Stillbirth among women prescribed nicotine replacement therapy in pregnancy: analysis of a large UK pregnancy cohort

Objective: To compare risk of stillbirth between maternal smokers and those prescribed NRT during pregnancy. Design: Cross-sectional analysis nested in a pregnancy cohort with longitudinal routinely-recorded medical data. Setting: United Kingdom primary care; The Health Improvement Network (THIN) general practice database Population: 220,630 singleton pregnancies ending in live or stillbirth, 2001-2012 Methods: Women were categorised into three groups: NRT (prescribed during pregnancy or one month before conception); smokers; controls (non-smokers without a pregnancy NRT prescription). Main Outcome Measure: odds ratios (OR) adjusted to maternal characteristics and 95% confidence intervals (CIs) for stillbirth Results: A total of 805 pregnancies ended in stillbirth (3.6/1,000 births). Absolute risks of stillbirth in NRT and smoker groups were both 5/1,000 births compared with 3.5/1,000 births in the control group. Compared with the control group, the adjusted odds of stillbirth in the NRT group was not statistically significant (OR=1.35, 95% CI 0.91-2.00), although it was similar in magnitude to that in the smokers group (OR=1.41, 95% CI 1.13-1.77). Conclusions: We found no evidence of a statistically significant association between being prescribed NRT during pregnancy and odds of stillbirth compared with non-smoking women. Although our study had much larger numbers than any previously, an even larger study with biochemically-validated smoking outcome data and close monitoring of NRT use throughout pregnancy is required to exclude effects on findings of potential exposure misclassification

N′′-(4-Methoxyphenyl)-N,N,N′-trimethyl-N′-phenylguanidine

In the title compound, C17H21N3O, the C—N bond lengths in the guanidine unit are 1.2889 (19), 1.3682 (19) and 1.408 (2) Å, indicating double- and single-bond character. The N—C—N angles are 115.10 (13), 119.29 (15) and 125.61 (14)°, showing a deviation of the CN3 plane from an ideal trigonal–planar geometry. In the crystal, non-classical C—H...O hydrogen bonds between methyl H atoms and methoxy O atoms are present, generating centrosymmetric dimers running in the [101] direction

N,N,N′-Trimethyl-N′′-(4-nitrophenyl)-N′-phenylguanidine

The C—N bond lengths in the guanidine unit of the title compound, C16H18N4O2, are 1.298 (2), 1.353 (2) and 1.401 (3) Å, indicating double- and single-bond character. The N—C—N angles are 115.81 (16), 118.90 (18) and 125.16 (18)°, showing a deviation of the CN3 plane from an ideal trigonal–planar geometry. In the crystal, C—H...O hydrogen bonds are observed between the methyl- and aromatic-H atoms and nitro-O atoms. One H atom of the phenyl ring and of the NMe2 group associate with the O atoms of the nitro group, giving chains along the a- and b-axis directions. Cross-linking of these two chains results in a two-dimensional network along bc

Orthoamide und Iminiumsalze, XCII. Synthese und Reaktionen von Orthoamiden aus ethinylierten Terpenderivatena

Abstract β-Ionone and camphor were ethynylated to give the alkynols 14, 16, 17 which can be transformed to the alkynolethers 5b, 5i, 5j, 5k, 5l, 5m by treatment with dimethylsulfate and chlorotrimethylsilane, respectively. From the alkynolethers 5h, 5i, 5j/5k, 5l/5m the orthoamide derivatives 4h, 4i, 4j/4k, 4l/4m can be prepared by treatment with N,N,N′,N′,N″,N″-hexamethylguanidinium chloride (8) in the presence of sodium hydride. The orthoamides 4h, 4i react with the sulfonamide 30 under condensation yielding the N-sulfonylated acrylamidines 31, 32. From the orthoamide 4h and p-nitroaniline the propiolamidine 29 could be obtained. The orthoamides 4j/4k and 4l/4m, react with benzamidine to give the pyrimidines 33, 34, respectively. In the reaction of malonodinitrile (9a) with the orthoamides 4i and 4j/4k, mixtures of 1,1-diamino-1,3-butadienes 36, 38 and 1,3-diamino-1,3-butadienes 37 and 39 are produced, respectively. From CH2-acidic compounds as ethylcyanacetate (9b), diethyl-malonate (9c) and nitromethane (9d) and the orthoamide 4i the 1,1-diamino-1,3-butadienes 36b–d were produced. The pyridone derivative 40 can be prepared from cyanoacetamide (9e) and the orthoamide 4i. The condensation of the orthoamides 4j/4k with cyanoacetamide (9e) affords a mixture of the pyrimidone 41 and the nicotinonitrile 42.</jats:p