Kristina Adachi

Risk Factors Associated With Infant Deaths From Pertussis: A Case-Control Study

BACKGROUND In the current era, most pertussis deaths occur in infants <3 months of age. Leukocytosis with lymphocytosis and pneumonia are commonly observed among cases of severe pertussis. METHODS Risk factors associated with fatal pertussis were identified by comparing fatal pertussis cases among patients <120 days of age occurring from 1 January 1998 through 26 December 2014, matched by age (<120 days), county of residence, and closest symptom onset date with 1-4 nonfatal hospitalized cases. California Department of Public Health surveillance data were reviewed to identify cases; demographics, clinical presentation, and course were abstracted from corresponding birth and medical records. Logistic regression and classification tree analyses were used to examine the risk of fatal pertussis with respect to identified factors. RESULTS Fifty-three fatal infant pertussis cases were identified and compared with 183 nonfatal hospitalized pertussis cases. Fatal cases had significantly lower birth weight, younger gestational age, younger age at time of cough onset, and higher peak white blood cell (WBC) and lymphocyte counts. Fatal cases were less likely to have received macrolide antibiotics and more likely to have received steroids or nitric oxide and to develop pulmonary hypertension, seizures, encephalitis, and pneumonia. Additionally, exchange transfusion, extracorporeal membrane oxygenation, and intubation occurred significantly more frequently among fatal cases. In multivariate analyses, peak WBC count, birth weight, intubation, and receipt of nitric oxide were predictors of death. CONCLUSIONS Early recognition of pertussis in young infants and treatment with appropriate antibiotic therapy are important in preventing death. Several risk factors are strongly associated with fatal pertussis in infants.

Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission.

Background Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. Methodology Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. Results Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9–2.3; P = 0.09). Conclusions This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.

Chlamydia trachomatis Infection in Pregnancy: The Global Challenge of Preventing Adverse Pregnancy and Infant Outcomes in Sub-Saharan Africa and Asia

Screening and treatment of sexually transmitted infections (STIs) in pregnancy represents an overlooked opportunity to improve the health outcomes of women and infants worldwide. Although Chlamydia trachomatis is the most common treatable bacterial STI, few countries have routine pregnancy screening and treatment programs. We reviewed the current literature surrounding Chlamydia trachomatis in pregnancy, particularly focusing on countries in sub-Saharan Africa and Asia. We discuss possible chlamydial adverse pregnancy and infant health outcomes (miscarriage, stillbirth, ectopic pregnancy, preterm birth, neonatal conjunctivitis, neonatal pneumonia, and other potential effects including HIV perinatal transmission) and review studies of chlamydial screening and treatment in pregnancy, while simultaneously highlighting research from resource-limited countries in sub-Saharan Africa and Asia.

Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies and their Relationship to Birth Outcomes

Background Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. Methods A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. Results 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). Conclusions Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies.

Screening Criteria for Ophthalmic Manifestations of Congenital Zika Virus Infection

Importance Current guidelines recommend screening eye examinations for infants with microcephaly or laboratory-confirmed Zika virus infection but not for all infants potentially exposed to Zika virus in utero. Objective To evaluate eye findings in a cohort of infants whose mothers had polymerase chain reaction–confirmed Zika virus infection during pregnancy. Design, Setting, and Participants In this descriptive case series performed from January 2 through October 30, 2016, infants were examined from birth to 1 year of age by a multidisciplinary medical team, including a pediatric ophthalmologist, from Fernandes Figueira Institute, a Ministry of Health referral center for high-risk pregnancies and infectious diseases in children in Rio de Janeiro, Brazil. Participants Mother-infant pairs from Rio de Janeiro, Brazil, who presented with suspected Zika virus infection during pregnancy were referred to our institution and had serum, urine, amniotic fluid, or placenta samples tested by real-time polymerase chain reaction for Zika virus. Main Outcomes and Measures Description of eye findings, presence of microcephaly or other central nervous system abnormalities, and timing of infection in infants with confirmed Zika virus during pregnancy. Eye abnormalities were correlated with central nervous system findings, microcephaly, and the timing of maternal infection. Results Of the 112 with polymerase chain reaction–confirmed Zika virus infection in maternal specimens, 24 infants (21.4%) examined had eye abnormalities (median age at first eye examination, 31 days; range, 0-305 days). Ten infants (41.7%) with eye abnormalities did not have microcephaly, and 8 (33.3%) did not have any central nervous system findings. Fourteen infants with eye abnormalities (58.3%) were born to women infected in the first trimester, 8 (33.3%) in the second trimester, and 2 (8.3%) in the third trimester. Optic nerve and retinal abnormalities were the most frequent findings. Eye abnormalities were statistically associated with microcephaly (odds ratio [OR], 19.1; 95% CI, 6.0-61.0), other central nervous system abnormalities (OR, 4.3; 95% CI, 1.6-11.2), arthrogryposis (OR, 29.0; 95% CI, 3.3-255.8), and maternal trimester of infection (first trimester OR, 5.1; 95% CI, 1.9-13.2; second trimester OR, 0.5; 95% CI, 0.2-1.2; and third trimester OR, 0.3; 95% CI, 0.1-1.2). Conclusions and Relevance Eye abnormalities may be the only initial finding in congenital Zika virus infection. All infants with potential maternal Zika virus exposure at any time during pregnancy should undergo screening eye examinations regardless of the presence or absence of central nervous system abnormalities.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Background: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Methods: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Results: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4–8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03–1.76). Conclusions: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

Frequency of maternal and newborn birth outcomes Lima Peru 2013.

Objective This study describes the pregnancy and birth outcomes at two hospitals in Lima, Peru. The data collection and analysis is intended to inform patients, providers, and policy makers on Peru’s progress toward achieving the Millennium Development Goals and to help set priorities for action and further research. Methods Data were collected retrospectively from a sample of 237 women who delivered between December 2012 and September 2013 at the Instituto Nacional Materno Perinatal or the Hospital Nacional Arzobispo Loayza. The outcomes were recorded by a trained mid-wife through telephone interviews with patients and by review of hospital records. Associations between participant demographic characteristics and pregnancy outcomes were tested with Chi-squared, Fisher’s exact, or Student’s t-test. Results Over 37% of women experienced at least one maternal or perinatal complication, and the most frequent were hypertension/preeclampsia and macrosomia. The women in our sample had a cesarean section rate of 50.2%. Conclusion Maternal and perinatal complications are not uncommon among women in the lower socioeconomic strata of Lima. Also, the high cesarean rate underpins the need for a more comprehensive understanding of the indications for cesarean section deliveries, which could help reduce the number of unnecessary procedures and preventable complications.

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1–3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5–7.7). Individually, maternal CMV (aOR 4.4 1.5–13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2–7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. Trial registration NCT00099359.

Eye Findings in Infants With Suspected or Confirmed Antenatal Zika Virus Exposure.

In this study, we characterize ophthalmic manifestations of antenatal ZIKV exposure in infants who were referred for evaluation during the 2015–2016 Rio de Janeiro outbreak. BrightcoveDefaultPlayer10.1542/6138644049001PEDS-VA_2018-1104 Video Abstract OBJECTIVES: To characterize ophthalmic manifestations of confirmed or suspected antenatal Zika virus (ZIKV) exposure. METHODS: Infants with antenatal ZIKV exposure were referred for evaluation during the 2015–2016 Rio de Janeiro outbreak. Mothers with symptomatic ZIKV infection during pregnancy and/or infants with microcephaly or other findings that were suggestive of suspected antenatal exposure were tested with reverse transcriptase polymerase chain reaction (RT-PCR). Complete eye examinations were performed by pediatric ophthalmologists between January 2016 and February 2017. The main outcome measure was eye abnormalities in RT-PCR–positive and suspected (ie, not tested or RT-PCR–negative) antenatal ZIKV cases. RESULTS: Of 224 infants, 189 had RT-PCR testing performed. Of 189 patients, 156 had positive RT-PCR results in their blood, urine, and/or placenta. Of 224 infants, 90 had central nervous system (CNS) abnormalities, including microcephaly (62 infants). Eye abnormalities were present in 57 of 224 (25.4%) infants. Optic nerve (44 of 57; 77.2%) and retina abnormalities (37 of 57; 64.9%) were the most common. The group with suspected ZIKV infection (68 infants) had proportionally more eye (36.8% vs 20.5%; P = .022) and CNS abnormalities (68.3% vs 28.1%; P = .008), likely because of referral patterns. Eye abnormalities consistent with ZIKV infection were clinically comparable in both RT-PCR–positive and unconfirmed groups, including 4 RT-PCR–positive infants of 5 without any CNS abnormalities. CONCLUSIONS: Similar eye manifestations were identified regardless of laboratory confirmation. Well-appearing infants were also found to have eye abnormalities. Therefore, all infants born after ZIKV outbreaks should be universally screened for eye abnormalities.

Zika clinical updates: implications for pediatrics

Purpose of review Zika virus (ZIKV), a mosquito-borne flavivirus, has gained recognition over the past few years as an important new cause of congenital infection. As a result, it is critical that pediatricians understand its epidemiology, clinical presentation, clinical sequelae, and management. Recent findings The recent ZIKV epidemiology, clinical presentation of acute infection in children and complications, perinatal infection, and congenital infection will be summarized in this ZIKV review. This will be followed by a brief summary on ZIKV diagnosis, management, treatment, and prevention. Summary The field of clinical research in ZIKV has rapidly evolved over recent months. It is critical that pediatricians continue to stay up-to-date with the continuously evolving understanding of the clinical aspects of ZIKV to ensure optimal identification and management of affected infants and children. Given the recent changes in Centers for Disease Control and Prevention guidelines to limit screening of asymptomatic pregnant women in the United States with possible ZIKV exposure, comprehensive ZIKV clinical knowledge becomes even more crucial.