Burden and consequence of birth defects in Nepal-evidence from prospective cohort study

Birth defects are anomalies in morphogenesis during early foetal life resulting in structural, behavioural, functional and metabolic disorders that can be detected prenatally, at birth or later in infancy [1]. Globally, more than 3 million babies with birth defect die within the first 28 days of life and a majority of the survivors suffer with disabilities [2, 3]. Lower- and middle-income countries (LMIC) carry the major burden (>90%) of these anomalies which are least prioritized as compared to other causes of neonatal and infant mortality for prevention and management [2, 3]. There is a high risk of mortality due to congenital heart disease and neural tube defects globally [2, 4].

South-East Asia has higher prevalence of cleft lip and palate [5], whereas neural tube defects is highly prevalent in Mexico, Central America, and India [3]. In Nepal in 2010, among the estimated 600,000 born 40,000 births were are born with malformations with cleft lip and palate, neural tube defects, congenital heart disease as the commonest conditions [5, 6]. The prevalence of birth defect is widely variable ranging from 0.3 to 7% implicating various known and unknown factors interplaying differently in varied time and geographical location [7]. Often, these factors are recognised as genetic in origin (10–30%), environmental (5–10%), multi-factorial (20–35%) and unknown (30–45%) [8]. Primarily these factors may affect the developing foetal organs during the first trimester while undergoing crucial stages of formation passing through stages of fertilization, implantation and organ formation [1, 8]. Identification of several maternal factors for birth defects like maternal age, lack of nutritious diet, no use of peri-conceptional folic acid, alcohol and tobacco consumption, exposure to pesticides and X-rays, and infection signifies the role of effective antenatal care (ANC) counselling and screening [9, 10].

To the best of the present evidence, therapy, medication, surgery, or assistive technology are different services available for management of birth defects and in most cases essential paediatric surgery can avert early mortality and long-term disability [11]. The Human capital approach to repair cleft lip and Palate in LMICs and favourable outcomes in High income Countries (HICs) in Gastrointestinal and other anomalies have refuted the traditional perception about Paediatric surgery [12]. Prenatal diagnostic techniques, genetic counselling, and access to termination of Pregnancy remain the cornerstone to curtail neonatal mortality and still birth [13].

In LMICs, lack of diagnostic and national screening programmes has led to paucity of nationally representative data, a major hurdle for in-depth understanding of the epidemiology [14]. In Nepal, no protocol regarding management and timely service provision to babies born with birth defects exists except for sporadic programmes for cleft lip and palate repair or few organisations providing care to disabled children. To further accelerate the reduction of 2016 neonatal mortality rate of 21 per 1000 live births to achieve SDG target of 12 per 1000 live birth, intervention to prevent birth defect and manage them is important [15, 16]. This study can be a basis for National Birth defect Surveillance Registry and thereafter, developing prevention and management guidelines on birth defects. The current study provides evidence on prevalence, patterns, factors and outcomes associated with birth defects across the 12 hospitals in Nepal.

Out of the total 104,223 admissions, a total of 87,989 deliveries were conducted during the study period of which 87,242 deliveries were live births and 747 deliveries were stillbirths. Among them, there were 506 reported cases of birth defects (Fig. 1). The prevalence of birth defects was found to be 5.8 per 1000 live births. The different types of birth defects as reported from the data show anencephaly (3.95%), cleft lip (2.77%), cleft and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). Most (75.89%) of the reported cases have not been classified (Fig. 2).

Univariate analysis showed significant association with birth defects for most of the socio-demographic, obstetric and neonatal characteristics. Socio-demographic characteristics such as ethnicity and type of fuel used for cooking in the household showed significant association (< 0.001) with birth defects. Female child was significantly associated with birth defects (p=0.002). Women with one previous birth (p=0.002) and two or more birth (< 0.001) were significantly associated with birth defects. Multiple delivery was significantly associated with birth defects (p=0.02). (Table 1).

Multivariate analysis showed significant association for various factors with birth defects. Mothers less than 20 years of age were 1.64 times more likely (aOR 1.64; 95% CI, 1.18–2.28, p-value=0.003) to be associated with birth defects compared to mothers 20-< 35 years of age. Mothers of ethnicity other than Brahmin/Chhetri were 1.78 times more likely (aOR 1.78; 95% CI, 1.46–2.18, p value=< 0.001) to have babies with birth defects. Female child had 1.35-fold risk (aOR 1.35; 95% CI, 1.13–1.61, p value < 0.001) of having birth defects compared to male child. Compared to women with no previous birth, the risk of birth defect was higher among women with 1 previous birth (aOR 1.58; 95% CI, 1.26–1.98; p< 0.001) and women with 2 or more previous birth (aOR 2.33; 95% CI, 1.84–2.95; p< 0.001). Also, mothers with multiple deliveries had 1.8-fold risk of having babies with birth defect compared to mothers with single deliveries (aOR 1.8; 95% CI, 0.98–3.28; p=0.06). (Table 2).

In a multi-variable analysis, babies with birth defect have 1.88-fold risk of birth asphyxia (aOR 1.88; 95% CI, 1.41–2.51; p< 0.001) in reference with babies without birth defect. Babies with birth defect have 1.82-fold risk of neonatal infection (aOR 1.82; 95% CI, 1.12–2.96; p< 0.02). The risk of pre-discharge mortality for babies with birth defects was 3.31 folds (cOR 3.31; 95% CI, 2.13–5.14; p< 0.001) higher compared to babies without any birth defects (Table 3).

The prevalence of birth defects in the present study is 0.58% which is comparable with the earlier studies in Iraq and Iran which reported an incidence of 0.69 and 0.36% [18‐20]. The patterns of system involved in our study show Musculoskeletal System to be most commonly affected presenting as cleft lip, cleft palate and club feet. This was in line with the study conducted in different parts of world in Egypt and India [21, 22]. A study in Iran and India reported higher prevalence of malformations from CNS, Cardiovascular system or Gastrointestinal system [23, 24]. This variation in patterns could possibly be explained by various genetic and environmental factors interplaying differently in varied time and geographical location [10].

Mothers of age group less than 20 years were found to have risk of delivering a newborn with birth defect which was similar to the study which concluded association between young mothers and congenital anomaly [25]. In contrast, several studies have identified the potential of maternal age above 35 years in the causation of this condition [10, 26]. Developmental and behavioural factors like poor diet, illicit drug use, smoking etc. in the adolescent group as compared to older mothers relative to conception could likely affect the developing foetus [25].

According to different literatures, congenital malformation is seen in twins rather than singleton pregnancy [10, 27]. Likewise, our finding enlisted this study as one among those many. However, multiple delivery did not pose a risk to birth defect in Europe [28]. Alterations of the blood flow within the vascular anastomoses supplying the twins and early primary abnormality that might develop during twinning itself can lead to birth defects [29].

In comparison to women with no previous birth, the likelihood of giving birth to a baby with congenital defect was seen among women with 1 or more previous birth in our study, which is similar to those reported in other studies [25, 30]. To the contrary, positive association between nulliparity and range of birth defects have also been successfully investigated earlier [31, 32]. The decrement in body nutrients stores among mothers who have previously delivered as compared to those who have never delivered a baby before explains the association between parity and congenital birth defects [33].

With regards to ethnicity, advantageous ethnic groups like Brahmin and Chettri were comparatively less likely to be associated with birth defects than the non-advantageous group. Association of ethnicity with birth defects has been depicted in the previously done studies [25, 34]. Ethnic variance as the risk for malformations may be linked to genetic susceptiveness or to socio-cultural and economic differences that might modify exposures [35].

This study showed that there was significant impact for female sex in regards to the causation of congenital birth anomalies and this significance is also supported by studies from neighbouring nations [36]. In contrast, male babies were found to have risk for birth defects in another study [36, 37]. This variation could probably be explained by potential of the hormonal hypothesis of sex ratio explaining the unusual concentrations of hormones during or preceding pregnancy could be more common in those malformations with established sex ratio biases [38].

Studies have documented that conditions like cleft lip and polydactyly are more common in males whereas neural tube defects and cleft palate are more seen among female babies [39, 40]. The high incidence of cleft palate and NTDs could also explain female preponderance to for birth defects. However, as we have not examined population-based resources in this study, this might not potentially explain the exact sex difference patterns in babies with congenital birth anomalies.

Babies with birth defects tend to have morbidities such as birth asphyxia and neonatal infection as found in this study. The risk of mortality among these babies at birth is higher similarly. Increased mortality arising from birth defects has also been identified in India [41]. This can be explained based on the type of defect or anomalies which describes the intensity or level of risk associated.

Birth defect is prevalent (0.58%) among newborn babies in the same way as reported elsewhere. Various socio-demographic factors like adolescent age and disadvantaged ethnic group are associated with birth defect. Obstetric factors like being female child and number of previous birth are associated with birth defect. Babies with birth defect have high risk for birth asphyxia, neonatal infection and pre-discharge mortality at birth. There is a need to evaluate the services available for babies with birth defect for better identification and management of these babies. Birth defects are major causes of neonatal mortality and morbidity, and national surveillance is very important.