Collaborative Home Infant Monitoring Evaluation Research Articles

Media Review: The Owlet Smart Sock—a “must have” for the baby registry?

Citation:Malik A, Ehsan Z. Media Review: The Owlet Smart Sock—a “must have” for the baby registry? J Clin Sleep Med. 2020;16(5):839–840.

Postdischarge Feeding Interactions and Neurodevelopmental Outcome at 1-Year Corrected Gestational Age

To determine the extent to which postdischarge feeding behaviors and interactions among caregiver-preterm infant dyads are associated with infant neurodevelopment at 1-year corrected gestational age (CGA). We studied 119 preterm infants born <34weeks gestation and <1750g at birth, and their caregivers, enrolled in the Collaborative Home Infant Monitoring Evaluation with in-person feeding assessments according to the Nursing Child Assessment Feeding Scale (NCAFS) at 39-59weeks postmenstrual age that completed Bayley Scales of Infant Development, Second Edition testing at 1year CGA. Mean±SD gestational age was 29.6±2.4weeks, and birth weight was 1260±320g. After adjustment for maternal and infant demographics, gestational age at birth, discharge and birth weight, mode of infant feeding, and caregiver type during the postdischarge NCAFS assessment, overall NCAFS scores were positively associated with higher 1-year CGA Bayleymental developmental index (MDI) scores (for each 1 SD increase in overall NCAFS score, MDI increased by 2.8 [95% CI 0.7, 4.9] points). Among individual NCAFS domains, strongest effects were seen for caregiver responsiveness to infant distress, such that, compared with dyads having domain scores of 11 (highest possible score), the adjusted mean difference in MDI was 8.3 points (95% CI -15.2, -1.4) lower among dyads with scores <9. Caregiver-preterm infant feeding interaction and caregiver responsiveness to preterm infant feeding distress were associated with preterm infant Bayley MDI at 1-year CGA. Caregiver-infant feeding interaction may represent a modifiable factor to improve the neurodevelopment of at-risk preterm infants.

Control of breathing

Late preterm infants have been called “great imposters” [1] because they often appear to be and are therefore treated as term infants, however their brainstem development and neural control of respiration are less mature than in full-term infants. During late gestation there are dramatic developmental changes in the brainstem and forebrain: at 34 gestational weeks the total brain weight is 65% of that at term [2]. The control of lung volume, laryngeal reflexes, upper airways, chemoreceptor activity, coordination of sucking, swallowing, breathing, the incidence of apnea and periodic breathing and the control of heart rate are still developing during late gestation and the degree of maturity of these mechanisms appears to lie on a continuum that extends from more immature infants to after term. Also, these reflexes are influenced by sleep-wake states whose neurobiological development is still evolving. The brainstem is not completely mature even at term, as confirmed by the fact that its myelination, the marker of completed neuronal/axonal maturation, is still incomplete at that time. This protracted maturation is not surprising, considering that the neurodevelopment of the respiratory control and sleep-wake cycle continues into infancy. The few data on control of breathing in late preterm infants indicate that ventilatory responses to CO2 and hypoxia as well as autonomic control of heart rate are not yet mature at 36 weeks PMA. Clinically, late preterm infants have more apnea and periodic breathing than term infants and immature coordination of sucking, swallowing and breathing often delay their ability to feed without episodes of bradycardia, desaturation and even apnea [3]. The incidence of apparent life-threatening events is more common in preterm infants (8-10%) than full-term infants (1% or less). In the Collaborative Home Infant Monitoring Evaluation studies the frequency of conventional and extreme (clinically relevant) events in near term infants is intermediate between preterm infants <34 weeks at birth and full-term infants [4]. Clinical data indicate that late preterm are also predisposed to wheezing in infancy and early childhood although not exposed to excessive supplemental oxygen or ventilator support [5]. Exposure to 21% oxygen could represent premature exposure to hyperoxic environment compared to that in utero, with long-term effects on the still immature conducting airways. Recent data demonstrate that immature human airway smooth muscle are highly sensitive to even short durations of hyperoxia, with increased proliferation at moderate levels of oxygen (< 60%) but apoptosis at higher levels [6].

Editorial introductions

Editorial introductions

The development of the circadian heart rate rhythm (CHR) in Asian infants

ObjectiveTo test the hypothesis that term-born Asian infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heart rate rhythm (CHR) at a later age than non-Asian term infants. MethodRepeated overnight heart rate (HR) traces obtained with a battery-operated Polar S810i heart-rate monitor at home in 17 Asian Torajan infants in Indonesia, were compared with those of 52 non-Asian infants monitored as part of the Collaborative Home Infant Monitoring Evaluation (CHIME). HR was determined using a moving window averaging technique. A comparison of median HR during quiet sleep (QS) episodes (identified by minimum HR variability), established the presence of CHR. ResultsSeventy three percent of non-Asian CHIME infants ≤7weeks exhibited CHR compared to 45% of Asian Torajan infants. Between 8 and 12weeks, 94% of non-Asian CHIME infants exhibited CHR, compared to 33% of Asian Torajan infants (p<0.001). Forty seven and 56% of Asian Torajan infants exhibited the CHR at the age intervals of 16–20weeks and 21–25weeks respectively. Active wakefulness percentages as a function of the entire recording and median QS HR were not significantly different in the two groups. ConclusionDespite the fact that Asian Torajan infants were on average a week older than non-Asian CHIME babies, between two and three months of age only one in three exhibited the CHR, compared to virtually all non-Asian CHIME infants. We speculate that the cause of this difference rests in the infants' environment rather than their genetic origin.

Algorithms for sleep–wake identification using actigraphy: a comparative study and new results

The aim of this study was to investigate two new scoring algorithms employing artificial neural networks and decision trees for distinguishing sleep and wake states in infants using actigraphy and to validate and compare the performance of the proposed algorithms with known actigraphy scoring algorithms. The study employed previously recorded longitudinal physiological infant data set from the Collaborative Home Infant Monitoring Evaluation (CHIME) study conducted between 1994 and 1998 [http://dccwww.bumc.bu.edu/ChimeNisp/Main_Chime.asp; Sleep26 (1997) 553] at five clinical sites around the USA. The original CHIME data set contains recordings of 1079 infants <1 year old. In our study, we used the overnight polysomnography scored data and ankle actimeter (Alice 3) raw data for 354 infants from this data set. The participants were heterogeneous and grouped into four categories: healthy term, preterm, siblings of SIDS and infants with apparent life-threatening events (apnea of infancy). The selection of the most discriminant actigraphy features was carried out using Fisher's discriminant analysis. Approximately 80% of all the epochs were used to train the artificial neural network and decision tree models. The models were then validated on the remaining 20% of the epochs. The use of artificial neural networks and decision trees was able to capture potentially nonlinear classification characteristics, when compared to the previously reported linear combination methods and hence showed improved performance. The quality of sleep-wake scoring was further improved by including more wake epochs in the training phase and by employing rescoring rules to remove artifacts. The large size of the database (approximately 337,000 epochs for 354 patients) provided a solid basis for determining the efficacy of actigraphy in sleep scoring. The study also suggested that artificial neural networks and decision trees could be much more routinely utilized in the context of clinical sleep search.

Extreme and Conventional Cardiorespiratory Events and Epidemiologic Risk Factors for SIDS

To test the hypotheses that there is a lack of correlation between extreme events and epidemiologic risk factors for sudden infant death syndrome (SIDS), and if conventional events are normal, their numbers should increase once a circadian decrease in breathing rate is established. In addition, the number of events should decrease with maternal smoking. Three outcome variables were derived from the Collaborative Home Infant Monitoring Evaluation (CHIME) of 1082 infants: (1) at least 1 extreme event lasting > or = 30 seconds, (2) at least 1 conventional event lasting > or = 20 seconds, and (3) being part of the 50% of infants with the most events. Multivariate logistic regression analyses found that extreme events were not statistically associated with any known SIDS risk factors and occurred less often during the early morning. Healthy term infants had significantly fewer of these events compared with preterm infants, subsequent siblings of infants with SIDS, and infants with an apparent life-threatening event, a finding that was not evident after 43 weeks (3 weeks postterm). Conventional events increased during the night, whereas maternal smoking was associated with a decrease in conventional events. Apneic episodes persisting for > or = 40 seconds occurred in 1.8% of the infants. Extreme events are associated with immaturity and do not seem to be immediate precursors of or causally related to SIDS.

Sleep Versus Wake Classification From Heart Rate Variability Using Computational Intelligence: Consideration of Rejection in Classification Models

Reliability of classification performance is important for many biomedical applications. A classification model which considers reliability in the development of the model such that unreliable segments are rejected would be useful, particularly, in large biomedical data sets. This approach is demonstrated in the development of a technique to reliably determine sleep and wake using only the electrocardiogram (ECG) of infants. Typically, sleep state scoring is a time consuming task in which sleep states are manually derived from many physiological signals. The method was tested with simultaneous 8-h ECG and polysomnogram (PSG) determined sleep scores from 190 infants enrolled in the collaborative home infant monitoring evaluation (CHIME) study. Learning vector quantization (LVQ) neural network, multilayer perceptron (MLP) neural network, and support vector machines (SVMs) are tested as the classifiers. After systematic rejection of difficult to classify segments, the models can achieve 85%-87% correct classification while rejecting only 30% of the data. This corresponds to a Kappa statistic of 0.65-0.68. With rejection, accuracy improves by about 8% over a model without rejection. Additionally, the impact of the PSG scored indeterminate state epochs is analyzed. The advantages of a reliable sleep/wake classifier based only on ECG include high accuracy, simplicity of use, and low intrusiveness. Reliability of the classification can be built directly in the model, such that unreliable segments are rejected.

Apparent Life-Threatening Events and Sudden Infant Death Syndrome: Comparison of Risk Factors

To compare the risk factors of 153 cases of apparent life-threatening event (ALTE) enrolled in the multicenter Collaborative Home Infant Monitoring Evaluation (CHIME) from 1994 to 1998 with the published risk factors for sudden infant death syndrome (SIDS). Trained CHIME interviewers gathered histories of infants with ALTE who met the criteria. The following risk factors were analyzed: male predominance, gestational age, low birth weight, very low birth weight, incidence of small for gestational age (SGA), age at the event, multiparity, maternal age, and smoking. Population-based SIDS studies with >100 deaths, focusing on 1 or more pertinent risk factors and carried out during the decade in which CHIME data were collected, were chosen for comparison. One of the 153 infants with ALTE in this study died during follow-up (0.6%). CHIME ALTE differed significantly from SIDS in 4 respects: fewer infants with low birth weight and SGA at birth, fewer teenage pregnancies, and a younger infant age at ALTE. Although a number of risk factors for ALTE are similar to those for SIDS, the differences warrant a separate focus on ALTE beyond that on SIDS.

Sudden Infant Death Syndrome

1. Rachel Y. Moon, MD* 2. Linda Y. Fu, MD, MSc† 1. *Director, Academic Development, Goldberg Center for Community Pediatric Health, Children's National Medical Center, Washington, DC 2. †Assistant Professor of Pediatrics, Goldberg Center for Community Pediatric Health, Children's National Medical Center, Washington, DC After completing this article, readers should be able to: 1. Describe possible etiologic mechanisms for sudden infant death syndrome (SIDS). 2. Identify the risk factors for SIDS. 3. Understand the relationship between apnea and SIDS. 4. Discuss the American Academy of Pediatrics SIDS Task Force recommendations and underlying rationale. Sudden infant death syndrome (SIDS) is defined as the sudden unexplained death of an infant younger than 1 year of age. It usually occurs in a previously healthy infant, and the cause of death remains unexplained despite a thorough case investigation, including a complete autopsy, death scene investigation, and review of the clinical history. Every year in the United States, approximately 2,500 infants die from SIDS. Risk factors have been identified through epidemiologic studies. SIDS is more likely to occur in male infants (3:2 ratio). Other risk factors include prone and side sleeping positions, maternal smoking during pregnancy, environmental tobacco smoke, overheating, soft bedding, inadequate prenatal care, young maternal age, prematurity or low birthweight, and African-American or American Indian/Alaskan Native heritage. For many years, apnea was believed to be the predecessor of SIDS, and home apnea monitors have been used in an attempt to prevent SIDS. However, studies such as the Collaborative Home Infant Monitoring Evaluation (CHIME) have demonstrated that apnea neither precedes nor predicts SIDS. Although apnea monitors may be useful in selected patients who have experienced apparent life-threatening events (ALTEs), there is no evidence that they are useful in reducing the risk of SIDS, and the American Academy of Pediatrics (AAP) recommends against using monitors as a SIDS prevention technique. (A more detailed discussion of ALTEs appears in this issue of Pediatrics in Review on page 203.) In 1992, the AAP first published its recommendation that infants should sleep in a nonprone position to reduce the risk of SIDS, and a national public …

Executive Summary of the Workshop on Oxygen in Neonatal Therapies: Controversies and Opportunities for Research

One of the most complex areas in perinatal/neonatal medicine is the use of oxygen in neonatal therapies. To address the knowledge gaps that preclude optimal, evidence-based care in this critical field of perinatal medicine, the National Institute of Child Health and Human Development organized a workshop, Oxygen in Neonatal Therapies: Controversies and Opportunities for Research, in August 2005. The information presented at the workshop included basic and translational oxygen research; a review of completed, ongoing, and planned clinical trials; oxygen administration for neonatal resuscitation; and a review of the collaborative home infant monitoring evaluation study. This article provides a summary of the discussions, focusing on major knowledge gaps, with prioritized suggestions for studies in this area.

Factors That Influence Use of a Home Cardiorespiratory Monitor for Infants

As part of the Collaborative Home Infant Monitoring Evaluation, a home monitor was developed to record breathing, heart rate, other physiologic variables, and the time the monitor was used. To determine the frequency of monitor use, factors that influence use, and validity of a model developed to predict use. We developed a model to predict monitor use using multiple linear regression analysis; we then tested the validity of this model to predict adherence for the first week of monitoring and for the subsequent 4-week period (weeks 2-5). Clinical research centers in Chicago, Ill; Cleveland, Ohio; Honolulu, Hawaii; Los Angeles, Calif; and Toledo, Ohio. Patients Preterm infants, infants younger than 1 month with a history of autopsy-confirmed sudden infant death syndrome in a sibling, and infants with an idiopathic apparent life-threatening event were divided into 2 cohorts based on enrollment date. Main Outcome Measure Mean hours of monitor use per week. In cohort 1, the variables available before monitoring were only weakly associated with total hours of monitor use in weeks 2 to 5 (total model r(2) = 0.08). However, when hours of monitor use in week 1 were included as a variable to predict monitor use in weeks 2 to 5, the r(2) increased to 0.64 for hours of monitor use per week. Our data show that monitor use in the first week was the most important variable for predicting subsequent monitor use. The study suggests that a major focus of home monitoring should be adherence in the first week, although it remains to be tested whether this adherence can be altered.

Cardiorespiratory events detected by home memory monitoring and one-year neurodevelopmental outcome

To determine if infants with cardiorespiratory events detected by home memory monitoring during early infancy have decreased neurodevelopmental performance. Infants (n = 256) enrolled in the Collaborative Home Infant Monitoring Evaluation also completed the Bayley Scales of Infant Development II at 92 weeks' postconceptional age. Infants were classified as having 0, 1 to 4, or 5+ cardiorespiratory events. Events were defined as apnea >or=20 seconds or heart rate <60 to 80 bpm or <50 to 60 bpm, for >or=5 to 15 seconds, depending on age. For term infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean Mental Developmental Index (MDI) values (+/-SD) of 103.6 (10.6), 104.2 (10.7), and 97.7 (10.9), respectively, and mean Psychomotor Developmental Index (PDI) values of 109.5 (16.6), 105.8 (16.5), and 100.2 (17.4). For preterm infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean MDI values of 100.4 (10.3), 96.8 (11.5), and 95.8 (10.6), respectively, and mean PDI values of 91.7 (19.2), 93.8 (15.5), and 94.4 (17.7). The adjusted difference in mean MDI scores with 5+ events compared with 0 events was 5.6 points lower in term infants ( P = .03) and 4.9 points lower in preterm infants ( P = .04). Having 5+ conventional events is associated with lower adjusted mean differences in MDI in term and preterm infants.

Japanese national SIDS project: 1998–2000 research for the improvement of infant mortality

The aim of the present study is to see if by conducting research on sudden infant death syndrome (SIDS), one of major contributing factors to infant mortality in Japan, infant mortality can be reduced. Concrete approaches taken in this study took four different directions: elucidation of SIDS etiology, prevention, elucidation of its social aspects (education) and the investigation of administrative aspects. At the same time, an attempt was made to get better grasp on the epidemiological trends in infant mortality, including that of SIDS. The idea behind this etiological approach was to unify hitherto separate approaches taken by those in epidemiological, physiological and pathological fields. A molecular-biological approach was also added. Physiologically hypothesized causes of SIDS—apnea and arousal disorder—together with the epidemiologically presumed risk factor of sleeping position, were examined jointly from a pathological viewpoint. Research in the first 2 years of the grant found that hypoxia reflected by gliosis in the brain stem arousal pathway was related to the duration of sleep apnea. Research in the final year of the grant found the possibility of organic fragility in the brain stem arousal pathway, particularly in periaqueducal gray matter and pedunculopontine nucleus reflected by apoptosis and neuronal plasticity. These findings gave support to the arousal disorder hypothesis in SIDS. Application of the restriction landmark genomic scanning (RLGS) method supported the possibility of locating a site for a SIDS-specific gene. The US collaborative home infant monitoring evaluation (CHIME) currently in use was evaluated. In addition, three new monitoring methods were developed: a non-invasive multi-channel pressure-sensing bed, microwave radar, and a pacifier that functions as a suckometer which can be used to evaluate a neonate’s autonomic nervous functions. Social (educational) activities included: surveys of the current state of educational campaigns on SIDS in other countries, epidemiological evaluation of campaigns run by the Japan SIDS families’ Association to evaluate the effectiveness of the SIDS campaign, and creation of a home page, mostly to inform the public about the output from this research group. “Guidelines for Death Scene Investigation of Sudden, Unexplained Infant Deaths: Recommendations of Interagency Panel on Sudden Infant Death Syndrome” was translated into japanese. Activities that concerned administrative measures included clarification of the unique nature of SIDS-related trials in Japan when compared to those in the United States. Other concrete administrative proposals were: a pressing need to increase the rate of SIDS-related autopsies to facilitate a better etiological understanding and, for this purpose, establishing regulations in local jurisdictions and amending Article 8 of the Postmortem Examination and Corpse Preservation Act, keeping in perspective the medico-economic evaluation of the japanese medical examiner system. For these proposals to be realized, establishment of a new office in charge of administrative and approved autopsies at the national level of government is desirable. Also pointed out were the different opinions held among specialists concerning the diagnosis of SIDS and their need to hold multiple conferences to unify their views. Basic data for these conferences were provided from epidemiological examinations of infant mortality.

Relationship between infant sleep position and motor development in preterm infants.

To determine whether motor development in premature infants varies according to sleep position, we evaluated 213 infants <1750 g birth weight enrolled in the Collaborative Home Infant Monitoring Evaluation (CHIME). At 56 weeks postconceptional age (PCA), sleep position was determined by maternal report, and the Bayley Scales of Infant Development 2nd Edition (BSID-II) were performed. Infants who slept supine were less likely than infants who slept prone to receive credit for maintaining the head elevated to 45 degrees (p = .021), and infants who slept nonprone were less likely than prone sleepers to receive credit for maintaining the head elevated to 90 degrees and lowering with control (p = .001). The Psychomotor and Mental Development Indices at 56 and 92 weeks PCA were not altered by usual sleep position at 56 weeks PCA. In summary, infants sleeping supine are less able to lift the head and lower with control at 56 weeks PCA, but global developmental status was unaffected. Supine sleeping has been associated with decreased risk for sudden infant death syndrome, but compensatory strategies while awake may be needed to avoid delayed acquisition of head control.

The Effect of Epoch Length and Smoothing on Infant Sleep and Waking State Architecture for Term Infants at 42 to 46 Weeks Postconceptional Age.

Epoch lengths from 20 seconds to 1 minute, and smoothing strategies from zero to three minutes are encountered in the infant sleep and waking literature. The present study systematically examined the impact of various epoch lengths and smoothing strategies on infant sleep state architecture. Overnight polysomnographic recordings were visually assessed by epoch as wake or as each of four sleep state parameters: electroencephalographic patterns, respiration, body movement, and eye movement. From these findings, sleep and waking states were assigned for each of six combinations of epoch length (30-second or 1-minute) and smoothing window length (none, 3-epoch, or 5-epoch). N/A. Subjects were 91 term infants, 42-46 weeks postconceptional age, from the Collaborative Home Infant Monitoring Evaluation (CHIME) study. N/A. A greater epoch length resulted in more active and less quiet sleep as a percentage of total study; however, the size of the smoothing window did not affect the percentage of sleep/waking states. In general, the greater the epoch length and the greater the smoothing window length, the fewer the number of, the greater the mean duration of, and the greater the longest continuous episode of sleep/waking states. Analysis of significant interactions indicated that a 1-minute epoch length relative to a 30-second epoch length resulted in increasingly longer episodes of quiet and especially active sleep with a greater smoothing window length. Smoothing strategy significantly altered sleep state architecture in infants and may explain part of the variability in infant sleep state findings between laboratories.

Apnea of Prematurity and Risk for SIDS

Apnea of Prematurity and Risk for SIDS

Accuracy of the Respiratory Inductance Plethysmography (RIP) Collaborative Home Infant Monitoring Evaluation (CHIME) Monitor in Identifying Obstructed Breaths ♦ 1972

Accuracy of the Respiratory Inductance Plethysmography (RIP) Collaborative Home Infant Monitoring Evaluation (CHIME) Monitor in Identifying Obstructed Breaths ♦ 1972

Infant Polysomnography: Reliability

Infant polysomnography (IPSG) is an increasingly important procedure for studying infants with sleep and breathing disorders. Since analyses of these IPSG data are subjective, an equally important issue is the reliability or strength of agreement among scorers (especially among experienced clinicians) of sleep parameters (SP) and sleep states (SS). One basic issue of this problem was examined by proposing and testing the hypothesis that infant SP and SS ratings can be reliably scored at substantial levels of agreement, that is, kappa (kappa) > or = 0.61. In light of the importance of IPSG reliability in the collaborative home infant monitoring evaluation (CHIME) study, a reliability training and evaluation process was developed and implemented. The bases for training on SP and SS scoring were CHIME criteria that were modifications and supplements to Anders, Emde, and Parmelee (10). The kappa statistic was adopted as the method for evaluating reliability between and among scorers. Scorers were three experienced investigators and four trainees. Inter- and intrarater reliabilities for SP codes and SSs were calculated for 408 randomly selected 30-second epochs of nocturnal IPSG recorded at five CHIME clinical sites from healthy full term (n = 5), preterm (n = 4), apnea of infancy (n = 2), and siblings of the sudden infant death syndrome (SIDS) (n = 4) enrolled subjects. Infant PSG data set 1 was scored by both experienced investigators and trained scorers and was used to assess initial interrater reliability. Infant PSG data set 2 was scored twice by the trained scorers and was used to reassess inter-rater reliability and to assess intrarater reliability. The kappa s for SS ranged from 0.45 to 0.58 for data set 1 and represented a moderate level of agreement. Therefore, rater disagreements were reviewed, and the scoring criteria were modified to clarify ambiguities. The kappa s and confidence intervals (CIs) computed for data set 2 yielded substantial inter-rater and intrarater agreements for the four trained scorers; for SS, the kappa = 0.68 and for SP the kappa s ranged from 0.62 to 0.76. Acceptance of the hypothesis supports the conclusion that the IPSG is a reliable source of clinical and research data when supported by significant kappa s and CIs. Reliability can be maximized with strictly detailed scoring guidelines and training.

Assessment of Sleep Position Over Time Among Infants At Risk of Sudden Infant Death Syndrom (SIDS) and Healthy Term Infants. † 462

The AAP continues to recommend avoidance of the prone sleep position to reduce the risk of SIDS. To evaluate compliance with this recommendation over time among families of at-risk and healthy term (HT) infants, we determined sleep position by interview among 630 enrollees in the Collaborative Home Infant Monitoring Evaluation (CHIME) at 5 sites across the USA from 5/1/94-4/30/96. Of these, 503 (89 SIDS siblings (SS), 88 apnea of infancy(AOI), 264 preterm (PT) infants ≤ 34 wks, 62 HT) completed the first follow up visit (≈30 days after enrollment). To determine adherence over time, we examined a subset of 208 infants (51 SS, 28 AOI, and 99 PT, 30 HT) who completed a minimum of 4 follow-up visits at the following postconceptional ages (mean wks ± SD): 44 ± 4, 49 ± 4, 56 ± 5, 71± 15. Table