Perinatal exposure to traffic related air pollutants and the risk of infection in the first six months of life: a cohort study from a low-middle income country.

OBJECTIVE: There is limited study from low-and-middle income countries on the effect of perinatal exposure to air pollution and the risk of infection in infant. We assessed the association between perinatal exposure to traffic related air pollution and the risk of infection in infant during their first six months of life. METHODS: A prospective cohort study was performed in Jakarta, March 2016-September 2020 among 298 mother-infant pairs. PM2.5, soot, NOx, and NO2 concentrations were assessed using land use regression models (LUR) at individual level. Repeated interviewer-administered questionnaires were used to obtain data on infection at 1, 2, 4 and 6 months of age. The infections were categorized as upper respiratory tract (runny nose, cough, wheezing or shortness of breath), lower respiratory tract (pneumonia, bronchiolitis) or gastrointestinal tract infection. Logistic regression models adjusted for covariates were used to assess the association between perinatal exposure to air pollution and the risk of infection in the first six months of life. RESULTS: The average concentrations of PM2.5 and NO2 were much higher than the WHO recommended levels. Upper respiratory tract infections (URTI) were much more common in the first six months of life than diagnosed lower respiratory tract or gastro-intestinal infections (35.6%, 3.5% and 5.8% respectively). Perinatal exposure to PM2.5 and soot suggested increase cumulative risk of upper respiratory tract infection (URTI) in the first 6 months of life per IQR increase with adjusted OR of 1.50 (95% CI 0.91; 2.47) and 1.14 (95% CI 0.79; 1.64), respectively. Soot was significantly associated with the risk of URTI at 4-6 months age interval (aOR of 1.45, 95%CI 1.02; 2.09). All air pollutants were also positively associated with lower respiratory tract infection, but all CIs include unity because of relatively small samples. Adjusted odds ratios for gastrointestinal infections were close to unity. CONCLUSION: Our study adds to the evidence that perinatal exposure to fine particles is associated with respiratory tract infection in infants in a low-middle income country.

The effect of exposure to traffic related air pollutants in pregnancy on birth anthropometry: a cohort study in a heavily polluted low-middle income country.

BACKGROUND: Ambient air pollution has been recognized as one of the most important environmental health threats. Exposure in early life may affect pregnancy outcomes and the health of the offspring. The main objective of our study was to assess the association between prenatal exposure to traffic related air pollutants during pregnancy on birth weight and length. Second, to evaluate the association between prenatal exposure to traffic related air pollutants and the risk of low birth weight (LBW). METHODS: Three hundred forty mother-infant pairs were included in this prospective cohort study performed in Jakarta, March 2016-September 2020. Exposure to outdoor PM2.5, soot, NOx, and NO2 was assessed by land use regression (LUR) models at individual level. Multiple linear regression models were built to evaluate the association between air pollutants with birth weight (BW) and birth length (BL). Logistic regression was used to assess the risk of low birth weight (LBW) associated with all air pollutants. RESULTS: The average PM2.5 concentration was almost eight times higher than the current WHO guideline and the NO2 level was three times higher. Soot and NOx were significantly associated with reduced birth length. Birth length was reduced by - 3.83 mm (95% CI -6.91; - 0.75) for every IQR (0.74 × 10- 5 per m) increase of soot, and reduced by - 2.82 mm (95% CI -5.33;-0.30) for every IQR (4.68 µg/m3) increase of NOx. Outdoor air pollutants were not significantly associated with reduced birth weight nor the risk of LBW. CONCLUSION: Exposure to soot and NOx during pregnancy was associated with reduced birth length. Associations between exposure to all air pollutants with birth weight and the risk of LBW were less convincing.

Factors associated with mortality of pediatric sepsis patients at the pediatric intensive care unit in a low-resource setting.

BACKGROUND: Sepsis is the leading cause of death worldwide in pediatric populations. Studies in low-resource settings showed that the majority of pediatric patients with sepsis still have a high mortality rate. METHODS: We retrospectively collected records from 2014 to 2019 of patients who had been diagnosed with sepsis and admitted to PICU in our tertiary hospital. Cox proportional hazard regression modeling was used to evaluate associations between patient characteristics and mortality. RESULTS: Overall, 665 patients were enrolled in this study, with 364 (54.7%) boys and 301 (46.3%) girls. As many as 385 patients (57.9%) died during the study period. The median age of patients admitted to PICU were 1.8 years old with interquartile range (IQR) ±8.36 years and the median length of stay was 144 h (1-1896 h). More than half 391 patients (58.8%) had a good nutritional status. Higher risk of mortality in PICU was associated fluid overload percentage of > 10% (HR 9.6, 95% CI: 7.4-12.6), the need of mechanical ventilation support (HR 2.7, 95% CI: 1.6-4.6), vasoactive drugs (HR 1.5, 95% CI: 1.2-2.0) and the presence of congenital anomaly (HR 1.4, 95% CI: 1.0-1.9). On the contrary, cerebral palsy (HR 0.3, 95% CI: 0.1-0.5) and post-operative patients (HR 0.4, 95% CI: 0.3-0.6) had lower mortality. CONCLUSION: PICU mortality in pediatric patients with sepsis is associated with fluid overload percentage of > 10%, the need for mechanical ventilation support, the need of vasoactive drugs, and the presence of congenital anomaly. In septic patients in PICU, those with cerebral palsy and admitted for post-operative care had better survival.

Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial.

Management of children with newly diagnosed immune thrombocytopenia (ITP) consists of careful observation or immunomodulatory treatment. Observational studies suggest a lower risk for chronic ITP in children after intravenous immunoglobulin (IVIg) treatment. In this multicenter randomized trial, children aged 3 months to 16 years with newly diagnosed ITP, platelet counts 20 × 109/L or less, and mild to moderate bleeding were randomly assigned to receive either a single infusion of 0.8 g/kg IVIg or careful observation. Primary outcome was development of chronic ITP, which at the time of study initiation was defined as a platelet count lower than 150 × 109/L after 6 months. Two hundred six children were allocated to receive IVIg (n = 102) or careful observation (n = 104). Chronic ITP occurred in 18.6% of the patients in the IVIg group and 28.9% in the observation group (relative risk [RR], 0.64; 95% confidence interval [CI], 0.38-1.08). Platelet counts lower than 100 × 109/L at 12 months (current definition of chronic ITP) were observed in 10% of children in the IVIg group and 12% in the observation group (RR, 0.83; 95% CI, 0.38-1.84). Complete response rates in the first 3 months were significantly higher in the IVIg group. Immunoglobulin G Fc receptor IIb genetic variations were associated with early complete response in both groups. Grade 4 to 5 bleeding occurred in 9% of the patients in the observation group vs 1% in the IVIg group. This trial was registered at www.trialregister.nl as NTR 1563.

The effect of non-organophosphate household pesticides exposure during pregnancy on infants birth sizes and growth rate: a cohort study.

BACKGROUND: To date, there is limited evidence on the effect of antenatal exposure to non-organophosphate household pesticides on infant health. Our hypothesis is that antenatal exposure to non-organophosphate household pesticides will be associated with birth sizes and infant growth rate. METHODS: In this prospective cohort study, 284 mother-infant pairs were studied. Mothers were recruited at the third trimester in two primary care centers and one private hospital in Jakarta, Indonesia. Mothers filled out questionnaires about exposure to non-organophosphate household pesticides at the 3rd trimester of pregnancy. Birth weight and length were measured at birth. Afterwards, the weight, height, and head circumference (HC) were measured at 7 days, 1, 2, 4, and 6 months of age. Linear mixed modeling and linear regression was performed to calculate growth rate of each infant. Multivariable linear regression adjusted for confounders was used to assess the association between household pesticides exposure and birth sizes and infant growth rate. RESULTS: Based on self-report questionnaires, 133 (46.8%) mothers were exposed to household pesticides during pregnancy. The mean HC at day 7 in the exposed group was - 7.1 mm (95%CI -13.1;-1.2) lower than in the non-exposed group. The difference was more prominent in the non-mosquito pesticide group (linear regression coefficient: - 22.1 mm, 95%CI -36.5;-7.6). No material associations were found between antenatal exposure to household pesticides with other growth measures, including weight gain, length gain, HC increment and weight-to-length gain rates. No modification of effects by breastfeeding was found. CONCLUSIONS: Our findings suggest that antenatal exposure to household non-organophosphate pesticides is associated with smaller head circumference at birth.

Prevalence and characteristics of older adults with a persistent death wish without severe illness: a large cross-sectional survey.

BACKGROUND: Some older persons develop a persistent death wish without being severely ill, often referred to as "completed life" or "tiredness of life". In the Netherlands and Belgium, the question whether these persons should have legal options for euthanasia or physician-assisted suicide (EAS) is intensely debated. Our main aim was to investigate the prevalence and characteristics of older adults with a persistent death wish without severe illness, as the lack of this knowledge is a crucial problem in de debate. METHODS: We conducted a survey among a representative sample of 32,477 Dutch citizens aged 55+, comprising questions about health, existential issues and the nature of the death wish. Descriptive statistics were used to describe the group with a persistent death wish and no severe illness (PDW-NSI) and several subgroups. RESULTS: A total of 21,294 respondents completed the questionnaire (response rate 65.6%). We identified 267 respondents (1.25%) as having a persistent death wish and no severe illness (PDW-NSI). PDW-NSI did not only occur among the oldest old. Although qualifying themselves as "not severely ill", those with PDW-NSI reported considerable health problems. A substantial minority of the PDW-NSI-group reported having had a death wish their whole lives. Within the group PDW-NSI 155 (0.73%) respondents had an active death wish, of which 36 (0.17% of the total response) reported a wish to actually end their lives. Thus, a death wish did not always equal a wish to actually end one's life. Moreover, the death wishes were often ambiguous. For example, almost half of the PDW-NSI-group (49.1%) indicated finding life worthwhile at this moment. CONCLUSIONS: The identified characteristics challenge the dominant "completed life" or "tiredness of life" image of healthy persons over the age of 75 who, overseeing their lives, reasonably decide they would prefer to die. The results also show that death wishes without severe illness are often ambiguous and do not necessarily signify a wish to end one's life. It is of great importance to acknowledge these nuances and variety in the debate and in clinical practice, to be able to adequately recognize the persons involved and tailor to their needs.

Tele-ECG consulting and outcomes on primary care patients in a low-to-middle income population: the first experience from Makassar telemedicine program, Indonesia.

BACKGROUND: Telemedicine has been a popular tool to overcome the lack of access to healthcare facilities, primarily in underprivileged populations. We aimed to describe and assess the implementation of a tele-electrocardiography (ECG) program in primary care settings in Indonesia, and subsequently examine the short- and mid-term outcomes of patients who have received tele-ECG consultations. METHODS: ECG recordings from thirty primary care centers were transmitted to Makassar Cardiac Center, Indonesia from January to July 2017. We cross-sectionally measured the performance of this tele-ECG program, and prospectively sent a detailed questionnaire to general practitioners (GPs) at the primary care centers. We performed follow-up at 30 days and at the end of the study period to assess the patient outcomes. RESULTS: Of 505 recordings, all (100%) ECGs were qualified for analysis, and about half showed normal findings. The mean age of participants was 53.3 ± 13.6 years, and 40.2% were male. Most (373, 73.9%) of these primary care patients exhibited manifested CVD symptom with at least one risk factor. Male patients had more ischemic ECGs compared to women (p < 0.01), while older age (> 55 years) was associated with ischemic or arrhythmic ECGs (p < 0.05). Factors significantly associated with a normal ECG were younger age, female gender, lower blood pressure and heart rate, and no history of previous cardiovascular disease (CVD) or medication. More patients with an abnormal ECG had a history of hypertension, known diabetes, and were current smokers (p < 0.05). Of all tele-consultations, GPs reported 95% of satisfaction rate, and 296 (58.6%) used tele-ECG for an expert opinion. Over the total follow-up (14 ± 6.6 months), seven (1.4%) patients died and 96 (19.0%) were hospitalized for CVD. Of 88 patients for whom hospital admission was advised, 72 (81.8%) were immediately referred within 48 h following the tele-ECG consultation. CONCLUSIONS: Tele-ECG can be implemented in Indonesian primary care settings with limited resources and may assist GPs in immediate triage, resulting in a higher rate of early hospitalization for indicated patients.

Perceived triggers of asthma impair quality of life in children with asthma.

BACKGROUND: Data on the impact of the number and nature of perceived asthma triggers on health-related quality of life (HRQL) in children are scarce. OBJECTIVE: To investigate the impact of perceived asthma triggers on both asthma-specific and generic HRQL in children. METHODS: A cross-sectional study was conducted among children (7-18 years) with asthma in secondary and tertiary care. Children were screened with electronic questionnaires regarding respiratory and allergic symptoms. Asthma-specific HRQL was assessed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) (score range 1-7) and generic HRQL using the RAND questionnaire (score range 7-32). The Kruskal-Wallis test and one-way ANOVA were used to test the difference of, respectively, the PAQLQ and RAND scores across the number of perceived asthma triggers (0, 1-2, 3-4, or ≥ 5). Univariable and multivariable linear regression analyses were performed to evaluate the association between individual triggers and HRQL. RESULTS: A total of 527 children with a mean (SD) age of 12.1 (2.9) years were included. Children with a higher number of perceived triggers had significantly lower PAQLQ and RAND scores (ie poorer HRQL). The difference in PAQLQ scores was clinically relevant between children with 0 versus 3-4 or ≥ 5 triggers and 1-2 versus ≥ 5 triggers (mean difference 0.66, 1.02 and 0.63, respectively). Especially, non-allergic triggers (physical exercise, the weather, (cigarette) smoke and emotions) were significantly associated with reduced PAQLQ scores. Emotions and food/drinks were associated with reduced RAND scores. CONCLUSION AND CLINICAL RELEVANCE: A higher number of perceived triggers of asthma were associated with reduced HRQL in children with asthma. Especially, non-allergic triggers were associated with reduced HRQL.

Equity in maternal health outcomes in a middle-income urban setting: a cohort study.

BACKGROUND: Low socioeconomic status (SES) is associated with more adverse perinatal health outcomes, risk factors and lower access to and use of maternal health care services. However, evidence for the association between SES and maternal health outcomes is limited, particularly for middle-income countries like sub-Saharan Ghana. We assessed the association between parental SES and adverse maternal and perinatal outcomes of Ghanaian women during pregnancy, delivery and the postpartum period. METHODS: A prospective cohort study of 1010 women of two public hospitals in Accra, Ghana (2012-2014). SES was proxied by maternal and paternal education, wealth and employment status. The association of SES with maternal and perinatal outcomes was analyzed with multivariable logistic and linear regression. RESULTS: The analysis included 790 women with information on pregnancy outcomes. Average age was 28.2 years (standard deviation, SD 5.0). Over a third (n = 292, 37.0%) had low SES, 176 (22.3%) were classified to have high SES using the assets index. Nearly half (n = 374, 47.3%) of women had lower secondary school or vocational training as highest education level. Compared to women with middle assets SES, women with low assets SES were at higher risk for miscarriage (odds ratio, OR 1.61, 95% CI 1.06 to 2.45) and instrumental delivery (OR 1.74, 95% CI 1.03 to 2.94), but this association was not observed for the other SES proxies. For any of the maternal or perinatal outcomes and SES proxies, no other statistically significant differences were found. CONCLUSION: Women attending public maternal health care services in urban Ghana had overall equitable maternal and perinatal health outcomes, with the exception of a higher risk of miscarriage and instrumental delivery associated with low assets SES. This suggests known associations between SES, risk factors and outcomes could be mitigated with universal and accessible maternal health services.

The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort.

BACKGROUND: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children. METHODS: A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population-based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental-reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician-diagnosed allergy during follow-up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician-diagnosed allergy and parental-reported allergy at age 5. RESULTS: The GRS was significantly associated with parental-reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07-233.73) at age 5, as well as with a physician-diagnosed allergy during follow-up (hazard ratio: 1.89, 95% CI: 1.05-3.41). The overall agreement between physician-diagnosed and parental-reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03-0.18). CONCLUSIONS: An adult-derived GRS for allergy predicts the risk of developing allergies in childhood.

Does body mass index early in pregnancy influence the risk of maternal anaemia? An observational study in Indonesian and Ghanaian women.

BACKGROUND: Anaemia is common among pregnant women, especially in low- and middle-income countries (LMICs). While body mass index (BMI) relates to many risk factors for anaemia in pregnancy, little is known about the direct relation with anaemia itself. This is particularly relevant in Southeast Asia and Sub-Saharan Africa where the prevalence of anaemia in pregnancy and the associated adverse outcomes is among the highest worldwide. This study aimed to assess the association between early pregnancy BMI and anaemia at first antenatal care visit in Indonesian and Ghanaian women. In addition, the associations between early pregnancy anaemia and adverse birth outcomes was assessed. METHODS: Prospective cohort studies of women in early pregnancy were conducted in Jakarta, Indonesia (n = 433) and in Accra, Ghana (n = 946), between 2012 and 2014. Linear regression analysis was used to assess relations between early pregnancy BMI and pregnancy haemoglobin levels at booking. Logistic regression analyses were used to assess associations between early pregnancy anaemia as defined by the World Health Organization (WHO) criteria and a composite of adverse birth outcomes including stillbirth, low birth weight and preterm birth. RESULTS: Indonesian women had lower BMI than Ghanaian women (23.0 vs 25.4 kg/m2, p < 0.001) and higher mean haemoglobin levels (12.4 vs 11.1 g/dL, p < 0.001), corresponding to anaemia prevalence of 10 and 44%, respectively. Higher early pregnancy BMI was associated with higher haemoglobin levels in Indonesian (0.054 g/dL/kg/m2, 95% CI 0.03 to 0.08, p < 0.001) and Ghanaian women (0.044 g/dL/kg/m2, 0.02 to 0.07, p < 0.001). Accordingly, risk for anaemia decreased with higher early pregnancy BMI for Indonesians (adjusted OR 0.88, 0.81 to 0.97, p = 0.01) and Ghanaians (adjusted OR 0.95, 0.92 to 0.98, p < 0.001). No association between anaemia and the composite of adverse birth outcomes was observed. CONCLUSION: Higher BMI in early pregnancy is associated with higher haemoglobin levels at antenatal booking and with a reduced risk of anaemia in Indonesian and Ghanaian women.

Long-chain polyunsaturated fatty acids in infant formula and cardiovascular markers in childhood.

To investigate whether children who consumed infant formula supplemented with long-chain polyunsaturated fatty acids (LCPUFAs) had a more favourable cardiovascular profile than children who consumed formula without these fatty acids, we used the Wheezing Illnesses Study Leidsche Rijn, a birth cohort that included 2,468 newborns between 2001 and 2014. Data on infant feeding were obtained by questionnaires. At age 5, blood pressure, carotid intima-media thickness (CIMT), and carotid distension were measured. We used multivariable linear regression analysis to compare levels of cardiovascular markers in formula-fed children born before and after the LCPUFA supplementation. To account for secular trends, we compared levels of cardiovascular markers in a control group of breastfed children from the same cohort born before and after the supplementation. Formula-fed children born after the LCPUFA supplementation (n = 48) had no different systolic blood pressure (-2.58 mmHg, 95% confidence interval, CI [-5.5, 0.30]), diastolic blood pressure (-0.13 mmHg, 95% CI [-2.3, 2.1]), or carotid distension (24.8 MPa-1 , 95% CI [-47.1, 96.6]) and had a higher CIMT (18.6 µm, 95% CI [3.7, 33.5]) than formula-fed children born before the supplementation (n = 163). In the control group, children born after the LCPUFA supplementation (n = 98) had no different systolic- or diastolic-blood pressure, or CIMT, and a higher carotid distension than children born before the supplementation (n = 142). In conclusion, children who consumed infant formula supplemented with LCPUFAs did not have a more favourable cardiovascular profile in early childhood than children who consumed formula without LCPUFAs.

Effects of paediatric HIV infection on childhood vasculature.

AIMS: Human immunodeficiency virus (HIV) infection may alter childhood vascular properties and influence future cardiovascular risk. Whether vascular changes are associated with HIV infection per se or antiretroviral therapy (ART) is unknown. We investigated the effects of ART-naive or ART-exposed HIV infection in children on childhood vascular characteristics. METHODS AND RESULTS: We performed vascular ultrasound to measure carotid intima media thickness (cIMT), distensibility, and elastic modulus on 114 children with vertically acquired HIV infection (56 ART-naive, 58 ART treated) and 51 healthy children in Jakarta, Indonesia. Children also underwent clinical and blood examinations. We used general linear modelling to estimate associations between HIV infection/treatment status and vascular characteristics with adjustment for confounders or possible mediators. Vascular measurements were successful in 42 ART-naive HIV-infected [median age 4.0 years (min 0.4-max 11.5)]; 53 ART-treated HIV infected [5.7 years (0.6-12.2), median ART duration 2.4 years (0.1-9.9)]; and 48 healthy children, 6.5 years (2.4-14.0). The ART-naive HIV infected had thicker cIMT (difference 70.4 µm, 95% CI 32.1-108.7, P < 0.001), adjusted for age, sex, socioeconomic status, parental smoking, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and HbA1c. Addition of high-sensitivity C-reactive protein (hs-CRP) level to the model did not affect the results (71.6 µm, 31.9-111.2, P = 0.001). The ART-exposed children had similar cIMT dimensions to healthy children. Distensibility was not significantly different between HIV infected, either ART-naive or -exposed, and healthy children, but adjusted analysis including only ART-exposed children with controlled HIV (CD4+ ≥200/mm3 or CD4+ ≥15%) showed that the ART-exposed had an increased elastic modulus (difference 37.9 kPa, 95% CI 6.5-69.3, P = 0.02), and following adjustment for hs-CRP (35.5 kPa, 95% CI 4.2-66.8, P = 0.03). CONCLUSION: ART-naive HIV infection in children is associated with increased cIMT. Children with ART-controlled HIV may have increased arterial stiffness, although further confirmation is required.

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery.

OBJECTIVE: Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery. METHODS: We collected IQ scores of children from the TTS cohort with both pre- and postoperative neuropsychological assessments (NPAs; n = 301) and analyzed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified as independently relating to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal. RESULTS: Mean interval to the latest NPA was 19.8 ± 18.9 months. Reduction of AEDs at the latest NPA significantly improved postoperative IQ and delta IQ (adjusted regression coefficient [RC] = 3.4, 95% confidence interval [CI] = 0.6-6.2, p = 0.018 and RC = 4.5, 95% CI = 1.7-7.4, p = 0.002), as did complete withdrawal (RC = 4.8, 95% CI = 1.4-8.3, p = 0.006 and RC = 5.1, 95% CI = 1.5-8.7, p = 0.006). AED reduction also predicted ≥ 10-point IQ increase (p = 0.019). The higher the number of AEDs reduced, the higher was the IQ (gain) after surgery (RC = 2.2, 95% CI = 0.6-3.7, p = 0.007 and RC = 2.6, 95% CI = 1.0-4.2, p = 0.001, IQ points per AED reduced). INTERPRETATION: Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome.

Hyperemesis gravidarum and placental dysfunction disorders.

BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was conducted in a maternal and child health primary care referral center, Budi Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women visiting the hospital for regular antenatal care visits from July 2012 until October 2014 were included at their first clinic visit. For women without, with mild and with severe hyperemesis, placental dysfunction disorders (gestational hypertension, preeclampsia (PE), stillbirth, miscarriage), neonatal outcomes (birth weight, small for gestational age (SGA), low birth weight (LBW), Apgar score at 5 min, gestational age at delivery) and placental outcomes (placental weight and placental-weight-to-birth-weight ratio (PW/BW ratio)) were studied. RESULTS: Compared to newborns of women without hyperemesis, newborns of women with severe hyperemesis had a 172 g lower birth weight in adjusted analysis (95%CI -333.26; -10.18; p = 0.04). There were no statistically significant effects on placental dysfunction disorders or other neonatal outcome measures. CONCLUSIONS: The results of our study suggest that hyperemesis gravidarum does not seem to induce placental dysfunction disorders, but does, if severe lead to lower birth weight.

Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

INTRODUCTION: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. METHODS: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. RESULTS: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR=0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend=0.029. While there was no significant effect modification by hormone receptor status (P=0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P=0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR=0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (Ptrend=0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR=0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. CONCLUSIONS: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.

Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study.

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.

Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study.

Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.

Maternal body mass index, neonatal lung function and respiratory symptoms in childhood.

Recent studies have shown that maternal obesity is associated with increased risk of wheezing in the offspring. We assessed whether impaired neonatal lung function could explain this association. We measured neonatal lung function in 2606 children of our prospective birth cohort. Information about daily symptoms of wheezing was obtained using questionnaires. Consultations and prescriptions for wheezing illnesses were derived from general practitioner patient files. Higher maternal body mass index (BMI) was associated with increased risk of wheezing in the first year of life and more consultations and prescriptions for wheezing illnesses until the age of 5 years. Lung function could partially explain the association with wheezing in the first year of life. Adding respiratory resistance to the model decreased the incidence rate ratio from 1.023 (95% CI 1.008-1.039) to 1.015 (95% CI 0.998-1.032). Anthropometrics of the 5-year-olds largely explained the association with consultations. Intermediates or confounders could not explain the association with prescriptions. There is an association between higher maternal BMI and increased risk of wheezing illnesses. In the first year of life, it is largely explained by an impaired lung function in early life, especially in children of nonatopic mothers. At the age of 5 years, infant lung function is of minor influence in this association.

Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-results from the EPIC cohort study.

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.