Prenatal cytomegalovirus, rubella, and Zika virus infections associated with developmental disabilities: past, present, and future.

Prenatal infections have long been recognized as important, preventable causes of developmental disabilities. The list of pathogens that are recognized to have deleterious effects on fetal brain development continues to grow, most recently with the association between Zika virus (ZIKV) and microcephaly. To answer clinical questions in real time about the impact of a novel infection on developmental disabilities, an historical framework is key. The lessons learned from three historically important pathogens: rubella, cytomegalovirus, and ZIKV, and how these lessons are useful to approach emerging congenital infections are discussed in this review. Congenital infections are preventable causes of developmental disabilities and several public health approaches may be used to prevent prenatal infection. When they cannot be prevented, the sequelae of prenatal infection may be treatable. WHAT THIS PAPER ADDS: The list of prenatal infections associated with developmental disabilities continues to increase. Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens. Severity of illness in the mother does not correlate with severity of sequelae in the infant.

Zika Virus Epidemic in Pregnant Women, Dominican Republic, 2016-2017.

Zika virus infection during pregnancy may result in birth defects and pregnancy complications. We describe the Zika virus outbreak in pregnant women in the Dominican Republic during 2016-2017. We conducted multinomial logistic regression to identify factors associated with fetal losses and preterm birth. The Ministry of Health identified 1,282 pregnant women with suspected Zika virus infection, a substantial proportion during their first trimester. Fetal loss was reported for ≈10% of the reported pregnancies, and 3 cases of fetal microcephaly were reported. Women infected during the first trimester were more likely to have early fetal loss (adjusted odds ratio 5.9, 95% CI 3.5-10.0). Experiencing fever during infection was associated with increased odds of premature birth (adjusted odds ratio 1.65, 95% CI 1.03-2.65). There was widespread morbidity during the epidemic. Our findings strengthen the evidence for a broad range of adverse pregnancy outcomes resulting from Zika virus infection.

Preventing Sexual Transmission of Zika Virus Infection during Pregnancy, Puerto Rico, USA, 20161.

We examined condom use throughout pregnancy during the Zika outbreak in Puerto Rico during 2016. Overall, <25% of women reported consistent condom use during pregnancy. However, healthcare provider counseling was associated with a 3-fold increase in consistent use, reinforcing the value of provider counseling in Zika prevention efforts.

Group B Streptococcus (GBS) Colonization and Disease among Pregnant Women: A Historical Cohort Study.

Background: Maternal GBS colonization is associated with early-onset neonatal sepsis and extensive efforts are directed to preventing this complication. Less is known about maternal risks of GBS colonization. We seek to provide a modern estimate of the incidence and impact of maternal GBS colonization and invasive GBS disease. Methods: A single center historical cohort study of all births between 2003 and 2015 was performed. Data was collected via electronic health record abstraction using an institutional specific tool. Descriptive statistics were performed regarding GBS status. Inferential statistics were performed comparing risk of adverse pregnancy outcomes in cohorts with and without GBS colonization as well as cohorts with GBS colonization and invasive GBS disease. Results: A total of 60,029 deliveries were included for analysis. Overall, 21.6% of the population was GBS colonized and 0.1% had invasive GBS disease. GBS colonization was associated with younger maternal age, Black race, non-Hispanic ethnicity, chronic hypertension, preexisting diabetes, and tobacco use (p<0.01). In the adjusted analyses, there was an increased risk of gestational diabetes (aRR 1.21, 95% CI 1.11-1.32) in colonized pregnancies and a decreased incidence of short cervix (aRR 0.64, 95% CI 0.52-0.79), chorioamnionitis (aRR 0.76, 95% CI 0.66-0.87), wound infection (aRR 0.75, 95% CI 0.64-0.88), and operative delivery (aRR 0.85, 95% CI 0.83-0.88). Conclusions: This modern-day large cohort of all births over a 12-year period demonstrates a GBS colonization rate of 21.6%. This data reflects a need to assess maternal and perinatal outcomes in addition to neonatal GBS sepsis rates to inform decisions regarding the utility of maternal vaccination.

Two Infants with Presumed Congenital Zika Syndrome, Brownsville, Texas, USA, 2016-2017.

Since 2007, Zika virus has spread through the Pacific Islands and the Americas. Beginning in 2016, women in Brownsville, Texas, USA, were identified as possibly being exposed to Zika virus during pregnancy. We identified 18 pregnant women during 2016-2017 who had supportive serologic or molecular test results indicating Zika virus or flavivirus infection. Two infants were evaluated for congenital Zika syndrome after identification of prenatal microcephaly. Despite standard of care testing of mothers and neonates, comparative results were unreliable for mothers and infants, which highlights the need for clinical and epidemiologic evidence for an accurate diagnosis. A high index of suspicion for congenital Zika syndrome for at-risk populations is useful because of current limitations of testing.

Zika Virus Infection during Pregnancy and Effects on Early Childhood Development, French Polynesia, 2013-2016.

Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.

Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013.

As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin-peginterferon-α therapy.

New York City's innovative epidemiologist: the life and career of Morris Greenberg.

Dr Morris Greenberg was an eminent American epidemiologist who served with the New York City Department of Health for a 40 year period, from 1920 until his passing in 1960. In 1946, he became Director of the department's Bureau of Preventable Diseases. In this role, he set very high standards for outbreak and epidemic investigations joined with a commitment to scholarly research and collaboration with the city's medical centers. He received his medical degree from Columbia University College of Physicians and Surgeons and then interned at Bellevue Hospital in New York City. He later trained in pediatrics in Vienna, Austria and received a Master of Science in Public Health degree from Columbia University School of Public Health. In 1942, he became a member of the teaching staff at the School of Public Health. During his years with the New York City Department of Health he led efforts to control outbreaks of smallpox and rickettsialpox, and initiated important studies of poliomyelitis, hepatitis, trichinosis, congenital cardiac anomalies in children, and the embryopathic effects of rubella in pregnancy. Dr. Greenberg's outbreak and epidemic investigations were popularized by The New Yorker writer, Berton Roueché, whose most widely read book remains, Eleven Blue Men and other Narratives of Medical Detection. The book's title is based on Greenberg's investigation of accidental sodium nitrite poisoning among eleven elderly men in Manhattan who as a result, became cyanotic. A pioneer in epidemiology and the prevention and control of communicable disease, Greenberg established very high performance standards for the discipline before there was a Center for Disease Control and Prevention and an Epidemic Intelligence Service in the United States.

Fatal outbreaks of jaundice in pregnancy and the epidemic history of hepatitis E.

Space-time clustering of people who fall acutely ill with jaundice, then slip into coma and death, is an alarming phenomenon, more markedly so when the victims are mostly or exclusively pregnant. Documentation of the peculiar, fatal predisposition of pregnant women during outbreaks of jaundice identifies hepatitis E and enables construction of its epidemic history. Between the last decade of the 18th century and the early decades of the 20th century, hepatitis E-like outbreaks were reported mainly from Western Europe and several of its colonies. During the latter half of the 20th century, reports of these epidemics, including those that became serologically confirmed as hepatitis E, emanated from, first, the eastern and southern Mediterranean littoral and, thereafter, Southern and Central Asia, Eastern Europe, and the rest of Africa. The dispersal has been accompanied by a trend towards more frequent and larger-scale occurrences. Epidemic and endemic hepatitis E still beset people inhabiting Asia and Africa, especially pregnant women and their fetuses and infants. Their relief necessitates not only accelerated access to potable water and sanitation but also vaccination against hepatitis E.

Standardized treatment and determinants on 9,059 syphilis-infected pregnant women during 2015-2018 in Hunan, China.

This study was aimed to describe the standardized treatment rate of syphilis-infected pregnant women in Hunan province and to explore the determinants for standardized treatment. All syphilis-infected pregnant women registered in the Information System of Prevention of Mother-to-Child Transmission of Syphilis Management (IPMTCT) in Hunan between January 2015 and December 2018 were included in this study. Among 9,059 pregnant women with syphilis, 7,797 received syphilis treatment, with a treatment rate of 86.1%, and 4,963 underwent standardized syphilis treatment, with an average standardized treatment rate of 54.8%. The facilitators for the standardized treatment included abnormal reproductive histories (aOR = 1.15, 95%CI:1.03-1.28), time of first prenatal care within 1-12 weeks (aOR = 5.17, 95%CI:4.19-6.37) or within 13-27 weeks (aOR = 5.56, 95%CI:4.46-6.92), previous syphilis infection (aOR = 1.64, 95%CI: 1.48-1.81), and definite syphilis infection status of sexual partner (negative: aOR = 1.73, 95%CI:1.57-1.91; positive: aOR = 1.62, 95%CI:1.34-1.95). The barriers included marital status being unmarried/divorced/widowed (aOR = 0.81, 95%CI: 0.65-0.99), pluripara (aOR = 0.58, 95%CI: 0.46-0.74), number of children ≥ 2 (aOR = 0.45, 95%CI: 0.35-0.57), and syphilis clinical stage being primary/secondary/tertiary (aOR = 0.72, 95%CI: 0.58-0.88) or unclear (aOR = 0.78, 95%CI: 0.70-0.86). Though the treatment rate of syphilis-infected pregnant women was high, the standardized treatment rate was low. The facilitators and barriers on standardized treatment of gestational syphilis were identified at the patient level.

Birthing life and death: women's reproductive health in early twentieth-century Rio de Janeiro.

This article explores women's reproductive health in early twentieth-century Rio de Janeiro, showing that elevated and sustained stillbirth and maternal mortality rates marked women's reproductive years. Syphilis and obstetric complications during childbirth were the main causes of stillbirths, while puerperal fever led maternal death rates. Utilizing traditional sources such as medical dissertations and lesser-used sources including criminal investigations, this article argues that despite official efforts to medicalize childbirth and increase access to clinical healthcare, no real improvements were made to women's reproductive health in the first half of the twentieth century. This, of course, did not make pregnancy and childbirth any easier for the women who embodied these statistics in their reproductive lives.

The long-run effects of pandemic influenza on the development of children from elite backgrounds: Evidence from industrializing Japan.

This study estimates the lingering effects of fetal exposure to the 1918 influenza pandemic on the development of secondary school and girls' high school students in industrializing Japan. In order to refine the verification of the fetal origins hypothesis, we tried not only to focus on children from elite schools but also to construct the continuous influenza mortality measure using monthly variations in the number of births and influenza deaths. By utilizing a nationwide multidimensional physical examination dataset, we found that fetal exposure to influenza in the pandemic years reduced the heights of boys and girls by approximately 0.3 cm and 0.1 cm, respectively. While the strongest negative magnitude was observed in the pandemic period, the lingering relapses in the post-pandemic period still had considerable adverse effects on height. In relation to the lowest decile group which experienced normal influenza mortality in non-pandemic years, the heights of the boys and girls who experienced pandemic influenza in the womb are approximately 0.6 and 0.3 cm lower. The lingering influenza relapse in the post-pandemic period has an adverse effect on the boys' height, accounting for roughly 80% of the maximum pandemic effect.