Long-term developmental follow-up of infants of diabetic mothers.

The neurodevelopmental consequences of maternal insulin-dependent diabetes were studied in 109 infants of diabetic mothers and 90 control infants. The infants born to diabetic mothers included 70 "early entry" subjects and 39 "late entry" subjects. Maternal diabetes control during pregnancy was significantly better in "early entry" mothers than in late-entry mothers, as determined by glycosylated hemoglobin levels. Infants were examined by a psychologist and a developmental pediatrician unaware of group status at 6, 12, 24, and 36 months of age; 71% of the subjects completed the 3-year-study. Neurodevelopment of early-entry subjects was similar to that of control subjects, whereas late-entry subjects scored less well on language measures. Mean head size in late-entry subjects was significantly less (p = 0.03) than in either control subjects or early-entry subjects at age 3 years, and correlated negatively with glycosylated hemoglobin levels during all three trimesters. Less optimal intellectual development was associated with reduced head circumference. In addition, the presence of major congenital malformations was associated with reduced developmental performance through age 2 years. Our results indicate that mothers with insulin-dependent diabetes who maintain good control during pregnancy can expect to have infants who are neurodevelopmentally normal; mothers whose diabetes is less well controlled may have infants with less optimal neurodevelopment.

Antiepileptics and the development of congenital anomalies.

We are conducting a prospective cohort study of epilepsy and pregnancy to determine the nature and extent of adverse pregnancy outcomes in infants of mothers with epilepsy (IME). Women with epilepsy were enrolled no later than the first trimester and were matched with controls; their infants were examined at 8 weeks by pediatricians blinded to maternal status. A number of variables were compared between case and control infants: birth weight, length, gestational age, head circumference, Apgar scores, feeding difficulties, neonatal irritability, and presence of major malformations and minor anomalies. The number of minor anomalies per infant was greater for IME than for controls (mean, 5.05 and 3.65, p less than 0.0001 per infant, respectively). Prominent occiput was the only anomaly seen significantly more often in IME than in controls (p less than 0.05).

Epilepsy in pregnancy: developmental outcome of offspring at 12 months.

Women were enrolled in our prospective cohort study of epilepsy and pregnancy to determine the developmental outcome of offspring and the immediate outcome of pregnancy. Women with epilepsy (case group) were enrolled before conception or during the first trimester, and women without epilepsy or chronic illness (control group) were recruited during pregnancy. We have now completed 12-month evaluation for 43 children in the case group and 41 in the control group. We found no difference in growth parameters between the groups. The children in the case group had a higher mean number of minor anomalies than did those in the control group, and their features were consistent with those previously reported for children exposed to AEDs in utero. Developmental differences between the two groups varied, with some differences reaching statistical significance. The findings reported here are preliminary, since the children will be evaluated through 3 years of age.

Pharmacokinetics of anticonvulsants in pregnancy: alterations in plasma protein binding.

Anticonvulsant levels decline as pregnancy progresses, even in the face of constant and, in some cases, increased dosages of medications. It has been suggested that this decline is responsible for the increase in seizure frequency seen in approximately one-third of the women with epilepsy who become pregnant. Changes in plasma protein binding may explain the declines in anticonvulsant concentrations during pregnancy. A prospective cohort study was designed to test this hypothesis. Carbamazepine, phenytoin and phenobarbital were studied. The mean total concentrations of all 3 drugs declined as pregnancy progressed, rising in the postpartum period. Free concentrations also declined, but did so significantly only for phenobarbital. The free fraction for all anticonvulsants studied rose significantly throughout pregnancy. Protein binding is significantly altered during pregnancy for all 3 drugs studied and appears to account for much of the decline in anticonvulsant concentrations seen in this condition. It is suggested that free rather than total drug concentrations be monitored in pregnant women with epilepsy.

Pediatrician and parent: a challenge for female physicians.

Of 141 women who finished their pediatric residencies between 1960 and 1987, 84 (60%) completed questionnaires concerning their decisions regarding marriage, pregnancy, child care, and career. Eighty-three percent of the physicians were married, and 77% had natural-born children. The mean age at conception of the first child was 29 years, timing that was based on education or career stage for 51%. When the child was born, 45% of the women were employed, 20% were fellows, 17% were residents, 3% were undergraduate or medical students, and 15% were on leave. Eighty percent found supervisors and peers to be supportive of their pregnancies, but 26% believed they were penalized for their maternity leaves and 24% believed their pregnancies were actively discouraged. The mean leave taken following delivery was 12 weeks; the mean leave time considered ideal was 16 weeks. All women had used some form of day care, and 79% felt generally satisfied with its role in their children's rearing. They did more than 50% of the housework and in-home child care, with the remainder split between spouse and hired help, even though nearly two thirds were working full-time. All subjects with children would become parents again if they had to make the decision again. Eighty-one percent of respondents would go into medicine again; 79% would enter the same specialty. Most found their life-styles challenging but rewarding and, with the benefit of hindsight, would make the same choices again.

Effects on infants of a first episode of genital herpes during pregnancy.

Although genital herpes simplex virus (HSV) infections occurring during pregnancy are known to be associated with neonatal and maternal complications, their frequency and contributing risk factors are not well understood. We prospectively followed 29 patients who acquired genital herpes during pregnancy, to evaluate the perinatal effects of the infection. The patients were classified on the basis of clinical or serologic criteria. Fifteen patients had a primary first episode of genital HSV Type 2 (HSV-2), and 14 had a nonprimary first episode. Although no patient had disseminated disease, 6 of the 15 with primary genital herpes but none of 14 with nonprimary first-episode infection had infants with serious perinatal morbidity (P less than 0.01). Four of the five infants whose mothers acquired primary HSV-2 in the third trimester had perinatal morbidity such as prematurity, intrauterine growth retardation, and neonatal infection with HSV-2. Perinatal complications occurred in one of five infants whose mothers acquired primary HSV-2 during the first trimester, as well as in one of five infants whose mothers had primary HSV-2 during the second trimester. Asymptomatic cervical shedding of HSV-2 was detected at 10.6 percent of weekly visits made after a primary first episode, as compared with 0.5 percent of visits after a nonprimary first episode (P less than 0.01). We conclude that infants born to women who acquire primary genital herpes during pregnancy are at high risk of exposure to HSV, either during premature labor at the time of the primary episode or subsequently because of asymptomatic cervical shedding of the virus. The 40 percent incidence of serious perinatal morbidity in such women suggests that studies of preventive measures such as the use of antiviral chemotherapy are warranted.

Effectiveness of the Denver Developmental Screening Test with biologically vulnerable infants.

The Denver Developmental Screening Test (DDST) was initially developed specifically to identify children with mental retardation. However, its use in screening low birth weight and other biologically at-risk infants for motor problems is widespread. In view of the absence of biologically vulnerable children in the DDST standardization sample, and the limited validational support available for its use with children under 30 months of age, the purpose of this study was to investigate the effectiveness of the DDST in screening 62 Neonatal Intensive Care Unit graduates during infancy. Categorical results (Normal, Questionable, Abnormal), obtained in the home setting by DDST, were compared with results of Neonatal Intensive Care Unit Follow-up Clinic evaluations. There was a marked underselection of the DDST's categorical results in identifying those infants with suspect or abnormal findings on the more detailed clinic evaluations. However, the effectiveness of the screeners' clinical impression ratings (based on observations made during administration of the DDST) in identifying infants with positive criterion results was encouraging. These findings suggest that, although the DDST's categorical results may be of limited value in screening biologically vulnerable infants, administration of the DDST may provide a useful framework for more systematically observing and documenting significant qualitative aspects of an infant's developmental status, particularly for the screener who is less experienced in neuromotor assessment. These observations need to be defined further, and validated.

Neuromotor development of graduates of the neonatal intensive care unit: patterns encountered in the first two years of life.

The neurodevelopmental course of 219 Neonatal Intensive Care Unit graduates followed prospectively over 2 years was determined on retrospective chart review. Mild neuromotor abnormalities during the first year were identified in 50%, three-quarters of which proved transient with normal development at 2 years of age. Moderate abnormalities were identified in 7%, half of which proved transient. Severe neuromotor abnormalities were identified in 20%, two-thirds of whom had cerebral palsy at 2 years. Persistent noncerebral palsy neuromotor abnormalities remained in one-third of those in the severe abnormality group, one-half of those in the moderate abnormality group, and one-quarter of those in the mild abnormality group. As birthweight decreased, the incidence of always normal development and transient neuromotor abnormalities decreased while the incidence of persistent neuromotor abnormalities increased. Small for gestational age infants demonstrated a slightly higher incidence of persistent abnormalities than their appropriate for gestational age counterparts. No significant sex differences were observed.

Genital herpes in pregnancy: risk factors associated with recurrences and asymptomatic viral shedding.

One hundred forty-seven women with recurrent symptomatic genital herpes simplex virus acquired prior to the start of pregnancy (group 1) and 15 women whose first symptomatic episode of genital herpes was acquired during pregnancy (group 2) were followed weekly during the course of gestation. Among women with recurrent genital herpes antedating pregnancy, the mean number of recurrences per trimester increased from 0.97 to 1.26 to 1.63 in the first through third trimester, respectively (p less than 0.05 for comparison between each trimester). The median number of symptomatic recurrences of genital herpes during gestation was four in women in group 1 compared to one in women in group 2 (p less than 0.01). Asymptomatic viral excretion from the genital tract was, however, more common in women in group 2 (33%) than in women in group 1 (12.9%) (p less than 0.05). Herpes simplex virus was isolated at 5.5% of routine visits in group 2 women compared to 1% of routine visits among group 1 women. Logistic regression analysis indicated young age also was associated with more frequent asymptomatic viral shedding. Asymptomatic herpes simplex virus excretion was more common from the vulvar area than the cervix, and women in group 2 were more likely to shed virus from both sites simultaneously than women in group 1. Age and recent acquisition of genital herpes are risk factors for asymptomatic excretion of herpes simplex virus during pregnancy.

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.

Vitamin and mineral supplementation in Down's syndrome.

The claim that large, nonspecific doses of vitamins and minerals improve the performance of mentally retarded children has recently reappeared in both the scientific literature and the public media. This hypothesis was examined in a double-blind, case-control study involving 20 home-reared children with Down's syndrome between 5 and 13 years of age. Children were randomly assigned by matched pairs to either a vitamin/mineral group or placebo group for an 8-month study period. No significant group differences or suggestive trends were found in any tested area of development or behavior, including intelligence (IQ), school achievement, speech and language, and neuromotor function. No group differences in appearance, growth, or health were seen. No support was found for the orthomolecular hypothesis in school-aged children with Down's syndrome.

Growth and development of infants weighing less than 800 grams at birth.

A prospective study of infants weighing less than 800 g at birth and cared for in a single neonatal intensive care unit between 1977 and 1980 was conducted. Neonatal mortality was 80%; neurodevelopmental outcome was assessed in 16 of the 18 survivors. Mean birth weight for these 16 was 730 g; mean gestational age was 26 weeks. Perinatal asphyxia, respiratory distress, apnea, mechanical ventilation, and chronic pulmonary disease were commonplace. Symptomatic intracranial hemorrhage, seizures, sepsis, or meningitis did not occur in survivors. Of the 16 infants, 13 (81%), including all three with birth weight less than 700 g, were without major CNS handicaps and were developing appropriately at 6 months to 3 years of age. Only one of the 16 had clearly subnormal mental development. None had a major visual or hearing impairment. Apgar scores at one and five minutes were significantly related to outcome; apnea, mechanical ventilation, and chronic pulmonary disease were not. These data suggest that a remarkably hopeful outcome is possible for the few survivors of extremely low birth weight.

Mortality in infants discharged from a neonatal intensive care unit.

In a three-year period, 3.8% (43) of 1,123 infants discharged from one neonatal intensive care unit (NICU) subsequently died, the vast majority before 1 year of age. Sudden infant death syndrome was responsible for 28% of the deaths, congenital heart disease for 25% of the deaths, chronic lung disease for 16%, and trauma, infections, and chromosomal disorders each accounted for 5% of the deaths. Postdischarge death rates in the three-year study period remained stable, while infant mortality in the NICU decreased from 26.5% to 16.3%. This study suggests that decreasing mortality among infants treated in NICUs is not necessarily reflected in improved postdischarge death rates and that the vast majority of deaths in these infants are currently not preventable.

Hyaline membrane disease, birth weight, and gestational age. Effects on development in the first two years.

Mean mental and motor developmental test scores (Bayley scales) at 4, 12, and 24 months of age were determined for 161 graduates of a neonatal intensive care unit during the period 1977 through 1979. Analysis of variance for our data showed significant effects of hyaline membrane disease (HMD) on mental and motor development at 4 months, but disappearance of these effects at 12 and 24 months of age. Conversely, birth weight was not significantly related to developmental performance at 4 months, but was strongly related to both mental and motor performance at 12 and 24 months of age. Gestational age was significantly related to mental performance at 24 months of age. No relationship was found between HMD and major CNS handicapping conditions; both birth weight and gestational age were highly related to the occurrence of neurologic handicaps. Of the three variables assessed, birth weight was the best predictor of neurodevelopmental outcome.

Spastic diplegia in premature infants. Etiologic and diagnostic considerations.

To investigate the etiology of spastic diplegia (SD) of prematurity, we compared the prenatal, perinatal, and neonatal course of 18 preterm infants with SD to that of a control group of preterm infants without SD. No significant differences between the group with SD and the control group were found in most of the perinatal and neonatal factors analyzed. Significant differences were found in birth weight, birth head circumference, and the one-minute Apgar score. Controlling for gestational age, infants with SD weighed less at birth, had smaller heads, and were more often briefly neurologically depressed. Intracranial hemorrhage and neonatal seizures occurred significantly more often in infants with SD. Fifteen infants with SD were believed to be neurologically normal at the time of nursery discharge. These findings suggest the importance of prenatal factors in optimally treated preterm infants in whom SD develops.

Influences on measured intelligence in Down's syndrome.

The measured IQ and parental educational level of 57 children with Down's syndrome were compared. The phenomenon of decreasing IW with increasing chronological age in Down's syndrome was considered in the data analysis. There was no trend toward better cognitive performance by children of higher-educated parents. Thirty-one of the children had attended an early, continuous stimulation program. This experience accounted for most of the observed IQ variance.

The Summitt syndrome: observations on a third case.

A 6 1/2 year old male presented with acrocephaly, brachydactyly, clinodactyly, mild syndactyly of the hands and feet, genu valgum, and marked obesity. Roentgenograms of the hands revealed hypoplasia or aplasia of the middle phalanges. Roentgenograms of the feet revealed hypoplasia of the middle phalanges and deformity of the proximal phalangeal epiphyses of the great toes. Chromosomes studies revealed a normal 46,XY karyotype, and psychological testing revealed low normal intelligence. Current data support autosomal recessive inheritance, although X-linkage cannot be excluded.