Preterm birth is a dire complication of pregnancy that poses huge long-term medical and financial burdens for affected children, their families, and the health care system. The aim of the present study was to identify characteristics associated with preterm births at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria from 2011 to 2013. We obtained Information from 5,561 maternal, fetal/neonatal and obstetric records from the labor ward. We excluded delivery at less than 22 weeks (0.25%), post-term birth at ≥42 weeks gestation (1.3%), and unknown gestation (1.4%). Additionally, we excluded records of multiple births (5.4%) and stillbirths (8.3%) leaving 4,691 records of singleton live-births for analysis. Logistic regression analysis was performed comparing preterm birth (22-36 weeks gestation) to term birth (37-41 weeks gestation). Multiple variable models adjusting for maternal age, parity, fetal position, delivery method and booking status were also evaluated. Multinomial regression was used to identify characteristics associated with preterm birth (PTB) defined as early PTB (22-31 weeks gestation), moderate PTB (32-34 weeks gestation), late PTB (35-36 weeks gestation), compared to term birth (37-41 completed weeks gestation). From our data, 16.8% of the singleton live-birth deliveries were preterm (<37 weeks gestation). Of these, 4.7% were early (22-31 weeks), 4.5% were moderate (32-34 weeks) and 7.7% were late (35-36) PTBs. Older maternal age (≥35 years) [odds ratio (OR) = 1.41], hypertension (OR = 3.44) and rupture of membranes (OR = 4.03) were significantly associated with increased odds of PTB. Women being treated for the prevention of mother-to-child transmission of HIV were at a significantly decreased risk for PTB (OR = 0.70). Sixteen percent of women in this cohort were not registered for antenatal care in LUTH. These non-registered subjects had significantly greater odds of all categories of PTB, including early (odds ratio (OR) = 20.8), moderate (OR = 8.68), and late (OR = 2.15). PTB and risks for PTB remain high in Nigeria. We recommend that any high risk pregnancy should be referred to a tertiary center for prenatal care in order to significantly reduce adverse birth outcomes such as PTBs.

Orofacial clefts are the most common malformations of the head and neck. In Africa, orofacial clefts are underascertained, with little or no surveillance system in most parts for clefts and other birth defects. A Nigerian craniofacial anomalies study, NigeriaCRAN, was established in 2006 to support cleft research specifically for epidemiological studies, treatment outcomes, and studies into etiology and prevention. We pooled data from seven of the largest Smile Train treatment centers in the six geopolitical zones in Nigeria. Data from September 2006 to June 2011 were analyzed and clefts compared between sides and genders using the Fisher exact test. A total of 2197 cases were identified during the study period, with an estimated prevalence rate of 0.5 per 1000. Of the total number of orofacial clefts, 54.4% occur in males and 45.6% in females. There was a significant difference ( P=.0001) between unilateral left clefts and unilateral right clefts, and there was a significant difference ( P=.0001) between bilateral clefts and clefts on either the left or right side. A significant gender difference ( P=.03) was also observed for cleft palate, with more females than males. A total of 103 (4.7%) associated anomalies were identified. There were nine syndromic cleft cases, and 10.4% of the total number of individuals with clefts have an affected relative. The significant difference between unilateral clefts and the gender differences in the proportion of cleft palate only are consistent with the literature. The present study emphasizes the need for birth defects registries in developing countries in order to estimate the exact prevalence of birth defects including orofacial clefts.

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10⁻³), 8q24 (rs987525, P = 1.22 × 10⁻³), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

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 theACTL6A, ARHGAP10, MINK1, TMEM5andTTNgenes; as well as missense variants inACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63,andTULP4. 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.