Congenital anatomical variants in human fetal embryological development and its risk factors in low-resource setting: A longitudinal study

INTRODUCTION

The macroscopic and microscopic structures of the human body and their characteristics follow an observed pattern of normality; therefore, deviations from this pattern produce anatomical variations or abnormalities, which may be congenital or acquired. Every year, about 3.0%–6.0% of infants worldwide are born with a severe congenital disability.^[1] These defects affect infants irrespective of race, ethnicity, or birthplace. In a report, an estimated 303,000 newborn deaths occurring within the first 4 weeks of life were attributed to congenital anomalies.^[2] Also, congenital anomalies represent a significant global disease burden among children, accounting for 25 million disability-adjusted life years (DALYs) worldwide.^[3] The prevalence of fetal congenital anomalies in Nigeria varies from 0.4% in the south-south,^[4,5] 6.2% in the south-west,^[6] and 5.8% in the north-west^[7] compared to 3.0% in the USA,^[8] 2.0–3.0% in the United Kingdom,^[9] and 2.5% in India.^[10]

Furthermore, it was reported that the prevalence is limited to gross anomalies seen in live births, while anomalies resulting in miscarriages or minor anomalies not routinely screened were missed.^[1] The actual prevalence is higher than was reported.^[1] Depending on the type and severity of the congenital anomaly, it may not result in death but contribute to long-term disability, potentially significantly impacting individuals, families, healthcare systems, and societies.^[11]

The advent of ultrasonography provides noninvasive access to the prenatal diagnosis of congenital anomalies. It has resulted in a significant improvement in the diagnosis and care of affected fetuses and neonates.^[12] The antenatal diagnosis of these anomalies prepares the parturient, her partner, the family, and the healthcare personnel for the challenges and possible solutions during and after delivery. Ultrasonography is safe for both the parturient and the fetus during the evaluation of the external and internal anatomy of the fetus for major congenital anomalies as well as soft markers of chromosomal anomalies and genetic syndromes.^[13] In Nigeria, available reports on the pattern of occurrence and distribution of these anomalies are mostly limited to retrospective analysis and a few studies that looked at congenital malformations at birth.^[5–7] Thus, the burden of prenatally diagnosed congenital malformation in Nigeria remains largely unknown. We, therefore, aimed to determine the variants of congenital anomalies in human fetal development using ultrasound diagnosis, its associated risk factors, and the outcomes of such pregnancies in a secondary health facility in north-central Nigeria.

MATERIAL AND METHODS

RESULTS

A total of 250 pregnant women had anomaly scans during the study period, out of which 29 had congenital anomalies, giving a prevalence of 11.6%. The mean maternal age was 30.8 ± 3.8 years old; 163 (65.2%) had tertiary education; 18 (7.2%) had chronic hypertension, among whom 13 (72.2%) have been hypertensive for less than 5 years; and 38 (15.2%) has used herbal preparations in index pregnancy [Table 1].

In Table 2, 7 (2.8%) had diabetes using fasting blood sugar and 5 (2.0) using the 2-hour postprandial evaluation, and 59 (23.9%) pregnant women had anemia (packed cell volume of <30%).

Pregnancy outcomes of the study participants showed that 34 (13.6%) had cesarean sections while 216 (86.4%) had spontaneous vaginal deliveries. Among the babies at birth, 22 (8.8%) weighed < 2,500g, 199 (79.6%) weighed between 2,500 and 3,900g, and 29 weighed ≥4,000g, while 159 (63.6%) were females. Among the participants’ newborns, 29 (11.6%) had congenital anomalies. Among the congenital malformations, seven (24.2%) were omphalocele (minor) and six (20.7%) were polydactyl [Figure 1].

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Figure 1:

Distribution of congenital anatomical variants among neonates with congenital anomalies.

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In Table 3, there was a significant association between the occurrence of fetal congenital anomalies and maternal age (p < 0.001), fasting blood sugar (p < 0.001), and 2-hour postprandial levels (p < 0.001).

In Table 4, the statistically significant predictors of fetal congenital anomalies using the binary logistic regression were maternal hypertension (p = 0.004), ingestion of herbal medication during pregnancy (p = 0.002), and maternal 2-hour postprandial blood glucose level (p < 0.001).

DISCUSSION

Our study shows a prevalence of 11.6% for fetal congenital anatomic variants, higher than reports from local studies in Nigeria that ranged from 0.4% to 6.2% ^[4–7,15]. It is also higher than studies in Baghdad, which ranged from 7.76 to 12.36 per 1,000.^[16,17] This higher prevalence of fetal congenital anomalies obtained in this study may be due to differences in the study methodology, as these reference studies were reports from physical examination of newborns after birth with the exclusion of abortuses, unlike this present study, which performed ultrasonographic evaluation of fetuses.

According to this study, congenital malformations are higher among older women (> 35 years). The preponderance of fetal anatomic variants among parturients aged over 35 years in this study may be related to the observation that with advanced maternal age, the oocytes become increasingly likely to form embryos with an imbalance in their chromosome content, resulting in increased risks of anatomic variants.^[18] This observation was corroborated by Singh et al.^[14] and Zhang et al.,^[19] who reported an association between advanced maternal age and fetal anatomic variants. The risk of congenital anomalies is also higher among multiparous women when compared to nulliparous women or women with low parity. This observation is also consistent with a study by Feng et al.^[20]

Medical disorders such as diabetes mellitus and chronic hypertension, mainly when poorly controlled, have been associated with an increased risk of congenital anomalies. This study shows that factors associated with fetal congenital anomalies included maternal hypertension, ingestion of herbal medication during pregnancy, and maternal 2-hour postprandial blood glucose level. The observed association between maternal chronic medical disorders (hypertension and diabetes mellitus) and fetal anatomic variations corroborates the report by Morrison et al.^[21] The poor glycemic control of diabetes mellitus, especially in early pregnancy when organogenesis begins, increases the risk for anomalies, especially congenital cardiac malformations.^[22,23] Also, it has been reported that maternal chronic hypertension significantly increases the risk of developing renal, limb, and lip/cleft/palate congenital anomalies. In contrast, the risk is further exacerbated by superimposed eclampsia.^[24,25] This observation is also in keeping with a study in Iraq that showed an increased risk of congenital anomalies in a parturient with poorly controlled hypertension and diabetes.^[26] Herbal medications are well advertised in Nigeria, and they are widely believed to have little or no side effects since they are obtained from natural sources. In addition, most herbal medications sold do not go through the standard pharmaceutical regulatory processes. Therefore, there is an increased risk of adulteration and contamination with products such as arsenic, known to be fetotoxic.^[27] Ingestion of herbal medication, especially during the first trimester, increases the risk of congenital malformations.^[24] The process of organogenesis in the face of ingesting herbal preparations whose composition and effects on the reproductive system are largely unclear may explain the relationship. Thus, herbal ingestion during pregnancy may cause harm, including congenital anomalies.^[27] The most common congenital anomalies in this study were omphalocele minor, polydactyly, and anencephaly, similar to a report in Nigeria by Akinmoladun et al.^[6]

The strength of this study included being a longitudinal study that involved a cohort of 250 pregnant women who had ultrasonography for the presence of congenital anatomic variants or otherwise and were all followed up until delivery. However, this study has some limitations; pregnancy less than 12 weeks was not included, possibly missing the early congenital anatomic variants that may end up as abortuses. Besides, this is a single hospital-based study and may not reflect what is obtained across the country. The outcomes of managing the babies born with congenital anatomic variants were also not reported.

CONCLUSION

The study shows a high incidence of congenital anomalies, emphasizes the need for adequate antenatal counseling and routine anomaly ultrasound scans, especially among women with hypertension in pregnancy, and discourages using herbal medication, particularly during pregnancy.

AUTHORS’ CONTRIBUTION

AM was responsible for the concept, design, data collection, interpretation, drafting, and approval of the final draft; AOO was in charge of the concept, design, data interpretation, drafting, and approval of the final draft; AD was involved with the concept, design, data interpretation, drafting, and approval of the final draft; FOA was responsible for the design, data collection, drafting, and final draft approval; ASA was in charge of the concept, design, data interpretation, drafting, and approval of the final draft; and IOR was responsible for the concept, design, data interpretation, drafting, and approval of the final draft.