Maternal Antibody Concentrations Research Articles

Initial levels of maternally derived antibodies predict persistence time in offspring circulation

Vertebrate mothers transmit antibodies to offspring that provide humoral immunity early in life. The duration of protection provided by maternal antibodies varies considerably among species and has not been widely examined in birds. Determination of the length of maternal protection can be a useful predictor of when young are most likely to be susceptible to infection. The duration of maternal antibody protection was determined in Japanese Quail (Coturnix japonica) by immunizing females with keyhole limpet hemocyanin (KLH) and then collecting blood samples from offspring. Maternal antibodies remained detectable in offspring circulation for an average of 14 days (range 3-28). The duration of persistence was predicted by antibody levels as measured in maternal circulation, within egg yolks, or measured in offspring shortly after hatch. Thus, the primary benefit to offspring of high concentrations of maternal antibodies is likely to be an extended period of maternal protection during early growth and development.

Cord blood cytokines and chemokines and development of allergic disease

Exposure to ubiquitous allergens early in life, even before birth, may influence the incidence of allergic diseases later in life. During pregnancy, the fetomaternal interface is surrounded by high levels of T-helper (Th)2-like cytokines, possibly favouring the development of Th2-like immune responses in the offspring. The aim of this study was to evaluate the relation between cord blood (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy and development of allergic disease during the first 2 yr of life in the offspring. The CB cytokine and chemokine levels from children of 20 allergic and 36 non-allergic women were determined by a multiplexed Luminex assay and ELISA. Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP technology. The maternal IgE levels during and after pregnancy correlated with CB IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels. Development of allergic disease and sensitization was associated with increased CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1-associated interferon-gamma inducible protein 10 [IP-10 (CXCL10)] and interferon-gamma inducible T-cell alpha-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs. n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC (CCL22) levels possibly indicate that the maternal immunity can affect the Th1/Th2 profile in the neonate. Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11).

Mother-to-child transmission of HIV infection: nutrition/HIV interactions.

to an increase in mother-to-child transmission of HIV.2 In a study of 338 HIV-infected women in Malawi, more than half of the women had vitamin A deficiency and HIV transmission was significantly associated with vitamin A stat~~ This association is plausible because vitamin A deficiency impairs T and B cell function, which could cause increased viral load and result in reduced maternal antibody concentrations. Alternatively, vitamin A deficiency could merely be a marker of advanced maternal disease, which could explain the higher rate of vertical transmission. Vitamin A supplementation could reduce chorioamnionitis in late pregnancy and improve immune function of the infant. Although it seems unlikely, a potentially harmful effect of vitamin A supplementation on maternal infection, and therefore on vertical transmission, could be through increasing HIV repli~ation.~ Preliminary findings from a trial in Tanzania comparing supplemental vitamin A with multivitamins that did not contain vitamin A or no supplementation in pregnancy showed a 40% reduction in fetal death and a reduction in adverse pregnancy outcome among the women taking multivitamins compared with those receiving no supplementation. Vitamin A alone had no significant effect. Multivitamins, but not vitamin A, also had a beneficial effect on T-cell subset count^.^ The efficacy in reducing vertical HIV transmission was not reported. In a similar trial in Malawi a benefit was reported with respect to fetal death and birthweight outcomes.6

Kinetics of Decline of Maternal Measles Virus-Neutralizing Antibodies in Sera of Infants in France in 2006

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (>or=120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.

What’s happening – Probing of HPA-1a antigen–antibody interaction by surface plasmon resonance technology

This brief report summarizes the use of surface plasmon resonance technology (SPRT) in probing HPA-1a antigen–antibody interactions, based on a poster presented at the 60th meeting of the American Association of Blood Banks. It was concluded that the GP purification method could affect the performance of antigen in SPRT. It also highlighted that chips immobilised with Monoclonal antibody (Mab)-purified GP-IIb/IIIa work satisfactorily with both monoclonal and recombinant Abs with the appropriate concentration and binding affinity, while determination of the avidity and concentration of maternal polyclonal antibodies in respect to clinical severity on NAIT warrants further development.

Analysis of rubella antibody distribution from newborn dried blood spots using finite mixture models

Eluted dried blood spot specimens from newborn screening, collected in 2004 in North Thames and anonymously linked to birth registration data, were tested for maternally acquired rubella IgG antibody as a proxy for maternal antibody concentration using an enzyme-linked immunosorbent assay. Finite mixture regression models were fitted to the antibody concentrations from 1964 specimens. The Bayesian Information Criterion (BIC) was used as a model selection criterion to avoid over-fitting the number of mixture model components. This allowed investigation of the independent effect of maternal age and maternal country of birth on rubella antibody concentration without dichotomizing the outcome variable using cut-off values set a priori. Mixture models are a highly useful method of analysis in seroprevalence studies of vaccine-preventable infections in which preset cut-off values may overestimate the size of the seronegative population.

Passive transmission and persistence of naturally acquired or vaccine-induced maternal antibodies against measles in newborns

This paper reviews literature on passively transferred maternal antibodies against measles in infants. The amount and decay of these antibodies can be a result of changing patterns in society: increasing cohorts of women are vaccinated against measles instead of having naturally acquired immunity, the age of first childbirth is increasing and young adults are less exposed to natural boosters. The concentration and persistence of maternal antibodies differ in infants of women vaccinated against measles versus infants of naturally immune women. The date for commencing universal measles vaccination should take into account the presence of these antibodies since they can hamper the immunological response to vaccination. Each country should therefore consider adapting the timing of vaccination in relation to its measles sero-epidemiological situation. The possibility of priming the immune system with an early vaccine dose and boosting later on offers opportunities for vaccination at very young age.

Predictors of Pneumococcal Conjugate Vaccine Immunogenicity among Infants and Toddlers in an American Indian PnCRM7 Efficacy Trial

Pneumococcal conjugate vaccines are important for the prevention of serious illness and death among infants. Factors associated with pneumococcal conjugate vaccine immunogenicity have not been explored. Children <24 months of age received 2, 3, or 4 doses of 7-valent pneumococcal conjugate vaccine (PnCRM7) or control vaccine depending on age at enrollment. Serum samples were tested for serotype-specific antibodies by enzyme-linked immunosorbant assay. Multiple linear regression was used to determine predictors of immunogenicity. Among 315 PnCRM7-vaccinated subjects and 295 control subjects enrolled at <7 months of age, geometric mean concentrations (GMCs) of antibodies were significantly higher after dose 3 than after dose 2 for all serotypes except type 4. The proportion of subjects with antibody concentrations > or =5.0 micro g/mL was higher for all serotypes, but the proportion with concentrations > or =0.35 micro g/mL was higher only for types 6B and 23F. Three-dose and 2-dose regimens for those 7-11 and 12-23 months of age, respectively, were highly immunogenic. Increased maternal antibody concentrations were associated with reduced responses to dose 1 and 3 but not to dose 4 of PnCRM7. Maternal antibody is associated with a reduced infant response to PnCRM7 but does not interfere with immune memory. In infants, a third priming dose increases the antibody GMC and the proportion achieving an antibody concentration > or =5.0 micro g/mL but has little impact on the proportion achieving a concentration > or =0.35 micro g/mL.

Perinatal exposure to low doses of PCB 153 and PCB 126 affects maternal and neonatal immunityin goat kids

Pregnant does (10 goats/group) were dosed orally either with polychlorinated biphenyl (PCB) 153 (98 µg/kg body weight/d) or PCB 126 (ng/kg body weight/d) dissolved in corn oil or with corn oil only (control group) from gestation day (GD) 60 until delivery. An additional group (n = 5) of pregnant does received the synthetic estrogen diethylstilbestrol (DES; 0.4 µg/kg body weight/d) by intramuscular injection using the same treatment schedule as for the PCB groups. Blood samples for immune analysis were collected at wk 0, 1, 2, 4, 6, and 8 of age. The effects of perinatal PCB exposure on postnatal humoral immune responses were examined by assessing the levels of total immunoglobulin G (IgG) and immunoglobulins to specific microbes at wk 0, 1, 2, 4, 6, and 8 of age, and immune responses following immunization of kids at 2 wk of age. PCB 153 exposure suppressed maternal and neonatal immunity, as demonstrated by reduced transfer of maternal IgG and specific antibodies to the environmental microbes Arcanobacterium pyogenes, Mannheimia haemolytica, and reovirus (REO-1). Furthermore, PCB 153 reduced the level of maternal antibodies to Mycobacterium avium paratuberculosis and equine influenza virus (EIV-1) in the newborn kids. The antibody response against EIV-1 was significantly higher in PCB 153-exposed kids 2 wk following immunization. PCB 126 exposure reduced the levels of maternal antibodies to REO-1. In contrast, gestational exposure to PCB 126 increased the concentrations of maternal antibodies to tetanus toxoid. No differences from controls in plasma total IgG levels at birth or colostrum IgG concentrations were observed in the PCB 126-treated does. However, a significant reduction in IgG levels from GD 60 until delivery was found in this group. Gestational exposure to DES reduced the concentrations of maternal antibodies against A. pyogenes, M. haemolytica, M. avium Paratuberculosis, and REO-1. These results suggest that perinatal exposure to low doses of PCB 126 and PCB 153 affects the maternal immunity in kids. The difference in responses between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms. The observation that the effects produced by PCB 153 resembled those produced by DES raises the question of whether this congener may modulate immunity by estrogenic mechanisms.

High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

Studies among HIV-1-infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1-specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks' gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1-specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1-exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1-exposed infants.

Role of Maternal Pertussis Antibodies in Infants

Pertussis remains a serious infection in young infants. Most deaths occur in the first 3 months of life, before administration of the first dose of pertussis vaccine. Pertussis antibodies are transferred from mother to infant; but because of the lack of serologic correlates of protection, it is difficult to determine the proportion of infants born with a protective concentration of maternal antibodies. Indirect evidence suggests that maternal antibodies provide short lived protection against fatal pertussis. It is hoped that the protection of young infants could be enhanced by maternal or neonatal vaccination. The possibility of protecting young infants against pertussis by immunizing their mothers during pregnancy was investigated in the 1930s and 1940s; no further studies have been published since. Recent animal and human studies have provided evidence that neonatal immunization with acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune response. The limited data on neonatal and maternal pertussis immunization are promising and call for further research to reduce the vulnerability of young infants to pertussis disease.

Dengue infection during pregnancy and transplacental antibody transfer in Thai mothers

Objectives The objectives of this study were to estimate dengue seroprevalence in a population of Thai pregnant women, living in a highly endemic area and placental transfer of dengue antibodies. Methods A cross-sectional seroprevalence study of 245 pregnant women at delivery. Results Dengue HAI antibodies were positive in 94.7%. Maternal age was the only risk factor associated with dengue infection as older mothers (>20 years) were significantly more likely to be seropositive than younger women ( p<0.0001). Cord antibody titres varied with maternal age and antibody titre, were significantly higher in babies born to younger mothers (<20 years) ( p=0.01), and were significantly correlated with maternal titre. Low birthweight babies had lower transfer ratios for DEN-2 antibody (1.06) compared to heavier babies (1.36, p=0.05). No mother or neonate had dengue IgM detected. Two women were classified as recently, but not currently infected with dengue virus and we consider it likely these were first trimester infections. As no infant became infected the fetal infection was 0%. Conclusions Younger mothers were more likely to have been recently infected, resulting in higher antibody titres. Maternal dengue antibody transfer was proportional to maternal antibody concentration.

Prediction of fetal anemia in rhesus disease by measurement of fetal middle cerebral artery peak systolic velocity.

In red blood cell (RBC) isoimmunized pregnancies fetal anemia is associated with a hyperdynamic circulation. The aim of the present study was to examine further the possible value of fetal middle cerebral artery peak systolic velocity (MCA-PSV) in the management of affected pregnancies. A reference range of fetal MCA-PSV with gestation was constructed from the study of 813 normal singleton pregnancies at 20-40 weeks' gestation. Fetal MCA-PSV was also measured in 58 fetuses from RBC isoimmunized pregnancies, with maternal hemolytic antibody concentration of >15 IU/mL at 19-38 weeks' gestation and within 10 days of measurement of fetal hemoglobin concentration in blood obtained either by cordocentesis (n = 43) or at delivery (n = 15). In the RBC isoimmunized pregnancies each of the measured MCA-PSV and hemoglobin concentrations was expressed as a delta value (difference in SDs from the normal mean for gestation). Regression analysis was used to determine the significance of the association between delta MCA-PSV and delta fetal hemoglobin concentration. In the normal pregnancies there was a significant increase in fetal MCA-PSV with gestation (mean MCA-PSV = 10(0.0223 x GA + 0.963)). In RBC isoimmunized pregnancies the fetal MCA-PSV was increased and there was a significant association between delta MCA-PSV and delta hemoglobin concentration (delta hemoglobin = (delta MCA-PSV + 0.093)/-0.356; R(2) = 0.638, P < 0.0001). An MCA-PSV of mean + 1.5 SDs detected 96% of severely anemic fetuses, with a hemoglobin deficit of at least 6 SDs, for a false-positive rate of 14%. Measurement of fetal MCA-PSV is a useful method of assessing fetal anemia. In the clinical management of isoimmunized pregnancies a cut-off in MCA-PSV of mean + 1.5 SDs can identify nearly all severely anemic fetuses with a low false-positive rate.

Maternal respiratory syncytial virus antibody titers: season and children matter

The seasonal variation in concentrations of maternal serum antibodies to respiratory syncytial virus fusion protein was investigated with the use of 761 maternal sera at delivery of term infants during a 12-month period. Mean antibody titers were significantly higher between April and September and significantly higher in women who already had children at home.

Maternal measles antibody decay in rural Bangladeshi infants — implications for vaccination schedules

Considerable numbers of measles cases occur below the target age for vaccination in the Indian sub-continent. The immunogenicity of measles vaccine in infancy is dependent on the rate of decay in maternal antibody since this antibody interferes with vaccine induced seroconversion. This study investigated maternal antibody decay in a rural population in Bangladesh and evaluated possible risk factors for early decay. Measles antibodies were assessed using both ELISA and Plaque Reduction Neutralization (PRN) test in 330 infant-mother pairs in a cross-sectional survey. PRN was more sensitive method than ELISA for determining antibody levels. Antibody levels decreased rapidly in infants with increasing age. By the age of 5 months, 67% ( 28 42 ) infants had practically no protective antibody left (30 mIU ml −1 or below). Only 12% infants at 5 months of age, and 5% at 8 months, had levels greater than 120 mIU ml −1—stated to ‘protect’ children. Multiple regression showed that maternal age was the only variable associated with the level of antibody (maternal weight, height and MUAC were not associated), decreasing by 1.06 mIU ml −1 for each year of age ( P = 0.002). Infant's antibody concentration decreased with age by an average 2 mIU ml −1 for every month of life ( P<0.0001), and was determined by the maternal antibody concentration ( P < 0.0001) (child's length, weight, MUAC, mother's gestational age and parity were not associated). The relatively rapid antibody decay suggests that the target age for measles vaccination might be reduced. Further, as the cohort of vaccinated mothers enters reproductive age in Bangladesh, a more rapid decay of antibody may be expected in future generations of Bangladeshi children. The information presented here suggests that a formal trial of standard measles vaccine at younger ages is justified in this population as it could confer considerable benefit in reducing infant measles.

Effect of the concentration of maternal antibodies on the neural invasion of Aujeszky's disease virus in neonatal pigs

The degree to which maternally derived antibodies may affect neural invasion of Aujeszky's disease virus (ADV) in neonatal pigs was examined. One-week-old pigs with different levels of maternal immunity were inoculated intranasally with 10 7.0 TCID 50 of the Ka strain. The invasion of the virus was studied in both the trigeminal neural pathway (nasal mucosa, trigeminal ganglion = 1st level, pons/medulla = 2nd level and cerebellum/thalamus = 3rd level) and the olfactory neural pathway (olfactory mucosa = 1st level, olfactory bulb = 2nd level and lateral olfactory gyrus = 3rd level) by virus titration and immunohistochemistry (IHC). In control pigs without specific antibodies, virus invaded all neuronal levels in both neural pathways. In pigs with a low concentration of maternal antibodies (SN-titer = 2–3), virus infected all neuronal levels in both neural pathways but, compared to the controls, virus titers were significantly lower (approximately 2 log 10) in the trigeminal pathway. In pigs with a high concentration of maternal antibodies (SN-titer = 272–384), virus reached the 2nd neuronal level of the olfactory pathway while no neural tissue had been infected in the trigeminal pathway. Virus titers in the affected neuronal levels of the latter pigs were significantly lower than in the controls. IHC revealed, in non-immune pigs, a fibroblast-mediated spread of the virus in the nasal lamina propria, and a local spread of the virus from neurons to their satellite cells in the trigeminal ganglion. Such a spread of the virus was rarely seen in the nasal mucosa and in the trigeminal ganglion of passively immune pigs. These findings suggest that, in the presence of maternal immunity, defence mechanisms operate at these sites. In conclusion, we can state that a correlation exists between the level of maternal immunity and the protection against invasion of ADV in the nervous system of neonatal pigs.

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.

Maternofetal Transfer of IgG Anti-Escherichia coli Antibodies with Enhanced Avidity and Opsonic Activity in Very Premature Neonates

Total IgG concentrations, IgG antibody concentrations to pooled Escherichia coli antigens, and IgG anti-E. coli antibody avidity were measured in cord and maternal serum samples collected from 52 mother-infant pairs after premature delivery (mean gestational age 28 wk, range 23-33 wk). The mean IgG anti-E. coli antibody concentration in cord serum (1.86 relative units/mL) was markedly lower than in maternal serum (5.42 relative units/mL) at this gestation (p less than 0.0001). Cord serum IgG anti-E. coli antibody concentrations correlated closely with maternal IgG anti-E. coli concentrations when controlled for the effect of gestational age (partial correlation coefficient 0.89; p less than 0.001) but only weakly with gestational age when controlled for maternal IgG antibody concentrations (partial correlation coefficient 0.23; p = 0.06). The mean ratio of cord to maternal IgG anti-E. coli antibody concentrations was considerably lower than the mean ratio for total IgG concentrations (0.34 versus 0.72; p less than 0.001). The mean avidity of IgG antibody for the pooled E. coli antigens was significantly greater in cord serum than in maternal serum (2.45 versus 1.99M; p less than 0.0001). There was a close correlation between cord and maternal antibody avidity (r = 0.70; p less than 0.001), but cord IgG antibody avidity did not correlate with gestational age (r = -0.07; p = 0.61), nor with cord IgG anti-E. coli antibody concentrations (r = 0.10; p = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Prepartum Vaccination with K99 Escherichia coli Vaccine on Maternal and Calf Blood Antibody Concentration and Calf Health

One hundred and two dry, pregnant Holstein cows were identified alternately as vaccinated or nonvaccinated (Group 0) animals. Vaccinated cows were scheduled for vaccination at 6 and 3 wk prior to expected calving date with Vicogen®, a commercial vaccine produced for the prevention of calf scours caused by entero-pathogenic Escherichia coli that possess the K99 antigen. Group 1 included cows that were less than 6 wk from freshening when the experiment started and, therefore, received only one vaccination and cows that received two vaccinations with less than 5 days between the second vaccination and freshening. Those cows with interval between the second vaccination and parturition greater than 5 days were classified as Group 2. Soon after birth, each calf was given 2 liters of colostrum from its dam. For at least 3 days, and longer when available, calves from control cows received pooled colostrum from control cows and calves from vaccinated cows received pooled colostrum from vaccinated cows.Anti-K99 antibody liters were determined by an agglutination test on blood from cows and calves and on colostrum. Other measurements were made by standard procedures. Results from Groups 0, 1, and 2 were cow blood titer at freshening 21, 355, 306; calf total plasma protein at 24h of age 6.45, 6.31, 6.22; calf packed cell volume at 24h of age 32.9, 30.0, 30.2; calf blood titer at 24h of age 34, 762, 1114; colostrum titer 74, 1637, 3404. For 93 calves, mortality was 10.6, 11.1, and 7.1%. Differences in scours scores and incidence of sickness were not significant.

In Utero Resuscitation after Cardiac Arrest in a Fetus

The present authors report on a hydropic fetus, with severe rhesus isoimmunization, that was resuscitated in utero by external cardiac massage. The procedure was carried out after 3 minutes of cardiac arrest during fetos-copic intravascular blood transfusion at 19 weeks of gestation. Real-time ultrasonography ruled out cerebral edema and periventricular or intraventricular hemorrhage, and the infant was delivered in good condition several weeks later. A 28-year-old woman whose blood group was A Rh-negative was in her ninth pregnancy. The first four had been uneventful and had resulted in normal deliveries at term. After the fourth delivery, she was found to have anti-D antibodies. In the four subsequent pregnancies, the fetuses had severe rhesus isoimmunization which resulted in two neonatal deaths at 36 and 33 weeks of gestation, respectively, followed by two intrauterine deaths at 30 and 26 weeks of gestation. In the ninth pregnancy, the maternal antibody concentration was 17 μ/ml at 14 weeks and 213 μ/ml at 18 weeks, despite plasmapheresis three times a week. Spectrophotometric measurements of amniotic fluid (change in optical density at 450 nm) at 17 and 18 weeks were 0.116 and 0.127, respectively. The patient was referred to the authors' unit at 18 weeks after ultrasound examination had shown a fetus with scalp edema associated with large pericardial, pleural, and ascitic effusions. At 18, 19, 23, 26, and 29 weeks freshly packed group 0, Rh-negative blood was infused into an umbilical cord artery under direct fetoscopic vision. After the first transfusion, the fetal edema and the pleural and pericardial effusions resolved rapidly, but there were some residual ascites. During an otherwise uneventful second transfusion, sudden, severe fetal bradycardia culminating in cardiac asystole within 2 minutes was seen on real-time ultrasound scanning. The patient was turned into the left lateral position, and under continuous ultrasound guidance the fetal heart was massaged at 40 compressions per minute by digital pressure through the maternal abdomen. The fetal chest was compressed against the posterior uterine wall during this procedure. Spontaneous cardiac activity was resumed in 3 minutes. The rest of the pregnancy and the subsequent transfusions were uneventful. Serial real-time ultrasound scans of the fetal brain and measurement of the anterior and posterior horns of the lateral ventricles ruled out cerebral edema and periventricular or intraventricular hemorrhage and their sequelae of hydrocephaly and porencephalic cysts. Fetal growth was normal, and the ascites were resolved. At 32 weeks, a 1932-gm, nonhydropic boy was delivered by elective cesarean section. His Apgar score was 3 at 1 minute and 9 at 5 minutes. His cord blood hemoglobin concentration was 6.1 gm/dl, and his plasma bilirubin concentration was 60 μmol (3.5 mg/100 ml). He required three exchange transfusions, but there were no neonatal complications. Subsequent growth and neurological development were normal.