Neuromotor Outcomes of Infants Exposed Prenatally to Cocaine:

The effect of prenatal cocaine exposure on the neuromotor outcome of infants has been investigated through animal research, neurophysiological studies of neonates, and longitudinal follow-up of exposed infants. The inconsistency in reported findings may reflect methodological problems as well as variations among study populations and individual infants. Several studies using the Movement Assessment of Infants (MAI) have reported significant differences in motor performance at four months of age in infants who were cocaine-exposed prenatally, but specific clinical findings vary. A review of relevant work is presented here with a discussion of issues and variables which must be considered in an evaluation of the neuromotor consequences of intrauterine cocaine exposure for the developing infant.     

Intrauterine growth correlation to postnatal growth — influence of risk factors and complications in pregnancy

In a population of 616 pregnant women with increased risk of intrauterine growth retardation, we examined the relationship of third trimester fetal growth to maternal and pregnancy risk factors, the infants condition at birth, and postnatal growth. Intrauterine growth velocity was calculated from repeated estimations of fetal weight using ultrasound. Postnatal growth up to 3 months was measured in 313 of the infants. Intrauterine growth velocity was directly correlated to birth weight deviation (R = 0.35, P < 0.0001) and inversely correlated to postnatal growth (R = 0.21, P = 0.0001). Heavy smoking throughout pregnancy was the most pronounced factor associated with loss of fetal growth percentiles (P = 0.006), and it was also associated with postnatal catchup (P = 0.01). Infants who needed neonatal care had significantly lower intrauterine growth velocities compared to the rest of the study group; no correlation was found between intrauterine growth velocity and Apgar scores or umbilical pH. It is concluded that growth retardation in the third trimester can be identified by ultrasound fetometry, and is associated with maladaptation at birth and postnatal catchup. However, the correlations were weak suggesting that deviation at birth reflects, only to a limited degree, acceleration or deceleration of growth in the third trimester.     

Predictive validity of the "Movement Assessment of Infants"

Early identification of neuromotor deficits, cerebral palsy or other neurological handicaps, is a focus of concern for neurologists, pediatricians, and developmental therapists. Among infants at risk for developing these handicaps are those with low birthweight, idiopathic respiratory distress syndrome, and early central nervous system insults. The Movement Assessment of infants (MAI), a neuromotor assessment tool, was developed for the purpose of evaluating high-risk infants participating in the University of Washington's Neonatal Intensive Care Unit Followup Clinic. The predictive validity of the MAI was evaluated for 246 infants for whom assessments had been completed at four months and for whom at least one set of followup data was available at either one or two years of age. Correlations between the MAI total risk score and all five of the outcome measures at one and two years were highly significant. The clinical relevance of this study in the use of the MAI as an evaluation tool for identifying infants with neuromotor dysfunction is discussed.     

A prospective comparison of developmental outcome of children with in utero cocaine exposure and controls using the Battelle Developmental Inventory

Children with in utero cocaine exposure may be at risk for adverse neurodevelopmental outcome. To evaluate such outcome in young children, we administered the Battelle Developmental Inventory (BDI) to a group of inner-city children with (COC) and without (CON) in utero cocaine exposure at ages 3 and 5 years. Sixty-five COC and 68 CON, similar at age of testing, were evaluated at both time points by examiners masked to child group status. Both groups scored poorly and worsened over time. Although Total BDI raw scores were lower in the COC group than in the CON group at 3 years, this difference was related to postnatal environmental factors, caregiver (p = .022), and home environment (p = .010), not to in utero cocaine exposure (p = .88). At 5 years, the Total BDI score was related to the home environment (p < .001) but not to the caregiver (p = .36) or in utero cocaine exposure (p = .83). We conclude that inner-city children are at risk for adverse developmental outcome regardless of in utero cocaine exposure.     

Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate

AIMS: To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms. METHODS: Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8). RESULTS: Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02). CONCLUSIONS: Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed.     

The Relationship Between the Movement Assessment of Infants and the Fagan Test of Infant Intelligence in Infants with Prenatal Cocaine Exposure

In the present study both the Fagan Test of Infant Intelligence (FTII) and the Motor Assessment of Infants (MAI) were administered to 36 full term infants previously exposed to cocaine in utero. The infants were participating in a program at the PACT (Parents and Children Together) clinic operated by Children's Hospital of Buffalo, New York. The FTII was administered at 69 weeks post-conceptional age and the MAI was administered 8 months from birth. It was hypothesized that significant relationships existed between the mean novelty preference scores on the FTII at 69 weeks and the risk scores on the subsections of the 8-month MAI. Moderate, but statistically significant, negative correlations were found between the FTII and both the automatic reactions and the primitive reflexes subsections of the MAI. The implications of these results are discussed in the context of a homeostatic model of functioning, under which the infants are viewed as having difficulties with internal regulation and motor control, leading to higher risk scores on the MAI and to lower novelty preference scores on the FTII.     

Effects of Prenatal Drug Exposure on Neurobehavioral Functioning in Young Infants

In the newborn period, infants prenatally exposed to cocaine and other drugs show low scores on the Neonatal Behavioral Assessment Scale. Beyond that period, research is limited on the effects of prenatal drug exposure on neurobehavioral functioning. In this study we compared infants exposed to cocaine and other drugs and control infants from low socioeconomic backgrounds on measures of neurobehavioral functioning during neuromotor assessment at 1, 4 and 7 months of life. None of the measures of neurobehavioral functioning showed any significant group differences. This study did not support the hypothesis of disrupted neurobehavioral functioning beyond the neonatal period in infants exposed to drugs prenatally.     

Performance of 6-Month-Old Asian American Infants on the Movement Assessment of Infants

The purpose of this study was to examine the performance of Asian American infants on the Movement Assessment of Infants (MAI). The sample consisted of 30 full-term 6-month-old Asian American infants. These infants tended to have slightly slower integration of some primitive reflexes and to acquire automatic reactions and volitional motor skills at a slightly different rate than the predominantly Caucasian group of infants in a previous study. When the Washington and Deitz 6-Month Profile was used with the Asian American infants, 40% of them were identified as having risk scores higher than any of the infants in the Washington and Deitz study. This occurred even though the Asian American infants were full term, with unremarkable birth histories and, according to parent report, had no developmental concerns identified by either a parent or a health care provider. This finding suggests that clinicians should be cautious when using the MAI 6-Month Profile to assess Asian American infants.     

Neurobehavioral assessment of infants born at term and in utero exposure to serotonin reuptake inhibitors

Background

Some studies report neurobehavioral symptoms in neonates exposed to serotonin reuptake inhibitors (SRIs) in utero. However, maternal psychiatric illness during the last trimester of pregnancy, as a confounding factor, has not always been assessed.

Aims

In this prospective study we compared neurobehavioral complications among neonates who were born to euthymic women who either took or did not take an SRI during the last trimester of pregnancy.

Study design

Exposed and unexposed infants were assessed for: 1) temperament as measured by the Neonatal Behavioral Assessment Scale (NBAS); 2) activity via Actiwatch electronic monitoring; 3) sleep state using trained observer ratings; and 4) perinatal complications through medical record review. T-tests, Fisher's exact tests, and analyses of covariance were used to assess the relationship between clinical and neurobehavioral factors and exposure status.

Subjects

67 infants (61 controls and 6 exposed to SRIs).

Outcome measures

Neonatal Assessment Behavioral Scale, APGAR scores, infant sleep state (% sleep, % wakeful), startles and tremulousness, gestational age, birth weight, and head circumference.

Results

Infants exposed to SRIs in the third trimester had poorer motor development, lower 5-minute APGAR scores, and shorter mean gestational age as compared to unexposed infants.

Conclusion

Results of this study show differences in autonomic and gross motor activity between neonates who were or were not exposed to SRIs in utero after controlling for active maternal psychiatric illness. Future longitudinal work should compare longer term outcomes of exposed and unexposed infants of depressed mothers.     

Prenatal cocaine exposure and child welfare outcomes

This study examines the relationship between prenatal cocaine exposure and child welfare outcomes. Seventy-six infants positive for cocaine at birth were matched to 76 negative infants. With prenatal care and maternal use of alcohol and tobacco controlled, cocaine-exposed infants had significant decrements in birth weight, length, head circumference, and depressed 5-min Apgar scores. This confirmed the health risk of prenatal cocaine exposure for the sample. Three-year follow-up data were obtained from the State Central Register and foster care records. Adjusting for prior maternal involvement with child welfare services the study groups did not differ in incidents of child maltreatment or foster care placement. These findings suggest that prenatal cocaine exposure is not a marker for abusive parenting. However, from the perspective of a cumulative risk model, the identification of cocaine-exposed infants at birth can form the starting point for the development of appropriate diagnostic and follow-up services for mother and child.     

Fetal origin of childhood disease: intrauterine growth restriction in term infants and risk for hypertension at 6 years of age

OBJECTIVE: To examine the association between intrauterine growth restriction (IUGR) status at birth among full-term infants, exposure to substance use during pregnancy, and risk of hypertension at 6 years of age. DESIGN: Prospective evaluation of high-risk children. SETTING: Four centers of the National Institute of Child Health and Human Development Neonatal Research Network. PARTICIPANTS: One thousand three hundred eighty-eight infants (600 cocaine exposed, 781 nonexposed, and 7 indeterminate, matched by gestational age, race, and sex), were enrolled at these sites. Nine hundred fifty children (415 exposed, 535 nonexposed) were followed up for 6 years.Intervention Right arm blood pressure was measured using the Dinamap portable adult/pediatric monitor with appropriate cuff size.Main Outcome Measure Blood pressure levels. Hypertension was defined as either systolic or diastolic blood pressure higher than the 95th percentile for sex, age, and height. RESULTS: Eight hundred ninety-one children had blood pressure data at 6 years of age: 516 were born at full term; 144 (28%) of the 516 children had a diagnosis of IUGR at birth. At 6 years of age, 93 (19%) of 516 children had hypertension. Of 144 children with IUGR, 35 (24%) had hypertension as compared with 58 (16%) of 372 children without IUGR (P<.05). Twenty percent of cocaine-exposed children had hypertension as compared with 16% of nonexposed children (P = .20). Intrauterine growth restriction status at birth was significantly associated with hypertension (relative risk, 1.8 [95% confidence interval, 1.2-2.7]) when multivariable Poisson regression analysis was performed adjusting for site; maternal race, education, and tobacco, marijuana, alcohol, and cocaine use during pregnancy; and child's current body mass index (calculated as weight in kilograms divided by height in meters squared). CONCLUSION: In term infants, IUGR is linked to risk of hypertension in early childhood, which may be a marker for adult cardiovascular disease.     

Early Predictors of One Year Neurodevelopmental Outcome fo ”At Risk” Infants

Early predictors of one year neurodevelopmental outcome were determined for a group of 27 “at risk” infants. Based on t-tests and a stepwise discriminant analysis for a variety of early physical and neuromotor measures, weight at 3 months adjusted age was the earliest and best predictor of 12 month neurological status. Developmental status at 12 months, as assessed by the Griffiths Developmental Mental Scales and the Bayley Motor Scale, was significantly correlated with certain risk scores from the Movement Assessment of Infants administered at 4 months adjusted age. Therapists are encouraged to incorporate measures of physical growth in their assessments of “at risk” infants. Further studies need to be conducted to determine the long-term predictive value of postnatal growth and the motor status at 4 months as evaluated by the Movement Assessment of Infants.     

不同孕期母亲免疫水平对婴儿牛奶蛋白过敏的影响

目的 探讨不同孕期母亲Th1/Th2免疫水平与婴儿牛奶蛋白过敏（CMPA）之间的关联。方法 选取2016年7月至2018年12月于山东省潍坊市益都中心医院及青州市中医院就诊的单胎健康孕妇及其子代为研究对象。检测母亲孕中期、孕后期的白细胞介素（IL）-2、干扰素-γ（IFN-γ）、IL-4和IL-10水平,并分别于出生后1年内进行CMPA问卷调查,对临床怀疑CMPA的婴儿进行食物回避及牛奶口服激发试验,将符合CMPA的48例婴儿纳入CMPA组,其余977例正常婴儿纳入对照组。对CMPA婴儿进行单因素分析,并采用泊松回归分析不同孕期母亲各Th1/Th2型细胞因子水平与CMPA之间的关联。结果 CMPA的检出率为4.68%,临床表现包括消化系统症状、皮肤表现、呼吸系统症状及其他表现。单因素分析结果显示,CMPA组母亲食物过敏、母亲过敏性疾病史的发生率均明显高于对照组（P < 0.05）,母乳喂养率明显低于对照组（P < 0.05）。CMPA组的母亲IL-2（孕中期和孕后期）、IFN-γ（孕后期）较对照组明显降低（P < 0.05）。母亲孕后期低IFN-γ及孕中期、孕后期低IL-2与婴儿CMPA存在显著关联（P < 0.05）;校正母乳喂养、母亲食物过敏及母亲过敏性疾病史等因子后发现,母亲孕后期低IL-2、低IFN-γ与婴儿CMPA仍存在显著关联（P < 0.05）。结论 孕后期母体的Th1型细胞因子水平下降,可能会导致胎儿的免疫改变,从而增加其子代出生后罹患CMPA的风险。     

Attentional functioning and impulse control in cocaine-exposed and control children at age ten years

Children with gestational cocaine exposure may be at risk of difficulties in attentional functioning and impulse control. We administered the Gordon Diagnostic System and subtests of the Halstead-Reitan Battery to inner-city children with (COC) and without (CON) gestational cocaine exposure at age 10 years. Subtle differences were found between groups, with differences in Gordon Delay (Efficiency Ratio) and Gordon Distractibility (Total Commissions). With these two exceptions, children had similar performance, with both groups performing poorly. Attentional functioning and impulse control were also assessed in school. Teachers did not distinguish between COC and CON, although both groups presented behavioral problems. We conclude that gestational cocaine exposure may be associated with subtle problems in attention and impulse control, putting exposed children at higher risk of developing significant behavioral problems as cognitive demands increase.     

Prenatal drug exposure and maternal and infant feeding behaviour

OBJECTIVE: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates. METHODS: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction. RESULTS: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions (638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts (29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems. CONCLUSIONS: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.     

Visual recognition memory in drug-exposed infants.

Visual recognition memory testing in high-risk infants has been shown to have significant predictive ability for later cognitive deficits. This study evaluated cognition in infants exposed prenatally to illicit stimulant drugs compared with nonexposed controls with a standardized test of visual recognition, the Fagan Test of Infant Intelligence (FTII). Thirty-six healthy, full-term infants with prenatal exposure to cocaine and/or amphetamines and 26 infants with no drug exposures, matched for race and socioeconomic status, were tested. Average FTII scores were significantly lower and the percentage testing at risk significantly higher in the drug-exposed group (p less than .01). Differences between groups were also noted in behaviors dealing with attention, distractibility, and activity level. These data support recent evidence from longitudinal studies showing that infants exposed to drugs prenatally may be at risk for later subtle neurological abnormalities and suggest these difficulties may be identifiable long before the children reach school age.     

Characteristics at four months follow-up of infants born small for gestational age: a controlled study

This prospective study compared 65 small-for-gestational-age (SGA) (birth weight < 3rd centile) and 71 control infants at a corrected age of 4 months. It was hypothesised that differences would exist in growth, development, temperament and minor neurological signs and that these would be predicted by type (proportional/disproportional) of growth restriction at birth and maternal mood disturbance at birth or at 4 months. Infants had a Griffith's developmental test and neuromotor assessment. Maternal mood and infant temperament were surveyed. Few differences were found between SGA and control infants. SGA infants showed catch-up growth with 63% being above the third percentile and 43% being above the tenth percentile for weight. SGA infants had lower Griffith's GQ scores (97 vs. 102, P = 0.02) and they were rated in temperament as more manageable than controls. There were no differences in subtle neuromotor signs. Neither type of SGA nor maternal mood disturbance at birth had prognostic significance for infant catch up growth, neuromotor scores, or temperament though level of maternal stress and anxiety at 4 months were related to lower GQ scores in SGA infants.     

Early developmental screening: sensitivity and specificity of chronological and adjusted scores.

The motor development of 75 preterm infants was assessed at 4 months chronological and 4 months adjusted ages using the Movement Assessment of Infants (MAI). Infants were followed until 18 months old when neurological and motor outcomes were assessed by a developmental pediatrician, and outcomes were classified as normal, suspicious, or abnormal. Sensitivity, specificity, and positive and negative predictive values were calculated at the two points in time using a variety of cutoff MAI scores. At 4 months, the practice of adjusting for prematurity resulted in the better combination of screening rates for the detection of both neurologically abnormal and neurologically abnormal/suspicious children. To obtain comparable rates, different cutoff MAI scores were used to identify the neurologically abnormal versus the neurologically abnormal/suspicious children. The optimal combination of sensitivity, specificity, positive and negative predictive values varies according to the age of assessment, the disorders being identified, and the cutoff scores employed.     

Central and autonomic system signs with in utero drug exposure

AIMS: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure. METHODS: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure. RESULTS: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more. CONCLUSION: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.     

Dose-response effect of fetal cocaine exposure on newborn neurologic function

BACKGROUND: Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. METHODS: Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores 相似文献