Progression of Enteral Feeding Volumes in Extremely Low Birth Weight Infants in the "Connection Trial".

OBJECTIVE: Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the "Connection Trial." STUDY DESIGN: A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes. RESULTS: Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22-0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension. CONCLUSION: This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression. KEY POINTS: · Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.. · Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.. · Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols..

In the grey zone-survival and morbidities of periviable births.

OBJECTIVE: To compare the survival and morbidities of infants born between 22 0/7-25 6/7 weeks of gestation. STUDY DESIGN: This observational cohort study consisted of 187 eligible infants liveborn at a single, Level III Neonatal Intensive Care Unit (NICU) between June 1, 2009, and December 31, 2016, in Cleveland, Ohio. Infants with recognized syndromes or major congenital malformations were excluded from the review. RESULT: The rate of survival to discharge for NICU-admitted infants born at 22- and 23- week was 56% and 54% respectively at our institution. There was no trend observed between gestational ages and incidence of necrotizing enterocolitis (NEC), patent ductus arteriousus (PDA), sepsis, or severe intraventricular hemorrhage (IVH- Grade 3 or 4). The infants born at 22 weeks had a higher incidence of retinopathy of prematurity (ROP) as compared to 25 weeks gestation (p < 0.001). The need for home oxygen was significantly higher in the smallest infants 70% at 22 weeks, 62% and 60% at 23 and 24 weeks versus 33% at 25 weeks gestation (p < 0.007). Those born at 22 weeks had the same rate of survival to discharge with severe IVH as those born at 23 weeks but required fewer VP shunts (p > 0.52). CONCLUSIONS: The course of extremely preterm infants shows no difference between those born at 22 and 23 weeks of gestation in our NICU with regards to both mortality and short-term morbidities, although they differed marginally from 24 week gestation infants and significantly from those born at 25 weeks gestation.

Anogenital distance is determined during early gestation in humans.

STUDY QUESTION: Does cord blood androgen level obtained at birth affect the AGD in human newborns? SUMMARY ANSWER: In human newborns, though males have a significantly longer AGD compared to females (as early as 22 weeks of gestation) the AGD is not affected by androgen levels at birth in both the sexes. WHAT IS KNOWN ALREADY: Animal studies have reported a critical time period in early fetal life, termed the masculinization programming window (MPW) during which AGD is fixed by in utero androgen action and is unaffected by testosterone levels later during gestation. Thus, AGD may serve as a lifelong biomarker of androgen exposure during this window. This MPW is hypothesized to occur in humans at 8-14 weeks of gestation during which AGD is fixed. The effect of androgens (testosterone) on AGD after the MPW in humans is not known. Furthermore, altered AGD has been associated with various human reproductive health disorders in both males and females. STUDY DESIGN, SIZE, DURATION: A prospective descriptive cohort study was performed using data from randomly selected neonates (n = 205) born at a single center over a period of 1 year (August 2015 to August 2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: AGDs in male (n = 117) and female infants (n = 88) together with penile width, glans girth and stretched penile length were measured by trained caregivers. Gestation ranged from 22 to 41 weeks and infants were examined within 24 h of birth (within 48-72 h in very sick preterm infants after clinical stabilization). AGD-1 was measured from the center of the anus to the posterior base of scrotum in males or to the posterior fourchette in females. AGD-2 was measured from the center of the anus to the anterior base of the penis in males or to the clitoris in females. Sex steroid hormones (testosterone, 17-OH progesterone (17-OHP) and androstenedione) were measured in serum prepared from umbilical cord blood samples taken at birth, using liquid chromatography-tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Males had a significantly lower gestational age (mean ± SD; 34.6 ± 4.9 versus 36.1 ± 4.1 weeks, P = 0.04), and a significantly longer AGD-1 (mean ± SD; 21.6 ± 6.0 versus 12.7 ± 3.8 mm, P < 0.001) and AGD-2 (41.9 ± 8.7 versus 33.9 ± 7.1 mm, P = 0.004) compared to female infants, respectively. The cord serum testosterone levels were significantly higher for male than female infants [median, interquartile range; 13.0 (7.3, 20.5) versus 4.1 (2.5, 5.9), ng/dl, P < 0.001]. There was no difference in levels of 17-OHP (P = 0.697) or androstenedione (P = 0.601) between the two sexes. On multiple regression analysis after adjusting for potential confounders, none of the AGD's in both males and females correlated with any sex steroid hormonal levels. We also provide normative charts for penile length, penile width and glans girth in preterm and term infants. LIMITATIONS, REASONS FOR CAUTION: No data were collected on family history of genital malformation, infertility or hormonal disorders, parental endocrine-disrupting chemical exposure or diet pattern, any of which might have influenced the AGD and/or sex steroid hormone levels in the offspring. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that AGD in humans, like animals, is fixed in early gestation (likely during the hypothesized MPW) and is unaffected by androgen levels thereafter. Thus, AGD can serve as a biomarker of in utero androgen action during early gestation (likely 8-14 weeks) in humans. As such, causes of human newborn and adult reproductive health disorders, such as endocrine disruptors, should be explored during early gestation. However, further larger studies are needed to help corroborate these findings. STUDY FUNDING/COMPETING INTERESTS: No specific funding was obtained for this study, and all authors have no conflict of interest to declare.

Comparison of different definitions of acute kidney injury in extremely low birth weight infants.

BACKGROUND: The definition of acute kidney injury (AKI) has evolved over the years, and three definitions have been adapted including pediatric risk injury failure, loss of kidney function (pRIFLE), Acute Kidney Injury Network (AKIN), and Neonatal Modified Kidney Disease Improving Global Outcomes (KDIGO). We sought to report the prevalence and outcome of (AKI) according to the three existing definitions in extremely low birth weight (ELBW) infants. METHODS: In a retrospective cohort study, medical records of all ELBW infants (<1000 g) admitted to our neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Infants' demographics, anthropometric measurements, and clinical characteristics were collected at the time of birth and at discharge from the NICU. Infants were staged according to the three different definitions. RESULTS: During the study period, 483 ELBW infants met our inclusion criteria. The incidence of AKI was 56, 59, and 60% according to pRIFLE, AKIN, and KDIGO, respectively. Mortality, NICU length of stay, and serum creatinine (SCr) at NICU discharge were higher in infants with advanced AKI stages regardless of the definition. In addition, discharge NICU weight and length z scores were lower in infants with advanced AKI stages. SCr at 72 h of life and SCr peak were predictable of NICU mortality [AUC 0.667 (95% CI 0.604-0.731), p < 0.001 and AUC 0.747 (95% CI 0.693-0.801), p < 0.001, respectively]. CONCLUSION: Regardless of the definition, advanced AKI is associated with increased mortality, prolonged NICU length of stay, and poor growth in ELBW infants. SCr at 72 h of life and SCr peak may be predictable of NICU mortality.

Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury.

OBJECTIVE: To study the outcome of extremely low birth weight (ELBW) infants with a history of acute kidney injury (AKI). METHOD: In a retrospective, case control study, medical records of all ELBW infants admitted to the neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Medical records were reviewed for infants' demographics, blood pressure (BP) at NICU discharge and at ≥3 years, and estimated glomerular filtration rate (eGFR) at ≥2 years. RESULTS: During the study period, 222 patients met the inclusion criteria, of whom 10% (23 out of 222) had AKI stage 2 and 3, 39% (87 out of 222) had AKI stage 1, and the rest did not have AKI. At NICU discharge, there was a difference in diastolic BP (DBP) among infants who had AKI stages 2 and 3, those who had stage 1, and those who did not have AKI (53 ± 12 vs 46 ± 9 vs 46 ± 11 mmHg respectively; p = 0.007), and 11% (23 out of 209) had hypertension (HTN). Although there was a significant correlation between the rise in SCr and DBP at NICU discharge in infants with AKI (R = 0.304; p = 0.004), there was no difference in HTN between infants with and those without AKI. At ≥2 years of age, 4% (5 out of 120) across all groups had an eGFR < 90 ml/min/1.73m2 or chronic kidney disease (CKD). At ≥3 years of age, 5% (11 out of 222) had HTN. CONCLUSION: At NICU discharge, infants with AKI stages 2 and 3 have a higher DBP than infants with stage 1 AKI and those who did not have AKI. However, there is no difference in the rate of HTN between the two groups. At ≥2 years ELBW infants are at risk for CKD independently of whether or not they develop neonatal AKI.