The Newborn BookSignificance of Physical Findings in the Neonate

Janelle L. Aby, MD

THE NEWBORN BOOK: Significance of Physical Findings in the Neonate

2014 by Janelle L. Aby

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3REVIEWERSDeborah Alcorn, MDAssociate ProfessorPediatric OphthalmologyStanford UniversityStanford, CA

J. Christopher Austin, MDAssociate ProfessorDepartment of UrologyPediatric UrologyOregon Health & Science UniversityPortland, OR

Teresa Bahr, RNLecturerSan Francisco State UniversitySchool of NursingSan Francisco, CA

William Benitz, MDProfessorDepartment of Neonatal and Developmental MedicineStanford University Stanford, CA

Anthony E. Burgos, MD, MPHGeneral PediatricsKaiser Permanente Medical CenterDowney, CA

Renee Dursun, RN, BSNPediatric Staff NurseShriners Hospital Chicago, IL

Yasser El-Sayed, MDProfessor and DirectorDepartment of Maternal-Fetal Medicine & ObstetricsStanford University Stanford, CA

Kimberly A. Horii, MDAssociate Professor Department of PediatricsDivision of DermatologyUniversity of Missouri, Kansas CityKansas City, MO

Noelle Johnstone, MDPediatric HospitalistPalo Alto Medical FoundationClinical InstructorDepartment of PediatricsStanford UniversityStanford, CA

Juliann Lipps Kim, MD Department LeadPediatric Hospitalist ProgramPalo Alto Medical FoundationClinical Assistant ProfessorDepartment of PediatricsStanford University Stanford, CA

Thomas G. McPartland, MDVolunteer Clinical InstructorDepartment of Orthopedic SurgeryRobert Wood Johnson Medical SchoolNew Brunswick, NJ

Anna H. Messner, MD ProfessorResidency DirectorPediatric OHNS Program DirectorDepartment of Otolaryngology andHead & Neck SurgeryStanford UniversityStanford, CA

Lauri Mulvey, MDAttending PhysicianDivision of OphthalmologyChildrens Hospital of PhiladelphiaPhiladelphia, PA

Pete Pellegrino, MD General PediatricsPrinceton Nassau PediatricsPrinceton, NJ

Carrie Anne Phillipi, MD, PhDAssociate Professor Department of PediatricsOregon Health & Science University Portland, OR

4Jocelyn Huang Schiller, MDClinical Assistant ProfessorDepartment of PediatricsUniversity of MichiganAnn Arbor, MI

James E. Shander, MD General PediatricsAurora Medical Group Courtesy Staff PhysicianChildrens Hospital of Wisconsin in MilwaukeeMilwaukee, WI

Mary Gayle Sweet, MDAssistant ProfessorDepartment of Family MedicineVirginia TechCarilion School of MedicineRoanoke, VA

PHOTO CONTRIBUTERSAmerican Association for Pediatric Ophthalmology and Strabismus

JoDee Anderson, MDNeonatologyOregon Health & Science UniversityPortland, OR

J. Christopher Austin, MDAssociate ProfessorDepartment of UrologyPediatric UrologyOregon Health & Science UniversityPortland, OR

Anthony E. Burgos, MD, MPHGeneral PediatricsKaiser Permanente Medical CenterDowney, CA

David A. Clark, MDProfessor and ChairmanDepartment of PediatricsAlbany Medical CollegeAlbany, NY

Dermatology Journal Online

Carly Heninger, MDGeneral PediatricsSea View PediatricsStaff PhysicianCHOC at Mission HospitalMission Viejo, CA

Kimberly A. Horii, MDAssociate ProfessorDepartment of PediatricsDivision of DermatologyUniversity of Missouri, Kansas CityKansas City, MO

Juin Yee Kong, MDFellowDepartment of Neonatology-PerinatologyUniversity of California, San DiegoSan Diego, CA

Prashant Malhotra, MDAssociate Staff PhysicianPediatric Otolaryngology, Head and Neck SurgeryHead and Neck InstituteCleveland Clinic FoundationCleveland, OH

Jane A. Morton, MDGeneral PediatricsBurgess PediatricsMenlo Park, CA

Auckland District Health BoardNewborn ServicesAuckland City HospitalAuckland, New Zealand

Department of Obstetrics & GynecologyStanford UniversityPalo Alto, CA

5Keely Olmsted, MDPediatric Hospitalist and ChairPediatrix Medical GroupAntioch, CA

Lisa Parnell, MDGeneral PediatricsMoses Cone HospitalGreensboro, NC

Pete Pellegrino, MDGeneral PediatricsPrinceton Nassau PediatricsPrinceton, NJ

Reeces Rainbow Adoption MinistryGaithersburg, MD

Kristin Shadman, MDAssistant ProfessorDepartment of PediatricsSchool of Medicine and Public HealthUniversity of WisconsinMadison, WI

Sujit Kumar Shrestha, MDResident PhysicianDepartment of PediatricsTribhuvan University Teaching HospitalMaharajgunj, Nepal

Vivian Shih, MDFellowDepartment of Pediatric NephrologyLucile Packard Childrens HospitalPalo Alto, CA

Swiss Society of Neonatology

Bin Xia, MDAssociate ProfessorDepartment of NeonatologyWest China Second University HospitalSichuan UniversitySichuan, China

Randy Young, MDCo-ChairmanDisaster Medicine DivisionKaiser PermanenteSan Diego, CA

9INTRODUCTIONThis is not an exhaustive reference. Rather, it is the book I wish I had owned for the past twenty years, ever since I started seeing babies in the well newborn nursery. I would have referred to it often.This volume focuses on conditions that may be present in infants who are

admitted to a regular-care nursery or seen in a general pediatric clinic. Ive included entities that are so common and benign that some may wonder at the need to discuss them at all (fingernail scratches, for example) as well as conditions that are so rare only a handful of case reports exist in the medical literature. Why? Because in any given day, both types of conditions may present themselves to the health care provider. Since awareness necessarily precedes recognition, and recognition precedes correct diagnosis and management, my audacious hope is that this work will ultimately improve the medical care we provide to this group of babies.

Ive purposely omitted conditions that fall exclusively into the realm of neonatology. Gastroschisis, for example, which is often discussed along with omphalocele, is notably absent here. Omphalocele is included because it can occur in a rather well-appearing baby and might be confused with an umbilical hernia. Gastroschisis, on the other hand, is unlikely to be confused with anything else and would readily be recognized by a lay person as a serious problem. For this same reason, I have only included photographs of late pre-term or term infants. While it certainly would be very informative to see the appearance of some of these conditions in extremely premature infants, that is not the focus here.

Ive also arranged the topics in an unconventional wayby body part. This means discussion of the palmar grasp reflex will be found in the hand chapter and not clustered together with the other primitive reflexes. My purpose is two-fold. First, I want this volume to be useful for people at all levels of medical training and practice. Although it can be academically useful to consider all neonatal infectious diseases together, in actual practice it isnt. In the nursery or clinic, one is simply presented with a baby who has a finding affecting some specific area. Despite our wishes otherwise, babies do not come with tags declaring I have an infectious disease or I have a genetic skin abnormality. We simply start with the finding and then consider all the possible etiologies for what we see.

Second, in order to research the appropriate evaluation or treatment for a given problem, we have to know its name. When looking at something weve never previously encountered, its sometimes hard to know where or what to start reading, or whom to consult. My hope is that this anatomically-oriented organizational system will allow practitioners to search for physical findings without knowing the names, and then find guidance for how to proceed.

Certainly, there are many additional entities that might legitimately be included, but arent. Frankly, I just had to stop somewhere. And, since I wanted this reference to include at least one photograph of the finding under discussion,

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the diagnoses that made the cut were those that could be associated with some sort of visual image, even if that image reflected a lack of visible abnormality (prenatal testicular torsion, for example).

Hopefully, this current collection is just the beginning. There is so much more to know! Despite the fact that medical science has expanded tremendously in the last 300 years, relatively little attention has been given to physical findings in infants, and even less to the specific group of babies highlighted here.

Janelle L. Aby, MD October 2014

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TABLE OF CONTENTSChapter 1

Prenatal UltrasoundVentriculomegaly.......................... 18Choroid Plexus Cyst ..................... 22Cavum Velum Interpositi ............. 25Enlarged Cisterna Magna ............. 28Absent Nasal Bone ....................... 33Increased Nuchal Translucency ..... 37

Echogenic Intracardiac Focus ....... 40Hyperechogenic Bowel ................. 43Dilated Bowel .............................. 46Pelviectasis .................................... 48Short Femurs ................................ 52

Chapter 2General Characteristics

Appropriate For Gestational Age ..56Small For Gestational Age ............ 58Large For Gestational Age ............ 62Twins ........................................... 66Discordant Twins ......................... 71Vernix Caseosa ............................. 74Meconium Staining ...................... 77

Acrocyanosis ................................. 80Perioral Cyanosis .......................... 83Cyanosis ....................................... 87Plethora ........................................ 90Jaundice ....................................... 94Hypotonia .................................... 99

Chapter 3Head

Hair Color ................................. 106White Forelock........................... 108Hair Whorls ............................... 111Microcephaly ............................. 113Macrocephaly ............................. 115Fontanels .................................... 118Sunken Fontanel ........................ 121Bulging Fontanel ........................ 123Molding ..................................... 125Overriding Sutures ..................... 128

Caput Succedaneum ................... 130Cephalohematoma ..................... 132Subgaleal Hemorrhage................ 135Craniotabes ................................ 139Congenital Skull Depression ...... 141Bruising...................................... 145Cephalocele ................................ 147Scalp Electrode Site .................... 151Vacuum Mark ............................ 154Forceps Mark ............................. 156

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Chapter 4Eyes

Normal Eyes ............................... 162Eye Asymmetry .......................... 166Hypotelorism ............................. 169Hypertelorism ............................ 171Eyelid Edema ............................. 174Ectropion ................................... 176Eyelid Coloboma ........................ 179Dacryostenosis ........................... 182Dacryocystocele .......................... 184Epicanthal Folds ......................... 187

Conjunctivitis ............................ 190Subconjunctival Hemorrhage ..... 193Scleral Icterus ............................. 195Blue Sclerae ................................ 199Limbal Dermoid ........................ 201Corneal Opacity ......................... 204Leukocoria ................................. 207Absent Red Reflex ...................... 210Iris Coloboma ............................ 213Unusual Eye Movements ............ 217

Chapter 5Ears

Normal Ear ................................ 226Ear Deformation ........................ 230Microtia ..................................... 234Low-Set Ear................................ 237

Posteriorly Rotated Ear ............... 240Hypertrichosis Pinna .................. 243Preauricular Pit ........................... 244Preauricular Tag .......................... 247

Chapter 6Nose

Normal Nose .............................. 252Positional Nasal Deformity ......... 256Nasal Septum Dislocation .......... 259Nasal Hypoplasia ........................ 262

Nasal Dermoid ........................... 265Nasal Rim Defect ....................... 267Choanal Atresia .......................... 269

Chapter 7Jaw and Mouth

Mandibular Asymmetry ............. 274Micrognathia .............................. 276Asymmetric Crying Facies .......... 281Facial Nerve Palsy ....................... 284Rooting Reflex ........................... 289Sucking Reflex ............................ 292Sucking Callus ........................... 297Cleft Lip..................................... 299Median Alveolar Notch .............. 303Gingival Cyst ............................. 304Congenital Epulis ....................... 307Eruption Cyst............................. 309

Natal Tooth ................................ 311Sucking Pads .............................. 314Ankyloglossia ............................. 316Macroglossia............................... 319Imperforate Whartons Duct ....... 322Epstein Pearls ............................. 325Palatal Cysts ............................... 327Thrush........................................ 329Bifid Uvula ................................. 333Cleft Palate ................................. 336High Arched Palate .................... 340

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Chapter 8Neck

Excess Nuchal Skin .................... 346Goiter ........................................ 348Sternocleidomastoid Tumor of Infancy ....................................... 352

Cystic Hygroma ......................... 355Clavicle Fracture......................... 358

Chapter 9Chest

Intercostal Retractions ................ 364Skin Tag ..................................... 367Supernumerary Nipple ............... 370Widely Spaced Nipples ............... 373Breast Hypertrophy .................... 376Witchs Milk ............................... 378

Bloody Nipple Discharge ........... 380Amastia ...................................... 382Prominent Xiphoid .................... 386Bifid Xiphoid ............................. 388Cleft Sternum ............................ 390Pectus Excavatum ....................... 393

Chapter 10Abdomen

Linea Nigra ................................ 398Diastasis Recti ............................ 399Epigastric Hernia........................ 402

Umbilical Hernia ....................... 404Prune Belly ................................. 408

Chapter 11Umbilicus

Normal Cord ............................. 414Cord Care .................................. 417Meconium Staining .................... 419Umbilical Vessel Coiling ............. 422Two-Vessel Cord ........................ 425Three-Vessel Cord ...................... 427Four-Vessel Cord ........................ 429

Whartons Jelly Cyst ................... 432Umbilical Cord Hematoma ........ 434Umbilical Granuloma ................. 437Patent Urachus ........................... 439Omphalitis ................................. 443Omphalocele .............................. 447

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Chapter 12Genitalia

Normal Male Genitalia ............... 452Smegma ..................................... 454Penile Pearl ................................. 455Buried Penis ............................... 458Webbed Penis ............................. 460Penile Torsion ............................. 463Chordee ..................................... 466Megameatus ............................... 468Megalourethra ............................ 471Hypospadias ............................... 474Epispadias .................................. 478Accessory Urethra ....................... 482Hydrocele ................................... 485

Inguinal Hernia .......................... 487Undescended Testicle ................. 490Ectopic Testicle........................... 494Testicular Torsion ....................... 496Ambiguous Genitalia .................. 499Normal Female Genitalia ........... 504Physiologic Vaginal Discharge .... 506Vaginal Withdrawl Bleeding ....... 507Hymenal Tag .............................. 510Imperforate Hymen .................... 512Paraurethral Cyst ........................ 515Prolapsed Ectopic Ureterocele .... 518Imperforate Anus ....................... 521

Chapter 13 Extremities

Moro Reflex ............................... 528Asymmetric Tonic Neck Reflex ... 532Palmar Grasp Reflex ................... 535Brachial Plexus Injury................. 539Radial Longitudinal Dysplasia .... 542Single Palmar Crease .................. 547Brachydactyly ............................. 549Syndactyly .................................. 553Preaxial Polydactyly .................... 555Central Polydactyly .................... 558Postaxial Polydactyly................... 562Clinodactyly ............................... 565Breech Leg Posture ..................... 567

Hip Dysplasia ............................. 571Joint Contracture ....................... 575Achondroplasia ........................... 581Positional Calcaneovalgus Foot ... 586Tibial Bowing............................. 588Rocker Bottom Foot ................... 591Clubfoot .................................... 594Foot Edema ................................ 597Underlapping Toes ..................... 600Sandal Gap Deformity ............... 602Stepping Reflex .......................... 605Plantar Grasp Reflex ................... 608Babinski Reflex ........................... 611

Chapter 14Back

Galant Reflex.............................. 616Deviated Gluteal Crease ............. 618Sacral Dimple ............................. 620Sacral Skin Tag ........................... 624

Sacral Hypertrichosis .................. 627Lumbosacral Strawberry Nevus ..629Paraspinal Mass .......................... 632Meningomyelocele ..................... 634

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Chapter 15Skin

Lanugo ....................................... 642Hypertrichosis ............................ 644Transient Hypermelanosis .......... 648Caf Au Lait Spot ....................... 651Congenital Melanocytic Nevus ... 654Mongolian Spot ......................... 657Nevus of Ito ............................... 660Nevus of Ota .............................. 662Phakomatosis Pigmentovascularis ..................... 665Port Wine Stain .......................... 670Salmon Patch ............................. 674Mottling ..................................... 677Cutis Marmorata Telangiectatica Congenita .................................. 682Harlequin Color Change ............ 685Neonatal Lupus .......................... 688Cutis Aplasia .............................. 693Subcutaneous Fat Necrosis ......... 698Congenital Hemangioma ........... 701Infantile Hemangioma ............... 704Hemangiomatosis ....................... 709Blueberry Muffin Spots .............. 712Purpura ...................................... 715

Petechiae .................................... 719Bruising...................................... 722Facial Bruising ............................ 726Nevus Anemicus ......................... 729Nevus Depigmentosus ................ 732Sebaceous Nevus ........................ 735Epidermal Nevus ........................ 739Smooth Muscle Hamartoma ...... 742Sebaceous Hyperplasia ................ 745Milia .......................................... 746Miliaria ...................................... 749Neonatal Acne ............................ 752Erythema Toxicum ..................... 755Incontinentia Pigmenti............... 759Sucking Blister ........................... 763Epidermolysis Bullosa ................. 766Herpes Simplex Virus Infection ..771Transient Neonatal Pustular Melanosis ................................... 778Familial Cold Urticaria ............... 781Physiologic Desquamation ......... 784Ichthyosis ................................... 787Fingernail Scratch Marks ............ 791

Chapter 16Body Fluids & Substances

Regurgitated Colostrum ............. 796Regurgitated Blood .................... 798Bilious Emesis ............................ 801Normal Urine ............................. 803Urate Crystals ............................. 806

Vaginal Withdrawal Bleeding ..... 809Meconium.................................. 811Meconium Plug .......................... 814Transitional Stool ....................... 817Newborn Stool ........................... 819

AppendixesAppendix A ................................ 824Appendix B ................................ 826

Appendix C ................................ 827Appendix D ............................... 828

Index .......................................... 833

Chapter 2

GENERAL CHARACTERISTICS

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APPROPRIATE FOR GESTATIONAL AGE

SYNONYMS Average for gestational age Eutrophic newborn

DEFINITIONAn infant is considered appropriate for gestational age (AGA) when the birth weight is between the 10th and 90th percentiles on a standard age-appropriate growth chart. At 40 weeks, an infant who weighs between 2.7 kg4 kg (5 lb 14 oz8 lb 13 oz) falls into this category. At 36 weeks, the AGA range is 2.1 kg3.3 kg (4 lb 10 oz7 lb 5 oz).

BACKGROUNDBy definition, 80% of newborns will have a weight that is appropriate for gestational age at birth. Because it is a normal finding, no predisposing factors have been identified.

PATHOPHYSIOLOGYNormal in utero growth is a result of maternal, placental, and fetal factors working together to allow adequate development of the infant.

DIFFERENTIAL DIAGNOSES Measurement error Incorrect gestational age

MANIFESTATIONS IN NEWBORNAn infant who is appropriate for gestational age normally has a body habitus that is neither overly filled out nor slender. All of the newborns pictured on page 57 are appropriate for gestational age. Even though the actual weights vary, the body proportions are similar for all these patients. The infant in the top photo was born at 40 weeks and weighed 3.1 kg (7 lbs).

RISK TO NEWBORNThere is no risk in being appropriate for gestational age. It is a normal finding.

RECOMMENDED MANAGEMENTParental reassurance regarding the range of sizes considered normal and appropriate may be necessary.

BREASTFEEDING CONSIDERATIONSFor the normal newborn, initiation of breastfeeding should ideally begin within the first hour of life. Frequent feedings (>8 times per day) with an adequate latch are believed to be necessary to initiate normal lactation.

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REFERENCESOlesson, J. 2011 The Newborn. In Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA:Saunders.

Appropriate for gestational age (AGA) infants. Photos provided by parents.

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SMALL FOR GESTATIONAL AGE

SYNONYMS Hypotrophic newborn

DEFINITIONAn infant is generally considered small for gestational age (SGA) when the birth weight is less than the 10th percentile on a standard age-appropriate growth chart. At 40 weeks, an infant with a birth weight of < 2.7 kg (5 lb 14 oz) would fall into this category. At 36 weeks, an infant

General Characteristics Small For Gestational Age 59

PATHOPHYSIOLOGYFetal growth can be restricted through multiple different pathways since growth is determined by maternal, placental, and fetal factors. Maternal diabetes is often associated with excessive infant growth but, if diabetic vascular disease is present, placental blood flow may be impaired and lead to fetal growth restriction. Alcohol, tobacco, and cocaine use can impact fetal growth by reducing maternal appetite, but they can also have vascular effects on the placenta and direct toxic effects on the developing fetus.

In addition to small size, restricted growth adversely affects glucose levels, hemato-crit, and immune function in the infant. The tendency for early hypoglycemia is a result of inadequate glycogen storage. Since the breakdown of glycogen through glycogenol-ysis is the primary source of glucose immediately after birth, adequate glycogen stores are important. Polycythemia is thought to be a result of fetal hypoxemia stimulating erythropoietin production and red blood cell formation. Impaired immune function is related to decreased numbers neutrophils and of T and B lymphocytes. In addition to low numbers at birth, the ability of T lymphocytes to proliferate seems to be reduced throughout childhood, even though the absolute numbers eventually normalize.

Previously, it was believed that symmetrically SGA measurements were evidence of poor growth relatively early in gestation, therefore putting these infants at higher risk for problems. This theory is now being questioned. Some would argue that at least half of the SGA infants with a normal ponderal index are constitutionally small, exhibiting normal growth for their potential, and are therefore not at risk for the problems seen in infants with impaired growth.

DIFFERENTIAL DIAGNOSES Measurement error Incorrect gestational age Growth chart not reflective of racial or ethnic group

MANIFESTATIONS IN NEWBORNInfants who are small for gestational age and have a low ponderal index (asymmetrically SGA) tend to have a thin, sometimes emaciated, appearance. The skin may be dry and relatively loose as a result of decreased subcutaneous tissue. The umbilical cord is often thin. The face may have a wizened appearance, particularly in term and post-term SGA infants. The Moro reflex is often exaggerated; jitteriness and hypertonia are frequently present, even in the absence of hypoglycemia.

Infants who are small for gestational age with a normal ponderal index (symmetrically SGA) will appear proportionate but little.The infants pictured on page 61 provide examples of mild and moderate growth

restriction. The infant in the first photo was born at 37 weeks weighing 2.2 kg (5 lbs) and is mildly affected. The overall appearance seems relatively normal, but the extremities are less plump than expected for an infant of average weight. Look particularly at the creases in the infants right thigh. The infant in the second photo is more mature (39 weeks) but also more noticeably affected. Notice the prominent rib shadows, the flat abdomen, the thin umbilical cord, and the thin extremities.

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Physical examination should include assessment for dysmorphic features, cataracts, hepatosplenomegaly, rash, or other abnormalities which may be associated with in utero infection or chromosomal abnormality. Hypoglycemia may be associated with low body temperature, jitteriness, or seizures. Polycythemia is frequently associated with a ruddy or plethoric appearance. When polycythemia is severe enough to cause impaired blood flow through the vessels (sludging), it may manifest as respiratory distress, feeding intolerance, or seizures. Hypoglycemia and polycythemia may occur in asymptomatic infants, so screening for these complications should be routine.

RISK TO NEWBORNHypoglycemia, hypothermia, polycythemia, and impaired immune function are known complications for SGA infants. SGA infants also have higher rates of cesarean section delivery, perinatal asphyxia, and perinatal mortality. Perinatal mortality occurs in SGA infants (constitutionally small babies excluded) at 1020 times the rate of appropriate for gestational age infants, mostly related to sequelae of hypoxia or chromosomal abnormality.

Later in life, there is an increased risk of obesity, insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and ischemic heart disease. Learning problems, poor fine motor coordination, attention deficit hyperactivity disorder (ADHD), and reduced adult height and weight are also more common among those who were SGA at birth.

RECOMMENDED MANAGEMENTBecause the SGA infant has a large head-to-body ratio, a large body surface-to-mass ratio, and little subcutaneous fat, rapid heat loss can occur. In order to prevent heat loss, the newly born infant should be dried quickly and warmed with with skin-to-skin contact, a radiant warmer, or blankets. Hypoglycemia is a known complication of small birth size, so glucose screening should begin within the first 12 hours of life and continue until the infant is 24 hours old. If hypoglycemia (glucose

General Characteristics Small For Gestational Age 61

infancy is associated with hypertension and obesity in early adulthood. Therefore, overly aggressive attempts to promote catch-up growth can lead to other problems. At present, there are no specific recommendations regarding optimal catch-up growth velocity for SGA infants.

BREASTFEEDING CONSIDERATIONSSmall-for-gestational-age babies do not need routine supplementation with formula. Although colostrum levels of glucose are low, breastfed infants are known to have higher levels of ketone bodies which provide an alternative energy source for the brain. In addition, breastfeeding immediately after delivery (within 30 minutes of birth) is believed to decrease the risk of hypoglycemia.

Small-for-gestational-age (SGA) infants. Top: Minimally SGA infant at 37 weeks. Bottom: Moderately SGA infant at 39 weeks.

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However, some maternal conditions associated with poor in utero growth for the infant can also create breastfeeding challenges. In particular, cesarean delivery, maternal obesity, and diabetes are associated with delayed lactogenesis. For these mothers, the rapid increase in milk volume that normally occurs 23 days after delivery may not occur until the infant is 610 days old. For the infants of these mothers, supplementation with pasteurized, banked breast milk or formula is almost certainly necessary. In addition, the mother should hand express and/or pump colostrum frequently (at least 8 times per day) in order to optimize breast stimulation, improve breast emptying, and collect as much maternal milk as possible for supplementation.

REFERENCESBattaglia, F. C. 2003. Classification by Birthweight and Gestational Age. Neorev 4 (4):e91e93.Battaglia, F. C., et al. 1967. A Practical Classification of Newborn Infants by Weight and Gestational Age. J Pediatr 71 (2):159163.Chard, T., et al. 1992. Evidence of Growth Retardation in Neonates of Apparently Normal Weight. Euro J Obstet Gynecol Reprod Bio

45 (1):5962.Committee Fetus and Newborn, AAP. 2011. Postnatal Glucose Homeostasis in Late-Preterm and Term Infants. Pediatr 127

(3):575579.Cooley, S. M., et al. 2012. Ponderal Index (PI) vs. Birth Weight Centiles in the Low-Risk Primigravid Population: Which is the

Better Predictor of Fetal Wellbeing? J Obstet Gynaecol 32 (5):439443.Das, U. G., et al. 2004 Abnormal Fetal Growth: Intrauterine Growth Retardation, Small for Gestational Age, Large for Gestational

Age. Pediatr Clin N Amer 51 (3):639654.de Rooy, L., et al. 2002. Nutritional Factors that Affect the Postnatal Metabolic Adaptation of Full-Term Small- and Large-for-

Gestational-Age Infants. Pediatr 109 (3):E42.Eglash, A., et al. 2008. Breastfeeding. DM 54 (6):343411.Lawrence, E.J. 2006. A Matter of Size: Part 1. Evaluating the Growth-Restricted Neonate. Adv Neonatal Care 6 (6):313322.Maitra, A. 2009. Diseases of Infancy and Childhood. Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th

edition. Philadephia, Pa: Saunders.Mandy, G. T. 2012 Small for Gestational Age Newborn. UpToDate. www.uptodate.com (accessed 11/13/12).Regnault, T. R. H., et al. 2001. Factors Influencing Fetal Growth. Neorev 2 (6):e119e127.Saenger, P., et al. 2007 Small for Gestational Age: Short Stature and Beyond. Endo Rev 28 (2):219251.Sifianou, P. 2006. Small and Growth-Restricted Babies: Drawing the Distinction. Acta Pdiatr, Int J Pduatr 95 (12):16201624.Thureen, P. J., et al. 2001. The Small-for-Gestational Age Infant. Neorev 2 (6):e139e149.

LARGE FOR GESTATIONAL AGE

SYNONYMS Hypertrophic newborn

DEFINITIONAn infant is considered large for gestational age (LGA) when the birth weight is

greater than the 90th percentile on a standard age-appropriate growth chart. At 40 weeks, an infant with a birth weight of >4 kg (8 lb 13 oz) falls into this category. At 36 weeks, an infant with a birth weight of >3.3 kg (7 lb 5oz) is LGA.

Macrosomia indicates large body size that is unrelated to gestational age and is used when the birth weight is >44.5 kg (8 lb 13 oz9 lb 14 oz). Although many term infants who are LGA are also macrosomic, the two conditions do not always coexist. Preterm LGA infants will rarely be large enough to be considered macrosomic.

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General Characteristics Large For Gestational Age 63

BACKGROUNDBy traditional definition, 1 in 10 babies is large for gestational age (LGA). In the United States, approximately 8% of newborns have a birth weight of >4 kg (8 lb 13 oz at birth and 1% are >4.5 kg (9 lb 14 oz). An increased risk of large infant size is known to be associated with the following:

PATHOPHYSIOLOGYExcessive fetal growth may be related to either genetic or nutritional factors, or both. In the case of maternal diabetes, chronic fetal hyperglycemia and hyperinsulinemia are thought to be the primary factors impacting somatic growth in utero (the Pedersen hypothesis). Insulin is known to have potent effects on growth, particularly of insulin-sensitive tissues such as fat, skeletal muscle, and cardiac muscle. Insulin-like growth factors are also thought to play a role; various authors have reported correlations between IGF-I or IGF-II levels and maternal diabetes or Beckwith-Wiedemann syndrome.

Hyperinsulinemia is even seen in LGA babies born to non-diabetic mothers. Infants with an HNF4A gene mutation are part of this group. The HNF4A gene is associated with maturity-onset diabetes of the young.

Whatever the cause of hyperinsulinemia in the fetus, when the glucose supply from the placenta is abruptly cut off at birth, an overproduction of endogenous insulin in the newborn (greater than needed to control the endogenous glucose supply) causes the glucose level to drop. Normal negative feedback mechanisms will eventually bring insulin and glucose levels into balance, but this may take some time.The polycythemia that is seen in some LGA infants is thought to result from

fetal hypoxemia stimulating erythropoietin production and increasing red blood cell formation.

Race or EthnicityIndigenous people groups in United States and Canada

Genetic SyndromesBeckwith-Wiedemann syndromeSotos syndromeSimpson-Golabi-Behmel syndromeWeaver syndrome

MiscellaneousProlonged gestationMacrosomia in siblingOther conditions

Maternal ConditionsMaternal diabetesMaternal obesityMultiparous motherMaternal weight gain >15.9 kg (35 lbs) during pregnancy

GenderMale infant

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DIFFERENTIAL DIAGNOSES Measurement error Incorrect gestational age Growth chart not reflective of racial or ethnic group

MANIFESTATIONS IN NEWBORNInfants who are large for gestational age tend to have a plump, stocky appearance. Physical examination should include assessment for large fontanels, hypertelorism, macroglossia, low set ears, muscular hypertrophy, hypotonia, supernumerary nipples, hepatosplenomegaly, umbilical hernia, omphalocele, inguinal hernia, undescended testicle, or polydactyly which may be associated with Beckwith-Wiedemann or other overgrowth syndrome.

Hypoglycemia may be associated with low body temperature, jitteriness, or seizures. Polycythemia is frequently associated with a ruddy or plethoric appearance. When polycythemia is severe enough to cause impaired blood flow through the vessels (sludging), it may manifest as respiratory distress, feeding intolerance, or seizures. Hypoglycemia and polycythemia may occur in asymptomatic infants, so screening for these complications should be routine.The most common birth injuries for LGA babies are clavicular fracture and brachial

plexus injury. Clavicular fracture often causes swelling or crepitus over the affected bone. Brachial plexus injury is manifest by an abnormal arm position and decreased arm movement on the affected side.The first infant shown on page 65 was born at term weighing 5.3 kg (11 lb 13 oz)

to a mother with gestational diabetes; the second infant was born at 36 weeks to a non-diabetic mother and weighed 5.5 kg (12 lb 3 oz). In both cases, there is a plump appearance of the neck, trunk, and extremities.

RISK TO NEWBORNHypoglycemia, polycythemia, hyperbilirubinemia and birth injury (bruising, fracture, brachial plexus injury) are known complications of macrosomia. Hypoglycemia has been noted in 2%5% of LGA infants compared with 1% of normal weight infants of non-diabetic mothers.

Risk of clavicular fracture and brachial plexus injury is higher for LGA babies than it is for AGA or SGA infants. Risk of cesarean delivery, respiratory distress syndrome, meconium aspiration, and the need for mechanical ventilation for more than 30 minutes is also increased. LGA infants who are >4.5 kg (9 lb 14 oz) also have higher rates of perinatal asphyxia (evidenced by low Apgar scores) and perinatal mortality rates. In one retrospective study, an increased incidence of adrenal hemorrhage was associated with birth weight >4 kg (8 lb 13 oz). A propensity to adult obesity is also associated with large infant size.

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General Characteristics Large For Gestational Age 65

RECOMMENDED MANAGEMENTBecause hypoglycemia is a known complication of large birth size, glucose screening should start within the first 12 hours of life and continue until the infant is 24 hours old. If hypoglycemia (glucose

66 The Newborn Book

BREASTFEEDING CONSIDERATIONSLarge-for-gestational-age babies do not need routine supplementation with formula. Although colostrum levels of glucose are low, breastfed infants are known to have higher levels of ketone bodies which provide an alternative energy source for the brain. One prospective study of 84 infants found that breastfeeding in the delivery room (within 30 minutes of birth) significantly decreased the incidence of hypoglycemia in infants of diabetic mothers when compared with either early formula feeding (in the delivery room) or delayed breastfeeding (2 hours after birth).

However, some maternal conditions associated with excessive in utero growth for the infant can also create breastfeeding challenges. In particular, cesarean delivery, maternal obesity, and diabetes are associated with delayed lactogenesis. For these mothers, the rapid increase in milk volume that normally occurs 23 days after delivery may not occur until the infant is 610 days old. For the infants of these mothers supplementation with pasteurized, banked breast milk or formula is almost certainly necessary. In addition, the mother should pump or hand express colostrum frequently (at least 8 times per day) in order to optimize breast stimulation, improve breast emptying, and collect as much maternal milk as possible for supplementation.

REFERENCESAkinbi, H. T., et al. 1995. Macrosomic Infants of Non-Diabetic Mothers and Elevated C-peptide Levels in Cord Blood. J Pediatr

127 (3):481484.Chertok, I.R. 2009. Effects of Early Breastfeeding on Neonatal Glucose Levels of Term Infants Born to Women with Gestational

Diabetes. J Hum Nutr Diet 22 (2):166169.Committee Fetus and Newborn, AAP. 2011. Postnatal Glucose Homeostasis in Late-Preterm and Term Infants. Pediatr 127 (3):575-

579.Das, U. G., et al. 2004. Abnormal Fetal Growth: Intrauterine Growth Retardation, Small for Gestational Age, Large for Gestational

Age. Pediatr Clin N Amer 51 (3):639654.de Rooy, L., et al. 2002 Nutritional Factors that Affect the Postnatal Metabolic Adaptation of Full-Term Small- and Large-for-

Gestational-Age Infants. Pediatr 109 (3):E42.Groenendaal, F., et al. 2006 Hypoglycaemia and Seizures in Large-for-Gestational-Age (LGA) Full-Term Neonates. Acta Paediatr 95

(7):874876.Gyurkovits, Z., et al. 2011. Neonatal Outcome of Macrosomic Infants: An Analysis of a Two-Year Period. Euro J Obstet Gynecol

Reprod Bio 159 (2):289292.Lawrence, E. J. 2007. A Matter of Size: Part 2. Evaluating the Large-for-Gestational-Age Neonate. Adv Neonatal Care 7 (4):187197.Mandy, G. T. 2012. Large-for-Gestational-Age Newborn. UpToDate. www.uptodate.com (accessed 11/13/12).Sayers, S. M. 2009. Indigenous Newborn Care. Pediatr Clin N Amer 56 (6):12431261.Verge, C. F., et al. 2010. Overgrowth. Arch Dis Child 95 (6):458463.

TWINS

SYNONYMS Multiple birth Multiples

DEFINITIONWhen two infants develop simultaneously in utero, they are known as twins.

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General Characteristics Twins 67

BACKGROUNDOverall twins are present in 1.3% of births, but rates vary. In the United States, for example, twins now account for more than 3% of births. Worldwide, the highest rate of twinning is in sub-Saharan Africa. Factors that are known to be associated with twin pregnancies include the following:

PATHOPHYSIOLOGYDizygotic (non-identical) twins are believed to be the result of two oocytes being released from the ovary during the same menstrual cycle (polyovulation). The two oocytes are then fertilized by two sperm, creating two separate ova. When this occurs naturally, higher levels of serum gonadotropins are believed to be responsible. This is the same process by which hormonal induction of ovulation occurs. A genetic mutation on chromosome 3 has also been correlated with dizygotic twinning.

Monozygotic (identical) twins are believed to be the result of one ovum splitting early in development, creating two embryos. One hypothesis is that a teratogenic event is responsible. Another hypothesis suggests that a reduction in calcium ions, which are necessary for normal cell adhesion, leads to the monozygotic twinning that is seen with in vitro fertilization. Composition of culture fluids and length of exposure are thought to be contributing factors.The chorion is the outer membrane surrounding the embryo and amniotic fluid.

It is vascularized, has villi, and forms the fetal portion of the placenta. The amnion (amniotic sac) is the inner membrane surrounding the embryo and amniotic fluid. When there is only one chorion for both babies, the developing twins are always monozygotic. When there are two chorions and two amnions, the twins are usually dizygotic, but not always. If separation of the zygote occurs within the first two days of fertilization, monozygotic twins can have separate chorions. A dichorionic diamniotic arrangement of membranes is the most common, since it is present in all dizygotic twins and some monozygotic twins. The least common arrangement of membranes, occurring in only 1% of twin pregnancies, is that of one chorion and one amnion which is shared by both twins. Conjoined twins always have this arrangement, but non-conjoined identical twins may also be monochorionic monoamniotic.

DIFFERENTIAL DIAGNOSIS None

MiscellaneousInfertility treatmentFamily history of twins

Maternal ConditionsAdvanced maternal ageMultiparous motherMaternal BMI >30Maternal height >164 cm

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MANIFESTATIONS IN NEWBORNTwins are more likely than singletons to be born before 37 weeks of gestation, to have low birth weight, and to have congenital anomalies. In particular, respiratory distress, temperature instability, poor feeding, and jaundice are common problems of small and preterm infants. Cyanosis, tachypnea, poor perfusion, an unusual heart murmur, or heart sounds that are maximal in the right chest are signs related to cardiac disease. Pallor due to anemia or plethora due to polycythemia may be related to twin-twin transfusion syndrome or to another underlying problem (prematurity, growth restriction, in utero infection, etc). In the twin pair pictured on page 69, notice the difference in color between the two siblings. Although neither would be described as plethoric or pale, the twin on the right side is somewhat pinker than the twin on the left. Deformations such as unusual head molding (positional plagiocephaly), bowing of the limbs, and clubfeet are also rather common in twins, presumably due to a constrained in utero environment.The determination of monozygotic (identical) or dizygotic (non-identical/fraternal)

status of twins cannot be reliably determined based on appearance. If the gender of the newborns is different, the twins are definitely dizygotic, but if the gender is the same, the determination is more difficult. Only 37% of same-sex twins are identical. Knowledge of the arrangement of placental membranes can help to some degree. All spontaneously conceived monochorionic twins are presumed to be identical, though rare exceptions do occur.

An important note: The designation of twin A and twin B may be different in utero than after birth. In utero, baby A is the one who is positioned lower in the womb. At birth, baby A is the one born first. Clarification is important, since fetal anomalies requiring further evaluation may be present in one and not the other. Some hospitals are now abandoning the practice of designation based on birth order and using only the prenatal designation to avoid this confusion.

RISK TO NEWBORNTwins are more likely than singletons to be born prematurely, small for gestational age, or with a congenital abnormality. Approximately 1 in 10 twins have a congenital anomaly. Compared with singletons, twins also have higher rates of velamentous cord attachment, developmental hip dysplasia, and congenital hypothyroidism. Monozygotic (identical) twins have an increased risk of congenital heart disease and twin-to-twin transfusion syndrome. Monochorionic monoamniotic twins are uniquely at risk for cord entanglement and twin interlocking during delivery.The increased infant mortality seen in twins is primarily due to the underlying

factors that are more common in multiple birthsprematurity, growth restriction, and congenital anomalies.

RECOMMENDED MANAGEMENTScreening for hypoglycemia is recommended for both preterm and small-for-gestational-age infants, and is therefore likely to be indicated for most twins. Hematocrits should be checked on both babies to screen for polycythemia and anemia.

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General Characteristics Twins 69

Both infants should be thoroughly evaluated for congenital malformations, since such problems are more common in twins than in singletons. Examining the twins next to each other is usefuldiscordance in size, color, facial appearance, or other characteristic should raise concerns for an underlying problem. A careful hip exam should be done at birth and at each well-child visit until walking is well established. For female infants born in a breech position, a hip ultrasound at 6 weeks of age is often recommended.

A careful cardiac examination is necessary for all, but monochorionic twins in particular have a significantly increased risk of heart disease (7%57%, depending on whether the twins have two amniotic sacs or one). If one twin has known cardiac disease, the other has a 25% chance of also having a cardiac condition. Screening with fetal echocardiogram has been recommended for twins who are at high risk of cardiac anomalies (monochorionic twins, twins with discordant nuchal translucencies, or twins with twin-twin transfusion syndrome). No recommendations have been made for newborns in these categories that did not have a fetal echocardiogram. However, a postnatal echocardiogram seems reasonable if the infant is symptomatic, has a sibling with cardiac disease, is known to be a twin-twin transfusion recipient, or is a monochorionic monoamniotic twin.

Zygosity testing will be needed for same sex, dichorionic twins if having such information is important. Benefits of knowing this information with certainty include the ability to provide better disease counseling regarding risk for one twin when the other has a medical diagnosis.

Twins at 38 weeks gestational age.

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70 The Newborn Book

In the case of same-sex twins, a repeat screening for congenital hypothyroidism should be considered at 2 weeks of life. Although uncommon in general, false negative tests for congenital hypothyroidism on the newborn screen are more common in twins (especially monozygotic twins) than in singletons. This is presumably due to placental blood sharing between the affected and the unaffected twin, causing an initially lower thyroid stimulating hormone (TSH) level in the affected twin.The need for further evaluation will depend on whether other problems are present.

Consultation with a neonatologist is recommended if appropriate management of an individual set of twins is uncertain.

BREASTFEEDING CONSIDERATIONSThe birth of twins poses some unique challenges for the breastfeeding mother. Not only is it a time- and energy-intensive effort to feed two babies, but because many twins are born prematurely or with low birth weight, they may not have the coordination or stamina to feed well. Frequent expression of breast milk (>8 times per day) with hands or breast pump in addition to direct breastfeeding may be necessary both to provide adequate stimulation for ongoing lactation and to collect milk that can be provided to the babies. Even infants who appear to be feeding well may not have adequate milk transfer, so weights should be monitored until steady gains are observed. Skin-to-skin contact between the mother and the infants should be encouraged whenever possible, especially for infants who are not feeding well. Consultation with a lactation specialist may be indicated.

It is helpful to initiate breastfeeding by feeding one infant at a time, in order to assess the ability of each infant to latch and nurse effectively. Once feeding is progressing smoothly, tandem (simultaneous) feedings are used by many mothers of twins in order to increase the efficiency of breastfeeding.

REFERENCESAzam, A., et al. 2012. Missed Congenital Hypothyroidism in an Identical Twin. J Pdiatr Child Health 48 (10):936938.Benirschke, K. 2008. Multiple Gestation: The Biology of Twinning. Creasy and Resniks Maternal-Fetal Medicine, 6th ed.

Philadephia, Pa: Saunders.Eserdag, S., et al. 2010. Cord Entanglement in Monochorionic Monoamniotic Twins. Bratis Med J 111 (12):673-675.Gromada, K. K., et al. 1998. Breastfeeding Twins and Higher Order Multiples. J Obstet Gynecol Neonatal Nurs 27 (4):441449.Hoekstra, C., et al. 2008. Dizygotic Twinning. Human Reprod Update14 (1):3747.Mandy, G. T. 2012. Neonatal Outcome, Complications, and Management of Multiple Births. UpToDate. www.uptodate.com

(accessed 11/25/12).Newman, R., et al. 2012. Multiple Gestations. Obstetrics: Normal and Problem Pregnancies, 6th edition. Philadephia, Pa:Saunders.Samanich, J., 2009. Health Care Supervision for Twin Pairs. Amer J Med Genet Part C Semin Med Genet 151C:162166.Santaloya, J., et al. 2012 TwinsTwice More Trouble? Clin Obstet Gynecol 55 (1):296306.Shipmen, S. A., et al. 2006. Screening for Developmental Dysplasia of the Hip: Systematic Literature Review for the US Preventative

Services Task Force. Pediatr 117 (3):e557e576.

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General Characteristics Discordant Twins 71

DISCORDANT TWINS

SYNONYMS Discordant growth

DEFINITIONThere is some controversy about the exact definition of discordant twins. In general, though, discordant size refers to twins (or higher-order multiples) whose birth weights are dissimilar by 15%25% or more.The degree of discordance is calculated by the following equation:

100 x (weight of larger twin weight of smaller twin) weight of larger twin = % discordant.

BACKGROUNDDiscordant birth weights are noted in as many as 30% of twin births, depending on the population studied. Sixteen percent have birth weights that differ by 20%, and 5% have differences 30%. Factors that are known to be associated with discordant size between twins include the following:

PATHOPHYSIOLOGYIn the case of twin-to-twin transfusion syndrome, vascular anastomosis within the placenta leads to unbalanced blood shunting from one twin to the other. This causes growth restriction of the donor twin. Uneven placental sharing impairs growth by limiting the placental mass that is available to supply nutrients.

Chromosomal or structural anomalies cause discordant size by limiting growth in the affected twin while the unaffected one develops normally.

DIFFERENTIAL DIAGNOSIS Measurement error

Neonatal ConditionsOpposite sex twinsTwin-twin transfusion syndromeChromosomal or structural anomalies in one twinDiscordant manifestation of in utero infectionConstitutional variance between individuals / differences in genetic potentialGestational age

72 The Newborn Book

MANIFESTATIONS IN NEWBORNThe diagnosis of discordance is based on birth weight, not appearance. However, as the difference in weight becomes greater, the physical differences between the siblings are more easily identified on physical examination. The twins in the first photo are discordant, but still fairly similar in overall appearance. The twins in the second photo are more noticeably discordant and had a 1 kg (30%) difference in birth weight. Notice also that this pair has some difference in color, with the smaller twin appearing ruddier than the larger one. Even if twin-to-twin transfusion is not a concern, other factors may lead to polycythemia or anemia.

Mildly discordant twins.

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General Characteristics Discordant Twins 73

RISK TO NEWBORNAn increased risk of neonatal death is associated with discordant size. In cases where the birth weights differ by 30%, the mortality rate of at least one of the twins is more than 4%.

In cases where the discordance is 20%, there is an increased risk of neonatal acidosis, respiratory distress syndrome, and admission to an intensive care unit.

Moderately discordant twins. The weight difference between the two was almost 30%.

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RECOMMENDED MANAGEMENTBoth infants should be thoroughly evaluated for signs of congenital malformations, infections, or genetic conditions that may impact growth. Screening for hypoglycemia is recommended for both preterm and small-for-gestational-age infants, and is therefore likely to be indicated for discordant twins. A hematocrit should be checked on both babies to screen for polycythemia and anemia.The need for further evaluation will depend on whether other problems are present.

Consultation with a neonatologist is recommended if appropriate management of an individual set of twins is uncertain.

BREASTFEEDING CONSIDERATIONSThe birth of twins poses some unique challenges for the breastfeeding mother. Not only is it a time- and energy-intensive effort to feed two babies, but because many twins are born prematurely or with low birth weight, they may not have the coordination or stamina to feed well. Frequent expression of breast milk (>8 times per day) with hands or breast pump in addition to direct breastfeeding may be necessary both to provide adequate stimulation for ongoing lactation and to collect milk that can be provided to the babies. Even infants who appear to be feeding well may not have adequate milk transfer, so weights should be monitored until steady gains are observed. Twins may also have different caloric needsa good feeding plan will be individualized for each one. Skin-to-skin contact between the mother and the infants should be encouraged whenever possible, especially for infants who are not feeding well. Consultation with a lactation specialist may be indicated.

It is helpful to initiate breastfeeding by feeding one infant at a time, in order to assess the ability of each infant to latch and nurse effectively. Once feeding is progressing more smoothly, tandem (simultaneous) feedings are used by many mothers of twins in order to increase the efficiency of breastfeeding.

REFERENCESCleary-Goldman, J., et al. 2008. Growth Abnormalities and Multiple Gestations. Semin Perinatol 32 (3):206212.Frezza, S., et al. 2011. Is Growth-Discordance in Twins a Substantial Risk Factor in Adverse Neonatal Outcomes? Twin Res Human

Genet 14 (5):463467.Gromada, K. K., et al. 1998. Breastfeeding Twins and Higher Order Multiples. J Obstet Gynecol Neonatal Nurs 27 (4):441449.Habli, M., et al. 2009. Twin-to-Twin Transfusion Syndrome: A Comprehensive Update. Clin Perinatol 36 (2):391416.Mandy, G.T. 2012. Neonatal Outcome, Complications, and Management of Multiple Births. UpToDate. www.uptodate.com

(accessed 11/24/12).Miller, J., et al. 2012. Discordant Twins: Diagnosis, Evaluation and Management. Am J Obstet Gynecol 206 (1):1020.Samanich, J. 2009 Health Care Supervision for Twin Pairs. Amer J Med Genet Part C Semin Med Genet 151C:162166.

VERNIX CASEOSA

SYNONYMSNone.

DEFINITIONVernix caseosa is a creamy white substance that is present to varying degrees on the skin at birth.

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General Characteristics Vernix Caseosa 75

BACKGROUNDThe likelihood that large amounts of vernix caseosa will be noted in a newborn depends on characteristics of the baby as well as the mode of delivery. Factors known to be associated with increased vernix include the following:

PATHOPHYSIOLOGYVernix caseosa is proteolipid biofilm composed of sebum, keratin, and hair produced, in part, by the sebaceous glands of the fetus during the third trimester of pregnancy. Its composition is 81% water, 9% lipid, and 10% protein. It is interesting that of the 41 proteins identified in vernix, 25 are not encountered anywhere else in human biology. Almost 40% of the proteins identified are components of innate immunity and 29% have antimicrobial properties.

DIFFERENTIAL DIAGNOSIS Topically applied cream

MANIFESTATIONS IN NEWBORNVernix can be seen on the skin of the newborn immediately after delivery. It may cover a significant portion of the skin surface or may be present only in protected areas (neck, axilla, inguinal creases, etc). It has a moist, rather greasy feel and is resistant to washing. These photos show the appearance of vernix in several newborns. The first photo on page 76 was taken shortly after birth and before bathing. A moderate amount of vernix is present on the forehead. The thick, pasty consistency can be appreciated. Notice how the material retains the imprint of the hat (anterior and superior to the ear) even after the hat is removed. The other two pictures show the typical appearance of vernix after bathing. Only a small residual amount remains in the intertriginous areas.

RISK TO NEWBORNThere is no risk associated with the presence of vernix. In fact, vernix is believed to confer a protective effect on the infant due to its moisture retention, antimicrobial, and antioxidant properties, and is thought to play a role in the normal adaptation of the newborn after delivery.

GenderFemale infant

Neonatal CharacteristicGestational age between 33 and 37 weeks

Race or EthnicityCaucasian ethnicity (as compared with African American)

Delivery ConditionCesarean section delivery

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RECOMMENDED MANAGEMENTAlthough removal of the vernix caseosa is practiced in some cultures, there is evidence that vernix plays a role in protecting and promoting normal bacterial colonization of the skin in the immediate newborn period. For this reason, some recommend that vernix be retained after birth and not removed. Natural elimination of vernix occurs within 510 days.

BREASTFEEDING CONSIDERATIONSNone.

Vernix caseosa. Top: Vernix on the forehead of an infant immediately after birth. The pasty consistency can be appreciated here. Bottom left and right: Residual vernix caseosa in the skin creases after bathing.

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General Characteristics Meconium Staining 77

REFERENCESSingh, G., et al. 2008. Unraveling the Mystery of Vernix Caseosa. Indian J Derm 53 (2):5460.Visscher, M. O., et al. 2005 Vernix Caseosa in Neonatal Adaptation. J Perinatol 25 (7):440446.

MECONIUM STAINING

SYNONYMSNone.

DEFINITIONMeconium staining is a yellow, green, or brown color seen in the amniotic fluid, vernix, umbilical cord, or nails of a newborn. It is caused by the infant stooling into the amniotic fluid before birth.

BACKGROUNDIn utero passage of meconium complicates approximately 13% of deliveries. Meconium staining results when meconium has been present in the amniotic fluid for some time, though the minimum exposure time required for staining to occur is not known. Conditions known to be associated with in utero passage of meconium include the following:

PATHOPHYSIOLOGYNormally, lack of intestinal peristalsis and tonic contraction of the anal sphincter in utero prevent the release of stool into the amniotic fluid. This is partly related to low motilin levels in the fetus. Because motilin levels rise toward the end of gestation, some cases of in utero meconium are thought to be related to the functioning of a more mature intestinal tract. This is also the reason why preterm infants rarely have meconium-stained amniotic fluid, even in the event of fetal distress.

Fetal distress is a widely recognized cause of meconium passage in utero and is thought to result from hypoxia or acidosis that lead to relaxation of the anal sphincter, allowing the release of stool. Compression of the umbilical cord or head of the infant is also thought to be related to relaxation of the anal sphincter, but as a result of vagal stimulation.

Antenatal ConditionsIntrauterine growth restrictionFetal hypoxiaFetal head compression

Environmental InfluenceMaternal heavy cigarette smoking

Maternal DiseasesMaternal hypertensionMaternal diabetesMaternal preeclampsia or eclampsiaMaternal chronic respiratory or cardiovascular disease

Neonatal ConditionGestational age >41 weeks

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78 The Newborn Book

DIFFERENTIAL DIAGNOSIS Bile-stained amniotic fluid

MANIFESTATIONS IN NEWBORNMeconium staining is typically seen on the umbilical cord and nails of the newborn as a yellow or green discoloration. The photos shown here demonstrate the appearance of meconium staining of the nails and the vernix. Nail discoloration can be subtle, but it is most easily appreciated in the free edge of the nail. The nail edges in this photo are visibly yellowed (compare to the examiners thumbnail). If vernix is present, the normally white material may also be discolored.

Signs of respiratory distress (tachypnea, intercostal retractions, cyanosis, grunting, or nasal flaring) in an infant born through meconium-stained amniotic fluid may signal the onset of meconium aspiration syndrome. The symptoms of meconium aspiration syndrome may be present at birth or may have an onset several hours later.

It is important to note that the presence of staining does not automatically imply that the infant has passed meconium or has a normally functioning gastrointestinal tract. In rare cases, the amniotic fluid may actually be discolored by bilious emesis that occurs in utero as a result of intestinal obstruction.

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General Characteristics Meconium Staining 79

RISK TO NEWBORNWhen meconium is present in the amniotic fluid, there is a risk of aspiration and subsequent pulmonary disease (meconium aspiration syndrome). Most newborns born through amniotic-stained fluid will do well, but up to 5% will have respiratory distress caused by meconium aspiration syndrome. Although severity of the condition is variable, it can be associated with persistent pulmonary hypertension and may be lethal.

RECOMMENDED MANAGEMENTThe management of infants in the delivery room who are born through meconium-stained fluid has changed in recent years. Previously, all such infants routinely had suctioning of the nose and mouth at the perineum (before delivery of the shoulders) and intubation post-delivery for suctioning of the trachea. Evidence now shows that these interventions do not change the incidence of meconium aspiration syndrome in vigorous infants and may cause harm. The management of depressed infants (low Apgar scores) has not been critically evaluated. In clinical practice, intubation and tracheal suctioning are still done in this setting, but the magnitude of the benefits (if any) remains unknown.

In the nursery, an asymptomatic infant with visible meconium staining needs no special evaluation.

Meconium staining of vernix caseosa.

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If respiratory symptoms develop, a neonatologist should be consulted and the infant transferred to a unit where intensive care (including ventilator support) is available; infants with meconium aspiration syndrome may deteriorate rapidly. The use of surfactant, inhaled nitric oxide, or extracorporeal membrane oxygenation (ECMO) is sometimes required in infants with severe disease.

BREASTFEEDING CONSIDERATIONSMeconium staining in an otherwise well infant has no impact on breastfeeding.

If the infant develops respiratory distress or other symptoms and needs to be separated from the mother, early (within the first 12 hours) and frequent expression of milk (at least 8 times per day) with hands or breast pump should be initiated to establish and maintain lactation. Aliquots of collected milk can be refrigerated or frozen for future use, and the baby should be reintroduced to the breast as soon as possible.

REFERENCESWalsh, M.C., et al. 2007. Meconium Stained Fluid: Approach to the Mother and Baby. Clin Perinatol 34 (4):653665.Wiswell, T. E. 2001. Handling the Meconium-Stained Infant. Semin Neonatol 6 (3):225231.Ahanya, S. N. 2005. Meconium Passage in Utero: Mechanisms, Consequences, and Management. Obstet Gynecol Surv 60 (1):4556.Griffiths, D. M., et al. 1988. When is Meconium-Stained Liquor Actually Bile Stained Vomit? Arch Dis Child 63 (2):201-202.Vijayakumar, P., et al. 2001. When is Meconium-Stained Cord Actually Bile-Stained Cord? Case Report and Literature Review. J

Perinatol 21 (7):467468.Aguilar, A. M., et al. 2011. The Suctioning in the Delivery Room Debate. Early Hum Develop 87 (Suppl 1):S13S15.

ACROCYANOSIS

SYNONYMS Peripheral cyanosis

DEFINITIONAcrocyanosis refers to a blue (cyanotic) appearance of the hands and feet despite normal oxygenation.

Perioral cyanosis is also technically a manifestation of acrocyanosis, but since it can occur in isolation or can be absent when acrocyanosis of the hands and feet is present, the two terms are frequently used separately in clinical practice.

BACKGROUNDAcrocyanosis is a normal finding immediately after birth as the infant transitions from the hypoxic environment of the womb to the outside world. In most infants it is physiologic and transient, but it may also be associated with the following conditions:

Environmental InfluencesCold exposureCatheter-related vasospasmMaternal heavy cigarette smoking

Neonatal ConditionsSepsisHeart failureCongenital hypothyroidismPolycythemiaSandifer syndromeThromboembolismVenous congestion

See Acrocyanosis conditions next page

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General Characteristics Acrocyanosis 81

PATHOPHYSIOLOGYAcrocyanosis of the newborn is thought to result from vasomotor instability. Peripheral acidosis, vasoconstriction, and slow capillary blood flow with increased oxygen extraction have been hypothesized as contributing factors, but the pathophysiology is not well understood. When acrocyanosis occurs in the setting of shock, heart failure, or sepsis, it is related primarily to vasoconstriction.

DIFFERENTIAL DIAGNOSES Slate grey patch (Mongolian spot) Bruising Central cyanosis Reynaud phenomenon Methemoglobinemia Hemangioma Ink from handprints or footprints

MANIFESTATIONS IN NEWBORNAcrocyanosis is most commonly encountered within the first few minutes of life. It is evident as a blue color of the hands and/or feet that may be subtle or striking. In most newborns, acrocyanosis resolves within the first several hours of life, but it may persist for weeks and can come and go unpredictably. When acrocyanosis is physiologic, the affected areas are generally warm to the touch. If the blue extremities are also cool, vasoconstriction associated with underlying pathology should be considered.

Examples of physiologic acrocyanosis in the first few hours of life are shown on page 82. In the first photo, taken one hour after birth, the entire hand is noticeably cyanotic compared with the rest of the baby. In the second photo, very mild cyanosis of the foot is visible. Compare the color of the sole of the foot with the thigh. In the third photo, several of the toes and part of the sole appear blue; other parts are pink. Several minutes before this photo was taken the entire foot was cyanotic, but since acrocyanosis is a transient and changeable finding, transitional states such as this one may be observed.

Acrocyanosis conditions from previous pageIf respiratory symptoms develop, a neonatologist should be consulted and the infant transferred to a unit where intensive care (including ventilator support) is available; infants with meconium aspiration syndrome may deteriorate rapidly. The use of surfactant, inhaled nitric oxide, or extracorporeal membrane oxygenation (ECMO) is sometimes required in infants with severe disease.

BREASTFEEDING CONSIDERATIONSMeconium staining in an otherwise well infant has no impact on breastfeeding.

If the infant develops respiratory distress or other symptoms and needs to be separated from the mother, early (within the first 12 hours) and frequent expression of milk (at least 8 times per day) with hands or breast pump should be initiated to establish and maintain lactation. Aliquots of collected milk can be refrigerated or frozen for future use, and the baby should be reintroduced to the breast as soon as possible.

REFERENCESWalsh, M.C., et al. 2007. Meconium Stained Fluid: Approach to the Mother and Baby. Clin Perinatol 34 (4):653665.Wiswell, T. E. 2001. Handling the Meconium-Stained Infant. Semin Neonatol 6 (3):225231.Ahanya, S. N. 2005. Meconium Passage in Utero: Mechanisms, Consequences, and Management. Obstet Gynecol Surv 60 (1):4556.Griffiths, D. M., et al. 1988. When is Meconium-Stained Liquor Actually Bile Stained Vomit? Arch Dis Child 63 (2):201-202.Vijayakumar, P., et al. 2001. When is Meconium-Stained Cord Actually Bile-Stained Cord? Case Report and Literature Review. J

Perinatol 21 (7):467468.Aguilar, A. M., et al. 2011. The Suctioning in the Delivery Room Debate. Early Hum Develop 87 (Suppl 1):S13S15.

ACROCYANOSIS

SYNONYMS Peripheral cyanosis

DEFINITIONAcrocyanosis refers to a blue (cyanotic) appearance of the hands and feet despite normal oxygenation.

Perioral cyanosis is also technically a manifestation of acrocyanosis, but since it can occur in isolation or can be absent when acrocyanosis of the hands and feet is present, the two terms are frequently used separately in clinical practice.

BACKGROUNDAcrocyanosis is a normal finding immediately after birth as the infant transitions from the hypoxic environment of the womb to the outside world. In most infants it is physiologic and transient, but it may also be associated with the following conditions:

Environmental InfluencesCold exposureCatheter-related vasospasmMaternal heavy cigarette smoking

Neonatal ConditionsSepsisHeart failureCongenital hypothyroidismPolycythemiaSandifer syndromeThromboembolismVenous congestion

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Acrocyanosis can appear in healthy infants during episodes of crying, regurgitation, vomiting, coughing, or breath-holding spells. When gastroesophageal reflux causes episodes of acrocyanosis associated with apnea, hypotonia, or seizure-like movements (Sandifer syndrome) treatment of the underlying problem is generally indicated.

RISK TO NEWBORNThe presence of acrocyanosis immediately after birth is not associated with any risk

for the infant. It is a normal finding.When acrocyanosis is a manifestation of sepsis, heart failure, or other pathology,

the risks to the infant can be severe (including death) if the condition is not promptly recognized and treated.

Acrocyanosis of the hands and feet shortly after birth. Top: The color of the hand is noticeably different than the color of the rest of the skin. Bottom left: Mild acrocyanosis with subtle color change. Bottom right: A transitional state in which marked acrocyanosis of the toes is still visible, but a portion of the sole has turned pink.

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CoverIntroductionTable of ContentsChapter 2