Disease Associated With Poor Child Nutrition Articles & Resources

Simple contingency table analysis was done by [.2] and Fisher exact test for comparison of the 2 groups on overall proportions and frequency distributions of categorical variables. P < .05 was accepted as significant. Stepwise logistic regression analysis was used to determine factors that independently predicted offspring microcephaly. Variables were added to the model provided that the P value for improvement was <.15. Statistical analyses were performed using SAS/STAT Software, version 8 of the SAS system for UNIX. (17)

RESULTS

Microcephaly

Women were divided into 2 groups: those who had blood Phe [less than or equal to]600 [micro]mol/L by 8 weeks' gestation and those who had blood Phe >600 [micro]mol/L by 8 weeks' gestation. Eighty-six (%) women maintained blood Phe control [less than or equal to]600 [micro]mol/L by 8 weeks' gestation, whereas the remaining 165 women had levels >600 [micro]mol/L by 8 weeks' gestation. Of the 251 offspring, 85 (%) were born with microcephaly. Of the 85 microcephalic offspring, 78 were born to women with blood Phe >600 [micro]mol/L by 8 weeks' gestation and represented 47% of this group, whereas only 7 (%) were born to women who had blood Phe [less than or equal to]600 [micro]mol/L (P < .0001; Table 1).

Weight gain data for 237 of the 251 women were evaluated. Normal weight gain during pregnancy was considered to be 70% to 134% of recommended weight gain, inadequate weight gain was <70% of recommended weight gain, and excess weight gain was >134% of recommended weight gain. Overall, 57 women had low weight gain (Table 2). Of these 57 women, 33 (58%) had offspring with microcephaly Eighty women who had adequate weight gain had a lower rate of offspring with microcephaly (24 [30%]), even with blood Phe >600 [micro]mol/L. Surprising is that women with >134% of recommended weight gain had the lowest number of microcephalic infants (19 of 100 [19%1).

Stepwise logistic regression analysis showed that higher average blood Phe exposure during the pregnancy, higher off-diet blood Phe level, low prepregnancy weight, poor weight gain during pregnancy, and low protein and high iron intakes during pregnancy were found to be associated with microcephaly in their offspring (Table 3).

CHD

The 251 women with PKU who had nutrient analysis had 22 (%) offspring with major cardiac malformations. None of the women who had blood Phe levels [less than or equal to] 600 [micro]mol/L by 8 weeks' gestation had offspring with CHD. Of the women with blood Phe >600 [micro]mol/L by 8 weeks' gestation, 36 ingested <50% of the recommended protein intake for pregnancy. Offspring of 11 (%) of these 36 pregnancies had CHD compared with 11 (%) of 132 offspring for whom mother's protein intake was >50% of the recommended dietary allowance (P < .0013). (18,19) In a previous report, stepwise discriminant analysis using first-trimester variables to discriminate CHD offspring identified protein intake, 4 to 8 weeks of blood Phe, fat intake, off-diet blood Phe level, and reduced vitamin [.12] intake as significant in development of CHD. (18,19) Seven (%) of 13 women with low vitamin [.12] intake had offspring with CHD, whereas only 7 of 106 women who had adequate [.12] intake had infants with CHD (odds ratio: ; 95% confidence interval: .6; P = .0001). (18)

DISCUSSION

The data presented confirm the deleterious effect of high blood Phe on brain growth, microcephaly, and CHD. The study also underscores the difficulty in achieving blood Phe [less than or equal to]360 [micro]mol/L or even [less than or equal to]600 [micro]mol/L. Nutrition factors other than high blood Phe levels play a role in preventing some of the deleterious effects of PKU during pregnancy. Unfortunately, blood folate levels were unavailable. The data presented show that microcephaly significantly decreased when weight gain was adequate. Similarly, CHD was dramatically decreased with adequate protein intake despite high blood Phe levels. These dietary components, often overlooked in the treatment of a PKU pregnancy, may alleviate some of the difficulties associated with high blood Phe levels. (20-22)

The data show the overall percentage of microcephaly in this group (85 of 251) to be % and the percentage of CHD (22 of 251) to be %. Although this is improved from untreated maternal PKU, 73% microeephaly and 12% CHD, the rates would have been lower if diet were started earlier in the pregnancy. The need for preconception education of women with PKU is indicated by the fact that 64% of the women entered the study after conception and failed to achieve blood Phe control by 8 weeks' gestation. (23) Efforts should be made by the primary care provider or obstetrician and nutrition counselor for education, reinforcement, and frequent follow-up to ensure compliance and adequate protein, energy, and fat intake. Prenatal vitamins should be prescribed.

The difficulty of controlling blood Phe levels as patients with PKU get older is now a widely recognized problem, (3) which brings new challenges to the treatment of PKU. New therapeutic modalities need to be developed for treatment of maternal PKU to eliminate the high rate of CHD and microcephaly.

ABBREVIATIONS. PKU, phenylketonuria; Phe, phenylalanine; CHD, congenital heart disease; HC, head circumference.

TABLE 1. HC of 251 Infants Born to Wome8 Weeks' Gestation
and Blood Phe [less than or equal to] 600 [micro]mol/L by 8
Weeks' Gestation

 Blood Phe [less than or Blood Phe
 equal to] 600 [micro]mol/L > 600 [micro]mol/L

 n % n %

Normal HC 79 92 87 53
Microcephaly 7 8 78 47
Total 86 100 165 100

Fisher exact P < .0001.

TABLE 2. Percentage of Recommended Weight Gain in 237 Women With PKU
During Pregnancy and Offspring HC

 Percentage of
 Recommended Weight Gain

 < 70% 70%-134% > 134%
 (n) (n) (n)

Normal HC 24 56 81
Microcephaly 33 24 19
Total 57 80 100
% with microcephaly 58% 30% 19%

[chi square] = , df = 2, P = .001.

TABLE 3. Stepwise Logistic Regression Analysis to Determine Factors
Associated With Offspring Microcephaly (n = 237)

 Variable P Value

Average blood Phe exposure .0001
Off-diet blood Phe .0008
Pre-pregnancy weight .0035
% recommended weight gain .0241
Iron intake .1094
Protein intake .1002

ACKNOWLEDGMENTS

This study was supported by National Institutes of Health contract no. N01-HD-2-3148 from the National Institute of Child Health and Human Development (Bethesda, MD).

REFERENCES

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(18.) Michals-Matalon K, Acosta P, Azen C, et al. Congenital heart disease in maternal phenylketonuria: effects of blood phenylalanine and nutrient intake. MRDD Res Rev. 1999;5:122-124

(19.) Michals-Matalon K, Platt LD, Acosta, P, Azen C, Walla CA. Nutrient intake and congenital heart defects in maternal phenylketonuria. Am J Obstet Gynecol. 2002;187:441-444

(20.) Acosta PB, Michals-Matalon K, Austin V, et al. Nutrition findings and requirements in pregnant women with phenylketonuria. In: Platt LD, Koch R, de la Cruz F, eds. Genetic Disorders and Pregnancy Outcome. New York, NY: The Parthenon Publishing Group; 1997;21-32

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Kimberlee Michals Matalon, PhD, RD *; Phyllis B. Acosta, DrPH, RD[double dagger]; and Colleen Azen, MS[section]

From the * Department of Health and Human Performance, University of Houston, Houston, Texas; [double dagger]Metabolic Diseases, Ross Products Division, Abbott Laboratories, Columbus, Ohio; and [section]Division of Medical Genetics, Children's Hospital Los Angeles, Los Angeles, California.

Reprint requests to (.M,) Department of Health and Human Performance, University of Houston, Houston, TX 77204-6020.