Kypros H. Nicolaides’s research while affiliated with King's College Hospital NHS Foundation Trust and other places

Objective To develop and validate a new first‐trimester model for the prediction of gestational diabetes mellitus (GDM) based on maternal demographic characteristics and elements of medical history. Design Prospective cohort study. Setting Inner‐city hospital. Population 41 587 women with singleton pregnancies at 11⁺⁰–13⁺⁶ weeks' gestation, including 4231 (10.2%) who subsequently developed GDM. Methods Logistic regression model for GDM was developed and fivefold cross‐validation was performed to assess the calibration and predictive performance of the model, assessed by the area under the receiver operating characteristic curve (AUROC) and detection rates (DRs) at different screen positive rates (SPRs). Main Outcome Measure GDM. Results In both parous women with a previous history of GDM and nulliparous women or parous women with no history of GDM, significant contributors to the prediction of GDM were maternal age, weight, height, ethnicity and family history of diabetes mellitus. In parous women with no previous history of GDM, there was a contribution from the birthweight z‐score of the previous pregnancy. There was good agreement between the predicted risk and observed incidence of GDM (intercept 0.000, 95% CI: −0.034, 0.034; slope 1.000, 95% CI: 0.967, 1.033). The AUROC curve was 0.757 (95% CI: 0.749, 0.765). The performance was higher for GDM treated with insulin versus metformin or diet alone. At SPR of 40%, the DR of the insulin, metformin and diet alone group was 87.2% (95% CI: 84.9, 89.3), 80.0% (77.8, 82.0) and 61.5% (59.2, 63.7), respectively. Conclusion Assessment of risk for GDM can be achieved in the first trimester based on maternal risk factors.

Aim of the Study Congenital lung malformations (CLM) are a heterogeneous group of anomalies diagnosed with increasing frequency antenatally. Postnatal management is dictated by the clinical status in the early neonatal period. We report our centre's experience in managing symptomatic neonates with CLM. Methods Single centre retrospective review (January 1995-December 2023) of all infants with CLM that underwent thoracotomy for resectional surgery during the neonatal period. Data are quoted as median (IQR), unless stated otherwise. SPSS version 28 (IBM) and GraphPad Prism were used for analysis of data. A P value of ≤ 0.05 was regarded as significant. Results During the study period 228 patients underwent surgery for CLM. Forty-nine infants (21.5%) (33 males) required surgery during the first 30 days of life. Surgery in those infants was performed at 5 (1-10) days (emergency surgery, n=24; expedited, n=25). The indications included respiratory distress (n=29; mechanical ventilation n=16) and size of lesion (n=20). Antenatal diagnosis was established in 45 (91.8%) infants and 18 had undergone antenatal intervention with 7 fetuses having more than one procedure. The CLM was left sided in 29 (59%). Postoperative stay for the surviving infants was 14 (7-21) days with extubation being achieved after 2 (1-4) days. The overall survival was 91.8% (45/49). Infants that underwent antenatal intervention had a higher rate of postnatal pneumothorax (P = 0.01) and required higher FiO2 delivery (P = 0.01). Infants that underwent surgery in an emergency setting were found to have a higher need for antenatal intervention (P = 0.01), postnatally required intubation (P < 0.001) with higher FiO2 delivery (p<0.001) and developed pneumothorax (P = 0.002). Histopathology findings showed the entire spectrum of CLM, with 6 cases of CPAM Type 1 associated with mucinous adenocarcinoma. Cross sectional radiological imaging was available for 31 patients and in 4 patients with malignancy, a solid component of the lesion was appreciable on CT. Median follow-up period was 6 (2.1-11) years. Sixteen (35%) children developed a degree of chest wall deformity through none have required surgical intervention. Conclusions This is one of the largest series documenting the postnatal management of symptomatic neonates with CLM. One fifth of the cohort undergoing surgery for CLM required neonatal intervention. Histology at surgery was heterogeneous with 12% of cases being associated with mucinous adenocarcinoma.

Objective The objective of this study is to examine the association between dietary calcium intake (Ca) and pre‐eclampsia (PE). Design Cohort study. Setting Inner‐city hospital. Population A total of 2838 women with singleton pregnancies at 35⁺⁰–36⁺⁶ weeks' gestation, including 96 (3.4%) who subsequently developed PE. Methods Online 24‐h dietary recall questionnaire was used to measure Ca intake. In the low (< 700 mg/d) vs. adequate (≥ 700 mg/d) Ca intake groups, we compared the prevalence of PE‐associated maternal risk factors and the incidence of PE. In multivariate regression, we examined the low Ca intake and PE relationship, adjusted for established PE risk factors (including blood pressure and angiogenic biomarkers) and any additional factors associated with low Ca intake specifically. Main Outcome Measure PE. Results Overall, 405 (14.3%) women had low Ca intake. Low (vs. adequate) Ca intake was associated with a higher incidence of PE (6.2% vs. 2.9%; odds ratio 2.2, 95% confidence interval 1.3–3.7), as well as more prevalent risk factors for PE, including Black ethnicity (34.1% vs. 11.8%), South Asian ethnicity (10.1% vs. 7.2%), high body mass index (29.8 vs. 28.3 kg/m²) and more deprived index of multiple deprivation (54.3% vs. 35.5%). In multivariate regression adjusting for other PE risk factors, low Ca intake was no longer associated with PE (OR 1.7, 95% CI 0.9–3.2). Conclusions Although some contribution from low Ca to the development of PE cannot be ruled out, after accounting for maternal characteristics, medical history and deprivation, low Ca intake did not make an independent contribution to the development of PE in this population of mixed‐ethnicity women.

We evaluated tumor necrosis factor alpha (TNFα) and uterine artery pulsatility index (UtA-PI) in the triage of patients with suspected preterm delivery (PTD), preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR. The study included 125 pregnant women attending high-risk pregnancy clinics for triage of pregnancy complications. There were 31 pure PE cases, 42 cases of PE combined with FGR, 16 pure FGR cases, 15 PTD cases, and 21 term normal delivery controls. Maternal serum TNFα was determined by immune-diagnostic testing. UtA-PI was measured by Doppler sonography. Demographic, medical and pregnancy history, and mean arterial blood pressure (MAP) were extracted from the hospital medical records. Linear regression coefficients, and Box and Whisker plots were calculated and depicted using non-parametric statistics (Kruskal Wallis and Mann-Whitney). Spearman's regression coefficient assessed marker accuracy; p<0.05 was considered significant. It was found that high TNFα in cases <34 weeks gestation, when coupled to low UtA-PI and normal blood pressure are found in early PTD most likely linked to maternal inflammation. At term, high TNFα combined with high UtA-PI is associated with any FGR (with/without PE), possibly reflecting inflammation and maternal and fetal hypoxia due to the very long period of altered placental perfusion. Accordingly, TNFα, and Doppler UtA-PI could be used for the differential diagnosis of early PTD, and FGR (with/without PE) near delivery.

Background: To assess the incidence of dysglycaemia and metabolic syndrome and factors associated with them 5 months postpartum in women with gestational diabetes mellitus (GDM) in their last pregnancy. Methods: We conducted an observational prospective cohort study in 558 women with previous GDM who attended a 5-month postpartum follow-up clinic. Backward elimination was performed to select significant factors for the multivariable logistic regression model. Dysglycaemia (prediabetes and type 2 diabetes (T2D)) and metabolic syndrome were used as outcomes in separate models. Results: Dysglycaemia was diagnosed in 202 (36.2%) women, including 174 (31.2%) with prediabetes and 28 (5.0%) with T2D. Women with dysglycaemia, compared with those with normoglycaemia, were more likely to be of black ethnicity (33.2 vs. 20.5%) and have severe GDM (31.7 vs. 16%), a higher postpartum BMI (29.5 vs. 27.6 kg/m²), and metabolic syndrome (20 vs. 7%). Multivariable logistic regression analysis showed that significant predictors of dysglycaemia were black (OR 2.09; 95% CI: 1.27–3.46) and mixed ethnicity (OR 3.05; 95% CI: 1.26–7.42), diagnosis of GDM before 24 weeks gestation (OR 3.05, 95% CI: 1.90–4.91), and treatment of GDM with metformin (OR 1.63; 95% CI: 1.05–2.55) or insulin (OR 2.08; 95% CI: 1.14–3.79) rather than diet alone. Significant predictors of metabolic syndrome were postpartum maternal BMI (OR 5.49; 95% CI: 2.60–11.59) and absence of breastfeeding (OR 2.14; 95% CI: 1.21–3.77). Conclusions: At 5 months postpartum, a high proportion of women who developed GDM showed evidence of dysglycaemia. Future studies should investigate interventions that could reduce the risk of short- and long-term consequences of suboptimal cardiometabolic health in such women.