Acta Pmdiatr Scand 70: 673-676, 1981

SCREENING FOR VIRAL INFECTIONS IN INFANTS WITH POOR INTRAUTERINE GROWTH

B. ANDREASSON, N. W. SVENNINGSEN and E. NORDENFELT

ABSTRACT. Andreasson, B. , Svenningsen, N. W. and Nordenfelt, E. (Department of Paediatrics and Department of Medical Microhiology, University Hospital, Lund, Sweden). Screening for viral infections in infants with poor intrauterine growth. Acta Paediatr Scand 70: 673, 1981.-Viral excretion and immunoglobulin concentration during the first 3 days of life were studied in a consecutive study of 104 infants with poor intrauterine growth. Other possible etiologies of poor intrauterine growth were analysed retrospectively. The etiology of poor intrauterine growth could not he found in 34 % of the babies. The data obtained showed no etiological relationship between poor intrauterine growth in our population and viral infection.

KEY WORDS: Intrauterine growth retardation, small for gestational age (SGA), viral infection

Over the years several reports on the high frequency of neurodevelopmental sequelas among babies born small for gestational age (SGA) have been published ( 1 , 2, 3). These findings stress the importance of understand- ing the etiology of impaired fetal growth.

Certain congenital viral infections such as rubella and cytomegalovirus are associated with poor intrauterine growth (4, 5 , 6, 7, 8). However, incidence studies for viral infec- tions during pregnancy or the neonatal period are few and without information concerning birth weight in relation to gestational age (9, 10, 1 1 , 12). The present investigation was therefore performed in order to study the inci- dence of viral infection in a material of SGA babies.

MATERIAL Newborn infants with birth weight at or below -2 S.D. according to Swedish intrauterine growth charts (13) who were treated in the Neonatal Unit, University Hospital in Lund, were consecutively included in this study.

From April 1976 until December 1978, 104 SGA infants of 102 mothers were studied, of those 39 were also short for gestational age. The mean birth weight was I970 g (range 630-2550) and the mean birth length 44.0 cm (range

34.0-49.0). Forty-seven babies were born before the 38th week of gestation and 7 of these before the 34th week. Three babies died: one baby with Dysplasia epiphysialis punctata because of respiratory failure at 2 months of age; one very low birth weight infant (b.w. 630 g) at 2 weeks of age; and one baby in cot death at S weeks of age.

METHODS All maternal files from the Maternal Health Care Service were reexamined, supplemented with questionnaires to the mothers regarding health problems, especially signs and symptoms compatible with infections during pregnan- cy as well as smoking habits. The degree of maturity at birth was evaluated by assessment of external features, neurological development and head circumference ac- cording to the criteria of Finnstrdm (14).

Urine. stool and saliva samples were collected during the first days of life from all SGA infants. For serological and immunoglobulin studies umbilical cord sera or capil- lary blood were taken within the first 3 days of life. Determinations of serum immunoglobulin M (S-IgM) was made in S2 babies and of immunoglobulin G (S-IgG) in 45 babies.

From the mothers blood samples for serological analy- sis and urine for virus isolation were also taken after delivery. All samples were immediately transported to the laboratory. If virus was isolated in the urine a second blood sample was taken as well.

Urine, stool extracts and saliva were inocculated into duplicate cultures of ( 1 ) diploid human embryonic fibrob- last cultures (HEL), (2) a continuous human cell line, A

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674 B . AndrPasson et al.

Day 1-3 To ta l s-lgG

( s i r ) I

2o I

+ 0

2 8 30 3 2 34 36 38 40 4 2 GEST A G E ( w )

Fig. 1 . S-IgG in 45 SGA babies days 1-3. Normal values (Meankl S.D.) according to Catty et al. (17).

The S-IgG measurements are shown in Fig. I . There is a wide scatter of values but they are all in the lower range at or below - 1 S.D. of normal newborn infants according to Berg (16) and Catty et al. (17).

Etiological factors of intrauterine growth retardation According to the maternal health care files and our questionnaires no signs of febrile disorders or severe infections were registered during pregnancy. As shown in Table 1 two mother had acute illnesses and 9 had chronic illnesses, in some cases requiring longterm drug treat- ment during pregnancy with thyreostatics, steroids or hydantoin. Three of these mothers

549, and (31 a continuous cell line of green monkey kidney cells (GMK). All cells were cultivated in medium RPMI had essential hypertension. These and other 1640 supplemented with I % L-glutamine, penicillin and possible maternal-fetal etiological factors of - streptomycin. Cultures were checked for cytopathic ef- poor intrauterine growth were found in 66 % of fects every second day for 2 weeks, HEL-cells for 3 weeks. Bv this procedure isolation of common viruses SGA infants. possible in the such as enterovirus, adenovirus, herpes simplex virus and cytomegaiovirus but not rubella virus is possible. When a virus had been isolated the blood samples were tested for antibodies by neutralisation tests.

same pregnancy occurred in several infants as Seen in Table 1. congenital malformations were found in 18 babies. Virus was isolated in the mothers of 2 of these babies.

RESULTS

Virus isolation and serology Table 1. Possibly maternal-fetal etiological No viruses were isolated from urine, stool or factors for poor intrauterine growth in 104 saliva specimens of the 104 SGA infants. Vi- small-for-gestational age (SGA) infants of ruses could be isolated in urine in 4 of 59 102 mothers mothers. The viruses were Adenovirus 3 , Different possible factors were found within several Adenovirus 16, Coxsackie virus B 4 and Her- pes simplex virus I . By neutralisation tests no antibody rise against the isolated viruses was detected in maternal sera taken at delivery and 8 to 16 weeks after delivery in these cases.

mother-baby pairs

Number

Total number of SGA infants

~ ~ ~ ~ ~ ~ ~ ~ f ~ ~ ' ~ ~ e r s )

104 102

4 (=3.8%) Three of the four infants to these mothers Earlier borns SGA infants 10

were both small and short for gestational age.

S-IgM and S-IgG Two babies had slightly increased S-IgM con- centrations which may be compatible with perinatal infection (i.e. more than 0.20 g/l) (15). However, these babies had no other signs or symptoms of infection and no virus was isolated.

Short maternal stature (S -2 S.D.) 2 Acute maternal illness 2 Chronic maternal illness 9 Alcohol abuse 1 Smokers 210 cigarettes a day 23 Pre-eclampsia 34 Congenital malformations

Possible etiological factors

No abnormalities found,

in SGA infants 18

for SGA found 69 (=66%)

i.e. unknown etiology 35 (=34%)

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Screening for viral infections in infants 675

nancy until delivery. This procedure was not available to us.

In the present material several other well- known possible maternal-fetal etiological fac- tors were associated with poor intrauterine growth (Table 1). We did not make specific evaluations of psycho-socio-economic factors or details of maternal nutrition during preg- nancy. However, according to the charts from the Maternal Health Care Service no gross abnormalities concerning these factors were present. The occurrence of still unknown en- vironmental pollution factors may play an im- portant role. Such factors may be related to the high incidence (17 %) of malformations among our SGA infants as compared to full- sized babies.

In conclusion our findings show that viral infection was not a common occurrence in SGA infants. As yet no major single cause for poor intrauterine growth is known. Continuing epidemiological studies are required to clarify the etiological background of intrauterine growth retardation which could vary in time and place.

DISCUSSION This material presents only the patterns of preterm and term SGA infants, in most cases with birth weights less than 2 400 g, referred to the Neonatal Unit. No virus was isolated from these SGA babies. The rate of viral infection is in accordance with the findings of Low & Galbraith who in a material of 182 SGA infants did not find any congenital viral infections (18). Screening studies for virus in full-sized babies have also been either negative or shown positive isolation only in singular cases (9, 10, 18).

In fetal viral infection an increase of S-IgM in the newborn baby has usually been found (15, 19, 20). The S-IgM values were slightly raised in only 2 of our SGA infants. This is in contrast to the findings of Matthews & O’Her- lihy, who found a higher incidence (12.5 %) of raised S-IgM levels in SGA infants (21). How- ever, prolonged duration of delivery in moth- ers with early rupture of membranes was the most common cause of increased S-IgM levels in their material.

The S-IgG values in our material are below the mean values earlier reported in AGA and SGA infants, respectively (16, 17, 22,23). The low S-IgG may indicate another pattern of this immunoglobulin or its subclasses in SGA ba- bies.

In 4 mothers a virus was isolated in the urine at the delivery. This could be an indica- tor of active viral infection which could have had an influence on the pregnancy. However, as no serological evidence of active infection was shown no conclusions can be drawn about this.

If poor intrauterine growth is caused by viral infection during pregnancy, the infection has started before delivery. It is possible that mother or baby may not still be excreting the virus at delivery. However, it is wellknown that congenital viral infections often cause longterm virus excretion from the babies (5, 20, 24). An alternative way to diagnose viral infection during pregnancy would be repeated sampling for virus isolation from early preg-

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Submitted Sept. 15, 1980 Accepted Febr. 25, 1981

(B. A,) Department of Paediatrics University Hospital S-22185 Lund Sweden

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