Delivery Outcomes of Patients with Acute Migraine in Pregnancy: A Retrospective Study.

OBJECTIVE: To describe labor and delivery outcomes in pregnant patients presenting to the hospital setting with an acute severe migraine headache attack earlier in the same gestation. METHODS: We retrospectively reviewed pregnancy and delivery records from a database of consecutive inpatient neurology consultations for acute headache in pregnant women over a 5 year period. RESULTS: We identified 86 pregnant women with acute migraine. The mean age was 29.3 (±6.4) years. Nearly half had migraine with aura (35/86 [40.7%]), 12.8% (12/86) had chronic migraine, and 31.4% (27/86) presented in status migrainosus. Complication rates included 54.7%([41/75], 95% CI 29.87, 52.13) for at least one adverse outcome, 28.0% ([21/75], 95% CI 11.78, 30.22) for preterm delivery, 21.3% ([16/75], 95% CI 7.7, 24.3) for preeclampsia, 30.6% ([23/75] 95% CI 13.48, 32.52) for cesarean delivery, and 18.7% ([14/75] 95% CI 6.15, 21.85) for low birthweight. CONCLUSIONS: Pregnant women seeking treatment for acute migraine headache experienced a higher rate of preterm delivery, preeclampsia, and low birthweight but a lower rate of cesarean delivery than the local and general populations. More than half (54.7% [41/75] 95% CI 29.87, 52.13) of the study patients experienced some type of adverse birth outcome, suggesting that pregnancies in migraine patients presenting to an acute care setting may benefit from more intense surveillance.

A Pregnant Adolescent with COVID-19 and Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C), a new condition related to coronavirus disease 2019 (COVID-19) in the pediatric population, was recognized by physicians in the United Kingdom in April 2020. Given those up to the age of 21 years can be affected, pregnant adolescents and young adults are susceptible. However, there is scant information on how MIS-C may affect pregnancy and whether the presentation differs in the pregnant population. We report a case of a pregnant adolescent with COVID-19 and MIS-C with a favorable outcome. This case highlights the considerations in managing a critically ill pregnant patient with a novel illness and the importance of a multidisciplinary team in coordinating care.

Arachnoid cysts: using prenatal imaging and need for pediatric neurosurgical intervention to better understand their natural history and prognosis.

OBJECTIVES: Intracranial arachnoid cysts are commonly characterized as congenital. Evidence to support a congenital origin is scant and documented evolution during infancy also calls into question the genesis of these lesions. To improve our understanding of the natural history and the clinical significance of arachnoid cysts on prenatal ultrasound, we conducted a study to describe the fate of these cysts after initial diagnosis. METHODS: We conducted a retrospective descriptive review of all prenatal ultrasounds with reported intracranial arachnoid cysts at a tertiary care center from 2010 to 2016 and cohort study comparing patients with additional ultrasound abnormalities to those with an isolated finding of arachnoid cyst. Data collected included gestational age at cyst diagnosis, cyst evolution on follow-up imaging, cyst size and cyst location, postnatal imaging and neurosurgical consultation and intervention. Statistical analysis including Chi-square and Fisher's exact tests and univariate logistic regressions were performed using Stata v. 13 (StataCorp 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP). Confidence intervals were reported at 95% and a p-value < .05 was considered significant. RESULTS: A total of 33,621 anatomical ultrasound scans were performed from 2010 to 2016. Seventy patients (0.2%) had prenatal findings of arachnoid cyst, of which the mean gestational age was 21.46 weeks. Ventriculomegaly was observed in one patient (1.4%) at the time of diagnosis and other abnormalities were found in twelve patients (17%). Complete sonographic follow-up prior to delivery was obtained in 53 (75.7%) patients with 5(9.4%) progression, 5(9.4%) regression, and 43(81.1%) no longer visualized. Forty-three cysts (81.1%) were no longer visualized on follow-up imaging, all of which were interhemispheric in location. All of the cysts that progressed in size on prenatal ultrasounds were > 2 cm in size on initial diagnosis. Cyst fenestration was performed in two patients (2.9%) that had arachnoid cysts measuring at least 3 cm in each dimension on prenatal imaging, one at eight months and one at six months of age. Patients with and without additional sonographic abnormalities had similar rates of AMA (23.1% vs 26.3%, p = .56), nulliparity (61.5% vs 70.2%, p = .38), obesity (0.0% vs 12.3%, p = .221), major medical comorbidities (38.5% vs 33.3%, p = .48) and pregnancy achieved via Assisted Reproductive Technology (38.5% vs 24.6%, p = .25), respectively. Patients with additional sonographic abnormalities were significantly more likely to have prenatal Magnetic Resonance Imaging (OR: 8.28, CI: 1.84-40.4, p = .07), prenatal neurosurgery consultation (OR: 8.25, CI: 1.23-69.05, p = .04) and invasive diagnostic genetic testing (OR: 11.25, CI: 2.33-64.35, p = .003). CONCLUSIONS: Arachnoid cysts are infrequently found on prenatal screening. Size greater than 2 cm on second trimester ultrasound and location outside of the interhemispheric fissure may indicate the need for further evaluation and eventual fenestration. Prenatally diagnosed arachnoid cysts are not typically associated with other anatomic or genetic abnormalities, although the presence of additional abnormalities usually leads to more intensive prenatal and postnatal investigations.

Association of SARS-CoV-2 placental histopathology findings with maternal-fetal comorbidities and severity of COVID-19 hypoxia.

OBJECTIVE: SARS-CoV-2 is known to impact multiple organ systems, with growing data to suggest the potential for placental infection and resultant pathology. Understanding how maternal COVID-19 disease can affect placental histopathology has been limited by small study cohorts with mild disease, review by multiple pathologists, and potential confounding by maternal-fetal comorbidities that can also influence placental findings. This study aims to identify pathologic placental findings associated with COVID-19 disease and severity, as well as to distinguish them from changes related to coexisting maternal-fetal comorbidities. METHODS: This is an observational study of 61 pregnant women with confirmed SARS-CoV-2 infection who delivered and had a placental histological evaluation at NYU Langone Health between March 19, 2020 and June 30, 2020. Primary outcomes were the prevalence of placental histopathologic features and their association with maternal-fetal comorbidities and severity of COVID-19 related hypoxia. Analysis was performed using Fisher's exact test and t-test with p < 0.05 considered significant. RESULTS: Sixty-one placentas were included in the study cohort, 71% from pregnancies complicated by at least one maternal-fetal comorbidity. Twenty-five percent of placentas were small for gestational age and 77% exhibited at least one feature of maternal vascular malperfusion. None of the histopathologic features in the examined placentas were associated with the presence of any specific maternal-fetal comorbidity. Thirteen percent of the cohort required maternal respiratory support for COVID-19 related hypoxia. Villous trophoblast necrosis was associated with maternal supplemental oxygen requirement (67 vs. 33%, p = 0.04) and intubation (67 vs. 33%, p = 0.01). CONCLUSION: In pregnancies complicated by COVID-19 disease, there was a high prevalence of placental histopathologic changes identified, particularly features of maternal vascular malperfusion, which could not be attributed solely to the presence of maternal-fetal comorbidities. The significantly increased prevalence of villous trophoblast necrosis in women needing respiratory support suggests a connection to the severity of COVID-19 illness.

Predictors of severe and critical disease in pregnant women with SARS-CoV-2.

BACKGROUND/OBJECTIVE: SARS-CoV-2 continues to spread widely in the US and worldwide. Pregnant women are more likely to develop severe or critical illness than their non-pregnant counterparts. Known risk factors for severe and critical disease outside of pregnancy, such as asthma, diabetes, and obesity have not been well-studied in pregnancy. We aimed to determine which clinical and pregnancy-related factors were associated with severe and critical COVID illness in pregnancy. STUDY DESIGN: This was a retrospective cohort study of women with confirmed intrauterine pregnancy and positive nasopharyngeal swab for SARS-CoV-2 who presented to an academic medical center in New York City from 1 March 2020 to 1 July 2020. Severe and critical COVID-19 disease was defined by World Health Organization criteria. Women with severe/critical disease were compared to women with asymptomatic/mild disease. Continuous variables were compared with Mann-Whitney or t-test and categorical variables were compared using chi-square and Fisher's exact. Statistical significance was set at p < .05. Multivariable logistic regression was performed including variables that were significantly different between groups. RESULTS: Two hundred and thirty-three patients were included, 186 (79.8%) with asymptomatic/mild disease and 47 (20.2%) with severe/critical disease. Women with asymptomatic/mild disease were compared to those with severe/critical disease. Women with severe/critical disease were more likely to have a history of current or former smoking (19.6 vs. 5.4%, p = .004), COVID-19 diagnosis in the 2nd trimester (42.6 vs. 11.8%, p = .001), and asthma or other respiratory condition (21.3 vs. 7.0%, p = .01). Women with severe/critical disease were more likely to have cesarean delivery (35.5 vs. 15.6%, p < .01) and preterm delivery <37 weeks (25.8 vs. 3.8%, p < .01). After adjustment, history of smoking remained significantly predictive of severe/critical disease [aOR 3.84 (95% CI, 1.25-11.82)]. CONCLUSION: Pregnant women with a history of smoking, asthma, or other respiratory condition, and COVID-19 diagnosis in the second trimester of pregnancy were more likely to develop severe/critical disease. These findings may be useful in counseling women on their individual risk of developing the severe or critical disease in pregnancy and may help determine which women are good candidates for vaccination during pregnancy.

Maternal morbidity of induction of labor compared to planned cesarean delivery in twin gestations.

OBJECTIVE: To compare maternal morbidity associated with induction of labor (IOL) with planned cesarean delivery (CD) in twin gestations. METHODS: This was a retrospective cohort study of vertex-presenting twin pregnancies ≥24-week gestation delivering at our institution from 2016 to 2017. We compared patients undergoing IOL with patients undergoing planned CD. Demographic and pregnancy outcome data were abstracted from the medical record. Our primary outcome was composite maternal morbidity including severe postpartum hemorrhage (PPH) (EBL >1500 cc), hysterectomy, transfusion, ICU admission, use of ≥2 uterotonic medications or maternal death. These morbidities were also assessed independently. Secondary analyses of maternal morbidity among unplanned CD versus planned CD and successful IOL versus planned CD was also performed. Chi-square, Mann-Whitney U and multivariate logistic regression were used in statistical analysis. RESULTS: Of 211 twin gestations included, 70.6% were nulliparous, the median age was 35.5 years [32-38], and the median gestational age at delivery was 37 weeks [35-38]. One hundred and five underwent IOL and 106 had a planned CD. Composite morbidity was higher in the IOL group versus planned CD group (30.5 versus 11.3%, p = .001). In the IOL group, 64 (61.0%) achieved a vaginal delivery. Patients in the planned CD group were more likely to be >35 years of age (62.3 versus 48.6%, p = .045), nulliparous (80.2 versus 61.0%, p = .002) and deliver preterm (53.8 versus 38.1%, p = .022). Patients with a planned CD had a significantly lower risk of composite morbidity compared to those who had CD after failed IOL (11.3 versus 48.8%, p ≤ .001) and there was no significant difference in composite morbidity in the successful IOL compared to the planned CD group (18.8 versus 11.3%, p = .18). There were four peri-partum hysterectomies, all within the IOL group. CONCLUSION: Labor induction in twins was associated with increased maternal morbidity compared to planned CD. The increase in adverse maternal outcomes was due to those who underwent an IOL and ultimately required CD.

Soluble T cell immunoglobulin mucin domain 3 (sTim-3) in maternal sera: a potential contributor to immune regulation during pregnancy.

OBJECTIVE: The immune checkpoint inhibitor, membrane-bound T cell immunoglobulin mucin domain 3 (Tim-3), binds to galectin-9 (gal-9) and promotes immune tolerance during pregnancy. Soluble Tim-3 (sTim-3) competes with Tim-3 for binding to gal-9 and modulates its activity. Our objective was to evaluate the influence of sTim-3 on immune responses and outcome in pregnant women. STUDY DESIGN: Peripheral blood from 71 pregnant women was separated into mononuclear cell (PBMC) and plasma fractions. The PBMCs were lysed and tested for Tim-3 by ELISA. Plasma was assayed for sTim-3, gal-9, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and the stress-inducible 70 kDa heat shock protein (hsp70) by enzyme-linked immunosorbent assay (ELISA). Correlations were analyzed by the Spearman rank correlation test. RESULTS: The higher the sTim-3 level in plasma the lower was the PBMC Tim-3 concentration (p = .0135), suggesting that sTim-3 results from the release of membrane-bound Tim-3. Plasma sTim3 levels were positively correlated with levels of gal-9 (p < .0001), TNF-α (p = .0071) and hsp70 (p = .0144), but not with IL-10. The sTim-3 level was positively associated (p = .0276) with gestational age at delivery. There was no association between sTim-3 and gestational age at sample collection, maternal age, gravidity, parity or body mass index. CONCLUSION: The release of Tim-3 from membranes and sTim-3 reacting with gal-9 may increase proinflammatory immunity and the stress response. The release of sTim-3 from lymphoid cells into the circulation and its binding to gal-9 may modulate Tim-3-mediated activity and help optimize immune regulation during pregnancy.

Abortion for Fetal Genetic Abnormalities: Type of Abnormality and Gestational Age at Diagnosis.

Background Advances in genetic screening can identify patients at high risk for common genetic conditions early in pregnancy and can facilitate early diagnosis and early abortion. Less common abnormalities might only be diagnosed with invasive testing is performed after structural abnormalities are identified. Objective Our objective was to compare gestational age (GA) at diagnosis and abortion for genetic abnormalities identified based on screening with abnormalities that were not discovered after screening. Study Design All prenatal diagnostic procedures from 2012 to 2017 were reviewed, and singleton pregnancies terminated following diagnosis of genetic abnormalities were identified. Cases diagnosed as the result of screening tests were compared with remaining cases. Conditions were considered "screened for" if they can be suspected by cell-free DNA testing, biochemistry, carrier screening, or if the patient was a known carrier of a single-gene disorder. When abnormal karyotype, microarray, or Noonan's syndrome was associated with abnormal NT, these cases were considered "screened for." GA at abortion was the primary outcome. Fisher's exact test and Mann-Whitney's U test were used for statistical comparison. Results In this study, 268 cases were included. A total of 227 (85%) of abortions were performed for "screened for" disorders, with 210 (93%) of these for karyotype abnormalities, 5 (2%) for microarray abnormalities, and 12 (5%) for single-gene disorders. Forty-one (15%) of abortions were performed for conditions not included in screening, with 8 (19%) of those for karyotype abnormalities, 25 (61%) for microarray abnormalities, and 8 (19%) for single-gene disorders. Invasive testing and abortion occurred at earlier median GA for those with conditions that were screened for: 12 2/7 versus 15 5/7 weeks, p ≤0.001 and 13 5/7 versus 20 0/7 weeks; p ≤0.001. Conclusion Most abortions were for abnormalities that can be suspected early in pregnancy. As many structural abnormalities associated with rare conditions are not identifiable until the mid-trimester, prenatal diagnosis and abortion occurred significantly later. Physicians and patients should be aware of the limitations of genetic screening.

Abnormal nuchal translucency: residual risk with normal cell-free DNA screening.

Objective: To determine the proportion of genetic abnormalities that could be identified by cell-free DNA screening in pregnancies with an abnormal nuchal translucency.Methods: From 2015-2017, pregnancies with nuchal translucency ≥ 3.0 mm on ultrasounds were identified. Pregnancies with genetic testing results were included, whether or not cell-free DNA screening was performed. Comparisons of the proportion of genetic abnormalities detectable on cell-free DNA screening versus not detectable were made based on nuchal translucency values (3.0-3.4 mm; ≥3.5 mm) and maternal age (≥35 versus <35 years). Chi-square analysis, Fisher's exact test, and Mann-Whitney U were used for statistical comparison.Results: One hundred ten patients were included, 60 had genetic abnormalities (54.5%), with 44 (73.3%) detectable on cell-free DNA screening and 16 (26.7%) not. In those with nuchal translucency ≥3.5 mm, only 40 of 56 (71.4%) of abnormalities could be detected by cell-free DNA screening. Cell-free DNA screening could identify 27 of 31 abnormalities with nuchal translucency ≥3.5 mm in women ≥35 years but could identify only 13 of 25 genetic abnormalities in younger women (87.1 versus 52.0%; p = .005).Conclusion: A significant proportion of abnormalities in those with nuchal translucency ≥3.5 mm would not be detected by cell-free DNA, especially in younger women.

Isolated acute funisitis in the absence of acute chorioamnionitis: What does it mean?

OBJECTIVE: Acute funisitis (AF) is most commonly associated with acute chorioamnionitis (AC) and ascending infection. The significance of cases of AF without associated AC or isolated funisitis (IF) is unknown. Our objective was to evaluate clinical and pathologic features of IF and to determine its significance. STUDY DESIGN: This was a retrospective review of placentas of patients delivering at our institution from 1997 to 2017. Placentas with the diagnosis of IF comprised the study population and placentas without either AF or AC served as controls. RESULTS: There were 156 cases and 181 controls identified. Maternal age, gestational age, birthweight and mode of delivery were similar in both groups. 132 (84.6%) of cases of IF had meconium, with 62 (47.0%) having meconium only in the membranes, 36 (27.3%) in the membranes and cord and 34 (25.6%) in the membranes and cord with associated myonecrosis. 72 (38.7%) of controls had microscopically identified meconium, with only one (1.4%) showing meconium in the cord. None had myonecrosis (p < .001). There was also a significantly higher rate of intrauterine fetal demise (IUFD) in the IF group (p = .027). but the rate of suspected Intrauterine growth restriction (IUGR) was significantly greater in the controls (p = .014). CONCLUSION: IF is highly associated with the presence of meconium discharge and meconium-associated myonecrosis of umbilical vessels. The inflammation in IF may be the result of damage to the muscle fibers of the cord due to meconium but additional studies are necessary to understand the significance of these findings.

Peripheral nerve blocks in the treatment of migraine in pregnancy.

OBJECTIVE: To describe the use of peripheral nerve blocks in a case series of pregnant women with migraine. METHODS: A retrospective chart review of all pregnant patients treated with peripheral nerve blocks for migraine over a 5-year period was performed. Injections targeted greater occipital, auriculotemporal, supraorbital, and supratrochlear nerves using local anesthetics. RESULTS: Peripheral nerve blocks were performed 27 times in 13 pregnant women either in a single (n=6) or multiple (n=7) injection series. Mean patient age was 28 years and gestational age was 23.5 weeks, and all women had migraine, including 38.5% who had chronic migraine. Peripheral nerve blocks were performed for status migrainosus (51.8%) or short-term prophylaxis of frequent headache attacks (48.1%). Before peripheral nerve blocks were performed, oral medications failed for all patients and intravenous medications failed for most. In patients with status migrainosus, average pain reduction was 4.0 (±2.6 standard deviation) (P<.001) immediately postprocedure and 4.0 (±4.4 standard deviation) (P=.007) 24 hours postprocedure in comparison to preprocedure pain. For patients receiving peripheral nerve blocks for short-term prophylaxis, immediate mean pain score reduction was 3.0 (±2.1 standard deviation). No patients had any serious immediate, procedurally related adverse events, and the two patients who had no acute pain reduction ultimately developed preeclampsia and had postpartum headache resolution. CONCLUSION: Peripheral nerve blocks for treatment-refractory migraine may be an effective therapeutic option in pregnancy.