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Original Articles

                                                                                                                                                                        Indian Pediatrics 1999; 35:1187-1191

Transplacental Transfer of Measles Antibody in Delhi

Jagvir Singh, Shashi Khare, Shashi Prabha, Rashmi Chandra, D.C. Jain, Rajesh Bhatia and Jotna Sokhey

From the National Institute of Communicable Diseases, 22 Shamnath Marg, Delhi 110 054, India.

Reprint requests: Dr. Jagvir Singh, Deputy Director, Epidemiology Division, National Institute of Communicable Diseases, n Shamnath Marg, Delhi 110 054, India.

Manuscript received: February 24, 1998; Initial review completed: May 12, 1998;
Revision accepted: July
6, 1998.

 

Abstract:

Objective: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. Design: Comparison of measles antibody titres in mothers .with titres in cord blood samples. Methods: Maternal and cord blood samples from 174full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. Results: Antibody were undetectable in both maternal and cprd samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend=5.4; p=0.02). Conclusions: The study failed to show appreciable concentration of measles antibodies across the placenta.

Key words: Measles antibody, Transplacental transfer of antibody.

KOHLER and Farr provided evidence of active placental transport of IgG from mother to fetus(1). Recent studies have however, shown that maternal IgG, tetanus antitoxins and measles antibodies do not cross the placenta in a facilitative manner in women in Africa as they do in women in the developed world(2). In a previous study, we demonstrated that although the protective levels of tetanus antitoxins were reached in newborns after giving two or more doses of TT during antenatal period in Delhi, active transport of tetanus antitoxins across the placenta was impaired(3). The purpose of the present study was to find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody in India.

Subjects and Methods

Two private maternity centres situated in congested localities of east and west Delhi participated in the study. The subjects were full term pregnant women who were admitted for delivery in these centres during October 1993 to January 1995. The entire pregnancy period was uneventful, and none had fever and/or rash during pregnancy. The women were 18-38 years of age and belonged to middle socio-economic strata. Nevertheless, they lived in areas inhabited by people of all socio-economic strata. They were interviewed for age and parity. Newborns were weighed by a lever balance. Inadvertently, the birth weight was recorded in only 113 children.


Maternal blood samples were obtained by venepuncture when the mothers were admitted for delivery, whereas cord samples were collected at the time of delivery by expressing the umbilical cord contents into a sterile container. The samples were left at room temperature for about 1 hour and then placed in a refrigerator at 2-8°C till transported to the laboratories of the National Institute of Communicable Diseases, Delhi (NICD). The sera were separated and stored at -20.C till tested for hemagglutination inhibition (HI) antibody against measles. All tl;1e mother-cord pairs were tested simultaneously. The reciprocal of the highest dilution of serum which completely inhibited hemagglutination was taken as the antibody titre. The analysis was done by expressing the titre in Log2 units. The number of cord samples showing transplacental concentration and dilution (at different maternal age or parity or birth weight) were compared by Chi-square for linear trend for proportions.

Results

Of 174 maternal blood samples, 16 (9.2%) did not show detectable titres of measles antibody. Nevertheless, in 12 such cases, cord samples were positive for titres ranging from 1 to 5 Log2. Thus, antibody was undetectable in both maternal and
cord samples in only 4 (2.3%) pairs (Table I). As shown in Table II, 69 of 174 (40%) mother-cora pairs had identical antibody titres, whereas 60 (34%) pairs showed higher levels in cord blood than maternal blood. Measles antibody was diluted on the fetal side of circulation in 26% of cases. The cord titres were ([lore often higher than the maternal values only if the maternal values were low. The proportion of cord samples showing transplacental concentration decreased significantly as the maternal titres increased (Chi-square for linear trend; p = 0.00002). The pattern remained same even when cord titres 2:2 Log2 higher than mother titres were considered (Table II).

TABLE I

Correlation Between Measles Antibody (HI, Log2) in Maternal-Cord
Samples in Delhi

Mother
Titre

Cord Titre

0 1 2 3 4 5 6 7 All
0 4 3 2 2 2 3 0 0 16
1 3 7 3 5 1 1 1 0 21
2 1 3 16 5 2 2 2 0 31
3 5 1 4 16 9 6 0 0 41
4 3 1 5 6 10 6 3 0 34
5 0 1 0 2 4 8 2 0 17
6 1 0 2 0 0 3 7 0 13
7 0 0 0 0 0 0 0 1 1
All 17 16 32 26 28 29 15 1 174

Consequently, there was concentration of measles antibody on the fetal side when the mean maternal antibody titres were low (0-2 Log2). When the mean maternal antibody titres were high (4 Log2), the cord titres were comparatively lower. Overall, there was only a slight concentration to- wards fetal side; the cord/maternal ratio of mean titre (Log2) was found to be 1.06.

 

TABLE II

Transplacental Transfer of Measles Antibody (HI, Log2) by Mother Titre, Delhi.

Mother
Titre
(M)
n No. (%) of cord
samples having titre
higher/lower (1 log2)
No. (%) of cord
samples having titre
higher/lower (2 log2)
Cord
titre
(C)
C/M
ratio
Difference
C-M
Higher Lower Higher Lower
0 16 12 (75) - 9 (56) - 2.25   +2.25
1 21 11 (52) 3(14) 8 (38) - 2.05 2.05 +1.05
2 31 11 (35) 4 (13) 6 (19) 1 (3) 2.58 1.29 +0.58
3 41 15 (37) 10 (24) 6 (15) 6 (15) 3.0 1.00 0
4 34 9 (26) 15 (44) 3 (9) 9 (27) 3.44 0.86 -0.56
5 17 2 (12) 7 (41) 0 3 (18) 4.41 0.88 -0.41
6 13 0 (0) 6 (46) 0 3 (23) 4.69 0.78 -1.31
7 1 0 (0) 0 (0) 0 - 7.0 1.00 0
2.94 174 60 (34) 45(26) 32(18) 22(13) 3.11 1.06 +0.17



Table III describes the transplacental transfer of measles antibody in relation to the age of mothers, parity and birth weight of newborns. The maternal age and parity had no significant bearing on the proportion of cord samples showing transplacental concentration or dilution of measles antibody. However, the proportion of cord samples showing concentration increased significantly as the birth weights increased (Chi-square for linear trend = 5.4; P = 0.02).
 

Table III

Transplacental Transfer of Measles Antibody (HI, Log2 in Relation to the age)

  No. tested Mean
mother
titre (M)
Mean
cord
titre (C)
C/M
Ratio
No. (%) of cord samples having
 titre
          higher Lower
Age of mother (yrs)
18-24 88 2.97 3.36 1.13 31 (35) 18 (21)
25-29 57 2.91 2.91 1.00 17 (30) 17 (30)
30-36 21 2.86 2.62 0.92 8 (38) 7 (33)
Para
1 68 3.19 3.44 1.08 25 (37) 15 (22)
2 64 2.89 3.03 1.05 19 (30) 18 (28)
3 23 2.65 2.83 1.07 7 (30) 6 (26)
4+ 13 2.69 2.38 0.88 6 (46) 4 (31)
Birth weight (kg)
<3 60 3.22 3.18 0.99 18 (30) 18 (30)
3.0-3.4 38 2.79 3.29 1.18 14 (37) 6 (16)
3.5+ 15 2.2 3.27 1.49 8 (53) 1 (7)
Total 174 2.94 3.11 1.06 60 (34) 45 (26)


Discussion

Measles vaccine was introduced in the National Immunization Programme in 1985-86(4). Therefore, mothers in this study who were born before 1976, were unlikely to be immunized against measles. Nevertheless, only 16 mothers (9%) were found negative for HI antibodies. Interestingly,

cord samples in 12 additional pairs were also positive for titres ranging from 1 to 5 Log2 thereby indicating that these mothers were also having immunity against measles. Failure to detect antibody in the remaining 4 (2%) pairs may be because of relatively insensitive HI tests employed in this study (Table 1)(5). Thus in conformity with the earlier observations that almost all persons are exposed to wild measles virus some times in life in the absence of immunization(6), all the mothers were considered having immunity induced by natural measles infection. Nevertheless, the mean
antibody titre (2.94 Log2) in these mothers was much less than that observed in early 1980s, for example, in Varanasi (4.69 Log2)(7) or Vellore (4.8 Log2)(8). It may be due to a decrease in the likelihood of boosting of immunity by circulating virus due to measles vaccination programme.

About 34% pairs showed higher levels in cord blood than in mothers, whereas 26% showed transplacental dilution. The cord titres were more often higher than the maternal values only if the maternal values were low. The proportion of cord samples
showing transplacental concentration decreased significantly as the maternal titres increased (Chi-square for linear trend; p = 0.00002). Consequently, the mean cord titers exceeded that of mother only if the maternal levels were low (
2 Log2). When the mother had high (4 Log2) levels of antibody titre, the mean cord titres remained below the maternal one. In fact, the study failed to show appreciable concentration of measles antibodies across the placenta; the cord/maternal ratio of mean titre (Log2) was found to be 1.06. The results are at variance with the observations made in the developed countries where maternal antibodies were found to be concentrated across the placenta at all titres (Pabst; personal communication)(9,10), but are in agreement with the findings that active placental transport of measles and tetanus antibodies from mother to fetus is impaired in Africa(2). Due to low antibody titre at birth, the infants in India become susceptible to measles and respond to measles vaccine sooner than infants of developed countries(8).

The lack of active placental transfer of antibodies has been mainly related to the excessively high maternal immunoglobulins
(IgG) as a result of continued antigenic stimulation in developing countries with a high endemicity of parasitic or infectious diseases(2). In the present study, the age of the mother and parity had no significant bearing on the transplacental transfer of measles antibody. However, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02) Whether the presence of excessively high IgG in mothers and low birth weights in the newborns act independently or through a common mechanism need to be established. However, both these risk factors are highly prevalent in developing countries including India.

In conclusion, the study failed to show appreciable concentration of measles anti- bodies across the placenta. It may inter alia be responsible for low antibody titre in newborns in India which makes them susceptible to measles and responsive to the vaccine at an earlier age than the babies born with high levels of measles antibody in developed countries.

 

References


1. Kohler PF, Farr RS. Elevation of cord over maternal IgG immunoglobulin: Evidence for an active placental IgG transport Na- ture 1966; 210: 1070-1071.

2. Gendrel D, Richard-Lenoble D, Massamba MB, Picaud A, Francoual C, Blot P. Placental transfer of tetanus anti- bodies and protection of the newborn. J Trop Pediatr 1990; 36: 279-282.

3. Singh J, Ichhpujani RL, Prabha S, Chandra R, Khare 5, Grover 55, et al. Transplacental dilution of tetanus antitoxins in Delhi. J Trop Pediatr 1997; 43: 275- 278.

4. Expanded Programme on Immunization. Measles control, India.. Weekly Epidemiological Record 1994; 69: 368-370.

5. Brunell P A. Measles control in the 1990s: Measles serology. Expanded programme on Immunization, WHO Document, WHO/EPI/Gen/90.4,1990.

6. Foster SO, McFarland DA, John AM. Measles. In: Disease Control Priorities in Developing Countries. Eds. Jamison DT, Mosley WH, Measham AR, Bobadilla JL. Oxford, Oxford University Press, 1993; pp 161-187.

7. Kaur G, Agarwal DK, Gulati. AK, Kalra A, Katiyar GP, Agarwal KN. Maternal and cord blood measles antibody titres. Indian J Med Res 1982; 76: 407-414.

8. Black FL, Berman LL, Borgono JM, Capper RA, Carvalho AA, Collins C, et al. Geographic variation in infant loss of maternal measles antibody and in prevalence of rubella antibody. Am J Epidemiol 1986;124:442-452.

9. Sato H, Albrecht P, Reynolds DW, Stagno S, Ennis FA. Transfer of measles, mumps, and rubella antibodies from mother to infant Am J Dis Child 1979; 133: 1240-1243.

10. Griffiths PD, Berney 51, Argent S, Heath RB. Antibody against viruses in maternal and cord sera: Specific antibody is concentrated on the fetal side of the circulation. J Hygiene 1982; 89: 303-310.

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