Damaging Mutations in AFDN Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate.

Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts.We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P case-parent African trios to identify pathogenic variants that contribute to the risk of clefting. We replicated this analysis using whole-exome sequence data from a Brazilian nsCL ± P cohort. Computational analyses were then used to predict the mechanism by which these variants could result in increased risks for nsCL ± P.We discovered damaging mutations within the AFDN gene, a cell adhesion molecule (CAMs) that was previously shown to contribute to cleft palate in mice. These mutations include p.Met1164Ile, p.Thr453Asn, p.Pro1638Ala, p.Arg669Gln, p.Ala1717Val, and p.Arg1596His. We also discovered a novel splicing p.Leu1588Leu mutation in this protein. Computational analysis suggests that these amino acid changes affect the interactions with other cleft-associated genes including nectins (PVRL1, PVRL2, PVRL3, and PVRL4) CDH1, CTNNA1, and CTNND1.This is the first report on the contribution of AFDN to the risk for nsCL ± P in humans. AFDN encodes AFADIN, an important CAM that forms calcium-independent complexes with nectins 1 and 4 (encoded by the genes PVRL1 and PVRL4). This discovery shows the power of NGS analysis of multiethnic cleft samples in combination with a computational approach in the understanding of the pathogenesis of nsCL ± P.

Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Perspectives on Resuscitation Decisions at the Margin of Viability among Specialist Newborn Care Providers in Ghana and Ethiopia: A Qualitative Analysis.

BACKGROUND: In high income countries, guidelines exist recommending gestational age thresholds for offering and obligating neonatal resuscitation for extremely preterm infants. In low- and middle- income countries, this approach may be impractical due to limited/inconsistent resource availability and challenges in gestational dating. Scant literature exists on how clinicians in these settings conceptualize viability or make resuscitation decisions for premature infants. METHODS: Qualitative interviews of interprofessional neonatal clinicians were conducted in Kumasi, Ghana, at Komfo Anokye Teaching Hospital and Suntreso Government Hospital, and in Addis Ababa, Ethiopia, at St. Paul's Hospital Millennium Medical College. Transcribed interviews were coded through the constant comparative method. RESULTS: Three discrete major themes were identified. The principal theme was a respect for all life, regardless of the likelihood for survival. This sense of duty arose from a duty to God, a duty to the patient, and a duty intrinsic to one's role as a medical provider. The duty to resuscitate was balanced by the second major theme, an acceptance of futility for many premature infants. Lack of resources, inappropriate staffing, and historically high local neonatal mortality rates were often described. The third theme was a desire to meet global standards of newborn care, including having resources to adopt the 22-25-week thresholds used in high income countries and being able to consistently provide life-saving measures to premature infants. CONCLUSIONS: Neonatal clinicians in Ghana and Ethiopia described respect for all life and desire to meet global standards of newborn care, balanced with an awareness of futility based on local resource limitations. In both countries, clinicians highlighted how wide variations in regional survival outcomes limited their ability to rely on structured resuscitation guidelines based on gestational age and/or birthweight.

Congenital complete arhinia with alobar holoprosencephaly.

Congenital arhinia is a life-threatening, rare craniofacial disorder, which, when not identified and managed early can cause severe respiratory distress at birth due to upper airway obstruction. Since neonates are obligate nasal breathers, simultaneous sucking and breathing requirement in neonates with arhinia leads to respiratory distress. Inspiration and expiration through the oral passage alone may result in thoracic retraction, thereby further exacerbating respiratory distress. We report a rare case of congenital complete arhinia with alobar holoprosencephaly in a 9-month-old. With no family history of congenital malformations, maternal risk factors and uneventful pregnancy, a term female neonate was delivered vaginally without immediate post-delivery respiratory distress. Examination revealed microcephaly, absent fontanelles, fused cranial sutures and bilateral microphthalmia. Breathing was spontaneous, with no immediate signs of respiratory distress. An additional diagnosis of alobar holoprosencephaly was made after a head computed tomography (CT) scan was done. Management included the initial stabilisation phase of supplemental oxygen and an orogastric tube for feeding. The baby did not require both tracheostomy and gastrostomy tubes, as she was not in severe respiratory distress requiring a tracheostomy tube nor having difficulties feeding with the orogastric tube.

Timing of initiation of breastfeeding and its determinants at a tertiary hospital in Ghana: a cross-sectional study.

BACKGROUND: Early initiation of breastfeeding (EIBF), breastfeeding within first hour after birth, is known to have major benefits for both the mother and newborn. EIBF rates, however, tends to vary between and within countries. This study set out to determine the prevalence of EIBF at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, and to evaluate the determinants of EIBF and time to initiation of breastfeeding. METHODS: A cross-sectional study was conducted at the KATH postnatal wards between August and October 2014. Three hundred and eighty-two mothers delivering at KATH were recruited and data on time to initiation of breastfeeding, antenatal, delivery and immediate postnatal periods were collected. Data analyses using both binary and ordinal logistic regressions with stepwise elimination were used to determine the relationship between EIBF and time to initiation of breastfeeding on one side, and the maternal, pregnancy, delivery and neonatal associated factors. RESULTS: EIBF was done in 39.4% (95%CI: 34.3-44.5) of the newborns with breastfeeding initiated between 1 to 6 h for 19.7%, 6 to 11 h in 4.8%, 11 to 16 h in 4.8% and after 16 h in 28.5% of the deliveries. A higher number of antenatal care visits (AOR = 1.14, 95%CI: 1.04-1.25, p = 0.006), delivery by caesarean section (AOR = 0.07, 95%CI: 0.01-0.79, p = 0.031) and infant rooming-in with mother (AOR: 31.67, 95%CI: 5.59-179.43, p <  0.001) were significantly and independently associated with EIBF. Factors independently associated with longer time to initiation of breastfeeding were older maternal age (AOR = 1.04, 95%CI: 1.00-1.09, p = 0.039), Akan ethnicity (AOR = 1.92, 95%CI: 1.14-3.22, p = 0.014), first-born child (AOR = 2.06, 95%CI: 1.18-3.58, p = 0.011), mother rooming-in with newborn (AOR = 0.01. 95%CI: 0.00-0.02, p <  0.001), increasing fifth minute APGAR score (AOR = 0.73, 95%CI: 0.58-0.93, p = 0.010) and using prelacteals (AOR = 2.42, 95%CI: 1.34-4.40, p = 0.004). CONCLUSIONS: The low EIBF rate and prolonged time to initiation of breastfeeding at a major tertiary health facility is a major concern. Key interventions will need to be implemented at KATH and possibly other tertiary healthcare facilities in Ghana and beyond to improve EIBF rate and time to breastfeeding.

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

BACKGROUND: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain. METHODS: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life. RESULTS: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care. CONCLUSIONS: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).

Provider perspectives on Asram in Ghana.

Neonatal mortality is one of the leading causes of under-five mortality globally, with the majority of these deaths occurring in low- and middle-income countries. In Ghana, there is a belief in an array of newborn conditions, called Asram, that are thought to have a spiritual, rather than physical, cause. These conditions are predominantly managed by traditional healers as they are considered unable to be treated by allopathic medical providers. Through a series of semi-structured qualitative interviews of medical providers in Kumasi, Ghana, conducted in July-August 2018, this study sought to elucidate perspectives of allopathic medical providers about Asram, including the perceived implications of traditional newborn care patterns on newborn health and higher-level neonatal care. Twenty health care providers participated and represented a tertiary care hospital and a district hospital. Medical providers were universally aware of Asram but varied on the latitude they gave this belief system within the arena of newborn care. Some providers rationalized the existence of Asram in the backdrop of high neonatal mortality rates and long-standing belief systems. Others highlighted their frustration with Asram, citing delays in care and complications due to traditional medical treatments. Providers utilized varying approaches to bridge culture gaps with families in their care and emphasized the importance of open communication with the shared goal of improved newborn health and survival. This study describes the importance of providers being aware of socio-cultural constructs within which pregnant women operate and suggests a focus on the shared goal of timely and effective newborn care in Ghana.

Small and sick newborn care during the COVID-19 pandemic: global survey and thematic analysis of healthcare providers' voices and experiences.

INTRODUCTION: The COVID-19 pandemic is disrupting health systems globally. Maternity care disruptions have been surveyed, but not those related to vulnerable small newborns. We aimed to survey reported disruptions to small and sick newborn care worldwide and undertake thematic analysis of healthcare providers' experiences and proposed mitigation strategies. METHODS: Using a widely disseminated online survey in three languages, we reached out to neonatal healthcare providers. We collected data on COVID-19 preparedness, effects on health personnel and on newborn care services, including kangaroo mother care (KMC), as well as disruptors and solutions. RESULTS: We analysed 1120 responses from 62 countries, mainly low and middle-income countries (LMICs). Preparedness for COVID-19 was suboptimal in terms of guidelines and availability of personal protective equipment. One-third reported routine testing of all pregnant women, but 13% had no testing capacity at all. More than 85% of health personnel feared for their own health and 89% had increased stress. Newborn care practices were disrupted both due to reduced care-seeking and a compromised workforce. More than half reported that evidence-based interventions such as KMC were discontinued or discouraged. Separation of the mother-baby dyad was reported for both COVID-positive mothers (50%) and those with unknown status (16%). Follow-up care was disrupted primarily due to families' fear of visiting hospitals (~73%). CONCLUSION: Newborn care providers are stressed and there is lack clarity and guidelines regarding care of small newborns during the pandemic. There is an urgent need to protect life-saving interventions, such as KMC, threatened by the pandemic, and to be ready to recover and build back better.

Co-occurrence of orofacial clefts and clubfoot phenotypes in a sub-Saharan African cohort: Whole-exome sequencing implicates multiple syndromes and genes.

BACKGROUND: Orofacial clefts (OFCs) are congenital malformations of the face and palate, with an incidence of 1 per 700 live births. Clubfoot or congenital talipes equinovarus (CTEV) is a three-dimensional abnormality of the leg, ankle, and feet that leads to the anomalous positioning of foot and ankle joints and has an incidence of 1 per 1000 live births. OFCs and CTEV may occur together or separately in certain genetic syndromes in addition to other congenital abnormalities. Here, we sought to decipher the genetic etiology of OFC and CTEV that occurred together in six probands. METHODS: At the time of recruitment, the most clinically obvious congenital anomalies in these individuals were the OFC and CTEV. We carried out whole-exome sequencing (WES) on DNA samples from probands and available parents employing the Agilent SureSelect XT kit and Illumina HiSeq2500 platform, followed by bioinformatics analyses. WES variants were validated by clinical Sanger Sequencing. RESULTS: Of the six probands, we observed probable pathogenic genetic variants in four. In three probands with probable pathogenic genetic variants, each individual had variants in three different genes, whereas one proband had probable pathogenic variant in just one gene. In one proband, we observed variants in DIS3L2, a gene associated with Perlman syndrome. A second proband had variants in EPG5 (associated with Vici Syndrome), BARX1 and MKI67, while another proband had potentially etiologic variants in FRAS1 (associated with Fraser Syndrome 1), TCOF1 (associated with Treacher Collins Syndrome 1) and MKI67. The last proband had variants in FRAS1, PRDM16 (associated with Cardiomyopathy, dilated, 1LL/Left ventricular noncompaction 8) and CHD7 (associated with CHARGE syndrome/Hypogonadotropic hypogonadism 5 with or without anosmia). CONCLUSION: Our results suggest that clubfoot and OFCs are two congenital abnormalities that can co-occur in certain individuals with varying genetic causes and expressivity, warranting the need for deep phenotyping.

Neonatal near-misses in Ghana: a prospective, observational, multi-center study.

BACKGROUND: For every newborn who dies within the first month, as many as eight more suffer life-threatening complications but survive (termed 'neonatal near-misses' (NNM)). However, there is no universally agreed-upon definition or assessment tool for NNM. This study sought to describe the development of the Neonatal Near-Miss Assessment Tool (NNMAT) for low-resource settings, as well as findings when implemented in Ghana. METHODS: This prospective, observational study was conducted at two tertiary care hospitals in southern Ghana from April - July 2015. Newborns with evidence of complications and those admitted to the NICUs were screened for inclusion using the NNMAT. Incidence of suspected NNM at enrollment and confirmed near-miss (surviving to 28 days) was determined and compared against institutional neonatal mortality rates. Suspected NNM cases were compared with newborns not classified as a suspected near-miss, and all were followed to 28 days to determine odds of survival. Confirmed near-misses were those identified as suspected near-misses at enrollment who survived to 28 days. The main outcome measures were incidence of NNM, NNM:mortality ratio, and factors associated with NNM classification. RESULTS: Out of 394 newborns with complications, 341 (86.5%) were initially classified as suspected near-misses at enrollment using the NNMAT, with 53 (13.4%) being classified as a non-near-miss. At 28-day follow-up, 68 (17%) had died, 52 (13%) were classified as a non-near-miss, and 274 were considered confirmed near-misses. Those newborns with complications who were classified as suspected near-misses using the NNMAT at enrollment had 12 times the odds of dying before 28 days than those classified as non-near-misses. While most confirmed near-misses qualified as NNM via intervention-based criteria, nearly two-thirds qualified based on two or more of the four NNMAT categories. When disaggregated, the most predictive elements of the NNMAT were gestational age < 33 weeks, neurologic dysfunction, respiratory dysfunction, and hemoglobin < 10 gd/dl. The ratio of near-misses to deaths was 0.55: 1, yet this varied across the study sites. CONCLUSIONS: This research suggests that the NNMAT is an effective tool for assessing neonatal near-misses in low-resource settings. We believe this approach has significant systems-level, continuous quality improvement, clinical and policy-level implications.

A randomized crossover trial comparing the Nifty cup to a medicine cup in preterm infants who have difficulty breastfeeding at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana.

INTRODUCTION: Preterm infants make up the majority of the 9 million babies born in Africa and South Asia requiring supplemental feedings as they transition to exclusive breastfeeding. The World Health Organization recommends the use of a cup to feed newborns with breastfeeding difficulties in low-resource settings. We set out to evaluate the Nifty cup, a new feeding cup designed specifically for infants with breastfeeding difficulties. MATERIALS AND METHODS: We conducted a randomized clinical trial in Ghana. We hypothesized infants would prefer the Nifty cup and that it would have less spillage as compared to a medicine cup. We enrolled mothers and preterm infants with breastfeeding difficulties indicated to cup feed at Komfo Anokye Teaching Hospital. Each mother-infant pair used the Nifty cup and a standard medicine cup; and two feeding assessments with each cup were conducted. We employed an intent-to-treat analysis comparing cup preference using a Wilcoxon signed rank test and spillage using generalized estimating equations. RESULTS: We enrolled 200 mothers and 237 infants. Many infants were very low birth weight (62%), less than two weeks old (62%), and multiple birth (29%). In response to separate questions about each cup, more mothers reported liking the Nifty cup a lot as compared to the medicine cup (85% versus 57%, p<0.001). When asked to choose between the two cups, more than 75% preferred the Nifty cup (p < 0.001). There was slightly less spillage with the Nifty cup (8.9%) versus the medicine cup (9.3%), which was not statistically significant (p = 0.35). Mothers reported greater confidence and ease of using the Nifty cup and greater use one-month post-discharge compared to the medicine cup (p-values <0.001). Nearly all mothers were breastfeeding and cup feeding their infants at study initiation and at one-month post-discharge. DISCUSSION: This is the first randomized clinical trial of cup feeding in sub-Saharan Africa. Mothers prefer the Nifty cup to a medicine cup for supplemental feeds to their preterm infant. The Nifty cup was used with greater ease and confidence. The Nifty cup can offer an improved feeding experience for the mother-infant pair.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts.

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. METHODS: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. RESULTS: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. CONCLUSION: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.

Pilot testing of the Becoming Breastfeeding Friendly toolbox in Ghana.

BACKGROUND: Ghana has achieved significant progress in breastfeeding practices in the past two decades. Further progress is, however, limited by insufficient government funding and declining donor support for breastfeeding programs. The current study pretested feasibility of the Becoming Breastfeeding Friendly (BBF) toolbox in Ghana, to assess the existing enabling environment and gaps for scaling-up effective actions. METHODS: Between June 2016 and April 2017, a 15-person expert country committee drawn from government and non-government agencies was established to implement the BBF toolbox. The committee used the BBF index (BBFI), comprising of 54 benchmarks and eight gears of the Breastfeeding Gear Model (advocacy; political will; legislation and policy; funding and resources; training and program delivery; promotion; research and evaluation; and coordination, goals and monitoring). Available evidence (document reviews, and key informant interviews) was used to arrive at consensus-scoring of benchmarks. Benchmark scores ranged between 0 (no progress) and 3 (major progress). Scores for each gear were averaged to estimate the Gear Total Score (GTS), ranging from 0 (least) to 3.0 (strong). GTS's were aggregated as a weighted average to estimate the BBFI which ranged from 0 (weak) to 3.0 (outstanding). Gaps in policy and program implementation and recommendations were proposed for decision-making. RESULTS: The BBFI score was 2.0, indicating a moderate scaling-up environment for breastfeeding in Ghana. Four gears recorded strong gear strength: advocacy (2.3); political will (2.3); legislation and policy (2.3); and coordination, goals and monitoring (2.7). The remaining four gears had moderate gear strength: funding and resources (1.3); training and program delivery (1.9); promotion (2.0); and research and evaluation (1.3). Key policy and program gaps identified by the committee included sub-optimal coordination across partners, inadequate coverage and quality of services, insufficient government funding, sub-optimal enforcement of policies, and inadequate monitoring of existing initiatives. Prioritized recommendations from the process were: 1) strengthen advocacy and empower breastfeeding champions, 2) strengthen breastfeeding regulations, including maternity protection, 3) strengthen capacity for providing breastfeeding services, and 4) expand and sustain breastfeeding awareness initiatives. CONCLUSIONS: The moderate environment for scaling-up breastfeeding in Ghana can be further strengthened by addressing identified gaps in policy and programs.

"We call them miracle babies": How health care providers understand neonatal near-misses at three teaching hospitals in Ghana.

Neonatal mortality is a significant problem in many low-resource countries, yet for every death there are many more newborns who suffer a life-threatening complication but survive. These "near-misses" are not well defined, nor are they well understood. This study sought to explore how health care providers at three tertiary care centers in Ghana (each with neonatal intensive care units (NICUs)) understand the term "near-miss." Eighteen providers from the NICUs at three teaching hospitals in Ghana (Korle Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and Cape Coast Teaching Hospital in Cape Coast) were interviewed in depth regarding their perceptions of neonatal morbidity, mortality, and survival. Near the end of the interview, they were specifically asked what they understood the term "near-miss" to mean. Participants included nurses and physicians at various levels and with varying years of practice (mean years of practice = 9.33, mean years in NICU = 3.66). Results indicate that the concept of "near-misses" is not universally understood, and providers differ on whether a baby is a near-miss or not. Providers disagreed on the utility of a near-miss classification for clinical practice, with some suggesting it would be helpful to draw their attention to those at highest risk of dying, with others suggesting that the acuity of illness in a NICU means any baby could become a 'near-miss' at any moment. Further efforts are needed to standardize the definitions of neonatal near-misses, including developing criteria that are able to be assessed in a low-resource setting. In addition, further research is warranted to determine the practical implications of using a near miss tool in the process of providing care in a resource-limited setting and whether it might be best reserved as a retrospective indicator of overall quality of care provided.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

OBJECTIVE: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. PATIENTS AND METHOD: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. RESULTS: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. CONCLUSION: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africa.

BACKGROUND: Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. METHODS: We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5' and 3' untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. RESULTS: We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175-2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. CONCLUSIONS: This study demonstrates that exons 4 and 7 of IRF6 are mutational 'hotspots' in our cohort and that IRF6 mutants-induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high-risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms.

Assessment of prison life of persons with disability in Ghana.

BACKGROUND: Persons with Disabilities (PWDs) are a unique group that are often overlooked in many developing countries due to systemic weaknesses, lack of political commitment and inadequate support from government and non-governmental agencies. The population of these individuals is however steadily on the increase and currently corresponds to 15 % of the world population. Although much data exist on lifestyle and conditions of prisoners with disabilities in the western world, scanty information is available in Africa. In Ghana, there is insufficient data on the occurrence and social characteristics of prisoners with disabilities. The purpose of this current study was therefore to identify the occurrence, types and causes of disabilities among prisoners serving sentences in Ghanaian prisons. METHODS: This study was a descriptive cross-sectional survey conducted in the Male and Female Regional Prisons in Kumasi, Sunyani and the Nsawam Medium Security Prison, from November to December 2011. PWDs were selected by prisons officers and interviewed using structured questionnaires on variables such as socio-demographic characteristics, causes of disabilities and accessibility to recreational facilities. Ethical approval was obtained from the security services and the Committee of Human Research Publications and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology (KNUST). RESULTS: We screened 6114 records of prisoners of which 1852 (30.3 %) were from the Kumasi Central Prisons, 3483 (57 %) from the Nsawam Medium Security and 779 (12.8 %) from the Sunyani Central Prisons. A total of 99 PWDs were identified with the commonest disability being physical, followed by visual, hearing, speech, mental and albinism. Most of the disabilities were caused by trauma (68.8 %) followed by infection (16.7 %), and drug related mental disabilities (6.3 %). Fifty (50.5 %) out of the 99 PWDs were not provided with assistive devices although they admitted the need for such. CONCLUSION: The present study has demonstrated the occurrence and conditions of PWDs in Ghanaian prisons. Major stakeholders including government agencies and other organisations could develop policies that would improve the conditions and livelihood of prisoners with disabilities in Ghana.

Perception and practice of Kangaroo Mother Care after discharge from hospital in Kumasi, Ghana: a longitudinal study.

BACKGROUND: The practice of Kangaroo Mother Care (KMC) is life saving in babies weighing less than 2000 g. Little is known about mothers' continued unsupervised practice after discharge from hospitals. This study aimed to evaluate its in-hospital and continued practice in the community among mothers of low birth weight (LBW) infants discharged from two hospitals in Kumasi, Ghana. METHODS: A longitudinal study of 202 mothers and their inpatient LBW neonates was conducted from November 2009 to May 2010. Mothers were interviewed at recruitment to ascertain their knowledge of KMC, and then oriented on its practice. After discharge, the mothers reported at weekly intervals for four follow up visits where data about their perceptions, attitudes and practices of KMC were recorded. A repeated measure logistic regression analysis was done to assess variability in the binary responses at the various reviews visits. RESULTS: At recruitment 23 (11.4%, 95%CI: 7.4 to 16.6%) mothers knew about KMC. At discharge 95.5% were willing to continue KMC at home with 93.1% willing to practice at night. 95.5% thought KMC was beneficial to them and 96.0% beneficial to their babies. 98.0% would recommend KMC to other mothers with 71.8% willing to practice KMC outdoors.At first follow up visit 99.5% (181) were still practicing either intermittent or continuous KMC. This proportion did not change significantly over the four weeks (OR: 1.4, 95%CI: 0.6 to 3.3, p-value: 0.333). Over the four weeks, increasingly more mothers practiced KMC at night (OR: 1.7, 95%CI: 1.2 to 2.6, p = 0.005), outside their homes (OR: 2.4, 95%CI: 1.7 to 3.3, p < 0.001) and received spousal help (OR: 1.6, 95%CI: 1.1 to 2.4, p = 0.007). Household chores and potentially negative community perceptions of KMC did not affect its practice with odds of 0.8 (95%CI: 0.5 to 1.2, p = 0.282) and 1.0 (95%CI: 0.6 to 1.7, p = 0.934) respectively. During the follow-up period the neonates gained 23.7 sg (95%CI: 22.6 g to 24.7 g) per day. CONCLUSION: Maternal knowledge of KMC was low at outset. Once initiated mothers continued practicing KMC in hospital and at home with their infants gaining optimal weight. Continued KMC practice was not affected by perceived community attitudes.

Komfo Anokye Teaching Hospital Multidisciplinary Cleft Clinic.

BACKGROUND: A retrospective review of cleft lip and palate surgeries at our hospital during 2001-2005 showed an increase in patients treated per year. The aim of the study was to review the activities of the clinic, hence to determine the variation in number of cleft lip and palate cases and surgeries from 2006 to 2009, and also to identify the commonest type of cleft cases during the same period. METHODS: Data for this retrospective study were obtained from the outpatient department records of the cleft clinic and operating theater. Information collected included demographic features of the patients, types of cleft lip/palate, number of attendance, and surgeries performed. The data were then analyzed using SPSS version 12.0. RESULTS: A total of 528 patients were operated on for cleft lip/and palate (ie, 132 surgeries per year). Most patients (54.2%, n=286) were boys. The age of the patients ranged from 1 to 25 months, with a mean age of 3.7 months. There was also an increase in cleft lip surgeries from 2006 to 2009, whereas cleft palate surgeries decreased toward the year 2009. In terms of types, cleft lip (73.1%, n=386) outnumbered cleft palate. Also, unilateral clefts (70.5%, n=372), in terms of position, were the majority. CONCLUSIONS: The number of cleft surgeries was found to increase per year, and unilateral cleft lip was identified as the commonest type of cleft cases. Financial, logistic, and training support to cleft clinics in developing countries would play an essential role in the treatment of cleft patients.