Antenatal and postnatal diagnoses of visible congenital malformations in a sub-Saharan African setting: a prospective multicenter cohort study

Every year, more than 7.9 million children, or 6% of all neonates worldwide, are born with severe congenital disorders (neural tube defects, heart defects and trisomy 21) [1]. Due to limited antenatal diagnostic tests in sub-Saharan Africa (SSA), visible congenital malformations (VCMs) are easier to diagnose than occult congenital malformations (CMs) [2]. While some VCMs may be fatal due to incompatibility with life, others lead to permanent physical or mental handicaps. Hence, VCMs constitute occupational hazards of significant economic consent to any society. Furthermore, children growing with such handicaps often face psychological trauma due to peer or societal stigmatization [1]. To this end, the importance of antenatal diagnosis of VCMs in SSA, cannot be overemphasized. In high-income countries antenatal diagnosis of CMs is a mandatory follow up during pregnancy and there are a lot of sophisticated diagnostic tests for this purpose. Contrarily, in SSA, these CMs are mostly diagnosed by ultrasound scans done during pregnancy [2]. Though not yet a routine practice in these resource-limited settings, we cannot argue the merits of antenatal diagnosis of CMs, especially VCMs which are easier to diagnose. Thus, we proposed to conduct this study to determine the frequency of antenatal diagnosis of VCMs in a SSA setting.

This prospective multicenter cohort study aimed to determine the incidence of antenatal diagnosis of VCMs in Yaoundé, a resource-limited setting of SSA. We found that the incidence of VCMs was 9 per 1000 births. Among the malformed newborns, 37% were premature and 18.5% were confirmed after a TTP following an antenatal diagnosis of a VCM. The prevalence of sonographic antenatal diagnosis of VCMs was 21% and hydrocephalus was the most diagnosed VCMs. The mean gestational age at which ANCs were initiated was 15 ± 5 weeks.

The overall incidence of VCMs in our study was 9 cases per 1000 births. This incidence is higher than that of the multicenter study carried out in the Democratic Republic of Congo in 2012 which found an incidence of VCMs of 6.7 newborns per 1000 births [4]. We observed the highest frequency (25.9%) of newborns with VCMs at the Gynaeco-Obstetrics and Pediatric Hospital of Yaoundé. This may be due to the fact that it is one of the main referral obstetrics and pediatrics hospital in Yaoundé and its environs. Hence, the Gynaeco-Obstetrics and Pediatric Hospital of Yaoundé is more likely to receive a lot referrals of VCMs detected during pregnancy and after delivery from other less equipped hospitals. This hospital is also more likely to be referred more cases of neonates with VCMs requiring surgical care due to the fact that it has more pediatric surgeons and a better surgical infrastructure for the management of VCMs requiring surgical interventions compared to other hospitals in Yaoundé. Moreover, these results are also certainly influenced by the fact that the obstetrical and pediatric staff of the hospital had recently undertaken a refresher course on the recognition of CMs at birth geared at their timely diagnosis and management.

The most common VCMs were: skeletal (4.3%), neurological (2.2%), and gastrointestinal (2.1%) and urogenital (1.2%) malformations. This order of frequency per system is closed to that found by several authors [5‐7]. Polymalformations were observed in 29.6% of VCMs. This prevalence rate is lower than those observed in Abidjan [8], Paris [9] and Belgium [10] which were 6.2, 3.7 and 3.3 per 1000 births, respectively. This disparity in prevalence rates may be due to under-reporting of VCMs which still seems to go unnoticed in at birth and the neonatal period in many settings.

In this study, the sole antenatal diagnostic test was obstetrical ultrasound scan. According to the WHO recommendations, at least three ultrasounds should be performed during pregnancy, one per trimester [3]. These scans aim to ensure foetal well-being, and the absence of CMs. This antenatal diagnosis is important to pregnant women because while some choose the continuation of their gestation, others seek a TTP. Of the 176 neonates who had at least one antenatal ultrasound, a sonographic-clinical match was only established in 37, an antenatal diagnosis rate of 21%. This low sonographic-clinical correspondence was observed for instance in case of “holoproencephaly” on antenatal ultrasound scans, but the presence of “myelomeningocele + hydrocephalus + cleft lip-palate” at birth; or in case of “gastrointestinal visible malformation” on ultrasound, but the presence of “agenesis of the abdominal wall with exposure of the viscera + absence of external genital organs + lumbosacral agenesis and lower limbs” at birth. This antenatal diagnosis makes it possible to terminate the pregnancy if the VCM seen on antenatal ultrasound is deemed incompatible with life, or if emergency management is necessary to improve the vital prognosis of the foetus. It is worth to mention that our prevalence rate of antenatal diagnosis was higher than the 16.3% found at the Douala General Hospital, Douala, Cameroon of in the year 2012 [2]. This discrepancy in prevalence rates could be explained by the fact that we included several health facilities specialized mainly in maternal and child health in Yaoundé compared to the Douala General Hospital which is not only specialized in maternal and child health. The frequency of antenatal diagnosis in our context is far below the 69.1% obtained in France [9]. The low rate of antenatal diagnosis in the present study could be explained by an insufficient number of prenatal ultrasound scans performed to pregnant women especially in the 2nd and 3rd trimester where VCMs are easily detectable and the fact that more than half (56%) of the sonographic scans were performed my ultrasound technicians who have are trained on elementary sonography such as pregnancy detection, foetal sex identification and rarely detection of CMs in our setting. We found that anencephaly had an antenatal diagnosis rate of 50 and 40% for gastroschisis. But in Europe, the antenatal diagnosis of anencephaly is made in 100% of cases since the twenty-first century, because this malformation is frequent and incompatible with life, no child should be born with this anomaly [9]. The antenatal diagnosis of gastroschisis was 98% in Paris [9]. It is therefore urgent to train all personnel performing an antenatal ultrasound scan because the sensitivity of the ultrasound depends greatly on the operator’s qualification [3]. Some malformations diagnosed prenatally that did not benefit from TTP were related to the family’s refusal.

According to the recommendations of the French College of Fetal Ultrasound for a good screening for prenatal malformations, ultrasounds should be performed at the 12^th, 22^nd and 32^nd week of gestational amenorrhea, with an optimal age between 21 and 23 week of gestational [3]. However, we found that antenatal ultrasounds, especially those of the 2^nd and 3^rd trimesters, were not performed at the right time, which could compound, contribute to the low antenatal diagnosis rate. More than one-third (36.3%) of mothers who delivered newborns with VCMs started ANCs after the first trimester of pregnancy. As a result, abnormalities of foetal morphology or nuchal translucency were not timely diagnosed antenatally, hindering adequate pregnancy follow-up and anticipation of TTP or timely surgical management of newborns with VCMs requiring surgery.

Fifteen newborns with VCMs were delivered stillborn, with majority of the deaths occurring intra-uterinelly. This result suggest the role of VCMs in neonatal mortality, which is one of the leading cause of neonatal mortality [1, 11‐13]. The main indication for caesarean section in our study was cephalo-pelvic disproportionation related to macrocranium due to either thanatophoric dwarfism (Fig. 3), hydrocephalus or Beckwith Wiedemann syndrome (Fig. 4).

We acknowledge the following limitations of the present study. Firstly, the diagnosis of VCMs was made antenatally with ultrasound scans and at birth through clinical examination of the newborn without in-depth investigations of probably associated occult CMs through cardiac ultrasound, abdominopelvic ultrasound scan, spinal x-ray, magenetic resonance imaging or more sophisticated tests like amniocentesis and chorionic villi sampling for genetic tests. Although this was not the scope of our study, it is likey that we may have overlooked some associated and even later fatal neonatal occult malformations in newborns presenting with a visible single malformation or polymalformation syndrome. The inability to carry out the aforementioned imaging and genetic tests due to their relatively expensive cost and invailability in our resource-challenged setting was a significant compounding factor to this shortcoming. Public health authorities’ integration (and subsidization of the price) of an algorithm for antenatal screening of VCMs in our context could significantly reduce the under-reporting of VCMs in our setting and go a long way to terminate VCMs incompatible with life during pregnancy or help anticipate the neonatal care of neonates with VCMs requiring specific treatment and attention at birth. However, through a cohort design we have contributed in providing data on the scarcity of both antenatal and postnatal diagnoses of VCMs in the tropics.

Visible congenital malformations are common in Yaoundé. The frequency of antenatal diagnosis is still very low due to an insufficient number of antenatal ultrasound scans performed and an inability to make the diagnosis during the realization of these ultrasound scans. Some major malformations diagnosed prenatally are not always followed by a therapeutic termination of pregnancy. It is therefore crucial to sensitize women to consult early in case of suspicion of pregnancy and to have obstetrical ultrasounds performed by qualified health care providers. The creation of a national registry of visible congenital malformations could become a sentinel and allow to consider a strategy of antenatal diagnosis, genetic counseling and prevention of these malformations.