Exposure to alcohol in utero: Influence on cognitive function and learning in a northern elementary school population.

OBJECTIVES: To establish the prevalence of fetal alcohol exposure; to compare physical, behavioural and learning patterns of children with significant alcohol exposure in utero with those of a group of children exposed to minimal alcohol; to assess the usefulness of a fetal alcohol syndrome (FAS)/fetal alcohol effect (FAE) score; and to provide feedback to parents, schools and communities. DESIGN: Parent questionnaire, complete physical examinations of children, psychometric tests of the children using elements of the Pediatric Early Elementary Examination (PEEX) and the Pediatric Examination of Educational Readiness (PEER), ADD-H comprehensive teachers rating scale (ACTeRS) score, the newly developed FAS/FAE Score, and the Brigance Comprehensive Inventory of Basic Skills to assess language and mathematical achievement. Testers were blinded to the results of the assessments and questionnaires. SETTING: Grades 1 to 3 at Sir Alexander MacKenzie School in Inuvik, Northwest Territories. RESULTS: Twenty-four per cent of mothers reported frequent or binge drinking, and 76% of mothers reported abstinence or moderate alcohol intake. There were significant ethnic differences; none of the Caucasian mothers reported frequent or binge drinking during pregnancy compared with 40% of Inuvialuit and 33% of Indian mothers. Children with exposure to frequent or binge drinking in utero had smaller palpebral fissures (2.3+/-0.1 cm versus 2.5+/-0.3 cm, P<0.01), smaller palpebral fissure to intercanthal distance ratios (0.77+/-0.05 versus 0.86+/-0.10, P<0.01) and smaller head circumferences (52.1+/-1.6 cm versus 53.6+/-1.6 cm, P<0.01) than those exposed to moderate drinking or abstinence. Children exposed to frequent or binge drinking in utero also demonstrated poorer coordination (P<0.005) and cortical function (P<0.01), attention problems, hyperactivity (ACTeRS), and poorer scholastic achievement in language (P<0.001) and mathematics (P<0.01) than their minimally exposed counterparts. In children in grades 2 and 3, a significant negative correlation was found between FAS/FAE scores and language (r=-0.55, P<0.001) and mathematical achievement (r=-0.28, P=0.20). CONCLUSIONS: The prevalence of drinking during pregnancy in the northern population studied was high, and exposure in utero was associated with physical abnormalities, difficulties with coordination and cortical function, and significant delays in language and mathematical achievement. The FAS/FAE score may be useful in predicting success or failure in language development.

Perinatal vitamin D and calcium status of northern Canadian mothers and their newborn infants.

OBJECTIVE: This study was undertaken to examine the vitamin D and calcium status of mothers and their newborns. METHODS: The intakes of vitamin D and calcium were determined prenatally in 121 women including 33 Caucasians, 51 Inuits, and 37 Native Indians, living in the Inuvik zone of the Northwest Territories. Plasma concentrations of 25-(OH)-D and calcium were also measured in mothers as well as in their offspring at delivery. RESULTS: The daily mean vitamin D intake of native mothers, including Inuits and Indians, with (8.1+/-5.5 microg) and without supplements (3.4+/-2.5 microg) was significantly lower than that of non-native mothers (13.2+/-5.9 microg and 5.8+/-4.3 microg, respectively). According to the predicted prevalence of low vitamin D intake, there existed a higher risk of vitamin D deficiency without supplementation in both native (88.6% vs 48.4%) and non-native (63.5% vs. 15.1%) mothers. The trend for calcium intakes with and without supplementation was similar to vitamin D intake. At the point of delivery, the plasma levels of 25-(OH)-D were lower in native mothers (50.1 19.3 nmol/L) and their offspring (34.2+/-13.1 nmol/L) than their counterparts (59.8+/-29.4 nmol/L and 41.4+/-23.5 nmol/L, respectively). Its plasma levels in newborn infants averaged only 67% of their mothers. None of these infants showed clinical evidence of vitamin D deficiency. In fact, their plasma calcium levels were significantly higher than their mothers. CONCLUSIONS: Plasma 25-(OH)-D concentrations of 60 to 70% of maternal levels may represent a "normal" range for newborn infants. However, a supplementation in native northern Canadian mothers during pregnancy and in their neonates during infancy may have a role to play in the prevention of vitamin D deficiency.

Perinatal vitamin A (retinol) status of northern Canadian mothers and their infants.

Vitamin A (retinol) status was determined in two groups living in the northern part of Canada: native (Indian and Inuit) and non-native (Caucasian). The dietary intake of vitamin A and its plasma concentration were measured prenatally, at delivery and postnatally in mothers. Plasma concentrations were also measured at birth and postnatally in their infants. The mean vitamin A intake of native mothers was significantly lower than that of non-native mothers, 661 +/- 485 versus 1,377 +/- 1,418 retinol equivalents (p < 0.00005), with a higher risk of deficiency without supplementation, 35% versus 8%. Plasma retinol concentrations, although not in the deficient range, were significantly lower in native than non-native mothers prenatally and postnatally. Infant mean plasma retinol concentrations at birth averaged only 52% of those of their mothers and were significantly lower among native than non-native infants although no clinical evidence of vitamin A deficiency was noted. We speculate that vitamin A supplementation in native Northern Canadian mothers during pregnancy and in their neonates during infancy may have a role to play in the prevention of vitamin A deficiency. We also postulate that plasma retinol concentrations of 50-60% of maternal levels and between 0.7 and 2.5 mumol/l represent a 'normal' range for newborn infants.

Vitamin D deficiency in a Manitoba community.

OBJECTIVE: Using a cross-sectional survey, to investigate the vitamin D status of a random sample of 80 mother-child pairs (child age 3-24 months) in a Manitoba community with a high incidence of rickets. METHOD: A questionnaire on feeding habits, gestational history, maternal diet and vitamin supplements was administered to mothers in their homes with the assistance of a local interpreter. Venous blood was collected from both mother and child for serum 25-hydroxyvitamin D levels. RESULTS: Of 91% babies initially breastfed, 36% received no formula or milk after weaning and 40% received no vitamin supplements. 24% of mothers took no vitamin supplements during pregnancy and lactation. Knowledge about rickets was poor. In 43% of children and 76% of mothers, serum 25-hydroxyvitamin D levels were below normal range. CONCLUSIONS: Vitamin D levels are low in this population due to lack of fortified dairy products and vitamin D supplements. A public health program should include counseling on rickets and vitamin D supplementation for all infants and pregnant or lactating women.

PIP: In the isolated Island Lake area of northern Manitoba, which has a high incidence of rickets, interviews were conducted with 80 mothers, each with a child at least 2 years old, living in St. Theresa Point and Garden Hill in their homes during June-July 1987 to determine their knowledge and attitudes towards rickets. Nurses obtained blood samples from the women and their young children so the researchers could determine the vitamin D status of both. The mother-child pairs were native Canadians from the Ojibway linguistic group that speaks its own dialect of Ojibway-Cree. Mothers initially breast fed 91% of the children. After weaning, 1/3 of infants received neither infant formula nor milk. No vitamin supplements were given to 40%. Many of the children who did receive vitamin supplements did not receive them regularly. 70% of the mothers did not drink any milk. 24% were milk-intolerant. 24% took no vitamin supplements during pregnancy and lactation. Mothers who did take supplements did not do so regularly. 17% claimed that their skin was sensitive to sunlight. 84% of mothers in one community had never heard of rickets. Most did not know its cause. Neither mothers nor the children were exposed to the sunlight in the summer. When outside, almost all small infants were completely covered to protect them from the elements. The mean 25-hydroxy-vitamin D level was 26.2 nmol/l for the children and 19.8 nmol/l for the mothers. 43% of children and 76% of mothers had a 25-hydroxy-vitamin D level below the normal range. These high levels of vitamin D insufficiency were even more troublesome given that the blood was taken in late June and July when vitamin D levels would be likely to be at their highest. The dearth of vitamin D fortified dairy products and vitamin supplements greatly contributed to the low level of vitamin D status in this area. The findings show a need for public health officials to include education on rickets and vitamin D supplementation for all infants and pregnant or lactating women.

Iron status and pregnancy in a northern Canadian population: relationship to diet and iron supplementation.

To determine the extent of iron deficiency, the prognostic value of prenatal ferritin levels and the desirability of prenatal iron supplementation in the western Canadian arctic, dietary iron intake was determined in 171 women and ferritin levels determined in 121 women during pregnancy, 79 at delivery and 77 postnatally, as well as in 65 of their infants at birth and 74 postnatally. Iron deficiency (ferritin < 15 ng/ml) was present in 34% of women during the first two trimesters, 25% (20/79) at delivery and in 51.7% (15/29) of mothers and 31% (9/29) of infants beyond four months after delivery. Maternal follow-up ferritin levels correlated poorly with dietary iron intake but well with prenatal ferritin levels, which appeared to be good predictors of the effectiveness of supplementation. Mean infant follow-up ferritin levels were 105.6 +/- 115.2 ng/ml with, and 46.7 +/- 63.5 without maternal prenatal supplementation (p = 0.03); maternal, 45.5 +/- 40.9 ng/ml with, and 12.8 +/- 9.2 without (p < 0.001). Measurement of prenatal ferritin levels to determine risk of iron deficiency and routine prenatal iron supplementation are recommended.

Smoking and caffeine and alcohol intake during pregnancy in a northern population: effect on fetal growth.

OBJECTIVES: To assess the prevalence of smoking and of caffeine and alcohol intake during pregnancy in a northern population and to determine the relation of these factors to birth weight, length and head circumference. DESIGN: Questionnaire survey and collection of maternal and newborn measurements. SETTING: Ten communities in the Inuvik Zone, NWT. PATIENTS: A total of 162 women (56 Inuit, 38 Indian, 37 white and 31 mixed race) who presented for prenatal care in their community and gave birth in Inuvik between September 1987 and January 1990 and their newborns. RESULTS: In all, 64% (101/159) of the women smoked, 57% (88/154) ingested more than 300 mg of caffeine daily, and 34% (50/145) drank alcohol during their pregnancy. Smoking, caffeine intake and binge drinking were most frequent among the Inuit and Indian mothers. Smoking was significantly associated with decreased birth weight (p less than 0.001) and length (p less than 0.05). Alcohol intake, especially binge drinking, was significantly associated with decreased head circumference (p less than 0.05). Caffeine was found not to be related to any of the outcome variables after smoking was controlled for through stepwise multiple regression. CONCLUSIONS: The marked prevalence of smoking and alcohol intake during pregnancy and their effects on the newborn are public health concerns in the Northwest Territories and warrant intensive countermeasures.

Prospective trial of timing of bacillus Calmette-Guérin vaccination in Canadian Cree infants.

We studied 184 Cree Indian infants in randomized, prospective fashion to assess the effect of age on lymphocyte sensitization to purified protein derivative (PPD) before and after and without bacillus Calmette-Guérin (BCG) vaccination. Lymphocyte responses to PPD, Candida, and streptokinase were measured at birth and at intervals later. The mean response of paired values from 26 infants without BCG vaccination rose for the PPD stimulation index (SI) from 2.7 at birth to 3.9 before 2 yr of age. The SI for both Candida and streptokinase for this group of infants rose significantly in the first 2 yr (p less than 0.05). In 66 infants who received BCG in the first 7 days of life, the PPD-SI rose from 3.1 to 35.3 (p less than 0.001). In 17 infants who received the vaccine later but before 9 months, it rose from 3.1 at birth to 24.9, and in 14 who received it between 9 months and 2 yr, it rose from 2.2 to 52.9. The lymphocyte responses to PPD after BCG in these two groups were significantly different (p less than 0.05). There was no evidence in the older infants that a raised PPD-SI before BCG vaccination affected lymphocyte sensitization by the vaccine. We conclude that increasing the age at vaccination with BCG from birth to more than 9 months enhances immunologic sensitization to PPD significantly in this population.

Vitamin E status of northern Canadian newborns: relation of vitamin E to blood lipids.

Vitamin E status was determined in two groups of Canadian newborns: a northern group, mainly aboriginal (Indian and Inuit), and a southern group, mainly nonnative. Serum vitamin E, cholesterol, and triglyceride levels were measured in cord blood and ratios of vitamin E to both cholesterol (E:chol) and cholesterol plus triglyceride (E:chol + TG) were calculated. For the combined groups the mean serum concentration of vitamin E (8.71 +/- 2.45 mumol/L), cholesterol (1.77 +/- 0.46 mmol/L), and triglyceride (0.65 +/- 0.30 mmol/L) as well as the ratios E:chol (5.00 X 10(-3) +/- 1.26 X 10(-3) and E:chol + TG (3.60 X 10(-3) +/- 0.77 X 10(-3) were within normal limits. Significant north-south differences were found only in the mean triglyceride concentration, which was lower (p = 0.03), and E:chol + TG, which was higher (p = 0.002), in the northern than in the southern group. No differences attributable to differences in race were found. Only one infant, an Inuit in the northern group, was found to be deficient in vitamin E.

Transfer of maternal specific cell-mediated immunity to the fetus.

The extent of specific cell-mediated immunity was measured in 67 consecutive newborns and their mothers. The stimulation index of blast transformation of the infants' lymphocytes in the presence of purified protein derivative, Candida extract and streptokinase was greater than 2.0 in 54%, 18% and 23% respectively. This was seen only in infants whose mothers' index was also greater than 2.0 to the same antigen. Leucocyte inhibition factor generated from lymphocytes of four babies in the presence of purified protein derivative inhibited migration of indicator cells over 50%; their stimulation index with purified protein derivative was greater than 2.0. Newborns have cell mediated immunity to the same antigens as their mothers, and this wanes during the first few months of life.

Northern infant syndrome: a deficiency state?

A syndrome is described that affected 16 Indian and Inuit infants roughly 3 months old, most of whom were born in settlements in the Canadian Arctic. The infants presented with a clinical picture that included hepatitis, hemolytic anemia, rickets and respiratory distress, a combination that resembled a syndrome first described in malnourished infants at the turn of the century by von Jaksch and Luzet. The clinical course was self-limited, and all the infants survived without sequelae. The cause of the syndrome was not determined; no infectious agents were discovered. However, low levels of vitamins A, C, D and E were found in a few infants in whom assays were done. The implications of these findings and their relation to the possible cause of this "northern infant syndrome" are discussed.

Trial of pyridoxine therapy for tetanus neonatorum.

Pyridoxine, a coenzyme in the production of gamma-amino-n-butyric acid, was added (100 mg per day) to conventional therapy for tetanus neonatorum in 20 infants who were graded according to prognosis and severity of spasms. Three infants died, for an overall mortality of 15%. All three were in prognostic group V; mortality in group V was 37.5%. Fifteen days after admission, 14 (70%) of the remaining 17 infants were free of spasms and three (15%) had only mild spasms. In comparison to other studies in which conventional therapy alone was used for tetanus neonatorum, the addition of pyridoxine appeared to decrease mortality and the duration of spasms.

Significance of Rh-sensitization during pregnancy: its relation to a preventive programme.

A study of the incidence of Rh-sensitization showed a 6.5% incidence of anti-D appearing for the first time during the last trimester of pregnancy. In 24 of the 29 subjects these antibodies were weak, and were found only when a sensitive technique using enzyme-treated Rh-deletion test cells was employed. The remaining five, however, had high-titre antibodies, which were associated with a positive Coombs test on cord blood.Rh-immune globulin administered at delivery resulted in disappearance of the anti-D in all but one of the subjects with weak antibody to whom it was given, suggesting that this treatment can reverse early sensitization. There was no effect when Rh-immune globulin was given to one subject with a high anti-D titre.Since sensitization has been found to occur frequently during the last trimester of pregnancy, an antenatal schedule of prophylaxis is advocated.