What is symptomatic? Neonatal hypoglycemia: how low can you go? Hypoglycemia and MRI. Conflicts. What s the problem? Hypoglycemia and MRI

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1 Neonatal hypoglycemia: how low can you go? Kristi Watterberg, MD Professor of Pediatrics, UNM What is symptomatic? Jitteriness Cyanosis Poor feeding Weak, high-pitched cry Seizures Apnea Lethargy, low tone Eye-rolling Coma Death Conflicts I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation. Hypoglycemia and MRI Volpe, Neurology of the Newborn text: 55 patients with abnormalities on MRI Occipital lesions ± parietal lesions Subsequent atrophy Neonatal blood glucose values 74% 20mg/dL 89% 25mg/dL 95% 30mg/dl What s the problem? Hypoglycemia and MRI First, what s not the problem: Symptomatic hypoglycemia must be treated expeditiously Diagnose with laboratory confirmation of low glucose value Treat with IV glucose ( minibolus ) Consider dextrose gel while starting IV If clinical signs get better after Rx, likely hypoglycemia-related But consider underlying disorders: sepsis, metabolic error, etc. - Counsell et al, Semin Perinat 2010; 34:67 1

2 Outcomes of severe hypoglycemia Complicated by co-existing pathology, variable reporting Outcome by neurologic signs Seizures: 50% abnormal outcomes Clinical signs but no seizures: 12% abnormal No neurologic signs: 6% abnormal Koivisto et al, Dev Med Child Neurol :603 What s the problem? Glucose of 30mg/dL common 1 2 o after birth Usually transient, asymptomatic Part of normal transition loss of constant supply from placenta Unnecessary treatment may interrupt normal mother/baby processes Breastfeeding Skin-to-skin care Bonding But.at some point, for some babies, it becomes pathologic how to prevent that? Outcomes after severe hypoglycemia From Volpe, in babies with abnormal MRIs: 84% with neurologic sequelae 84% with developmental delay 66% with seizures 37% with visual impairment 32% with microcephaly Data may be unclear about specifics, but.. No debate: if you think it s symptomatic hypoglycemia, treat it. Outcomes after asymptomatic Retrospective cohort of 1395 newborns assessed at age 10 years (Arkansas) Transient hypoglycemia <45mg/dL in 19% These children had school achievement test scores for literacy Kaiser et al, JAMA Pediatr 2015;169:913 Retrospective cohort 832 moderately preterm infants at age 4 (Netherlands) Hypoglycemia <30mg/dL reduced odds of normal development Kerstjens et al, Pediatr 2012;130:e265 So what is the problem? transitional neonatal hypoglycemia Peripartum factors influence initial values Values are lower in the first 48 o Average values mg/dl After the first two days, should be the same as older children/adults But no one knows at what point glucose concentrations are too low Outcomes after asymptomatic Prospective cohort of 543 infants <32 weeks EGA (England) Measured glucose daily x 10 days 47 babies had glucose <47mg/dL on 3 occasions and survived to age 2 Glucose <47mg/dL NOT associated with adverse outcomes 38 also seen at age 15 still no adverse effect of hypoglycemia Tin W et al, Pediatr 2012; 130:1497 2

3 Outcomes after asymptomatic Prospective cohort study of 528 at-risk term/late preterm infants (New Zealand) Glucose monitored x7 days, Rx if <47mg/dL AND: interstitial glucose concentrations were continuously monitored (staff masked) Hypoglycemia was common: 53% AND: unrecognized hypoglycemia (on the interstitial monitor) was also common: 24% At 2 years, neither treated nor untreated hypoglycemia was associated with any adverse developmental outcomes McKinlay at al, NEJM 2015; 373:1507 HIE and hypoglycemia Hypoxic-ischemic encephalopathy may increase vulnerability to low glucose Signs of HIE and hypoglycemia may be very similar Monitor babies with neonatal depression ( Apgar scores), acidosis on cord blood gases, other signs of stress (meconium) Consider maintaining glucose >45mg/dL Boardman/Hawdon, Dev Med Child Neurol 2015; 57 Suppl 3:29-33 So we can screen for specific glucose values? there is not a specific glucose or duration of hypoglycemia that can predict permanent neurologic injury in high-risk infants and no single concentration or range of values that is associated with clinical signs We need a pragmatic approach to a controversial area for which evidence is lacking but guidance is needed Need to balance infant safety with adverse effects of overtreatment AAP committee on fetus & newborn, Pediatr 2011; 127:575 Frequency of hypoglycemia Prospective cohort 514 at-risk babies ½ of the babies had glucose <47mg/dL 19% were <36mg/dL (severe) 19% had >1 episode Half of the first episodes occurred within 6 o Only 6% of first episodes occurred after 24 o 90% of severe episodes occurred in 1 st 12 o Harris et al, J Pediatr 2012;161:787 Who to screen? Every baby? Not necessary Increases cost and stress At-risk babies Infants of diabetic mothers (IDM) Large for gestation infants not IDM? Small for gestation infants Late preterm infants Intrauterine stress (meconium, Apgars)? Why is the guidance so confusing? Because there is disagreement... And conflicting evidence... And potential consequences The AAP has adopted and recommends use of operational thresholds Providing a margin of safety and flexibility But because expected glucose values change over the first hours and days, the threshold changes and the charts are complicated. 3

4 AAP screening guideline 2011 What about persistent After 24 o glucose should be >45mg/dL After 48 o use normal normal ranges For infants who have required (received) IV dextrose, or have borderline glucose >48 o Consider delaying discharge until glucose remains >70mg/dL through several normal feed/fast cycles Adamkin & Polin, J Pediatr 2016; 176:195 DRAFT: UNM screening protocol (L&D) And what about late Retrospective brief report from Cincinnati Children s Hospital 11 newborns presenting at DOL 2 5 with symptomatic hypoglycemia (8 35mg/dL) 9/11 vaginal deliveries 9/11 primiparous women 9/11 exclusively breastfeeding 5/6 MRIs abnormal 4/7 followed have neurologic sequelae Seske et al, Hosp Pediatr 2015; 5:501 DRAFT UNM screening protocol (ICN) NO >4 o A better safety net for newborns? Delayed onset of lactogenesis (>72 0 ) is common (25 40%) Risk factors Primiparity, overweight or obesity Stage II labor > 1 hour or Cesarean section Birthweight > 3600g Flat or inverted nipples Lack of nipple discomfort 0 3 days postpartum Excess weight loss 7x with delayed onset Dewey et al, Pediatr 2003; 112:607 Nommsen-Rivers et al, am J Clin Nutr 2010; 92:574 4

5 A better safety net? Most moms and babies will do fine with exclusive breastfeeding But they need support And maybe we could have a risk score for closer follow-up after discharge First time mom High BMI Lack of social support system Bilirubin in high-risk zone Excess newborn weight loss Newborn weight tool Website: newbornweight.org To set up on your phone or other device: Use your phone/device to go to their website Tap this icon: Choose add to home screen You will see (hopefully) the Newt icon on your phone Breastfeeding infant: Postnatal weight loss (vaginal birth) Thanks for listening! Questions, comments? kwatterberg@salud.unm.edu Flaherman et al. Pediatr 2015; 135:1 Breastfeeding infant: Postnatal weight loss (C-section) Flaherman et al. Pediatr 2015; 135:1 5