DOI: 10.1002/pd.4179
ORIGINAL ARTICLE
Postnatal outcome of congenital anomalies in low resource setting Manisha Kumar1*, Sumedha Sharma2, Manisha Bhagat1, Usha Gupta1, Rama Anand3, Archana Puri4, Anuradha Singh1 and Abha Singh1 1
Department of Obstetrics & Gynaecology, Lady Hardinge Medical College, New Delhi, India Department of Obstetrics & Gynaecology, All India Institute of Medical sciences, New Delhi, India 3 Department of Radiology, Lady Hardinge Medical College, New Delhi, India 4 Department of Paediatric Surgery, Lady Hardinge Medical College, New Delhi, India *Correspondence to: Manisha Kumar. E-mail:
[email protected] 2
ABSTRACT Objective This study aimed to determine the postnatal outcome of congenital malformations in a tertiary care hospital of India. Material and methods This was a prospective study of all women with prenatally detected major congenital malformations. Postnatal follow-up of live born babies was carried out for 1 year. Results There were 574 cases with major congenital anomalies, 523 of which were fully followed. Only 69 women (13.6%) had the initial scan before 20 weeks of gestation. Craniospinal defects were the most common (42.7%), followed by genitourinary anomalies (28%). There was no live birth in cases such as anencephaly, iniencephaly, bilateral renal agenesis, gastroschisis, and cystic hygroma. Survival at 1 year was less than 25% in spina bifida, bilateral cystic kidneys, complex cardiac disease, and non-immune hydrops fetalis. In cases with mild hydrocephalus or unilateral and mild renal disease, the survival was over 75%.
Conclusion In India, the majority of congenital anomalies present late in gestation. Although fetal outcome is invariably poor for severe defects, existing legislation in the country leaves pregnancy continuation as the only option. © 2013 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION The prevalence of major malformations has been variously reported as 3% to 4% of all neonates (in passive surveillance systems) or 6% to 8% of all neonates (in active surveillance systems). Approximately one-fifth of all such malformations are severe and life threatening.1,2 As the developing countries together constitute more than 80% of the world population, the burden of mortality and morbidity in children due to congenital anomaly is far greater in the developing nations. Facilities for early detection and counselling of the couple regarding the risk of recurrence of such anomalies are also more limited. Moreover, the expertise and resources to treat and manage children with congenital anomalies is far from adequate in the developing countries leading to poor outcome of affected children. Congenital anomalies account for 8% to 15% of perinatal deaths and 13% to 16% of neonatal deaths in India.3,4 The birth of a child with severe mental and physical limitation is emotionally and financially taxing for the parents and caregivers. The decision whether to continue or terminate such a pregnancy is influenced by the religious, social, medical, and ethical norms prevailing in that country. The issue becomes Prenatal Diagnosis 2013, 33, 983–989
more complex if these defects are diagnosed in late gestation or after attainment of viability. Termination of such pregnancies is guided by legislation, which varies in different countries. The Indian Medical Termination of Pregnancy (MTP) Act allows for termination of pregnancy till 20 weeks in case of fetal defects. Apart from lethal conditions such as anencephaly, pregnancies diagnosed later than 20 weeks with severe fetal defects cannot be terminated under the law; therefore, there is no option but to continue such a pregnancy. We planned this study to follow the antenatal and postnatal course of such pregnancies so as to provide us with future guidance for prognostication, to provide better management of these cases, and also to find evidence favouring the need for an amendment to the existing MTP laws.
MATERIALS AND METHODS In this prospective study, we included all cases of antenatally detected major anomalies referred to the fetal medicine clinic for the first 3 years of the 4-year study period (February 2008 to January 2011). After diagnosis, women underwent targeted scanning to rule out other congenital malformations as well as © 2013 John Wiley & Sons, Ltd.
M. Kumar et al.
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fetal echocardiography. Appropriate counselling was provided regarding prognosis. Invasive prenatal testing was offered wherever indicated; repeat ultrasound examinations were carried out to follow the evolution of the anomaly. All patients delivered at the institute of study. The women who delivered outside were considered lost to follow-up. When diagnosis of major fetal anomalies was made at less than 20 weeks, termination was offered. If the couple desired continuation of pregnancy or whenever the gestational age was more than 20 weeks, karyotyping and genetic and paediatric surgery consultation was advised. Paediatric cardiology consultation was carried out in cases with cardiac anomalies. The paediatricians were informed about the fetal condition at the time of delivery, so that necessary arrangements for immediate postnatal management could be planned. A comprehensive newborn assessment was carried out especially when the prenatal diagnosis was unclear. Cases resulting in stillbirth or termination of pregnancy underwent fetal autopsy if consented by the parents. Fetal autopsy included photographs to document phenotype, X-rays of the fetus (anteroposterior and lateral), and external and internal examination including histopathological examination of the kidneys and other viscera. Chromosome analysis was attempted whenever fetal sample was available, and the parents gave consent. All live born babies underwent appropriate tests within 3 to 5 days of birth, such as ultrasound, chest X-ray, echocardiography, and electrocardiogram. Other investigations such as intravenous pyelonephrography and retrograde cystourethrography were performed wherever indicated. All cases requiring surgical intervention were referred to specialized departments for further management. Surgery was always offered as an option even if the outcome was seemingly poor, such as in the presence of large or multiple defects. All babies were followed up by phone contact at 1 month, 6 months, and 1 year. Mothers were requested to bring their babies for follow-up, and those who were brought were examined, but because all could not come for follow-up, survival was the only outcome observed.
RESULTS In the first 4 years of the study period, there were 574 cases of major congenital anomalies referred to our fetal medicine unit; of which, 51 were lost to follow-up leaving 523 cases with complete follow-up. The antenatal profile of the women is shown in Table 1. The mean age of women was 25 years. A history of one or more previous stillbirth or neonatal deaths was present in 8.8% and one or more abortions in 19.9% of them. The mean gestational age at presentation was 31.3 weeks. The women presented on or before 20 weeks in only 69 cases (13.2%) and before 24 weeks in 143 cases. Multiple anomalies were observed in 183 cases (35%). Fetal gender was male in 53.9% of cases. Among the 69 women with major fetal anomaly detected before 20 weeks gestation, only one delivered at term (talipes equinovarus); the others chose termination of pregnancy or experienced stillbirth. Among the 454 women who delivered after 20 weeks’ gestation, Prenatal Diagnosis 2013, 33, 983–989
Table 1 Antenatal characteristics of the women with congenital fetal anomalies
Antenatal characteristics
Pregnancy with fetal anomaly (523)
%
Age groups (years) 18–22
149
26.6
23–26
221
41.8
27–30
116
22.3
31–34
29
5.7
≥35 Nulliparity History of stillbirth/neonatal death
18
3.6
277
54.6
44
8.8
1
41
8.1
2
25
4.9
8
1.6
500
98.6
7
1.4
≤20 weeks at diagnosis
69
13.6
21–25 weeks at diagnosis
74
14.6
26–30 weeks at diagnosis
127
25.1
31–35 weeks at diagnosis
114
22.5
36–40 weeks at diagnosis
123
24.3
Low
387
76.3
Middle
112
22.1
8
1.6
≥3 Singletons Twins
Socio-economic status
High
there were 259 (57.0%) stillbirths. Karyotyping was carried out in 50 cases, and abnormal results were found in ten, including monosomy X in two cases (both with cystic hygromas), trisomy 18 in one (cystic hygroma), trisomy 13 in one (polydactyly with holoprosencephaly), trisomy 21 in five (duodenal atresias, ventricular septal defects, bilateral hydronephrosis with increased nuchal fold, IUGR microcephaly), and unbalanced translocation in one (hydrocephalus). Fetal autopsy was carried out in 210 cases. Table 2 displays the type of anomalies, gestational age at delivery, and survival. The most common anomaly was central nervous system anomaly (194 cases) followed by genitourinary (127). In pregnancies presenting before 20 weeks, there were 36 cases with craniospinal defects, most commonly spina bifida (16 cases) and anencephaly (15 cases). Termination of pregnancy was offered and accepted by all (Table 2). Among the cases presenting after 20 weeks’ gestation, anencephaly was the most common anomaly seen (54 cases) followed by hydrocephalous (53 cases). The mean gestational age at presentation of craniospinal anomalies ranged from 24 weeks in anencephaly to as late as 33.9 weeks in spina bifida. Only the cases of anencephaly were terminated before term. There were no live birth in anencephaly and iniencephaly. Live births were highest (77.8%) in mild hydrocephalous, and highest stillbirth was observed in Dandy–Walker malformation and holoprosencephaly. At 1-year follow-up, survival was highest with mild hydrocephalous © 2013 John Wiley & Sons, Ltd.
Prenatal Diagnosis 2013, 33, 983–989 0
3
0
Encephalocele
0
2
0
1
0
Bilateral cystic kidney(multicystic/ polycystic)
Bilateral gross hydronephrosis
Megacystis
Unilateral renal disease
Bilateral mild pylectasis
Genital
0
0
Arrhythmia
Pericardial effusion
TTTS/TRAP
0
2
2
Duodenal atresia
Meconium peritonitis/ascites/ calcification
Omphalocele
Gastrointestinal tract
0
0
Complex heart defect
2
ASD/VSD
Cardiovascular system
4
7
Bilateral renal agenesis
Genitourinary
Misc
18.7
1
Iniencephaly
0
17
21.5
0
0
0
0
0
20
0
21
0
15
0
18.3
19
19
0
0
0
Dandy–Walker malformation/variant
18.5
17.6
0
18
GA at delivery (mean weeks)
Holoprosencephaly
15
16
Spina bifida
0
Anencephaly
2
Severe hydrocephalous
Total
Mild hydrocephalous
Craniospinal defect
Type of anomaly
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Live at delivery
Cases diagnosed at 20 weeks (n = 454)
(Continues)
0
5 (33.3)
7 (43.8)
1 (33.3)
2 (50.0)
2 (35.3)
2 (25)
6 (35.3)
2 (66.7)
14 (78.9)
19 (95.0)
0
11 (42.3)
2 (3.9)
0
1 (25.0)
4 (36.4)
0
0
4 (28.6)
10 (23.3)
0
12 (27.3)
7 (77.8)
Survived at 1 year (%)
Postnatal outcome of congenital anomalies in low resource setting
985
© 2013 John Wiley & Sons, Ltd.
Prenatal Diagnosis 2013, 33, 983–989
0
0
0
0
Gastrochisis
Esophageal atresia
Diaphragmatic hernia
Pleural effusion/lung cyst
6
Immune
Cystic hygroma
1
Conjoined twins
19
0
38
0
18.5
19
0
19.8
0
0
0
0
GA at delivery (mean weeks)
0
0
1
0
0
0
0
0
0
0
0
0
Live at delivery
Cases diagnosed at 20 weeks (n = 454)
0
0
2 (100)
0
1 (8.3)
0
2 (50.0)
2 (9.1)
2 (66.7)
1 (20.0)
4 (57.1)
0
Survived at 1 year (%)
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Table 3 Outcome of some major anomalies in previous studies compared with that in the present study Present study Name of author
Anomaly
Total patients
Falip et al.9
Mild hydrocephalous
10
Severe hydrocephalous
Gaglioti et al.
Spina bifida
Bowman et al.11 12
Follow-up period
Outcome survival (%)
Cases
Follow-up period (months)
Outcome survival (%)
7
12
77
51
>24 months
94
8
>24 months
62.5
44
12
12
25 years
76
43
12
23
118
Dandy–Walker malformation/variant
Ecker et al.
99
1 year
16.2
14
12
28.6
Bilateral hydronephrosis
Damen-Elias et al.13
402
8 years
69.9
26
12
42.3
Bilateral echogenic kidneys
Tsatsaris et al.14
43
34–132 months
44.2
20
12
10
Omphalocele
Salihu et al.15 Fratelli et al.16
29 16
Perinatal outcome
>75 44
2
12
0
Gastroschisis
Fratelli et al.16
40
Postnatal outcome
80
3
12
0
Duodenal atresia
Dalla Vecchia et al.17
138
25 year
86
16
12
43.8
Oesophageal atresia
Sparey et al.18
108
12 months
78.4
7
12
57.1
Table 4 Termination of pregnancy laws in different countries S no
Country 8
1.
India
2.
Turkey
6
Gestation till which termination allowed
Circumstances in which allowed
Up till 20 weeks
Grave risk to mother’s health, congenital anomaly with grave risk to life, failure of contraception, rape
Any gestation
Serious maternal condition Fetus at high risk of severe disability
7
Any gestation
Severe risk to maternal life Severe fetal anomalies
3.
Italy
4.
Spain7
After 22 weeks
Risk to mother’s physical and mental condition
5.
France7
Any gestation
Baby suffering from serious incurable condition
6.
Germany7
Any gestation
Grave injury to maternal health
7.
The Netherlands7
After 24 weeks
Condition that will lead to early neonatal death, survival with irreparable defect
8.
Luxumburg7
After 12 weeks
Very serious threat to life of mother and unborn child
7
Any gestation
Physical and mental leading to serious handicap
After 22 weeks
Allowed if fetus cannot survive
11.
USA
19
Any gestation
Threat to life, health of the mother (any time), on request till viability
12.
Israel5
Any gestation
Approved by regional supreme committee
Not specified
On request
Threat to life
Not specified
9.
UK
10.
Sweden7
19
13.
China
14.
Pakistan19
(77.8%). Survival was only 23.3% and 27.3% in spina bifida and severe hydrocephalous, respectively; none of the babies with holoprosencephaly survived beyond 1 year of life. Among cases with genitourinary malformations, presenting before 20 weeks, bilateral cystic kidneys (either multicystic or Prenatal Diagnosis 2013, 33, 983–989
polycystic) were the most common (seven cases) followed by bilateral renal agenesis (four cases). One case of mild pyelectasis experienced fetal death at 20 weeks. In cases presenting after 20 weeks’ gestation, bilateral cystic kidneys (either multicystic or polycystic) was the most common © 2013 John Wiley & Sons, Ltd.
988
diagnosis (51 cases), unilateral renal disease was seen in 20 cases, and severe bilateral hydronephrosis in 26. The cases with bilateral renal agenesis did not survive; pregnancies were carried till term in most cases of unilateral renal disease and mild renal disease, with overall survival at 1 year of 95% and 78.9%, respectively. Of the cardiovascular defect cases, only two presented before 20 weeks’ gestation, 37 were initially seen after 20 weeks. The highest number were septal defects (17 cases) followed by complex cardiac defects such Ebstein anomaly, tetralogy of Fallot, and transposition of the great vessels. Most of the cases with heart defects were diagnosed late in gestation (mean gestational age: 33 weeks); the pregnancy was carried out till term in most of the cases, with a mean gestational age at delivery of 36 weeks. The survival was good in both cases with pericardial effusion. The outcome was worse in twin–twin transfusion syndrome and twin reverse transfusion syndrome. In gastrointestinal and abdominal wall defects (Table 2), duodenal atresia (16 cases) was the most common diagnosis, and meconium peritonitis was observed in 15 cases. The cases with duodenal atresia and meconium peritonitis had mean gestational age at delivery of 35 weeks. The outcome and survival after 1 year was best in duodenal atresia cases because of operative intervention after delivery. Of the thoracic abnormalities (15 cases), tracheoesophageal fistula (TEF) was the most common followed by diaphragmatic hernia in five cases. Patients presented late in gestation (mean gestational age: 34 weeks), and the pregnancies were mostly carried till term. Although the live birth rate of TEF and diaphragmatic hernia was 85.7% and 40%, respectively, survival at 1 year was only 57% and 20%, respectively. Hydrops fetalis accounted for 26 cases; most of them seen after 28 weeks’ gestation. Intrauterine transfusion allowed survival in two of the isoimmunized babies; the prognosis of nonimmune hydrops was poor with 22% live birth and only 9.1% survival after a year. The outcome of neuromuscular disorder (e.g. Pena– Shokeir, three cases) was poor except for cases with isolated abnormality (namely talipes and polydactyly).
DISCUSSION We have found that gestational age at diagnosis in our series was late in the majority of cases. There were only 13.2% of cases who presented at or before 20 weeks. In women who presented after 20 weeks, termination could be offered only to those with fetal anencephaly. In the rest of cases, pregnancy had to be continued till intrauterine death or delivery. Although cardiac defects are usually the most prevalent, in our study, neural tube defects were the most common anomaly seen. This may be due to missed diagnoses of cardiac anomalies as fetal echocardiography was carried out only in cases with other malformations present or in which gross cardiac anomaly was suspected on routine ultrasound. Similar to our findings, in the study by Vaknin et al. on causes of late termination of pregnancy, central nervous system defects were the most common; the authors concluded that fetal anomalies could have been diagnosed earlier in more than half of the Prenatal Diagnosis 2013, 33, 983–989
M. Kumar et al.
women undergoing late terminations, suggesting that early scanning and screening in pregnancy must be promoted.5 Interesting observations can be made by a comparison of outcome data between our series and those published from developed countries, where facilities and expertise available differ greatly from those of developing nations. We did a literature search on the subject selecting the most recent series with the largest number of cases and with a minimum followup of 12 months (Table 3). The outcome of anomalies in our cohort was different from that published in the literature (Table 3). The long-term outcome of anomalies such as spina bifida, complex cardiac defects, diaphragmatic hernia, nonimmune hydrops, bilateral cystic kidneys, and bilateral renal agenesis reveals survival in less than 25% of cases. Providing outcome information of a particular anomaly in our setting will help both care givers and parents to form realistic expectations regarding the prognosis of a particular anomaly under existing conditions. More such studies such as ours are required regarding outcome in specific settings and with longer follow-up of individual anomalies. Termination of pregnancies in cases destined to adverse outcome if offered could have saved the trauma that the family underwent in carrying the pregnancy till spontaneous labour and delivery. The MTP Act of 1971 was the first act all over the world that allowed women to seek abortion up to 20 weeks on the ground of contraceptive failure. With time, many countries subsequently have allowed termination of pregnancy after 20 weeks if pregnancy poses a danger to maternal life or if fetal defects are severe. We have reviewed the literature searching for laws related to late pregnancy terminations. Most of the developed nations allow termination if fetal malformations are severe (Table 4). In many European countries, termination of pregnancy can be performed up to term in cases with lethal or severe fetal abnormalities. These include France, England, Wales, Belgium, Finland, and Norway under restricted conditions and Sweden following approval by national board of health and welfare 6. The full text of the world’s abortion laws can be consulted at the web site of the Annual Review of Population Law at www. hsph.harvard.edu/population/abortion/abortionlaws.htm. At present, with the advent of new drugs, pregnancy termination has become safer even if carried out at later gestation. A study carried out by Aslan et al. shows no differences in maternal complications for termination performed before 22 weeks compared with that after 22 weeks gestation.6 In the study carried out by Habiba et al. regarding obstetricians’ experience about late termination in eight European countries, the authors concluded that most obstetricians were satisfied with the current practice and law regarding termination in their respective countries.7 In our country, though, the situation is quite different: Phadke et al. have examined the physician and patients’ view of late terminations; they concluded that both lay persons and the medical community in India would favour a revision of the legislation to allow late termination particularly for fetal conditions with poor outcome.8 Indications for terminations should include not only lethal fetal conditions but also those conditions that lead to severe impairment later in life. Maternal autonomy with a balanced legislation is the need of the hour. © 2013 John Wiley & Sons, Ltd.
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WHAT’S ALREADY KNOWN ABOUT THIS TOPIC?
WHAT DOES THIS STUDY ADD?
• The outcome of various congenital anomalies in developed countries is well documented. • The availability of expertise and resources to manage and treat children with congenital anomalies has a major impact on subsequent morbidity and mortality.
• This study provides data regarding postnatal outcome of various fetal anomalies in a low resource setting. • It highlights the need to make screening for fetal anomalies affordable and available to all women as well as the importance of timely diagnosis of major fetal anomalies so that the option of termination in cases with poor prognosis can be offered.
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