Objective To develop and test markers of neonatal severe morbidity for the identification of neonatal near-miss cases.Design This is a database analysis of two World Health Organization cross-sectional studies: the Global Survey on Maternal and Perinatal Health (WHOGS) and the Multicountry Survey on Maternal and Newborn Health (WHOMCS).Setting The WHOGS was performed in 373 health facilities in 24 countries (2004)(2005)(2006)(2007)(2008). The WHOMCS was conducted in 359 health facilities in 29 countries (2010)(2011).Population Data were collected from hospital records of all women admitted for delivery and their respective neonates.Methods Pragmatic markers (birthweight <1750 g, Apgar score at 5 minutes <7, and gestational age <33 weeks) were developed with WHOGS data and validated with WHOMCS data. The diagnostic accuracy of neonatal characteristics and management markers of severity was determined in the WHOMCS.Results This analysis included 290 610 liveborn neonates from WHOGS and 310 436 liveborn neonates from WHOMCS. The diagnostic accuracy of pragmatic and management markers of severity for identifying early neonatal deaths was very high: sensitivity, 92.8% (95% CI 91.8-93.7%); specificity, 92.7% (95% CI 92.6-92.8%); positive likelihood ratio, 12.7 (95% CI 12.5-12.9); negative likelihood ratio, 0.08 (95% CI 0.07-0.09); diagnostic odds ratio, 163.4 (95% CI 141.6-188.4). A positive association was found between the frequency of neonatal near-miss cases and Human Development Index.Conclusion Newborn infants presenting selected markers of severity and surviving the first neonatal week could be considered as neonatal near-miss cases. This definition and criteria may be seen as a basis for future applications of the near-miss concept in neonatal health. These tools can be used to inform policy makers on how best to apply scarce resources for improving the quality of care and reducing neonatal mortality.Keywords Early neonatal death, neonatal morbidity assessment, neonatal near-miss criteria, perinatal care assessment, quality of care.

Background The natural history of congenital CMV infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated birth prevalence, clinical findings at birth, and hearing outcome in infected children from such a population. Methods Infants consecutively born were screened for the presence of CMV in urine and/or saliva within the first two weeks. Neonatal clinical findings were recorded and infected children were tested to document hearing function during follow-up. A subset of mothers of infected infants was prenatally tested for the presence of anti-CMV IgG antibodies. Results Congenital CMV infection was confirmed in 87/8047 infants (1.08%; 95%CI: 0.86–1.33). Seven (8.1%; 95%CI: 3.3–15.9) infants had at least one clinical finding suggestive of CMV infection and 4 (4.6%; CI95%: 1.3–11.3) had ≥ 3 findings of systemic disease. Sensorineural hearing loss was found in 5/58 (8.6%; CI95%: 2.9–19.0) children tested at a median age of 21 months. Bilateral profound hearing loss was observed in two children and hearing threshold was >60 dBHL in all five children with hearing loss, including two children born to mothers with probable non primary CMV infection. Conclusions The results of this first large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates with a similar incidence of CMV-related hearing loss to that reported in offspring of women from populations in the developed countries with lower rates of seroimmunity to CMV.

Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ∼25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts.human cytomegalovirus | HCMV | congenital CMV | virology | evolution

Background The burden of CMV-associated sensorineural hearing loss (SNHL) in populations with CMV seroprevalence approaching 100% is unknown. The purpose of this study was to assess the rate, associated factors and predictors of SNHL in CMV-infected infants identified by newborn screening in a highly seropositive maternal population. Methods Newborns with positive saliva CMV-DNA and confirmed by virus isolation in the first two weeks of life were enrolled in a prospective follow-up study to monitor hearing outcome. Results Of 12,195 infants screened, 121 (1%) were CMV-infected and 12 (10%) had symptomatic infection at birth. Hearing function could be assessed in 102/121 children who underwent at least one ABR testing at a median age of 12 months. SNHL was observed in 10/102 (9.8%; 95%CI: 5.1–16.7) children. Median age at the latest hearing evaluation was 47 months (12 to 84 months). Profound loss (>90dB) was found in 4/5 children with bilateral SNHL while all 5 children with unilateral loss had moderate to severe deficit. The presence of symptomatic infection at birth (OR 38.1; 95%CI: 1.6– 916.7) was independently associated with SNHL after adjusting for IUGR, gestational age, gravidity and maternal age. Among 10 infants with SNHL, six (60%) were born to mothers with non-primary CMV infection. Conclusions Even in populations with near universal immunity to CMV, congenital CMV infection is a significant cause of SNHL demonstrating the importance of CMV as a major cause of SNHL in children worldwide. As in other populations, SNHL is more frequently observed in symptomatic CMV infection.

Background The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. Methods Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. Results A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan–Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intra-partum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P = 0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P = 0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P = 0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). Conclusions In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

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Close monitoring of HIV-1-exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.