1. F LUIDS, E LECTROLYTES, AND N UTRITION FOR THE N EONATE : Melissa Nelson, MD Neonatal-Perinatal Fellow Yale-New Haven Hospital

2. L ECTURE O BJECTIVES : Understand principles of fluid balance in neonates and appropriate postnatal fluid management Learn concepts of electrolyte balance in neonates Recognize signs and symptoms of certain electrolyte abnormalities and learn how to treat them Learn about neonatal nutritional requirements and feeding methods

3. P RINCIPLES OF F LUID B ALANCE : TBW = ICF + ECF ECF = Intravascular + Interstitial http://akramania.byethost11.com/OHCM/16%20-%20Clinical%20Chemistry.htm

4. TOTAL BODY WATER COMPOSITION: Adult TBW = 60% (40% ICF + 20% ECF) Full-term TBW = 75% (35% ICF + 40% ECF) Pre-term TBW = 90% (30% ICF + 60% ECF) * Excess TBW esp. ECF at birth, hence diuresis within 1 st week of life (up to 10% in FT, up to 15% in pre-term) http://www.revivenaturally.com/dr-yoshitaka-ohno-md-phd/maintaining-intracellular-hydration-water.html

5. SENSIBLE VS. INSENSIBLE WATER LOSS: Sensible water loss (SWL): Easily measured Urine, stool, NG/OG output, CSF Insensible water loss (IWL): Not readily measured Evaporation from skin (66%) or respiratory tract (33%) IWL greater in lower GA (immature skin) Factors that increase: Immature skin, fever, radiant warmers, phototherapy, skin defects/breakdown Factors that decrease: Mature skin, humidity, heat shields

6. RENAL FUNCTION IN NEONATES: Decreased capacity to concentrate or dilute urine in response to intravascular fluid status Risk dehydration or fluid overload http://www.yalemedicalgroup.org/stw/Page.asp?PageID=STW028984 Adults: FE Na < 1% vs. Term infants: FE Na < 1% (except transient increase during diuretic phase) vs. Pre-term infants: FE Na 5-6%

7. A SSESSING F LUID S TATUS : Factors that can affect fluid status: Maternal history : Neonate’s status reflects mother’s Neonatal history (ie. In utero hypoxemia associated with ATN and hypervolemia) Clinical evaluation : weight changes, UOP, IWL factors (humidity, phototherapy, ventilation, etc.), vital signs, perfusion Laboratory evaluation : serum electrolytes, BUN/Cr

8. FEN M ANAGEMENT : Goals: Maintain ICF and ECF volumes and osmolalities Allowing diuresis within 1 st week of life Maintain appropriate electrolyte concentrations Provide adequate nutrition for growth

9. T OTAL F LUID R EQUIREMENTS : Total fluids = Maintenance + Growth Maintenance = SWL + IWL http://www.champ-sportsline.de/en/nutrients-active-ingredients/fluids.html

10. STARTING POINTS AND ADVANCEMENT: Starting Points: BW < 1250g: TF = 80 - 100 BW 1250-1750g: TF = 60 - 80 BW > 1750g: TF = 60 Advancement Example: ELBW infant Start DOL 1 with TF = 100 Adjust daily to maintain wt loss within 10% BW DOL 2 with TF ~100-120 DOL 3-4 with TF ~120-130 DOL 4-5 with TF ~130-140 Goal TF ~140-150

11. FLUID ISSUES ASSOCIATED WITH COMMON NEONATAL CONDITIONS: Issues requiring fluid restriction : RDS : Excessive fluid can lead to fluid overload and increased risk of BPD BPD : Excessive fluid can worsen therefore treated with diuretics to reduce pulmonary edema PDA : Volume overload can open ductus and worsen respiratory status HIE : Associated with ATN and/or SIADH and can lead to subsequent volume overload

12. C OMMON F LUID P ROBLEMS : Hypervolemia/volume overload Hypovolemia/dehydration Oliguria: UOP < 1 mL/kg/hr Pre-renal, Renal, Post-renal

13. E LECTROLYTE R EQUIREMENTS : First 24h of life: No electrolytes (except Ca) Ca especially important for preterm infants At 24h of life: Na: 1-3 mEq/kg/day K: 1-2 mEq/kg/day At 1 week of life: Na: 3-5 mEq/kg/day K: 2-3 mEq/kg/day * Extremely pre-term infants with metabolic acidosis (loss of bicarb in urine) may benefit from sodium acetate ** Electrolyte requirements vary based on medications, etc.

14. COMMON ELECTROLYTE ABNORMALITIES: Hypo/hypernatremia Hypo/hyperkalemia Hypocalcemia Hypermagnesemia http://www.coconutwaterlife.com/electrolytes

15. S ODIUM A BNORMALITIES : Hyponatremia: Na < 130 mEq/L Causes: Usually due to excess free water but can be increased Na losses/inadequate Na intake Signs/sx: lethargy, seizures, coma Tx: Restrict fluids and/or Na supplements Hypernatremia: Na > 150 mEq/L Causes: Usually due to high water losses, rarely excess intake Signs/sx: lethargy, seizures, coma Tx: Increase fluids and/or restrict Na

16. P OTASSIUM A BNORMALITIES : Hypokalemia: K < 3.5 mEq/L Causes: Diuretics, NG losses Signs/sx: EKG changes (flat T waves, prolonged QT, U waves), arrhythmias, ileus, lethargy Tx: Slowly correct IV or orally Hyperkalemia: K > 6 mEq/L Causes: Iatrogenic, severe acidosis, ARF, RBC breakdown s/p transfusion, CAH Signs/sx: EKG changes (peaked T waves, wide QRS, brady/tachycardia, SVT, V Tach, V fib), arrhythmias, death Tx: D/C all K, Ca gluconate, sodium bicarbonate, albuterol, insulin + glucose, lasix, kayexalate, dialysis/exchange * Most K is intracellular, thus serum levels might not accurately depict total body stores ** pH affects K levels: Acidosis drives K out of cell vs. Alkalosis pushes K into cell

17. C ALCIUM A BNORMALITIES : Hypocalcemia: Ca < 7 mg/dL (iCa < 1) Causes: Prematurity, IUGR, IDM, HIE, hypoparathyroidism, Vitamin D deficiency Signs/sx: Asymptomatic, jitteriness, irritability, seizures Tx: Observation, repletion (Ca gluconate), or supplementation Hypercalcemia: Ca > 11mg/dL (iCa > 5) Rare in neonates Usually associated with preterm fortifiers (HMF) * Important to follow Ca levels as well as Phos and Alk Phos levels ~every 2 weeks once on full feeds to screen for osteopenia

18. M AGNESIUM A BNORMALITIES : Hypermagnesemia: Mg > 2.3 mEq/L Causes: Maternal treatment with magnesium for PEC or tocolysis Signs/sx: Respiratory depression, apnea, hypotonia, decreased GI motility Tx: Self-limited, resolves within a few days

19. P RINCIPLES OF N UTRITION : Nutrient requirements: Carbohydrates Protein Fat Water Minerals and trace elements Vitamins

20. E NERGY R EQUIREMENTS : Depend on: GA Postnatal age Weight Route of intake (less calories if parenteral) Growth rate Activity level Thermal environment Medical problems Ideally energy from: 65% carbohydrate + 35% lipid Protein building block for growth

21. E NERGY R EQUIREMENTS : Typical needs: 100-120 cal/kg/day for growth Term = 100 vs. Preterm = 120 cal/kg/day Many need more! (ie. BPD or CHD might need 160-180) “Healthy” enterally fed premie: 125 cal/kg/day Resting energy expenditure: 50 cal/kg/day Activity level (minimal): 5 cal/kg/day Occasional cold stress: 10 cal/kg/day Stool loss (10-15% of intake): 15 cal/kg/day Growth (4.5 cal/g of growth): 45 cal/kg/day

22. M ETHODS OF P ROVIDING N UTRITION : Total Parenteral Nutrition (TPN): Peripheral vs. Central Combination Parenteral/Enteral Nutrition: Advancing feeds but still giving TPN Total Enteral Nutrition: Per oral route (PO) (ie. Bottle/breast) Per gavage route (PG) (ie. NG/OG on pump) Chronic feeding tube feeds (ie. G-tube)

23. T OTAL P ARENTERAL N UTRITION : Goal: Provide energy and nutrients to promote growth when unable to adequately feed by enteral means Calculations typically based on birth weight for first week of life, then use actual weight thereafter Must account for: Total fluid volume (mL/kg/day) Total daily caloric requirements (cal/kg/day) Dextrose concentration and glucose infusion rate (mg/kg/min) Protein (g/kg/day) Lipid (g/kg/day) Electrolytes, trace elements, minerals, vitamins

24. STARTING POINTS AND ADVANCEMENT: Variable:Starting Point:Advancement:Goal: Dextrose & Glucose Infusion Rate: Initial GIR: 6-8 (Usually start D10) 1-2/day depending on glucose levels Typical max ~14-15 Protein (g/kg/day):30.5-1/day<1500g/32 wks :4 >1500g/32 wks: 3 Lipid (g/kg/day):< 1000g: 0.5 1000-2000g: 1-2 >2000g: 2-3 *Start at 24-30h life 0.5-1/day 1-2/day 3 *Check TG levels prn @ 2-3g Vitamins:MVI for neonatal/peds Minerals:“Electrolyte-free” except Ca for first few days -Start Na at ~2 days -Start K once voiding & serum K<3.5 -Ca, Mg, Phos, Cl, Acetate Trace Elements:Zn, Cu, Mn, Cr, Mo, I

25. OFF-HOURS TPN FOR PREMIES BW < 1750G: Goal: Provide protein and calcium within first 24h of life (when can’t order regular TPN yet) Rationale: ELBW infants lose >1% of protein stores daily, must provide protein to balance loss Run at 50 mL/kg/day Components: Dextrose 10% Protein (60 g/L): 3g/kg/day Calcium (4 mEq/L) Minimal electrolytes Heparin

26. T YPES OF E NTERAL N UTRITION : Breast milk is the best milk! Lactation counselors can help NBSCU moms Donor breast milk an option for some premies Variety of formulas available: Term (20 cal) : Good Start, Enfamil, Similac Late Pre-term/Transitional (22cal) : Enfacare, Neosure Pre-term (24 cal) : Similac Special Care Supplements to increase calories, etc.: HMF (protein, Ca), Neosure powder, MCT oil

27. T YPES OF E NTERAL N UTRITION : Specialty formulas available: Lactose Intolerance/Galactosemia: Soy varieties Feeding Intolerance: GentleEase, Similac sensitive Semi-Elemental: Alimentum, Nutramigen, Pregestimil Elemental: Neocate, Elecare Renal disease: Similac PM 60/40 Chylothorax: Enfaport

28. INITIATION OF ENTERAL FEEDING: Preterm < 1250g: Goal to start preterm feedings within first 12 hours of life Start with non-nutritive feeds q4h: Low volume (usually 10-15 mL/kg/day) Acclimate the GI tract to feeds Stimulate gut hormone secretion Promote GI tract maturation Preterm 1250-1750g: Start within first 12 hours of life with ~20 mL/kg/day (ie. 4-5 mL/kg/feed q2-3h) Preterm > 1750g or Fullterm: If stable, start feeds within first 6 hours of life q3-4h May consider ad lib feeds

29. ADVANCEMENT OF ENTERAL FEEDING: Goal: Advance slowly to reach full enteral feeds within ~2 weeks of life Advance daily as tolerated per feeding protocol (~10-20 mL/kg/day for premies) Monitor for symptoms of intolerance: Abdominal distension Vomiting Bilious aspirates/residuals

30. ADVANCEMENT OF ENTERAL FEEDING: Feeding Day (Volume – mL/kg/d) < 0.550g0.551- 0.650g 0.651- 0.750g 0.751- 0.850g 0.851- 0.950g 0.951- 1.050g 1.051- 1.150g 1.151- 1.250g 1 (~12) 1.0 mL q4h 1.2 mL q4h 1.4 mL q4h 1.6 mL q4h 1.8 mL q4h 2.0 mL q4h 2.2 mL q4h 2.4 mL q4h 2 (~24) 2.0 mL q4h 2.4 mL q4h 2.8 mL q4h 3.2 mL q4h 3.6 mL q4h 4.0 mL q4h 4.4 mL q4h 4.8 mL q4h 3 (~36) 1.5 mL q2h 1.8 mL q2h 2.1 mL q2h 2.4 mL q2h 2.7 mL q2h 3.0 mL q2h 3.3 mL q2h 3.6 mL q2h 4 (~48) 2.0 mL q2h 2.4 mL q2h 2.8 mL q2h 3.2 mL q2h 3.6 mL q2h 4.0 mL q2h 4.4 mL q2h 4.8 mL q2h 5 (~60) 2.5 mL q2h 3.0 mL q2h 3.5 mL q2h 4.0 mL q2h 4.5 mL q2h 5.0 mL q2h 5.5 mL q2h 6.0 mL q2h 6 (~72) 3.0 mL q2h 4.0 mL q2h 5.0 mL q2h 6.0 mL q2h 7.0 mL q2h After Feeding Day 6: increase 1 mL/feed q24h for 2-3 days and then increase 1 mL/feed q12h until full enteral feeds Adapted from Y-NHH NBSCU guidelines

31. ADVANCEMENT OF ENTERAL FEEDING: As enteral feedings increase, amount of parenteral feedings decrease Write TPN for NPO rate in case feeds stopped Decrease lipid rate accordingly (ie. Decrease to 50% once at ½ full feeds, etc.) Fortify feeds with HMF once infant receiving 100 mL/kg/day of human milk First fortify to 22 cal then to 24 cal Consider further increase in calories overtime from to 27 or 30 cal formula +/- MCT depending on growth curves

32. TRANSITION FROM PG TO PO FEEDING: Infant must: Weight > 1000 grams and corrected GA > 32 wks Clinically stable with full strength feeds Developmental cues of readiness (suck/swallow) Advancement: Start with trial of po once daily Then twice daily Then every few/every other feed (PG/PG/PO, PO/PG, PO/PO/PG) Then all po (PO Ad Lib with minimum, PO Ad Lib) * Some infants 32-34 weeks might not be ready for all po, consider alternating po/pg feeds

33. ADDITIONAL NUTRITIONAL CONSIDERATIONS: Iron fortification: Prevent Fe-deficient anemia Fe supplement given to breast-fed term/pre-term infants Some formula-fed might need if insufficient volume Vitamin supplementation: Polyvisol for term/pre-term breast-fed infants once full feeds Vitamin D supplementation: Term/pre-term breast-fed infants need 400 IU daily Supplement amount depends on feeding method/amount

34. PREP BOARD REVIEW QUESTION #1: Item 34 (2011): A mother in your pediatric practice recently delivered a 28 weeks’ gestation infant who is in the NICU. She exclusively breastfed her previous child who was born at 36 weeks’ gestation. She is concerned that something is wrong with her milk for this infant because it is being combined with HMF. You reassure her that fortification helps to meet the additional needs of her preterm infant. Of the following, the MOST important role of such fortification is to: A. augment the immunologic properties of human milk B. boost the carbohydrate content of human milk C. decrease the osmolality of human milk D. enhance the absorption of iron from human milk E. increase the protein content of human milk

35. PREP BOARD REVIEW QUESTION #1: Answer: E. increase the protein content of human milk Preterm infants need more protein. Preterm 3-4 g/kg/day Term 1.5-2 g/kg/day HMF provides extra protein to be added to breast milk.

36. PREP BOARD REVIEW QUESTION #2: Item 226 (2010): A 30 weeks’ gestation very low-birthweight (VLBW) 1,400-g infant has respiratory distress syndrome (RDS). He is receiving assisted ventilation following administration of 3 doses of surfactant. On his second postnatal day, his mother asks if she can breastfeed her infant. You explain that he will not be able to breastfeed until he is extubated and able to suckle. She asks whether she should pump her breast milk. Of the following, the BEST response is that expressed human milk feedings: A. are contraindicated in VLBW infants who have RDS B. are too difficult for VLBW infants to digest C. can be fed by NG tube D. have no net benefit for VLBW infants once frozen E. have too much protein for VLBW infants

37. PREP BOARD REVIEW QUESTION #2: Answer: B. are too difficult for VLBW infants to digest Breast milk is the best milk! NG feeds can be given when babies cannot yet tolerate po feeds.

38. PREP BOARD REVIEW QUESTION #3: Item 50 (2011): A 27 weeks’ gestation preterm male infant who weighs 900g is delivered at a community hospital by emergent cesarean section. After intubation in the delivery room, he is taken to the nursery for stabilization, including umbilical venous line placement, prior to transfer to a tertiary care center. Of the following, the MOST appropriate initial solution for parenteral administration would include: A. 5% dextrose B. 5% dextrose and 0.2% sodium chloride C. 10% dextrose D. 10% dextrose and 0.2% sodium chloride E. 0.9% sodium chloride

39. PREP BOARD REVIEW QUESTION #3: Answer: C. 10% dextrose Preterm babies are at risk of hypoglycemia and need to have careful blood glucose monitoring. Initial parenteral fluids typically include 10% dextrose solutions. Infants do not need sodium administration within the first few days of life.

40. PREP BOARD REVIEW QUESTION #4: Item 174 (2011): A 4-month-old male infant presents with abdominal distension, vomiting, and poor weight gain. His temperature is 37.3°C, heart rate is 110 beats/min, respiratory rate is 32 breaths/min, and blood pressure is 96/56 mm Hg. On physical examination, you note abdominal distension, with a palpable mass above the pubic symphysis. Results of laboratory tests include: Na 136, K 7.2, Cl 110, Bicarb 16, BUN 25, Cr 1.3, Ca 9.5, Mg 1.8, P 5.5 Of the following, the next BEST step in the management of this patient’s electrolyte abnormality is administration of: A. intravenous calcium gluconate B. intravenous dextrose and insulin C. nebulized albuterol D. oral furosemide E. oral sodium polystyrene sulfonate

41. PREP BOARD REVIEW QUESTION #4: Answer: A. intravenous calcium gluconate All treatment options are correct but first-line approach to decrease K level rapidly is Ca gluconate. (See NBSCU algorithm) The infant has abdominal distension, FTT, palpable suprapubic mass, hyperkalemia, azotemia, and normal anion gap metabolic acidosis. Diagnosis is likely obstructive uropathy (posterior urethral valves) with Type IV RTA and hyperkalemia.

42. References: Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant Ambalavanan, N et al. Fluid, Electrolyte, and Nutrition Management of the Newborn. emedicine.com, Last updated June 29, 2010. Yale-New Haven Hospital NBSCU Guidelines: - Basic Concepts: Fluid, Electrolyte, and Nutritional Management of Preterm Infants (June 2009) - Basic Concepts: Total Parenteral Nutrition in the Newborn (June 2009) - Breastfeeding Initiation and Advancement (April 2006) - Feeding Intolerance Assessment (April 2006) - Oral Feedings Initiation and Advancement (April 2006) - Iron Supplementation (September 2011) - Vitamin D Supplementation (October 2011) - Nutrient Contents: Preterm Formulas, Fortified Human Milk Admixtures (June 2008) PREP Self-Assessment Pediatrics Review and Education Program, AAP, 2009-2011