Progesterone for prevention of preterm birth in women with short cervical length: 2-year infant outcomes.

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3-year follow-up study.

OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. RESULTS: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. CONCLUSION: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Acute respiratory effects of summer smog in primary school children.

In 535 primary school children we studied the effects of exposure to summer smog on respiratory health. Baseline measurements were performed during low air pollution levels (max. 24-h concentrations of SO2, O3 and NO2 were 55, 49 and 58 micrograms/m3, respectively) consisting of lung function measurements using spirometry and the forced oscillation technique (FOT) and the prevalence of respiratory symptoms, determined by a written questionnaire. During a summer smog episode, 212 randomly chosen children were re-examined, characterised by 8-h ozone levels > 120 micrograms/m3 (max. 163 micrograms/m3) and 1-h ozone levels > 160 micrograms/m3 (max. 215 micrograms/m3). Overall, small decrements were observed in the forced expiratory volume in 1 s (FEV1), (P < 0.05) and the forced expiratory volume between 25 and 75% of the vital capacity (FEF25-75%) (P < 0.01). On the contrary, there was a statistically significant decrease in resistance parameters. No increases were observed in the prevalence of acute respiratory symptoms. In conclusion, in this study we found small inconsistent changes in lung function and no increase of respiratory symptoms after short-time exposure to moderately high ozone levels.

Asthma-related symptoms and lung function in primary school children.

The aim of the present study was to determine the prevalence of asthma-related symptoms in a group of primary school children, by means of a questionnaire completed by their parents, and their lung function using spirometry and the forced oscillation technique (FOT). Also investigated were diagnostic labeling and medical prescription. We approached 535 children, from two primary schools in Maastricht, the Netherlands. Completed questionnaires were received from 482 children (90%). Valid lung function values were obtained in 470 of these children (98%). The lifetime prevalence of wheeze and attacks of shortness of breath with wheeze was 29% and 19%, respectively. The period prevalence of wheeze was 15%, 13% reported chronic cough, and 10% attacks of shortness of breath with wheeze. The doctor-diagnosed asthma and bronchitis prevalence was 6% and 19%, respectively. Of the children diagnosed as having asthma, 69% used antiasthma medication; none of the children diagnosed as having bronchitis used antiasthma medication. A symptom-based asthma prevalence of 11% was calculated. Statistically significant differences in spirometric and FOT indices were found between the children with and without complaints. In conclusion, among the 482 investigated children a relatively high prevalence of unrecognized or misclassified, and therefore undertreated, asthma-related symptoms was found. These observations were confirmed by the lung function data, in that we found significant differences in spirometric and FOT indices between children with and without complaints.

Frequency dependence of oscillatory resistance in healthy primary school children.

With the use of the forced oscillation technique, respiratory input impedance was measured in 371 healthy children, aged 5-12 years. How impedance values varied with height (age) and gender and to what extent negative frequency dependence of oscillatory resistance existed in these children was investigated. Negative frequency dependence of resistance between 8 and 28 Hz was a common finding in all height categories. With increasing height, resistance decreased and reactance increased in all children. Below 140 cm of height, resistance values at 8 Hz were higher, and reactance values at 8 Hz were more negative in girls than in boys. At heights above 140 cm the reverse was found. Resonant frequency was found to be higher in boys than in girls. The incidence of negative frequency dependence of resistance (FD) decreases during growth. Over heights of 130-160 cm, more negative FD existed in boys than in girls. It can be concluded that negative FD between 8 and 28 Hz can be found in healthy children up to 12 years of age, most pronounced in boys, not necessarily implicating pulmonary pathology.

Adverse effects of the indoor environment on respiratory health in primary school children.

Exposure to various factors from the indoor environment on respiratory health of 470 Dutch primary school children was studied. We investigated which of the factors, such as home dampness, passive smoking, unvented kitchen geysers, or pets, affected children's respiratory health the most, and whether airway sensitivity to these indoors exposures differed between boys and girls. Information on respiratory morbidity and characteristics of the housing was obtained by a written questionnaire, completed by the parents of the children. Lung function of the children was measured at school, by forced oscillation technique (FOT) and spirometry. In boys, all investigated lung function parameters were significantly affected by exposure to passive smoking during the child's entire life. Although mostly nonsignificant, all of the reported asthma-like symptoms were related especially to maternal smoking, with a trend of a dose-response relationship. Furthermore, damp stains (P < 0.05) and mold growth (ns) were associated with chronic cough and with small but significant impairments in part of the lung function parameters. No consistent patterns were observed with unvented kitchen geysers and pets. Although passive smoking (cumulative dose) in girls was also associated with lung function impairments, the effects were smaller than those in boys and not all significant. Associations between the asthma-like symptoms and the dose of maternal and paternal smoking also were less consistent. Furthermore, no associations were found with the dampness indicators and with pets, but unvented kitchen geysers were significantly related to impairments in some of the impedance indices. This study shows detrimental effects of several indoor factors on the prevalence of chronic respiratory symptoms and lung function in children, which are most pronounced for passive smoking, and somewhat less pronounced for dampness and the presence of unvented kitchen geysers. Airway sensitivity to these exposures appeared to be higher in boys than in girls.

Acute respiratory effects of low level summer smog in primary school children.

We aimed to study the possible effects of exposure to a summer smog episode on the respiratory health of 212 school children. Furthermore, the suitability of the forced oscillation technique (FOT) to demonstrate such effects was evaluated. Acute respiratory symptoms were evaluated by questionnaire and lung function was assessed by spirometry and respiratory impedance measurements. For each child, comparisons were made between measurements performed at baseline (low levels of air pollutant: 55 micrograms.m-3 for SO2 and 58 micrograms.m-3 for NO2 (maximum 24 h means); O3 levels ranged from 2-56 micrograms.m-3 (8 h mean)); and after a summer smog episode (characterized by 8 h O3 levels > 120 micrograms.m-3 (163 micrograms.m-3) and 1 h levels > 160 micrograms.m-3 (215 micrograms.m-3). No significant effects were observed on the prevalence of acute respiratory symptoms. When individual changes in lung function indices (delta LF) were regressed on changes in previous day ozone (8 h mean) and changes in mean daily temperature (delta MTemp), using multiple linear regression analysis, a significant negative association was observed with peak expiratory flow (PEF), but not with other spirometry indices. Although significant associations were observed with reactance at 8 Hz (Xrs8), resonant frequency (f0) and frequency dependence of resistance (FD), the signs of the beta s were opposite to the direction expected when O3 adversely affected the impedance outcomes. In conclusion, in this study short-term exposure to moderately high levels of ozone did not result in clear adverse effects on the respiratory health of the children.(ABSTRACT TRUNCATED AT 250 WORDS)

The rate of respiratory symptoms among primary school children in two Dutch regions.

UNLABELLED: A cross-sectional study was conducted to evaluate possible interregional differences in respiratory health in primary school children living in two different towns of the Netherlands, Melick/Herkenbosch Asenray (MHA) (n = 511) and Leek (LK) (n = 612). The prevalence of respiratory symptoms was determined by means of a questionnaire and respiratory impedance was measures using the forced oscillation technique (FOT). Respiratory symptoms were reported consistently more often in MHA than in LK; chronic cough (17% MHA vs 5% LK), shortness of breath (15% vs 8%), wheeze (16% vs 13%) and attacks of shortness of breath with wheeze (10% vs 7%). However, doctor-diagnosed asthma was reported as 7% in MHA and 6% in LK. The prevalence rates expressed as odds ratios of MHA versus LK were all > 1 even when adjusted for known indoor environmental factors. Living in MHA appeared to be a statistically significant determinant of the reported symptom prevalence. Furthermore, the child's age, maternal smoking (> 10 cigarettes/day), and having had domestic animals were positively associated with one or more respiratory symptoms. Calculating adjusted differences in respiratory impedance between the regions resulted in a small but statistically significant difference in resonant frequency, LK being slightly at a disadvantage. Measured outdoor air pollution levels of SO2, NO2, O3 and PM10 were in general higher in MHA. In both regions however, the average levels remained below the present WHO guidelines, except for NO2 in MHA where the guideline was slightly exceeded. CONCLUSION: In this study prevalence rates of key symptoms of asthma were found to be significantly higher in children living in one region of the Netherlands (MHA) compared to another (LK). Known (indoor) risk factors for respiratory disease could not explain the observed differences in symptom prevalence between the regions. However, statistically but not clinically significant interregional differences in respiratory impedance values were found between children living in MHA and children living in LK. Further research will have to incorporate techniques to evaluate the potential influence of information bias.

Low diagnostic value of respiratory impedance measurements in children.

The aim of this study was to determine whether impedance values in children with various chronic respiratory complaints differed from those observed in symptom-free children. Respiratory impedance was measured using the forced oscillation technique in 1,776 Dutch children aged 6-12 yrs. In addition to the commonly used parameters of resistance and reactance, further impedance parameters were obtained by using linear and quadratic regression to describe individual resistance and reactance curves as a function of frequency. Furthermore, the diagnostic value of the individual impedance parameters was evaluated by means of receiver operator characteristic (ROC) curves. Statistically significant differences in impedance values were found in girls with symptoms suggesting asthma compared to symptom-free girls, but not in boys. In children with chronic cough, impedance was not significantly different from the values of symptom-free children. The results obtained by the additional impedance parameters were comparable to those of the commonly used measures. We conclude that the diagnostic values of the impedance parameters appeared to be low, as no cut-off points were found to discriminate clearly between symptomatic and symptom-free children. These findings may reflect absence of functional abnormalities in symptomatic children at this age.