Autopsy case of linear nevus sebaceous syndrome with KRAS (G12D) mutation.

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous syndrome associated with systemic complications that involve multiple organs, including the skin, central nervous system, eyes, and skeleton. LNSS is considered to be caused by mosaic RAS gene mutation. In this report, we present an autopsy case of LNSS in a Japanese boy. The affected neonate had hydrops fetalis and was born at 28 weeks and 4 days of gestation, weighing 2104 g. He had bilateral inverted eyelids, verrucous linear nevus separated along Blaschko's line, myocardial hypertrophy, and pharyngeal constriction, and underwent intensive treatment in NICU for arrhythmia, hydrocephalus, and respiratory distress. The hydrocephalus progressed gradually and he died at the age of 181 days, 12 days after a sudden cardiac arrest and recovery. KRAS G12D mutation was found in a skin biopsy specimen but not in blood cells, suggesting a postzygotic mosaicism. Autopsy revealed novel pathological findings related to LNSS, including intracranial lipomatous hamartoma and mesenteric lymphangioma, in addition to previously reported findings such as multicystic dysplastic kidney. There was the limited expression of mutated KRAS protein in kidneys.

Safety and accuracy of neonatal continuous glucose monitoring.

BACKGROUND: Hypoglycemia is a significant problem for all neonates and requires minimally invasive and reliable monitoring. The primary objective of this study was to verify the safety and accuracy of the continuous glucose monitoring (CGM) of full-term neonates using Freestyle Libre, a flash glucose monitoring (FGM) device. METHODS: The study was conducted on 20 neonates. Shortly after birth, we placed the FGM sensor on the outside of the neonates' thighs. We scanned the CGM values at 60, 120, 180, and 360 min after birth and simultaneously obtained blood glucose values with plantar capillaries by heel puncture. The neonates wore the sensors for up to 6 h and then they were removed. RESULTS: Of the 75 data points to be measured, 65 points (86.7%) were obtained by scan. There was no change in the sensor attachment site in 12 of 18 completed cases in this study but we observed slight induration in four cases (22.2%) and slight redness in one case (5.5%) at the sensor puncture site. A moderate correlation was observed between the CGM and blood glucose values. The CGM values tended to be low at 120, 180, and 360 min after birth, and tended to be high only at 60 min after birth. CONCLUSIONS: The CGM device was safe to wear on the neonate and the CGM data correlated well with blood glucose levels. There was dissociation between CGM data and blood glucose levels in the acute period soon after birth when the blood glucose levels changed rapidly.

The association between congenital heart disease and small for gestational age with regard to the prevalence and outcomes.

AIM: To evaluate the association between small for gestational age (SGA) and the prevalence of congenital heart disease (CHD) and the association of the SGA status with the outcomes among infants with CHD. METHODS: Echocardiography was performed within the first 5 days of life in 5664 consecutive infants. Infants were classified into four groups according to the presence or absence of SGA and CHD. All CHD infants were followed up until either spontaneous resolution of all cardiac lesions, invasive intervention or death. All newborns without CHD were followed for mortality until the final follow-up date. RESULTS: A total of 303 infants were diagnosed with CHD, while 610 were diagnosed with SGA. Among the CHD infants, 56 were SGA, and 247 were not. A multivariable logistic regression analysis showed that the adjusted odds ratio of SGA (9.71, P < .001) was significantly higher than that of other parameters concerning predictors of invasive intervention or death. The mortality rate in the presence of both SGA and CHD (hazard ratio: 33.6, P < .001) was markedly higher than in the absence of both. CONCLUSION: SGA was a significant predictor of invasive intervention for CHD. The combination of CHD and SGA carried a high risk of death beyond that of either alone.

De novo ZBTB7A variant in a patient with macrocephaly, intellectual disability, and sleep apnea: implications for the phenotypic development in 19p13.3 microdeletions.

Interstitial microdeletions at chromosome 19p13.3 are frequently associated with a constellation of clinical features including macrocephaly, characteristic face, intellectual disability, and sleep apnea. Previous studies in 25 patients with 19p13.3 microdeletions have revealed loss of MAP2K2 in 24 patients and that of PIAS4 and ZBTB7A in 23 patients, suggesting that these three adjacent genes are candidate genes for the phenotypic development in 19p13.3 microdeletions. We identified a de novo likely pathogenic heterozygous missense variant of ZBTB7A (NM_015898.3:c.1152C>G, p.(Cys384Trp)) in a Japanese boy with macrocephaly, intellectual disability, and sleep apnea. This variant affects the conserved cysteine residue forming the coordinate bond with Zn2+ ion at the first zinc finger domain, and is predicted to exert a dominant-negative effect because of the generation of homo- and hetero-dimers with the wild-type and variant ZBTB7A proteins. The results argue for a critical relevance of ZBTB7A to the development of most, but probably not all, of the 19p13.3 microdeletion phenotype.

Pitfalls in the assessment of gestational transient thyrotoxicosis.

Gestational transient thyrotoxicosis (GTT) is associated with direct stimulation of the maternal thyroid gland by human chorionic gonadotropin (hCG). It is characterized by slightly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels in early pregnancy and mild or no symptoms. While GTT must be distinguished from Graves' disease (GD), which is associated with maternal and fetal complications, treated GD and new-onset GD in pregnancy are occasionally challenging to distinguish. Evaluating serum hCG levels and TSH receptor antibody (TRAb) titers can help, but the results are not irrefutable due to pregnancy-related immunosuppression. Moreover, GTT can follow unusual clinical courses in relation to some pregnancy complications. Excessive hCG production can cause severe GTT symptoms in patients with hyperemesis gravidarum, trophoblastic disease, or multiple pregnancies. Thyrotoxicosis can emerge beyond the second trimester in patients with gestational diabetes mellitus and mirror syndrome, because of delayed elevations in the hCG levels. Detailed knowledge about GTT is necessary for correct diagnoses and its appropriate management. This review focuses on the diagnosis of GTT, and, particularly, its differentiation from GD, and unusual clinical conditions associated with GTT that require comprehensive management.

Impact of maternal pheochromocytoma on the fetus and neonate.

Pheochromocytoma during pregnancy is rare but potentially harmful to the mother and fetus. Fetal risks are mainly determined by the vasoconstrictive effects of maternal catecholamine on uteroplacental circulation, because the fetus is protected from the direct effects of high catecholamine levels at the placental interface. Uteroplacental insufficiency may lead to spontaneous abortion, fetal growth restriction, premature delivery, and fetal hypoxia, followed by fetal distress and/or birth asphyxia. Adrenalectomy is recommended during the second trimester. When a diagnosis is made during the late second or third trimester, appropriate medical treatment until term and planned delivery with concurrent or delayed adrenalectomy can result in good fetal outcomes. Moreover, when adrenalectomy is planned after delivery, there is concern regarding the potential of antihypertensive drugs to be transferred to breast milk. It is generally known that early detection and proper treatment of pheochromocytoma during pregnancy decrease maternal and fetal mortality. However, in recent case series, antenatal maternal pheochromocytoma diagnosis did not significantly decrease the risk of fetal and neonatal mortality and morbidity, contrary to the maternal death and complication rates. Although intrauterine ischemia and hypoxia due to uteroplacental insufficiency can affect the long-term outcomes of neonates, no systematic studies have been performed.

Sonographic evaluation of adrenal size in neonates (23 to 41 weeks of gestation).

BACKGROUND: Fetal adrenal gland size is known to have a positive correlation with both gestational age and estimated body weight. In contrast, some clinical observations suggest that maturation of the adrenal stress response occurs after 30 weeks of gestation. In this study, adrenal gland size at birth in extremely preterm to term neonates was investigated using ultrasonography to evaluate the adrenal developmental pattern and the impact of prematurity and perinatal factors. METHODS: The area of the right adrenal gland was measured in the first 3 h of life in 350 neonates and corrected for birth weight (BW) to determine the corrected adrenal area index (cAI). The neonates were subdivided into three groups: group 1 (before 30 weeks of gestation), group 2 (30 to 36 weeks), and group 3 (after 37 weeks). Differences in the cAI among the 3 groups were compared to estimate the impact of perinatal factors. RESULTS: The adrenal gland size was measurable in all neonates with gestational age ranging from 23 to 41 weeks. Right adrenal gland area was highly correlated with BW (r = 0.75, p < 0.01). cAI showed a significant negative correlation with gestational age in group 1 (r = - 0.67, p < 0.01), whereas it showed no correlation with gestational age in both groups 2 and 3. As for the impact of perinatal parameters on cAI, only gestational age in group 1 and only fetal distress in group 2 were correlated with cAI. In group 3, perinatal parameters such as fetal distress and low Apgar score were correlated with cAI. CONCLUSIONS: The present study demonstrated that the developmental pattern of fetal adrenal gland was different before and after 30 weeks of gestation, suggesting that the magnitude of adrenal stress response might mature after 30 weeks of gestation.

Hypertrophic pyloric stenosis following persistent pulmonary hypertension of the newborn: a case report and literature review.

BACKGROUND: Although persistent pulmonary hypertension of the newborn (PPHN) and infantile hypertrophic pyloric stenosis (HPS) are both well-known diseases that occur in early infancy, PPHN complicated by HPS is rare. As nitric oxide (NO) is an important mediator of biological functions, on both the vascular endothelium and smooth muscle cells, the decreased production of NO might play a role in the pathogenesis of both PPHN and HPS. We present the case of a neonate who developed HPS following PPHN, including a detailed review on research published to date, and we discuss the pathogenesis of PPHN and HPS. CASE PRESENTATION: A female neonate born at 38 weeks of gestation, weighing 3140 g, developed PPHN due to meconium aspiration syndrome. Intensive treatment with high frequency oscillations and inhaled NO were initiated, and sildenafil and bosentan were added. She gradually recovered. At 15 days of age, the patient developed recurrent vomiting after feeding and the diagnosis of HPS was made. Intravenous atropine therapy was started at 20 days of age, but the efficacy was clinically unsatisfactory. The coadministration with transdermal nitroglycerin improved the symptoms, and oral feeding was successfully re-introduced. CONCLUSIONS: Our patient recovered from both PPHN and HPS using NO-related medications. A decrease in NO synthesis is likely to be a common pathway for PPHN and HPS.

Can echocardiographic screening in the early days of life detect critical congenital heart disease among apparently healthy newborns?

BACKGROUND: Delayed diagnosis of critical congenital heart disease (CCHD) carries a serious risk of mortality, morbidity, and handicap. As echocardiography is commonly used to diagnose congenital heart disease (CHD), echocardiographic investigations in newborns may be helpful in detecting CCHD earlier and with higher sensitivity than when using other screening methods. The present study aimed to evaluate the effectiveness of echocardiographic screening for CCHD in a tertiary care center. METHODS: A retrospective chart review was conducted among newborns delivered at Hamamatsu University Hospital between June 2009 and May 2016. The study included consecutive newborns who underwent early echocardiographic screening (within the first 5 days of life) performed by pediatric cardiologists, were born at ≥36 weeks of gestation, had a birthweight ≥2300 g, and were cared for in the well-baby nursery. Newborns admitted to the neonatal intensive care unit, as well as those with prenatal diagnosis of CHD and/or clinical symptoms or signs of CHD were excluded. Four CHD outcome categories were defined: critical, serious, clinically significant, and clinically non-significant. RESULTS: A total of 4082 live newborns were delivered during the study period. Of 3434 newborns who met the inclusion criteria and had complete echocardiography data, 104 (3.0%) were diagnosed as having CHD. Among these, none was initially diagnosed as having critical or serious CHD. Of the 95 newborns who continued follow-up with a cardiologist, 61 (64%) were determined to have non-significant CHDs that resolved within 6 months of life. Review of excluded newborns revealed nine cases of critical or serious CHD; among these newborns, six were diagnosed prenatally and three had some clinical signs of CHD prior to hospital discharge. CONCLUSIONS: In our tertiary care center, echocardiography screening within the first 5 days of life did not help improve CCHD detection rate in newborns without prenatal diagnosis or clinical signs of CHD. Echocardiographic screening may be associated with increased rate of false-positives (defects resulting in clinically non-significant CHDs) in newborns without prenatal diagnosis or suspicion of CHD.

Sporadic isolated congenital asplenia with fulminant pneumococcal meningitis: a case report and updated literature review.

BACKGROUND: Isolated congenital asplenia (ICA) is a rare and life-threatening condition that predisposes patients to severe bacterial infections. Most of the reported cases are familial and the mode of inheritance is usually autosomal dominant. Here, we report a case of sporadic isolated asplenia and review the literature while focusing on sporadic cases. CASE PRESENTATION: We report the case of an 11-month-old female infant who developed fulminant pneumococcal meningitis. The pneumococcal vaccine-unimmunized patient was hospitalized with fever, irritability, and purpura, and was diagnosed as having meningitis, septic shock, and disseminated intravascular coagulation. Streptococcus pneumoniae was isolated from both cerebrospinal fluid and blood. She was successfully treated with prompt antibiotic therapy. During hospitalization, abdominal ultrasonography and computed tomography findings, scintigraphy results, and Howell-Jolly body-containing red blood cells indicated the presence of asplenia without any visceroarterial anomalies. Moreover, the findings of peripheral blood smears and spleen ultrasonographic examinations of her parents were normal. CONCLUSIONS: Majority of sporadic ICA cases were detected only after the onset of overwhelming infection and had a high mortality. In cases of severe invasive pneumococcal disease, a systematic search for Howell-Jolly bodies on blood smears and the presence of asplenia on abdominal imaging are essential for detecting ICA even in the absence of any family history. After the diagnosis of ICA, patient and parent education, vaccinations, antibiotic prophylaxis, and prompt empiric treatment of febrile episode should be provided.

Seasonal variation in the international normalized ratio of neonates and its relationship with ambient temperature.

BACKGROUND: The morbidity and mortality rates due to cardiovascular events such as myocardial infarction are known to exhibit seasonal variations. Moreover, changes in the ambient temperature are reportedly associated with an increase in these events, which may potentially involve blood coagulation markers. Bleeding due to vitamin K deficiency in neonates, which is associated with high mortality and a high frequency of neurological sequelae, is more commonly observed during the summer season and in warm regions in Japan. To determine the presence of seasonal variation and the influence of ambient temperature on blood coagulation markers in healthy term neonates, we assessed the international normalized ratio (INR) values measured using CoaguChek XS. METHODS: We studied 488 consecutive healthy term neonates who were born at a perinatal center between July 2012 and June 2013. The INR values were measured using CoaguChek XS in 4-day-old neonates who received nursing care in the newborn nursery throughout the duration of hospitalization. The seasonal variations in the INR values and environmental effects on the INR were assessed. RESULTS: The mean monthly INR values peaked in July (1.13 ± 0.08), whereas the lowest values were observed in January (1.05 ± 0.08). Higher levels of INR were observed during the summer season (June to August) than during the winter season (December to February). Simple linear regression analysis indicated the presence of weakly positive but significant correlations between INR and outdoor temperature (r = 0.25, p < 0.001), outdoor relative humidity (r = 0.19, p < 0.001), and room relative humidity (r = 0.24, p < 0.001), and the presence of a significant negative correlation between INR and room temperature (r = -0.13, p = 0.02). Furthermore, multiple linear regression analysis showed that only outdoor temperature significantly influenced the INR. CONCLUSIONS: A seasonal variation in the INR values was observed among neonates, possibly due to the variation in ambient temperature. Even though the neonates received nursing care in the newborn nursery that was constantly air-conditioned, the outdoor temperature was the most influential factor on INR.

International normalized ratio testing with point-of-care coagulometer in healthy term neonates.

BACKGROUND: Neonates routinely receive vitamin K to prevent vitamin K deficiency bleeding, which is associated with a high mortality rate and a high frequency of neurological sequelae. A coagulation screening test might be necessary to detect prophylactic failure or incomplete prophylaxis. However, venous access and the volume of blood required for such testing can be problematic. CoaguChek XS is a portable device designed to monitor prothrombin time while only drawing a small volume of blood. Although the device is used in adults and children, studies have not been performed to evaluate its clinical utility in neonates, and the reference value is unknown in this population. The objectives of the present study were to determine the reference intervals (RIs) for international normalized ratio (INR) using the CoaguChek XS by capillary puncture in healthy term neonates, to evaluate factors that correlate with INR, and to evaluate the device by assessing its ease of use in clinical practice. METHODS: This study included 488 healthy term neonates born at a perinatal center between July 2012 and June 2013. The INRs determined by CoaguChek XS were measured in 4-day-old neonates. RESULTS: The enrolled neonates were orally administered vitamin K 6-12 h after birth. A RI for INRs in 4-day-old neonates was established using the CoaguChek XS with a median value of 1.10 and a range of 0.90-1.30. A significant difference in the INR was noted between male (median value, 1.10; RI, 0.90-1.30) and female (median value, 1.10; RI, 0.90-1.24) neonates (p = 0.049). The INR was found to correlate with gestational age, birth weight, and hematocrit value. CONCLUSIONS: The CoaguChek XS device is safe, fast, and convenient for performing INR assays in neonates. Our study is the first to establish a RI for INRs that were measured using the CoaguChek XS in healthy term neonates.

Umbilical Vein Calcification Associated with Double-Lumen Catheter Malpositioning in an Extremely Low-Birth-Weight Infant.

Umbilical venous (UV) catheters (UVCs) are commonly used in severely ill neonates. Complications associated with UVC often result from an inappropriate UVC position. Calcification of the UV, a rare complication, was observed in an extremely low-birth-weight infant born at 23 weeks of gestation. After birth, the infant experienced respiratory and circulatory dysfunction, followed by disseminated intravascular coagulation (DIC). A UVC was inserted, and circulatory agonists and blood transfusions were administered, as well as a calcium gluconate infusion for hypocalcemia and hyperkalemia. Ten days after birth, calcification was detected in the UV, likely due to a tunica intima injury caused by UVC, a hypercoagulable state due to DIC, and a high-dose calcium gluconate infusion. Additionally, proximal port malpositioning of the double-lumen catheter might have contributed to calcification within the UV. To prevent such complications, real-time ultrasound confirmation with agitated saline contrast during UVC placement is recommended; in the absence of the facility or skills for ultrasonography, X-rays should be performed in the lateral and anteroposterior views. Furthermore, when using multi-lumen catheters, physicians should not only verify the tip position but also ensure proper placement of proximal ports and carefully select medications administered through the ports.

Umbilical Granuloma: Frequency, Associated Factors, 10-Year Treatment Trends, and Effectiveness at a Single Hospital in Japan.

Umbilical granuloma (UG) is a common problem during the neonatal period; however, its epidemiology and etiology are poorly studied, and the best treatment option has not yet been established. We examined the medical records of neonates who were born and underwent 1-month evaluations at our hospital between 2013 and 2022 to investigate the frequency of-and factors associated with-UG, as well as the annual trends of UG treatments and their efficacy. Of the 6680 eligible neonates, 395 (5.9%) had UG. The annual incidence rate ranged from 3.8% to 7.3%. Gestational age, birth weight, and incidence of meconium-stained amniotic fluid were significantly associated with UG. Silver nitrate cauterization was the predominant UG treatment from 2013 to 2016. Silver nitrate cauterization and topical betamethasone valerate were nearly equally applied in 2017. Betamethasone application became predominant in 2018. The healing rates during the initial treatment period were 91% for silver nitrate cauterization, 97.7% for betamethasone application, 60% for ethanol disinfection, and 88% for ligation; these rates were significantly different (p < 0.001). Topical steroid application may be the most effective treatment. If steroid application is ineffective, then silver nitrate cauterization and ligation may be important treatment options.

Clinical Dilemma Involving Treatments for Very Low-Birth-Weight Infants and the Potential Risk of Necrotizing Enterocolitis: A Narrative Literature Review.

Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency with substantial morbidity and mortality risks, especially for very low-birth-weight (VLBW) infants, and unclear multifactorial pathophysiology. Whether common treatments for VLBW infants increase the NEC risk remains controversial. Indomethacin (utilized for patent ductus arteriosus) offers benefits but is concerning because of its vasoconstrictive impact on NEC susceptibility. Similarly, corticosteroids used to treat bronchopulmonary dysplasia may increase vulnerability to NEC by compromising immunity and altering the mesenteric blood flow. Histamine-2 receptor blockers (used to treat gastric bleeding) may inadvertently promote NEC by affecting bacterial colonization and translocation. Doxapram (used to treat apnea) poses a risk of gastrointestinal disturbance via gastric acid hypersecretion and circulatory changes. Glycerin enemas aid meconium evacuation but disrupt microbial equilibrium and trigger stress-related effects associated with the NEC risk. Prolonged antibiotic use may unintentionally increase the NEC risk. Blood transfusions for anemia can promote NEC via interactions between the immune response and ischemia-reperfusion injury. Probiotics for NEC prevention are associated with concerns regarding sepsis and bacteremia. Amid conflicting evidence, this review unveils NEC risk factors related to treatments for VLBW infants, offers a comprehensive overview of the current research, and guides personalized management strategies, thereby elucidating this clinical dilemma.

Accuracy of transcutaneous bilirubin level measured by a JM-105 bilirubinometer.

BACKGROUND: Transcutaneous bilirubin (TcB) measurement is useful, but dissociation with total serum bilirubin (TSB) is a clinical problem in measurement. We verified the accuracy of the latest version of the JM-105 jaundice meter. METHODS: The TcB, TSB, and hematocrit (Hct) measurements obtained in the first 4 days of life in 2788 term neonates were analyzed. RESULTS: When divided into 2-mg/dL classes, the difference between the TcB and TSB measurements did not change as TcB increased, but both overestimation and underestimation of TcB increased as TcB increased. At TcB greater than 11 mg/dL, inaccurate measurements with dissociation greater than 2 mg/dL exceeded 10% of the TcB measurements. The Hct value was associated with overestimation and underestimation. CONCLUSION: To evaluate neonatal jaundice accurately, it is desirable to measure TSB by blood sampling before discharge from obstetrics or in the case of worsening jaundice on day 4 or 5 of life.

Intestinal volvulus in utero causing torsion of dilated bowel with ileal atresia: a case report.

BACKGROUND: In utero intestinal volvulus with intestinal atresia is a rare and life-threatening condition that can cause torsion of the dilated bowel. The management and outcomes of this disease remain unclear. CASE PRESENTATION: A 19-year-old woman noticed a decrease in fetal motion at 35 weeks. Fetal ultrasound showed dilated fetal bowel and the whirlpool sign. The patient was referred to our hospital for an emergency cesarean section. The neonate's abdomen was dark and severely distended, and a laparotomy was performed. Necrotic ileum and cord-type intestinal atresia (Type II) were observed in the dilated terminal ileum. The necrotic ileum was resected, and a second-look surgery was performed the following day. Then, we anastomosed the remaining intestine, and the total intestine length was 52 cm. There were no surgical complications, and the patient was discharged without requiring total parenteral nutrition or fluid infusion. The patient's height and weight were within the - 2 standard deviation range of the growth curve at 5 months. CONCLUSIONS: Emergency and appropriate management of intestinal volvulus in utero causing torsion of the dilated bowel resulted in good outcomes in a patient with intestinal atresia. Perinatal physicians should be aware of this emergency condition and plan their treatment approach accordingly.

Exchange Transfusion in Neonatal Sepsis: A Narrative Literature Review of Pros and Cons.

Neonatal sepsis remains a leading cause of morbidity and mortality worldwide. It is widely considered that exchange transfusion (ET) as an adjunctive treatment for neonatal sepsis has the ability to reduce mortality. This review summarizes the current knowledge regarding the efficacy of ET for neonatal sepsis. In neonatal sepsis, immune responses such as proinflammatory and anti-inflammatory cytokines play an important role in pathogenesis and can lead to septic shock, multiple organ failure, and death. Between the 1970s and 1990s several authors reported that ET was effective in the treatment of neonatal sepsis with sclerema. ET removes bacterial toxins and inflammatory cytokines from the blood by replacing it with fresh and immunologically abundant blood, thereby leading to improvement in tissue perfusion and oxygenation. Moreover, ET with fresh whole blood increases neutrophil count and immunoglobulin levels as well as enhancing neutrophil function. However, there is a lack of clear evidence for the clinical efficacy of ET. In addition, adverse events associated with ET have been reported. Although most complications are transient, ET can lead to life-threatening complications. Therefore, ET can be considered a last resort treatment to rescue neonates with severe sepsis with sclerema and disseminated intravascular coagulation.

Pitfalls in the Serological Evaluation of Maternal Cytomegalovirus Infection as a Potential Cause of Fetal and Neonatal Involvements: A Narrative Literature Review.

Cytomegalovirus (CMV) is the most common cause of intrauterine infection and serological assays are the primary tools for assessing CMV infections during pregnancy. CMV-specific immunoglobulin M (IgM) antibodies have been used as a diagnostic marker for primary CMV infection in pregnant women, although CMV-IgM has been detected in non-primary CMV infections. IgG avidity testing may aid the distinguishing of primary from non-primary CMV infection; however, there is no standardized assay for detecting this difference. Moreover, when maternal serology shows positive CMV-IgG with negative CMV-IgM findings, vertical transmission probability following primary CMV infection is often excluded. However, symptomatic congenital CMV infections in the context of negative findings for maternal CMV-IgM have been reported recently. The absence of CMV-IgM is recognized in both primary and non-primary CMV infections. Furthermore, maternal non-primary CMV infections during pregnancy may yield a greater proportion of symptomatic congenital CMV infections than previously thought. If universal prenatal screening is performed, ultrasonography for abnormal fetal findings should be conducted regardless of CMV-IgM antibody status. If not universally screened, CMV antibody screening should be performed whenever routine fetal ultrasound reveals abnormal findings. For suspected fetal CMV infection, amniotic fluid or postnatal infant urine CMV-DNA testing is required.