Major Congenital Anomalies: A New Rising Tide of Concern to the Health System

,


Introduction
In Oman, LBW was 10.2% out of a total live birth of over 66,000 live birth during 2013.The worldwide prevalence of low birth weight (LBW) is 15.5%, which amounts to about 20 million LBW infants born each year, 96.5% of them in the developing countries (1).For example, in Oman, the prevalence of LBW was 4.2% in 1980, which doubled (8.1%) in 2000 and has shown a slow but steady increase reaching 10.2% in 2013.This also causes an increase in the rate of LBW infants, and subsequently an increased rate of long-term medical sequalae.
LBW has been increasing globally and regionally with various advancement in medical care; including that of obstetric and neonatal care and technological development with restricted growth, and pregnancy complications are taking place as live births.
Recently, over the last few decades, devotion has been steered toward the contribution of the intrauterine environment to the development of chronic and noncommunicable diseases (NCD).Epidemiological studies have demonstrated that a poor intrauterine environment is associated with an increased risk of various non-communicable diseases such as chronic kidney disease, and diabetes (1)(2)(3)(4)(5).Many of these diseases may be associated with birth anomalies.Birth defects are an important cause of infant mortality and disproportionately occur among LBW infants.
Congenital anomalies, also commonly referred to as birth defects, are conditions of prenatal origin that are present at birth.Congenital anomalies have a lifelong impact on children's health and survival (6).It is estimated that 1 in 33 newborns have birth defects and it leads to 300 000 yearly deaths of neonates (1) and linked to 3.2 million birth related disabilities (7).Congenital anomalies encompass a wide array of structural and functional abnormalities that can occur in isolation (i.e., single defect) or as a group of defects (i.e., multiple defects).Multiple defects may occur as part of well-described associations, such as the non-random co-occurrence of vertebral anomalies, anal atresia, cardiac defects, trachea-esophageal fistula, and/or esophageal atresia, renal and radial anomalies, and limb defects (VACTERL) (8,9).Such disabilities can impose social stigma and economic burden on poor families, society and health care organizations (6).Cardiac system, neural tube defects and Down syndrome are most common type of anomalies seen (6).
In 2013 the Global Burden of Disease reported that congenital anomalies are one of the top ten causes of mortality in children under five years old (10).Globally, the trend of childhood mortality due to infection and malnutrition is decreasing.This is likely due to the wide availability of vaccination, infection control and improvement in nutrition supply (11).Besides, the availability of standard pediatric and maternal health services, the contribution of congenital anomalies upon mortality and morbidity of neonates is on the rise (12).Early diagnosis of congenital anomalies in antenatal period is important for effective counseling, fetal or neonatal timely intervention and termination of pregnancy if needed, planning delivery and future prevention (13,14).The world health Assembly has highlighted the importance of taking actions in prevention diagnosis and timely intervention (15,16).
To deal with the problem efficiently, accurate data is crucial to establish the appropriate methods of surveillance of congenital anomalies (17)(18)(19)(20).Accurate estimate on the prevalence and mortality linked to birth defects are limited in low-and middle-income countries in contrast with high-income countries.For instance, in UK, the prevalence of congenital anomalies estimated to be 2-3 % and the 20-year survival rate is about 85.55% (21).In United State it is estimated to be 2-3% (17), 1.07% in Japan (22), in India 2.5 % (17) and in KSA 52.17 per 1000 pregnancies (7,23).However, government actions and efforts on improving risk factors and primary prevention is more effective when based on accurate data and information gathered about the causes, patterns and outcomes of congenital anomalies (7,23).In this study, we gathered data from the only tertiary hospital for obstetric cases that seen in the Obstetric Ultrasound and Fetal Medicine units, of fetuses with major congenital anomalies, for a duration of 10 years.Main aim was to identify the prevalence, patterns, maternal characteristics and perinatal outcomes.

Study setting
This study was conducted at Fetal Medicine Unit of the Obstetrics and Gynecology Department at Royal Hospital.Royal Hospital is the only major tertiary Hospital, Muscat, the capital city of Sultanate of Oman.The institution provides multi specialist care and considered as an official referral center for congenital anomalies in Oman, as appointed by the Ministry of Health.
Pregnant women who followed at obstetric antenatal clinics had a routine anatomy scan between 18 -22 weeks of gestation, patients with high risk can be referred even earlier for first trimester scan, according to the obstetric history and condition.Women with antenatally diagnosed with major congenital anomalies had antenatal follow up with Fetal Medicine Unit.Most patients had two or more ultrasound examinations by fetal medicine senior consultants.

Study design
This was a retrospective descriptive study of antenatal diagnosis of major congenital anomalies found in the Obstetrics and Gynecology department, Fetal Medicine Unit, over 10 years period from January 2009 to December 2018.Ethical approval for the study obtained from the Scientific Research Committee at Royal Hospital.
Data were obtained from the following sources: a registry book for congenital anomalies in Ultrasound Unit, patient information obtained from computerized records at Royal Hospital, records from the labor ward and antenatal clinics.All patients with antenatal diagnosis of major congenital anomalies were included.Pregnancy outcomes included in the study were live births, Stillbirth (fetal loss at a gestational age of 22 weeks and older), Neonatal death (infant death up to 28 days of life).Perinatal mortality was recorded as fetal demise or neonatal death from 22 weeks of gestation to the 28th day of infant life.Major congenital anomalies were classified according to the system included (Nervous, Cardiothoracic, gastrointestinal, genitourinary, musculoskeletal, anterior abdominal wall defect, hydrops, orofacial, Tumors, Miscellaneous and others).
Data included demographics, ultrasound findings and other pertinent maternal and fetal information such as maternal age, maternal parity, and gestational age at diagnosis, history of consanguinity, coexistence of maternal factors and history of previous fetal anomalies.Antenatal prevalence of congenital anomalies was calculated from the total number of obstetric patients seen.All data were analyzed statistically using STATA software (Stata Corporation, College Station, TX).

Results:
The number of obstetric patients seen at RH in the Ultrasound and Fetal Medicine Units were 147563 patients.Of which, 1502 cases found to have major congenital anomalies, among them 947 (63.05 %) fetuses with isolated major anomalies and 555 cases (36.95%) with complex or multiple congenital anomalies, during the period of 10 year.Figure 1 shows the progressive rise of number of major congenital anomalies over the years in Oman.The average antenatal prevalence of congenital anomalies for 10 years was 10.1 per 1000 pregnancies.
The mean (SD) of age of study population was 30.22 (SD 6.00) and ranged from .Most common identified medical history were as follow: diabetes, chronic hypertension, cardiac disease, connective tissue disease, hypothyroidism, epilepsy, iron deficiency anemia, asthma and subfertility.
Table 1 shows the distribution of cases according to regions, frequencies and most frequent organ system identified from each area.Most (42.9%) of referrals were from Muscat and 19.4% from Al Batinah (North) and (17.6%) cases from South Al Batinah, more details illustrated in figure 2. Among the 11 governorates, cases were mostly referred from Muscat and ALBatinah.From ALWusta region least number of cases were referred with the smallest mean maternal age.AlWusta became a governorate in October 2011, its capital is Hima.It occupies a large area in the middle of Oman and the population density is one of the least comparing to other governorates (5).Many referrals were at 27 weeks (mean 27.47, SD5.5) which was almost consistent across all the governorates.Coexisting maternal factors were observed in 481 (32%) of patients including diabetes in pregnancy (10.15%), advanced maternal age (6.59%) and recurrent early pregnancy loss (7.12%).The consanguinity rate of first cousins was 22%.Two hundred and sixty-two cases (18%) had a previous family history of similar anomalies.
Of all the major congenital anomalies, the nervous system was the most common (29%) abnormalities observed and cardiothoracic system (24.9%) was the second most common.92 cases presented with Hydrops (6.17%), out of which 15.2% cases with Immune Hydrops.
Perinatal outcomes showed that 9.6 % had early neonatal death, 19% had still births and 4 % had neonatal death.The perinatal mortality rate was 32.6% among fetuses with major congenital anomalies.

Discussion
Our study site is a tertiary hospital that is appointed by ministry of health, as an official referral center for congenital anomalies in Oman.Over a decade period of time, there were 147563 obstetric patients seen in the Ultrasound and Fetal Medicine units, of which 1502 cases found antenatally to have major congenital anomalies.The study population is quite young, >10% were diabetic, have high consanguinity and a significant previous history of MCA with one third perinatal mortality rate, and majority from the capital area and the coastal region.The average antenatal prevalence of congenital anomalies over 10 years was 10.1 per 1000 pregnancies.The most common anomalies seen in this study were those of the nervous system (29.2%),followed by cardiothoracic system.Over the 10 years, the trend of recorded anomalies was fluctuating, recording the highest in 2018 were 11.3 anomalies per 1000 pregnancies and lowest in 2011 (5.2 per 1000 pregnancies).
In the present study, the prevalence of major congenital anomalies was lower compared to two studies were conducted in Oman, the first one as an abstract that reported rate of 16.8 per 1000 pregnancies (24).This study was conducted for a period of one year, in a single center which receives only selected cases from limited regions of the country.The second study was an abstract as well, which reported rate of 6.7 %, also it was a one-year study representing one regional hospital which receives cases of that region only (25).However, our cases are from all over the country and done over many years to provide a better overall rate of major congenital anomalies.
Many studies from different regions or countries report different anomaly rates, which might be attributed to the diversity in study methods, classifications of birth defects and times of studies (7,17,19,22,(26)(27)(28).In addition, differences in cultural, genetic, socio-economic elements among studied populations.
Several studies demonstrated an increase rate of birth defects associated with advanced maternal age, especially in females older than 35 years old (17,26).In our study sample, advanced maternal age was one of the common coexisting factors found in our cohort.
In Middle Eastern countries, the prevalence of consanguinity is known to be high.Besides that, important association between consanguinity among couples and increased rate of congenital anomalies has been reported in previous studies (23,(29)(30)(31)(32)(33).In our study sample, 22% of mothers were married to their first cousins.Almost consistent with a study was conducted in Oman, which showed about 24.1% of studied couples married from their first cousins (34).
The burden of congenital anomalies in high risk pregnancies is known to be high (35).Our study described females with bad obstetric history like repeated miscarriages, previous congenital anomalies and perinatal deaths, which might play a role in the development of birth defects in future offspring's, as reported by Sunitha etal.They concluded in her study that females with high risk pregnancy and bad obstetric history found to have double rate (11%) of congenital anomalies, compared to general population (6%) (35).
Many epidemiologic studies have illustrated the association between pregestational diabetes (particularly DM type2) and increased risk of specific birth defects in offspring's (36).In our study, the most common coexisting maternal risk was pregnancy with diabetes.This emphasizes the importance of pre-pregnancy counselling and planning with aim of optimal glycemic control for women with preexisting diabetics before they conceive.While the general population risk for having a baby with an MCA is one to three percent, that for a woman who has pregestational diabetes mellitus is three to six times as great.Fetal organogenesis takes place from the fifth to the eighth post-menstrual weeks.A body of evidence suggests that maternal hyperglycemia early in gestation is either contributory to fetal teratogenesis or is a surrogate marker for the causative agent of MCAs in infants of diabetic mothers (37).
As illustrated in figure 1 , what can be noticed that, the number of cases diagnosed with congenital anomalies was increasing throughout the years and it is likely due to advancement in ultrasound scan technology, with the utilization of skilled and professional sonographers.Hence, we anticipate an increase in early detection of major congenital anomalies in the coming decade.
Prevalence studies are very beneficial in identifying the baseline rates of congenital anomalies and changes over time.Which is crucial in public health planning and establishment of preventative measures.This study highlights the prevalent nature of antenatal fetal anomalies over a decade of time.Nevertheless, we may have remarkably under-estimated the real incidence of congenital anomalies in the general population.As our hospital is a tertiary health organization, mostly complicated cases are referred, on the other hand, uncomplicated cases may have been followed in other peripheral hospitals.
Early referrals and antenatal diagnoses of major anomalies is crucial for the proper counselling of parents, timely fetal or neonatal intervention, elective termination of pregnancy if needed (38).In addition to that, it helps in planning the delivery in suitable health facility and future prevention.In this study, cases where firstly referred and seen between 10 to 40 weeks of gestation (mean gestational age 27.4 weeks).One case referred early at 10 weeks of gestation, for multiparous women found to have Anencephaly and body stalk anomaly.Early diagnoses enabled timey counselling and elective termination of pregnancy (23,39) .
There are 11 main geographical areas (regions) in Oman, figure 3 (Provincial map of the Sultanate of Oman).Muscat region is the capital city and around 50% of the population lives there.Al Batinah region contains the largest amount of provenance and was split to Al Batinah North and South.The study showed that majority of referred cases (42.9%) were from Muscat and Al Batinah, Costal, regions (37.15% cases), which is expected due to the higher density of population in these areas.
The most common anomalies seen in this study were those of the nervous system (29.2%),followed by cardiothoracic system.Similar findings were identified in unpublished data from maternal child health unit at ministry of health.Neural tube defects were the most common types of anomalies seen in Nervous system.The dominance and high frequency of neural tube defects in this study was also reported in previous studies in same geographical areas as in Oman Saudi Arabia (7,23,29), UAE (40)(41)(42)(43), Iran (26,44,45), Pakistan (28,46,47) and India (17,35,(48)(49)(50).Besides, this finding was similar to studies reported by Sawardekar Kiran in 2005, a decade review of major congenital anomalies in Nizwa, Interior provenance, in Oman (51).On the other hand, some countries have reported a decrease in reported incidence of neural tube defects, due to the active intervention in promoting and implement preventative measures, like folic acid fortification in food and supplementation in preconception period (52).
Various randomized trials with other observational studies have illustrated that maternal intake of folic acid with or without multivitamin supplements in preconception period and in early pregnancy could reduce the occurrence and recurrence of neural tube defects (53).In our setting, we need to emphasize more in implementing preventative measures, like food fortification, pre-pregnancy supplementation with effective preconception counselling to emphasize the importance of folic acid and multivitamins intake before planning for pregnancy.
Many increasing evidences showing the link between preconception maternal environmental exposures like tobacco smoke, outdoor air pollution, water with disinfection byproducts, outdoor air pollution and pesticides and elevated risk of congenital anomalies (52,54).In addition, modified maternal lifestyle habits can predispose to the development of congenital anomalies (55).In the present study, 32% of mothers described to have coexisting maternal factors, the most common one was diabetes in pregnancy (8.8%).This modifiable risk can be significantly reduced by effective preconception counselling and aiming for a controlled glycemic index before conception.
Congenital anomalies are one of the leading causes of perinatal morbidities and mortalities (52).The perinatal mortality rate in our study was 32.6% among fetus with major congenital anomalies.This was almost similar to the unpublished data at MOH (almost 30 %) and 34.9% reported in Saudi Arabia (7,23,29).It is important to have further future studies, assessing factors which can affect outcome and survival in neonates born with major birth defects.

Limitations
Our study was a descriptive retrospective review and might have a bias associated with this type of studies.Some information's we could not retrieve in view of inadequate documentations of characteristics, factors and outcomes.Furthermore, the study may significantly underestimate the real incidence of anomalies in general population, as our sample was from a single tertiary heath organization.

Conclusion
The important findings from this study indicates the need for birth defect policy to establish a national surveillance system for birth defects.This measure will help in recording of the epidemiology of congenital anomalies, measuring the burden on public health and anticipate the health care needs with the implementation of preconception preventative measures.Currently we have only a notification system at ministry of health and compliance to fill the form is not 100 percent in all the regions and health care centers.Preconception genetic counselling, folic acid fortification and supplement, healthy lifestyle promotion and sufficient nourishment advice can contribute effectively in birth defect prevention programs.Therefore, major efforts are needed to increase awareness of the occurrence and risk factors of congenital anomalies through public Figure 2; shows the major congenital anomalies by organ system in Oman

Figure 3 :
Figure 3: illustrates the various regions of Oman