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The effects of an early developmental mother-child intervention program on neurodevelopment outcome in very low birth weight infants: a pilot study.

BACKGROUND: Several studies report increased minor neurodevelopment dysfunctions in children born very low birth weight (VLBW). Usefulness of preventive early intervention programs to improve neurodevelopment outcome of VLBW infants is still under investigation. AIMS: To evaluate the effects of an early post-discharge developmental mother-child intervention program on neurodevelopment outcome at 36 months in VLBW infants. STUDY DESIGN: Prospective study. SUBJECTS: 36 VLBW infants ([mean (S.D.)] birthweight=864 g (204 g); gestational age=27.9 weeks (2.4 weeks)), consecutively born January-August 2001, randomized in intervention and control groups. OUTCOME MEASURES: Neurodevelopment assessment at 36 months of chronological age with use of the Griffiths Mental Development Scale and related subscales. RESULTS: At 36 months of chronological age, as compared to controls, children in intervention group exhibited higher scores in personal-social subscales ([mean (S.D.)]=101.4 (9.3) vs. 92.9 (12.1), P=0.02), eye-hand coordination (92.7 (4.5) vs. 87.1 (9.9), P=0.041), practical reasoning (98.6 (8.2) vs. 89.4 (10.1), P=0.01). Development Scale were 97.6 (5.5) and 92.4 (9.9), respectively, in intervention and control groups (P=0.074). CONCLUSIONS: Early post-discharge developmental mother-child intervention program may have a positive effect on later neurodevelopment outcome of VLBW children.

Central Nervous System↗

[Evaluation of relationship between early brain response and neurodevelopment in newborns by using near infrared spectroscopy].

OBJECTIVE: To study the relationship between early brain response to extrinsic stimulation and neurodevelopment in preterm infants, assess the brain function of preterm infants in the early stage, and thereby to provide objective evidence for the degree of neurodevelopment in preterm infants and to evaluate prognosis. METHODS: Using near infrared spectroscopy (NIRS), the brain response to sound stimulation of 90 preterm infants at different gestational age was observed and compared with the result obtained from 20 full term infants. The neonatal behavioral neurological assessment (NBNA) was performed at corrected age of 40 weeks, and the infants were followed up for 2 years. The effect of gestational age and brain damage on preterm infants, the relation between early brain response in preterm infants and their neurodevelopment was evaluated. RESULTS: All the preterm infants responded to different degrees to auditory stimulation after birth. The time to beginning to react and the time to appearance of the peak reaction were attained after auditory stimulation and the time to beginning to resume when the auditory stimulation was stopped was (278 +/- 94) s, (446 +/- 67) s and (199 +/- 52) s, respectively, which were significantly longer than those observed in the full term infants (107 +/- 30) s, (264 +/- 51) s and (131 +/- 46) s, respectively. The maximum reactions of hemoglobin, oxyhemoglobin and regional oxygen saturation in the infants after gestational age 32 weeks was (0.3 +/- 0.3)%, (0.7 +/- 0.5)% and (0.3 +/- 0.3)%, respectively, which were significantly lower than those in the full term infants (1.7 +/- 0.7)%, (1.7 +/- 0.8)% and (1.6 +/- 0.7)%, respectively. When the brain response of preterm infants was compared with that in infants without brain damage, the speed of the reaction was slow, the maximum reaction was low. The brain response in preterm infant was correlated with NBNA at corrected age of 40 weeks. It was found during the following-up that abnormal neurodevelopment was associated with poor brain reaction. CONCLUSIONS: NIRS can be used to evaluate brain response of infants. Preterm infants display brain response to auditory stimulation. Early brain response is correlated with neurodevelopment.

Acoustic Stimulation↗

Head growth and neurodevelopment of infants born to HIV-1-infected drug-using women.

OBJECTIVE: To describe neurodevelopment and head growth in HIV-1-infected and exposed uninfected infants with and without in utero exposure to opiates and cocaine. METHODS: Using data from a multicenter cohort study of HIV-1-infected women and their children, the authors fit repeated measures regression models to estimate the effects of HIV-1 infection and in utero hard drug exposure on head circumference and Bayley Scales of Infant Development standard scores during the first 30 months. RESULTS: Of the 1,094 infants included in the analysis, 147 (13%) were HIV-1-positive and 383 (35%) were exposed in utero to opiates or cocaine (drug-positive). Mean 4- month Bayley mental scores were lower in infants with only HIV-1 positivity (HIV-positive and drug-negative) (-8.2 points, p < 0.0001) or only drug exposure (HIV-negative and drug-positive) (-4.4 points, p = 0.0001) and tended to be lower in infants with both factors (HIV-positive and drug-positive) (-3.7 points, p = 0.0596), compared with those who were HIV-1-negative and not drug exposed (HIV-negative and drug-negative). However, by 24 months of age, there was no longer a decrement among HIV-negative and drug-positive infants, whereas HIV-1 infection was still associated with a decrement relative to uninfected infants. Similar results were seen for Bayley motor scores and for head circumference Z scores. CONCLUSIONS: HIV-1 infection and in utero opiate and cocaine exposure decrease birth head circumference and slow neurodevelopment at 4 months. At 24 months of age, however, only HIV-1 infection is associated with decreased neurodevelopment and head circumference. There may be some postnatal recovery from the effects of in utero hard drug exposure. Importantly, the detrimental effects of HIV-1 positivity and maternal hard drug use on neurodevelopment at 4 months are not additive, although they are additive for birth head circumference.

Adolescent↗

Neurodevelopment after neonatal hypoglycemia: a systematic review and design of an optimal future study.

OBJECTIVE: Our goal was to assess the effect of episodes of neonatal hypoglycemia on subsequent neurodevelopment. METHODS: We searched Medline and Embase for cohort studies on subsequent neurodevelopment after episodes of hypoglycemia in the first week of life. Reference lists of available studies were reviewed, and content experts were contacted for additional studies. Included studies were selected and appraised for methodologic quality by 2 reviewers. Methodologic quality was assessed according to well-accepted criteria for prognostic studies. Eventually, all studies were given an overall quality score: poor, moderate, or high quality. Studies in the latter 2 categories were considered for quantitative data analysis. RESULTS: Eighteen eligible studies were identified. The overall methodologic quality of the included studies was considered poor in 16 studies and high in 2 studies. Pooling of results of the 2 high-quality studies was deemed inappropriate because of major clinical and methodologic heterogeneity. None of the studies provided a valid estimate of the effect of neonatal hypoglycemia on neurodevelopment. Building on the strengths and weaknesses of existing studies, we developed a proposal for an "optimal" future study design. CONCLUSIONS: Recommendations for clinical practice cannot be based on valid scientific evidence in this field. To assess the effect of neonatal hypoglycemia on subsequent neurodevelopment, a well-designed prospective study should be undertaken. We submit a design for a study that may answer the still-open questions.

Humans↗

Early childhood neurodevelopment in very low birth weight infants with predischarge apnea.

Apnea commonly occurs in preterm infants and may persist beyond term. We prospectively investigated the relationship between apnea that persisted beyond 35 weeks post-conceptional age and subsequent neurodevelopment in early childhood. Between January, 1990-November, 1993, we performed predischarge respiratory recordings, using 24-hr, 4-channel pneumography, at 35 weeks or more of postconceptional age in 164 infants (birth weight, <1,250 g; gestational age, < or = 32 weeks), who subsequently underwent multidisciplinary neurodevelopmental assessment at 15-64 (median 24) months of adjusted age. The duration of initial artificial ventilation for respiratory distress syndrome and the grade of intraventricular hemorrhage were independent predictors of neurodevelopmental outcome. Mean oximetry desaturation and frequency of predischarge apnea correlated with mental and motor developmental scores. Mean oximetry desaturation during apnea was an independent predictor for motor score in the total population, and for both mental and motor scores in 50 infants with grade 3 or 4 intraventricular hemorrhage, but not in 114 infants without grade 3 or 4 intraventricular hemorrhage. Despite its limited predictability for early childhood neurodevelopment, predischarge respiratory recordings may be useful in predicting subsequent neurodevelopment of high-risk preterm infants, especially those with severe intraventricular hemorrhage.

Analysis of Variance↗

Polyunsaturated fatty acid status and neurodevelopment: a summary and critical analysis of the literature.

The rationale for randomized trials designed to measure the effects of variable docosahexaenoic acid (DHA) status on neurodevelopment in human infants came from earlier studies of neurodevelopment in animals that were deficient in DHA owing to diets low in alpha-linolenic acid. The session on neurodevelopment looked at the results of these animal studies and discussed outcomes that appear to be analogous in human infants with variable DHA status. Presentations focused mainly on measures of development that may be attributed to more specific developmental domains (e.g., visual attention, recognition memory, problem-solving), some of which have been shown to be affected by long-chain polyunsaturated fatty acid (LCPUFA) status. This paper derives from discussions that took place during the session and reviews subsequent developments in this area. Although more difficult to interpret, global measures of infant development (e.g., the Bayley Scales of Infant Development, and Brunet-Lezine) can only suggest a relationship to specific developmental domains, but they have been applied in some randomized trials of LCPUFA and infant development. Those results are also summarized here.

Animals↗

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0&#x2009;y), 7&#x2009;y and 15-17&#x2009;y (ALSPAC), and ~27&#x2009;y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0&#x2009;y, 7&#x2009;y, 15-17&#x2009;y, and 27&#x2009;y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

DNA Methylation↗

The timing of mother-to-child transmission of human immunodeficiency virus infection and the neurodevelopment of children in Tanzania.

OBJECTIVE: To determine the association between the timing of mother-to-child transmission of human immunodeficiency virus (HIV)-1 and neurodevelopment among children born to HIV-1 infected mothers in Tanzania. METHODS: Bayley Scales of Infant Development (2nd edition) were administered at 6, 12 and 18 months to a subset of children (N = 327). Linear regression models and Cox proportional hazard models were separately fitted for the mental development index (MDI) and the psychomotor development index (PDI). RESULTS: Children who tested HIV-1-positive at birth had significantly higher decreases per month in MDI and PDI than HIV-1-negative children; 1.1 [95% confidence interval (95% CI), 0.4, 1.8] for MDI and 1.4 (95% CI 0.0, 2.7] for PDI. Children who tested HIV-1-positive after birth had an additional 0.6 (95% CI 0.1, 1.1) point decrease in MDI per month and a 0.6 (95% CI 0.0, 1.1) higher decrease in PDI each month than HIV-1-negative children. Testing HIV-1-positive at birth was associated with a 14.9 (95% CI 5.0, 44.7) times higher rate of becoming developmentally delayed in mental function, while testing HIV-1-positive after birth was associated with a 3.2 (95% CI 1.6, 6.4) times higher rate than in uninfected children. CONCLUSIONS: HIV-1 infected infants performed worse on tests of neurodevelopment and were significantly more likely to be identified as developmentally delayed in the first 18 months of life than HIV-1-negative children. The effect of HIV-1 infection on neurodevelopment scores and the risk of developmental delay may be highest among those who are already HIV-1 infected at birth.

Adult↗

Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.

Chromatography, Gas↗

Breastfeeding, exposure to organochlorine compounds, and neurodevelopment in infants.

OBJECTIVE: Exposure to organochlorine compounds (OCs) occurs both in utero and through breastfeeding. Levels of hexachlorobenzene (HCB) found in the cord serum of newborns from a population located in the vicinity of an electrochemical factory in Spain were among the highest ever reported. We studied the association between exposure to OCs and breastfeeding on neurodevelopment in the 1-year-old infants of this population. METHODS: A birth cohort including 92 mother-infant pairs was recruited between 1997 and 1999 in 5 neighboring villages (84% of possible recruits). The mental and psychomotor development of each infant was assessed at 13 months using the Bayley and the Griffiths Scales of Infant Development. OCs were measured in cord serum. RESULTS: Dichlorodiphenyl dichloroethylene (p,p'DDE) cord serum levels were negatively associated with both mental and psychomotor development. For each doubling of a dose of p,p'DDE, we found a resultant decrease of 3.50 points (standard error: 1.39) on the mental scale and 4.01 points (standard error: 1.37) on the psychomotor scale. Exposure to polychlorinated biphenyls was only marginally associated with psychomotor development. Prenatal exposure to HCB had no effect on child neurodevelopment. Long-term breastfeeding was associated with better performance on both the mental and motor scales. Short-term breastfed infants with higher p,p'DDE levels in cord serum were associated with the lowest scores on both the mental and the psychomotor scales. CONCLUSIONS: Prenatal exposure to p,p'DDE was associated with a delay in mental and psychomotor development at 13 months. No association was found for exposure to HCB. Long-term breastfeeding was found to be beneficial to neurodevelopment, potentially counterbalancing the impact of exposure to these chemicals through breast milk.

Breast Feeding↗

A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy.

OBJECTIVE: Our intent was to investigate the neurodevelopment of HIV-uninfected children exposed to combination highly active antiretroviral therapy in pregnancy compared with children not exposed to highly active antiretroviral therapy but with similar socioeconomic backgrounds. PATIENTS AND METHODS: A prospective controlled cross-sectional study of the neurodevelopment of children exposed to highly active antiretroviral therapy versus those not exposed was performed by using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales at 18 to 36 months of age. The highly active antiretroviral therapy-exposed children were born to HIV-infected women but were uninfected themselves. The control children were born to HIV-uninfected women with similar anticipated socioeconomic background (hepatitis C infected and high proportion of substance use). Sociodemographic, clinical, highly active antiretroviral therapy (antenatal, intrapartum, neonatal), and substance-use histories were collected. Results were compared by using analyses of covariance and chi2 analysis. RESULTS: Thirty-nine highly active antiretroviral therapy-exposed and 24 control children were assessed. All mean scores were lower for those in the highly active antiretroviral therapy-exposed group than those in the control group (Bayley Mental Development Index: 85.4 vs 94.3; Bayley Psychomotor Development Index: 93.4 vs 96.6; Vineland mean communication score: 90.1 vs 94.4; Vineland mean daily-living score: 91.2 vs 93.6; Vineland mean socialization score: 97.1 vs 98.4). However, when maternal substance use during pregnancy was controlled for, there were no significant differences between the groups in any domains assessed. Children in both groups exposed to maternal substance use scored significantly lower than children not exposed in all domains except communication skills. It is important to note that there were no differences between the highly active antiretroviral therapy-exposed children with no substance exposure and the control children with no substance exposure in any of the scores. CONCLUSIONS: HIV- and highly active antiretroviral therapy-exposed HIV-uninfected children had lower development and adaptive behavior scores when compared with children who had not been exposed. However, these differences were not significant after correcting for maternal substance use, which had a greater impact on neurodevelopment than highly active antiretroviral therapy exposure. These results suggest that perinatal highly active antiretroviral therapy exposure is not associated with altered development and behavior at 18 to 36 months of age.

Adult↗

Necrotizing enterocolitis in infants: clinical outcome and influence on growth and neurodevelopment.

BACKGROUND AND PURPOSE: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency in neonates. Whether NEC affects infants' growth and development is controversial. The purpose of this study was to explore the clinical characteristics and outcome and to assess the effect of NEC on growth and neurodevelopment in infants. METHODS: A total of 80 neonates admitted to the neonatal intensive care unit from January 1991 to April 2002 with definite, advanced NEC, including 48 with modified Bell's stage II and 32 with stage III. Sixty six of the patients were premature. Very low birth weight (VLBW) preterm infants without NEC were used as matching controls for the 15 infants with VLBW. The growth and neurodevelopment of patients and controls were assessed using the Bayley Scales of Infant Development-II and compared at 6 and 18 months of corrected age. RESULTS: NEC developed an average of 27.7 days after feeding began. The most common initial signs were abdominal distension, decreased activity, hematochezia, and abdominal tenderness. Thirty four patients (43%) required surgical intervention. Three infants developed short bowel syndrome after surgical resection. The overall mortality was 24% (19/80) and was mostly associated with extensive bowel involvement and NEC-related sepsis or multiple organ failure. Of the surviving 61 infants, 12 (20%) developed intestinal strictures, 2 in the ileum, 6 in the colon, and 4 in both ileum and colon. Compared with controls, the VLBW infants with NEC were shorter and had delayed psychomotor development at 18 months of corrected age. Mental development, however, did not differ significantly. CONCLUSIONS: Intestinal stricture was the most common gastrointestinal complication in this series of infants with NEC. Besides the bowel sequelae, VLBW infants who survive NEC are at risk for impairment of growth and neurodevelopment.

Body Height↗

Cannabis and neurodevelopment: implications for psychiatric disorders.

The developing brain is susceptible to the effects of exogenous cannabinoids both during the perinatal period through maternal cannabis use and in young adolescent users. Emerging data from human and animal perinatal exposure studies demonstrate a subtle rather than gross effect of cannabis upon later functioning including; specific cognitive deficits especially in visuospatial function; impulsivity, inattention and hyperactivity; depressive symptoms; and substance use disorders. From animal studies motor control systems, neuroendocrine function and nociception may additionally be affected. Fetal studies indicate that these outcomes may be through cannabinoid mediated influences on the ontogeny of, especially dopamine and opioid, neurotransmitter systems. The effect of cannabinoids in the adolescent suggest long-term deleterious outcomes in cognition, depressive symptoms, schizophrenia and substance use disorders. Much of these data support a neurodevelopmental effect, however, predisposing genetic and/or environmental factors cannot be excluded from human studies. Gender specific differences have been observed in both human and animal studies implying sex hormone and related factors may interact with cannabinoids in neurodevelopment. Further understanding how cannabinoids influence neurodevelopment will inform public debate about the health effects of cannabis but also open avenues in discerning how modulation of the endocannabinoid system may assist in the development of therapeutic tools for a variety of neuropsychiatric disorders.

Affect↗

Neurodevelopment, growth, and viral load in HIV-infected infants.

The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed.

Body Height↗

Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment.

Amiodarone, a benzofuranic derivative, iodine-rich drug, has been used in pregnancy for either maternal or fetal tachyarrhythmias. Amiodarone, its main metabolite (desethylamiodarone) and iodine are transferred, albeit incompletely, through the placenta, resulting in a relevant fetal exposure to the drug and iodine overload. Since the fetus acquires the capacity to escape from the acute Wolff-Chaikoff effect only late in gestation, the iodine overload may cause fetal/neonatal hypothyroidism and goiter. Among the reported 64 pregnancies in which amiodarone was given to the mother, 11 cases (17%) of hypothyroidism in the progeny (10 detected at birth, 1 in utero) were reported, 9 non-goitrous (82%) and 2 (18%) associated with goiter. Hypothyroidism was transient in all cases, and only 5 infants were treated short-term with thyroid hormones. Only 2 newborns had transient hyperthyroxinemia, associated with low serum TSH concentrations in one. Neurodevelopment assessment of the hypothyroid infants, when carried out, showed in some instances mild abnormalities, most often reminiscent of the Non-verbal Learning Disability Syndrome; however, these features were also reported in some amiodarone-exposed euthyroid infants, suggesting that there might be a direct neurotoxic effect of amiodarone during fetal life. Breast-feeding was associated with a substantial ingestion of amiodarone by the infant, but in the few cases followed it did not cause changes in the newborn's thyroid function. In conclusion, amiodarone therapy during pregnancy may cause fetal/neonatal hypothyroidism and, less frequently, goiter. Thus, the use of amiodarone in pregnancy should be limited to maternal/fetal tachyarrhythmias which are resistant to other drugs or life-threatening. If amiodarone is used during gestation, a careful fetal/neonatal evaluation of thyroid function and morphology is warranted. It seems prudent to advise that fetal/neonatal hypothyroidism be treated, as soon as the diagnosis is made, even in utero, to avoid neurodevelopment abnormalities, although the latter may occur independently of hypothyroidism. If breast-feeding is allowed, careful evaluation of the infant's thyroid function and morphology is required because of the continuing exposure of the infant to the drug.

Amiodarone↗

Assessment of fetal neurodevelopment via fetal magnetocardiography.

Fetal magnetocardiography (fMCG) offers unique capabilities for assessment of fetal heart rate (FHR) and fetal behavior, which are fundamental aspects of neurodevelopment. The most important attribute of fMCG for FHR monitoring is its high precision, which allows accurate assessment of beat-to-beat fetal heart rate variability (FHRV), including respiratory sinus arrhythmia. Using mathematical indices to assess FHRV, we find that short- and long-term FHRV both increase during gestation but not in the same manner. The largest increases in short-term FHRV occur during the last trimester, while the largest increases in long-term FHRV occur early on, with smaller changes occurring during the last trimester. The fMCG also allows assessment of fetal activity. This results from the high sensitivity of the signal to the position and orientation of the fetal heart. FMCG actograms are therefore specific for fetal trunk movement, which are thought to be more important than isolated extremity movements and other small fetal movements. The ability to assess FHR, FHRV, and fetal trunk movement simultaneously makes fMCG a valuable tool for neurodevelopment research.

Electrocardiography↗

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

OBJECTIVE: To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. METHODS: MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." RESULTS: Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. CONCLUSIONS: Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Adult↗

Relationship between fetal acidemia at cordocentesis and subsequent neurodevelopment.

To determine whether there is a relationship between chronic fetal acidemia and subsequent neurodevelopment, a follow-up study was undertaken of 36 children with normal karyotype and morphology, who had prenatal cordocentesis for severe growth retardation. The main outcome measure was the Griffiths neurodevelopmental quotient. The children who had acidemia as fetuses (n = 13) had a significantly lower developmental quotient (mean = 91.8, SD = 6.3) than those with normal (n = 23) fetal blood pH (mean = 100.3, SD = 10.3; t = -2.68, p = 0.011). There was also a significant correlation between developmental quotient and the degree of fetal acidemia (r = 0.41, n = 36, p = 0.012). The pregnancies with acidemic fetuses had similar epidemiological characteristics to those with fetuses with a normal pH, except for a higher incidence of smoking. There was no significant correlation between the degree of growth retardation (birth weight expressed as multiples of SD from the mean for gestational age and sex) and fetal acidemia (r = -0.23, n = 36, NS) or subsequent Griffiths developmental quotient (r = -0.005, n = 36, NS). The results show an association between chronic fetal acidemia and subsequent impaired neurodevelopment. This observation suggests that future preventative interventions may be possible.

Journal Article↗