Corpus Callosum Length and Cerebellar Vermian Height in Fetal Growth Restriction.

INTRODUCTION: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses. METHODS: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC). RESULTS: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [-0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = -0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI. CONCLUSIONS: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations.

Adverse perinatal outcomes in pregnancies affected by severe COVID-19 infection.

BACKGROUND: Severe COVID-19 infection in pregnancy has been associated with an increase in adverse perinatal outcomes, although studies differ regarding which outcomes are affected. Increased characterization of obstetrical and neonatal outcomes is needed, including details on indications for preterm delivery and additional neonatal adverse outcomes. OBJECTIVE: This study aimed to determine whether there is a higher rate of adverse perinatal outcomes with severe-to-critical COVID-19 infection compared with nonsevere COVID-19 diagnosed during pregnancy. STUDY DESIGN: This was a retrospective observational cohort study that compared rates of adverse perinatal outcomes between patients with severe-to-critical and those with nonsevere (asymptomatic, mild, or moderate) COVID-19 infection. Patients had singleton pregnancies and a positive laboratory polymerase chain reaction result for COVID-19. Primary outcomes included hypertensive disorders of pregnancy, cesarean delivery, fetal growth restriction, preterm birth, and neonatal intensive care unit admission. Additional neonatal outcomes analyzed included need for cardiopulmonary resuscitation, low birthweight (<2500 g), 1- or 5-minute Apgar score <7, need for supplemental oxygen, need for intubation, intraventricular hemorrhage, sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, blood transfusion, necrotizing enterocolitis, hypoxic-ischemic encephalopathy, birth trauma, or neonatal death. Appropriate bivariate analyses were used to compare groups. Logistic regression was used to examine primary outcomes while adjusting for confounders. RESULTS: A total of 441 participants were identified and confirmed via detailed chart review to be pregnant with a singleton pregnancy while diagnosed with COVID-19. Of these, 44 (10%) met National Institutes of Health criteria for severe-to-critical COVID-19 infection. The median gestational age at the time of maternal COVID-19 diagnosis was 36.4 weeks (interquartile range, 29.6-38.6). Severe-to-critical COVID-19 infection had a higher risk of a composite adverse neonatal outcome (36.4% vs 21.4%; P=.03). There was a high incidence of hypertensive disorders of pregnancy overall (20.6%), but this outcome was not higher in the severe-to-critical vs nonsevere group. There were no maternal deaths. There was a low incidence of neonatal COVID-19 test positivity among those tested (1.8%). When adjusting for presence of heart disease and gestational age at COVID-19 diagnosis, severe-to-critical COVID-19 was strongly associated with fetal growth restriction (adjusted odds ratio, 2.73; confidence interval, 1.03-7.25) and neonatal intensive care unit admission (adjusted odds ratio, 3.50; confidence interval, 1.56-7.87). Preterm delivery was more common but was no longer significant after adjustment (adjusted odds ratio, 2.23; confidence interval, 0.99-5.05). CONCLUSION: Severe-to-critical COVID-19 infection during pregnancy is associated with higher rates of adverse neonatal outcomes and strongly associated with neonatal intensive care unit admission and fetal growth restriction compared with nonsevere disease. There is a high rate of hypertensive disorders of pregnancy overall in all those affected by COVID-19, regardless of severity. Pregnant persons should be counseled on these risks to encourage vaccination, and those with infection during pregnancy should be monitored for fetal growth disorders.

Patterns of Brain Sparing in a Fetal Growth Restriction Cohort.

Objective: Our objective was to compare differences in Doppler blood flow in four fetal intracranial blood vessels in fetuses with late-onset fetal growth restriction (FGR) vs. those with small for gestational age (SGA). Methods: Fetuses with estimated fetal weight (EFW) <10th percentile were divided into SGA (n = 30) and FGR (n = 51) via Delphi criteria and had Doppler waveforms obtained from the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and vertebral artery (VA). A pulsatility index (PI) <5th centile was considered "abnormal". Outcomes included birth metrics and neonatal intensive care unit (NICU) admission. Results: There were more abnormal cerebral vessel PIs in the FGR group versus the SGA group (36 vs. 4; p = 0.055). In FGR, ACA + MCA vessel abnormalities outnumbered PCA + VA abnormalities. All 8 fetuses with abnormal VA PIs had at least one other abnormal vessel. Fetuses with abnormal VA PIs had lower BW (1712 vs. 2500 g; p < 0.0001), delivered earlier (35.22 vs. 37.89 wks; p = 0.0052), and had more admissions to the NICU (71.43% vs. 24.44%; p = 0.023). Conclusions: There were more anterior vessels showing vasodilation than posterior vessels, but when the VA was abnormal, the fetuses were more severely affected clinically than those showing normal VA PIs.

3D Fractional Limb Volume Identifies Reduced Subcutaneous and Lean Mass in Fetal Growth Restriction.

OBJECTIVES: Fetal 2D and 3D fractional limb volume (FLV) measurements by ultrasound can detect fetal lean and subcutaneous mass and possibly percent body fat. Our objectives were to 1) compare FLV measurements in fetuses with fetal growth restriction (FGR) versus small for gestational age (SGA) defined by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-supported international Delphi consensus and 2) correlate FLV findings with birth metrics. We hypothesize that FLV measurements will be significantly smaller in FGR versus SGA fetuses and will correlate closer with Ponderal index (PIx) in the neonate than abdominal circumference (AC). METHODS: Patients were categorized as FGR or SGA as defined by ISUOG. Total thigh volume (TTV), volumes of lean mass (LMV), and fat mass volume (FMV) were calculated from 3D acquisitions. Measurements were compared between groups and correlated with birthweight (BW) and PIx (BW/crown-heal length). RESULTS: The FGR group (n = 37) delivered earlier (37/2 versus 38/0; P = .0847), were lighter (2.2 kg versus 2.6 kg; P = .0003) and had lower PIx (0.023 versus 0.025; P = .0013) than SGAs (n = 22). FGRs had reduced TTV (40.6 versus 48.4 cm3 ; P = .0164), FMV (20.8 versus 25.3 cm3 ; P = .0413), and LMV (19.8 versus 23.1 cm3 ; P = .0387). AC had the highest area under the curve (0.69) for FGR. FMV was more strongly associated with PIx than the AC (P = .0032). CONCLUSIONS: The AC and FLV measurements were significantly reduced in FGR fetuses compared to SGAs. While the AC outperformed FLV in predicting FGR, the FLV correlated best with PIx, which holds investigative promise.

Evaluating for disparities in prenatal genetic counseling.

BACKGROUND: Guidelines recommend that all pregnant women should be offered prenatal genetic counseling, which includes discussions of aneuploidy and carrier screening. Previous studies have demonstrated racial and ethnic disparities in the completion of prenatal genetic testing, but few studies have evaluated for disparities in the offering of these tests. Prenatal genetic screening is a covered provision of Colorado Medicaid. We hypothesized that in the absence of a financial barrier, disparities in prenatal genetic counseling would be eliminated. OBJECTIVE: To evaluate disparities in prenatal genetic counseling by directly assessing if patients received counseling at the time of their first prenatal visit. STUDY DESIGN: This retrospective cross-sectional study included patients presenting for their first prenatal visit at <20 weeks' gestation. Patients who completed prenatal genetic testing were classified as counseled, and the remaining patients' medical records were reviewed. Moreover, patients were divided into 2 groups based on their counseling status (yes or no), separately for aneuploidy and carrier screening. RESULTS: Of 1103 patients who met the inclusion criteria, 97.2% were counseled for aneuploidy screening, whereas 73.3% were counseled on carrier screening. For aneuploidy, younger age, Black race, a relationship status of single, and presentation at a later gestational age were associated with lack of aneuploidy counseling on univariate analysis. After multivariable analysis, only maternal age (odds ratio, 1.09; 95% confidence interval, 1.01-1.19) and gestational age (odds ratio, 0.84; 95% confidence interval, 0.76-0.93) were statistically significantly associated with aneuploidy counseling. Treatment by a physician care team, having a comorbidity score of ≥1, and presenting at a later gestational age were associated with not receiving carrier screening counseling (univariate analysis). Multivariable analysis indicated significant associations with gestational age (odds ratio, 0.90; 95% confidence interval, 0.86-0.94) and having a comorbidity (odds ratio, 0.72; 95% confidence interval, 0.55-0.94). CONCLUSION: Prenatal genetic counseling was less likely to be provided to women who present for prenatal care at a later gestational age. This finding was of concern because women who are less privileged were more likely to present to prenatal care at a later gestational age. Providing access to early prenatal care and developing specialized care pathways for women entering prenatal care in the second trimester of pregnancy could address disparities in prenatal genetic counseling.

Immune Thrombocytopenia Following Booster Dose of the Moderna mRNA-1273 Vaccine.

Vaccine-mediated immune thrombocytopenia, although previously reported, is considered exceedingly rare. The probability of the incidence of profound thrombocytopenia following the COVID-19 mRNA-based vaccine has been less elucidated. We present the case of an 81-year-old female patient who became profoundly thrombocytopenic with bleeding manifestations six days after the Moderna mRNA-1273 vaccine administration. Fortunately, she exhibited platelet count recovery after treatment with intravenous immunoglobulins and steroid therapy. Furthermore, we show that the inherent risk of COVID-19 infection leading to thrombocytopenia significantly outweighs the vaccine's risk.

Identification of obstetric anal sphincter injuries (OASIs) and other lacerations: a national survey of nurse-midwives.

INTRODUCTION AND HYPOTHESIS: Clinical quality improvement relies on accurate understanding of current practice. We performed a cross-sectional national survey of certified nurse-midwives (CNMs) assessing classification and identification of obstetric anal sphincter injury (OASI) and other delivery lacerations. We hypothesized laceration diagnoses are frequently inaccurate, and delivery records for obstetric lacerations may be of questionable quality. METHODS: We emailed 6909 American College of Nurse Midwives members an internet-based survey link. Of respondents, we included clinically active CNMs who perform at least one delivery per month. We evaluated laceration knowledge and application using standard descriptive text and images and asked about processes for recording lacerations in the delivery record. RESULTS: We received 1070 (15.5%) completed surveys and 832 (77.8%) met inclusion criteria. Over 50% characterized their OASI training and ability to identify OASI as good/excellent. Most (79%) had never attended education review on OASI. The overall accuracy for classification and identification of perineal lacerations ranged from 49 to 99%. Non-perineal lacerations were frequently categorized using the perineal/OASI system. Half of respondents (51%) document their deliveries in an electronic medical record but a quarter (28%) are not personally responsible for approving delivery data. Younger participants without a doctoral degree, with self-assessed good/excellent laceration training, and caring for < 50% publicly insured patients had higher accuracy for laceration identification and diagnosis. CONCLUSIONS: We found high rates of inaccurate laceration diagnosis and inappropriate application of the perineal OASI degree system, suggesting education and training are needed. Clinical studies that rely on delivery diagnosis of OASI may not be reliable.

Prevention and Management of Severe Obstetric Anal Sphincter Injuries (OASIs): a National Survey of Nurse- Midwives.

INTRODUCTION AND HYPOTHESIS: There are no data on midwives' knowledge and management of obstetric anal sphincter injuries (OASIs) in the USA. We performed a cross-sectional national survey characterizing OASI practice by certified nurse midwives (CNMs), hypothesizing that few midwives personally repair OASIs and that there are gaps in CNM OASI training/education. METHODS: We emailed a REDCap internet-based survey to 6909 American College of Nurse Midwives members (ACNM). We analyzed responses from active clinicians performing at least one delivery per month, asking about OASI risks, prevention, repair, and management. We summarized descriptive data then evaluated OASI knowledge by patient and provider characteristics. RESULTS: We received 1070 (15.5%) completed surveys, and 832 (77.8%) met the inclusion/exclusion criteria. Participants were similar to ACNM membership. Respondents most frequently identified prior OASI (87%) and nutrition (71%) as antepartum OASI risk factors and, less frequently, nulliparity (36%) and race (22%). Identified intrapartum risks included forceps delivery (94%) and midline episiotomy (88%). When obstetric laceration is suspected, 13.6% of respondents perform a rectal examination routinely. Only 15% of participants personally perform OASI repair. Overall, participants matched 64% of evidence-based answers. OASI education/training courses were attended by 30% of respondents, and 44% knew of OASI protocols within their group/institution. Of all factors evaluated, the percent of evidence-based responses was only different for respondent education/CME and protocols. CONCLUSIONS: Quality initiatives regarding OASI prevention and management may improve care. Our data suggest OASI training for midwives may improve delivery care in the US. Further studies of other obstetric providers are needed.

Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach.

Yersinia pestis causes a rapid, lethal disease referred to as plague. Y. pestis actively inhibits the innate immune system to generate a noninflammatory environment during early stages of infection to promote colonization. The ability of Y. pestis to create this early noninflammatory environment is in part due to the action of seven Yop effector proteins that are directly injected into host cells via a type 3 secretion system (T3SS). While each Yop effector interacts with specific host proteins to inhibit their function, several Yop effectors either target the same host protein or inhibit converging signaling pathways, leading to functional redundancy. Previous work established that Y. pestis uses the T3SS to inhibit neutrophil respiratory burst, phagocytosis, and release of inflammatory cytokines. Here, we show that Y. pestis also inhibits release of granules in a T3SS-dependent manner. Moreover, using a gain-of-function approach, we discovered previously hidden contributions of YpkA and YopJ to inhibition and that cooperative actions by multiple Yop effectors are required to effectively inhibit degranulation. Independent from degranulation, we also show that multiple Yop effectors can inhibit synthesis of leukotriene B4 (LTB4), a potent lipid mediator released by neutrophils early during infection to promote inflammation. Together, inhibition of these two arms of the neutrophil response likely contributes to the noninflammatory environment needed for Y. pestis colonization and proliferation.

Modified Hysterotomy Closure Technique for Open Fetal Surgery.

OBJECTIVE: We reviewed our experience with open fetal surgical myelomeningocele repair to assess the efficacy of a new modification of the hysterotomy closure technique regarding hysterotomy complication rates at the time of cesarean delivery. METHODS: A modification of the standard hysterotomy closure was performed on all patients undergoing prenatal myelomeningocele repair. The closure consisted of an interrupted full-thickness #0 polydioxanone (PDS) retention suture as well as a running #0 PDS suture to re-approximate the myometrial edges, and the modification was a third imbricating layer resulting in serosal-to-serosal apposition. A standard omental patch was placed per our routine. Both operative reports and verbal descriptions of hysterotomy from delivering obstetricians were reviewed. RESULTS: A total of 49 patients underwent prenatal repair of myelomeningocele, 43 having adequate follow-up for evaluation. Of those, 95.4% had completely intact hysterotomy closures, with only 1 partial dehiscence (2.3%) and 1 thinned scar (2.3%). There were no instances of uterine rupture. DISCUSSION: In patients undergoing this modified hysterotomy closure technique, a much lower than expected complication rate was observed. This simple modified closure technique may improve hysterotomy healing and reduce obstetric morbidity.

Umbilical cord cysts in the first trimester: are they associated with pregnancy complications?

OBJECTIVES: To determine whether umbilical cord cysts found by transvaginal sonography in the first trimester of pregnancy are associated with poor pregnancy outcomes. METHODS: We conducted a matched cohort study between July 2006 and July 2008. Patients with umbilical cord cysts found on transvaginal sonography in the first trimester were matched to patients with normal umbilical cords. After the completion of these pregnancies, medical histories and pregnancy outcomes were reviewed from the hospital's electronic record. Sonograms were reviewed to obtain descriptive information about the umbilical cord cysts. Outcomes between the cohorts were compared. RESULTS: Forty-five patients with umbilical cord cysts were identified and compared to 85 patients with normal umbilical cords. The mean gestational age of the cysts ± SD at diagnosis was 8 weeks 3 days ± 3.5 days. The mean cyst diameter was 3 ± 2.1 mm. All cysts resolved on follow-up sonography, which was performed between 9 weeks 4 days and 20 weeks 5 days. Patients with umbilical cord cysts were found to have a lower body mass index than those with normal umbilical cords. There was no significant difference in abnormal sonographic findings between cohorts. Five sonographic fetal abnormalities were found in the umbilical cord cyst cohort (11.1%) and 8 in the normal umbilical cord cohort (9.4%). There were 2 intrauterine fetal demises in the umbilical cord cyst cohort and 1 in the normal umbilical cord cohort. There was no difference between the cohorts when comparing gestational age at delivery and birth weight. CONCLUSIONS: There does not appear to be an association between poor pregnancy outcomes and umbilical cord cysts during the first trimester.

Magnesium for fetal neuroprotection.

Available evidence now suggests that magnesium sulfate administered to mothers prior to early preterm delivery reduces the risk of cerebral palsy in surviving neonates. The American College of Obstetricians and Gynecologists along with the Society for Maternal-Fetal Medicine state that physicians who choose to administer magnesium sulfate for neuroprotection should do so in accordance with one of the larger randomized trials. Due to the heterogeneity of the methods, many clinicians may find it difficult to proceed with a therapeutic protocol that adheres to the available literature. Here, we present one reasonable approach that identifies the specific patients who qualify for magnesium sulfate therapy, and it outlines a treatment algorithm while addressing retreatment and concomitant tocolysis.

Resistance artery adaptation to pregnancy counteracts the vasoconstricting influence of plasma from normal pregnant women.

Using a rat model, we investigated the effects of circulating factors in pregnancy on cerebrovascular and systemic vascular function by comparing myogenic reactivity, tone, and endothelial vasodilator production of the posterior cerebral artery (PCA) and mesenteric artery (MA) of nonpregnant (NP) animals perfused with nonpregnant and pregnant human plasma. Arteries from late pregnant (LP) animals were then perfused similarly to evaluate a potential adaptive effect of pregnancy on vessel function. A 3-hour exposure to pregnant plasma caused increased myogenic reactivity and tone in vessels from NP animals and produced a decreased endothelium-derived hyperpolarizing factor response in NP PCAs, findings that were not seen with MAs. The increased reactivity and tone noted in NP vessels was abolished when pregnant plasma was perfused through LP arteries, suggesting these vessels adapt during pregnancy to the vasoconstricting influence of pregnant plasma.

Optimal growth modeling.

Abnormal fetal growth is associated with preterm birth, stillbirth, neonatal death, respiratory distress syndrome, and necrotizing enterocolitis. An optimal fetal growth standard would be one that most correctly identifies the fetus at risk for poor perinatal outcome. A growth standard that is created using population-specific data is more applicable than generalized growth curves since there is evidence that optimal neonatal outcome is achieved at different birth weights in different populations. The development of fetal growth standards based exclusively on neonatal birth weights is flawed as fetal growth restriction is associated with preterm delivery. Likewise, employing clinically derived ultrasound standards for term gestations would include a population that is more likely to have abnormal growth. Novel approaches to defining normal intrauterine growth combine birth weights at term and fetal growth patterns in-utero to create growth curves useful in defining the normal intrauterine growth experience. This review examines the performance of a variety of the growth characterizing standards that have been employed to define abnormal growth and examines their performance in the prediction of adverse perinatal outcome.

Effects of maternal tobacco-smoke exposure on fetal growth and neonatal size.

Exposure to tobacco smoke, through both active and passive measures, has a significant impact on women's health, including effects on the cardiovascular, pulmonary and reproductive systems. Of particular interest is the effect of smoking on pregnancy outcomes. One crucial outcome that has been linked to the subsequent development of both neonatal and adult disease is intrauterine or fetal growth restriction. In this article, we will summarize the effects of smoking on newborn size and fetal growth. We will review evidence showing that tobacco consumption during pregnancy leads to a reduction in birthweight, largely through affecting specific anthropometric measures and newborn body composition. We will highlight the role of genetic susceptibility to these effects and discuss how smoking cessation prior to the third trimester results in a reduction in the risk of fetal growth restriction.