Open Neural Tube Defects Research Articles

Maternal serum alpha-fetoprotein level and the relationship to ventriculomegaly in fetal neural tube defect: A retrospective cohort study

ObjectiveTo estimate the significance of the association between mid-trimester maternal serum alpha-fetoprotein (MSAFP) level and fetal neuroanatomic findings in cases of open neural tube defect (ONTD). MethodsRetrospective study of patients referred for prenatal ONTD repair between 2012 and 2018. Cases were classified into three groups based on their MSAFP level: 1)High MSAFP (>3.8MoM – n = 22), 2)Moderately high MSAFP (≤3.8 and ≥2.5MoM – n = 28), 3)Normal MSAFP (<2.5MoM – n = 18). MRI scans at the time of referral were used to assess the relationship between MSAFP and: A)Type of ONTD; B) Ventriculomegaly; C) Size of the myeloschisis lesion; D) Volume of myelomeningocele; E) Anatomical level of the lesion (LL). ResultsHaving a high MSAFP level was more likely to be associated ventriculomegaly at mid-gestation than a moderately high or normal MSAFP level (OR = 8.4;CI95[0.9–73.4];p = 0.05 and OR = 2.8;CI95[0.9–8.8];p = 0.07). There were no differences between the three groups regarding type of lesion, size of the myeloschisis lesion, anatomic LL, or volume of the myelomeningocele sac. Myeloschisis cases with normal MSAFP had a larger surface area when compared to myeloschisis cases with moderately high MSAFP (219.8[104.4−551] vs 155.4[38.5−502.4] mm², p = 0.04). ConclusionA 2nd trimester MSAFP level >3.8MoM in a fetus with ONTD is associated with mid-gestation ventriculomegaly.

657 The impact of fetal intervention on maternal perinatal mental health

The Edinburg postpartum depression scale (EPDS) is a valuable tool to screen for perinatal depression. Recognizing depression after diagnosis of fetal anomaly is important to protect mother and baby from adverse outcomes. Our objective is to assess the impact of fetal intervention (FI) on mothers diagnosed with fetal anomaly. Retrospective review of patients with confirmed fetal anomaly receiving prenatal care at our center from January 2018 to January 2020. FI was offered for open neural tube defects, fetal anemia, congenital diaphragmatic hernia, pleural effusion, bladder obstruction, and twin-twin transfusion syndrome. EPDS surveys were administered during perinatal care. Patients were separated into two groups: Fetal anomaly-intervention (FA-FI) and no intervention (FA-non FI). Women with elevated EPDS scores (≥ 10) or indication for assessment were referred to psychiatry. Fisher’s exact test and logistic regression analyses were performed, with statistical significance defined as p<0.05. 462 patients met criteria, 77 in the FA-FI and 385 in the FA-non FI group. There was no significant difference in mean EPDS scores between FA-FI and FA-non FI, antenatal [5.48 (±4.60), 5.95 (±5.53), p = 0.25] or postnatal [6.44 (±4.56), 6.62 (±5.93), p = 0.39]. However, women with a diagnosis of cardiac anomaly who underwent FI had greater antenatal EPDS scores [7.75 (±1.50) vs. 5.49 (±5.21), p = 0.02]. Positive psychiatric history was a significant predictor of depression (p < 0.0001). Neither intervention (p = 0.24) nor anomaly (p = 0.43) were predictive of depression. The FA-non FI group had a higher EPDS score in the postnatal period in patients followed and treated by psychiatry [8.29 (±4.60) vs 12.18 (±5.97), p = 0.007; 6.33 (±3.33) vs 10.58 (±4.49), p = 0.01]. Type of anomaly or need for intervention were not predictive of depression in the perinatal period. The greatest predictor of depression is a history of a pre-existing psychiatric disorder. For patients with fetal anomaly, not receiving FI, depression presents in the postnatal period during psychiatric treatment.

Open Neural Tube Defects in COVID-19 Pandemic: An Analysis of 26 Neonatal Patients in a Tertiary Care Center.

ABSTRACTCoronavirus disease-2019 (COVID-19) pandemic has severely affected and disrupted medical practice all over the world since December 2019 till date. This has affected the pediatric surgical practice in general and neurosurgical practice in particular. An analysis of 26 neonatal patients with open neural tube defects who underwent surgery in the neurosurgery department at the King Edward VII Memorial Hospital (KEM), Mumbai during the period of March 2020 till December 2020 is presented. The cumulative experience and challenges encountered in the comprehensive management of these cohort of patients in the difficult period of the pandemic is discussed in accordance with relevant literature on the subject.

Timeliness of postnatal surgery in newborns with open neural tube defects: a single center experience.

This study aims to evaluate the experience of a tertiary health center on the timeliness of postnatal management in newborns with open neural tube defects (NTDs). This is a retrospective review of 38 neonates with NTDs who were treated surgically at a tertiary health care center between January 2009 and January 2019. Five neonates with genetic syndromes were excluded. Twenty-six neonates with NTD underwent surgery on the first postnatal day while 12 neonates with NTD had surgery after the first postnatal day. The reasons for the latency in operative treatment were the delay in the referral of the affected newborn from other health care centers (n=8) and the transient abnormalities in coagulation tests (n=4). Rural residence was significantly more frequent, gestational age at delivery was significantly lower, preterm delivery was significantly more frequent and prenatal diagnosis was significantly less frequent in neonates that underwent surgery for NTD repair after the first postnatal day (p=0.001, p=0.048, p=0.024 and p=0.003 respectively). Postoperative motor dysfunction was significantly more severe (p=0.002), postoperative complications were significantly more frequent (p=0.008), the reoperation and postoperative mortality rates were significantly higher (p=0.009 and p=0.048 respectively) and the duration of hospital stay was significantly longer (p=0.033) for the neonates who underwent surgery after the first postnatal day. Our study appears to favor the early repair of NTD`s within the first 24 hours of life. Such an approach may reduce the risk of infectious and neurological complications significantly.

Fetoscopic Multilayer, Dural Patch Closure Technique for Intrauterine Myelomeningocele Repair: 2-Dimensional Operative Video.

Myelomeningocele (MMC) is the most common open neural tube defect associated with long-term survival. In 2011, The Management of Myelomeningocele Study (MOMS) trial demonstrated that fetal repair for MMC reduced the rate of shunted hydrocephalus and improved developmental, motor, and ambulation outcomes at 30 mo compared to postnatal intervention.1 Recent studies have demonstrated the safety and feasibility of fetoscopic MMC repair as well as reduction in preterm birth, lower risk of uterine dehiscence, and the option of vaginal delivery with this approach compared to open fetal repair.2-4 The patient is a 25-yr-old female, G4 P2, who presented at 20 wk's gestation with ultrasound findings concerning for MMC and Chiari II malformation. These findings were further corroborated with fetal magnetic resonance imaging. After extensive prenatal counseling in a multidisciplinary fashion and discussion regarding risks and benefits of prenatal closure of the MMC, the patient chose to undergo prenatal repair and surgical consent was obtained. At 25 wk's gestation, the patient underwent a fetoscopic multilayer closure with dural patch repair using a standardized, 3-port, carbon dioxide insufflation technique for the intrauterine treatment of MMC without any postoperative complications. The duration of the entire procedure was 275 min. At 36 wk's and 1 d's gestational age, the patient had a spontaneous vaginal delivery, resulting in a healthy male newborn. The surgical site was well healed without complications, and follow-up radiographic imaging was reassuring. This edited, 2-dimensional operative video highlights the key steps of the fetoscopic closure with follow-up postnatal clinical and radiographic outcomes.

New cut-off values for screening of trisomy 21, 18 and open neural tube defects (ONTD) during the second trimester in pregnant women with advanced maternal age

BackgroundTo determine whether advanced maternal age (AMA) causes changes in the maternal serum markers of Trisomy 21, 18 and open neural tube defects (ONTD) during the second trimester of pregnancy. Our research aims to develop new cut-off values for AMA in order to reduce the need for further invasive testing.MethodsThis retrospective cohort study involved 12,739 pregnant women with AMA and 197,101 pregnant women with non-AMA. We then compared the two groups with respect to the positive rate and positive predictive value (PPV) of Trisomy 21, 18 and ONTD. Pregnant women with Trisomy 21, 18 and ONTD were diagnosed by karyotyping the amniotic fluid and by ultrasound diagnosis.ResultsCompared to the non-AMA group, the multiple of the median (MOM) of free beta- human chorionic gonadotropin (free β-hCG), alpha-fetoprotein (AFP), and the risk value forTrisomy 21, were significantly higher in the AMA group (all P < 0.001). The positive rates of Trisomy 21, 18, and ONTD in the AMA group were significantly higher than those in the control group (all P < 0.001). In the AMA group, the PPVs for Trisomy 21 and other deformities were significantly higher (all P < 0.001), although the PPVs for Trisomy 18 and ONTD were similar to those of the non-AMA group. The area under the curve (AUC) values for the AMA group were higher than the non-AMA group, based on free β-hCG MoM, AFP MoM, and the risk value of Trisomy 21. The cut-off value for the risk value of Trisomy 21 was 1/172 for the AMA, group and 1/780 for the non-AMA group.ConclusionsThe positive rates for Trisomy 21, 18 and ONTD, and the PPV for Trisomy 21 and other deformities were significantly higher in the AMA group. It is essential for pregnant women with AMA to be tested using appropriate cut-off values of serum markers screening for Trisomy 21 during the second trimester of pregnancy to improve the efficacy of prenatal screening and reduce the need for further invasive testing.

Open Fetal Surgical Outcomes for Myelomeningocele Closure Stratified by Maternal Body Mass Index in a Large Single-Center Cohort

Background: Open maternal-fetal surgery for in utero closure of myelomeningocele (MMC) has become an accepted treatment option for prenatally diagnosed open neural tube defects. Historically, this option has been limited to women with BMI < 35 due to concern for increasing complications in patients with obesity. Objective: The aim of this study was to evaluate maternal, obstetric, and fetal/neonatal outcomes stratified by maternal BMI classification in women who undergo open maternal-fetal surgery for fetal myelomeningocele (fMMC) closure. Methods: A single-center fMMC closure registry was queried for maternal demographics, preoperative factors, fetal surgery outcomes, delivery outcomes, and neonatal outcomes. Data were stratified based on maternal BMI: <30, 30–34.99, and ≥35–40, corresponding to normal weight/overweight, obesity class I, and obesity class II. Statistical analysis was performed using statistical software SAS v.9.4 (SAS Institute Inc., Cary, NC, USA). Results: A total of 264 patients were analyzed, including 196 (74.2%) with BMI <30, 54 (20.5%) with BMI 30–34.99, and 14 (5.3%) with BMI ≥ 35–40. Maternal demographics and preoperative characteristics were similar among the groups. Operative time increased with increasing BMI; otherwise, perioperative outcomes were similar among the groups. Obstetric and neonatal outcomes were similar among the groups. Conclusion: Increasing maternal BMI did not result in a negative impact on maternal, obstetric, and fetal/neonatal outcomes in a large cohort of patients undergoing open maternal-fetal surgery for fMMC closure. Further study is warranted to determine the generalizability of these results.

Prevalence of open neural tube defects and risk factors related to isolated anencephaly and spina bifida in live births from the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Jalisco, Mexico).

We determine the prevalence and trends of open neural tube defects (ONTDs) during 1991 to 2019 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Mexico). Also, details of potential risks were obtained in 662 newborns, including those 143 patients with anencephaly and open spina bifida (OSB) classified as isolated (cases) and 519 controls. Data were analyzed using multivariable logistic regression. Among 267 201 live births during the study period, 336 were born with ONTDs, yielding an overall prevalence of 12.6 per 10 000. After folic acid (FA)-related programs began in Mexico (2003-2019), only OSB showed a decline of 20.6%. For anencephaly, associated risks included relatives with neural tube defects (NTDs) (adjusted odds ratio [aOR]: 67.9, 95% confidence interval [95% CI]: 11.3-409.8), pre-pregnancy body mass index (BMI) ≥25 kg/m2 (aOR: 2.6, 95% CI: 1.1-6.0), insufficient gestational weight gain (aOR: 3.0, 95% CI: 1.3-7.1), parity ≥4 (aOR: 3.2, 95% CI: 1.3-7.7), and exposure to analgesic/antipyretic drugs (aOR: 9.0; 95% CI: 2.5-33.0). For OSB, associated risks included consanguinity (aOR: 14.0, 95% CI: 3.5-55.9), relatives with NTDs (aOR: 22.4, 95% CI: 4.5-112.9), BMI ≥25 kg/m2 (aOR: 2.5, 95% CI: 1.6-4.2), insufficient gestational weight gain (aOR: 1.9, 95% CI: 1.1-3.1), and exposures to hyperthermia (aOR: 2.3, 95% CI: 1.2-4.3), common cold (aOR: 6.8, 95% CI: 3.6-12.7), and analgesic/antipyretic drugs (aOR: 3.6, 95% CI: 1.3-10.0). Our high rate probably results from exposures to preventable risks, most related to FA, indicating a need for strengthening existing FA-related programs in Mexico.

VP21.02: Impact of the type of open neural tube defect on the fetal motor function in candidates for prenatal repair

VP21.02: Impact of the type of open neural tube defect on the fetal motor function in candidates for prenatal repair

Fetal Intraventricular Hemorrhage in Open Neural Tube Defects: Prenatal Imaging Evaluation and Perinatal Outcomes.

Fetal imaging is crucial in the evaluation of open neural tube defects. The identification of intraventricular hemorrhage prenatally has unclear clinical implications. We aimed to explore fetal imaging findings in open neural tube defects and evaluate associations between intraventricular hemorrhage with prenatal and postnatal hindbrain herniation, postnatal intraventricular hemorrhage, and ventricular shunt placement. After institutional review board approval, open neural tube defect cases evaluated by prenatal sonography between January 1, 2013 and April 24, 2018 were enrolled (n = 504). The presence of intraventricular hemorrhage and gray matter heterotopia by both prenatal sonography and MR imaging studies was used for classification. Cases of intraventricular hemorrhage had intraventricular hemorrhage without gray matter heterotopia (n = 33) and controls had neither intraventricular hemorrhage nor gray matter heterotopia (n = 229). A total of 135 subjects with findings of gray matter heterotopia were excluded. Outcomes were compared with regression analyses. Prenatal and postnatal hindbrain herniation and postnatal intraventricular hemorrhage were more frequent in cases of prenatal intraventricular hemorrhage compared with controls (97% versus 79%, 50% versus 25%, and 63% versus 12%, respectively). Increased third ventricular diameter, specifically >1 mm, predicted hindbrain herniation (OR = 3.7 [95% CI, 1.5-11]) independent of lateral ventricular size and prenatal intraventricular hemorrhage. Fetal closure (n = 86) was independently protective against postnatal hindbrain herniation (OR = 0.04 [95% CI, 0.01-0.15]) and postnatal intraventricular hemorrhage (OR = 0.2 [95% CI, 0.02-0.98]). Prenatal intraventricular hemorrhage was not associated with ventricular shunt placement. Intraventricular hemorrhage is relatively common in the prenatal evaluation of open neural tube defects. Hindbrain herniation is more common in cases of intraventricular hemorrhage, but in association with increased third ventricular size. Fetal closure reverses hindbrain herniation and decreases the rate of intraventricular hemorrhage postnatally, regardless of the presence of prenatal intraventricular hemorrhage.

New surgical paradigm for open neural tube defects.

An open neural tube defect (ONTD) features an exposed, unclosed neural plate in the form of an expanded, flat, and frequently hefty neural placode. Traditional philosophy of ONTD repair aims at preserving function at any cost, which often means stuffing the entire thick and unwieldy but non-functional placode into a tight dural sac, increasing the likelihood of future tethering of the spinal cord. The same philosophy of attempting to save the whole perimetry of the placode also sometimes leads to inadvertent inclusion of parts of the squamous epithelial membrane surrounding the placode into the reconstructed product, only to form inclusion dermoid cyst causing further injury to the neural tissues. Lastly, defective closure of the caudal primary neural tube usually results in abolition of secondary and junctional neurulation, leaving a defective conus and sacral nerve roots, clinically presenting in most cases with neurogenic bladder and bowel dysfunction. Preserving this trapped but locally active sacral micturition center, isolated from suprasegmental inhibitory moderation, leads to a spastic, hyperactive, low compliance, and high-pressure bladder predisposing to upstream kidney damage, without benefits of normal bladder function. We report the post-natal surgical treatment of 8 newborn infants with ONTD, in which we resected the non-functional portion of the neural placode identified as such by direct spinal cord/placode and nerve root stimulation, as well as by transcortical evoked motor responses to check for suprasegmental corticospinal connectivity. Any part of the placode without local function or upstream connections was resected, and the small caudal spinal cord stump closed with pia-to-pia microsutures. The patients were followed for pre- and post-operative neuro-urological status and with serial magnetic resonance imaging (MRI) at 3weeks, 6months, and 2years post-repair. Follow-up period ranged from birth to 3years (mean of 24months). Of the 8 patients analyzed, 7 had a terminal and one a segmental ONTD. Pre-operative neurological level ranged from L4 to S2. Applying our new surgical paradigm, we found no neurological worsening post-operatively. All patients had a neurogenic bladder and bowel dysfunction but none had a high-pressure bladder on urodynamics studies. Early and late MRIs all showed a loose and capacious neural placode to dural sac relationship. None had an inclusion dermoid cyst. We propose a new paradigm for the surgical repair of open neural tube defects with intraoperative neuromonitoring and introduce a safe and reliable technique of placode debulking.

Retrieving the Moral in the Ethics of Maternal-Fetal Surgery.

Open-uterine surgery to repair spina bifida, or 'fetal surgery of open neural tube defects,' has generated questions throughout its history-and continues to do so in a variety of contexts. As clinical ethics consultants who worked (Mark J. Bliton) and trained (Virginia L. Bartlett) at Vanderbilt University-where the first successful cases of open-uterine repair of spina bifida were carried out-we lived with these questions for nearly two decades. We worked with clinicians as they were developing and offering the procedure, with researchers in refining and studying the procedure, and with pregnant women and their partners as they considered whether to undergo the procedure. From this experience in the early studies at Vanderbilt, we learned that pregnant women and their partners approach the clinical uncertainty of such a risky procedure with a curious and unique combination of practicality, self-reflection, fear, and overwhelming hope. These early experiences were a major contributing factor to the inclusion of an ethics-focused interview in the informed consent process for the Management of Myelomeningocele Study (MOMS) trial study design.

Open Neural Tube Defect in a Fetus with MURCS Association: Value Addition of Fetal Autopsy in Counseling

Open Neural Tube Defect in a Fetus with MURCS Association: Value Addition of Fetal Autopsy in Counseling

Neonatal ten-year retrospective study on neural tube defects in a second level University Hospital

BackgroundAim of this retrospective study was to describe clinical characteristics, diagnostic work-up, management and follow-up of newborns with neural tube defects (NTDs), admitted to the Mother and Child Department of the University Hospital of Palermo, in a ten years period.MethodsThe medical records of 7 newborns (5 males and 2 females) admitted, over a 10-year period from January 2010 to March 2020, to our Department on the first day of life were reviewed. Analyzed data were related to familiar and/or maternal risk factors (consanguinity, maternal preexisting and/or gestational diseases, exposure to teratogen/infectious agents, lack of preconception folic acid supplement), demographic (ethnicity/origin, residence) and clinical features (eventual use of assisted reproduction techniques, prenatal diagnosis, gestational age, fetal presentation, type of delivery, birth weight, preoperative imaging, antibiotics and analgesics use, description of the surgery intervention, length of hospital stay, comorbidities, complications), and follow-up.ResultsIn our sample we observed a wide spectrum of NTDs: 3 newborns had open NTDs, namely myelomeningocele (2 lumbosacral, one of which associated with extradural lipoma, and 1 sacral), and 4 closed ones, including 2 with meningocele (occipital), 1 filar lipoma associated with dermal sinus, and 1 terminal myelocystocele. Our patients were discharged between 8 and 22 days of life.The neurodevelopmental follow-up showed a favorable outcome for 4 of the 7 patients, and the appearance over time of neurological impairment (motor and/or autonomic) in the newborns with open NTDs.ConclusionsThis study describes familiar and/or maternal risk factors and demographic and clinical features of a single-center series of newborns with NTDs. It may provide a further outline of the actual phenotypic spectrum of these malformations, and new insights into epidemiological aspects and comprehensive management of the patients, including diagnostic work-up and follow-up evaluations.

To Document The Clinical Presentation and Outcome of Open Neural Tube Defect at Teaching Hospital, Dera Ghazi Khan

Objectives: To study clinical presentation and to determine outcome of open Neural Tube Defects at ourrespected institution. We took a review of all cases of open neural tube defects seen at the Neurosurgery Unit of hospital in the last years to document their medical patterns, assess their neonatal outcome.Materials and Methods: This retrospective study included 74 patients, admitted to the Department ofNeurosurgery, D. G. Khan Medical College and Hospital, Dera Ghazi Khan. The procedure for history takingand clinical examination was completed to measure Folic Acid Intake in first trimester, ultra sound abdomen,pre-natal diagnosis, hydrocephalous, CSF leak from swelling, sphincter involvement, weakness of lower limb,previous baby affected, type &amp; location of open neural tube defects along the cranio-vertebral axis. Spine X-rays,neurosonograms, MRIs were carried out to find associated irregularities and complications if exist.Results: Out of 74 children born with open neural tube defects, 9 (12%) mothers received antenatal care only, 7(9%) get folic acid regularly. Prenatal diagnosis was made in 11 (14.8%) mothers whose antenatal abdominalultrasound was done. The most common type of myelomeningocele was lumbosacral 58 (79%). Forty-four(59.4%) babies have hydrocephalous while five babies were microcephaly. Increased risk of rupturedmyelomeningocele was linked with vaginal delivery. Sphincter disturbance and limb paralysis was present in 35(47%) and 32 (43.7%) of babies respectively. The mortality was in 12% patients.Conclusion: We suggest that efforts should be made in this respect to prenatal diagnosis of such lesions to getbetter neonatal outcome

The diagnostic accuracy of maternal serum alpha-fetoprotein variants (AFP-L2 and AFP-L3) in predicting fetal open neural tube defects and abdominal wall defects

IntroductionTo evaluate a risk model of the maternal serum α-fetoprotein variants L2 and L3 (AFP-L2 and AFP-L3) for predicting fetal open neural tube defects (ONTD) and abdominal wall defects (AWD). MethodsSubjects were divided into the ONTD group (21), the AWD group (16) and the control group (38). Comparative analysis was performed using a risk model, receiver operating characteristic (ROC) curves and area under the curve (AUC) were used for screening performance of AFP-L2 and AFP-L3. ResultsAFP-L2 and AFP-L3 concentrations in the ONTD group and the AWD group were both significantly higher than those in the control group (P < 0.001). The AUC for screening ONTD or AWD using AFP-L2 was 0.830 [95% confidence interval (CI):0.734–0.926, P < 0.001], while using AFP-L3 was 0.886 (95% CI: 0.809–0.963, P < 0.001). ROC curves indicated that the optimal threshold values for ONTD or AWD by AFP-L2 and AFP-L3 were 1.467 multiple of the median (MoM) and 1.944 MoM. The corresponding sensitivity, specificity and Youden index for AFP-L2 and AFP-L3 were 0.703, 0.947, 0.650 and 0.730, 0.974, 0.703, respectively. ConclusionAFP-L2 and AFP-L3 are favorable biomarkers for screening ONTD and AWD fetuses, and the risk model using AFP-L2 and AFP-L3 is of superior sensitivity and specificity.

Improved Coverage of Mouse Myelomeningocele With a Mussel Inspired Reverse Thermal Gel

BackgroundMyelomeningocele (MMC) is an open neural tube defect of the spinal column. Our laboratory previously introduced a reverse thermal gel (RTG) as the first in situ forming patch for in utero MMC application. To overcome the challenges of anchoring the RTG in the wet amniotic environment to improve MMC coverage, we modified the RTG to mimic the underwater adhesive properties of mussels. We have separated this study into three separate hypotheses-based components:1Based on mussel inspired chemistry, modification of the RTG with dopamine will increase the underwater adhesive properties to improve RTG anchoring ability in a wet environment. Methods: The dopamine-modified RTG (DRTG) was synthesized using carbonyldiimidazole chemistry and characterized with proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy. Rheology and underwater adhesive tests measured mechanical properties. Results: DRTG synthesis was confirmed with proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy. Rheology demonstrated increased elasticity. Underwater adhesion testing revealed DRTG has similar wet adhesive strength to Tisseel fibrin sealant.2The DRTG will support in vitro skin cell growth and will be safe for injection in a mouse animal model. Methods: Biocompatibility testing included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DRTG-fibroblast and keratinocyte cultures, and subcutaneous injections to quantify macrophages stained with immunohistochemistry. Results: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and DRTG cell cultures revealed no cytotoxicity and demonstrated the growth of fibroblasts and keratinocytes. Subcutaneous injections cause a macrophage response that decreases after 4 wk.3In utero injection of novel DRTG into a mouse MMC model will be effective with improved patch coverage of the MMC defect. Methods: MMC coverage by DRTG was assessed using in utero mouse injections in the Grainy head-like 3 (Grhl3) mouse model. Results: In utero Grhl3 mouse injections demonstrate statistically significant (P = 0.012) improved MMC coverage of DRTG compared with previous RTG coverage with no significant macrophage response. ConclusionsThe DRTG demonstrates increased elasticity, cellular scaffolding properties, and improved MMC coverage in the Grhl3 mouse model. Future studies will be translated to the preclinical ovine model to evaluate this novel gel.

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is made, options include termination, surgery after delivery, or in utero surgery, depending on factors such as location and size of the defect, and the presence of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.

Use of an abdominal reapproximation anchor system in the closure of large, open myelomeningoceles.

Open neural tube defects are complex congenital abnormalities of the nervous system in which nervous tissue is exposed on the patient's back at the time of delivery. These malformations require surgical correction, and although replacement of the neural placode internally is fairly standard, providing skin closure can be very challenging especially in large defects. An abdominal reapproximation anchor (ABRA) device may be of value in attaining skin closure in these large, open myelomeningocele defects in which primary closure cannot be accomplished surgically. In a study period during which 65 patients underwent surgical closure of open myelomeningocele defects, 5 of them underwent ABRA-assisted closure.The average surgical intervention for myelomeningocele repair occurred on day 2.2 of life (range 2-3 days). The average defect size was 37 cm2 (range 16-56 cm2), and the average time to formal closure was 30.8 days (range 8-63 days). One of the patients had natural closure with just ABRA approximation. The remaining 4 patients underwent formal delayed primary closure when the skin edges became approximated. Use of the ABRA system in the closure of a large, open myelomeningocele may be valuable in select patients but requires further follow-up and comparison to identify truly significant differences with traditional techniques.

Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein

ObjectiveThe aim of this study was to investigate the overall distribution of pregnancy outcomes in women with elevated second-trimester maternal serum alpha-fetoprotein (MS-AFP), and to determine the risk of adverse pregnancy outcomes (APOs) by MS-AFP level. Materials and methodsWe retrospectively analyzed the clinical data of 429 women with elevated MS-AFP (≥2.5 multiple of the median (MOM)) and 1555 women with normal MS-AFP (0.5–2.49MOM) from a total of 46,741 prenatally screened singleton pregnant women. The overall distribution of APOs of the two groups, the risk of APOs by MS-AFP level, and the predictive value of elevated MS-AFP to APOs were analyzed. ResultsThe incidence rate of APOs in elevated MS-AFP group was significantly higher than that in normal MS-AFP group (42.89 vs. 8.23%). In elevated MS-AFP group, the top three APOs, in term of incidence rate, were structural fetal abnormalities (7.93%), spontaneous abortion (7.46%) and preterm birth (7.23%); regarding to the risk, the top three APOs were stillbirth, spontaneous abortion and early-onset preeclampsia (odds ratio 35.98, 20.81 and 8.58 respectively). For structural fetal abnormalities, MS-AFP had predictive values for fetal open neural tube defects (ONTDs), gastroschisis and multiple malformations. ConclusionElevated MS-AFP is associated with increased risks of APOs. ONTDs complicate merely a small proportion of pregnancies with elevated MS-AFP, and the rest of them have high risks of obstetric complications. MS-AFP can help to identify these women at high risk of APOs in earlier second-trimester.