Jeanne S. Sheffield

Ocular effects of Zika virus—a review

Zika virus was considered an innocent pathogen while restricted to the African and Asian population; however, after reaching the Americas in March 2015, it became a global threat. Despite usually causing mild or no symptoms in infected adults, Zika virus displays a different behavior toward fetuses. When infected during gestation, fetuses have their immature neural cells killed by the virus and consequently have devastating findings at birth. In the past year the drastic effects of Zika virus infection in newborns include neurological, ophthalmological, audiological, and skeletal abnormalities. These findings represent a new entity called congenital Zika syndrome. We summarize the ocular findings of congenital Zika Syndrome, as well as the current understanding of the illness, systemic manifestations, laboratory investigation, differential diagnosis, prophylaxis, and treatment for this disorder.

Association of a Best-Practice Alert and Prenatal Administration With Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination Rates.

OBJECTIVE: To evaluate how implementation of a best-practice alert, a reminder of clinical guidelines within the electronic medical record, in combination with the recommended change in immunization timing from postpartum to antepartum, affected tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) rates, and to examine the association of vaccination with local pertussis attack rates. METHODS: A Tdap best-practice alert was introduced into the electronic prenatal charting system in June 2013. The best-practice alert was designed to appear starting at 32 weeks of gestation and to reappear at every subsequent encounter until vaccine acceptance was recorded or delivery occurred. The overall acceptance rate was then compared with postpartum vaccination rates at our institution from the previous year. Records of pertussis cases in children younger than 2 years of age diagnosed since 2012 in Dallas County were also reviewed to correlate local trends with vaccination efforts. RESULTS: Of the 10,201 women offered Tdap during prenatal care, 9,879 (96.8%) ultimately accepted. This is compared with a 48% (5,064 of 10,600) Tdap postpartum immunization rate in the year prior, before introduction of the best-practice alert. The incidence of pertussis among neonates born to mothers who received prenatal care at Parkland Hospital showed a nonsignificant decline from 13 cases per 10,000 deliveries (19 of 14,834, 95% confidence interval [CI] 7–19) between January 2012 and May 2013 to seven per 10,000 deliveries during the study period (eight of 11,788, 95% CI 2–11, P=.174). CONCLUSION: The use of a best-practice alert, in concert with the recommended change in timing of maternal vaccination from postpartum to antepartum, was associated with an increase in the Tdap immunization rate to 97%. LEVEL OF EVIDENCE: II

Maternal Titers After Adequate Syphilotherapy During Pregnancy

BACKGROUND We aimed to construct a timeline for nontreponemal titer decline specific to pregnancy and evaluate factors associated with inadequate decline by delivery. METHODS This was a retrospective medical records review from September 1984 to June 2011 of women diagnosed with syphilis after 18 weeks of gestation. Women were treated according to stage of syphilis per Centers for Disease Control and Prevention guidelines. Patients with both pretreatment and delivery titers were included for data analysis. Demographics, stage of syphilis, maternal titers, delivery, and infant outcomes were recorded. Standard statistical analyses were performed for categorical and continuous data. The titer decline was analyzed using mixed-effects regression modeling. RESULTS A total of 166 patients met inclusion criteria. Mean gestational age at treatment was 29.1 ± 5 weeks, and 93 (56%) women were diagnosed with early-stage syphilis. For all stages of syphilis, maternal titers declined after syphilotherapy. Pretreatment titers were higher and declined more rapidly in primary and secondary disease than in latent-stage disease and syphilis of unknown duration. Sixty-three (38%) patients achieved a 4-fold decline by delivery. Patients without a 4-fold decline by delivery were older (24.6 vs 21.5 years; P < .001), treated later in pregnancy (30.3 vs 27.3 weeks; P < .001), diagnosed with latent syphilis or syphilis of unknown duration, and had less time from treatment to delivery (7.8 vs 11.1 weeks; P < .001). CONCLUSIONS Maternal serologic response during pregnancy after adequate syphilotherapy varied by stage of disease. Failure to achieve a 4-fold decline in titers by delivery is more a reflection of treatment timing than of treatment failure.

Update on syphilis and pregnancy

While the origins of syphilis remain unknown, it has long been recognized as an infectious entity with complex pathophysiology. In this review, we highlighted the epidemiology and risk factors associated with syphilis. The incidence of syphilis in most populations showed a consistent upward trend until the 1940s with the introduction of penicillin as the preferred treatment. The emergence of congenital syphilis and vertical transmission has been a direct result of heterosexual syphilis transmission. We also explore the microbiology and pathogenesis of Treponema pallidum as it directly correlates with its route of transmission and infectivity. The clinical features are best categorized into stages (primary, secondary, early, and late latent and tertiary). The primary stage presents as a characteristic chancre and inguinal adenopathy, while the secondary “bacteremia” stage has a predilection to dermatologic manifestations and constitutional symptoms. The latent phase of syphilis witnesses a quiescent period with variable relapse of symptoms and finally, one‐third of untreated patients undergo tertiary syphilis years after the initial infection characterized by severe neurologic or cardiovascular symptomatology. We will also review the data collected for congenital syphilis from the CDC as this can manifest with stillbirth, neonatal death, and nonimmune hydrops. The diagnosis of syphilis focuses on a combination of nontreponemal and treponemal antibody tests with the CDC recommending a traditional algorithm from screening to confirmation. However, other agencies have recently adopted the reverse testing algorithm which has outperformed the traditional algorithm in certain populations. We finally focus on syphilotherapy and monitoring response to treatment with a specific emphasis on pregnancy. Birth Defects Research 109:347–352, 2017.

Pharmacokinetics of amlodipine besylate at delivery and during lactation

BACKGROUND Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. OBJECTIVE To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. STUDY DESIGN This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24-48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. RESULTS Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL. CONCLUSIONS Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24-48 h of life indicating that it is likely safe to use during the peripartum period.

Asymptomatic pregnant women returning to the United States from countries experiencing a Zika virus outbreak should be tested for Zika virus: FOR: Importance of identification in ALL pregnant women

FOR: Importance of identification in ALL pregnant women JEANNE S SHEFFIELD, DIRECTOR OF MATERNAL-FETAL MEDICINE, JOHNS HOPKINS MEDICINE, BALTIMORE, MD, USA ....................................................................................................................................................................... The Zika virus is a mosquito-borne flavivirus closely related to yellow fever and dengue viruses. It was first identified in 1947 in rhesus monkeys and subsequently noted to cause mild disease in humans throughout Africa and Asia. It was not until May 2015 that local transmission of the virus in the Americas was reported in Brazil. This virus has now spread throughout South and Central America and the Caribbean following the global distribution of the Aedes aegypti mosquito, with 41 countries and territories reporting active local transmission. Although the continental USA has not identified a case of local transmission, there are now > 350 confirmed travel-related Zika cases, a number of these being pregnant women.

Hepatitis C and Pregnancy

Hepatitis C virus (HCV) is one of the leading causes of liver disease, affecting 130–150 million people worldwide (World Health Organization. Media Centre. Hepatitis C. Fact Sheet, 2016). The virus causes chronic liver disease in 70–85% of persons infected with HCV with associated sequelae such as cirrhosis, liver cancer, and death. While the most common cause of transmission is injection drug use with shared needles, HCV can be transmitted from an infected mother to her fetus. Close follow-up is critical for the HCV-exposed infant, as approximately 5% of exposed infants will become infected. The focus of this chapter is to review hepatitis C in pregnancy and its implications for the neonate.

Hepatitis B in the Perinatal Period

Chronic hepatitis B virus (HBV) is a significant threat to public health, with an estimated 240 million people living with the disease worldwide (http://www.who.int/mediacentre/factsheets/fs204/en/). HBV and the associated complications, such as cirrhosis and hepatocellular carcinoma, cause >600,000 deaths yearly (GBD 2013 Mortality and Causes of Death Collaborators, Lancet 385:117–71, 2015). Since the development of the HBV vaccine in the 1980s, new cases have decreased, yet the disease remains a global health concern, especially due to high rates of mother-to-child transmission (MTCT) in many countries (http://www.who.int/mediacentre/factsheets/fs204/en/). The focus of this chapter is to explore the current management of hepatitis B in pregnancy, with an emphasis on treatment and prevention of transmission to the neonate.

SMFM Special Report: Putting the “M” back in MFM: Addressing education about disparities in maternal outcomes and care

At the 36th Annual meeting of the Society for Maternal-Fetal Medicine (SMFM), leaders in the field of maternal-fetal medicine (MFM) convened to address maternal outcome and care inequities from 3 perspectives: (1) education, (2) clinical care, and (3) research. Meeting attendees identified knowledge gaps regarding disparities within the provider community; reviewed possible frameworks to address these knowledge gaps; and identified models with which to address key clinical issues. Collaboration and communication between all stakeholders will be needed to gain a better understanding of these prevailing disparities and formulate strategies to eliminate them.