Early childhood neurodevelopment after intrauterine growth restriction: a systematic review

BACKGROUND AND OBJECTIVE: Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR.

METHODS: PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines.

RESULTS: Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR.

CONCLUSIONS: Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies.

Intra-uterine growth restriction and increased risk of hypertension in adult life: A follow-up study of 50-year-olds

OBJECTIVE:

To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight =10th centile).

STUDY DESIGN:

Controlled comparative study.

METHODS:

Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations.

RESULTS:

The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference.

CONCLUSIONS:

IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life.

Postweaning exposure to aflatoxin results in impaired child growth: A longitudinal study in Benin, west Africa

Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.

Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate

Background: Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200 µg/day, but not at the higher doses that are often used.

Methods: Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/creatinine ratio in one.

Findings: Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have adrenal suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500 µg/day.

Interpretation: When high doses of fluticasone propionate are used, growth may be retarded and adrenal suppression may occur.

Levels of Neonatal Thyroid Hormone in Preterm Infants and Neurodevelopmental Outcome at 51/2 Years: Millennium Cohort Study

Context: Transient hypothyroxinemia is the commonest thyroid dysfunction of premature infants, and recent studies have found adverse associations with neurodevelopment. The validity of these associations is unclear because the studies adjusted for a differing range of factors likely to influence neurodevelopment. Objective: The aim was to describe the association of transient hypothyroxinemia with neurodevelopment at 5.5 yr corrected age. Design: We conducted a follow-up study of a cohort of infants born in Scotland from 1999 to 2001 =34 wk gestation. Main Outcome Measures: We measured scores on the McCarthy scale adjusted for 26 influences of neurodevelopment including parental intellect, home environment, breast or formula fed, growth retardation, and use of postnatal drugs. Results: A total of 442 infants =34 wk gestation who had serum T4 measurements on postnatal d 7, 14, or 28 and 100 term infants who had serum T4 measured in cord blood were followed up at 5.5 yr. Infants with hypothyroxinemia (T4 level = 10th percentile on d 7, 14, or 28 corrected for gestational age) scored significantly lower than euthyroid infants (T4 level greater than the 10th percentile and less than the 90th percentile on all days) on all McCarthy scales, except the quantitative. After adjustment for confounders of neurodevelopment, hypothyroxinemic infants scored significantly lower than euthyroid infants on the general cognitive and verbal scales. Conclusions: Our findings do not support the view that the hypothyroxinemic state, in the context of this analysis, is harmless in preterm infants. Many factors contribute both to the etiology of hypothyroxinemia and neurodevelopment; strategies for correction of hypothyroxinemia should acknowledge its complex etiology and not rely solely on one approach.