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Medical Underwriting of High Risk Infant

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Fetal development

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Infant on diabetic mellitus mother

3 - 10% 80% abnormal glucose control of pregnancy gestational diabetes mellitus

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Mortality/Morbidity Birth defect 8 - 15% ,

major congenital malformation 5 - 9%

perinatal MR 2 neonatal MR 3 general population

morbidity : large for GA, hypoglcemia, prematurity, respirarory distress, intrapartum asphyxia

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hyperglycemia first trimaster--> Congenital malformation hyperglycemia fetal macrosomia, neonatal electrolyte abnormalities, cardiomegaly fetal macrosomia 26% IDMs (10%) Impaired fetal growth 20% diabetes pregnancy (10%) maternal renovascular disease Pulmonary disease RDS : insulin restrics substrate availability for surfactant biosynthesis, block fibroblast-pneumatocyte factor

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Metabolic/electrolyte abnormalities 25 - 40% hypoglycemia beta cells hyperplasia hypocalcemia / hypomagnecemia --> jitteriness , seizure : seconary to PTH suppression Hematologic problems polycythemia chronic fetal hypoxia --> Hyperbilirubinemia thrombocytopenia

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Cardiovascular anomalies
30% cardiomyopathy with intravascular hypertrophy and outflow tract obstruction : insulin receptors congenital heart defect : VSD, transposition of the great arteries (TGA) Congenital malformation : insulin-.mesoderm,neural crest cells; metabolic disturbance; glucose induced free radical central nervous malformation 16 anencephaly 13 spina bifida 20 caudal dysplasia 600 renal (hydronephrosis, renal agenesis, ureteral duplication), ear, cardiovascular (single umbilical artery,VSD, ASD, TGA, coarctation of aorta, cardiomegaly), GI (duodenal or anorectal atresia, small left colon syndrome) anomalies Overall risk 8 - 15%

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Causes
HbA1C levels : complication HbA1C < 8.5% -----> 3.4%

HbA1C > 8.5% -----> 22.4%

- LGA, , stillbirth, hypertension, gestational diabetes, obesity, glycosuria,

Prognosis 50% gestational diabetes IDM 15

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Neurodevelopmental outcome 1991, Rizzo et al : 223 pregnant women (89 DM, 99 gestational diabetes, 35 normal) - mental development index scores 2 - Standford-Binet Intelligence scores 3, 4, 5

- perinatal complication cognitive development

early school-aged : Ornoy and associates follow 32 well-controled gestational diabetes/57 control -- minor neurological deficits

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Growth Silverman and association : birth to 8yr

at birth 50% BW > 90 percentile

at 12 mo normal wt and length at 7 yr slightly higher than average

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SGA
Long term consequence

Hospitalization
G&D Neurodevelopment

:
: :

more frequently
shorter, lighter, smaller 5 - 10 times neurologic disorders & morbidities obesity, insulin resistance, diabetes, cardiovascular disease

Possible adult disorders :

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Cause Mother Placenta Fetus Symmetrical Asymmetrical Problems perinatal asphyxia, hypoglycemia, polycythemia, congenital infection

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Congenital infection
Risk assessment

ANC lab results, risk of sexual transmitted diseases

birth weight, head circumference, physical examination, jaundice, liver/spleen, lab investigation

G&D Toxoplasmosis, rubella, cytomegalovirus, syphylis, HIV

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Polycythemia
Hct > 65%

6.7% hyperviscosity
Cause - fetal hypoxia - endocrine - genetic - hypertransfusion - dehydration risk neurological defect - speech abnormalities, fine-motor delays, gross motor delays

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Anemia of prematurity
80% VLBW

95% ELBW
HB 4 - 8 3 - 6 GA > 32

Lab

Hct < 10 6 - 7

g/dl g/dl

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Respiratory distress syndrome

Hyaline membrane disease

Incidence GA

28 - 32 weeks --> 50% < 28 weeks --> 45 - 80%

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Pathophysiology deficiency of surfactant (hypoxia, acidosis, hypotherma, hypotension) decrease lung compliance and funtional capacity increase dead space

Require higher pressure

barotrauma, volutrauma oxygentoxicity

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Increase risk for RDS Prematurity maternal diabetes cesarean intrapartum asphyxia pulmonary infection pulmonary hemorrhage meconium aspiration syndrome

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Treatment Surfactant replacement therapy

50% mortality decrease

RDS with Fio2 > 0.40 Oxygen and continuous positive airway pressure continuous positive airway pressure (CPAP) conventional ventilator

complication - airleak, BPD, airway damage, intraventricular hemorrhage

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Newer ventilation Synchronous intermittent mandatory ventilation

decrease BPD 47% vs 72%

Assist control ventilation High-frquency ventilation (HFV) study result in human - unclear some study - reduce BPD

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Acute complication Alveolar rupture : pneumothorex, pneumomediastinum, pneumopericardium, interstitial emphysema Infection Intracranial hemorrhage and periventricular leukomalacia PDA Pulmonary hemorrhage Necrotizing enterocolitis/bowel perforation Apnea of prematurity

Chronic complication

Brochopulmonary dysplasia Retinopathy of prematurity Neurologic impairment Familial psychopathology

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Chronic lung diseases of the Newborn

Bronchopulmonary dysplasia Oxygen dependent Respiratory distress Abnormal CXR High risk - severe respiratory distress, prolong mechanical ventilation/oxygen therapy, low GA, PDA, high peak inspiratory pressure Antenatal glucocorticosteroids, early surfactant therapy, genter modalities ventilation ---> BPD

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Pulmonary mechanics
- increased airway resistance, decreased lung compliance, increase airway reactivity, increase airway obstruction

Risk serious infection airway hyperreactivity cardiac dysfunction neurologic impairments

2 RSV Poor prognosis : persistent RVH or fixed pulmonary HT

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Retinopathy of prematurity (ROP)

Pathophysiology
Frequency

Risk : low birth weight, oxygen supplement, sepsis, blood transfusion, mechanical ventilation, PDA, intraventricular hemorrhage

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(International Committee on Classification of Acute ROP 2525) 1 vascularied & nonvascularized retina 2 3 4 5

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optic disc ( optic disc ) Zone 1 2 optic disc Zone 2 zone 1 Zone 3 zone 2

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Plus sign

Threshold disease ROP ROP 3 Zone 1 2 5 8 plus sign

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Treatment : Cryotherapy Laser surgery - better VA, refractive error - myopia. amblyopia, strabismus, late retinal detachment, blindness

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Periventricular leukomalacia
white matter lesion preterm (GA <32 wk, BW < 1,500 gm) Pathophysiology : vessle, infection 4 - 26% preterm infant

60 - 100% CP

mild --> spastic diplegia

severe --> quadriplegia

Intellectual impairment visual dysfunction : fixation difficulties, nystagmus, strabismus, blindness

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: mechanical ventilation, hypotension, hypoxia, acidosis, mark hypocarbia, chorioamnionitis Ultrasound - earliest abnormal --> increased echotexture in the periventricular white matter CT scan --> ventriculomegaly, irregular margin ventricle deep white matter MRI

Betamethsone to mother at 24 - 31 GA ---> reduce risk

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Periventricular - Intraventricular Hemorrhage

subependymal germinal matrix

Pathogenesis : Loss of cerebral autoregulation

Abrupt alterations in cerebral blood flow and pressure Classification grade 1 grade 2

grade 3 grade 4

subependymal region and/or germinal matrix subependymal hemorrhage with extension into lateral ventricle grade 2 with ventricular enlargement intraparechymal hemorrhage

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Cranial sonography Frequency : US 12% with indomethacin prophylaxis 18% without prophylaxis Complication obstructive hydrocephalus non-obstructive hydrocephalus development impairment cerebral palsy Prognosis seizures grade 1 / 2 grade 3 30 - 40% cognitive motor disorders grade 4 90% neurologic sequelae : cognitive & motor disturbances

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Perinatal asphyxia
Apgar score 1 5

cerebral palsy 1. Apgar score 10 0-3 2. hypotonia 3.

- metabolic acidosis umbilical cord blood

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Risk : GA < 36 wk, intrauterine growth retardation (IUGR), breech deliveries, preeclampsia Central nervous system (CNS):

hypoxic-ischemic encephalopathy (HIE) --> cerebral

edema
HIE : 1. tone hypertonia, flaccid 2. stupor, coma 3. periodic breathing, apnea 4. subtle tonic multifocal clonic seizures 72

12 -

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Poor prognosis
Frequent and difficult control seizure Abnormal neurological findings beyond the first 7 - 10 days

Persistent feeding difficulty

Poor head growth in the first year of life Sequelae : MR, epilepsy, cerebral palsy
Long term complication : Mild free from serious CNS complication 30 - 50% have serious CNS complication 20% minor Severe 80% serious 10 - 20% moderately serious, 10% normal

Moderate

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cardiovascularsystem : hypotesion, tachycardia, congestive heart failure hypoxic myocardiopathy cardiogenic shock prognosis 3

--> renal failure

risk : meconium aspiration, respiratory distress (RDS), persistent pulmonary hypertension (PPHN), pulmonary hemorrhage, pulmonary edema

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--> hepatic damage, hypoglycemia gastrointestinal system --> bowel ischemia, necrotizing enterocolitis

--> disseminated intravascular coagulation (DIC)

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Extremely low birth weight (ELBW)

BW < 1,000 g

Surviability
BW < 500 g BW 500 - 749 g BW 750 - 1,000 g 11.6% 50.7% 83.9%

Thermoregulation Hypoglycemia Fluid and electrolyte Hyperbilirubinemia RDS PDA Infection NEC IVH PVL Vision Hearing

Extremely Low-Birth Weight Survivor (ELBW)

<1000 g
20-Month Neurosensory Outcomes Outcome Major neurologic abnormality Cerebral palsy Diplegia Dihemiplegia Hemiplegia Quadriplegia Hypertonia Hypotonia Shunt-dependent hydrocephalus Blindness (unilateral or bilateral) Deafness (unilateral or bilateral) Total No(%) of children 44 (20) 33 (15) 1970-1992 7- 10% 15 (7) 3 (1) 6 (3) 9 (4) 5 (2) 4 (2) 2 (1) 2 (1) 20 (9) 54 (24)

N=221,1992 - 1995,Ohio,meanBW 813 g, mean GA 26.4 wk Hack M. Arch Pediatr Adlesc Med 2000;154:725-731

Results of multiple stepwise logistic regression as significant predictors outcomes Outcome MDI score<70 Predictor OR(95%CI)

Male sex 2.73 (1.52-4.92) Social risk 1.48 (1.09-2.00) CLD 2.18 (1.20-3.94) Neurologic Abnormal ultrasound finding* 8.09 (3.69-17.7) abnormality CLD 2.46 (1.12-5.40) Deafness Male sex 2.79 (1.02-7.62) Sepsis 3.15 (1.05-9.48) Jaundice** 4.80 (1.46-15.73) Impairment# Male sex 3.12 (1.71-5.68) Social risk 1.50 (1.10-2.05) Abnormal ultrasound finding 2.80 (1.37-5.72) CLD 2.04 (1.11-3.76) MDI=Baley mental developmental Index,<70 42% (10%) Neuroensory abnormality and/or MDI score<70 48% * gradeIII to IV bleed, periventricular leukomalacia and ventricular dilatation ** maximun bilirubin > 10 mg/dl # MDI score<70, neurologic abnormality,unilateral or bilateral blindness or deafness

Pubertal data at 14 years ELBW Girls Menarche (%girls) Breast stage>3(%girls) Boys Mean left teticular volume(mL) (mean,SD) Mean right testicular volume(mL) (mean SD) Volume testes>=12mL(%boys) 33/39(84.6%) 29/39(74.4%) 18.4(6.6) 19.2(6.2) 30/34(88.2%) NBW 15/16(93.8%) 12/16(75%) 19.6(6.5) 20.2(6.2) 22/25(88%)

86 ELBW, 1977-1982, Melbourne,IPPV,no surfactant

Doyle LW. Clin Perinatol. 2000;27(2):421-433

Respiratory health At 14 years of age 72 ELBW, 39 NBW ELBW BPD 30(42%) Similar clinical respiratory health
Readmission to hospital for pneumonia or asthma in the year before assessment Asthma Asthma

ELBW 1%
15%(11/72) no BPD 17%(4/30)

NBW 0%
23%(9/39) not significant BPD 13%(7/42)

Lung function Overall lung function - mostly normal

Very low birthweight (VLBW) <1500 g

Prevalence and risk of respiratory morbidity in the VLBW population No(%)VLBW (n=241) Wheeze Alone With cold After exercise Frequent cough and cold Visit GP for cough and cold School absences for chest problems Respiratory hospital admissions Inhaler 22(9) 56(23) 28(12) 55(23) 67(28) 31(13) 40(17) 40(13) No(%)control (n=508) 23(5) 67(13) 32(6) 52(10) 80(16) 24(5) 23(5) 45(8) OR 2.1 2.0 2.0 2.6 2.1 3.0 4.3 1.9 95%CI 1.2 to 3.9 1.3 to 3.0 1.2 to 3.3 1.7 to 3.9 1.4 to 3.0 1.7 to 5.2 2.5 to 7.4 1.2 to 2.9

At 8 - 9yr, Scotland Impair lung function McLeod A. Arch Dis Child. 1996;74:188-194

Medical history and health in the receding year of VLBW children BPD no BPD n=36 n=107 Medical history Allergies 8(22) 24(23) Tympanostomy 11(31) 24(23) Adenotomy 12(33) 37(35) Hearing problems 1(3) 5(5) Vision problems 10(28) 4(4) Squint 9(27) 11(10) Health in the preceding year Respiratory infections >1/y 25(69) 77(73) >5/y 5(14) 8(8) Antibiotic courses 28(78) 75(74) >1/y 21(58) 43(42) >2/yr 17(47) 21(21) >3/y 10(28) 12(12) Cough or wheezing Cold 5(14) 10(9) Exercise 6(17) 19(18)

Term n=131 37(28) 19(15) 26(20) 1(1) 2(2) 1(1) 81(62) 6(5) 77(59) 42(32) 21(16) 13(10) 10(8) 3(2)

Medical history and health in the receding year of VLBW children BPD no BPD n=36 n=107 Medications Inhaled corticosteroids 6(17) 15(14) Bronchodilators 5(14) 19(18) Other 2(6) 4(4) Hospitalisation for Respiratory infection 3(8) 13(12) Other reason 9(25) 20(19) Follow-up in a hospital 17(47) 32(30)
at 2 - 8 yr of age Korhonen P. Acta Paediatr 1999;88:1385-91

Term n=131 2(2) 5(4) 5(4) 0(0) 7(5) 11(8)

Adjusted odds ratio (95%CI) for outcome measures indicating developmental delay for children in the MMIHS DenverII sample of birth to Missouri residents from December1, 1989 through March 31,1991 VLBW (n=320) vs NBW OR 95%CI 2.74 4.81 1.74-4.31 2.51-9.23

Outcome measure Overall performance Questionable Abnormal Domain-specific performance Personal-social >/=1cations >/=1delays Language >/=1cations >/=1delays Fine motor-adaptive >/=1cations >/=1delays Gross motor >/=1cations >/=1delays

MLBW OR 1.66 2.02

95%CI 1.09-2.51 1.18-3.45

1.64 2.74 1.41 1.79 1.42 1.60 2.16 2.54

1.09-2.48 1.36-5.53 0.93-2.12 1.04-3.09 0.88-2.28 0.90-2.84 1.39-3.34 1.38-4.68

2.12 3.21 2.16 2.97 2.10 4.88 4.95 6.26

1.38-3.24 1.54-6.68 1.39-3.37 1.61-5.47 1.26-3.50 2.34-10.20 2.89-8.47 2.87-13.65

Preschool children Schendel DE. Am J Epidemiol 1997;146(9):740-749

Low Birth Weight (LBW)

<2000 g Respiratory Symptoms Respiratory history obtained at 7 years. Results are No (%)
LBW (n=121) Asthma Whooping cough Croup(stridor) Previous chest infections Previous hospitalization chest illness * p<0.05
Chan KN. Arch Dis Child.1989;64:1294 - 1304

Reference (n=100) 13 (13) 11 (11) 4 (4) 7 (7) 8 (8)

13 (11) 29 (24)* 13 (11) 19 (16)* 24 (20)*

First 2 years of life

Prevalence of chest infection
No neonatal resp. illness 2% oxygen treatment only 20% Mechanical ventilation 18% BPD 30%

Admission to hospital for respiratory illness

6% 12% 18% 40%

Current symptoms Respiratory symptoms

LBW (n=121) Wheeze with exercise unrelated to colds Wheeze with or without colds Cough with exercise unrelated to colds Cough with or without colds Frequent nocturnal cough unrelated to colds * p < 0.05 ** p < 0.01 13(11) 19(16) 26(22)* 41(34)** 11(9) Reference (n=100) 9(9) 16(16) 10(10) 17(17) 8(8)

Impact of LBW on early childhood asthma in the United States

Reported asthma prevalence and independent associations for asthma diagnosis In selected characteristics : 1988 National Maternal-Infant Health Survey and 1991 Longitudinal Follow-up Survey Characteristics % with asthma OR 95%CI

Overall 7.1 BW,g <1500 21.9 1500 - 2499 10.9 >/= 2500 6.7 Sex Male 8.4 Female 5.5 chronic lung disease (n = 8058) Yes 20.4 No 6.4
Cross sectional analysis,1988 Brooks AM. Arch Pediatr Adolesc Med. 2001;155:401-406

2.9 1.4 referent 1.6 referent 3.4 referent

2.3 - 3.6 1.1 - 1.8

1.3 - 2.0 2.4 - 4.8

Asthma prevalence and attributable risk calculations based on weighted, national sample sizes
Risk factor Prevalence of risk factor,% Prevalence of Asthma,% 21.9 12.4 9.3 6.0 12.0 AR,% PAR,% Asthma VLBW (N=8071) 0.8 LBW (MLBW+VLBW) 7.0 Maternal smoking 31.2 VLBW(white)(N=3913) 0.6 VLBW 1.8 (African American) (N=3884) 68 46 36 60 56 0.8 1.8 16.0 1.2 2.7 1881 4379 38129 1943 1714 No. of Excess Cases of

Prevalence of diagnosis and respiratory symptoms in premature and term children Premature (%) M (n=107) 7.0 3.0 18.0 8.7 25.0* 17.0 6.7* 27.1* 16.8* Term(%) M (n=2241) 7.2 4.0 20.0 10.1 14.5 12.6 2.7 39.1 9.6

Current asthma Former asthma Recurrent wheezing Recurrent shortness of breath Prolong cough with cold Cough with exercise Pneumonia in 1st year FH of atopy FH of asthma

F (n=146) 10.4* 3.7 22.1* 15.4*

20.7* 17.1* 7.1* 32.2 13.7*

F (n=2333) 4.3 2.3 14.1 7.1

14.6 10.2 1.4 37.2 8.8

9 - 11 yr,Germany Mutius EV. J Pedtric. 1993,123(2);223 - 229

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- - - neonate

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SGA symmetrical G&D

BPD, ROP, PVL, IVH neurosensor impairment

BPD 2