Nansi S. Boghossian

Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple-Gestation Births

OBJECTIVES To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs. STUDY DESIGN The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs. RESULTS LOS occurred in 25.0% (3797 of 15,178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs. CONCLUSION LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.

Changes in diabetes status between pregnancies and impact on subsequent newborn outcomes

OBJECTIVE Pregnancies complicated by gestational diabetes mellitus (GDM) or preexisting diabetes mellitus (DM) are at high risk for adverse newborn outcomes. Whether GDM history, recurrence, or transition to DM modifies such risks is unknown. STUDY DESIGN Medical record data on 62,013 repeat singleton pregnancies were collected retrospectively from women who delivered at least twice in Utah (2002 through 2010). Poisson regression models with robust variance estimators were used to estimate relative risks (RR) and 95% confidence intervals (CI) associated with GDM/DM status at the previous and/or current pregnancy relative to those without GDM/DM at either. Large for gestational age (LGA), shoulder dystocia, preterm birth (<37 weeks), respiratory distress syndrome, and other neonatal morbidities were examined adjusting for study site, maternal age, race, parity, interpregnancy interval, prepregnancy body mass index, and smoking status. RESULTS GDM in the previous pregnancy alone increased the risk of LGA in the current pregnancy (RR, 1.20; 95% CI, 1.05-1.38). Recurrent GDM increased the risks of LGA (RR, 1.76; 95% CI, 1.56-1.98), shoulder dystocia (RR, 1.98; 95% CI, 1.46-2.70), and preterm birth (RR, 1.68; 95% CI, 1.44-1.96) beyond that observed for pregnancies with current GDM alone. Women with GDM in a previous pregnancy that transitioned to DM in the current pregnancy and women with DM prior to the previous pregnancy had increased risks of all above outcomes. CONCLUSION GDM in a previous pregnancy alone without recurrence may still confer an increased LGA risk. Pregnancies complicated by GDM that transition to DM and those with DM prior to the previous pregnancy have the highest risks of adverse newborn outcomes.

Mortality and Morbidity of VLBW Infants With Trisomy 13 or Trisomy 18

OBJECTIVE: Little is known about how very low birth weight (VLBW) affects survival and morbidities among infants with trisomy 13 (T13) or trisomy 18 (T18). We examined the care plans for VLBW infants with T13 or T18 and compared their risks of mortality and neonatal morbidities with VLBW infants with trisomy 21 and VLBW infants without birth defects. METHODS: Infants with birth weight 401 to 1500 g born or cared for at a participating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network during the period 1994–2009 were studied. Poisson regression models were used to examine risk of death and neonatal morbidities among infants with T13 or T18. RESULTS: Of 52 262 VLBW infants, 38 (0.07%) had T13 and 128 (0.24%) had T18. Intensity of care in the delivery room varied depending on whether the trisomy was diagnosed before or after birth. The plan for subsequent care for the majority of the infants was to withdraw care or to provide comfort care. Eleven percent of infants with T13 and 9% of infants with T18 survived to hospital discharge. Survivors with T13 or T18 had significantly increased risk of patent ductus arteriosus and respiratory distress syndrome compared with infants without birth defects. No infant with T13 or T18 developed necrotizing enterocolitis. CONCLUSIONS: In this cohort of liveborn VLBW infants with T13 or T18, the timing of trisomy diagnosis affected the plan for care, survival was poor, and death usually occurred early.

Newborn Adipokines and Birth Outcomes

BACKGROUND Adipokines can serve as a measure of adipose tissue activity. Although birthweight correlates with neonatal adiposity, findings for cord blood levels of adipokines and birth outcomes have been conflicted. Therefore, we determined the cross-sectional associations between adipokines measured in newborn dried blood spots (DBS) and birth outcomes. METHODS The Upstate KIDS study enrolled mothers and infants from 2008 to 2010. Among infants whose parents consented to the use of residual DBS from newborn screening, 2397 singletons and 1240 twins had adipokine measurements from the Human Obesity Panel (R&D Systems) by Luminex. Odds ratios were estimated by multivariable logistic regression for risk of birth outcomes of preterm delivery (<37 weeks for singletons, <32 for twins) and small-for-gestational age (SGA <10th for singletons and <3rd for twins age- and sex-specific percentiles) by adipokine quintiles. Generalised estimating equations were applied to account for correlations between twins. RESULTS Singletons in the lowest compared with the highest quintile of adiponectin were more likely preterm (adjusted odds ratio 3.26; 95% confidence interval [CI] 1.99, 5.34) and SGA (1.81; [95% CI 1.18, 2.77]). Similar associations were observed among twins. Resistin was associated with preterm birth (Q1 vs. Q5: 2.08; [95% CI 1.20, 3.62]) only among singletons. Adipsin had inconsistent associations after adjustment. CONCLUSIONS This large population-based study demonstrates that newborn DBS-measured adipokines are associated with birth outcomes, particularly preterm birth and SGA among those with lower adiponectin levels regardless of plurality.

Maternal Dietary Patterns during Third Trimester in Association with Birthweight Characteristics and Early Infant Growth.

Our analysis examined the impact of maternal dietary patterns and lifestyle factors on markers of fetal growth, specifically birthweight and size for gestational age (small- (SGA) or large-for-gestational age (LGA)). The Infant Feeding Practices Study II, a prospective cohort study, surveyed pregnant women during their 3rd trimester, of which a subgroup (n = 893) completed a food frequency questionnaire. Maternal dietary patterns were evaluated by diet scores (Alternative Healthy Eating Index for Pregnancy and alternate Mediterranean diet) and by carbohydrate quality (glycemic index and glycemic load). Poisson regression with robust standard errors was used to examine the relative risk of SGA and separately LGA, with dietary patterns and other lifestyle factors. Linear regression was used to determine the association of birthweight and early infant growth with better dietary patterns. Relative risk of SGA and LGA was not associated with dietary patterns. Birthweight and infant growth were not associated with maternal diet. Smoking, however, increased the risk of delivering an SGA infant (RR = 2.92, 95% CI: 1.58–5.39), while higher prepregnancy BMI increased the risk of delivering an LGA infant (RR = 1.06, 95% CI: 1.03–1.09). Future studies are needed to evaluate whether deficiencies in more specific maternal dietary nutrients play a role in fetal growth.

Survival and morbidity outcomes for very low birth weight infants with Down syndrome.

OBJECTIVE: Our objective was to compare survival and neonatal morbidity rates between very low birth weight (VLBW) infants with Down syndrome (DS) and VLBW infants with non–DS chromosomal anomalies, nonchromosomal birth defects (BDs), and no chromosomal anomaly or major BD. METHODS: Data were collected prospectively for infants weighing 401 to 1500 g who were born and/or cared for at one of the study centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network in 1994–2008. Risk of death and morbidities, including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late-onset sepsis (LOS), retinopathy of prematurity, and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups. RESULTS: Infants with DS were at increased risk of death (adjusted relative risk: 2.47 [95% confidence interval: 2.00–3.07]), PDA, NEC, LOS, and BPD, relative to infants with no BDs. Decreased risk of death (relative risk: 0.40 [95% confidence interval: 0.31–0.52]) and increased risks of NEC and LOS were observed when infants with DS were compared with infants with other non–DS chromosomal anomalies. Relative to infants with nonchromosomal BDs, infants with DS were at increased risk of PDA and NEC. CONCLUSION: The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for anticipating the need for enhanced surveillance for prevention of these morbidities.

Differences in risk factors for incident and recurrent small-for-gestational-age birthweight: a hospital-based cohort study

Examine whether small‐for‐gestational‐age (SGA) risk factors differed by prior SGA birth.

Ten-Year Review of Major Birth Defects in VLBW Infants

OBJECTIVE: Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care. METHODS: Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics. RESULTS: A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41–3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001). CONCLUSIONS: Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women

Background/objectives:Adherence to the Mediterranean diet (MD), high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean diet score (aMED), anthropometry and measured adiposity by dual-energy x-ray absorptiometry (DXA).Subjects/methods:This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-h dietary recalls over 1–2 menstrual cycles (>97% had ⩾7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake.Results:Participants had an average (s.d.) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist-to-hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% confidence interval (CI): −0.09, −0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI: −0.550, −0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI: 0.002, 0.117).Conclusions:Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD.

Developmental Origins of Cardiovascular Disease

Although cardiovascular disease has traditionally been viewed as a condition of aging individuals, increasing focus has turned to its developmental origins. Since birth weight has been related to cardiovascular disease risk, research into factors such as gravid conditions that affect fetal growth have grown. Associations between maternal diabetes and childhood obesity from sibling studies suggest a causal role, but prospective studies of gestational diabetes remain mixed. Preeclampsia and increased offspring blood pressure have been consistently observed, but evidence for other cardiovascular outcomes is lacking. While maternal obesity is associated with childhood obesity, causality remains unclear and paternal obesity should be investigated as an independent risk factor. Environmental chemical exposures in utero, particularly obesogens, are now emerging as another concern, as is conception via infertility treatment. Few studies have investigated the subclinical measures of endothelial function or atherosclerosis, and more research in these areas may help to reveal the underlying pathogenesis.