CC BY
15
UDC: 618.396
FLORENCE MURILA1, ROBERTSON MARCUS2, MOSES M. OBIMBO1, VICTOR YU2, WALLACE EUAN2
INFANT OUTCOME IN PRETERM PREGNANCIES WITH ABSENT UMBILICAL END DIASTOLIC FLOW
'University of Nairobi, Nairobi, Kenya 2Monash Medical Centre, Melbourne, Australia
Department of Human Anatomy, Obstetrics and Gynecology
Moses M. Obimbo- PhD, Senior Lecturer, P.O.BOX 30197-00100 NAIROBI.
Phone +254721585906,
Fax +2540204450011,
e-mail: [email protected];
Department of Pediatrics
Florence Murila- MBchB, MMeD (Paeds), Senior Lecturer,
e-mail:[email protected];
Monash Medical Centre
Robertson Marcus- MBBS, HMO supervisor,
e-mail: [email protected];
Victor Yu-FRCP, DCH, Professor,
e-mail: [email protected];
Wallace Euan- Professor,
e-mail: [email protected].
ABSTRACT. Aim: To compare the outcome of infants born at a different gestational ages with absent end-diastolic flow in the umbilical artery and those with gestational matched healthy controls.
Methods: A group of 55 pregnancies and later on infants at Monash Medical Centre had AEDF investigated with a matched group of 55 for gestational age, date of birth and sex. Pre and perinatal outcome variables were retrospectively reviewed. The variables included daily surveillance of fetal wellbeing by biophysical profile.
Results: Of 110 preterm infants, gestational age 24-34 weeks and birth weight 460-1500g 49/55 (89%) in AEDF group survived until discharge compared to 54/55 (99%) in the control group (P < 0.05). The infants in former group had a significantly lower birth weight with growth restriction, delivered by caesarean section, had intraventricular hemorrhage, stayed longer in hospital, required a longer duration of ventilation and easily developed chronic lung disease (p<0.05)
Conclusion: This study reiterates that absent end-diastolic flow velocity is associated with a longer duration of hospital stay, higher mortality and morbidity during the neonatal period. Prenatal routine check to ascertain normalcy of umbilical blood flow should be promoted to inform planning within Health systems.
Key words: absent end diastolic flow, fetal, neonate, morbidity, mortality
INTRODUCTION
The investigation of fetal circulation of high risk pregnancies by Doppler ultrasound is increasingly being used with absent umbilical artery end diastolic flow (ADEF) offering an opportunity to apply intensive fetal surveillance and timing of delivery [1-3]. The overall aim of such investigation is directed towards reducing fetal morbidity and mortality.
Abnormal fetal circulation indicated by absent or reversed end diastolic
flow velocity in the fetal umbilical artery or aorta suggests intrauterine fetal compromise [4, 5]. The absent flow velocity is thought to result from increased downstream vascular resistance resulting in circulatory redistribution [6, 7]. The resultant effect is reduction in visceral perfusion that is associated with high risk of acidaemia at birth, growth restriction, necrotizing enterocolitis, cerebral haemorrhage, neonatal morbidity, intraventricular haemorrhage,
periventricular leukomalacia, chronic lung disease and a higher rate of both major and minor neurological sequalae [8 -10]. The surviving infants of this high risk group have an increased risk of mental retardation and severe motor impairment as compared with age matched for gestation preterm infants [11].
There is paucity of information that relates outcomes between neonates born with AEDF to a normal group matched for gestation age and sex. Such a comparison would exclude pregnancies that have poor fetal outcome as a result of impaired placentation and prematurity. The data obtained would be helpful in guiding policy formulation regarding timing of delivery and informing ante-, peri-, and postnatal care.
METHODS
This was a retrospective case control study of all the fetuses born to pregnancies with AEDF at the Monash Medical Centre between January 1995 and October 2005. Women with a pregnancy complicated by umbilical artery AEDF and who received betamethasone as prophylaxis for neonatal respiratory distress were studied. Betamethasone (Celestone Chronodose, Schering-Plough Baulkham Hills NSW, Australia) was administered as two 11.4 mg doses intramuscularly 24 hours apart according to the hospital's recommended regimen and International recommendations [12]. Ultrasound examinations were performed on a daily basis according to the hospital's routine fetal surveillance program for these pregnancies, using an ATL HDI 3000 ultrasound machine® (Advanced Technology Laboratories, DEE Why ,NSW, Australia) with either a 5-2 or MHz curved array probe. A combination of real-time gray-scale and colour flow imaging with pulsed-wave Doppler studies was performed with the high pass filter set on low. Flow velocity waveforms were obtained from the umbilical artery in a
free loop cord at least 5 cm from either the ^ distress syndrome (RDS) and chronic lung ^ 5 minute Apgar scores between the 2
placental or fetal insertion and recorded ^ disease (CLD); (IV) Intestinal morbidity ^ groups showed a trend towards statistical
as an S/D ratio. All recordings were taken ^(necrotizing enterocolitis (NEC) and age at ^difference (p=0.09) but the need for
during episodes of fetal inactivity and ^ full feeds; (V) Central nervous morbidity ^ active resuscitation was not statistically
apnoea, ensuring a steady non- pulsatile ^ - intraventricular hemorrhage (IVH);. (V1) ^ significant difference between the 2
signal in the venous channel. Cardiovascular morbidity (hypotension) groups (p =0.21). Although there was
We retrospectively reviewed the ^ Statistical analysis: The infants were ^ no statistically significant difference
case notes of the 55 women and their ^ grouped into two groups, those with AEDF ^ in pH between the 2 groups the AEDF
babies. The intrauterine, perinatal, (cases) and those with present umbilical group had a trend towards a higher base
neonatal and infant deaths were ^ waveforms (controls). For categorical ^ excess (p=0.05) and a higher lactate level
registered. The postnatal course was ^ outcomes the results were reported as ^ (p=0.08). Both groups required oxygen for
followed until the date of discharge from ^ percentages. For all other outcomes the ^ a similar duration. The need for assisted
the neonatal unit. results were reported as median with ventilation was similar between the 2
Controls consisted of women whose ^ interquartile ranges. Statistical analysis ^ groups with 73 % of the cases requiring
fetuses showed the presence of umbilical ^ was performed using Chi square test and ^ ventilation compared to 80 % of the
end diastolic flow velocity. These fetuses ^ Mann-Whitney Rank Sum Test. A p value ^ controls with a p value of 0.37. The cases,
were matched to the cases for sex, ^ of <0.05 was considered to be significant. ^ however, had a trend towards requiring
gestational age and date of delivery. ^ RESULTS ^ a longer period of ventilation 21.5 days
Outcome parameters were divided into ^ For each group, fifty five patients ^ as compared to the controls, 8.5 days
six groups; (I) Maternal / predelivery ^ met the inclusion criteria. More, 93% ^ (p=0.05).
characteristics (maternal disease and of the infants in the AEDF group were The rate of respiratory distress
mode of delivery) ^ born by caesarean section than those in ^ syndrome between cases and controls
(II) Delivery outcomes (birth weight, ^ the group with normal umbilical blood ^ was similar, 75% for controls and 73% for
Apgar score, first pH value, lactate and flow,75%, (p= 0.01). The median birth cases. There were more infants among
base excess, need for active resuscitation weight in the control group was much those with AEDF who developed chronic
(III) Pulmonary morbidity (need for ^ higher than that in the cases, 1198 ^ lung disease 36% than among those
ventilation and oxygen, respiratory ^ grams against 940grams (p<0.05). The ^ with normal umbilical blood flow 20%
Table 1: Summary of infant outcome in cases and the controls
Normal EDF N=55 Absent EDF N=55 p value
Delivery by C/S 41(75%) 51(93%) 0.01
Birth weight median, (IQR) 1198 (900-1500) 940 (686-1140) 0.05
SGA % 6 (11%) 27 (49%) 0.05
Apgar score <5 5 (9%) 1(1.8%) 0.09
Active resuscitation % 30 (55%) 24(44%) 0.21
Base excess, median (IQR) -2 (-4.3_ -0.8) -3 (-5.9 _ -1.2) 0.05
Lactate, median(IQR) 3.4 (2.2-5.6) 5.1 (2.8-9.3) 0.08
pH,median (IQR) 7.38 (7.3-7.4) 7.32 (7.3-7.4) 0.415
Oxygen use % 40(73%) 47(85%) 0.10
Oxygen use duration ,median(IQR) 12.5 (5-52.5) 30.5 (4-80) 0.49
Assisted ventilation % 40(73%) 44(80%) 0.37
Assisted Ventilation duration,median(IQR) 8.5 (1-35.5) 21.5 (4-53.3) 0.05
RDS % 41(75%) 40(73%) 0.83
CLD % 11(20%) 20 (36%) 0.06
Age at full feeds Median (IQR) 11.5 (7.8-20) 16.5 (10.8-21) 0.06
NEC % 2(3.6%) 0(0%) 0.15
IVH % 2(3.6%) 11(20%) 0.01
PVL % 4(3.6%) 2(3.7%) 0.00
Hypotension % 20(36%) 19(35%) 0.84
Duration of stay in days,median(IQR) 38 (24-77) 60 (36-93.5) 0.03
Mortality % 1(1.8%) 6(11%) 0.05
(p=0.06). The cases needed a longer time ^ insufficient gaseous and nutrient supply ^ AEDF had a longer duration of hospital for the establishment of full feeds 16.5 ^ to allow for the fetus to thrive in utero. ^ stay is most probably attributable to days than did the controls, 11.5 days. ^ A comparative incidence of RDS ^ the high patterns of morbidity like IVH There were only 2 cases of necrotizing in the cases and controls suggest that and PVL, need for a longer period for enterocolitis (NEC) and both were found the former had some form of lung establishment of oral feeds and chronic in the control group (p = 0.03). maturity adaptation. The fetuses with lung disease. Similar observations have
Interventricular hemorrhage IVH ^ absent end diastolic flow velocity might ^ been made in earlier reports [27, 28, 29]. was found in a much higher proportion have had some degree of intrauterine As the effects of AEDF are long term and of the cases,20%, than of the controls stress that resulted in them mounting may persist into adult life, it is important ,3.6% (p=0.01). Hypotension occurred ^ adequate hormonal response to induce ^ that optimal timing of delivery of affected at a similar rate among both groups, ^ better lung maturity all other factors ^ infants is determined so that these effects 35% and 36% for the cases and controls notwithstanding. It has been suggested can be reduced [30, 31]. respectively (p= 0.84). that intrauterine stress may increase CONCLUSION
The median duration of hospital fetal circulating catecholamines, The current study reiterates that
stay for the cases was much higher 60 corticosteroids, and thyroid hormones, absent end-diastolic flow velocity is days, than that of the controls, 38 days, ^ which enhance lung maturity [20]. ^ associated with a higher mortality and (p= 0.03). The deaths among the cases ^ These hormones in addition to prolactin ^ morbidity during the neonatal period. The were 6 times as many as those among the ^ may influence maturation process of ^ surviving infants of AEDF in addition, have controls (p=0.05) [Table 1] lung tissue by promoting production of a longer duration of hospital stay and are
DISCUSSION surfactant, maturing lung parenchyma likely to have neurological deficits that
The current study findings are ^ through decreasing lung permeability and ^ may necessitate long term care. Prenatal in concordance with findings of other increasing the elastic fibre content of the routine check to ascertain normalcy of studies that have associated AEDF with | lung [21]. | umbilical blood flow should be promoted
poor fetal outcome [4, 13, 14]. In this ^ Those born to a pregnancy ^ to inform planning within Health systems. study infants with AEDF had an adverse ^ complicated by absent end diastolic ^ Conflict of interest outcome more often than controls with flow had a statistically significant trend The authors declare no conflict of
11% of them dying. The high mortality ^ towards requiring longer assisted ^ interest. There were no external sources rate of 11% is similar to that found by ^ ventilation and towards developing ^ of funding Volcamonico et al., 1994 [15], Yildirim | chronic lung disease. It is possible that | REFERENCES: et al., 2008 [16] and Tasic et al, 2010 [5]. | long term academia causes intrauterine ^ 1. Tyrrell SN, Lilford RJ, The absence of umbilical artery waveform ^ lung damage that leads to chronic lung ^ Macdonald HN, Nelson EJ, Porter J, which indicates redistribution of vascular ^ disease. The development of lung damage ^ Gupta JK. Randomized comparison of flow to some organs while denying others during antenatal life is probably reflected routine vs highly selective use of Doppler blood with accompanying neurological by a higher resistance in the pulmonary ultrasound and biophysical scoring to sequelae, result in complications that arteries in growth restricted fetuses investigate high-risk pregnancies. Br J may lead to death [17]. | compared to normal controls [22, 23]. | Obstet Gynaecol 1990;97:909-16
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TYMIH | РЕЗЮМЕ
FLORENCE MURILA1, ROBERTSON MARCUS2, OBIMBO M. | FLORENCE MURILA1, ROBERTSON MARCUS2, OBIMBO M.
MOSES1, VICTOR YU2, WALLACE EUAN2 | MOSES1, VICTOR YU2, WALLACE EUAN2
К1НД1КГЩ ШЕТК1 ДИАСТОЛИКАЛЫК, КАИ АГЫСЫ ЖОК | ПРОГНОЗ ПРЕЖДЕВРЕМЕННО РОДИВШИХСЯ
ШАЛА ТуылГАН БАЛАЛАРДЫ БОЛЖАУ | детей с отсутствием пуповинного конечно-
1Найроби университету Найроби, Кения | ДИАСТОЛИЧЕСКОГО КРОВОТОКА
2Монаш Медицина 0рталыfы, lМельбУPн, Австралия | 1университет Найроби, Найроби, Кения
Максаты. шнщк артериясында шеткидиастоликалык | 2Медицинский центр Монаш, Мельбурн, Австралия Кан ^ысы жок эртYрлi гестациялык, жYктiлiк мерзмЫде | Цель. Сравнение детей, родившихся в различные туыл«н балаларды бакылаУ тобындаfы жYктi эйелдердщ | гестационные сроки беременности с отсутствием конечно-болжамымен салыстыру. ^ диастолического кровотока в пупочной артерии с прогнозом
ЭдктерГ Монаш унж^р^тетчилн, Медициналык | у беременных контрольной группы. орталь^ында кiндiк шеткi-диастоликалык Кан а^ысы | Методы. Группа из 55 беременных и дети в Медицинском жоКты^ын аныктау^а 55 жYктi эйел мен балалар гестациялык | центре при университете Монаш прошли обследование на жасын туылу мерзiмiн жэне жынысын аныктау Yшiн УКсас | отсутствие пуповинного конечно-диастолического кровотока
сэйкес т°пт^ы 55 ^кл эйелмен бiрге тексеруден eттi. | с идентичной соответствующей группой из 55 беременных
I'
ретр°спектив^ бiрiктiрiлдi. Зерттеулер би°физикалык, I и пола. Пренатальные и перинатальные показатели были
Пренатальды жэне перенатальды кУбылмалы нэтижелерi |для определения гестационного возраста, даты рождения
профилвд анык,тау мак,сатында урык жа^дайы кYнДелiктi | ретроспективно обобщены. Исследования включали ба^ыланып отырды. ^ ежедневное наблюдение за состоянием плода с целью
Нэтижелер. Kiндiк шеткi-диастоликалык кан а^ысы | определения биофизического профиля. жоК топта^ы 24-34 апталык дэне салма^ы 460-1500 грамм | Результаты. Из 110 недоношенных детей с гестационным гестациялыК жас шамасындаfы 110 ыэрестеден 49/55 (89%) | возрастом 24-34 недель и массой тела 460-1500 грамм в (р<0,05) бакылаУ тобымен 54/55 (99%%) ^^(стыр^ыда аман^ группе с отсутствием пуповинного конечно-диастолического есен жазылып шыкты, бiPiншi топтаfы нэрестелер бойлары | кровотока 49/55 (89%%) были благополучно выписаны по КысКа болып туылып, салмактары айтарлыктай темен болды, | сравнению с 54/55 (99%%) в контрольной группе (Р<0,05), у кесарь тiлiгi жолымен туьтды, асказанiшiлiк кан куйылулар | младенцев в первой группе вес был значительно ниже при болды, ауруханада УзаКемделдi, УзаКмеPзiмДi желдетул^ | рождении с ограничением роста, родились путем кесарева Кажет еттi ж^не екпенЩ созылмалы ауруы (р<0,05) жылдап | сечения, имели внутрижелудочковое кровоизлияние, долго eршiп отырды. ^ находились в больнице, требовался более длительный срок
Тужырым. БУл зерттеу кiндiк шеткi-диастоликалык кан | вентиляции и легко развилась хроническая болезнь легких а^сы жылдамды^ынын, жоктыfы неонатальды кезенде ^ (р<0 05)
айтарлыКтай Узак меPзiмДе стационарда емделу, жоfаPы | Выводы. Это исследование подтверждает, что аурушандык жэне eлiм жа^дайымен байланысты екендiгiн | отсутствие скорости пуповинного конечно-диастолического дэлелдейдк К,о«мдык, денсаулык сактау ЖYЙесiнде | кровотока связана с более длительным сроком пребывания в кулактандырыл^ан жоспарлаум ыкпал ету Yшiн кiнДiк Кан | стационаре, более высокой заболеваемостью и смертностью ^ысын аныктауда пренатальды жоспарлы бакылауды | в неонатальный период. Следует улучшить пренатальный жак,сарту керек. ^плановый контроль, чтобы установить норму пуповинного
Нег1зг1 сездер: кШштн, шетк ^смлшмыц к,т | кровотока для того, чтобы содействовать в информированном ыысьшын, болмс/уь/, к.так.Ыл^ жща тус нэресте | планировании в системе общественного здравоохранения.
аурушан,дык„елМ жагдшы. | Ключевые слова: отсутствие пуповинного
^ конечно-диастолического кровотока, внутриутробный, ^ новорожденный, заболеваемость, смертность.
