Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: the IVHU study.

BACKGROUND: Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage (IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda. METHODS: This is a prospective cohort study of neonates with birthweights of ≤2000 g admitted to a neonatal unit (NU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival. RESULTS: Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) < 32 weeks and resuscitation in the NU increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. CONCLUSION: In this resource limited NU in eastern Uganda, more than a third of neonates born weighing ≤2000 g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation and need for resuscitation after admission to the NU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.

Detection of small for gestational age babies and perinatal outcomes following implementation of the Growth Assessment Protocol at a New Zealand tertiary facility: An observational intervention study.

BACKGROUND: Timely detection of small for gestational age (SGA) fetuses is important for reducing severe perinatal morbidity and mortality, and better tools are needed to detect SGA in maternity care. AIM: We evaluated the effect of the introduction of the Perinatal Institute's Growth Assessment Protocol (GAP) in the Counties Manukau Health region, South Auckland, New Zealand, on antenatal detection of SGA and maternal and perinatal outcomes. MATERIALS AND METHODS: Uncontrolled before and after study in women booked under hospital community midwife care with a singleton, non-anomalous pregnancy. Antenatal detection of SGA (birthweight <10th customised centile) was compared pre-GAP (2012, N = 1105) and post-GAP (2017, N = 1082). Composite adverse neonatal outcome was defined as neonatal unit admission >48 h, five-minute Apgar score <7, and/or any ventilation. Analyses were adjusted for maternal age, body mass index, deprivation, smoking and ethnicity. RESULTS: SGA rates were similar across epochs (13.8% vs 12.9%) but antenatal detection of SGA increased from 22.9% (35/153) to 57.9% (81/140) post-GAP (adjusted odds ratio (aOR) = 4.8, 95% CI 2.82-8.18). Rates of induction of labour and caesarean section increased between epochs but were similar in SGA, non-SGA, and detected and non-detected SGA subgroups. Among SGA babies, there was some evidence that antenatal detection of SGA may be associated with lower composite adverse neonatal outcome (detected SGA: aOR 0.44 95% CI 0.17-1.15; non-detected SGA: aOR = 1.81 95% CI 0.73-4.48; interaction P = 0.03). Pre-term birth did not appear to be influenced by GAP. CONCLUSION: Implementation of GAP was associated with a nearly five-fold increase in SGA detection without increasing obstetric intervention for SGA.

Effects of Maternal Suicidal Ideation on Child Cognitive Development: A Longitudinal Analysis.

This study aimed to assess the association between suicidal ideation among mothers living with HIV in Zimbabwe and the cognitive development of their children. Participants were mother-child dyads recruited from two rural districts in Zimbabwe. Data were collected at baseline and 12 months follow-up. Suicidal ideation was assessed using item-10 from the Edinburgh postnatal depression scale. Mixed-effects linear regression was used to assess the association of child cognitive outcomes at follow-up (using the Mullen scales of early learning) with maternal suicidal ideation. Mothers with suicidal ideation at baseline (n = 171) tended to be younger, unmarried, experienced moderate to severe hunger, had elevated parental stress and depression symptoms compared with non-suicidal mothers (n = 391). At follow-up, emerging maternal suicidal ideation was associated with poorer child cognitive outcomes (adjusted mean difference - 6.1; 95% CI - 10.3 to - 1.8; p = 0.03). Suicidal ideation affects child cognitive development and should be addressed, particularly in HIV positive mothers.

Motor performance and cognitive correlates in children cooled for neonatal encephalopathy without cerebral palsy at school age.

AIM: To investigate whether motor performance in school-age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18-month developmental scores and to explore relationships between school-age motor and cognitive performance. METHODS: Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children-2 (MABC-2) and the Wechsler Intelligence Scale for Children (WISC-IV). Associations between MABC-2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18-month Bayley-III scores and WISC-IV scores were explored. RESULTS: Eleven of the 29 (38%) children had MABC-2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio-economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC-2 scores ≤15th centile. MABC-2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01). CONCLUSION: A third of cooled children without CP had MABC-2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley-III. Most children with low MABC scores needed support at school. Sub-optimal MABC-2 scores indicate need for detailed school-age cognitive evaluation.

Evaluating the effectiveness of a multi-component intervention on early childhood development in paediatric HIV care and treatment programmes: a randomised controlled trial.

BACKGROUND: HIV infection in a family may affect optimum child development. Our hypothesis is that child development outcomes among HIV-exposed infants will be improved through a complex early childhood stimulation (ECS) programme, and income and loans saving programme for HIV positive parents. METHODS: The study was a cluster-randomized controlled trial in 30 clinic sites in two districts in Zimbabwe. Clinics were randomised in a 1:1 allocation ratio to the Child Health Intervention for Development Outcomes (CHIDO) intervention or Ministry of Health standard care. The CHIDO intervention comprises three elements: a group ECS parenting programme, an internal savings and lending scheme (ISALS) and case-management home visits by village health workers. The intervention was aimed at caregiver-child dyads (child aged 0-24 months) where the infant was HIV exposed or infected. The primary outcomes were cognitive development (assessed by the Mullen Scales of Early Learning) and retention of the child in HIV care, at 12 months after enrolment. A comprehensive process evaluation was conducted. DISCUSSION: The results of this cluster-randomised trial will provide important information regarding the effects of multi-component interventions in mitigating developmental delays in HIV-exposed infants living in resource-limited environments. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry ( www.pactr.org ), registration number PACTR201701001387209; the trial was registered on 16th January 2017 (retrospectively registered).

Overlapping HIV and sex-work stigma among female sex workers recruited to 14 respondent-driven sampling surveys across Zimbabwe, 2013.

HIV stigma can inhibit uptake of HIV testing and antiretroviral therapy as well as negatively affect mental health. Efforts to reduce discrimination against people living with HIV (LWH) have contributed to greater acceptance of the infection. Female sex workers (FSW) LWH may experience overlapping stigma due to both their work and HIV status, although this is poorly understood. We examined HIV and sex-work stigma experienced by FSW LWH in Zimbabwe. Using the SAPPH-IRe cluster-randomised trial baseline survey, we analysed the data from 1039 FSW self-reporting HIV. The women were recruited in 14 sites using respondent-driven sampling. We asked five questions to assess internalised and experienced stigma related to working as a sex worker, and the same questions were asked in reference to HIV. Among all FSW, 91% reported some form of sex-work stigma. This was not associated with sociodemographic or sex-work characteristics. Rates of sex-work stigma were higher than those of HIV-related stigma. For example, 38% reported being "talked badly about" for LWH compared with 77% for their involvement in sex work. Those who reported any sex-work stigma also reported experiencing more HIV stigma compared to those who did not report sex-work stigma, suggesting a layering effect. FSW in Zimbabwe experience stigma for their role as "immoral" women and this appears more prevalent than HIV stigma. As HIV stigma attenuates, other forms of social stigma associated with the disease may persist and continue to pose barriers to effective care.

Developmental venous anomaly in the newborn brain.

INTRODUCTION: Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. METHODS: Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. RESULTS: DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. CONCLUSIONS: This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy.

INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy.

Process evaluation of peer-to-peer delivery of HIV self-testing and sexual health information to support HIV prevention among youth in rural KwaZulu-Natal, South Africa: qualitative analysis.

OBJECTIVE: Peer-to-peer (PTP) HIV self-testing (HIVST) distribution models can increase uptake of HIV testing and potentially create demand for HIV treatment and pre-exposure prophylaxis (PrEP). We describe the acceptability and experiences of young women and men participating in a cluster randomised trial of PTP HIVST distribution and antiretroviral/PrEP promotion in rural KwaZulu-Natal. METHODS: Between March and September 2019, 24 pairs of trained peer navigators were randomised to two approaches to distribute HIVST packs (kits+HIV prevention information): incentivised-peer-networks where peer-age friends distributed packs within their social network for a small incentive, or direct distribution where peer navigators distributed HIVST packs directly. Standard-of-care peer navigators distributed information without HIVST kits. For the process evaluation, we conducted semi-structured interviews with purposively sampled young women (n=30) and men (n=15) aged 18-29 years from all arms. Qualitative data were transcribed, translated, coded manually and thematically analysed using an interpretivist approach. RESULTS: Overall, PTP approaches were acceptable and valued by young people. Participants were comfortable sharing sexual health issues they would not share with adults. Coupled with HIVST, peer (friends) support facilitated HIV testing and solidarity for HIV status disclosure and treatment. However, some young people showed limited interest in other sexual health information provided. Some young people were wary of receiving health information from friends perceived as non-professionals while others avoided sharing personal issues with peer navigators from their community. Referral slips and youth-friendly clinics were facilitators to PrEP uptake. Family disapproval, limited information, daily pills and perceived risks were major barriers to PrEP uptake. CONCLUSION: Both professional (peer navigators) and social network (friends) approaches were acceptable methods to receive HIVST and sexual health information. Doubts about the professionalism of friends and overly exclusive focus on HIVST information materials may in part explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

How Can We Support the Use of Oral PrEP Among Young Women who Sell Sex? A PrEP Cascade Analysis.

BACKGROUND: We constructed self-reported pre-exposure prophylaxis (PrEP) cascades and explored factors associated with and barriers to PrEP use to inform efforts to support PrEP use among young women who sell sex. METHODS: Using self-reported data from HIV-negative young women who sell sex enrolled into a cohort study using respondent-driven sampling in Zimbabwe, we constructed PrEP cascades assessing knowledge of, ever offered, ever used, and current PrEP use in 2017 and 2019. We used logistic regression to examine factors associated with PrEP use by 2019. Through qualitative interviews with 43 women enrolled in the cohort, we investigated barriers to PrEP use. RESULTS: At enrollment, 50% of women had heard of PrEP, 12% had ever been offered PrEP, and 7% ever used PrEP. Over time, all cascade domains: 96% of women had heard of and 55% reported an active offer of PrEP. Among women retained in the study in 2019 (56%; n = 538), 34% ever took PrEP by 2019. PrEP use was associated with, at enrollment, reporting more clients in the past month (10+: 45% vs 1-3: 27% adjOR = 1.71 95% CI: 1.06 to 2.76), duration of selling sex (24% <2 years vs 38% 2-3 years; adjOR = 0.51 95% CI: 0.32 to 0.83), and having visited a female sex worker program in the past 12 months (55% vs 27%; adjOR = 2.92 95% CI: 1.91 to 4.46). Qualitative interviews revealed fear of disclosing sex work, HIV-related/ART-related stigma, and (opportunity) costs of accessing PrEP as barriers to use. CONCLUSION: PrEP use was associated with factors known to increase HIV risk. Fear of stigma, disclosure, and supply-side barriers need to be addressed to increase women's ability to use PrEP.

A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm.

Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2years. We acquired magnetic resonance images from 80 preterm infants at term equivalent (mean gestational age 29(+6)weeks) and 20 control infants (mean GA 39(+2)weeks). Diffuse white matter injury was defined by abnormal apparent diffusion coefficient values in one or more white matter region (frontal, central or posterior white matter at the level of the centrum semiovale), and morphological difference between groups was calculated from 3D images using deformation based morphometry. Neurodevelopmental assessments were obtained from preterm infants at a mean chronological age of 27.5months, and from controls at a mean age of 31.1months. We identified a common image phenotype in 66 of 80 preterm infants at term equivalent comprising: diffuse white matter injury; and tissue volume reduction in the dorsomedial nucleus of the thalamus, the globus pallidus, periventricular white matter, the corona radiata and within the central region of the centrum semiovale (t=4.42 p<0.001 false discovery rate corrected). The abnormal image phenotype is associated with reduced median developmental quotient (DQ) at 2years (DQ=92) compared with control infants (DQ=112), p<0.001. These findings indicate that specific neural systems are susceptible to maldevelopment after preterm birth, and suggest that neonatal image phenotype may serve as a useful biomarker for studying mechanisms of injury and the effect of putative therapeutic interventions.

Do behavioural differences help to explain variations in HIV prevalence in adolescents in sub-Saharan Africa?

OBJECTIVE: To compare adolescent risk factors for HIV infection in two countries with high adolescent HIV prevalence and two lower prevalence countries with the aim of identifying risk factors that may help explain differences in adolescent HIV prevalence. METHODS: Data were available from two nationally representative surveys (South Africa, Zimbabwe), two behavioural intervention trials (Tanzania, Zimbabwe) and one population-based cohort (Uganda). Data on variables known or postulated to be risk factors for HIV infection were compared. RESULTS: Few risk behaviours were markedly more common in the high HIV prevalence populations. Risk factors more common in high HIV prevalence settings were genital ulcers and discharge, and women were more likely to report older male partners. DISCUSSION: Age mixing may be an important determinate of HIV prevalence in adolescents. Potential reasons for the general lack of association between other adolescent risk factors and adolescent HIV prevalence include adult HIV prevalence, misreported behaviour, different survey methods and other unmeasured adolescent behaviours. If adult factors dominate adolescent HIV risk, it would help explain the failure of behavioural interventions targeted at adolescents and suggests future interventions should include adults.

Increased risk of HIV-infection among school-attending orphans in rural Zimbabwe.

In Zimbabwe around 1.1 million children have been orphaned due to AIDS. We conducted a survey among school-attending youth in rural south-eastern Zimbabwe in 2003, and examined the association between orphaning and risk of HIV. We enrolled 30 communities in three provinces. All students attending Year 2 of secondary school were eligible. Each completed a questionnaire and provided a finger-prick blood specimen for testing for HIV-1 and HSV-2 antibodies. Female participants were tested for pregnancy. Six thousand seven hundred and ninety-one participants were recruited (87% of eligible); 35% had lost one or both parents (20% of participants had lost their father; 6% their mother; and 9% both parents). Orphans were not poorer than non-orphans based on reported access to income, household structure and ownership of assets. There was strong evidence that orphans, and particularly those who had lost both parents, were at increased sexual risk, being more likely to have experienced early sexual debut; to have been forced to have sex; and less likely to have used condoms. Fifty-one students were HIV positive (0.75%). Orphans were three times more likely to be HIV infected than non-orphans (adjusted odds ratio = 3.4; 95% confidence interval: 1.8-6.6). Over 60% of those HIV positive were orphaned. Among school-going youth, the rates of orphaning were very high; there was a strong association between orphaning and increased risk of HIV, and evidence of greater sexual risk taking among orphans. It is essential that we understand the mechanisms by which orphaned children are at increased risk of HIV in order to target prevention and support appropriately.

Costs and economies of scale in the accelerated program for prevention of mother-to-child transmission of HIV in Zimbabwe.

BACKGROUND: Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis. METHODS: We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy. RESULTS: The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01). CONCLUSIONS: These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.

The burden and determinants of HIV and sexually transmitted infections in a population-based sample of female sex workers in Goa, India.

BACKGROUND: Interventions targeting sex workers are central to the National AIDS Control programme of India's third 5-year plan. Understanding the way in which societal and individual factors interact to shape sex workers' vulnerability would better inform interventions. METHODS: 326 female sex workers, recruited throughout Goa using respondent-driven sampling, completed interviewer-administered questionnaires. Biological samples were tested for Trichomonas vaginalis, Neisseria gonorrhoea, Chlamydia trachomatis and antibodies to herpes simplex virus type 2 (HSV-2) and HIV. Multivariate analysis was used to define the determinants of HIV infection and any bacterial sexually transmitted infection (STI). RESULTS: Infections were common, with 25.7% prevalence of HIV and 22.5% prevalence of bacterial STI; chlamydia 7.3%, gonorrhoea 8.9% and trichomonas 9.4%. Antibodies to HSV-2 were detected in 57.2% of women. STI were independently associated with factors reflecting gender disadvantage and disempowerment, namely young age, lack of schooling, no financial autonomy, deliberate self-harm, sexual abuse and sex work-related factors, such as having regular customers and working on the streets. Other factors associated with STI were Goan ethnicity, not having an intimate partner and being asymptomatic. Having knowledge about HIV and access to free STI services were associated with a lower likelihood of STI. HIV was independently associated with being Hindu, recent migration to Goa, lodge or brothel-based sex work and dysuria. CONCLUSION: Sex workers working in medium prevalence states of India are highly vulnerable to HIV and STI and need to be rapidly incorporated into existing interventions. Structural and gender-based determinants of HIV and STI are integral to HIV prevention strategies.

Transfusional fetal complications after single intrauterine death in monochorionic multiple pregnancy are reduced but not prevented by vascular occlusion.

OBJECTIVE: To document co-twin death/pregnancy loss and brain injury after single intrauterine death (sIUD) in monochorionic pregnancies. DESIGN: A total of 135 pregnancies with sIUD were reviewed for co-twin IUD, miscarriage and abnormal antenatal and postnatal neuro-imaging. SETTING: A tertiary referral fetal medicine unit from 2000 to 2007. POPULATION OR SAMPLE: All cases referred with a single fetal death in monochorionic pregnancy, including those where sIUD was spontaneous or occurred after fetoscopic laser treatment, or resulted from selective termination by cord occlusion with bipolar diathermy or intrafetal vascular ablation with interstitial laser. METHODS: Clinical details and ultrasound findings of the study population were retrieved from ultrasound and institutional databases. Delivery and neonatal outcome data were obtained from discharge summaries supplemented by individual chart review. MAIN OUTCOME MEASURES: Co-twin death or pregnancy loss and neurologic injury assessed on antenatal ultrasound and MR-imaging. RESULTS: A total of 81 sIUDs resulted from vascular occlusive feticide (diathermy or interstitial laser), 22 followed placental laser and 32 were spontaneous. In 22 pregnancies (16.8%), the co-twin died in utero and eight pregnancies miscarried (6.1%). Antenatal magnetic resonance (MR) imaging in 76/91 (83.5%) continuing pregnancies detected antenatal brain injury in five (6.6%). Three infants (two not scanned antenatally) had abnormalities detected postnatally. Brain abnormality was detected less often after procedure related (2.6%, 2/77) than spontaneous sIUD (22.2%, 6/27, P = 0.003) and after early compared with late gestation sIUD (3.6%, 4/111 versus 20.0%, 4/20; P = 0.02). CONCLUSIONS: We confirm substantial co-twin loss (22.9%) after monochorionic sIUD, but a low risk of antenatally acquired MRI-identified brain injury, suggesting this risk has been overestimated. Procedures restricting inter-twin transfusion reduce, but do not negate risk of brain injury.

Cerebellar cleft: confirmation of the neuroimaging pattern.

We recently described the neuroimaging and clinical findings in 6 children with cerebellar clefts and proposed that they result from disruptive changes following prenatal cerebellar hemorrhage. We now report an additional series of 9 patients analyzing the clinical and neuroimaging findings. The clefts were located in the left cerebellar hemisphere in 5 cases, in the right in 3, and bilaterally in one child who had bilateral cerebellar hemorrhages as a preterm infant at 30 weeks gestation. In one patient born at 24 weeks of gestation a unilateral cerebellar hemorrhage has been found at the age of 4 months. Other findings included disordered alignment of the folia and fissures, an irregular gray/white matter junction, and abnormal arborization of the white matter in all cases. Supratentorial abnormalities were found in 4 cases. All but 2 patients were born at term. We confirm the distinct neuroimaging pattern of cerebellar clefts. Considering the documented fetal cerebellar hemorrhage in our first series, we postulate that cerebellar clefts usually represent residual disruptive changes after a prenatal cerebellar hemorrhage. Exceptionally, as now documented in 2 patients, cerebellar clefts can be found after neonatal cerebellar hemorrhages in preterm infants. The short-term outcome in these children was variable.

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.

OBJECTIVES: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers. METHODS: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women. RESULTS: All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced. CONCLUSION: Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

BACKGROUND AND PURPOSE: Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. MATERIALS AND METHODS: Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. RESULTS: A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. CONCLUSIONS: Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.