Unaffected Children Research Articles

Health care expenditures among Medicaid enrolled children with and without orofacial clefts in North Carolina, 1995–2002

National data that examine health costs among children with special needs are limited and do not address children with orofacial clefts (OFC). This study examines Medicaid expenditures among children with and without OFC. North Carolina vital statistics, health services, birth defects registry, and Medicaid enrollment and paid claims were linked to identify resident children born 1995-2002 with and without OFC who were continuously enrolled in Medicaid. Outcome measures included average cost per child for medical, inpatient, outpatient, dental, well-child care, mental health, and home health. Average expenditures per child were also determined and were examined by the child's phenotypic characteristics including type of cleft and whether the defect was isolated or non-isolated. Expenditure ratios were calculated to compare cases and controls and differences in expenditures among cases by cleft type and by isolated/non-isolated occurrence. During infancy, average mental health expenditure per child with OFC was 37.2 times higher than for a child without OFC. Average home health expenditure per case was 45.0 times higher than for a control. Mean expenditure per child with OFC was $22,642 compared to $3,900 for an unaffected child. Mean expenditure for a child with cleft palate and child with cleft lip with cleft palate were about three times more than a child with cleft lip alone. Mean expenditure per child with non-isolated OFC also was substantially higher than the expenditure for a child with isolated OFC. Children with OFC have significantly higher health-related Medicaid expenditures than unaffected children. These findings are important for targeting care coordination and early intervention and for program planning and policy development related to special needs children.

The dopamine receptor D4 7‐repeat allele and prenatal smoking in ADHD‐affected children and their unaffected siblings: no gene–environment interaction

The dopamine receptor D4 (DRD4) 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (GxE) interaction of the DRD4 7-repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-repeat allele differs between ADHD affected and unaffected children. Linear mixed models were used to assess main and interactive effects of the DRD4 7-repeat allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6-17 years. There was some evidence pointing to differential effects of the DRD4 7-repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for GxE interactions. Despite the large sample size, no GxE interactions were found. The impact of the DRD4 7-repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater-specific behaviors.

The effects of a motor and a cognitive concurrent task on walking in children with developmental coordination disorder

The effects of type (cognitive vs. motor) and difficulty level (easy vs. hard) of a concurrent task on walking were examined in 10 boys and 4 girls (age 4–6 years) with developmental coordination disorder (DCD) and 28 age- and gender-matched unaffected children. Each child performed free walking (single task), walking while carrying an empty tray (dual task, the concurrent task being motor and easy), walking while carrying a tray with 7 marbles (the concurrent task being motor and hard), walking while repeating a series of digits forward (the concurrent task being cognitive and easy), and walking while repeating the digits backward (the concurrent task being cognitive and hard). Walking was affected by the concurrent task (i.e., dual-task cost) in the children with DCD more so than in the comparison children. Greater task difficulty also increased the dual-task cost in the children with DCD more so than in the comparison children. These patterns were only noted for the motor concurrent task. The cognitive concurrent task also affected walking, but the dual-task costs did not differ between difficulty levels, nor between the groups.

Autoantibodies to folate receptor during pregnancy and neural tube defect risk

Periconceptional folic acid can reduce the occurrence of neural tube defects (NTDs) by up to 70%, and autoantibodies for folate receptors (FRs) have been observed in serum from women with a pregnancy complicated by an NTD. This population-based cohort study has examined serum from pregnant mothers for autoantibodies to FRs, antibodies to bovine folate binding protein (FBP), and inhibition of folic acid binding to FR and FBP in association with NTD risk. The mid-gestational maternal serum specimens used for this study were collected during the 15–18th week of pregnancy. Samples were obtained from the California Birth Defects Monitoring Program; 29 mothers had a pregnancy complicated by spina bifida and 76 mothers had unaffected children. The presence of IgG and IgM antibodies to human FR, bovine FBP, and inhibition of folic acid binding to FR and FBP was determined. Higher activity of IgM to FBP in cases verses controls was observed ( P = 0.04). Higher activity of IgM and IgG autoantibodies to FR was observed ( P < 0.001 and P = 0.04, respectively). Risk estimates at two standard deviations above average control antibody concentrations were OR = 2.07 (CI = 1.02, 4.06) for anti-FBP IgM, OR = 2.15 (CI = 1.02, 4.69) for anti-FR IgG and OR = 3.19 (CI = 1.47, 6.92) for anti-FR IgM. These data support the hypothesis that high titers of antibodies and blocking of folic acid binding to FRs by maternal serum should be regarded as risk factors for NTDs.

Antiepileptic Drug Use, Folic Acid Supplementation, and Congenital Abnormalities: A Population-based Case-control Study

Objective To investigate whether folic acid supplementation in early pregnancy modifies the association between the prevalence of congenital abnormalities in the offspring and maternal use of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and primidone (PRI). Design A population-based case–control study. Setting The Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA) (1980–1996) and its information on children from the Hungarian Congenital Abnormality Registry and the Hungarian National Birth Registry. Population Children with congenital abnormalities (cases; n= 20 792, of whom 148 had been exposed to antiepileptic drugs [AEDs]) and unaffected children (controls; n= 38 151, of whom 184 had been exposed to AEDs). Methods Information on drug exposure and background variables for the mothers were collected from antenatal logbooks, discharge summaries, and structured questionnaires completed by the mothers at the time of HCCSCA registration. Main outcome measures Congenital abnormalities detected at termination of pregnancy, at birth or until 3 months of age according to CBZ, PB, PHT, or PRI exposure at 5–12 weeks from first day of the last menstrual period (LMP), stratified by folic acid supplementation. Results Compared with children unexposed to AEDs and folic acid, the odds ratio of congenital abnormalities was 1.47 (95% CI 1.13–1.90) in children exposed to AEDs without folic acid supplementation and 1.27 (95% CI 0.85–1.89) for children exposed to AEDs with folic acid supplementation. Conclusion The results indicate that the risk of congenital abnormalities in children exposed in utero to CBZ, PB, PHT, and PRI is reduced but not eliminated by folic acid supplementation at 5–12 weeks from LMP. The statistical precision in our study is limited due to rarity of the exposures, and further studies are needed.

Cognitive and adaptive deficits in young children with Duchenne muscular dystrophy (DMD)

The goal of the current investigation was to examine adaptive behavior and cognitive skills in young children with Duchenne muscular dystrophy (DMD), a genetic disorder that causes progressive muscular weakness and concomitant cognitive deficits. Previous studies have documented specific language deficits in older children with DMD, but there are limited data on younger children. Twenty children with DMD who were between 3 and 6 years old and 20 unaffected family control children were recruited. Parents completed questionnaires relating to development and adaptive functioning, while children completed neuropsychological testing. Results of paired t tests indicate that children with DMD are rated as delayed relative to familial controls on measures of adaptive functioning, as assessed by the Vineland Adaptive Behavior Scales. Furthermore, children with DMD exhibit impairments on multiple measures of cognition, including measures of receptive language, expressive language, visuo-spatial skills, fine-motor skills, attention, and memory skills. Across all domains examined, the young children with DMD performed more poorly than their familial controls. These deficits appear to be more generalized than those reported in older children with this disorder. Dystrophin, a missing protein product, is hypothesized to be responsible for these cognitive and behavioral impairments.

Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block

Maternal autoantibodies to the p200-epitope of Ro52 have been suggested to correlate with development of congenital heart block. The aim of the present study was to evaluate the clinical relevance and predictive value of p200-antibodies in high-risk pregnancies. Sera from 515 Finnish, Swedish and American women were included in the study. Sera originated from 202 mothers with an infant affected by second- or third-degree atrioventricular block (AVB), 177 mothers with rheumatic disease having infants with normal heart rate and female blood donors (n = 136). A novel serological assay for Ro52 p200-antibodies with intra- and inter-assay variability of 3% and 3.8% respectively was developed. Mothers of children affected by AVB II-III had significantly higher p200-antibody levels than mothers with rheumatic disease having children with normal heart rate (P < 0.001). In the Swedish cohort, a distinction between foetuses with normal conduction, AVB I, AVB II and III was possible. A significant difference in anti-p200 levels between AVB I and AVB II-III groups compared with foetuses with normal conduction (P < 0.05 and P < 0.01) was observed. Using p200-antibodies as a second step analysis in Ro52-positive pregnancies increased the positive predictive value for foetal cardiac involvement (AVB I, II or III) from 0.39 (0.27-0.51) to 0.53 (0.37-0.68). In conclusion, Ro52 p200-antibodies may occur in women with unaffected children, but levels are significantly higher in mothers of children with congenital heart block and are suggested as a relevant marker in evaluating the risk for foetal AV block.

Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus.

This study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery of a child with NLE (21 with congenital heart disease block (CHB) and 20 with dermatologic NLE) and 19 sera from anti-Ro and/or anti-La antibody-positive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La and anti-r-Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-r-La antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (0.67 +/- 0.43 versus 0.14 +/- 0.30; P < 0.0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0.51 +/- 0.45 versus 0.83 +/- 0.37 respectively; P = 0.0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0.77 +/- 0.35) compared with non-NLE mothers (0.29 +/- 0.39; P < 0.0001). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0.82 +/- 0.37 versus 0.71 +/- 0.74; P = 0.32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (5.1 +/- 0.54 versus 2.3 +/- 0.54 respectively; P < 0.001). More importantly, when we examined the individual polypeptides, we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30% versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference in the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis of heterozygous familial hypercholesterolaemia in children

Most children with familial hypercholesterolaemia (FH) are diagnosed by raised blood cholesterol levels, but the test lacks sensitivity and specificity. As such children have evidence of vascular dysfunction at an early age, correct identification of affected individuals is important so that treatment can be started. To determine levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in children with genetically proven FH and their unaffected siblings, in order to identify a diagnostic cut-off point if possible. Retrospective case-note survey. We studied the notes of 115 children aged 3-16 years, 69 proven FH and 46 unaffected sibs, 65 boys and 50 girls, from 31 families and 21 different mutations. Data recorded were age, sex, TC, and (when available) LDL-C. The lowest TC level in an affected individual was 4.7 mmol/l and the highest in normal individual was 6.05 mmol/l. This overlap range included 21 children (18% of the total). The corresponding figures for LDL-C were 3.0 and 3.7 mmol/l, which included eight children (8%). TC is not an effective test for differentiating affected and unaffected children with FH. LDL-C is better, but genetic testing remains the method of choice, especially if treatment decisions are to be taken.

Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome

Structural equation modeling (SEM) was used to examine the development of intellectual functioning in 145 school-age pairs of siblings. Each pair included one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of children were evaluated on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) at time 1 and 80 pairs of children received a second evaluation at time 2 approximately 4 years later. Compared to their unaffected siblings, children with FXS obtained significantly lower percentage correct scores on all subtests of the WISC at both time points. During the time between the first and second assessments, the annual rate of intellectual development was approximately 2.2 times faster in the unaffected children compared to the children with FXS. Levels of the fragile X mental retardation protein (FMRP) were highly associated with intellectual ability scores of the children with FXS at both time points (r=0.55 and 0.64 respectively). However, when gender, age, and the time between assessments were included as covariates in the structural equation model, FMRP accounted for only 5% of the variance in intellectual ability scores at time 1 and 13% of the variance at time 2. The results of this study suggest that slower learning contributes to the low and declining standardized IQ scores observed in children with FXS.

Antibodies against fetal brain in sera of mothers with autistic children

Serum antibodies in 100 mothers of children with autistic disorder (MCAD) were compared to 100 age-matched mothers with unaffected children (MUC) using as antigenic substrates human and rodent fetal and adult brain tissues, GFAP, and MBP. MCAD had significantly more individuals with Western immunoblot bands at 36 kDa in human fetal and rodent embryonic brain tissue. The density of bands was greater in fetal brain at 61 kDa. MCAD plus developmental regression had greater reactivity against human fetal brain at 36 and 39 kDa. Data support a possible complex association between genetic/metabolic/environmental factors and the placental transfer of maternal antibodies in autism.

Relation among mannose-binding lectin 2 genotype, β-cell autoantibodies, and risk for type 1 diabetes in Finnish children

Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of beta-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for > or =3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28; p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency.

Maternal reports of family history from the National Birth Defects Prevention Study, 1997–2001

PurposeTo assess usefulness of family history information obtained in pediatric practice, we evaluated maternally reported family history data. MethodsWe analyzed family history responses from the National Birth Defects Prevention Study using interview data from mothers of children with birth defects (n = 9,331) and of unaffected liveborn children (n = 3,390) with 1997–2001 estimated delivery dates. We examined the effects of demographic factors, case–control status, and type of defect on birth defect family history reports. Interview information was compared with occurrence of prenatal testing. ResultsAmong case mothers, 1,577 (17%) reported a first- or second-degree relative with a birth defect, compared with 327 (10%) control mothers (odds ratio = 1.91, 95% confidence interval = 1.68–2.16). Reports of affected relatives were also more frequent among mothers who were non-Hispanic white, were 25 years or older, had more than 12 years of education, had an annual household income greater than $20,000, were born in the United States, and completed an English-language interview. ConclusionReporting a family history of birth defects might be influenced by maternal demographic factors, which should be considered in developing pediatric family history tools.

Late Language Emergence at 24 Months: An Epidemiological Study of Prevalence, Predictors, and Covariates

The primary objectives of this study were to determine the prevalence of late language emergence (LLE) and to investigate the predictive status of maternal, family, and child variables. This is a prospective cohort study of 1,766 epidemiologically ascertained 24-month-old singleton children. The framework was an ecological model of child development encompassing a wide range of maternal, family, and child variables. Data were obtained using a postal questionnaire. Item analyses of the 6-item Communication scale of the Ages and Stages Questionnaire (ASQ; D. Bricker & J. Squires, 1999; J. Squires & D. Bricker, 1993; J. Squires, D. Bricker, & L. Potter, 1997; J. Squires, L. Potter, & D. Bricker, 1999) yielded a composite score encompassing comprehension as well as production items. One SD below the mean yielded good separation of affected from unaffected children. Analyses of bivariate relationships with maternal, family, and child variables were carried out, followed by multivariate logistic regression to predict LLE group membership. 13.4% of the sample showed LLE via the ASQ criterion, with 19.1% using the single item of "combining words." Risk for LLE at 24 months was not associated with particular strata of parental educational levels, socioeconomic resources, parental mental health, parenting practices, or family functioning. Significant predictors included familial history of LLE, male gender, and early neurobiological growth. Covariates included psychosocial indicators. Results are congruent with models of language emergence and impairment that posit a strong role for neurobiological and genetic mechanisms of onset that operate across a wide variation in maternal and family characteristics.

Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population‐based case–control study

To investigate whether folic acid supplementation in early pregnancy modifies the association between the prevalence of congenital abnormalities in the offspring and maternal use of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and primidone (PRI). A population-based case-control study. The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) (1980-1996) and its information on children from the Hungarian Congenital Abnormality Registry and the Hungarian National Birth Registry. Children with congenital abnormalities (cases; n= 20 792, of whom 148 had been exposed to antiepileptic drugs [AEDs]) and unaffected children (controls; n= 38 151, of whom 184 had been exposed to AEDs). Information on drug exposure and background variables for the mothers were collected from antenatal logbooks, discharge summaries, and structured questionnaires completed by the mothers at the time of HCCSCA registration. Congenital abnormalities detected at termination of pregnancy, at birth or until 3 months of age according to CBZ, PB, PHT, or PRI exposure at 5-12 weeks from first day of the last menstrual period (LMP), stratified by folic acid supplementation. Compared with children unexposed to AEDs and folic acid, the odds ratio of congenital abnormalities was 1.47 (95% CI 1.13-1.90) in children exposed to AEDs without folic acid supplementation and 1.27 (95% CI 0.85-1.89) for children exposed to AEDs with folic acid supplementation. The results indicate that the risk of congenital abnormalities in children exposed in utero to CBZ, PB, PHT, and PRI is reduced but not eliminated by folic acid supplementation at 5-12 weeks from LMP. The statistical precision in our study is limited due to rarity of the exposures, and further studies are needed.

Distinct Clones are Associated with the Development of Transient Myeloproliferative Disorder and Acute Megakaryocytic Leukemia in a Patient with Down Syndrome

Children with Down syndrome (DS) have an approximately 20-fold higher incidence of leukemia than unaffected children, and most leukemia cases with DS present as acute megakaryocytic leukemia (AMKL). At least 10% of neonates with DS develop transient myeloproliferative disorder (TMD), and 20% to 30% of patients with TMD develop AMKL. Mutations in the GATA1 gene are identified not only in AMKL patients but also in TMD patients; however, sequential analysis of GATA1 is not often performed in the same patients. We describe a child with DS who developed TMD followed by AMKL and have identified different mutations in the GATA1 gene during the course of TMD and AMKL. Distinct clones were associated with the development of TMD and AMKL in this patient.

Memory and Response Inhibition in Young Children with Single-Suture Craniosynostosis

Using two versions of the A-not-B task, memory and response inhibition were assessed in 17- to 24-month-old children with surgically corrected single-suture craniosynostosis (cases) and unaffected children (controls). Children's development and language were initially assessed on average at 6–7 months of age and again at this second visit. Cases and controls performed at equivalent levels on average, with cases performing slightly better than controls on several of the variables measured. However, fewer cases than controls were able to complete the more challenging of the two tasks, which may have predictive significance for later functioning. Children's age and cognitive ability were related to successful performance on the A-not-B task. Among cases, age of cranioplastic surgery was unrelated to performance. Our findings suggest that children with single-suture craniosynostosis show normal development of visual memory and response inhibition in the age range studied here.

Filaggrin Mutations in Children with Severe Atopic Dermatitis

Atopic dermatitis (AD) results from strong genetic and environmental interactions. AD shows genetic linkage to Chromosome 1q21. This region contains the epidermal differentiation complex (EDC), which consists of genes that form essential components of epidermal surfaces. Filaggrin (FLG) is one of these. Mutations in FLG/(R501X and 2282del4) are reported to be strongly associated with AD and to influence asthma accompanying AD. We investigated these effects in families recruited through a child with severe AD. We genotyped two panels of families, totalling 426, containing 990 affected and unaffected children. We found significant associations with AD (P=0.0001), asthma (P=0.006), and atopy (P=0.002). The FLG mutations were present in 26.7% of patients with AD, but were also present in 14.4% of children without AD. They were weakly associated with disease severity. The variants were not independently associated with asthma. The overall LOD score for genetic linkage of markers to the region was 3.57. This fell to 2.03 after accounting for the FLG mutations, indicating the presence of other genetic variants influencing AD at this locus. Our results provide further confirmation of the importance of mutations in FLG and the skin barrier in AD pathogenesis. The results indicate that investigations of other genes within the EDC should be undertaken.

Ten-year experience with preimplantation genetic diagnosis (PGD) at the New York University School of Medicine Fertility Center

We describe our experience of over 300 cycles of preimplantation genetic diagnosis (PGD) and report clinical pregnancy rates (35%-67%) that support using this technology to screen for genetic disorders and chromosomal abnormalities. In clinical practice for over ten years, PGD offers couples the earliest form of genetic screening and may help improve ongoing pregnancy rates in poor-prognosis patients.

Maternal plasma zinc and the risk of isolated oral clefts in children in Utah

We reported that low plasma zinc levels were common in Filipino women of reproductive age and higher plasma zinc was associated with a lower risk for cleft lip with or without cleft palate (CL/P) in their children. An IRB approved case-control study was conducted in 169 case-mothers of children with CL/P and 369 control-mothers of unaffected children in Utah. The mean age of children was 4.1 (± 2.1, SD) years old, when maternal blood samples were obtained for zinc assay between 2000 and 2005. Odds ratios (OR) of the relative risk of CL/P were calculated for plasma zinc quartiles. The mean plasma zinc of case-mothers (11.0 ± 2.1 μmol/L) was similar to that in control-mothers (11.3 ± 5.9 μmol/L; p =0.59). Low plasma zinc (< 11.0 μmol/L) was found in 50% of cases and in 56% of controls (p = 0.10). The ORs for CL/P, adjusted for potential confounding factors, were similar for plasma zinc quartiles: 1.0 (lowest quartile reference), 0.67 (95% CI, 0.37 – 1.21), 1.00 (0.57 – 1.79), and 0.91 (0.51 – 1.65) (p trend = 0.92). We were able to detect that poor zinc status is a risk factor for oral clefts in Filipino mothers, where the overall prevalence of CL/P is high and plasma zinc was generally low. In this study, however, we did not detect such an association in mothers with relatively high plasma zinc, suggesting that poor zinc status is considered as a risk only when the status is severely compromised.