Review

Authors: Marcia Roeper, Henrike Hoermann, Sebastian Kummer...

Neonatal hypoglycemia affects up to 15% of all newborns. Despite the high prevalence there is no uniform definition of neonatal hypoglycemia, and existing guidelines differ significantly in terms of when and whom to screen for hypoglycemia, and where to set interventional thresholds and treatment goals. In this review, we discuss the difficulties to define hypoglycemia in neonates. Existing knowledge on different strategies to approach this problem will be reviewed with a focus on long-term neurodevelopmental outcome studies and results of interventional trials. Furthermore, we compare existing guidelines on the screening and management of neonatal hypoglycemia. We summarize that evidence-based knowledge about whom to screen, how to screen, and how to manage neonatal hypoglycemia is limited - particularly regarding operational thresholds (single values at which to intervene) and treatment goals (what blood glucose to aim for) to reliably prevent neurodevelopmental sequelae. These research gaps need to be addressed in future studies, systematically comparing different management strategies to progressively optimize the balance between prevention of neurodevelopmental sequelae and the burden of diagnostic or therapeutic procedures. Unfortunately, such studies are exceptionally challenging because they require large numbers of participants to be followed for years, as mild but relevant neurological consequences may not become apparent until mid-childhood or even later. Until there is clear, reproducible evidence on what blood glucose levels may be tolerated without negative impact, the operational threshold needs to include some safety margin to prevent potential long-term neurocognitive impairment from outweighing the short-term burden of hypoglycemia prevention during neonatal period.

Topics: Female; Infant, Newborn; Humans; Child; Blood Glucose; Hypoglycemia; Infant, Newborn, Diseases; Fetal Diseases; Disease Progression

PubMed: 37361517
DOI: 10.3389/fendo.2023.1179102

Review

Authors: Carlos R Ferreira, Clara D M van Karnebeek

Inborn errors of metabolism, also known as inherited metabolic diseases, constitute an important group of conditions presenting with neurologic signs in newborns. They are individually rare but collectively common. Many are treatable through restoration of homeostasis of a disrupted metabolic pathway. Given their frequency and potential for treatment, the clinician should be aware of this group of conditions and learn to identify the typical manifestations of the different inborn errors of metabolism. In this review, we summarize the clinical, laboratory, electrophysiologic, and neuroimaging findings of the different inborn errors of metabolism that can present with florid neurologic signs and symptoms in the neonatal period.

Topics: Adult; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Metabolism, Inborn Errors; Neuroimaging; Pregnancy

PubMed: 31324325
DOI: 10.1016/B978-0-444-64029-1.00022-9

Review

Authors: Amy G Feldman, Ronald J Sokol

Neonatal cholestasis is characterized by conjugated hyperbilirubinemia in the newborn and young infant and is a sign common to over 100 hepatobiliary and/or metabolic disorders. A timely evaluation for its etiology is critical in order to quickly identify treatable causes such as biliary atresia, many of which benefit from early therapy. An expanding group of molecularly defined disorders involving bile formation, canalicular transporters, tight junction proteins and inborn errors of metabolism are being continuously discovered because of advances in genetic testing and bioinformatics. The advent of next generation sequencing has transformed our ability to test for multiple genes and whole exome or whole genome sequencing within days to weeks, enabling rapid and affordable molecular diagnosis for disorders that cannot be directly diagnosed from standard blood tests or liver biopsy. Thus, our diagnostic algorithms for neonatal cholestasis are undergoing transformation, moving genetic sequencing to earlier in the evaluation pathway once biliary atresia, "red flag" disorders and treatable disorders are excluded. Current therapies focus on promoting bile flow, reducing pruritus, ensuring optimal nutrition, and monitoring for complications, without addressing the underlying cause of cholestasis in most instances. Our improved understanding of bile formation and the enterohepatic circulation of bile acids has led to emerging therapies for cholestasis which require appropriate pediatric clinical trials. Despite these advances, the cause and optimal therapy for biliary atresia remain elusive. The goals of this review are to outline the etiologies, diagnostic pathways and current and emerging management strategies for neonatal cholestasis.

Topics: Cholestasis; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases

PubMed: 32861449
DOI: 10.1016/j.sempedsurg.2020.150945

Review

Authors: Shunsuke Araki, Akira Shirahata

Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants.

Topics: Administration, Oral; Breast Feeding; Female; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Milk, Human; Vitamin K; Vitamin K Deficiency Bleeding

PubMed: 32187975
DOI: 10.3390/nu12030780

Authors: Ivo Bendix, Suzanne L Miller, Elke Winterhager...

Topics: Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Small for Gestational Age; Pregnancy

PubMed: 32351451
DOI: 10.3389/fendo.2020.00205

Authors: Ängla Mantel, Angelica Lindén Hirschberg, Olof Stephansson...

IMPORTANCE

The prevalence of eating disorders is high among women of reproductive age, yet the association of eating disorders with pregnancy complications and neonatal health has not been investigated in detail, to our knowledge.

OBJECTIVE

To investigate the relative risk of adverse pregnancy and neonatal outcomes for women with eating disorders.

DESIGN, SETTING, AND PARTICIPANTS

This population-based cohort study included all singleton births included in the Swedish Medical Birth Register from January 1, 2003, to December 31, 2014. A total of 7542 women with eating disorders were compared with 1 225 321 women without eating disorders. Statistical analysis was performed from January 1, 2018, to April 30, 2019. Via linkage with the national patient register, women with eating disorders were identified and compared with women free of any eating disorder. Eating disorders were further stratified into active or previous disease based on last time of diagnosis.

MAIN OUTCOMES AND MEASURES

The risk of adverse pregnancy outcomes (hyperemesis, anemia, preeclampsia, and antepartum hemorrhage), the mode of delivery (cesarean delivery, vaginal delivery, or instrumental vaginal delivery), and the neonatal outcomes (preterm birth, small and large sizes for gestational age, Apgar score <7 at 5 minutes, and microcephaly) were calculated using Poisson regression analysis to estimate risk ratios (RRs). Models were adjusted for age, parity, smoking status, and birth year.

RESULTS

There were 2769 women with anorexia nervosa (mean [SD] age, 29.4 [5.3] years), 1378 women with bulimia nervosa (mean [SD] age, 30.2 [4.9] years), and 3395 women with an eating disorder not otherwise specified (EDNOS; mean [SD] age, 28.9 [5.3] years), and they were analyzed and compared with 1 225 321 women without eating disorders (mean [SD] age, 30.3 [5.2] years). All subtypes of maternal eating disorders were associated with an approximately 2-fold increased risk of hyperemesis during pregnancy (anorexia nervosa: RR, 2.1 [95% CI, 1.8-2.5]; bulimia nervosa: RR, 2.1 [95% CI, 1.6-2.7]; EDNOS: RR, 2.6 [95% CI, 2.3-3.0]). The risk of anemia during pregnancy was doubled for women with active anorexia nervosa (RR, 2.1 [95% CI, 1.3-3.2]) or EDNOS (RR, 2.1 [95% CI, 1.5-2.8]). Maternal anorexia nervosa was associated with an increased risk of antepartum hemorrhage (RR, 1.6 [95% CI, 1.2-2.1]), which was more pronounced in active vs previous disease. Women with anorexia nervosa (RR, 0.7 [95% CI, 0.6-0.9]) and women with EDNOS (RR, 0.8 [95% CI, 0.7-1.0]) were at decreased risk of instrumental-assisted vaginal births; otherwise, there were no major differences in mode of delivery. Women with eating disorders, all subtypes, were at increased risk of a preterm birth (anorexia nervosa: RR, 1.6 [95% CI, 1.4-1.8]; bulimia nervosa: RR, 1.3 [95% CI, 1.0-1.6]; and EDNOS: RR, 1.4 [95% CI, 1.2-1.6]) and of delivering neonates with microcephaly (anorexia nervosa: RR, 1.9 [95% CI, 1.5-2.4]; bulimia nervosa: RR, 1.6 [95% CI, 1.1-2.4]; EDNOS: RR, 1.4 [95% CI, 1.2-1.9]).

CONCLUSIONS AND RELEVANCE

The findings of this study suggest that women with active or previous eating disorders, regardless of subtype, are at increased risk of adverse pregnancy and neonatal outcomes and may need increased surveillance in antenatal and delivery care.

Topics: Adult; Anorexia Nervosa; Birth Weight; Bulimia Nervosa; Feeding and Eating Disorders; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Registries; Sweden; Young Adult

PubMed: 31746972
DOI: 10.1001/jamapsychiatry.2019.3664

Review

Authors: Swathi Chacham, Rachna Pasi, Madhuradhar Chegondi...

Metabolic bone disease (MBD) is an important cause of morbidity in premature, very low birth weight (VLBW) and sick infants and, if left undiagnosed, may lead to structural deformities and spontaneous fractures. MBD is defined as impaired bone mineralization in a neonate with lower than expected bone mineral levels in either a fetus or a neonate of comparable gestational age and/or weight, coupled with biochemical abnormalities with or without accompanying radiological manifestations. MBD has been reported to occur in 16% to 40% of extremely low birth weight neonates and presents by 6-16 weeks after birth. Insufficient calcium and phosphorous stores during the phase of accelerated growth predispose to MBD in neonates along with the use of some medications such as caffeine or steroids, prolonged parenteral nutrition and chronic immobilization. Enhanced physical activity in preterm infants facilitates bone mineralization and weight gain. Biochemical abnormalities tend to worsen significantly, as the severity of disease progresses. These abnormalities may include hypocalcemia, hypophosphatemia, hyperphosphatasia and secondary hyperparathyroidism. In addition, urinary phosphate wasting and hypovitaminosis D can be additional complications. Conversely, biochemical abnormalities may not be accompanied by rachitic changes. Newer diagnostic modalities include non-invasive bone densitometry by quantitative ultrasound over the mid-tibial shaft. The management of MBD includes adequate calcium, phosphorous and vitamin D supplementation, along with optimum nutrition and physical activity. Similarly, preventive strategies for MBD should target nutritional enhancement in combination with enhanced physical activity. MBD usually results in preventable morbidity in preterm and VLBW neonates. Treatment consists of optimum nutritional supplementation and enhanced physical activity.

Topics: Bone Diseases, Metabolic; Disease Management; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature

PubMed: 31674171
DOI: 10.4274/jcrpe.galenos.2019.2019.0091

Review

Authors: Girija Natarajan, Athina Pappas, Seetha Shankaran...

In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described.

Topics: Alanine Transaminase; Apgar Score; Aspartate Aminotransferases; Asphyxia Neonatorum; Biomarkers; Child; Creatinine; Developmental Disabilities; Disability Evaluation; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Magnetic Resonance Imaging; Neurologic Examination; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Severity of Illness Index

PubMed: 27863707
DOI: 10.1053/j.semperi.2016.09.007

Meta-Analysis Review

Authors: Lola Madrid, Anna C Seale, Maya Kohli-Lynch...

BACKGROUND

Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates.

METHODS

We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0-89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence.

RESULTS

We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43-.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36-.47); late-onset disease incidence was 0.26 (95% CI, .21-.30). CFR was 8.4% (95% CI, 6.6%-10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V.

CONCLUSIONS

The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.

Topics: Global Health; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Risk Factors; Serogroup; Streptococcal Infections; Streptococcus agalactiae

PubMed: 29117326
DOI: 10.1093/cid/cix656

Review

Authors: Stephen H LaFranchi

Maternal thyroid hormone crosses the placenta to the fetus beginning in the first trimester, likely playing an important role in fetal development. The fetal thyroid gland begins to produce thyroid hormone in the second trimester, with fetal serum T4 levels gradually rising to term. Full maturation of the hypothalamic-pituitary-thyroid (HPT) axis does not occur until term gestation or the early neonatal period. Postnatal thyroid function in preterm babies is qualitatively similar to term infants, but the TSH surge is reduced, with a corresponding decrease in the rise in T4 and T3 levels. Serum T4 levels are reduced in proportion to the degree of prematurity, representing both loss of the maternal contribution and immaturity of the HPT axis. Other factors, such as neonatal drugs, e.g., dopamine, and non-thyroidal illness syndrome (NTIS) related to co-morbidities contribute to the "hypothyroxinemia of prematurity". Iodine, both deficiency and excess, may impact thyroid function in infants born preterm. Overall, the incidence of permanent congenital hypothyroidism in preterm infants appears to be similar to term infants. However, in newborn screening (NBS) that employ a total T4-reflex TSH test approach, a higher proportion of preterm babies will have a T4 below the cutoff, associated with a non-elevated TSH level. In NBS programs with a primary TSH test combined with serial testing, there is a relatively high incidence of "delayed TSH elevation" in preterm neonates. On follow-up, the majority of these cases have transient hypothyroidism. Preterm/LBW infants have many clinical manifestations that might be ascribed to hypothyroidism. The question then arises whether the hypothyroxinemia of prematurity, with thyroid function tests compatible with either non-thyroidal illness syndrome or central hypothyroidism, is a physiologic or pathologic process. In particular, does hypothyroxinemia contribute to the neurodevelopmental impairment common to preterm infants? Results from multiple studies are mixed, with some randomized controlled trials in the most preterm infants born <28 weeks gestation appearing to show benefit. This review will summarize fetal and neonatal thyroid physiology, thyroid disorders specific to preterm/LBW infants and their impact on NBS for congenital hypothyroidism, examine treatment studies, and finish with comments on unresolved questions and areas of controversy.

Topics: Disease Management; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Pregnancy; Prognosis; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones

PubMed: 34211436
DOI: 10.3389/fendo.2021.666207