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1.  Mothers of Very Low Birth Weight Children at School Age: Quality of Life Outcomes from the Newborn Lung Project Statewide Cohort Study 
This study aimed to: (1) determine the health-related quality of life (HRQoL) in mothers of five year old very low birth weight (VLBW) and normal birth weight (NBW) children; (2) determine what extent stress mediates the relationship between case status and maternal HRQoL; and (3) examine the pre-pregnancy, pregnancy, birth, and child health-related factors in predicting maternal HRQoL among mothers of five year old VLBW children.
A telephone interview was administered to 297 mothers of VLBW children and 290 mothers of NBW children who were enrolled in the Newborn Lung Project Statewide Cohort Study.
Mothers of VLBW children experienced worse physical and mental HRQoL than mothers of NBW children (52.8 versus 55.3 points, p<0.0001, and 48.9 versus 50.5 points, p=0.02, respectively). Adjusted analyses showed that maternal mental HRQoL was similar between cases and controls while physical HRQoL when children were age five was significantly different between cases and controls (Beta:−2.02, p=0.0006); this relationship was mediated by maternal stress. Among mothers of VLBW children, stress significantly contributed to adverse HRQoL outcomes when children were age five. Child behavior problems at age two were also associated with worse subsequent maternal mental HRQoL (Beta: −1.8 per SD, p=0.004), while each week of neonatal intensive care unit stay was associated with worse physical HRQoL (Beta: −0.26, p=0.02).
While caring for a VLBW child negatively impacts the HRQoL of mothers, this relationship was partially explained by maternal stress. Addressing maternal stress may be an important way to improve long-term HRQoL.
PMCID: PMC3390448  PMID: 22161725
Very low birth weight; maternal stress; maternal health-related quality of life; life course
2.  The Contribution of Infant, Maternal, and Family Conditions to Maternal Feeding Competencies 
Because little is known about the role of family problem-solving processes in the development of mothers’ competencies in feeding a very low birth-weight (VLBW) infant, we explored the contribution made by the competence in negotiating displayed by a mother and family member as they jointly problem solve infant-care issues. The infant’s neonatal biomedical condition, maternal depressive symptoms, and family poverty status may also contribute to feeding competencies.
A sample of 41 mothers of VLBW infants from 2 longitudinal studies who were observed during feeding at 1 and 8 months infant postterm age, with a family member of their choosing, participated in a dyadic problem-solving exercise. We assessed maternal feeding competencies with the Parent–Child Early Relational Assessment (Clark, 1997) and dyadic negotiating competence using an observational scale from the Iowa Family Interaction Rating Scales (Melby & Conger, 2001). We classified infant condition through medical record audit. Maternal depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression (CES-D) Scale (L. S. Radloff, 1977), and family poverty status was determined through the mother’s report of family income.
Mothers’ feeding competencies, structured into 2 factors, Parental Positive Affective Involvement, Sensitivity, and Responsiveness (PPAISR) and Parental Negative Affect and Behavior (PNAB, scored in the direction of low negativity) were stable from 1 to 8 months, accounting for the entire set of predictor variables. Neonatal biomedical condition had no effect on either PPAISR or PNAB; depressive symptoms were negatively associated with PNAB at 8 months; poverty status negatively predicted both PPAISR and PNAB at 1 and 8 months; and negotiating competence of the mother–family member dyad was positively associated with PNAB at 1 month.
Evidence that family poverty status and dyadic negotiating competence were both associated with maternal feeding competencies supports inclusion of these family-level variables in a model of feeding competencies. A mother’s negotiating competence with another family member who takes a responsible role in infant care may support maternal feeding competencies during a VLBW infant’s early weeks when parenting patterns are forming.
PMCID: PMC3227219  PMID: 22140356
3.  Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study 
BMC Pediatrics  2012;12:124.
To determine the effect of human milk, maternal and donor, on in-hospital growth of very low birthweight (VLBW) infants. We performed a retrospective cohort study comparing in-hospital growth in VLBW infants by proportion of human milk diet, including subgroup analysis by maternal or donor milk type. Primary outcome was change in weight z-score from birth to hospital discharge.
Retrospective cohort study.
171 infants with median gestational age 27 weeks (IQR 25.4, 28.9) and median birthweight 899 g (IQR 724, 1064) were included. 97% of infants received human milk, 51% received > 75% of all enteral intake as human milk. 16% of infants were small-for-gestational age (SGA, < 10th percentile) at birth, and 34% of infants were SGA at discharge. Infants fed >75% human milk had a greater negative change in weight z-score from birth to discharge compared to infants receiving < 75% (−0.6 vs, -0.4, p = 0.03). Protein and caloric supplementation beyond standard human milk fortifier was related to human milk intake (p = 0.04). Among infants receiving > 75% human milk, there was no significant difference in change in weight z-score by milk type (donor −0.84, maternal −0.56, mixed −0.45, p = 0.54). Infants receiving >75% donor milk had higher rates of SGA status at discharge than those fed maternal or mixed milk (56% vs. 35% (maternal), 21% (mixed), p = 0.08).
VLBW infants can grow appropriately when fed predominantly fortified human milk. However, VLBW infants fed >75% human milk are at greater risk of poor growth than those fed less human milk. This risk may be highest in those fed predominantly donor human milk.
PMCID: PMC3464178  PMID: 22900590
4.  Differential ethnic associations between maternal flexibility and play sophistication in toddlers born very low birth weight 
Infant behavior & development  2012;35(4):860-869.
Children born very low birth weight (<1500 grams, VLBW) are at increased risk for developmental delays. Play is an important developmental outcome to the extent that child’s play and social communication are related to later development of self-regulation and effective functional skills, and play serves as an important avenue of early intervention. The current study investigated associations between maternal flexibility and toddler play sophistication in Caucasian, Spanish speaking Hispanic, English speaking Hispanic, and Native American toddlers (18-22 months adjusted age) in a cross-sectional cohort of 73 toddlers born VLBW and their mothers. We found that the association between maternal flexibility and toddler play sophistication differed by ethnicity (F(3,65) = 3.34, p = .02). In particular, Spanish speaking Hispanic dyads evidenced a significant positive association between maternal flexibility and play sophistication of medium effect size. Results for Native Americans were parallel to those of Spanish speaking Hispanic dyads: the relationship between flexibility and play sophistication was positive and of small-medium effect size. Findings indicate that for Caucasians and English speaking Hispanics, flexibility evidenced a non-significant (negative and small effect size) association with toddler play sophistication. Significant follow-up contrasts revealed that the associations for Caucasian and English speaking Hispanic dyads were significantly different from those of the other two ethnic groups. Results remained unchanged after adjusting for the amount of maternal language, an index of maternal engagement and stimulation; and after adjusting for birth weight, gestational age, gender, test age, cognitive ability, as well maternal age, education, and income. Our results provide preliminary evidence that ethnicity and acculturation may mediate the association between maternal interactive behavior such as flexibility and toddler developmental outcomes, as indexed by play sophistication. Addressing these association differences is particularly important in children born VLBW because interventions targeting parent interaction strategies such as maternal flexibility must account for ethnic-cultural differences in order to promote toddler developmental outcomes through play paradigms.
PMCID: PMC3589984  PMID: 22982287
Very Low Birth Weight; Toddlers; Maternal Intrusiveness; Developmental Outcome; Ethnicity
5.  Using parent questionnaires to assess neurodevelopment in former preterm infants: a validation study 
Former preterm and very low birth weight (VLBW) infants require close neurodevelopmental surveillance after hospital discharge, but in-person professional testing is resource-intensive and inconvenient for families. A standardised developmental questionnaire completed by parents offers an alternative to in-person testing, but few such questionnaires have been validated. Our aim was to validate the Motor and Social Development (MSD) scale in a sample of former preterm infants.
We studied 321 visits to a neonatal follow-up clinic. Parents completed the MSD, which measures cognitive, motor, and social abilities. Psychologists and physical therapists administered the Bayley Scales of Infant Development, 3rd edition (Bayley-III) cognitive and motor scales.
The median (range) gestational age was 28 (23, 34) weeks and birthweight 980 (400, 2700) g. Corrected age at study participation ranged 5–35 months. The mean (standard deviation) Bayley-III motor score was 94 (16); cognitive 98 (16); and MSD 91 (18). Internal consistency of the MSD was moderate to high (Cronbach alpha of 0.65 to 0.88). The MSD was moderately correlated with the Bayley-III motor (Pearson r=0.49, P<0.001) and cognitive (r=0.45, P<0.001) scales. The area under the receiver operating characteristic curve was 0.88 (95% confidence interval [CI] 0.81, 0.95) for the MSD to detect a low Bayley-III motor score (<70); and 0.88 (95% CI 0.82, 0.95) for a low cognitive score, indicating good discrimination.
The MSD has good internal and concurrent validity, and may be useful for neurodevelopmental assessment of former preterm and VLBW infants in clinical and research settings.
PMCID: PMC3564502  PMID: 23374065
6.  Dermatoglyphic patterns, very low birth weight, and blood pressure in adolescence 
AIMS—To test the null hypotheses that finger and palm prints have no relation with fetal growth or adolescent blood pressure.
METHODS—All 128 singleton, unimpaired, very low birth weight (VLBW; ⩽1500 g) infants born to mothers resident in the county of Merseyside in 1980 and 1981 were studied retospectively. The comparison group consisted of 128 age, sex, and school matched children. Main outcome measures were blood pressure at age 15 years, birth weight ratio, fingerprint patterns, and palmar AtD angles.
RESULTS—The VLBW index population had a significantly higher systolic blood pressure than the comparison group (mean difference 3.2mm Hg). The difference in diastolic blood pressure between the VLBW index and the matched comparison group was not significant. No significant differences were found in the palmar AtD angles or in the fingerprint proportions of arches, loops, and whorls and no correlation was found between fingerprint patterns and blood pressure. Among the VLBW index population, both height and right palmar AtD angle were independently and significantly correlated with and explained 12.1% of the variance in the systolic blood pressure. Birth weight ratio, as a measure of fetal growth restriction, had no significant correlation with systolic blood pressure.
CONCLUSIONS—The higher systolic blood pressure of adolescents who were of very low birth weight compared with the matched comparison group is not associated with fingerprint patterns or birth weight ratio as markers for fetal growth restriction.

PMCID: PMC1721212  PMID: 11124918
7.  Effect of early postnatal neutropenia in very low birth weight infants born to mothers with pregnancy-induced hypertension 
Korean Journal of Pediatrics  2012;55(12):462-469.
In this study, we aimed to investigate the perinatal clinical conditions of very low birth weight (VLBW) infants born to mothers with pregnancy-induced hypertension (PIH) focusing on the effects of early postnatal neutropenia.
We reviewed the medical records of 191 VLBW infants who were born at Konyang University Hospital, between March 2003 and May 2011. We retrospectively analyzed the clinical characteristics of the infants and their mothers and compared the incidence of perinatal diseases and mortality of the infants according to the presence or absence of maternal PIH and neutropenia on the first postnatal day.
Infants born to mothers with PIH showed an increased incidence of neutropenia on the first postnatal day (47.4%), cesarean delivery, and intrauterine growth restriction. When the infants born to mothers with PIH showed neutropenia on the first postnatal day, their incidence of respiratory distress syndrome (RDS) was increased (P=0.031); however, the difference was not found to be significant through logistic regression analysis. In all the VLBW infants, neutropenia on the first postnatal day was correlated with the development of RDS. The incidence of the other perinatal diseases involving sepsis and mortality did not significantly differ according to the presence or absence of neutropenia in infants born to mothers with PIH.
In VLBW infants born to mothers with PIH, the incidence of neutropenia on the first postnatal day was increased and it was not significantly correlated with the development of perinatal diseases involving RDS, sepsis, and mortality.
PMCID: PMC3534159  PMID: 23300501
Pregnancy-induced hypertension; Neutropenia; Very low birth weight; Preterm infants; Perinatal diseases
8.  Racial disparities in health-related quality of life in a cohort of very low birth weight 2- and 3-year olds with and without asthma 
Journal of epidemiology and community health  2011;66(7):10.1136/jech.2010.132886.
Children born very low birth weight (VLBW) are at risk for low health-related quality of life (HRQoL), compared to normal birthweight peers, and racial disparities may compound the difference. Asthma is the most pervasive health problem among VLBW children, and is also more common among black than white children, partly due to unfavorable environmental exposures. This study explores racial disparities in HRQoL among VLBW children and examines whether potential disparities can be explained by asthma and neighborhood disadvantage.
The study population was the Newborn Lung Project, a cohort of infants (n=660) born VLBW in 2003–2004 in Wisconsin, USA, who were followed up at age 2–3. Multi-level linear regression models were used to examine the contributions of asthma, neighborhood disadvantage, and other child and family socio-demographic covariates, to racial disparities in HRQoL at age 2–3. Child’s HRQoL was measured using the Pediatric Quality of Life Inventory (PedsQL 4.0).
VLBW, Black, non-Hispanic children, on average, score nearly 4-points lower (p<0.01) on HRQoL than do white, non-Hispanic children. Including asthma reduces the difference between black and white children from −3.6 (p<0.01) to 0.08 (p>0.05). We found no evidence that the relationship between asthma and HRQoL differs by race. The interaction between neighborhood disadvantage and asthma is statistically significant, with further examination suggesting that racial disparities are particularly pronounced in the most advantaged neighborhoods.
We found that the black disadvantage in HRQoL among 2–3 year old VLBW children likely stems from high prevalence of asthma. Neighborhood attributes did not further explain the disparity, as the racial difference was particularly pronounced in advantaged neighborhoods.
PMCID: PMC3879152  PMID: 21330462
very low birth weight; health-related quality of life; neighborhood; disadvantage; asthma
9.  Reference Values of Urinary Neutrophil Gelatinase-Associated Lipocalin in Very Low Birth Weight Infants 
Pediatric research  2009;66(5):528-532.
In very low birth weight (VLBW) infants, acute renal impairment (ARI) is common but there is no consensus about criteria for its diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is an early and sensitive indicator of renal impairment in experimental animals, children, and adults. Urinary NGAL (UNGAL) is detectable in VLBW infants; however, there is no reference range in this population. The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for ARI. UNGAL concentration was determined in urine samples collected from day of life (DOL) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses, selected from a total of 145 prospectively enrolled appropriate for gestational age (AGA) inborn VLBW premature infants. The birth weight and gestational age ranges were 790–1490 grams and 26–33 weeks, respectively. The median, 95th and 99th percentiles, and range of pooled UNGAL values were 5 ng/ml, 50 ng/ml, 120ng/ml, and 2–150 ng/ml, respectively. Greater variability and higher quantile levels of UNGAL were observed in females vs. males. In conclusion, a reference range for UNGAL in VLBW infants, similar to that in children and adults, has been established.
PMCID: PMC3482111  PMID: 19680166
10.  Maternal support in the delivery room and birthweight among African-American women. 
OBJECTIVES: We performed a hospital-based case control study of African-American mothers to explore the relationship between maternal support by a significant other in the delivery room and very low birthweight (VLBW). METHODS: We administered a structured questionnaire to mothers of VLBW (less than 1,500 g; N=104) and normal birthweight (greater or equal to 2,500 g; N=208) infants. RESULTS: The odds ratio for VLBW comparing women without social support in the delivery room to those with a companion was 3.5 (2.1-5.8). Several traditional risk factors were not associated with VLBW, but older maternal age and perceived racial discrimination were. CONCLUSIONS: Maternal support in the delivery room or factors closely associated with it significantly decreases the odds of delivering a VLBW infant for African-American women.
PMCID: PMC2594958  PMID: 14977277
11.  Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: Longitudinal assessment during the first 15 months of corrected age 
BMC Pediatrics  2012;12:37.
Very low birth weight (VLBW) infants (< 1,500 g) with bronchopulmonary dysplasia (BPD) develop lung damage caused by mechanical ventilation and maturational arrest. We compared functional lung development after discharge from hospital between VLBW infants with and without BPD.
Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O2 supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]). Mean gestational age (26 vs. 29 weeks), birth weight (815 g vs. 1,125 g), and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%), differed significantly between BPD infants and controls.
Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRCpleth), maximal expiratory flow at the FRC (V'max FRC), or blood gas (pO2, pCO2) levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways) were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight.
Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.
PMCID: PMC3362756  PMID: 22443188
12.  Expressed breast milk as 'connection' and its influence on the construction of 'motherhood' for mothers of preterm infants: a qualitative study 
Breast milk is considered the optimal nutrition for all newborn infants. While there is high initiation of lactation among mothers of preterm infants in Australia, there is a rapid decline of continued lactation. Furthermore, there is an inverse relationship between infant gestation and duration of lactation. To better understand the breastfeeding experience of parents of very low birth weight (VLBW) preterm infants an interpretive phenomenological study was conducted.
This longitudinal study was conducted using an interpretive phenomenological approach. Data were collected from 17 parents through 45 individual interviews with both mothers and fathers, from birth to 12 months of age. This data was then transcribed verbatim and analysed using thematic analysis.
The analysis identified six primary themes: the intention to breastfeed naturally; breast milk as connection; the maternal role of breast milk producer; breast milk as the object of attention; breastfeeding and parenting the hospitalised baby and the demise of breastfeeding. This paper reports on the theme of 'breast milk as connection'.
Providing expressed breast milk offered one way the mothers could be physiologically and emotionally connected to their preterm infant while they were in the constant care of hospital staff. Indeed, breast milk was considered the only way the new mother could connect her body (or part there of) to her preterm baby in hospital. This sense of connection however, comes at a cost. On the one hand, the breast milk offers a feeling of connection to the baby, but, on the other, this connection comes only after disconnection of the mother and baby and – through breast expression – mother and her milk. This ability of breast milk to connect mother and baby makes the expressed breast milk highly valued, and places unexpected pressure on the mother to produce milk as integral to her sense of motherhood.
The findings of this study have implications for healthcare practice. It is evident that the association of breastfeeding success with mothering success only jeopardises some families' self-esteem and sense of parenting ability. These findings suggest it would be beneficial to find alternate ways to connect preterm infants and their parents in the preterm nursery environment, and find more positive ways to support breastfeeding.
PMCID: PMC2628335  PMID: 19091075
13.  Immune responses in mothers of term and preterm very-low-birth-weight infants. 
Differences in the levels of immune cell subsets present in peripheral blood have been demonstrated based on sociodemographic factors such as age and race. Postpartal women, who are recovering from the immune changes that are concomitant with pregnancy, have lymphocyte and monocyte values that differ from other populations. A subgroup of postpartal women, mothers who deliver preterm very-low-birth-weight (VLBW) (< or = 1,500 g) infants, may have further differences in values of immune cell subsets and in immune functioning either because of hormonal factors or lifestyle changes or because of the stress they experience after their infant's birth and for the first few months of infant caretaking. This study examined anxiety, depression, and immune cell phenotypes in 30 mothers of VLBW infants and in 30 mothers of healthy term infants over the first 4 postpartal months to determine if mothers of preterm VLBW infants differed from mothers of healthy term infants in psychological and immunologic parameters. Additionally, lymphocyte proliferation and natural killer cell functional assays were performed in a subset of mothers. Mothers of VLBW infants had increased anxiety and decreased lymphocyte proliferation compared to mothers of term infants. When lymphocyte and monocyte subsets were compared over time between the two groups of mothers differences were found in CD8, CD20, CD3-/CD56+, CD14, and HLA class II Ia on monocytes. Mothers with high-fat diets had lower percentages of some monocytes (CD14), lymphocytes (CD4+/CD45RA+), and natural killer cells (CD3-/CD57+) during the first 4 postpartal months.
PMCID: PMC170597  PMID: 9302206
14.  The Initial Maternal Cost of Providing 100 mL of Human Milk for Very Low Birth Weight Infants in the Neonatal Intensive Care Unit 
Human milk (HM) feeding is associated with lower incidence and severity of costly prematurity-specific morbidities compared to formula feeding in very low birth weight (VLBW; <1,500 g) infants. However, the costs of providing HM are not routinely reimbursed by payers and can be a significant barrier for mothers. This study determined the initial maternal cost of providing 100 mL of HM for VLBW infants during the early neonatal intensive care unit (NICU) stay.
This secondary analysis examined data from 111 mothers who provided HM for their VLBW infants during the early NICU stay. These data were collected during a multisite, randomized clinical trial where milk output and time spent pumping were recorded for every pumping session (n = 13,273). The cost analysis examined the cost of the breast pump rental, pump kit, and maternal opportunity cost (an estimate of the cost of maternal time).
Mean daily milk output and time spent pumping were 558.2 mL (SD = 320.7; range = 0–2,024) and 98.7 minutes (SD = 38.6; range = 0–295), respectively. The mean cost of providing 100 mL of HM varied from $2.60 to $6.18 when maternal opportunity cost was included and from $0.95 to $1.55 when it was excluded. The cost per 100 mL of HM declined with every additional day of pumping and was most sensitive to the costs of the breast pump rental and pump kit.
These findings indicate that HM is reasonably inexpensive to provide and that the maternal cost of providing milk is mitigated by increasing milk output over the early NICU stay.
PMCID: PMC2879042  PMID: 20113201
15.  The Initial Maternal Cost of Providing 100 mL of Human Milk for Very Low Birth Weight Infants in the Neonatal Intensive Care Unit 
Breastfeeding Medicine  2010;5(2):71-77.
Human milk (HM) feeding is associated with lower incidence and severity of costly prematurity-specific morbidities compared to formula feeding in very low birth weight (VLBW; <1,500 g) infants. However, the costs of providing HM are not routinely reimbursed by payers and can be a significant barrier for mothers. This study determined the initial maternal cost of providing 100 mL of HM for VLBW infants during the early neonatal intensive care unit (NICU) stay.
This secondary analysis examined data from 111 mothers who provided HM for their VLBW infants during the early NICU stay. These data were collected during a multisite, randomized clinical trial where milk output and time spent pumping were recorded for every pumping session (n = 13,273). The cost analysis examined the cost of the breast pump rental, pump kit, and maternal opportunity cost (an estimate of the cost of maternal time).
Mean daily milk output and time spent pumping were 558.2 mL (SD = 320.7; range = 0–2,024) and 98.7 minutes (SD = 38.6; range = 0–295), respectively. The mean cost of providing 100 mL of HM varied from $2.60 to $6.18 when maternal opportunity cost was included and from $0.95 to $1.55 when it was excluded. The cost per 100 mL of HM declined with every additional day of pumping and was most sensitive to the costs of the breast pump rental and pump kit.
These findings indicate that HM is reasonably inexpensive to provide and that the maternal cost of providing milk is mitigated by increasing milk output over the early NICU stay.
PMCID: PMC2879042  PMID: 20113201
16.  Risk Factors for Umbilical Venous Catheter-Associated Thrombosis in Very Low Birth Weight Infants 
Pediatric blood & cancer  2009;52(1):75-79.
Thrombosis in neonates is a rare but serious occurrence, usually associated with central catheterization. The objective of this study was to investigate the risk factors associated with catheter related thrombosis in very low birth weight (VLBW) infants.
The present retrospective study was performed using data from a randomized trial of duration of umbilical venous catheters (UVC) placement among infants <1250 g birth weight. Twenty-two cases of UVC-associated thrombosis were identified in this sample. The remaining study sample (n=188) served as the comparison group. Data on thrombosis, platelets, gestational age, birth weight, hematocrit, serum sodium, maternal preeclampsia, blood group, infant of diabetic mother and demographic factors were collected using database and record review.
Among the total subjects (n=210), 112 (53%) were males and 126 (60%) were Caucasians, with mean gestational age of 27.7 ± 2.1 weeks (standard deviation) and mean birth weight of 923 ± 195 grams. Bivariate analysis revealed significant association of thrombosis with hematocrit >55% in the first week (odds ratio [OR] 5.4; 95% confidence interval [CI] 2.0-14.6; p=0.0003), being small for gestational age (OR, 2.9; 95% CI, 1.2-7.4; p=0.02) and maternal preeclampsia (OR, 3.97; 95% CI, 1.6-9.84; p=0.0017). In multivariate logistic regression analysis, only hematocrit >55% was independently associated with thrombus (OR, 3.7; 95% CI 1.1-11.8; p=0.03).
This study demonstrates a significant, independent association between elevated hematocrit and development of UVC-associated thrombosis. Careful monitoring for catheter-associated thrombosis may be indicated in VLBW infants who have hematocrit >55% in the first week of life.
PMCID: PMC2585148  PMID: 18680150
neonate; thrombosis; risk factors; umbilical venous catheters
17.  Dynamic Change of Fecal Calprotectin in Very Low Birth Weight Infants during the First Month of Life 
Neonatology  2008;94(4):267-271.
Calprotectin is a cytosolic component of neutrophils. Fecal calprotectin (FC) level is a useful marker for exacerbation of inflammatory bowel disease in children. FC may be a useful marker for necrotizing enterocolitis (NEC).
To determine normal baseline levels of FC and observe dynamic changes of FC levels over the first postnatal month in very low birth weight (VLBW) infants.
FC levels of 14 VLBW infants (gestational age 23–30 weeks, birth weight ≤1,500 g) were serially measured in the first postnatal month. Demographics, feeding regimens, antibiotic use, laboratory and x-ray results, and maternal information were recorded. We assessed how FC levels changed over time, varied with nutritional source and differed between sick versus well infants.
FC levels were not related to gestational age or feedings regimen. FC levels tended to decrease with increasing age (p = 0.121) and feeding volumes (p = 0.179). FC levels differed between ‘well’ and ‘sick’ infants (122.8 ± 98.9 vs. 380.4 ± 246.3 μg/g stool, p < 0.001). FC >350 μg/g stool was noted with signs of gastrointestinal injury, such as bloody stool and bowel perforation. FC levels decreased after initiation of treatments in sick infants who recovered.
FC levels may be a marker for early diagnosis and resolution of gastrointestinal illnesses in VLBW infants. Its utility for early diagnosis and assessment of resolution of NEC should be studied in a larger cohort of VLBW infants.
PMCID: PMC2790758  PMID: 18784422
Fecal calprotectin; Very low birth weight infant; Necrotizing enterocolitis; Diagnostic marker
18.  Delayed Cord Clamping in Very Preterm Infants Reduces the Incidence of Intraventricular Hemorrhage and Late-Onset Sepsis: A Randomized, Controlled Trial 
Pediatrics  2006;117(4):1235-1242.
This study compared the effects of immediate (ICC) and delayed (DCC) cord clamping on very low birth weight (VLBW) infants on 2 primary variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC). Other outcome variables were late-onset sepsis (LOS) and intraventricular hemorrhage (IVH).
Study Design
This was a randomized, controlled unmasked trial in which women in labor with singleton fetuses <32 weeks' gestation were randomly assigned to ICC (cord clamped at 5–10 seconds) or DCC (30–45 seconds) groups. Women were excluded for the following reasons: their obstetrician refused to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa, or rapid delivery after admission.
Seventy-two mother/infant pairs were randomized. Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in maternal and infant demographic, clinical, and safety variables. There were no differences in the incidence of our primary outcomes (BPD and suspected NEC). However, significant differences were found between the ICC and DCC groups in the rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus 8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There was a trend toward higher initial hematocrit in the infants in the DCC group.
Delayed cord clamping seems to protect VLBW infants from IVH and LOS, especially for male infants.
PMCID: PMC1564438  PMID: 16585320
delayed cord clamping; intraventricular hemorrhage; IVH; late-onset sepsis; VLBW infants; randomized; controlled trial
19.  Day care attendance and risk for respiratory morbidity among young very low birth weight children 
Pediatric pulmonology  2009;44(11):1093-1099.
Daycare attendance and very low birth weight (VLBW, ≤1500 grams) are associated with respiratory morbidity during childhood. The objective of this study was to evaluate whether daycare attendance is associated with even higher risk for respiratory problems among VLBW children. We hypothesized that VLBW children attending daycare, in a private home or daycare center, are at higher risk for respiratory problems than VLBW children not attending daycare. We also investigated whether the effect of daycare is independent or synergistic with respiratory risk resulting from being VLBW, as indicated by having bronchopulmonary dysplasia (BPD) as a neonate. We conducted a prospective study of VLBW children followed from birth to age 2–3 (N=715). Logistic regression was used to evaluate the relationship between daycare attendance and respiratory problems, adjusting for known neonatal risk factors for poor respiratory outcomes. Attending daycare in either a private home or in a daycare center was significantly associated with higher risk of lower respiratory infections than never attending. Attending a daycare center was also associated with higher risk for wheezy chest, cough without a cold, and respiratory medication use. While having BPD was associated with increased risk for respiratory problems, daycare attendance and BPD were not found to be synergistic risk factors for respiratory problems among VLBW children, but acted independently to increase risk. This implies that the increase in risk for respiratory problems associated with daycare attendance maybe similar among VLBW children and those of normal birth weight.
PMCID: PMC2783181  PMID: 19824048
Very low birth weight; Respiratory morbidity; Child daycare centers; Population-based study
20.  Home uterine activity monitoring in the prevention of very low birth weight. 
Public Health Reports  1997;112(5):433-439.
OBJECTIVES: Despite controversy regarding the efficacy of home uterine activity monitoring (HUAM), it is currently licensed for detection of preterm labor in women with previous preterm deliveries. In practice, however, it is being more widely utilized in an effort to prevent preterm delivery. This study seeks to determine which group of mothers delivering very low birth weight (VLBW) infants would have qualified for HUAM given three different sets of criteria and in which women it could have been used to help prolong gestation. METHODS: The authors reviewed the medical records of mothers of VLBW infants born in five U.S. locations (N = 1440), retrospectively applying three sets of eligibility criteria for HUAM use: (a) the current FDA licensing criterion for use of HUAM, a previous preterm birth; (b) indication for HUAM commonly cited in published reports; (c) a broad set of criteria based on the presence of any reproductive or medical conditions that might predispose to premature delivery. The authors then analyzed the conditions precipitating delivery for each group to determine whether delivery might have been prevented with HUAM and tocolytic therapy. RESULTS: Only 4.4% of the total group of women delivering VLBW infants would have been eligible for HUAM under the FDA criterion and might potentially have benefited from this technology. If extremely broad criteria had been applied to identify those eligible for monitoring, under which almost 80% of all women who delivered VLBW infants would have been monitored, only 20.3% of the total group would have been found eligible and would potentially have benefited. If such broad criteria were applied to all pregnant women, a sizable proportion of pregnancies would be monitored at great expense with small potential clinical benefit. CONCLUSIONS: Because VLBW births are usually precipitated by conditions that are unlikely to benefit from HUAM, this technology will have little impact on reducing VLBW and neonatal mortality rates. More comprehensive preventive strategies should be sought.
PMCID: PMC1381952  PMID: 9323396
21.  Heart rate characteristics and neurodevelopmental outcome in very low birth weight infants 
Journal of Perinatology  2009;29(11):750-756.
Sepsis in very low birth weight (VLBW) infants has been associated with an increased risk of adverse developmental outcome. We have identified abnormal heart rate characteristics (HRCs) that are predictive of impending sepsis, and we have developed a summary measure of an infant's abnormal HRCs during the neonatal hospitalization that we refer to as the cumulative HRC score (cHRC).
In this study, we tested the hypothesis that increasing cHRC is associated with an increasing risk of adverse neurodevelopmental outcome in VLBW infants.
Data were collected on 65 VLBW infants whose HRCs were monitored while in the neonatal intensive care unit and who were examined at 12 to 18 months adjusted age. Using the Bayley Scale of Infant Development-II, we identified delays in early cognitive function (i.e., Mental Developmental Index <70) and psychomotor development (i.e., Psychomotor Developmental Index <70). Cerebral palsy (CP) was diagnosed using a standard neurological examination.
Increasing cHRC score was associated with an increased risk of CP (odds ratio per 1 standard deviation increase in cHRC: 2.6, 95% confidence limits: 1.42, 5.1) and delayed early cognitive development [odds ratio: 2.3 (1.3; 4.3)]. These associations remain statistically significant when adjusted for major cranial ultrasound abnormality. There was an association of increasing cHRC and delayed psychomotor development, which did not reach statistical significance [odds ratio: 1.7 (1.0, 3.0)].
Among VLBW infants, the cumulative frequency of abnormal HRCs, which can be assessed non-invasively in the neonatal intensive care unit, is associated with an increased risk of adverse neurodevelopmental outcome.
PMCID: PMC2834345  PMID: 19554011
cerebral palsy; developmental delay; very low birth weight; bayley scales of infant development; heart rate characteristics; heart rate variability
22.  Controlled study of ocular morbidity in school children born preterm. 
Two hundred children who were of very low birth weight (VLBW) (1500 g or less) and 193 controls who were of normal birth weight (NBW) were examined at approximately 9 years of age. Binocular visual acuity of 6/6 or better was noted in 178 (89.5%) VLBW children and 189 (97.9%) NBW children. Visual morbidity was significantly higher among VLBW children. Strabismus was present in 38 (19%), cicatricial retinopathy of prematurity in 13 (6.5%), and optic atrophy in six (3%) children in this group. Children who were VLBW were also more myopic than the NBW controls. Optic atrophy was frequently associated with cerebral dysfunction. Regular assessments to identify ocular abnormalities in children who were VLBW are recommended.
PMCID: PMC504339  PMID: 1420053
23.  Early working memory and maternal communication in toddlers born very low birth weight 
Early working memory is emerging as an important indicator of developmental outcome predicting later cognitive, behavioural and academic competencies. The current study compared early working memory in a sample of toddlers (18–22 months) born very low birth weight (VLBW; n = 40) and full term (n = 51) and the relationship between early working memory, mental developmental index (MDI), and maternal communication in both samples.
Early working memory, measured by object permanence; Bayley mental developmental index; and maternal communication, coded during mother-toddler play interaction, were examined in 39 toddlers born VLBW and 41 toddlers born full term.
Toddlers born VLBW were found to be 6.4 times less likely to demonstrate attainment of object permanence than were toddlers born full term, adjusting for age at testing. MDI and maternal communication were found to be positively associated with attainment of object permanence in the VLBW group only.
The difference found in the early working memory performance of toddlers born VLBW, compared with those born full term, emphasizes the importance of assessing early working memory in at-risk populations, while the maternal communication finding highlights potential targets of intervention for improving working memory in toddlers born VLBW.
PMCID: PMC3014313  PMID: 19154525
Early working memory; Maternal communication; Object permanence; Very low birth weight
24.  Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years 
Children born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW, <1500 g; hereafter called VP/VLBW) are at risk for behavioural and emotional problems during school age and adolescence. At school entrance these problems may hamper academic functioning, but evidence on their occurrence at this age in VP/VLBW children is lacking.
To provide information on academic functioning of VP/VLBW children and to examine the association of behavioural and emotional problems with other developmental problems assessed by paediatricians.
Design, setting and participants
A cohort of 431 VP/VLBW children aged 5 years (response rate 76.1%) was compared with two large national samples of children of the same age (n = 6007, response rate 86.9%).
Outcome measures
Behavioural and emotional problems measured by the Child Behavior Checklist (CBCL), and paediatrician assessment of other developmental domains among VP/VLBW children.
The prevalence rate of a CBCL total problems score in the clinical range was higher among VP/VLBW children than among children of the same age from the general population (13.2% v 8.7%, odds ratio 1.60 (95% confidence interval 1.18 to 2.17)). Mean differences were largest for social and attention problems. Moreover, they were larger in children with paediatrician‐diagnosed developmental problems at 5 years, and somewhat larger in children with severe perinatal problems.
At school entrance, VP/VLBW children are more likely to have behavioural and emotional problems that are detrimental for academic functioning. Targeted and timely help is needed to support them and their parents in overcoming these problems and in enabling them to be socially successful.
PMCID: PMC2672756  PMID: 16877476
25.  Hospital Volume and Mortality of Very Low Birth Weight Infants in South America 
Health Services Research  2012;47(4):1502-1521.
To assess the effects of hospital volume of very low birth weight (VLBW) infants on in-hospital mortality of VLBW and very preterm birth (VPB) infants in South America. Data sources/study setting: Birth registry data for infants born in 1982–2008 at VLBW or very preterm in 66 hospitals in Argentina, Brazil and Chile.
Regression analyses that adjust for several individual-level demographic, socioeconomic and health factors, hospital-level characteristics, and country fixed effects are employed. Data collection/extraction methods: Physicians interviewed mothers before hospital discharge and abstracted hospital medical records using similar methods at all hospitals.
Principal Findings
Volume has significant non-linear beneficial effects on VLBW and VPB in-hospital survival. The largest survival benefits – more than 80% decrease in mortality rates – are with volume increases from low to medium or medium-high levels (from ≤ 25 to 72 infants annually) with significantly lower incremental benefits thereafter. The cumulative volume effects are maximized at the 121–144 annual VLBW infant range – about 90% decrease in mortality rates compared to <25 VLBW infants annually.
Increasing the access of pregnancies at-risk of VLBW and VPB to medium or high volume hospitals up to 144 VLBW infants per year may substantially improve in-hospital infant survival in the study countries.
PMCID: PMC3360993  PMID: 22352946

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