Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Agreement between routine and research measurement of infant height and weight.

UNLABELLED: In many countries, routine data relating to growth of infants are collected as a means of tracking health and illness up to school age. These have potential to be used in research. For health monitoring and research, data should be accurate and reliable. This study aimed to determine the agreement between length/height and weight measurements from routine infant records and researcher-collected data. METHODS: Height/length and weight at ages 6, 12 and 24 months from the longitudinal UK birth cohort (born in Bradford; n=836-1280) were compared with routine data collected by health visitors within 2 months of the research data (n=104-573 for different comparisons). Data were age adjusted and compared using Bland Altman plots. RESULTS: There was agreement between data sources, albeit weaker for height than for weight. Routine data tended to underestimate length/height at 6 months (0.5 cm (95% CI -4.0 to 4.9)) and overestimate it at 12 (-0.3 cm (95% CI -0.5 to 4.0)) and 24 months (0.3 cm (95% CI -4.0 to 3.4)). Routine data slightly overestimated weight at all three ages (range -0.04 kg (95% CI -1.2 to 0.9) to -0.04 (95% CI -0.7 to 0.6)). Limits of agreement were wide, particularly for height. Differences were generally random, although routine data tended to underestimate length in taller infants and underestimate weight in lighter infants. CONCLUSIONS: Routine data can provide an accurate and feasible method of data collection for research, though wide limits of agreement between data sources may be observed. Differences could be due to methodological issues; but may relate to variability in clinical practice. Continued provision of appropriate training and assessment is essential for health professionals responsible for collecting routine data.

A comparison of South Asian specific and established BMI thresholds for determining obesity prevalence in pregnancy and predicting pregnancy complications: findings from the Born in Bradford cohort.

OBJECTIVE: To describe how maternal obesity prevalence varies by established international and South Asian specific body mass index (BMI) cut-offs in women of Pakistani origin and investigate whether different BMI thresholds can help to identify women at risk of adverse pregnancy and birth outcomes. DESIGN: Prospective bi-ethnic birth cohort study (the Born in Bradford (BiB) cohort). SETTING: Bradford, a deprived city in the North of the UK. PARTICIPANTS: A total of 8478 South Asian and White British pregnant women participated in the BiB cohort study. MAIN OUTCOME MEASURES: Maternal obesity prevalence; prevalence of known obesity-related adverse pregnancy outcomes: mode of birth, hypertensive disorders of pregnancy (HDP), gestational diabetes, macrosomia and pre-term births. RESULTS: Application of South Asian BMI cut-offs increased prevalence of obesity in Pakistani women from 18.8 (95% confidence interval (CI) 17.6-19.9) to 30.9% (95% CI 29.5-32.2). With the exception of pre-term births, there was a positive linear relationship between BMI and prevalence of adverse pregnancy and birth outcomes, across almost the whole BMI distribution. Risk of gestational diabetes and HDP increased more sharply in Pakistani women after a BMI threshold of at least 30 kg m(-2), but there was no evidence of a sharp increase in any risk factors at the new, lower thresholds suggested for use in South Asian women. BMI was a good single predictor of outcomes (area under the receiver operating curve: 0.596-0.685 for different outcomes); prediction was more discriminatory and accurate with BMI as a continuous variable than as a binary variable for any possible cut-off point. CONCLUSION: Applying the new South Asian threshold to pregnant women would markedly increase those who were referred for monitoring and lifestyle advice. However, our results suggest that lowering the BMI threshold in South Asian women would not improve the predictive ability for identifying those who were at risk of adverse pregnancy outcomes.

Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis.

BACKGROUND: Insulin resistance is a key feature of nonalcoholic fatty liver disease. Patients with hereditary hemochromatosis, a disease characterized by progressive iron overload due, in most cases, to homozygosity for C282Y mutation in the HFE gene, have often decreased insulin sensitivity and release. AIMS: To determine whether increased iron parameters/heterozygosity for the mutations of the HFE gene confer susceptibility to nonalcoholic fatty liver disease. PATIENTS: One hundred and thirty-four consecutive Italian patients with clinical and ultrasonographic diagnosis of nonalcoholic fatty liver disease (82 with hyperferritinemia), half confirmed by liver biopsy. METHODS: Insulin was determined by radioimmunoassay. HFE gene mutations were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: (1) Prevalence of C282Y HFE mutation was significantly higher in patients with nonalcoholic fatty liver disease compared to controls, the difference being more striking in patients with hyperferritinemia than in those without. (2) The presence of mild iron overload was associated with a lower insulin release. (3) Carriers of C282Y mutation developed nonalcoholic fatty liver disease despite lower body mass index and triglycerides. CONCLUSION: The mild iron overload associated with heterozygosity for C282Y HFE mutation confers susceptibility to nonalcoholic fatty liver disease, causing relative insulin deficiency.

Synthesis and properties of 2-(naphthosultamyl)methyl-carbapenems with potent anti-MRSA activity: discovery of L-786,392.

A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation.

Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: I. 4", 11 and 12-OMe derivatives via direct methylation.

A series of O-Me derivatives of 9-deoxo-8a-aza-8a-homoerythromycin has been prepared and evaluated for antibacterial activity. The relative rates of methylation of the four available hydroxyls (4", 6, 11 and 12) in 2',3'-bis-Cbz protected 9-deoxo-8a-aza-8a-homoerythromycin were compared to those given in a published report for the similarly protected 9a-azalide. An incongruity in the results prompted reinvestigation of the O-methylation of the 9a-azalide, and an error in structure assignment in the published report was discovered: the compound reported as the 6-OMe-9a-azalide has been determined to be the 12-OMe derivative.

Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: II. 6-OME derivatives via clarithromycin.

Direct O-methylation of various derivatives of 9-deoxo-8a- and 9a-aza-8a-homo-erythromycin (2',3'-bis-Cbz protected) gives 6-OMe derivatives only in a small number of special cases. The 6-OMe-azalides can, however, be synthesized beginning from clarithromycin.