PATTERN AND RISK FACTOR ASSOCIATED WITH CONGENITAL ANOMALIES AMONG YOUNG INFANTS ADMITTED IN DHULIKHEL HOSPITAL

1 Associate Professor, Department of Pediatrics Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal. 2. Assistant Professor, Department of Community medicine, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal. 3. Lecturer, Department of Community medicine, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal. 4. Professor, Department of Pediatrics, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal. 5. Lecturer, Department of Pediatrics, Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel, Nepal.


Objec ve
The main objec ve of the study was to determine the associa on of certain risk factors with birth defects occurring in newborn and infant seeking care in Dhulikhel Hospital, Kavre, Nepal.

Methodology
This is a hospital based, cross sec onal and compara ve study involving 219 young infant below 2 months of age admi ed in the Dhulikhel Hospital, Kathmandu University Hospital.We enrolled infants admi ed at Neonatal intensive care unit, Neonatal ward, and neonates staying with mother in st st post natal wards, from 1 January 2015 to 31 December 2017.

Results
Incidence of congenital malforma ons involvement of neonates in our hospital was 1.1% among the live births.The most frequent was cardiovascular systems 29(26.8%)followed by musculoskeletal system 17(15.7%)and face 15(13.8%).Less than 4 in number of Antenatal visit (p=0.017),not using folic acid during early pregnancy (p<0.001) and low socioeconomic condi ons (p<0.001) were significantly associated with congenital malforma ons.Among all congenital anomalies complex congenital heart disease has poor outcome.

Conclusion
The most common congenital defects involved cardiovascular and musculoskeletal system.Lack of antenatal visit, lack of folic acid during periconcep onal age and low socioeconomic condi ons are the most common risk factors iden fied for congenital anomalies.

INTRODUCTION
Congenital anomalies are defined as structural or func onal abnormali es including metabolic disorders present at birth.It can be isolated abnormality or part of syndrome that con nue to be an important cause of neonatal and 2% and in South Africa it is 1.49%.In India it was found that, 2.5% of newborns were iden fied to have congenital anomalies at births.Congenital malforma ons are known to be the third commonest cause of perinatal mortality 3 following infec on and hypoxia.
There has been a tremendous progress in the prenatal diagnosis of congenital malforma on because of improvements in fetal ultrasound and prenatal gene c tes ng.This allows parents for the choice of termina ng the pregnancy.Some studies have shown that prenatal folic acid and other mul vitamins supplementa ons significantly reduce the 6-8 birth prevalence of some congenital malforma ons.Early antenatal diagnosis of correctable defects gives the clinician an op on for early referral of the mother to a center with pediatric surgical facili es for further plan and management in case of need.
There is no accurate quan fica on of congenital anomalies within certain popula ons and only few studies have been done regarding prevalence of congenital anomalies and its risk factors in country like Nepal.Therefore it is essen al for es ma ng their burden and documen ng the need for preven on and for evalua ng the effects of preven ve measures and treatment services.Even though congenital anomalies are a highly reported topic in scien fic literature, very li le informa on is available regarding the poten al risk factors associated with these anomalies and their perinatal outcomes.

OBJECTIVE
To establish the prevalence and pa ern of congenital anomalies and to iden fy associa on of the risk factor for congenital anomalies this study has been carried out.Echocardiography was executed by a pediatrician who has done fellowship on pediatrics echocardiography.Due to lack of relevant equipment and qualified staffs, gene c and newborn metabolic assessments could not be performed.

METHODOLOGY
A er diagnosing congenital anomalies, informed consent was taken from parents and structured Proforma was filled.
The pa erns of congenital anomalies along with their system wise distribu on were documented.The demographic pa erns, risk factors associated with malforma ons and their outcomes were also documented.Christensen et al. defined mul ple organ system involvement as live births with congenital anomalies that involved two or more organ 9 systems.If they correspond with any iden fied syndrome, were categorized into the specific syndrome.Remaining uniden fied anomalies were classified as others.

Data analysis
Data were entered and analyzed using SPSS, version 23.The prevalence of congenital anomalies was expressed per 1000 live births.The associa on between congenital anomalies and socio-demographics were assessed applying binomial logis c regression analysis for the study and reference group and chi square test was done between the study and reference group.

RESULTS
Within the study periods of 36 months 108 babies with congenital anomalies were iden fied.The age range was between first days of life up to 60 days of life with a median age of 3 days.Among 108 babies with congenital anomalies 98(90.7%)babies were in born and 10 (9.25%) babies were out born.In born babies were those who born within our hospital and out born babies were those who born outside our hospital including other hospital, health center, home delivery and ambulance delivery.The birth prevalence of congenital anomalies was 11.4 per 1000 live births.
Ninety one (84.2%)babies had a single malforma on while 17(15.7%)babies had mul ple malforma ons.The most frequent site of malforma ons involved cardiovascular systems 29(26.8%)followed by musculoskeletal system 17(15.7%)and face 15 (13.8%).Distribu on of congenital anomalies in the study group is shown in Figure 1.The specific congenital anomalies, found within different system in the present study is shown in table 1.
Among the socio demographic studies there was no significant difference in maternal age, paternal age, residence, week of gesta on, religion and ethnicity.Number of Antenatal care visit was significantly associated with congenital anomalies (OR=2.6;95% CI=1.8-5.8;p=0.017)(Table 2).
Maternal TORCHinfec ons, smoking during pregnancy and alcohol intake during pregnancy were more common in the study group but these differences were not significant.Failure in use of folic acid during early phase of pregnancy has a strong associa on with congenital anomalies with p value of 0.000 (Table 3).
Male babies (p=0.002) and Low socioeconomic condi on (p=0.000) were also significantly associated with congenital anomalies (Table 4).

DISCUSSION
The joint World Health Organiza on (WHO) and March of Dimes (MOD) mee ng reported that 7% of all neonatal mortality and 3.3 million under five death were due to 9 congenital anomalies.Several studies have been done to determine its prevalence.However, since most of the studies done were limited to a single ins tute or region and not na on-wide, birth defect prevalence varied widely from 10,11 0.5% to 6.8%.
In our study incidence of congenital malforma ons in neonates was 1.1% among the live births which was significantly higher than previous two studies done in maternity hospital (0.36%) and Western regional 12,13 hospital (0.42%) in Nepal.
In England and United State, 5,14 the prevalence is 2% and 2-3% respec vely.The prevalence of congenital malforma on in our study is also comparable to another study done in United Arab Emirates 14 (1%) and china (1.1%).
The prevalence by type of anomaly showed known global trends, with congenital heart defects being the most prevalent type of birth defect.The prevalence of congenital heart defect was 3.3 per 1000 live birth that is nearly threefold lower than the es mated prevalence of 9.3 per 1000 live 15 births for Asia.Another mul ethnic birth cohort study done in Brandford UK, also reported congenital heart disease as 16 the most common anomaly in newborn in UK.In contrast to our study, other studies done in developing countries like in 17 18 India and Pakistan demonstrated highest frequency of CNS anomalies and lowest frequency of congenital heart disease.The varia on in the frequencies could be due to gene c background, geographical area, socioeconomic and nutri onal status along with folic acid intake.This may be due to rou ne performance of echocardiography in all babies admi ed in NICU and all suspected congenital heart disease admi ed in our center which leads to the increased detec on of CHD in our study.During the study periods there was a predominance in infants with cardiovascular system, followed by musculoskeletal system and facial malforma on, resembling those found in other na onal studies and in first World countries like the United States

Brazil by Costa C et al
Antenatal visits are an important aspect of prenatal care.These visits aim to ensuring a normal pregnancy with the delivery of a healthy baby from a healthy mother.Inadequate ANC visits (<4) have previously been associated 22,23 with the occurrence of congenital anomalies.
A significant associa on between congenital anomalies and the lack of periconcep onal use of folic acid (p = ≤0.001) was found in this study.Folic acid is necessary for the growth and smooth func oning of human cells, as it is crucial for the biosynthesis and methyla on of deoxyribonucleic acid 24 (DNA) and ribonucleic acid (RNA).This is important for cell division, differen a on and regula on of gene expression, especially at the me of rapid cell division that is during 24 embryogenesis.The associa on between a low usage of folic acid during pregnancy and the occurrence of congenital 23,25,26 anomalies has also been reported in other studies.
Maternal cigare es smoking and alcohol consump on have previously been reported as risk factors for the occurrence of congenital anomalies including orofacial cle s and 27, 28 congenital heart disease.The current study did not show a significant difference in smoking or alcohol consump on during pregnancy when comparing mothers of newborns with or without a diagnosis of congenital malforma on.This may be due to awareness programs and cultural norms.Similar to our study, other studies done in Brazil and Tanzania also showed insignificant associa on between maternal cigare e smoking and alcohol consump on for the in other studies as well.Socioeconomic status for most was low class.This could be one of the reasons for a high percentage of affected pa ents in our se ng as socioeconomic status in an important risk [32][33][34] factor for birth defect.Some hypothesis can be raised, including the possibility that mother may having inadequate nutri on, less ANC visit and lack of awareness about folic acid and risk of congenital anomalies .Among all congenital anomalies mortality was high among those with complex congenital heart disease due to unavailability of advance neonatal cardiac surgical facility in our country.
Congenital malforma on has gained increasing importance due to both its morbidity and mortality.There are no well accepted preven ve measures for it.Increasing awareness about maternal care during pregnancy, educa on programs on risk factor for congenital malforma on and preconcep on use of folic acid needs to be highlighted to decrease the incidence of congenital anomalies and their co morbidi es.

LIMITATIONS
There are several limita ons in our study.As this is a hospital-based study, its result is unlikely to represent na onally.Chromosomal abnormali es and metabolic disease could not be diagnosed and confirmed because of lack of availability of Karyotyping and metabolic screening test.Since our study was conducted in just one ter ary care center, many cases could not be included.This has led to a low percentage of this rela vely common birth defect in our sample.

CONCLUSION
The prevalence of congenital malforma on in this study was 11.4 per 1000 total lives births.Less than 4 antenatal visits, lack of intake of folic acid and low socioeconomic condi on were three most common risk factors as determined from our study.Regular antenatal visits to emphasize the intake of folic acid in early pregnancy and prenatal diagnosis are recommended for preven on, early interven on and even planned termina on when needed.

Funding
This study did not receive funding.

CONFLICTS OF INTEREST
We declare that we have no conflicts of interest.

Figure 1 :
Figure 1: Distribu on of congenital anomalies

Table 1 :
Specific congenital anomalies in different system

Table 2 :
Logis c regression analysis of sociodemographic between study and reference group.

Table 3 :
Logis c regression analysis of risk factor between study and reference group.

Table 4 :
Chi-sauare test analysis of sociodemographics between study and reference group