 78% DHA); the mean DHA intake for the treated group was 469 mg/d. In comparison with placebo, DHA supplementation resulted in higher maternal and cord RBC-phospholipid-DHA (2.6%; P < 0.001), longer gestation duration (2.9 d; P = 0.041), and greater birth weight (172 g; P = 0.004), length (0.7 cm; P = 0.022), and head circumference (0.5 cm; P = 0.012). In addition, the DHA group had fewer infants born at <34 wk of gestation (P = 0.025) and shorter hospital stays for infants born preterm (40.8 compared with 8.9 d; P = 0.026) than did the placebo group. No safety concerns were identified. CONCLUSIONS: A supplement of 600 mg DHA/d in the last half of gestation resulted in overall greater gestation duration and infant size. A reduction in early preterm and very-low birth weight could be important clinical and public health outcomes of DHA supplementation. This trial was registered at clinicaltrials.gov as NCT00266825.

Umbilical artery Doppler in the assessment of fetal growth restriction.

Antepartum fetal surveillance with Doppler ultrasound of umbilical artery has shown significant diagnostic efficacy in identifying fetal compromise in pregnancies complicated with fetal growth restriction (FGR). Its effectiveness in decreasing perinatal mortality has been shown by randomized clinical trials (Level I evidence). This test is the only antepartum fetal test that has shown this level of effectiveness and should be the standard of practice in managing FGR (Level A recommendation). The overall management considerations should encompass other standard fetal monitoring tests (Level B and C recommendations).

Evidence-based approach to umbilical artery Doppler fetal surveillance in high-risk pregnancies: an update.

Antepartum fetal surveillance with Doppler ultrasound of umbilical artery has shown significant diagnostic efficacy in identifying fetal compromise in pregnancies complicated with fetal growth restriction and preeclampsia. Moreover, randomized clinical trials and their meta-analyses have shown its effectiveness in decreasing perinatal mortality (level I evidence). This is the only antepartum fetal test that has shown this level of effectiveness. There is no evidence that routine Doppler in low-risk pregnancies improves the outcome. It is recommended that umbilical artery Doppler should be the standard of practice in managing high-risk pregnancies complicated with fetal growth restriction and preeclampsia (level A recommendation). However, its use should be integrated with other current fetal monitoring tests (levels B and C recommendation). The overall management should also be guided by additional clinical considerations such as the gestational age, fetal and maternal status, and obstetrical conditions.

The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid.

BACKGROUND: The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date. OBJECTIVE: The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events. DESIGN: This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination. RESULTS: Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested. CONCLUSIONS: DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.

Combining phenobarbital and indomethacin to improve early neonatal outcomes in the extremely low birth weight infant.

In this retrospective study, we tested the following hypotheses: rates of severe intraventricular hemorrhage (SIVH) and early neonatal survival are similar among extremely low birth weight (ELBW) infants treated with combination prophylaxis of phenobarbital and indomethacin compared with phenobarbital alone or no prophylaxis; and rates of patent ductus arteriosus (PDA) and necrotizing enterocolitis (NEC) are similar among indomethacin-exposed and nonexposed ELBW infants. Data were abstracted on 265 ELBW infants admitted into a level 3 neonatal intensive care unit from 1994 through 2002. Combination prophylaxis neither reduced the odds ratio (OR) of SIVH (OR = 1.53; 95% confidence interval [CI], 0.43 to 1.16) versus phenobarbital (OR = 2.91; 95% CI, 0.91 to 9.27 versus none (OR = 1; 95% CI, reference) nor increased the odds of early neonatal survival (OR = 0.72; 95% CI, 0.17 to 3.09 for combination prophylaxis versus OR = 0.66; 95% CI, 0.16 to 2.67 for phenobarbital versus OR = 1; 95% CI, reference for none). Indomethacin exposure reduced the odds of PDA (OR = 0.35; 95% CI, 0.17 to 0.75) without increasing the risk of NEC (OR = 1.37; 95% CI, 0.60 to 3.12). In conclusion, combination prophylaxis does not improve SIVH and early neonatal survival outcomes. Early exposure to indomethacin offers some benefits without any added risks.

Role of mental illness in drug use by urban pregnant heavy smokers.

The object of the study was to test the hypothesis that mental illness is associated with drug abuse by pregnant smokers. We abstracted data from the State of Missouri Risk Appraisal of Pregnant Women database on 239 (115 black and 124 white) women who attended an inner-city hospital from 1999 through 2000. Thirty-four percent abused drugs, 16% used alcohol, and 8% reported having a history of mental illness or psychiatric treatment. On multivariable logistic regression analyses, pregnant smokers were more likely to use drugs if they had mental illness (odds ration [OR], 7), consumed alcohol (OR, 2), or were black (OR, 3). In conclusion, drug abuse is associated with mental illness, suggesting that this behavior may be a marker of underlying mental illness among pregnant smokers. Therefore, in addition to initiating social service intervention, the identification of drug abuse by pregnant smokers should prompt a mental health evaluation.

A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy.

OBJECTIVE: To hypothesize that higher intake of docosahexaenoic acid, an n-3 long chain polyunsaturated fatty acid, would increase duration of gestation and birth weight in US women. METHODS: This was a randomized, double-blind, controlled, clinical trial. Subjects were enrolled in an ambulatory clinic where they received prenatal care. This was a population-based sample. Most subjects received government assistance for medical care and most were black (73%). Subjects were enrolled between the 24th and 28th week of pregnancy and consumed docosahexaenoic acid (33 or 133 mg) from eggs until parturition. Gestational age and birth weight were the main study outcomes. Infant length and head circumference, preterm birth, and low birth weight were secondary outcomes. RESULTS: Eighty-three percent of subjects completed the study (291 of 350 enrolled). No subject was discontinued for an adverse event. After controlling for important predefined risk factors and confounding variables, gestation increased by 6.0 +/- 2.3 days (P =.009) in the higher docosahexaenoic acid group. Birth weight, length, and head circumference increased, but did not reach statistical significance (P =.06-.18), although the increases could be clinically important indications of enhanced intrauterine growth. No safety concerns were raised by the study. CONCLUSION: Duration of gestation increased significantly when docosahexaenoic acid intake was increased during the last trimester of pregnancy. The increase in gestation was similar to that reported for interventions with much larger amounts of n-3 long chain polyunsaturated fatty acids.