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LITHUANIAN UNIVERISTY OF HEALTH SCIENCES FACULTY OF MEDICINE
Department of Obstetrics and Gynaecology
Antenatal diagnosis, Maternal and Neonatal outcome analysis of
Myelomeningocele, Spina bifida at the Lithuanian University of Health Sciences Hospital (2016-2017)
Submitted in partial fulfilment of the requirements for the degree of Master of Medicine
Author: Mobby Elizabeth Mathew Supervisor: Dr Daiva Simanavičiūtė
Kaunas
2018
2 Table of Contents
Summary 3
Summary in Lithuanian 5
Acknowledgements 8
Conflicts of interest 8
Ethics committee clearance 8
Abbreviations 9
1. Introduction 10
2. Aims and Objectives of the thesis 12
3. Literature review 13
4. Methods and methodology 21
5. Results 23
6. Discussion of the results 36
7. Conclusions 43
8. Practical recommendations 44
References 45
Annex 50
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Summary
Author’s name and surname: Mobby Elizabeth Mathew
Research Title: “Antenatal diagnosis, Maternal and Neonatal outcome analysis of Myelomeningocele, Spina bifida at the Lithuanian University of Health Sciences Hospital 2016-2017”.
Aims: The aim of this study is analysing the accuracy of antenatal diagnosis, maternal and neonatal outcomes for pregnancies diagnosed with myelomeningocele- Spina Bifida (MMC-SB).
Objectives:
1. To calculate the incidence of SB-MMC in Lithuania and the demand for potential foetal therapy through evaluating all the delivered and/or terminated cases for SB-MMC in 2016-2017.
2. To assess the sensitivity of SB-MMC antenatal diagnosis and precision of SB level diagnosis as an indicator for prognosis to aid parents make informed decisions.
3. To evaluate obstetrical outcomes including gestation and mode of delivery.
4. To evaluate neonatal outcomes such as hydrocephalus, need for ventriculo-peritoneal shunting, clean intermittent catheterisation and administration of antibiotics postnatally during hospital stay at the neonatal unit.
Methodology: A group of 25 mothers with a diagnosis of SB and/or MMC was selected during the years 2016-2017. All cases that underwent MMC surgical repair or termination of pregnancy for SB-MMC in 2016-2017 were included into the study. Parameters that were analysed included maternal and neonatal demographic statistical features, the adequacy of antenatal diagnosis, gestation at diagnosis, gestational age at delivery, mode of delivery, postnatal neurological status, operations, need for catheterisation of new born, postnatal complications of infections, and the duration of neonatal hospital stay. All collated data were analysed using IBM SPSS 24.0 Statistics®.
Results: Although the overall sensitivity of antenatal SB/MMC diagnosis was 72%, only 5 cases out of
the 25 were diagnosed prior to 23 weeks gestation. In three cases pregnancy was terminated shortly after
antenatal diagnosis of SB-MMC. The earliest gestational age at diagnosis was 19 weeks with the latest
at 39 weeks, a median of 32 weeks gestation and, 6 cases were not diagnosed antenatally. All but one
delivery was at term with no record of induced deliveries. 50% of mothers delivered naturally and the
other half was delivered through C-Section. Elective and emergency C-Sections were 6 and 2
respectively. The median birthweight of 22 babies were 3250 grams and the lowest and highest recorded
birthweight was 2160g and 4190g respectively. Three neonates (3/22= 13.6%) were Small for gestational
age (SGA) with the birth weight under the 5
thcentile. Overall, 19/22 and 20/22 neonates had an APGAR
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score of >7 at 1 and 5 minutes respectively. More boys had SB/MMC diagnosis than girls, the difference was not statistically significant. Of the 21, 9 had open and 12 was concluded to have myelomeningocele.
Out of 22 patients, there was 36% absolute and 28% relative accuracy at diagnosing the correct level of SB lesion antenatally. Therefore, absolute or partial was in 64% and in 2/3. 17 cases did not report on any antenatal leg movements, while 2/3 had no leg movements recorded on the antenatal notes. All but one case had antenatal hydrocephalus, in 6 cases there was missing information, as no antenatal records were available. Postnatally 17 babies out of the 19 had hydrocephalus with 3 missing cases. Over 50%
neonates had MMC diagnosis with 26% MRI scans indicating Arnold Chiari II malformation. 65% of neonates had a VP shunt placement. Also, 61% of babies developed infections during their stay at the hospital with highly resistant bacteria. While CIC was performed, 40% of whom developed UTI with an increased risk of nosocomial infection as their stay at the hospital got longer.
Conclusions and Recommendations:
1. With the assumption that all SB cases within Lithuania were transferred to Lithuanian University of Health Sciences Hospital for neurosurgical treatment, the incidence rate for SB/MMC was 3.6 per 10,000.
2. A) Although the overall sensitivity of SB and/or MMC antenatal diagnosis is >70%, at present SB is not diagnosed early enough to suggest foetal therapy, especially since less than a quarter of cases were diagnosed prior to 25 weeks. In 28% of SB diagnosis the lesion levels were par- tially accurate antenatally in comparison to postnatal diagnosis.
B) There however was, a lack of compliance by the physicians to note leg movements antenatally as only 2 cases were reported as having any form of movements antenatally that increased to 15 cases postnatally. This discrepancy needs rectification.
3. There was a 50% split among C-sections and vaginal deliveries. 10 women underwent C-Sec- tions of whom 6 underwent an elective procedure. There was no stillbirth reported and apart from the SB diagnosis no further complications were reported for obstetrical outcomes.
4. A) Most neonates were term deliveries with a good APGAR score. 3/22 were SGA and all neo- nates underwent meningoplasty for SB on the first day postnatally.
B) 17/22, 77% of the neonates had hydrocephalus. Likewise, 2/3 cases needed VP shunting. This
is an important procedure since it is accompanied by comorbidities including infections and re-
vision surgical repairs that could potentiallybe prevented by implementing foetal surgery.
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C) Clean intermittent catheterisation was started during the neonatal period for 15 babies of whom 6 or 40% developed highly resistant Hospital Acquired UTI and PN. The neonatal infec- tion control policies need auditing to ensure these numbers are lowered.
Summary in Lithuanian
Įskilo stuburo ir mielomeningocelės prenatalinės diagnostikos bei perinatalinių ir naujagimystės komplikacijų analizė Lietuvos Sveikatos Mokslų Universiteto Klinikose 2016-2017 metais.
VI Kurso LSMU studentės Mobby Elizabeth Mathew
Tyrimo tikslas: Išanalizuoti įskilo stuburo ir mielomeningocelės prenatalinės diagnostikos tikslumą bei perinatalines ir naujagimystės komplikacijas visais atvejais, kai buvo diagnoztuoas įskilas stuburas ar mielomeningocelė naujagimiams, operuotiems LSMUL 2016-2017m. ar dėl šios diagnozės buvo nutrauktas nėštumas.
Tyrimo uždaviniai: 1. Apskaičiuoti įskilo stuburo ir/ar mielomeningocelės naujų atvejų per metus dažnį Lietuvoje ir potencialų vaisiaus terapijos poreikį, analizuojant gimusių LSMUL 2016-2017 metais įskilu stuburu ir/ar mielomeningocele sergančių ir/ar operuotų naujagimių ar kai nėštumas dėl šios patologijos buvo nutrauktas medicininę dokumentaciją.
2. Įvertinti įskilo stuburo-mielomeningocelės prenantalinės diagnostikos jautrumą ir įskilo stuburo aukščio nustatymo tikslumą, kaip svarbiausius faktorius, suteikiančius tėvams daugiausiai informacijos, kad jie galėtų apsispręsti dėl tolimesnės nėštumo eigos ir gydymo naudos-rizikos santykio,
3. Įvertinti perinatalinę baigtį, gestacinį amžių ir gimdymo būdą, kai buvo diagnozuotas įskilas stuburas ir/ar mielomenigocelė prenataliai ar gimė naujagimis, kuriam buvo nustatyta ši diagnozė.
4. Įvertinti naujagimystės komplikacijas, hidrocefalijos dažnį, ventrikuloperitoninio šuntavimo ir protarpinės švarios kateterizacijos poreikį, infekcines komplikacijas ir antibiotikų skyrimo dažnį, neurologinę naujagimio būklę pirmosios hospitalizacijos LSMUL naujagimių ligų skyriuje metu.
Tyrimo metodai: 2016-2017 metais buvo rasti iš viso 25 atvejai, kai naujagimiai, gydomi LSMUL
naujagimių skyriuje buvo operuoti dėl įskilo stuburo ir/ar mielomeningocelės ar nėštumas dėl šios
diagnozės buvo nutrauktas. Analizuojant akušerines ir naujagimio ligos istorijas bei ambulatorines
LSMUL Moterų konsultacijos korteles buvo išanalizuotos nėštumo, gimdymo ir naujagimystės
komplikacijos, antenatalinės diagnostikos jautrumas ir tikslumas, gestacija diagnozės nustatymo ir
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gimdymo metu, gimdymo būdas, naujagimio neurologinė būklė, atliktos operacijos, protarpinės švarios kateterizacijos poreikis, infekcinės komplikacijos ir naujagimio hospitalizacijos trukmė. Statistinė analizė atlikta naudojant IBM SPSS 24.0 Statistics® paketą.
Rezultatai: Nors apskaičiuotas bendras Spina bifida su/ar be mielomeningocelės prenatalinio ultragarsinio tyrimo jautrumas 76%, tik 6 atvejais iš 25 ši patologija buvo diagnozuota iki 25 gestacijos savaičių. Trim iš jų nėštumas buvo nutrauktas. Anksčiausiai diagnozė buvo nustatyta 19 nėštumo savaičių, vėliausiai 39 nėštumo savaičių, mediana 32 nėštumo savaitės, 6 atvejais diagnozė buvo nustatyta tik naujagimiui gimus.. Visi naujagimiai, išskyrus vieną, buvo išnešioti. 50% nėščiųjų pagimdė natūraliais gimdymo takais, kitai pusei atliktas cezario pjūvis. Planinis cezario pjūvis buvo atlikas 6 iš 10 atvejų, skubus 2 iš 10, kitais dviem atvejais duomenų nepavyko rasti. Gimimo svorio mediana buvo 3250 gramai, mažiausias ir didžiausias svoris buvo 2160 g ir 4190 g atitinkamai. Trys naujagimiai iš 22 (13,6%) buvo maži pagal gestaciją, (gimimo svoris mažesnis nei 5 tas procentilis). 19 iš 22 ir 20 iš 22 naujagimių buvo įvertinti pagal APGAR aukštesniu įvertinimu nei 7 po 1 ir 5 minučių atitinkamai. Spina bifida ir/ar mielomeningocelės diagnozė buvo nustatyta daugiau berniukų nei mergaičių, bet skirtumas nebuvo statistiškai patikimas. 9 atvejais buvo nustatyta atvira Spina bifida, likusiems 12 - mielomeningocelė. Iš 22 pacientų, 36% atvejų Spina Bifida aukštis (lygis) prenataliai buvo nustatytas teisingai, 28% atvejų – reliatyviai teisingai. Dviem trečdaliams atvejų prenatalinio ultragarsinio tyrimo apraše nebuvo jokių komentarų apie vaisiaus kojų judesius. Visais atvejais, išskyrus vieną, prenataliai buvo nustatyta hidrocefalija, 6 atvejais, tikriausiai, kai Spina bifida buvo diagnozuota po gimimo, nebuvo informacijos apie prenatalinį ultragarsinį tyrimą. Naujagimystėje hidrocefalija buvo nustatyta 17 naujagimių. Po gimimo kiek daugiau nei 50% naujagimių buvo nustatyta Mielomeningocelės diagnozė, 26% BMR diagnozuotas Arnold Chiari II sindromas. 65% naujagimių prireikė ventrikuloperitoninio šunto. 61% naujagimių buvo gydomi dėl infekcijos. 40% naujagimių, kuriems reikėjo švarios protarpinės kateterizacijos pasireiškė hospitalinės rezistentiškos floros sukelta šlapimo takų infekcija ar pielonefritas, rizika didėjo ilgėjant hospitalizacijos trukmei.
Išvados ir rekomendacijos:
1. Darant prielaidą, kad visais atvejais, kai prenataliai arba gimus naujagimiui buvo diagnozuota spina bifida ir/ar mielomeningocelė, naujagimiai gimė ar buvo pervežti į LSMUL neurochirurginiam gydymui, apskaičiuotas naujų Spina bifida/mielomeningocelės atvejų per metus dažnis Lietuvoje buvo 3.6 /10,000 gyvų gimusių.
2. 2.A. Nors bandras prenatalinio ultragarsinio tyrimo jautrumas nustatyti Spina Bifida ir/ar
mielomeningocelę yra didesnis nei 75%, šiuo metu Spina bifida dažniausiai nenustatoma pakankamai
anksti, kad būtų galima siūlyti gydymą vaisiui, iki 25 gestacijos savaičių diagnozė buvo nustatyta rečiau
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kaip kas ketvirtam sergančiajam. 2.B. Spina bifida aukštis tiriant ultragarsu prenataliai buvo nustatytas pakankamai tiksliai, lyginant su naujagimystės diagnoze. Tiriantys nėščiąsias ultragarsu daugiau nei dveim trečdaliais atvejų nesilaikė rekomendacijos atžymėti kojų judesius ultrgarso apraše, nors tai yra svarbu aptariant su tėvais naujagimio judėjimo prognozę.
3. Pusė nėščiųjų pagimdė natūraliai, kitai pusei buvo atlikti cezario pjūviai. Perinatalinių netekčių nebuvo. Dažniausiai nebuvo jokių kitų nėštumo komplikacijų ir Spina bifida ir Mielomeningocelė buvo vienintelė diagnozė.
4.A. Dauguma naujagimių gimę buvo įvertinti gerais ir labai gerais balais pagal Apgar. 3 naujagimiai iš 22 buvo maži pagal gestacinį amžių.
4.B. 17 iš 22 naujagimių (77%) buvo diagnozuota hidrocefalija. Visiem naujagimiaims Spina bifida meningoplastika buvo atlikta pirmąją gyvenimo parą. Ventrikuloperitoninio šunto prireikė dviem iš trijų naujagimių. Vienas iš aprašomų vaisiaus gydymo potencialių privalumų yra tai, kad ventrikuloperitoninio šuntavimo galimai prireiktų rečiau.
4.C. Protarpinės švarios kateterizacijos dėl neurogeninės pūslės prireikė beveik 70% naujagimių, 40%
iš jų prisidėjo rezistentiškos hospitalinės floros sukelta šlapimo takų infekcija ar pielonefritas. Būtina
naujagimių infekcijų kontrolės politika, siekiant sumažinti šių komplikacijų riziką.
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Acknowledgements
I am forever grateful to Dr Daiva Simanaviciute for her unwavering support and guidance throughout the course of the study. Thank you for being an exemplary role model to aspire to become and for setting the best example possible in terms of being an ardent teacher. Your passion for medicine and positive outlook on life is truly inspirational.
Conflict of interest
The author reports no conflict of interest.
Ethics committee clearance
Ethics approval was obtained from Lietuvos Sveikatos Moklsų Universitetas Bioethikos centras.
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Abbreviations
1. CM-II – Arnold Chiari II malformation 2. MMC - Myelomeningocele
3. MRI – Magnetic Resonance Imaging 4. NTD - Neural Tube Defect
5. PN - Pyelonephritis 6. QOL – Quality of Life 7. SB - Spina Bifida
8. SDG – Sustainable Development Goals 9. SGA – Small for Gestational Age 10. TOP – Termination of Pregnancy 11. USS – Ultrasound scan
12. UTI – Urinary Tract Infection
13. VP shunt: Ventriculo-peritoneal shunt
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1. Introduction
Spina bifida (SB), is known to be the second most prevalent congenital disorder after Down’s syndrome worldwide and in Lithuania(1–5). Spina bifida is a largely preventable neural tube defect (NTD), and is one of the leading cause for lifelong disability(6). With the proportion of under-five deaths from birth defects increasing, this serious health concern cannot be overlooked, especially by countries that are currently aiming to attain the health-related targets before 2030 - Sustainable Development Goals (SDG)(1). The clear majority of individuals living with SB have had ventriculo-peritoneal (VP) shunts placed that has contributed to their improved quality of life. While, there are people living well into their 60’s and 70’s, their life expectancy is remain unknown(6,7).
Myelomeningocele and open spina bifida is the most severe form of NTD affecting the central nervous system and is characterised by the meninges and spinal cord protruding through the open vertebral arches that could result in lifelong paralysis(6,8,9). Causes of SB are thought to be the complex interaction of genetical and environmental factors that affect pregnancy. Bowman and McClone, 2001, concluded from their studies that a minimum of 75% individuals with SB live onto adulthood because of advanced treatment options, surgeries and other therapies that are readily available(2,4,10,11).
Approximately 1500 babies are born with spina bifida in the USA alone and around 300,000 infants are born having a neural tube defect worldwide(8,12–14). Alongside being hospitalised an average of 2.4 times during their first year of life as indicated in one study, the cost is considerably higher than uncomplicated births(13).
Preventative measures are known worldwide yet, prevalence remain high together with increased termination rates which are often misunderstood to be a form of preventative measure by some European countries(8,15,16)). Folic acid, a B vitamin is scientifically proven to significantly lower the risk of NTD, is graded level A recommendation based on evidence from meta-analysis of randomised controlled trials, though this does not guarantee the baby will not have SB (6–10,16–18). Up to 70% of NTD defects including SB can be prevented if women planning pregnancy if folic acid is taken daily prior to conception and during the first trimester(19).
Medical issues related with SB include hydrocephalus which, could occur because of Arnold Chiari II
malformation (CM-II)(2,5,10,12,13,20–22). Arnold Chiari II malformation is a more severe form of
brain displacement into the neck(21,22). Mobility is a concern and depend on the level of lesion. One of
the more important arguments for prenatal repair of MMC is being able to prevent CM-II and thus
knowing about reversing the effects postnatally is of tremendous value(21,22).
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Most children with SB are able to walk with the help of orthopaedic braces and other assistive devices including crutches(4). Lesions within the thoracic and or high lumbar regions are said to end up using a wheelchair as a main mode of movement(10,23,24). Another issue is that SB babies will have a neurogenic bowel and bladder(6,18,25). This is due to the small segments of the sigmoid colon, bladder and the anus are controlled by the sacral nerve roots, namely S2-S4 and continence is achieved through medical and surgical interventions(6,10,25–27).
In-utero surgical repair was first established in the late 1990’s showing initial promise particularly for hydrocephalus and Arnold Chiari II malformation outcomes(10,16,28). A seven year NIH funded Management of Myelomeningocele Study, MoMS, with evidence level 1, found reduced incidence for VP shunt placements, decrease in hindbrain herniation and other complications normally associated with MMC(2,5,29).
The rational for this study is to look at the current situation regarding antenatal diagnosis of SB, more
specifically if SB and lesion level is accurately established early on during pregnancy to include foetal
therapy as a potential treatment outcome for mothers. Also, to explore outcomes and measures that can
be taken to improve.
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2. Aim & Objectives
Aims: The aim of this study is to analyse the accuracy of antenatal diagnosis, maternal and neonatal outcomes for pregnancies diagnosed with myelomeningocele- Spina Bifida (MMC-SB).
Objectives:
1. To calculate the incidence of SB-MMC in Lithuania and the demand for potential foetal therapy through evaluating all the delivered and/or terminated cases for SB-MMC in 2016-2017.
2. To assess the sensitivity of SB-MMC antenatal diagnosis and precision of SB level diagnosis as an indicator for prognosis to aid parents make informed decisions.
3. To evaluate obstetrical outcomes including gestation and mode of delivery.
4. To evaluate neonatal outcomes such as hydrocephalus, need for ventriculo-peritoneal shunting,
clean intermittent catheterisation and administration of antibiotics postnatally during hospital
stay at the neonatal unit.
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3. Review of the Literature
3.1 What is Myelomeningocele?
Myelomeningocele (MMC) or open spina bifida is a congenital defect of the central nervous system that is characterised by the meninges and spinal cord protruding through the open vertebral arches that could result in lifelong paralysis(3,5,6,30,31). MMC is characterised by a fluid-filled sac containing an exposed spinal cord and nerves. The main consequence of an open NTD is that the central nervous system develops abnormally that can lead to hydrocephalus, hindbrain herniation, and neural elements that can be damaged due to being exposed to toxic effects of the amniotic fluid(2,29,31,32). This eventually can lead to long-term morbidity and mortality. While 75% of affected individuals survive to adulthood, one-year survival rate for infants is 88-96%. MMC is one of the most common birth defects that affect the central nervous system giving rise to permanent disability(2,31).
MMC is a NTD where the spinal cord is unable to develop completely due to improper closure of the neural tube at around 28 days of gestation(6,31,33). Since the overlying bones and skin are incompletely formed and there is no musculoskeletal cover, the corresponding area of spinal cord is thus exposed to amniotic fluid in utero(6,31,33). MMC is one of the most common birth defect affecting the central nervous system giving rise to permanent disability(6,8,10). Since there is no musculoskeletal cover, neural tissue can be destructed secondarily via trauma or amniotic fluid exposure that takes place throughout gestation(6,8,10).
Decompressing hydrocephalus requires a ventriculo-peritoneal shunt to be placed that diverts cerebrospinal fluid (CSF). This is performed in over 80% of the cases(8,10,26). The need for shunt placement depend on level of lesion with an increased need when the level of lesion is higher and is associated with more complications including infection, obstruction, displacement and even shunt revision(2,12,13,18,34).
Caudal mispositioning of the brain creates the Arnold Chiari ll malformation involving the small posterior fossa and associated pathology of the cerebellum and brain-stem(12,18). Obstructive hydrocephalus occurs when the midbrain is compressed at the level of the fourth ventricle(5,15,35).
Symptoms may need urgent neurosurgical intervention and they include pseudobulbar palsy, difficulty
regulating breathing, dysfunctioning vocal cord, difficulty swallowing food and decreased strength or
function of the upper limb(6). The Arnold-Chiari ll malformation is present in over 75% of patients and
can clinically manifest as apnoea, swallowing difficulties, quadriparesis and difficulties
coordinating(12).
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Most infants with spina bifida have a lesion at or above sacral level. Since the sacral nerves S2-S4 control bladder, they are almost always abnormal and normal physiology is rare.(6,8,13,18,36) The risk for recurrent urinary tract infection is increased because a neurogenic bladder does not empty properly and this could also lead to kidney failure(4,25,26). It is the increased pressure in the bladder from poor emptying that can lead to vesicoureteral reflux, hydronephrosis and subsequent kidney damage(2,18,26).
Kidney failure used to be the leading cause of death in spina bifida before realising the need for improved bladder management(6,37).
Clean intermittent catheterisation and using anticholinergic medication can decrease bladder spasms and is a way of managing neurogenic bladder(25,26). Maintaining intra-vesicular pressure in a low to normal range can help preserve the kidney's in infants(6). As children grow older, the goal of the bladder program expands to include social continence(18). Periodic renal and bladder scans are essential for maintaining healthy kidneys. Hydronephrosis and bladder wall thickening can be monitored periodically(6,18,25,38). Also, DMSA scan and VCUG are indicated in recurrent UTI(6,38). A neurogenic bowel is also common in spina bifida affecting 90% of patients, since the rectal sphincter like the bladder is innervated by sacral nerves S2(4,25). When there is a loss of voluntary control of the external anal sphincter, the recto-anal sensitivity is lost resulting in abnormal rectosigmoid compliance and recto-anal reflexes(6).
3.2 Epidemiology
While an estimated 300,000 children are born with NTD in USA, almost half of which constitute spina bifida(1,6,8). Alongside being hospitalised an average of 2.4 times during their first year of life as indicated in one study, the neonatal cost is considerably higher than uncomplicated births(1,39,40). The past few decades have witnessed a drastic and improved development at diagnosing and treating neural tube defects, NTD. Nonetheless, in spite of these advancements NTDs are still a major contributor to morbidity and mortality across the globe(18,24). In the USA alone, 1 in 1000 live births have a diagnosis of MMC. This has a greater impact especially because the lifetime risk of death in almost 10 times higher for SB compared to the general population(18,41,42).
3.3 How can you prevent SB?
Spina bifida, associated with severe motor, sensory and structural malformations is a preventable
neural tube defect. One of the most studied risk factors for neural tube defects is the maternal
consumption of folic acid at pre-conception period and early pregnancy(6,19,31,32). De-Regil et al, from
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their systematic review on the effects of folic acid supplementation found substantial evidence to support the notion that folic acid intake did prevent neural tube defects(43). There is substantial amount of evidence to suggest the majority of spina bifida cases can be prevented through optimal intake of folic acid, approximately 400mcg/day during the peri -conceptional period with level IA evidence from the meta-analysis of randomised control trials(6,10,15,16,19,31,32).
Wang et all, also conducted a meta-analysis on decreased vitamin B12 and the risk for NTD since, vitamin B12 is necessary to metabolise folic acid and low levels resulted in the accumulation of methylmalonic acid and homocysteine in the blood(4). They also found evidence that mothers with low vitamin B12 had an increased risk of giving birth to children with neural tube defects with level IA evidence from the meta-analysis of randomised control trials with grade A recommendation(24,43).
3.4 Diagnosis and current treatment options
Prenatal diagnosis of spina bifida is performed by measuring maternal alpha feto protein at 16 weeks of gestation or by foetal ultrasound at 18-20 weeks of gestation with a testing accuracy of 85- 90%(6,7,14,24,27).
Spina bifida is managed at or even before birth and will continue throughout life. Firstly, the MMC must be repaired. Research has shown early closure of the defect can lead to increased protection of the spinal cord and its nerve roots(9,18,27). MMC repair is usually done as soon as possible after delivery within 24-48 hours. Intrauterine surgical repair prenatally gives the nervous system a normal period for development and is known to show positive outcomes, however, prenatal risk is increased(28).
Treatment modalities have advanced a great deal and together with improved evidence based medical knowledge, people with the condition live well into adulthood in the United States. Currently, managing MMC includes life-long comprehensive neurological, urological and musculoskeletal, management (6,28,34).
Based on the level of paralysis, muscle imbalance can occur around joints which, can lead to a variety
of difficulties including hip dysplasia, talipes equinovarus or clubbed feet, calcaneus foot or the
imbalance between active dorsiflexion and paralysed plantar flexion, vertical talus, cavovarus foot, ankle
valgus, femoral torsion, tibial torsion and scoliosis. Surgical intervention is a better way to manage
muscle imbalance when indicated, by a paediatric orthopaedic surgeon(6,13,39,44).
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3.5 In-Utero Surgical Repair
The concept of in-utero closure to improve outcomes was proposed mainly because of the ability to reliably diagnosis the condition prenatally and the life-long implications associated with MMC(5,10,45,46).
Animal studies were initially completed using sheep model since they mimic human pathophysiology most reliably(8,16,28). Mid-gestation, a spinal defect was introduced and was exposed to the un-utero environment. Later, the defect was closed using the latissimus dorsi flap and then delivery at term. The lambs that underwent in-utero closure had almost normal motor function, intact sensation and improved bladder and bowel control as well as the reversal of hindbrain herniation(8,16,28). This was not the case in unrepaired lambs that had flaccid paraplegia, lack of sensation in the hind limbs and bowel and bladder incontinence. It was these animal studies that laid the groundwork for advancing to human pilot studies(8,13,26).
Initially MMC closures in-utero were performed endoscopically using skin graft. However, the outcomes were poor and thus, open foetal techniques were then explored(35,47,48). Preliminary reports from a series of open foetal MMC closure undertaken between 22-30 weeks of gestation by the Children's Hospital of Philadelphia showed promising results. Overall, there was a significantly decreased need for shunting with improvement in motor function. Moreover, the procedures proved to be technically feasible(16,17,28).
On the other hand, studies were limited in that historical controls included potential patient selection bias. Therefore, to identify the true usefulness of in-utero MMC closure, a randomised control study needed to take place and that gave rise to the Management of Myelomeningocele Study MOMS trial(2,29,32).
Before the twenty-first century, expectant parents who received the diagnosis of an open NTD had two options, to either terminate the pregnancy or delivery closely followed by postnatal closure of the defect.
Since most abnormalities are routinely found through scans and sampling, prenatal therapy is a possibility. The rationale behind prenatal surgery is the hope of preventing progressive neurological decline in the child(13,28,36).
Other than dealing with the life-long impact of spina bifida on affected individuals, the associated
increased financial demands cannot be omitted. A cost-effective model of foetal surgery for MMC
closure projected to save US$2,066,778 for every 100 cases that were performed(2,16,18).
17
3.6 MOMS Trial
The MOMS trial was stopped after randomising 183 patients due to its efficacy. A 30 month follow up report showed a significant interaction between gender and surgery on subgroup analysis. The boys in the subgroup demonstrated improved functional and psychomotor developmental index(2,16,29,32).
Inclusion criteria consisted of singleton pregnancy, lesion from T1-S1, evidence of hindbrain herniation, Gestational age of 19.0-25.9 weeks, normal karyotype and maternal age of 18 years or older(2,29).
Exclusion criteria consisted of foetal anomaly that was unrelated to myelomeningocele, severe kyphosis greater or equal to 30 degrees, multiple gestation, previous spontaneous preterm birth <37 weeks, short cervix <20mm, placental abruption or abnormal placentation such as placenta previa, obesity defined as BMI>35, maternal medical condition that would pose increased risk such as insulin-dependent diabetes, poorly controlled hypertension, documented history of incompetent cervix, maternal HIV, HepB,C positivity, uterine anomaly such as multiple fibroids or Mullerian duct abnormality, previous hysterotomy, patient does not have a support system, unable to comply with travel and follow-up requirement, does not meet other psychosocial criteria to handle the implications of the trial(2,29).
In the prenatal surgical category, no sac over the lesion with the presence of in-utero ankle, knee and hip movements together with a MMC lesion of above L3 had a significant correlation with independent ambulation(2,4,29).
The data presented from the 30-month cohort study on the cognitive development and outcomes for motor function in utero surgical repair to be an effective treatment for foetuses with MMC(29).
Although, prenatal surgery did not necessarily reduce the need for clean intermittent catheterisation (CIC) within 30 months, there was however a decrease in bladder trabeculation, vesicoureteral reflux and an open bladder neck(29).
The primary outcome or the composite score was significantly better in the prenatal surgery group than in postnatal and this was validated in the full cohort (P=0.004)(3,5). The primary outcome was death under 30 months, Bayley Scale of Infant Development II (BSID II) mental development index and the difference in motor function and anatomical lesion levels(29,39).
Three deaths were recorded in each group <30 months with 1 foetal, 1 neonatal and 1 at 28 months in the prenatal surgical group and 2 neonatal and 1 at 14 months for the postnatal surgery group(29,39).
Overall, there was no difference in mortality rates between the groups (P=.72)(29). Children in the
prenatal group had the level of function more than 2 levels better than expected based on the anatomical
level of the defect (P=0.2)(29). This group was also more likely to walk independently (P=.004)(29).
18
A subgroup analysis was performed and it was based on the superior level of MMC lesion i.e., T1-L2 vs L3-S1, Gender of the foetus, ventricular size (<10, 10-<15, >15mm) and degree of hindbrain herniation classified as mild, moderate or severe(2). There was a substantial interaction between gender and the outcome of surgery. 30.8% of girls in the prenatal surgical group as opposed to 17.9% in the postnatal group, P=.14, had the function level at least 2 better than anatomical level(2)(5,29). Although this was not statistically significant, among boys, 22.9% of the prenatal group had functional level at least 2 better than the anatomical level compared to none in the post-natal group (P=.003)(5,29).
In prenatal surgical group, a detectable ankle, knee, and hip movements by an ultrasound scan were associated with the ability to walk independently by 30 months(5,29).
On the other hand, 9 prenatal surgical patients did show no hip movement and was unable to walk independently within 30 months. MMC lesion of above L3, a dilated third ventricle and an absent sac over the lesion were significantly correlated with being able to walk independently with P= 0.002, 0.02 and 0.02 respectively(29)(3).
Results from the 30 months follow up on all the children whose mothers underwent surgery in MOMS does validate original results. Even though prognostic indicators were worse for the prenatal group, this group had improved composite of mental and motor function(2,3,29). Secondary outcomes such as motor function as measured by the difference between anatomical level and neuromuscular functional level and the chances of being able to walk independently were also significantly improved among the prenatal group(2,3,29). Preterm delivery was 11% <30 weeks in the prenatal surgical group. Despite being premature, neurodevelopmental outcomes were the same. Furthermore, there was no need for VP shunting at 30 months(2,3,29).
The risks and benefits of prenatal surgery must be noted. While, it is true that 30-month full cohort outcomes for motor and development are favourable, the increased maternal risk cannot be overlooked.
Strong emphasis must be placed on mothers who undergo prenatal surgery that future pregnancies must
be delivered by C-section before the onset of labour to prevent uterine rupture and potential foetal and
maternal death(2,3,29,40).
19
3.7 Strengths and Limitations for MOMS trial
The data from full cohort of 183 patients does validate in-utero surgical repair to be effective in treating patients with foetal MMC. Results of longer-term follow-up at school age can verify if results remain durable(2,3,13,29).
3.8 Complications of Prenatal MMC Closure
Prematurity, the major complication of prenatal MMC closure was the rate of prematurity.
MOMS trial average gestational age at delivery for prenatal group was 34.1 weeks compared to postnatal group that had 37.3weeks with, 13% of prenatal patients being born before 30 weeks(2,3,29).
The increase in prematurity could be related to chorioamniotic membrane separation, PROM that results in preterm labour(24,40). Chorioamniotic membrane separation was observed in 26% in prenatal group.
Other studied have suggested this risk could be minimised by operating after 23.0 weeks gestation(24,40). While it is true that there is a great deal of evidence to show the benefits of prenatal surgical outcomes, it is necessary to consider maternal surgical risks as they undergo two major operative procedures in a short period of time (8,36,40,49). Hysterotomy during foetal surgery is performed at the thick fundal region that also happens to be the active portion of the uterus. This part can be associated with uterine dehiscence in 7-9%(8,36,40,49).
To further minimise complications whilst maximising benefits, it is prudent to perform foetal surgery using a multidisciplinary team that includes neurosurgery, foetal surgery, maternal foetal medicine, anaesthesiology, foetal cardiology and experienced nursing staff on board(6,16,40,45).
3.9 Significance of SB Lesion Level and its implications
Patients born with MMC at birth are likely to have tonsillar herniation of Cerebellum in over 80% of the cases. One of the more important arguments for prenatal repair of MMC is being able to prevent CM-II and thus knowing about reversing the effects postnatally is of tremendous value(20).
Beuriat et all study on the complete reversibility of Arnold Chiari II malformation studied a large group
of postnatally repaired MMC was evaluated on the long-term complete ascent or total reversing of CM-
II(22). Results showed a correlation between the anatomical level of MMC and the presence of CM-II
at birth out of the 61 patients who met the inclusion for the study (p=0.003). the study also stressed on
every patient who had a malformation above L-4 had CM-II malformation at birth(22).
20
The inclusion criteria consisted of all MMC neonates who were operated postnatally with MRI confirmation of diagnosis to assess the presence or absence of CM-II. A post-op MRI or CT scan to measure the reversibility of CM-II(22).
After MMC closure, 28/61 or 45.9% of the patients had the remaining CM-II and thus the reversibility
rate was 40.4%(22). Furthermore, reversibility rates were even higher among lower-level malformations
with p=0.004. Reversibility also took place among patients who did not benefit from CSF shunt
placement. 28/61 patients did not have hydrocephalus and out of the 28, 19 of them or 67.9% had CM-
II at birth and 10/19 had it reversed(22).
21
4. Methods and methodology
Analysis of the current literature: Search strategy involved using the following key words: spina bifida or management of myelomeningocele or myelomeningocele foetal therapy for MMC under inclusion criteria. PubMed, Cochrane database and Science Direct were employed as main search engines. A systematic review was not performed. However, the biggest trial on the Management of Myelomeningocele study was studied and follow-up is ongoing. Additionally, 3 systematic reviews were also included in the review and 2 case-control studies. Publications were only included in the analysis if they were published in the last eight years. Over 70 studies were screen based on the above-mentioned search criteria, 30 studied were carefully reviewed and 15 have been included. Exclusion criteria was also set up to filter out excess papers that had no relevance to the main objective at hand.
A descriptive case-study approach was chosen to allow a deeper insight into all the 25 cases who underwent SB-MMC surgical repair or were terminated for SB-MMC at the set period from the 1
stof January 2016 until 31
stof December 2017. The study was carried out from September 2017 through to December 2017. A total number of 25 mothers were identified with the diagnoses of which 22 gave birth and three terminations of pregnancies took place during the study period. This study included patients with all forms of SB, requiring surgery, mostly myelomeningocele with or without liquorrhoea. Ethical approval was obtained from the Department of Bioethics prior to recoding and collecting case histories from archive. The data was initially collected from post op theatre notes performed for meningoplasty and from the records kept for cases at the registry antenatal foetal abnormality diagnosis to detect terminations. Following, the final decision to collect data on set number of variables, all case notes of the mother and baby from outpatients’ clinic were identified and sourced from the Obstetrics and Gynaecology outpatient’s files at Lithuanian University of Health Sciences Hospital, before attaining the actual case histories that were stored in archive. Additional information was obtained from antenatal notes, out patients case files and obstetrical case files. There is reason to believe all the case files with a diagnosis of spina bifida were obtained for the time 2016-2017 from Lithuanian University of Health Sciences Hospital.
Statistical features of the mother included if spina bifida was diagnosed antenatally, level of spina bifida, whether it was open spina bifida or myelomeningocele, whether the pregnancy was singlet or multiplet, if the delivery was via C-section, normal vaginal delivery, or emergency operation.
Demographic features of the new-born included gestational age, gender, birth weight (in grams),
APGAR score at 1 and 5 minutes respectively. Postnatally, if the neonate was catheterised, if a
ventriculo-peritoneal shunt was placed, if the neonate had hydrocephalus, day of operation after delivery,
notes on antenatal and postnatal leg movements, if the neonate suffered infection and if so what kind
22
post operatively, the duration of hospital stay, head circumference before and after birth, gestational age at delivery, and gender.
Statistical analysis: All collated data were analysed using IBM SPSS 24.0 Statistics®. Median,
minimum, maximum was calculated. Non-parametric tests analysis used 95% CI. All tests used a (2-
sided) p value of 0.05 to be significant.
23
5. Results
25 cases were analysed in total. 3/25 were terminated earlier after antenatal diagnosis was made during 19 and 20 weeks gestation. Assuming all SB cases from Lithuania were transferred to Lithuanian University of Health Sciences Hospital for neurosurgical treatment, with the concentrated SB cases in Kaunas, we tried to calculate the incidence of SB-MMC in Lithuania for 2016-2017.
Live births registered in Lithuania were 30,623 in 2016 and 29,871 births in 2017. 25 cases from 60494 corresponds to 1:2327 otherwise 4.1 per 10,000. Therefore, the incidence rate is 3.6 per 10,000 (23/60494) of live births.
5.1 Diagnosis of SB/MMC antenatally
Table 1 shows gestational age at diagnosis. 7 cases were missing while some cases were diagnosed while at the hospital and therefore no antenatal diagnosis was made earlier during pregnancy and is very unlikely these mothers knew about the disease. Of the small sample size obtained 18/25 of cases were diagnosed antenatally of which 4 of them were diagnosed prior to 20 weeks gestation. Cases with missing antenatal records were treated as not being diagnosed antenatally and therefore neonatal transfer was required. Pie chart one shows a valid percent of 72% antenatal diagnosis.
72%
28%
PIE CHART 1: PERCENTAGE OF SB/MMC DIAGNOSED ANTENATALLY
Yes No Table 1: Was SB/MMC diagnosed antenatally
Frequency Valid Percent
Valid No 7 28.0
Yes 18 72.0
Total 25 100.0
24
Five cases were diagnosed 23 weeks gestation and before. Pie chart 2 shows 19% of antenatal diagnosis were made prior to 23 weeks gestation.
5.2 Gestational age at diagnosis
Table 2.1: Gestational age at diagnosis
Frequency Valid Percent
Valid 19 3 15.8
20 1 5.3
23 1 5.3
25 1 5.3
27 1 5.3
31 2 10.5
32 3 15.8
33 3 15.8
35 1 5.3
37 1 5.3
39 2 10.5
Total 19 100.0
Missing 6
Total 25
19%
81%
PIE CHART 2: REPRESENTING THE PERCENTAGE OF ANTENATAL DIAGNOSIS MADE PRIOR TO 23 WEEKS
Antenatal diagnosis prior to/by 23 weeks gestation Antenatal diagnosis after 23 weeks gestation
25 Table2.2 Statistics
Gestational age at diagnosis
N Valid 19
Missing 6
Median 32
Minimum 19
Maximum 39
The median age at diagnosis was 32 weeks with the earliest one latest diagnosis being confirmed at 19 and 39 weeks gestation respectively. 6 cases were found to be missing. Out of the total 25 confirmed cases for spina bifida, 4 cases were diagnosed prior to 20 weeks and 3 of the pregnancies were discontinued thereafter.
5.3 Gestational age at delivery
All but one delivery was at term. No cases were induced. The median age at delivery was 39 weeks. The earliest delivery was at 35 weeks.
Table 3.1: Gestational age at delivery
Frequency Valid Percent
Valid 35 1 4.8
37 3 14.3
38 3 14.3
39 9 42.9
40 5 23.8
Total 21 100.0
Total 22
26 Table 3.2: Statistics
Gestational age at delivery
N Valid 21
Missing 2
Mean 38.62
Median 39.00
Mode 39
Std. Deviation 1.284
Minimum 35
Maximum 40
5.4 Vaginal delivery and C-section (elective and emergencies)
There was a 50% split among vaginal deliveries and C-sections performed on 20 mothers. In 2 cases of neonatal transfer from other hospitals there was no information on mode of delivery in neonatal notes and hence mode of delivery was not recorded. Out of the 10 C-sections, 6 were elective with 2 emergency C-sections with, 2 missing case notes. Majority of women delivered at term with 3 mothers who had a history of previous C-sections.
Table 4: Natural delivery or C-section
Frequency Valid Percent
Valid Vaginal 10 50.0
C-Section 10 50.0
Total 20 100.0
50%
50%
PIE CHART 3: VAGINAL DELIVERY VS C- SECTION
Vaginal C-Section
27
5.5 Birthweight and centiles
Table 5: Babies and their centiles
No Gender GA at delivery Birthweight (grams) Percentile
1 Boy 40 4040 90
2 Girl 39 2650 5
3 Boy 39 3550 50
4 Boy 35 2670 50
5 Girl 30 3250 97
6 Girl 39 2200 3
7 Boy 39 3345 50
8 Girl 40 3125 25
9 Boy 39 2160 <3
10 Boy 38 3410 50
11 Girl 38 3370 50
12 Boy 37 2470 25
13 Boy 37 4190 97
14 Boy 37 2890 25
29%
71%
PIE CHART 4: PERCENTAGE OF BABIES WITH BIRTHWEIGHT ABOVE AND BELOW
3KG
<3kg >3kg
28
The table 5 denotes the percentile for all known birthweights and gestational age during delivery
using WHO growth chart as reference point. The median birthweight of 22 babies were 3250 grams and the lowest and highest recorded birthweight was 2160g and 4190g respectively.
Three neonates (3/22= 13.6%) were Small for gestational age (SGA) with the birth weight under the 5
thcentile. While 5 babies were above the 90
thpercentile. Most babies with a total count of 10 was on the 25
thcentile or below. 6 neonates were above the 75
thpercentile.
5.6 APGAR scores
19/22 babies had >7 at 1 minute with two neonates with a score of 6 at 1 minute which went up to an 8 at five and a further one baby with a score of 5 at 1 minute that rose to 9 by the fifth minute. 20/22 babies had an APGAR score of >7 at five minutes.
5.7 Gender
Table 6: Gender
Frequency Valid Percent
Valid Boy 14 58.3
Girl 10 41.7
Total 24 100.0
15 Boy 39 3090 25
16 Girl 39 3790 90
17 Girl 40 3180 25
18 Girl 40 3030 25
19 Girl 40 3155 25
20 Boy 39 3844 75
21 Girl 39 3750 90
29
Gender was also known from TOP and therefore a total of 24 babies had their gender revealed antenatally, with 58% of boys having the diagnosis over girls. P value was calculated to be 0.181 suggesting no statistically significant result between gender and open SB or MMC. Because of the small sample size, Cramer’s V test was performed which showed p=0.352 indicating a strong relationship between gender and SB diagnosis. With 15/25 being boys with an open SB or MMC, 10 were girls.
5.8 Open Spina Bifida and Myelomeningocele
Table 7: Open SB vs MMC
Frequency Valid Percent
Valid Open SB 9 42.9
MMC 12 57.1
Total 21 100.0
21 babies were initially diagnosed as either having an open spina bifida or myelomeningocele. Of the 21, 9 had open and 12 was concluded to have myelomeningocele, the severe form. 5 cases had missing information for this variable.
5.9 Accuracy of antenatal SB lesion level diagnosis
Table 8: SB_LESION_LEVEL_CORRESPONDANCE
Frequency Valid Percent Yes, SB level was diagnosed with absolute
accuracy
9 36.0
Missing Antenatal notes 6 24.0
Yes, SB level was diagnosed with partial accuracy 7 28.0
TOP 3 12.0
Total 25 100.0
The level of SB lesion was formulated antenatally and postnatally. Furthermore, an additional category
was added to calculate absolute accuracy and partial accuracy for SB diagnosis level. Absolute accuracy
corresponds to the SB level being the same throughout antenatal and postnatal diagnosis and partial
30
accuracy relates to the postnatal diagnosis being slightly different than antenatal diagnosis. For instance, antenatal diagnosis of lumbar lesion could be changed to lumbosacral postnatally after confirmation with neurosurgeons postoperatively.
Out of 22 patients excluding 3 TOP, 6 case did not have any information for the level of Spina bifida lesion antenatally. All case notes were examined and nowhere was this key information written. There is an absolute accuracy of 36% of diagnosing the level of SB antenatally with confirmation postnatally.
Still, there is 28% probability of partially diagnosing the SB level accurately antenatally and postnatal correlation.
5.10 Leg movements antenatally and postnatal
Table 9a: Presence of leg movements antenatally
Frequency Valid Percent
No 4 66.7
Yes 2 33.3
Total 6 100.0
Missing 17
17 cases did not report on any antenatal leg movements, while 66.7% had no leg movements recorded on the antenatal notes, 33.3% did note some movements.
Table 9b: Presence of leg movements postnatally
Frequency Valid Percent
no 5 25.0
yes 15 75.0
Total 20 100.0
Missing 3
31
Postnatal notes only had 3 missing description for leg movements after delivery, and a significant 75%
did move their legs postnatally.
Table 9c: Symmetric Measures
Value Approximate Significance
Nominal by Nominal Phi .316 .439
Cramer's V .316 .439
N of Valid Cases 6
By using nominal Cramer’s V statistics test the p value= 0.439 for the presence of leg movements both antenatally and postnatally showed moderate relationship. However, it is important to note that the sample size was too small due to missing antenatal data.
5.11 Antenatal and postnatal hydrocephalus
Table 10a: Presence of antenatal hydrocephalus
Frequency Valid Percent
No 1 5.3
Yes 18 94.8
Total 19 100.0
Missing 6
All but one case had antenatal hydrocephalus, in 6 cases there was missing information, as no antenatal
records were available.
32 Table 10b: Presence of postnatal hydrocephalus
Frequency Valid Percent
No 2 10.5
Yes 17 89.5
Total 19 100.0
Postnatally 17 babies out of the 19 had hydrocephalus with 3 missing cases.
Table 10c: Comparative statistics of head circumference antenatally & postnatally
Head circumference antenatally Head circumference postnatally
N Valid 14 21
Missing 11 2
Mean 335.86 355.24
Median 330.00 350.00
Mode 328a 350
Std. Deviation 54.931 48.515
Minimum 239 290
Maximum 492 520
The median head circumference was 330mm antenatally
The median head circumference was 330mm antenatally and postnatally it was 350mm. While the
smallest and biggest value antenatally was 239mm and 492mm, the postnatal measurements all of
which were not recorded on day 1 was 290mm and 520mm respectively.
33
5.12 Arnold Chiari II malformation postnatally
26.1% neonates had Arnold Chiari II malformation present postnatally on MRI scan. In 6 cases CM II was confirmed on MRI in early neonatal period.
5.13 Ventriculo-peritoneal shunt placement
With two missing cases and 7 cases with no shunt placements, the remaining 65% of the neonates had a Ventriculo-peritoneal shunt placement during their stay at the hospital. Of the 13 neonates, 1 baby had shunt placement done three times and another twice yet, another baby’s shunt placement was delayed to 14 days due to infection.
5.14 Hospital acquired infections
Table 11: Was there infections?
Frequency Valid Percent
No 7 38.9
yes 11 61.1
Total 18 100.0
65%
35%
PIE CHART 5: WAS VENTRICULO- PERITONEAL SHUNT PLACED?
Yes No
34
With four missing cases, 61% of neonates developed hospital acquired infections during their stay at the hospital. Of the infections developed postnatally, 3 neonates suffered UTI to resistant bacteria namely K. pneumonia, E. coli resistant to meropenem.
5.15 Clean Intermittent Catheterisation
Postnatal catheterisation in the neonate resulted in UTI and PN. 15/22 new-born babies were catheterised postnatally. 40% of catheterised patients developed UTI caused by highly resistant hospital borne microorganism during their first hospital stay and were mostly managed by clean- intermittent catheterisation.
5.16 Duration of Hospital Stay
Table 12a: Duration of hospital stay
Frequency Valid Percent Number of days
spent in Hospital
9 1 6.7
12 2 13.3
16 1 6.7
19 1 6.7
20 2 13.3
23 2 13.3
28 1 6.7
29 1 6.7
35 1 6.7
48 1 6.7
49 1 6.7
61 1 6.7
Total 15 100.0
Missing 10
Total 25
Table 12b: Statistics
Duration of hospital stay
N Valid 15
Missing 10
Mode 12
35
Range 52
Minimum 9
Maximum 61
With all neonates staying in hospital for over a week, the minimum number of days stayed in the hospital
was 9 and a maximum of over two months.
36
6. Discussion of the results
If all SB cases from Lithuania were transferred to Lithuanian University of Health Sciences Hospital for Neurosurgical treatment, 3.6 per 10 000 life birth SB/MMC prevalence rate was calculated.
It is comparable with other countries. Because of growing rates in pregnancy termination after antenatal diagnosis of SB/MMC, prevalence rates are falling in Europe during the last decades. In the meantime, it is reported that the prevalence to be 2 per 10 000 in UK and 3.4 per 10 000 in USA(1,48).
6.1 Diagnosis of SB/MMC antenatally
72% of SB cases were diagnosed antenatally, of which 24% were prior to 27 weeks gestation.
This percentages can be improved further.
6.2 Gestational Age at diagnosis
The median age for diagnosis of SB was calculated to be 32 weeks from a sample. While it is true the size of the sample is in fact limited, if we assume that missing antenatal data were because of late diagnosis, where emergency neonatal transfer was required for undiagnosed SB and include gestational age at delivery to the calculations, the median gestational age at diagnosis would approximately be 32% that were diagnosed after 38 weeks gestation.
In the year of 2000, Lithuania was selected to be part of a 30-month study where from a total of 95,469 births 10.5-11.5 NTDs were isolated per 10,000 births(14). The prevalence for isolated spina bifida per 10,000 births were calculated to be 6.3 with only 38% being diagnosed prenatally. 63 cases were analysed with only 5 diagnoses <23 weeks in the year 2000-2001(14). Over the course of fifteen years, out of the 25 cases used in our study, 5 cases were diagnosed <23 weeks and over 70%, 14/19 cases were diagnosed after 24 weeks gestation in the years 2016-2017.
17% of prenatally diagnoses pregnancies were terminated. Over 30% of diagnoses were made after 24 weeks. The current gestational age limit for terminating pregnancies for foetal anomaly is <22 weeks (33). No stillbirths were recorded and It is calculated that less than 5% of pregnancies primarily affected by NTDs will result in a stillborn child or preterm delivery.
The gestational age required for any form of foetal therapy would be prior to 24 weeks and only 5 cases
were diagnosed in that time frame. Only 4 patients were diagnosed before 20 weeks gestation, in 3 cases
pregnancy was terminated and these 3 cases would have potentially benefited from foetal therapy if such
an option were to be available. It is also important to note that one of the case lesion level was low sacral
37
