The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative.

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers.

Studying the Effects of Shoulder Dystocia and Neonate-Focused Delivery Maneuvers on Brachial Plexus Strain: A Computational Study.

The purpose of this computational study was to investigate the effects of neonate-focused clinical delivery maneuvers on brachial plexus (BP) during shoulder dystocia. During shoulder dystocia, the anterior shoulder of the neonate is obstructed behind the symphysis pubis of the maternal pelvis, postdelivery of the neonate's head. This is managed by a series of clinical delivery maneuvers. The goal of this study was to simulate these delivery maneuvers and study their effects on neonatal BP strain. Using madymo models of a maternal pelvis and a 90th-percentile neonate, various delivery maneuvers and positions were simulated including the lithotomy position alone of the maternal pelvis, delivery with the application of various suprapubic pressures (SPPs), neonate in an oblique position, and during posterior arm delivery maneuver. The resulting BP strain (%) along with the required maternal delivery force was reported in these independently simulated scenarios. The lithotomy position alone served as the baseline. Each of the successive maneuvers reported a decrease in the required delivery force and resulting neonatal BP strain. As the applied SPP force increased (three scenarios simulated), the required maternal delivery force and neonatal BP strain decreased. A further decrease in both delivery force and neonatal BP strain was observed in the oblique position, with the lowest delivery force and neonatal BP strain reported during the posterior arm delivery maneuver. Data obtained from the improved computational models in this study enhance our understanding of the effects of clinical maneuvers on neonatal BP strain during complicated birthing scenarios such as shoulder dystocia.

Chronological age enhances aging phenomena and protein nitration in oocyte.

Background: The average age of childbearing has increased over the years contributing to infertility, miscarriages, and chromosomal abnormalities largely invoked by an age-related decline in oocyte quality. In this study, we investigate the role of nitric oxide (NO) insufficiency and protein nitration in oocyte chronological aging. Methods: Mouse oocytes were retrieved from young breeders (YB, 8-14 weeks [w]), retired breeders (RB, 48-52w) and old animals (OA, 80-84w) at 13.5 and 17 hours after ovulation trigger. They were assessed for zona pellucida dissolution time (ZPDT); ooplasmic microtubule dynamics (OMD); cortical granule (CG) status and spindle morphology (SM), as markers of oocyte quality. Sibling oocytes from RB were exposed to NO supplementation and assessed for aging phenomena (AP). All oocyte cumulus complexes were subjected to fluorescence nitrotyrosine (NT) immunocytochemistry and confocal microscopy to assess morphology and protein nitration. Results: At 13.5 h from hCG trigger, oocytes from RB compared to YB had significantly increased ZPDT (37.8 ± 11.9 vs 22.1 ± 4.1 seconds [s]), OMD (46.9 vs 0%), CG loss (39.4 vs 0%), and decreased normal SM (30.3 vs 81.3%), indicating premature AP that worsened among oocytes from RB at 17 hours post-hCG trigger. When exposed to SNAP, RB AP significantly decreased (ZPDT: 35.1 ± 5.5 vs 46.3 ± 8.9s, OMD: 13.3 vs 75.0% and CG loss: 50.0 vs 93.3%) and SM improved (80.0 vs 14.3%). The incidence of NT positivity was significantly higher in cumulus cells (13.5 h, 46.7 ± 4.5 vs 3.4 ± 0.7%; 17 h, 82.2 ± 2.9 vs 23.3 ± 3.6%) and oocytes (13.5 h, 57.1 vs 0%; 17 h, 100.0 vs 55.5%) from RB compared to YB. Oocytes retrieved decreased with advancing age (29.8 ± 4.1 per animal in the YB group compared to 10.2 ± 2.1 in RB and 4.0 ± 1.6 in OA). Oocytes from OA displayed increased ZPDT, major CG loss, increased OMD and spindle abnormalities, as well as pronuclear formation, confirming spontaneous meiosis to interphase transition. Conclusions: Oocytes undergo zona pellucida hardening, altered spindle and ooplasmic microtubules, and premature cortical granule release, indicative of spontaneous meiosis-interphase transition, as a function of chronological aging. These changes are also associated with NO insufficiency and protein nitration and may be alleviated through supplementation with an NO-donor.

A Diagnosis of Maternal 22q Duplication and Mosaic Deletion following Prenatal Cell-Free DNA Screening.

Concurrent microduplication and microdeletion of the chromosome 22q11.2 region are a rarely reported phenomenon. We describe a case of germline 22q11.21 microduplication syndrome with concurrent mosaic 22q11.2 deletion in a pregnant patient, identified by chromosomal microarray and FISH after noninvasive prenatal genetic screening (cfDNA) results discordant with family history. The patient was referred to maternal-fetal medicine (MFM) at 14 weeks' gestation secondary to an SNP-based cfDNA result of a suspected maternal 22q11.2 deletion and a fetal risk of 1 in 2 for 22q11.2 deletion syndrome. The patient reported a similar cfDNA result in a previous pregnancy; however postnatal chromosomal microarray on that child identified an atypical 22q11.21 microduplication. We report the maternal chromosomal microarray findings of a germline 726 kb 22q11.21 duplication and a mosaic 1.33 Mb 22q11.2 deletion and highlight the copy number variant data generated by cfDNA in this unique case. This family adds to the limited literature of concurrent 22q11.2 microduplication and microdeletion carriers.

Prenatal Lethal Diagnosis of 8p23.1 Duplication Syndrome Associated with Omphalocele and Encephalocele.

Despite increased prenatal and postnatal use of array comparative genomic hybridization (aCGH), isolated 8p23.1 duplication remains rare and has been associated with a widely variable phenotype. Here, we report an isolated 8p23.1 duplication in a fetus with an omphalocele and encephalocele that were incompatible with life. Prenatal aCGH demonstrated a 3.75 Mb de novo duplication of 8p23.1. This region encompassed 54 genes, 21 of which are described in OMIM, including SOX7 and GATA4. The summarized case demonstrates phenotypic features not previously described in 8p23.1 duplication syndrome and is reported in order to enhance understanding of the phenotypic variation.

SARS-CoV-2 Seroprevalence in Florida Department of Health in Palm Beach County Obstetric Clinics: A Cross-Sectional Study during the First Pandemic Surge.

OBJECTIVE: Estimating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is an important part of the public health approach to coronavirus disease 2019 (COVID-19) understanding and containment. This is particularly relevant to an obstetric population because of implications in the management of the pregnant host, care of the newborn, and disease progression within the community. STUDY DESIGN: A cross-sectional seroprevalence study was performed in four Department of Health Palm Beach County clinics from June 29, 2020, to August 5, 2020. Samples were collected from asymptomatic antepartum and postpartum participants. A web-based surveillance system was used to identify subsequent antibody or polymerase chain reaction (PCR) testing encounters. RESULTS: A total of 163 of 618 subjects were seropositive (26.4%). Racial makeup was white 2.5%, black 19.0%, and Hispanic 78.5%. Positive serology was seen in 16.0, 35.6, and 30.1% of first, second, and third trimesters, respectively; 18.4% were positive postpartum. Only four patients voluntarily reported PCR positivity prior to antibody testing. Six home zip codes accounted for the majority (68.1%) of positive results. Thirty-two patients had repeat serology (65.6% positive and 34.4% negative). Of the 163 subjects, 65 underwent later PCR testing with 92% negative for SAR-CoV-2. CONCLUSION: Almost one in four subjects had serologic evidence of previous SARS-CoV-2 infection. These very high seroprevalence rates have not been previously reported and highlight the concern for health disparities in the United States. Most were asymptomatic and without a history for SARS-CoV-2 exposure. There was a loss of seropositivity in a significant number of subjects, raising concern for risk of reinfection, inadequate transplacental antibody transfer, and subsequent limited passive protection to the newborn. These seroprevalence data will also allow for better newborn follow-up of unanticipated consequences of COVID-19 infection in pregnancy. KEY POINTS: · SAR-CoV-2 seroprevalence is disproportionately high in this obstetric population. · The majority of subjects who tested positive for SAR-CoV-2 were asymptomatic for COVID-19 infection. · Estimating seroprevalence is an important public health approach to disease surveillance and understanding.

Effects of Prestretch on Neonatal Peripheral Nerve: An In Vitro Study.

Background Characterizing the biomechanical failure responses of neonatal peripheral nerves is critical in understanding stretch-related peripheral nerve injury mechanisms in neonates. Objective This in vitro study investigated the effects of prestretch magnitude and duration on the biomechanical failure behavior of neonatal piglet brachial plexus (BP) and tibial nerves. Methods BP and tibial nerves from 32 neonatal piglets were harvested and prestretched to 0, 10, or 20% strain for 90 or 300 seconds. These prestretched samples were then subjected to tensile loading until failure. Failure stress and strain were calculated from the obtained load-displacement data. Results Prestretch magnitude significantly affected failure stress but not the failure strain. BP nerves prestretched to 10 or 20% strain, exhibiting significantly lower failure stress than those prestretched to 0% strain for both prestretch durations (90 and 300 seconds). Likewise, tibial nerves prestretched to 10 or 20% strain for 300 seconds, exhibiting significantly lower failure stress than the 0% prestretch group. An effect of prestretch duration on failure stress was also observed in the BP nerves when subjected to 20% prestretch strain such that the failure stress was significantly lower for 300 seconds group than 90 seconds group. No significant differences in the failure strains were observed. When comparing BP and tibial nerve failure responses, significantly higher failure stress was reported in tibial nerve prestretched to 20% strain for 300 seconds than BP nerve. Conclusion These data suggest that neonatal peripheral nerves exhibit lower injury thresholds with increasing prestretch magnitude and duration while exhibiting regional differences.

First reported case of pregnancy in a patient with ornithine aminotransferase deficiency.

Ornithine aminotransferase deficiency is a rare autosomalrecessive human inborn error of the metabolism resulting in hyperornithinemia and progressive chorioretinal degeneration (gyrate atrophy) with blindness. There are few reports in the literature and none, to our knowledge, that address this condition during pregnancy. We report on a novel case of ornithine aminotransferase deficiency during pregnancy that was managed actively with arginine and protein restriction with serial amino acid and fetal growth monitoring, resulting in an uncomplicated term live birth.

Seroprevalence of SARS-CoV-2 immunoglobulins in pregnant women and neonatal cord blood from a highly impacted region.

There is inadequate screening for SARS-COV-2 during pregnancy. We aimed to determine the impact of maternal and neonatal cord blood SARS-COV-2 antibodies and placental transfer ratios in a region with a low screening plan. We performed a blind study in one of the SARS-CoV-2 epicenters in South America. 32% of pregnant women were serological positive. Importantly, there is an efficient passive immunization of the fetus to SARS-CoV-2. We report high incidence of SARS-CoV-2 infection during pregnancy, which is higher than officially reported. Therefore the need of active immunization to enhance maternal protection and fetal passive immunization.

In-vitro stress relaxation response of neonatal peripheral nerves.

Characterizing the viscoelastic behavior of neonatal peripheral nerves is critical in understanding stretch-related peripheral nerve injuries (PNIs) in neonates. This study investigated the in-vitro viscoelastic stress relaxation response of neonatal piglet brachial plexus (BP) and tibial nerves at two different strain levels (10% and 20%) and stress relaxation testing durations (90- and 300-seconds). BP and tibial nerves from 20 neonatal piglets were harvested and pre-stretched to either 10% or 20% strain at a dynamic rate of 100 mm/min to simulate conditions, such as shoulder dystocia, that may lead to stretch-related PNIs in neonates. At constant strain, the reduction in stress was recorded for 90- or 300-seconds. The biomechanical data were then fit to a viscoelastic model to acquire the short- and long-term stress relaxation time-constants. Though no significant differences in the degree of stress relaxation were found between the two tested strain levels after 90 seconds in both nerve types, reduction in stress was moderately greater (p = 0.056) at 10% strain than at 20% for BP after 300 seconds. The reduction in stress was significantly higher in nerves subjected to a 300 second testing duration than 90 second for both strain levels and nerve types. When comparing BP and tibial nerve stress relaxation response, BP nerve relaxed significantly more than tibial at both strain levels after 90 seconds, but no significant differences were observed after 300 seconds. Our results confirm that neonatal peripheral nerve tissue is highly viscoelastic. These novel biomechanical data can be incorporated into finite element and computational models studying neonatal PNIs.

Adjustable Algorithmic Tool for Assessing the Effectiveness of Maternal Respiratory Syncytial Virus (RSV) Vaccination on Infant Mortality in Developing Countries.

Acute lower respiratory infection (ALRI) due to RSV is a common cause of global infant mortality, with most cases occurring in developing countries. Using data aggregated from priority countries as designated by the United States Agency for International Development's (USAID) Maternal Child Health and Nutrition (MCHN) program, we created an adjustable algorithmic tool for visualizing the effectiveness of candidate maternal RSV vaccination on infant mortality. Country-specific estimates for disease burden and case fatality rates were computed based on established data. Country-specific RSV-ALRI incidence rates for infants 0-5 months were scaled based on the reported incidence rates for children 0-59 months. Using in-hospital mortality rates and predetermined "inflation factor," we estimated the mortality of infants aged 0-5 months. Given implementation of a candidate maternal vaccination program, estimated reduction in infant RSV-ALRI incidence and mortality rates were calculated. User input is used to determine the coverage of the program and the efficacy of the vaccine. Using the generated algorithm, the overall reduction in infant mortality varied considerably depending on vaccine efficacy and distribution. Given a potential efficacy of 70% and a maternal distribution rate of 50% in every USAID MCHN priority country, annual RSV-ALRI-related infant mortality is estimated to be reduced by 14,862 cases. The absolute country-specific reduction is dependent on the number of live births; countries with the highest birth rates had the greatest impact on annual mortality reduction. The adjustable algorithm provides a standardized analytical tool in the evaluation of candidate maternal RSV vaccines. Ultimately, it can be used to guide public health initiatives, research funding, and policy implementation concerning the effectiveness of potential maternal RSV vaccination on reducing infant mortality.

Varicella zoster meningitis in a pregnant woman with uncontrolled type 1 diabetes mellitus.

We report the case of retrograde varicella zoster virus (VZV) reactivation presenting as aseptic meningitis without rash in a generally healthy pregnant patient. A 27-year-old nulliparous woman at 25 weeks of gestation presented to the emergency department with a 1-day history of severe headache associated with nausea, photophobia and neck stiffness. After ruling out a space-occupying lesion by brain imaging, lumbar puncture was performed. Cerebrospinal fluid analysis by PCR revealed the presence of VZV, making the diagnosis of acute varicella meningitis. The patient had immunoglobulin studies consistent with a history of primary VZV infection, thus confirming reactivation of VZV rather than primary infection. The patient was treated with acyclovir for 14 days and recovered fully. Her neonate was delivered full term without any evidence of vertical transmission. This is only the second reported case of VZV meningitis in a pregnant patient in the medical literature, and the first case in the US that was reported.

Pregnant patient with extranodal CNS Rosai-Dorfman disease with new-onset seizures: the conundrum of differentiating disease progression from eclampsia.

A 31-year-old woman at 30 weeks gestation presented to the emergency department following multiple seizures. Her history was significant for extranodal Rosai-Dorfman Disease (RDD) with central nervous system (CNS) lesions. RDD, a rare form of non-Langerhans cell histiocytosis, commonly presents with non-tender cervical lymphadenopathy. CNS involvement accounts for a small number of cases in those with extranodal disease. Patients with CNS RDD can have a variety of neurological symptoms, including seizures. Eclampsia, a relatively rare obstetric hypertensive disorder, is always within the differential diagnosis for patients presenting with late gestation seizures. We present the challenging evaluation and treatment of a patient whose clinical picture did not clearly differentiate eclampsia from new onset seizures related to progression of her RDD. This conundrum perhaps resulted in unnecessary preterm operative delivery of a critically ill patient. Only follow-up of the patient helped clarify the likely antepartum diagnosis.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Perinatal Oral Health: A Novel Collaborative Initiative to Improve Access, Attitudes, Comfort Level, and Knowledge of Pregnant Women and Dental Providers.

Objectives The objectives of this program were to increase access to dental care among pregnant women and to improve dental students' exposure, comfort level, and knowledge of the potential impact of poor oral health on pregnancy outcomes. Study Design Through collaborative efforts of a School of Dentistry and a School of Medicine, the Oral Health Pregnancy Day Initiative (OHPDI) was developed. Dental students were educated on the impact poor oral health may have on pregnancy outcomes and the importance of access to care. Pregnant women received perinatal oral health education and needed dental care. Results Thirty-four pregnant women presented for the OHPDI. Thirty-nine dental students participated. Eighty-five percent of students reported they learned how poor oral health may have a negative impact on pregnancy and birth outcomes; 79% agreed as a result of the event they were more likely to treat pregnant women. Ninety-four percent of pregnant women reported not having a dentist and 100% received perinatal oral health education and needed dental care. Eighty-eight pregnant women were seen subsequent to the OHPDI. Conclusion This initiative resulted in increased students' knowledge, exposure, and comfort level to treating pregnant women and pregnant women received needed oral health care education and dental treatment.

Adolescence and risk of preterm birth in multifetal gestations.

OBJECTIVE: The objective of this study is to evaluate if adolescence confers additional risk for preterm delivery in multifetal gestations. METHODS: This is a retrospective review of all twin and triplet deliveries from 8/2008 to 12/2012 at two Detroit Hospitals. Outcomes in adolescent mothers aged 19 or younger (n = 59) were compared with adult controls aged 20-34 (n = 350). RESULTS: Mean gestational age at delivery in adolescents was 31.3 (SD: 5.8) weeks versus 34.2 (SD: 4.3) weeks in adults (p < .001). On multivariable analysis, adolescence was associated with preterm delivery (adjusted odds ratio [aOR], 2.3; 95% confidence intervals [95% CI], 1.1-4.7, p = .02) and early-preterm delivery (aOR, 2.2; 95% CI 1.2-4; p = .01). Adjusted rates of preterm and early-preterm delivery were markedly higher in adolescents compared with controls. Being an adolescent was also a significant risk factor for iatrogenic preterm delivery (aOR, 2.4; 95% CI 1.1-5.5; p = .04). CONCLUSIONS: Adolescents pregnant with twins or triplets deliver 3 weeks, on average, before adults and are at markedly increased risk of preterm and early-preterm delivery.

Incarcerated Uterus Presenting as Short Cervix and Placenta Previa.

INTRODUCTION: Incarcerated uterus is a rare complication of pregnancy, usually associated with retroversion. CASE: A 26-year-old woman presents at 19 4/7 weeks for evaluation of a short cervix and placenta previa. On ultrasound scan, the placenta was considered previa and the cervix was not visualized. The cervix was not identified by pelvic examination and the presumptive diagnosis of short cervix was done. The patient was followed up closely and remained asymptomatic. Retrospective analysis of the ultrasound images showed a retroverted uterus with an elongated cervix compressed towards the anterior vaginal wall. At 26 weeks of gestation, ultrasound showed a cervical length of 41 mm and a fundal placenta and the diagnosis of spontaneous correction of an incarcerated uterus was made. The patient had an uncomplicated vaginal delivery at 39 3/7 weeks. COMMENT: Identification and close follow-up of incarcerated uterus may potentially help in avoiding serious obstetrical and surgical complications.

Genomic detection of a familial 382 Kb 6q27 deletion in a fetus with isolated severe ventriculomegaly and her affected mother.

Terminal deletions of the chromosome 6q27 region are rare genomic abnormalities, linked to specific brain malformations and other neurological phenotypes. Reported cases have variable sized genomic deletions that harbor several genes including the DLL1 and TBP. We report on an inherited 0.38 Mb terminal deletion of chromosome 6q27 in a 22-week fetus with isolated bilateral ventriculomegaly and her affected mother using microarray-based comparative genomic hybridization and fluorescent in situ hybridization (FISH). The deleted region harbors at least seven genes including DLL1 and TBP. The affected mother had a history of hydrocephalus, developmental delay, and seizures commonly associated with DLL1 and TBP 6q27 deletions. This deletion is one of the smallest reported isolated 6q27 terminal deletions. Our data provides additional evidence that haploinsufficiency of the DLL1 and TBP genes may be sufficient to cause the ventriculomegaly, seizures, and developmental delays associated with terminal 6q27 deletions, indicating a plausible role in the abnormal development of the central nervous system.