Morbidity and Mortality Among Exclusively Breastfed Neonates With MCAD Deficiency
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1 Morbidity and Mortality Among Exclusively Breastfed Neonates With MCAD Deficiency Can (John) Ficicioglu, MD, PhD The Children s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Division of Human Genetics/Metabolism Director, Newborn screening program
2 Study objectives 1) To quantify the current risk of early decompensation in neonates with MCAD 2) To identify factors associated with poor outcomes
3 Study design We completed a retrospective analysis of all neonates referred to our center for an elevated C8 level by the state laboratories of PA, NJ, and Delaware. Inclusion criteria included: - Birth date between Jan 1 st Sept. 1 st 2015, - Elevated C8 on NBS, - Referral to our center by the state laboratory. All patients underwent clinical and laboratory confirmation of the diagnosis
4 Patient population Overall, 66 neonates were evaluated and 47 (70%) were confirmed to have MCAD. 33 confirmed cases 55% of all PA cases 12 confirmed cases 44% of all NJ cases 1 confirmed case
5 One patient had incomplete medical records and excluded from the study Of the 46 MCAD patients, 11 (23.9%) demonstrated signs of metabolic decompensation prior to or at the time of the return of NBS result. Overall, 4 of 46 (8.7%) died or survived sudden cardiac arrest before their newborn screen resulted. Three infants died in the neonatal period, among these two had fatal cardiac arrhythmias and one had a SIDS-like presentation. One patient presented with a fatal cardiac arrhythmia but was resuscitated.
6 Patient characteristics
7 Patient characteristics
8 Adverse Outcomes in Neonates with MCAD Patient Gestational Age (weeks) Birth weight Genotype C8 on NBS Umol/L Initial feeding method Clinical presentation ca985g/c.a985g Breast Hypoglycemia (blood sugar of 12 mg/dl) on day of life 3, followed by cardiac arrest and death ca985g/c.a985g Breast Hypoglycemia and lethargy (blood sugar of 12 mg/dl) on day of life 4, cardiac arrhythmia and death on day of life days 3.60 ca985g/c.a985g 54 Breast Progressive lethargy over days of life 1-2, cardiac arrest at 3 daysof life, resuscitated after 30 minutes of CPR, resulting in hypoxic ischemic encephalopathy days 3.09 ca985g/c.a985g Breast Died while sleeping overnight on day of life ca985g/c.a985g Breast Lethargy and poor feeding on day of life 4 when NBS reported, hypoglycemic (blood glucose 47 mg/dl), acidotic with a serum bicarbonate of 8 mmol/l
9 Adverse Outcomes in Neonates with Patient MCAD Gestational Age (weeks) Birth weight Genotype C8 on NBS Umol/L Initial feeding method Clinical presentation days 3.00 ca985g/c.a985g Breast Lethargy at 24 hours of life, borderline gluocse of 54 mg/dl, started on supplemental formula in response to glucose level ca985g/c.a985g 3.53 Breast Hypoglycemia (blood sugar of 30 mg/dl) on first day of life, required IV glucose and 7 day NICU stay ca985g/c.a985g 8.16 Breast Lethargy on day of life 4, 12 hours after NBS reported, borderline glucose of 58 mg/dl, acidotic with a serum bicarbonate of <5 mmol/l day 3.72 ca985g/c.a985g Breast Noted by family to be lethargic on day of life 4,simultaneously referred to ED because of abnormal NBS, found to be hypoglycemic (blood sugar of 13 mg/dl) ca985g/c.a985g Breast Emesis and poor feeding on day of life 4 when NBS reported, borderline blood glucose of 51 mg/dl, acidotic with a serum bicarbonate of 14 mmol/l, elevated liver enzymes with an ALT of 556 U/L and AST of 267 U/L ca985g/c.a985g Breast Hypoglycemia (blood sugar of 38 mg/dl) after breastfeeding on day of life 4 during ED visit to evaluate abnormal NBS result
10 Rates of early decompensation are higher in breastfed infants with MCAD 44% of exclusively breastfed infants with MCAD were symptomatic as compared to 0% of formula- supplemented infants (p= by two-tailed Fisher s exact test). N = 24 for exclusively breastfed infants, N=19 for not exclusively breastfed infants.
11 Rates of early decompensation are higher in breastfed infants with MCAD These two groups did not differ in: Mean birth weight exclusively breastfed (mean 3.4 kg) not exclusively breastfed ( mean 3.4 kg) Frequency of the severe c.a985g mutation exclusively breastfed (15 of 24 were c.a985g / c.a985g) not exclusively breastfed (8 of 19 were c.a985g / c.a985g). p=0.5, Fisher s exact t- test) Rate of cesarean section exclusively breastfed (8 of 21) not exclusively breastfed ( 4 of 16) p=0.5, Fisher s exact t-test) Rate of comorbid conditions exclusively breastfed NONE not exclusively breastfed- 2 (chorioamionitis, respiratory distress )
12 Exclusive breastfeeding is associated with higher C8 levels on NBS Exclusively breastfed infants C8 level: ± μmol/l Infants receiving some formula C8 level: 9.89 ± 2.0 μmol/l Exclusive breastfeeding is associated with higher octanoylcarnitine levels on newborn screen (p=0.01 by two-tailed unpaired t-test) in neonates with MCAD (normal <0.3 μmol/l)
13 Rates of early metabolic decompensation and exclusive breastfeeding are rising The percentage of neonates with MCAD that were exclusively breastfed (dashed line) showed a trend towards increased rates over the study period (p=0.06 by chi-squared test for trend). Over the same time period there was a significant increase in the frequency of symptomatic presentations (black line, p=0.003 by chi-squared test for trend).
14 Conclusions Exclusively breastfed neonates with MCAD have a significantly increased risk of morbidity and mortality before NBS results are available. Exclusive breastfeeding is associated with higher levels of C8 on NBS. Symptomatic neonates are at risk for lethal cardiac arrhythmias, an often overlooked feature of MCAD. More work is required to develop tools and algorithms to detect and support poor-feeding infants, especially prior to the return of their NBS results.
15 Thank You
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