OVERVIEW: What every practitioner needs to know

Are you sure your patient has symptoms of an infant of a diabetic mother? What are the typical findings for this disease?

The most common attributes of an infant of a diabetic mother (IDM) are:

History of maternal diabetes: (Type 2 diabetes mellitus (DM), gestational DM, requiring insulin or not requiring insulin, or insulin-dependent Type I diabetes mellitus or IDDM).

Large for gestational age: (LGA, weight >95%tile for age) or ≥4000 gm birth weight infant, often plethoric and Cushingoid in appearance, and often with hypoglycemia in the first 2-4 hours of life. If the mother had longstanding DM with vascular disease, the infant may actually be growth restricted (IUGR) rather than LGA.

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Hypoglycemia: Hypoglycemia is transient and generally resolves within 24-48 hours with feedings and IV glucose therapy when needed. Only 5% of IDMs continue to have hypoglycemia at two days of age. Infants of insulin-dependent Type 1 diabetic mothers are more likely to have moderate to severe hypoglycemia. Over 50% of IDM infants have glucose ≤39 mg%, and 20% have glucose <30 mg%, compared with only 15% incidence of glucose ≤39 mg% in infants of gestational, noninsulin-dependent diabetic mothers.

Hypoglycemia may be asymptomatic, or may present as any combination of poor feeding, diaphoresis, tremors and jitteriness, hypotonia, hypothermia, lethargy, irritability, abnormal cry, cyanosis, pallor, tachypnea, apnea, or seizures.

Prematurity: IDMs are frequently late preterm (34-36 completed weeks of gestation) or early term (37-38 completed weeks of gestation), and frequently manifest exaggerated hyperbilirubinemia, respiratory distress syndrome, and other problems related to prematurity such as feeding difficulties and hypocalcemia.

Other common problems: These are related to the need for operative delivery and the possibility of birth trauma (related to macrosomia), birth defects (if mother is IDDM or has Type 2 DM pre-conception), polycythemia, and certain other metabolic abnormalities (hypocalcemia, hypomagnesemia).

If the clinical appearance and behavior of the newborn suggests maternal diabetes, maternal glycosylated hemoglobin (HbA1c) can be tested. Elevated HbA1c (>6%) suggests abnormal maternal glucose homeostasis during the pregnancy as a possible explanation for the clinical picture.

What other disease/condition shares some of these symptoms?

Some infants are LGA and hypoglycemic without a maternal history of DM. Of non-IDM LGA infants screened for hypoglycemia, approximately 16% will have a blood glucose ≤30 mg% within the first 24 hours after birth (9% in the first 1 hour, 3.5% between 2-5 hours, and 2.4% between 6-24 hours of age). In mothers who had an oral GTT during the latter part of pregnancy, an elevated 1-hour glucose was related to the incidence of hypoglycemia in these LGA infants. If the 1-hour glucose was 180-239 mg%, 22% of the infants had hypoglycemia, and if the 1-hour glucose was ≥240 mg%, 50% of the infants had hypoglycemia, implying that at least some of these infants probably were IDM’s.

Some infants may have severe (glucose <20-25 mg%), persistent and recurrent episodes of hypoglycemia lasting >1-2 days, usually without a history of maternal DM, and with or without size abnormalities (LGA or IUGR). Such infants should be evaluated for other causes of hypoglycemia depending on family history, physical examination, and amount of glucose infusion rate needed to maintain euglycemia. Other causes of hyperinsulinemic hypoglycemia (HH) include congenital sporadic or genetic hyperinsulinism (with at least nine different genetic abnormalities described), Rh isoimmunization, and Beckwith-Wiedemann syndrome (hyperinsulinism accompanied by macrosomia, macroglossia, dysmorphic features and omphalocele). There is also a subgroup of IUGR infants with perinatal asphyxia who have protracted HH (weeks to months until resolution, rather than days), the exact mechanism of which is unclear, and which frequently requires further medical treatment, such as diazoxide.

Infants with HH may require a glucose infusion rate of more than 10-15 mg/kg/min to maintain euglycemia, and are often macrosomic with hepatomegaly and cardiomegaly due to the chronic intrauterine hyperinsulinemic state, which results in increased stores of glycogen and fat. Infants with HH appear to have a greater propensity to brain injury from the hypoglycemia than infants with other causes of hypoglycemia as HH is more severe and persistent, and is associated with poor formation of ketone bodies (the brain’s alternate fuel in the newborn period) due to suppressive effects of insulin on lipolysis and ketogenesis.

Other causes of hypoglycemia

These infants will require further evaluation and management. Consultation with an endocrinologist or metabolic specialist is advised.

  • Deficiency of the counter-regulatory hormone response to hypoglycemia including hypopituitarism, growth hormone deficiency, and adrenal steroid disorders (such infants may have associated midline defects, micropenis, or ambiguous genitalia), and fatty acid oxidation disorders (may have family history of sudden infant deaths, Reye’s syndrome, or developmental delay).

  • Other causes of hypoglycemia include glycogen storage disorders, congenital disorders of glycosylation (CDG syndromes), and metabolic disorders such as galactosemia, maple syrup urine disease, propionic acidemia.

These infants will require further evaluation and management. Consultation with an endocrinologist or metabolic specialist is advised.

What caused this disease to develop at this time?

Pregnancy is associated with relative insulin resistance and increased concentrations of counter-regulatory hormones, which predispose to diabetes. Approximately 5-10% of pregnancies are complicated by diabetes, of which 80-88% is gestational diabetes, or diabetes first recognized during pregnancy, and 12-20% is pre-existing. Of these cases in which the diabetes is diagnosed before the pregnancy, 35% are Type 1 DM, and 65% are Type 2. With the current epidemic of obesity in women of childbearing age, Type 2 DM has become much more common prior to pregnancy, but unlike women with Type 1 DM, these women are less likely to receive pre-pregnancy counseling or intervention capable of achieving tight control of their blood sugars prior to conception and during the pregnancy. Their infants may therefore be larger, and have more problems related to the poorly controlled maternal metabolic state. It is estimated that the prevalence of diabetes in pregnancy could double in the next 10 years.

The effect of maternal diabetes on the fetus has to do with the abnormal metabolic milieu to which the fetus is exposed, as well as the fetal response to this abnormality. It is possible that specific fetuses are genetically predisposed to the teratogenic effects of the abnormal metabolic products present. In early pregnancy, the hyperglycemia may affect organogenesis, leading to a higher incidence of congenital malformations, and an increased incidence of spontaneous abortion. In later pregnancy, the hyperglycemia leads to a state of chronic hyperglycemia in the fetus, with resultant pancreatic β-cell hyperplasia, hyperinsulinemia, macrosomia, organomegaly, hypoxemia and acidemia, and polycythemia. There are also increased rates of intrapartum hypoxemia, and birth trauma related to the macrosomia.

Other pregnancy related problems like chronic hypertension and pre-eclampsia are more common in diabetic mothers, and the risk is increased with duration and severity of the diabetic state and the presence of obesity, as well as degree of diabetic control during the pregnancy. These issues can also lead to placental insufficiency and fetal compromise.

For these reasons, and because late pregnancy loss (stillbirth) remains a problem (11-21/1000, most seen in women requiring insulin therapy, and those with poor glycemic control), caesarean section, often before term, is very common. The caesarean section rate is approximately 50% in diabetic pregnancies.

Following delivery, the transplacental glucose supply is abruptly interrupted, but the infant’s hyperinsulinemia continues. This leads to hypoglycemia, and possibly also to disordered counter-regulatory mechanisms, in that excessive insulin suppresses the normal transitional processes of glycogenolysis and lipolysis, both important in normal metabolic transition as they provide the newborn with alternate fuels (ketone bodies) for cerebral metabolism.

Glucose concentrations fall transiently in all mammals, including human infants, in the first 2 hours after birth, commonly to <40 mg%, but most infants are asymptomatic and go on to establish stable concentrations >45 mg% by 3 hours, even with minimal intake (such as breastfeeding), due to their efficient mobilization of glucose from glycogen in the liver, and fatty acids and ketone bodies from fat stores. Ketone bodies and lactate also function as alternative fuels for the brain, preventing symptoms related to the low glucose concentrations. Breastfed infants produce more ketone bodies than formula fed infants, likely due to their lower intake of food in the first days. The hyperinsulinemia in the IDM can interfere with these transitional processes, making the hypoglycemia more pronounced, and potentially more likely to be symptomatic than in the non-IDM infant.

In addition, there may be respiratory distress following elective caesarean section without labor related to retained fetal lung fluid, as well as complications related to late preterm or early term delivery that could interfere with the infant’s ability to feed.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Maternal pregnancy history, oral glucose tolerance testing results, and HbA1c are all helpful in the diagnosis.

  • Maternal HbA1c >6% is suggestive of abnormal carbohydrate metabolism during the pregnancy.

  • Abnormal maternal oral glucose tolerance test results are as follows:

    Screening 50 gm oral glucose challenge at 24-28 weeks: threshold for abnormal plasma glucose is 130-140 mg%. If this occurs, a 3-hour OGTT is recommended.

    Screening 75 gm oral glucose challenge at 24-32 weeks: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Trial found that increasing maternal glucose concentrations were associated with a progressive increase in adverse outcomes such as increasing birth weight and cord-blood C-peptide (~insulin) concentrations, increased incidence of caesarean delivery, and increased incidence of neonatal hypoglycemia.

    ▪ Using 2-hour maternal glucose concentrations of 140-200 mg% as criteria for treatment, a moderate improvement in neonatal outcomes was seen (NNT=43).

Would imaging studies be helpful? If so, which ones?

Chest radiograph (X-ray) may be helpful to diagnose a fractured clavicle, or to evaluate for cardiomegaly in the macrosomic infant, especially if there is respiratory distress. If cardiomegaly is seen, an echocardiogram to evaluate the severity of myocardial hypertrophy and to look for possible left ventricular outlet obstruction is indicated.

If respiratory distress is present, a chest x-ray is indicated to determine the likely cause.

If anomalies are present or suspected, imaging is indicated to evaluate them further.

If renal vein thrombosis (RVT) is suspected because of blood in the urine, poor urine output, flank mass, hypertension, or thrombocytopenia, renal ultrasound with Doppler flows is indicated.

If central venous access (UVC) is placed for glucose administration, abdominal x-ray is indicated for proper positioning.

If you are able to confirm that the patient is an infant of a diabetic mother, what treatment should be initiated?

Infants of diabetic mothers (IDMs) and LGA infants even if not known to be IDM, should be screened for hypoglycemia routinely following birth and during the first 12 hours. For asymptomatic infants, the first feeding should occur within 1 hour of birth, and the glucose should be screened 30 minutes after the feeding. Glucose should then be screened prior to each subsequent feeding. Feedings should occur every 2 to 3 hours.

Infants who have symptoms of possible hypoglycemia, should be tested immediately with a bedside glucose, and, if low (<40 mg%), a confirmatory sample should be obtained for laboratory testing. IV glucose should be given without waiting for the result if the infant is symptomatic.

Most IDMs with hypoglycemia are asymptomatic, and the hypoglycemia is usually transient and responds to feeding. If the glucos concentration is very low (<35 mg%) and does not increase to >40-45 mg% after feeding, or if the infant is unable to feed (e.g. respiratory distress, prematurity), or shows symptoms of hypoglycemia, then IV glucose should be supplied.

If the infant is breastfeeding, supplemental formula or expressed breast milk can be given to prevent and treat hypoglycemia until the breast milk supply is established.

If IV glucose is needed, a “minibolus” of 2 ml/kg D10W (200 mg/kg glucose) is given followed by an infusion of D10W at a glucose infusion rate of 4-8 mg/kg/min (60-100 ml/kg/day), which in most instances will maintain euglycemia and an adequate supply of glucose for the metabolic needs of the brain. The goal of IV glucose is to keep the blood glucose between 40-50 mg%, avoiding higher glucose concentrations so as to avoid further stimulation of insulin production.

A treatment algorithm is supplied (See Figure 1) and is taken from a consensus of experts in the literature. In the absence of a definitive blood glucose concentration below which brain injury is known to occur with certainty, it seems reasonable to use 45 mg% as a lower limit target value for maintaining glucose concentrations once IV infusion is begun, to avoid further stimulating insulin production. Getting the glucose to this concentration quickly, and keeping it there or slightly above may be even more important if the infant has been exposed to much lower concentrations for a longer period of time, or has shown seizures or coma prior to being treated.

Figure 1.n

Treatment Algorithm

If IV access cannot be obtained and the infant is symptomatic, glucagon 100-200 mcg/kg IM can be given to promote glycogenolysis and raise the glucose concentration acutely.

Almost all hypoglycemia related to maternal diabetes resolves within 1-2 days. Hypoglycemia that persists beyond the first few days should be investigated further, as other treatment options, such as diazoxide might be needed. At that point, further laboratory evaluation and consultation with an endocrinologist or metabolic specialist is recommended.

What are the adverse effects associated with each treatment option?

The adverse effects of IV glucose therapy include IV infiltration, malposition of central venous catheters, and perpetuation of the hyperinsulinemia. If too much IV glucose is used, or if wide swings in glucose concentration with episodes of hyperglycemia occur, further insulin secretion and worse rebound hypoglycemia can occur.

What are the possible outcomes of an infant of a diabetic mother?

There is no evidence that transient, (minutes to hours) mild hypoglycemia (25-45 mg%) in otherwise healthy infants is associated with abnormal neurodevelopmental outcome. There are some data that IDMs who had glucose concentrations <20-25 mg%, compared with those who had glucose concentrations above this range (mean glucose 34 mg%), duration unknown for both groups, had more likelihood of brain deficits at 8 years of age than matched control children who were not IDM.

Infants who have prolonged, recurrent and symptomatic hypoglycemia, especially if seizures are present, are known to be at a higher risk for neurodevelopmental abnormalities and abnormal imaging (magnetic resonance imaging [MRI]) studies.

There is also evidence that hypoglycemia in the face of hypoxic-ischemic encephalopathy leads to worse outcome than either condition alone. MRI findings include abnormalities in the upper cortical layers and subcortical white matter, particularly in the parietal and occipital regions, as well as in the hippocampus and caudate. The mechanism of injury is believed to be both lack of energy substrate for neurons, and secondary injury to the superficial cortex from excitatory amino acids in the CSF.

Note that the studies of MRI and neurodevelopmental outcome in human infants who have had hypoglycemia are limited to small numbers, most of whom are IUGR infants and infants born to mothers with hypertension, rather than IDMs, perhaps confounding the effects of hypoglycemia with those of hypoxia-ischemia or chronic intrauterine stress.

To say that symtoms are related to the hypoglycemia, Cornblath has suggested that Whipple’s triad be fulfilled:

The presence of characteristic clinical signs attributable to hypoglycemia;

Coincident low blood glucose concentrations, measured accurately;

Resolution of clinical signs within minutes to hours once normoglycemia is re-established.

Cornblath and others have also suggested that the term “neonatal hypoglycemia” should be reserved for prolonged, recurrent instances of hypoglycemia, and the term “adaptive fluctuations in glucose levels” be used for the transient, easily corrected, and minimally symptomatic variety.

There is an association of both IDM status and LGA birth weight, with or without maternal diabetes, to the future development of obesity, insulin resistance, and metabolic syndrome in the child and future adult, but no specific percentage can be given.

What causes this disease and how frequent is it?

Approximately 5-10% of pregnancies are complicated by diabetes, of which 80-88% is gestational diabetes, or diabetes first recognized during pregnancy, and 12-20% is pre-existing. Of these cases in which the diabetes is diagnosed before pregnancy, 35% are Type 1 DM, and 65% are Type 2. With the current epidemic of obesity in women of childbearing age, Type 2 DM has become much more common prior to pregnancy, but unlike women withType 1 DM, these women are less likely to receive pre-pregnancy counseling or intervention capable of achieving tight control of their blood sugars prior to conception and during the pregnancy. Their infants may therefore be larger, and have more problems related to the poorly controlled maternal metabolic state. It is estimated that the prevalence of diabetes in pregnancy could double in the next 10 years.

Other clinical manifestations that might help with diagnosis and management

Maternal diabetes prior to conception (Type 1 or Type 2) is associated with an increased incidence of congenital malformations. Better maternal glucose control (lower HbA1c) improves this outcome. Ideally, HbA1c should be in the normal range prior to conception (4-6%) to minimize risk, although this is difficult to achieve. Even mild elevations of HbA1c are associated with an increased incidence of malformations.

Congenital malformations are more common in diabetic (3.1%) than non-diabetic (1.4%) pregnancies. Congenital heart disease is increased in incidence, particularly conotruncal malformations and visceral heterotaxias. Examples of malformations and the increase in incidence in IDMs are:

Conotruncal Malformations: Persistent truncus arteriosus (odds ratio [OR] 4.72 compared with nondiabetic population).

Transposition of the great arteries (OR 2.85).

Single ventricle (OR 18.24).

Visceral heterotaxia (OR 6.22).

Central nervous system malformations: anencephaly, spina bifida, and caudal regression syndrome (which is seen almost exclusively to IDMs).

Renal malformations including agenesis, cystic kidneys and hydronephrosis.

Small left colon syndrome presenting as a lower intestinal obstruction.

Perinatal mortality is increased compared to nondiabetic pregnancies with all forms of diabetes, but is lessened by better metabolic control during the pregnancy.

Perinatal mortality is 3% versus 1% in the nondiabetic population.

Stillbirth rate is 2.4% versus 0.4% in the nondiabetic.

Neonatal death rate is 5.3/1000 versus 2.1/1000 in the nondiabetic.

Lethal congenital malformations are 2.4% versus 0.6% in the nondiabetic.

IDMs often have polycythemia (7-10% versus <5% in nondiabetic infants) and are hypercoagulable, potentially leading to large vessel thrombosis, most notably RVT, as well as exaggerated hyperbilirubinemia. Presenting signs of RVT include hematuria, flank mass, thrombocytopenia, hypertension and, sometimes, decreased urine output. It is diagnosed by renal ultrasound with Doppler flows. Treatment is controversial regarding anticoagulation, and for what duration, but heparinization for some period of time is often recommended. Fibrinolytic therapy is not generally employed due to the potential for hemorrhagic side effects. The long-term outcome is generally good, although atrophy of the affected kidney and systemic hypertension are possible.

Hypertrophic cardiomyopathy

Some IDMs, especially those whose mothers had poor metabolic control and who are macrosomic, manifest significant hypertrophic cardiomyopathy (HCM). The true incidence of HCM in the general population of IDMs is unknown, but has been estimated at approximately 20%. A review of 87 pregnancies (97 infants) showed pathologic ventricular hypertrophy in 50% of infants born to mothers with Type 1 DM, 28% in infants born to mothers with Type 2 DM, and 2% in infants born to mothers with gestational DM. HCM in IDMs usually manifests as a murmur with cardiomegaly on chest x-ray, and resolves within a few weeks without specific therapy once the baby is no longer subjected to the abnormal metabolic milieu. HCM, however, can manifest as respiratory distress with a congestive appearance on x-ray and exam, caused by poor cardiac output due to inadequate ventricular filling and outlet obstruction. In these cases, consultation with a pediatric cardiologist to discuss the possible benefit of beta-blocker therapy is warranted. Additionally, cardiotonic agents such as dopamine should be used with caution in this situation due to the possibility of further compromise of cardiac output and worsened tissue perfusion.

Hypocalcemia and hypomagnesemia

Some IDM infants, especially those who are also premature, may develop hypocalcemia manifesting as jitteriness, but with normal blood glucose. If the hypocalcemia is difficult to correct with IV calcium gluconate therapy, hypomagnesemia should also be suspected, and if present, treated.


If the hematocrit is >65-70%, a reduction transfusion (blood removed, normal saline infused in an equal volume) may be indicated, as polycythemia will potentiate the likelihood of hypoglycemia, respiratory distress, hyperbilirubinemia and RVT. The volume of blood to remove and replace is calculated as follows (but is usually approximately 20-25 ml/kg):

           (Hct [observed] – Hct [desired])/Hct [observed] × Blood volume/kg (~80 ml/kg) × birth weight (in kg) = X ml

Birth Trauma

The trauma most likely to be seen in the macrosomic infant delivered vaginally is clavicular or humeral fracture, and/or brachial plexus injury related to shoulder dystocia. The incidence of shoulder dystocia for infants weighing >4500 gm is 15-20%. Erb’s palsy and clavicular fracture each occur in approximately 25% of deliveries complicated by shoulder dystocia. Because of these risks, elective caesarean delivery is common in women with estimated fetal weight over 4000-4500 gm.

What complications might you expect from the disease or treatment of the disease?

Symptomatic hypoglycemia, especially with clear neurologic signs such as seizures, apnea and coma, particularly if prolonged or recurring, results in brain injury. MRI scanning, on a limited number of neonates, showed diffuse cortical and subcortical white matter changes, particularly in the parietal and occipital lobes, which had disappeared in some by several months of age.

The degree of hypoglycemia required to produce brain injury in animal models of hypoglycemia varies greatly by species. Less severe hypoglycemia in human neonates has not been shown conclusively to alter the long-term outcome. The effects of hypoglycemia are probably additive to those of other insults, such as hypoxic-ischemic encephalopathy or sepsis/chorioamnionitis.

Are additional laboratory studies available; even some that are not widely available?

It is important to remember that while bedside glucose analyzers efficiently provide rapid results on minimal blood volumes, they are not as accurate for detecting hypoglycemia as for hyperglycemia, as they were developed primarily for home use in adult diabetic patients. Laboratory plasma glucose should be obtained to confirm suspected hypoglycemia, although treatment should not be delayed while awaiting the result.

It is also important to remember that whole blood glucose (bedside) is generally lower than plasma glucose (laboratory) by as much as 10-15 mg%, and may be affected by high hematocrits, bilirubin levels or blood oxygen tension, depending on the methodology used by the screening device. Blood gas analyzers with glucose modules have accuracy comparable to laboratory measurement.

How can infants of diabetic mothers be prevented?

Given the prevalence of obesity, insulin resistance and Type 2 DM, as well as the increasing prevalence of Type 1 DM in women of childbearing age, prevention would appear to be difficult. Nevertheless, dietary counseling and weight loss in women with obesity and more aggressive treatment of Type 2 DM prior to conception if possible, and during the pregnancy, is likely to improve pregnancy outcomes.

What is the evidence?

Adamkin, DH. “Metabolic screening and postnatal glucose homeostasis in the newborn”. Pediatr Clin N Am. vol. 62. 2015. pp. 385-409. (Updated discussion of difficulties in defining hypoglycemia, and the rationale for the American Academy of Pediatrics consensus guideline.)

Adamkin, DH. “Clinical Report – postnatal glucose homeostasis in late-preterm and term infants”. Pediatrics. vol. 127. 2011. pp. 575-579. (Latest recommendations from the AAP regarding screening, diagnosis and treatment.)

Beardsall, K. “Measurement of glucose levels in the newborn”. Early Human Development. vol. 86. 2010. pp. 263-267. (Review of bedside glucose testing methods, accuracy, errors.)

Burns, CM, Rutherford, MA, Boardman, JP, Cowan, FM. “Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia”. Pediatrics. vol. 122. 2008. pp. 65-74. (Review of outcomes and imaging in a series of 35 newborns with significant hypoglycemia [median 18 mg%].)

Cornblath, M. “A personal view of a bittersweet journey”. NeoReviews. vol. 4. 2003. pp. e2-e5. (Reflections by the master on the history of consensus (or not) in defining neonatal hypoglycemia.)

Cornblath, M, Hawdon, JM, Williams, AF. “Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds”. Pediatrics. vol. 105. 2000. pp. 1141-1145. (Excellent discussion of the controversy over how to define hypoglycemia in the newborn.)

Deshpande, S, Platt, MW. “The investigation and management of neonatal hypoglycemia”. Seminars in Fetal & Neonatal Medicine. vol. 10. 2005. pp. 351-361. (Good discussion of how to define hypoglycemia, when to proceed with further investigations of hypoglycemia, suggested screening and management plan.)

Ecker, JL, Greene, MF. “Gestational diabetes – setting limits, exploring treatments”. N Engl J Med. vol. 358. 2008. pp. 2061-2063. (Editorial related to the Hyperglycemia and Adverse Pregnancy Outcomes study and its importance.)

Harris, DL, Weston, PJ, Harding, JE. “Incidence of neonatal hypoglycemia in babies identified as at risk”. J Pediatr. vol. 161. 2012. pp. 787-791. (No difference in incidence or course of hypoglycemia in different "at risk" groups, but presence of 3 risk factors does increase the likelihood of severe hypoglycemia.)

Hawkins, JS, Casey, BM. “Labor and delivery management for women with diabetes”. Obstet Gynecol Clin N Am. vol. 34. 2007. pp. 323-334. (Excellent overview of the obstetrical issues in management, route of delivery, incidence of shoulder dystocia and birth trauma.)

Hay, WW. “Transient symptomatic neonatal hypoglycemia”. NeoReviews. vol. 4. 2003. pp. e1-e2. (Editorial introduction to Dr. Cornblath's "bittersweet journey" above, by another well-known expert in the area.)

Hay, WW, Raju, TNK, Higgins, RD, Kalhan, SC, Devaskar, SU. “Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: Workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development”. J Pediatr. vol. 155. 2009. pp. 612-617. (Review by an expert panel of what is known and what is not regarding neonatal hypoglycemia.)

Inder, T. “How low can I go? The impact of hypoglycemia on the immature brain”. Pediatrics. vol. 122. 2008. pp. 440-441. (Commentary on the study by Burns, above, putting their findings into a broader perspective.)

Kapoor, RR, Flanagan, SE, James, C, Shield, J, Ellard, S, Hussain, K. “Hyperinsulinaemic hypoglycemia”. Arch Dis Child. vol. 94. 2009. pp. 450-457. (Excellent review of the diagnosis, genetics, evaluation and treatment of persistent hyperinsulinemic hypoglycemia in neonates.)

Kinsley, B. “Achieving better outcomes in pregnancies complicated by Type 1 and Type 2 diabetes mellitus”. Clinical Therapeutics. vol. 29. 2007. pp. S153-S160. (Review of the evidence supporting improved pregnancy outcomes with better maternal metabolic control, including rates for perinatal mortality.)

Lisowski, LA, Verheijen, PM, Copel, JA. “Congenital heart disease in pregnancies complicated by maternal diabetes mellitus: an international clinical collaboration, literature review, and meta-analysis”. Herz. vol. 35. 2010. pp. 19-26. (Review of the teratogenic effects of maternal diabetes during early pregnancy and incidence of congenital heart malformations.)

Maayan-Metzger, A, Lubin, D, Kuint, J. “Hypoglycemia rates in the first days of life among term infants born to diabetic mothers”. Neonatology (formerly Biology of the Neonate). vol. 96. 2009. pp. 80-85. (Retrospective review of incidence of low blood glucose in IDMs and correlation to severity of maternal diabetes.)

Metzger, BE, Lowe, LP, Dyer, AR. “Hyperglycemia and adverse pregnancy outcome (the HAPO Study Cooperative Research Group)”. N Engl J Med. vol. 358. 2008. pp. 1991-2002. (Large multicenter study of maternal hyperglycemia less severe than that in overt diabetes and pregnancy outcome.)

Mohamed, Z, Hussain, K. “The genetics of hyperinsulinemic hypoglycemia”. NeoReviews. vol. 14. 2013. pp. e179-e188. (Up-to-date description of the known genetic etiologies of HH.)

Rozance, PJ, Hay, WW. “Hypoglycemia in newborn infants: features associated with adverse outcomes”. Biology of the Neonate. vol. 90. 2006. pp. 74-86. (Excellent review of the evidence for and against the damaging effects of hypoglycemia, and a suggested management strategy for treatment of transient neonatal hypoglycemia.)

Schaefer-Graf, UM, Rossi, R, Buhrer, C. “Rate and risk factors of hypoglycemia in large-for-gestational-age newborn infants of nondiabetic mothers”. Am J Obstet Gynecol. vol. 187. 2002. pp. 913-917.

Sperling, MA, Menon, RK. “Differential diagnosis and management of neonatal hypoglycemia”. Pediatr Clin N Am. vol. 51. 2004. pp. 703-723. (Review of causes, differential diagnosis and pathways involved in neonatal hypoglycemia.)

Yeh, J, Berger, S. “Cardiac findings in infants of diabetic mothers”. NeoReviews. vol. 16. 2015. pp. e624-e628. (Review of hypertrophic cardiomyopathy in infants of diabetic mothers.)

Ongoing controversies regarding etiology, diagnosis, treatment

The biggest controversy remains how best to define hypoglycemia in the neonate. Most neonatologist experts prefer to use a glucose of <30-35 mg% in asymptomatic healthy infants in the first 2 hours of age, and <40-45 mg% in those who are older than 3 hours or who are symptomatic at any time. Some endocrine specialists suggest defining hypoglycemia as glucose <50 mg% or even <60 mg%, similar to the operational threshold in older children and adults, although evidence for improved outcomes using this definition is not available.