First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia.

BACKGROUND: First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth. OBJECTIVE: The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia. STUDY DESIGN: This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks' gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios. RESULTS: The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001). CONCLUSION: In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

First-trimester prediction of preterm pre-eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth.

OBJECTIVE: To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. DESIGN: Secondary analysis of data from the SPREE study and the ASPRE trial. SETTING: Multicentre studies. POPULATION: In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. METHODS: Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. MAIN OUTCOME MEASURE: Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). RESULTS: Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. CONCLUSION: Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

Knot the Best Scenario: A Case of a Knotted Nasogastric Tube.

ABSTRACT: Nasogastric tubes are widely used in clinical practice for enteral nutrition, medication administration, and gastric decompression. Common complications of their use-such as tube blockage, displacement, and accidental removal-are well described in the literature. However, knotting-a complication that occurs when a knot forms in the nasogastric tube in situ-is rare. This report presents the case of a nasogastric tube that became knotted, causing difficulty in its removal. Key takeaways from this case are discussed, among them that more emphasis should be placed on safe nasogastric tube removal in practitioner training to better prevent such complications in the future.

Incidence tendency, etiological classification and outcome of congenital hypothyroidism in Guangzhou, China: an 11-year retrospective population-based study.

OBJECTIVES: An increased incidence of congenital hypothyroidism (CH) has been described worldwide over the years. In this study, we aimed to investigate the epidemiologic characteristics of CH, the iodine status in Guangzhou, China and to investigate which factors might influence the CH incidence during the period 2010-2020. METHODS: We retrospectively reviewed all cases of CH detected by newborn screening during the period 2010-2020. CH was classified as either suspected thyroid dyshormonogenesis (SDH) or thyroid dysgenesis (TD) based on thyroid ultrasound at first diagnosis. Patients were re-evaluated after 4 weeks of L-thyroxine withdrawal at age of 2-3 years to confirm the diagnosis of permanent CH (PCH) or transient CH (TCH). RESULTS: From 2010 to 2020, 1,655 patients with CH were confirmed from 2,400,383 newborns (1:1,450). The CH incidence increased from 1:2,584 in period [2010-2014] to 1:1,086 in period [2015-2020]. Among the 1,337 patients with thyroid ultrasound, 84.29% were SDH whereas 15.71% had TD. Further analysis revealed that more SDH (78.32%) were TCH whereas more TD (87.12%) turned to be PCH. The proportion of blood spot thyrotropin values >5 mIU/L ranged from 8.03 to 20.46%, indicating iodine deficiency. The prevalence of preterm infants increased from 5.50% in period [2010-2014] to 7.06% in period [2015-2020] (p<0.001). CONCLUSIONS: In the past decade, the CH incidence has increased progressively. SDH was the majority of CH, most of which were TCH, while most patients with TD were PCH. The increased incidence might be mainly due to iodine deficiency and increased rates of preterm infants in our study.

When to give aspirin to prevent preeclampsia: application of Bayesian decision theory.

BACKGROUND: There is good evidence that first-trimester assessment of the risk for preterm preeclampsia and treatment of the high-risk group with aspirin reduces the incidence of preterm preeclampsia. Furthermore, there is evidence that aspirin is associated with an increased risk of maternal and neonatal hemorrhagic complications. Against this background, there are ongoing debates whether aspirin should be recommended for all women or to a subpopulation of women predicted to be at increased risk of developing preeclampsia. Moreover, if a strategy of the prediction and prevention of preterm preeclampsia is to be used, what method should be used for the prediction, and what risk cutoff should be used to decide on who to treat? OBJECTIVE: This study aimed to compare the policies of universal treatment, stratified treatment, and no treatment with aspirin. STUDY DESIGN: Decisions about aspirin prophylaxis were considered from the perspective of the Bayesian decision theory. Using this approach, the treatment policies were evaluated for risks of preterm preeclampsia, effects of aspirin, and trade-offs between the harms and benefits of the treatment. Evidence on the risk of preterm preeclampsia was taken from the Screening programme for pre-eclampsia study, which was a first-trimester screening study for the prediction of preeclampsia. Evidence of the effect of aspirin was taken from the Aspirin for Evidence-Based Preeclampsia Prevention trial, which was a trial of aspirin vs placebo in the prevention of preterm preeclampsia. The trade-off between the benefits and harms of aspirin was specified by addressing the question, "What is the maximum number of women that should be treated to prevent 1 case of preterm preeclampsia?" The number can be considered as an exchange rate between the harms and benefits of using aspirin to prevent preterm PE. Given the uncertainty about the harms associated with aspirin, the treatment policies were compared across a wide range of exchange rates. RESULTS: For exchange rates between 10 and 1000 women treated with aspirin to prevent 1 case of preterm preeclampsia, the net benefit achieved from the risk assessment and targeted treatment of women at high risk of preterm preeclampsia was higher than that from women with no treatment or women with universal treatment with aspirin. CONCLUSION: Universal treatment with aspirin should be avoided. Risk-based screening should be used, and the cutoff for taking aspirin should be determined from the consideration of the trade-off between the benefits and harms and detection, false-positive, and screen-positive rates.

Serum PlGF compared with PAPP-A in first trimester screening for preterm pre-eclampsia: Adjusting for the effect of aspirin treatment.

OBJECTIVE: To compare the predictive performance for preterm-pre-eclampsia (PE) in first-trimester screening by serum placental growth factor (PlGF) versus pregnancy associated plasma protein-A (PAPP-A), in combination with maternal risk factors, mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI), after adjustment for the effect of aspirin in women receiving this treatment. DESIGN: Non-intervention multicentre screening studies for PE in singleton pregnancies. SETTING: Maternity hospitals. POPULATION: Two independent prospective studies of 8775 and 16 451 women with singleton pregnancies attending for routine assessment at 11+0 -13+6 weeks' gestation. METHODS: The competing risks model was used to estimate patient-specific risks of delivery with PE at <37 weeks' gestation based on maternal risk factors and combinations with MAP, UtA-PI and either PlGF or PAPP-A. McNemar's test was used to compare the detection rate (DR) of preterm-PE of screening utilising PlGF versus PAPP-A, after adjustments for the effects of aspirin. MAIN OUTCOME MEASURE: Predictive performance for preterm-PE. RESULTS: In the combined data of 25 226 women, including 678 (2.7%) who developed PE, there were 194(0.8%) with preterm-PE. Addition of PlGF improved the DR of preterm-PE, at 10% screen positive rate, by 18.4% (95% CI 12.2-24.6) in screening by maternal risk factors, by 19.9% (95% CI 13.6-26.2) in screening by maternal factors and MAP, and by 7.0% (95% CI 2.3-11.6) in screening by maternal factors, MAP and UtA-PI. PAPP-A did not significantly improve the DR provided by any combination of biomarkers. CONCLUSION: The predictive performance of first trimester PlGF for preterm-PE is superior to that of PAPP-A.

The clinical value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) semi-quantitative parameters in monitoring neoadjuvant chemotherapy response of osteosarcoma.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive technique which could monitor tumor morphology, blood vessel dynamics, and micro-environmental changes. PURPOSE: To evaluate the value of DCE-MRI semi-quantitative parameters in monitoring the neoadjuvant chemotherapy (NAC) response of osteosarcoma. MATERIAL AND METHODS: Twenty-five patients pathologically confirmed as osteosarcoma received four cycles of NAC followed by surgery. All patients underwent conventional and dynamic MRI twice, before starting chemotherapy and before surgical treatment. With a reference standard of histological response (tumor necrosis rate), semi-quantitative parameters were compared between good response group (TNR ≥ 90%) and non-response group (TNR < 90%). The differences between intra- and inter-group parameters before and after NAC were analyzed by Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was generated to assess the parameters' efficacy in predicting the outcome of NAC. RESULTS: The changes were statistically significant on slope, maximum signal intensity (SImax), time to peak (TTP), signal enhanced extent (SEE), peak percent enhancement (PPE), washout rate (WOR), and enhancement rate (ER) in the good response group (P < 0.05), while only SImax and SEE were different in the non-response group after NAC. The changes in Slope, SImax, TTP, SEE, WOR, and ER were markedly different (P < 0.05) between the two groups after NAC. Also, at the threshold values of 3.2%/s, 175 s, and 5.4% (slope, TTP, and ER), the sensitivity and specificity for predicting good response to chemotherapy were 83.3% and 92.3%, 91.7% and 69.2%, 84.6% and 75.0%, respectively. CONCLUSION: Slope, TTP, and ER values could be used to evaluate and predict the response to NAC in osteosarcoma.

Endoscopic management of idiopathic subglottic stenosis in pregnancy.

AIMS: To describe the use of laser, endoscopic balloon dilatation with jet ventilation anaesthesia in the treatment of pregnant women with idiopathic subglottic stenosis. MATERIALS AND METHODS: This is a case review of pregnant women with idiopathic subglottic stenosis, presenting to a tertiary referral centre with worsening breathlessness. Data were extracted from patient case notes. RESULTS: Four women underwent surgical management of subglottic stenosis in pregnancy. One patient required two procedures during the course of their pregnancy due to restenosis. All women had improvement in symptoms post-operatively and went on to deliver healthy babies at term. CONCLUSION: Endoscopic balloon dilatation of idiopathic subglottic stenosis is a safe and viable treatment option in pregnancy and should be offered as first-line treatment in symptomatic women.

Euglycaemic ketoacidosis in pregnant women with COVID-19: two case reports.

BACKGROUND: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals. CASE PRESENTATIONS: We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery. CONCLUSION: We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.

Predictive performance of the competing risk model in screening for preeclampsia.

BACKGROUND: The established method of screening for preeclampsia is to identify risk factors from maternal demographic characteristics and medical history; in the presence of such factors the patient is classified as high risk and in their absence as low risk. However, the performance of such an approach is poor. We developed a competing risks model, which allows combination of maternal factors (age, weight, height, race, parity, personal and family history of preeclampsia, chronic hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, method of conception and interpregnancy interval), with biomarkers to estimate the individual patient-specific risks of preeclampsia requiring delivery before any specified gestation. The performance of this approach is by far superior to that of the risk scoring systems. OBJECTIVE: The objective of the study was to examine the predictive performance of the competing risks model in screening for preeclampsia by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, referred to as the triple test, in a training data set for the development of the model and 2 validation studies. STUDY DESIGN: The data for this study were derived from 3 previously reported prospective, nonintervention, multicenter screening studies for preeclampsia in singleton pregnancies at 11+0 to 13+6 weeks' gestation. In all 3 studies, there was recording of maternal factors and biomarkers and ascertainment of outcome by appropriately trained personnel. The first study of 35,948 women, which was carried out between February 2010 and July 2014, was used to develop the competing risks model for prediction of preeclampsia and is therefore considered to be the training set. The 2 validation studies were comprised of 8775 and 16,451 women, respectively, and they were carried out between February and September 2015 and between April and December 2016, respectively. Patient-specific risks of delivery with preeclampsia at <34, <37, and <41+3 weeks' gestation were calculated using the competing risks model and the performance of screening for preeclampsia by maternal factors alone and the triple test in each of the 3 data sets was assessed. We examined the predictive performance of the model by first, the ability of the model to discriminate between the preeclampsia and no-preeclampsia groups using the area under the receiver operating characteristic curve and the detection rate at fixed screen-positive rate of 10%, and second, calibration by measurements of calibration slope and calibration in the large. RESULTS: The detection rate at the screen-positive rate of 10% of early-preeclampsia, preterm-preeclampsia, and all-preeclampsia was about 90%, 75%, and 50%, respectively, and the results were consistent between the training and 2 validation data sets. The area under the receiver operating characteristic curve was >0.95, >0.90, and >0.80, respectively, demonstrating a very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slopes were very close to 1.0, demonstrating a good agreement between the predicted risks and observed incidence of preeclampsia. In the prediction of early-preeclampsia and preterm-preeclampsia, the observed incidence in the training set and 1 of the validation data sets was consistent with the predicted one. In the other validation data set, which was specifically designed for evaluation of the model, the incidence was higher than predicted, presumably because of better ascertainment of outcome. The incidence of all-preeclampsia was lower than predicted in all 3 data sets because at term many pregnancies deliver for reasons other than preeclampsia, and therefore, pregnancies considered to be at high risk for preeclampsia that deliver for other reasons before they develop preeclampsia can be wrongly considered to be false positives. CONCLUSION: The competing risks model provides an effective and reproducible method for first-trimester prediction of early preeclampsia and preterm preeclampsia as long as the various components of screening are carried out by appropriately trained and audited practitioners. Early prediction of preterm preeclampsia is beneficial because treatment of the high-risk group with aspirin is highly effective in the prevention of the disease.

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit.

BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women who develop preterm preeclampsia with delivery at <37 weeks' gestation and 90% of those with early preeclampsia at <32 weeks, at a screen-positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high risk for preeclampsia, use of aspirin (150 mg/d from the first to the third trimester), compared to placebo, reduced the incidence of preterm preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio, 0.93; 95% confidence interval, 0.62-1.40). OBJECTIVE: We sought to examine the effect of prophylactic use of aspirin during pregnancy in women at high risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs 31.4 days), a reduction of 20.3 days (95% confidence interval, 7.0-38.6; P = .008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio, 0.42; 95% confidence interval, 0.19-0.93; P = .033). Overall, in the whole population, including 0 lengths of stay for those not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days; 95% confidence interval, 0.45-2.81; P = .014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSION: In pregnancies at high risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term health care costs as well as infant survival and handicap.

[Characteristics of DUOXA2 gene mutation in children with congenital hypothyroidism].

OBJECTIVE: To investigate the characteristics of DUOXA2 gene mutation and the genotype-phenotype relationship in children with congenital hypothyroidism (CH) in Guangzhou, China. METHODS: A total of 20 CH patients with suspected thyroid dyshormonogenesis who had no DUOX2 gene mutation were enrolled. These patients who were born between 2011 and 2012 were screened and diagnosed with CH in the Guangzhou Newborn Screening Center. PCR and direct sequencing were used to analyze DUOXA2 gene mutation. RESULTS: Among the 20 patients, 2 had p.Y246X/p.Y246X homozygous mutation; 4 had monoallelic heterozygous mutation, among whom 2 carried the known pathogenic mutation c.413-414insA, 1 carried p.Y246X, and 1 carried a novel mutation, p.G79R. Reevaluation was performed at the age of 2-3 years, and the results showed that the two patients with p.Y246X/p.Y246X homozygous mutation were manifested as transient and mild permanent CH, respectively. Among the four patients with monoallelic heterozygous mutation, the one who carried p.Y246X mutation was manifested as typical permanent CH, and the other three were manifested as transient CH. CONCLUSIONS: DUOXA2 gene mutation is a common molecular pathogenic basis for CH children with suspected thyroid dyshormonogenesis in Guangzhou, and most of them are manifested as transient CH. There is no association between DUOXA2 genotypes and phenotypes. The novel mutation p.G79R is probably a pathogenic mutation.

Recent advances in the prevention and management of preterm birth.

The management of preterm birth has seen major transformations in the last few decades with increasing interest worldwide, due to the impact of preterm birth on neonatal morbidity and mortality. The prevention strategies currently available for asymptomatic women at risk of preterm birth include progesterone, cervical cerclage and cervical pessary. Each approach has varying effects depending on the patient's prior history of preterm birth, cervical length and the presence of multiple gestations. There is a shift in the focus of antenatal treatment, with the use of prenatal magnesium sulphate and corticosteroids, to reduce neonatal intensive care admissions and longer-term disabilities associated with preterm birth, consequently relieving emotional and economical burden. This article provides an update on the recent advances in prevention and management approaches available for women at risk of preterm birth.

[Clinical features and StAR gene mutations in children with congenital lipoid adrenal hyperplasia].

This article reported the clinical manifestations, steroid profiles and adrenal ultrasound findings in two unrelated Chinese girls with lipoid congenital adrenal hyperplasia (LCAH). Direct DNA sequencing and restriction fragment length polymorphism (RFLP) analysis were used to identify the mutations of steroidogenic acute regulatory protein (StAR) gene. The two patients with 46,XX karyotype, presented hyperpigmentation, growth retardation, and hyponatremia. Steroid profiles analysis revealed elevated plasma adrenocorticotrophic hormone levels, decreased or normal serum cortisol levels and low levels of androgens. Ultrasound examinations revealed that enlarged adrenals in patient 1 and normal adrenals in patient 2. Direct DNA sequencing of StAR gene showed a reported homozygous for c.772C>T(p.Q258X) in patient 1. Compound heterozygous for c.367G>A(p.E123K) and IVS4+2T>A (both novel mutations) were found in patient 2, inherited from her mother and father respectively. The amino acid of mutant position of the novel p.E123K was highly conserved in ten different species and was predicted to have impacts on the structure and function of StAR protein by the PolyPhen-2 prediction software. RFLP analysis revealed three bands (670, 423 and 247 bp) in patient 2 and her father and two bands (423 and 247 bp) in her mother and 50 controls. It is concluded that LCAH should be considered in girls with early onset of adrenal insufficiency and that steroid profiles, karyotype analysis, adrenal ultrasound and StAR gene analysis may be helpful for the definite diagnosis of LCAH.