Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Increased maternal BMI is associated with infant wheezing in early life: a prospective cohort study.

Rates of obesity are increasing in women of child bearing age with negative impacts on maternal and offspring health. Emerging evidence suggests in utero origins of respiratory health in offspring of obese mothers but mechanisms are unknown. Changes in maternal cortisol levels are one potential factor as cortisol levels are altered in obesity and cortisol is separately implicated in development of offspring wheeze. We aimed to assess whether increased pre-pregnancy maternal body mass index (BMI) was associated with offspring early life wheezing, and whether this was mediated by altered cortisol levels in the mother. In a prospective community-based cohort (Amsterdam Born Children and their Development cohort), women completed questionnaires during pregnancy and at 3-5 months post-delivery regarding self-history of asthma and atopy, and of wheezing of their offspring (n=4860). Pre-pregnancy BMI was recorded and serum total cortisol levels were measured in a subset of women (n=2227) at their first antenatal visit. A total of 20.2% (n=984) women were overweight or obese and 10.3% reported wheezing in their offspring. Maternal BMI was associated with offspring wheezing (1 unit (kg/m2) increase, OR: 1.03; 95% CI: 1.00-1.05), after correction for confounders. Although maternal cortisol levels were lower in overweight mothers and those with a history of asthma, maternal cortisol levels did not mediate the increased offspring wheezing. Pre-pregnancy BMI impacts on baby wheezing, which is not mediated by lower cortisol levels. As the prevalence of obesity in women of child-bearing age is increasing, further studies are needed to investigate modifiable maternal factors to avoid risk of wheezing in young children.

Contribution of overweight and obesity to the occurrence of adverse pregnancy outcomes in a multi-ethnic cohort: population attributive fractions for Amsterdam.

OBJECTIVE: To estimate the contribution of pre-pregnancy excessive weight to the occurrence of adverse pregnancy outcomes and to detect the differences in these contributions between different ethnic groups. DESIGN: Prospective multi-ethnic community-based cohort study. SETTING: The prevalence of excessive weight is increasing and in general higher in immigrant groups in many industrialised countries. Maternal excessive weight, like smoking during pregnancy, is an important risk factor for adverse pregnancy outcomes. POPULATION: A total of 8266 pregnant women, living in the Netherlands, were included in the ABCD study between January 2003 and March 2004. METHODS: After applying the exclusion criteria, the analysis included 7871 pregnancies. Binomial log-linear regression analyses were performed to estimate relative risks (RRs) expressing the association between overweight/obesity and small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm birth (PTB; <37 weeks of gestation) and extreme PTB (<32 weeks of gestation), controlling for parity, maternal age, education level and smoking. Next, the RRs were used to estimate population attributive fractions (PAF) for Amsterdam and separately for several ethnic groups. MAIN OUTCOME MEASURES: The RRs and PAFs. RESULTS: The PAFs for overweight/obesity were: SGA -4.9%, LGA 15.3%, PTB 6.6% and extreme PTB 22.0%. In absolute terms, this corresponds to -47 SGA infants, 126 LGA infants, 35 PTB and 20 extreme PTB per year in Amsterdam. Except for SGA, these PAFs were higher than those for smoking (6.2%, -3.9%, 5.5% and 10.6%, respectively). The contribution of overweight/obesity to LGA and PTB was higher in non-Western immigrant groups. CONCLUSIONS: Overweight/obesity has become an important contributor to the occurrence of adverse pregnancy outcomes in Amsterdam. For most outcomes, these contributions are larger than those for smoking. Development of special obesity prevention programmes for young women is required, especially focused on immigrant groups.

Ethnic differences in maternal total cholesterol and triglyceride levels during pregnancy: the contribution of demographics, behavioural factors and clinical characteristics.

BACKGROUND/OBJECTIVES: Lipid disturbances during pregnancy may lead to early onset of metabolic diseases in the offspring. However, there is little knowledge on ethnic differences in lipid levels during pregnancy. We evaluated ethnic differences in non-fasting total cholesterol (TC) and triglyceride (TG) levels during early gestation and the role of demographics, behavioural factors and clinical characteristics. SUBJECTS/METHODS: Non-diabetic pregnant women (N=3025) from the Amsterdam Born Children and their Development (ABCD) study. The studied ethnic groups were Dutch, Surinam-Hindustani, African-Caribbean, Turkish, Moroccan and Ghanaian. A multilingual questionnaire was used to gather information on maternal demographics, behavioural factors and clinical characteristics. Non-fasting TC, TG, percentage saturated fatty acid (%SFA) and percentage linoleic acid status (%LA) were assessed in blood samples collected at the first antenatal visit. RESULTS: Ghanaian (-0.51 mmol/l), African-Caribbean (-0.19 mmol/l) and Moroccan (-0.15 mmol/l) women had significant lower TC levels compared with Dutch women. TG levels were lower in Ghanaian (log transformed -0.12 mmol/l) but significantly higher in Surinam-Hindustani (0.10 mmol/l) and Turkish women (0.07 mmol/l). Age, physical activity, pre-pregnancy body mass index (BMI), smoking, %SFA and %LA were independently related to TC and/or TG. However, only pre-pregnancy BMI could partly explain observed disparities. Furthermore, pre-pregnancy BMI had a relatively large effect on TG levels in Surinam-Hindustani and Turkish women. CONCLUSIONS: TC and TG levels differed between ethnic groups during early gestation. Only pre-pregnancy BMI partly explained the ethnic differences to a relevant degree. Reduction in BMI before pregnancy may improve lipid profile, especially in Surinam-Hindustani and Turkish women.

Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death.

BACKGROUND: To examine the relationship between maternal TSH and free thyroxine (FT(4)) concentrations in early pregnancy and the risk of miscarriage, fetal or neonatal death. METHOD: Cohort study of 2497 Dutch women. TSH, FT(4), and thyroid peroxidase antibodies concentrations were determined at first booking. Child loss was operationalized as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. RESULTS: Twenty-seven cases of child loss were observed. The mean TSH and FT(4) level in the women with child loss was 1.48 mU/l and 9.82 pmol/l compared with 1.11 mU/l and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95% confidence interval (CI): 1.04-2.47)) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratio=1.80 (95% CI: 1.07-3.03)). This was not true for FT(4) concentrations (OR=1.41 (95% CI: 0.21-9.40); P=0.724). CONCLUSION: In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal FT(4) concentrations and child loss were not associated.

Risk factors for the presence of non-rhesus D red blood cell antibodies in pregnancy.

OBJECTIVE: To identify risk factors for the presence of non-rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years. DESIGN: Case-control study. SETTING: Nationwide evaluation of screening programme for non-RhD RBC antibodies. CASES: consecutive pregnancies (n=900) with non-RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n=968): matched for obstetric caregiver and gestational age. METHODS: Data collection from the medical records and/or from the respondents by a structured phone interview. MAIN OUTCOME MEASURES: Significant risk factors for non-RhD immunisation in multivariate analysis. RESULTS: Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4-24.6), parity (para-1 versus para-0: OR 1.3; 95% CI: 1.0-1.7; para-2 versus para-0: OR 1.4; 95% CI: 1.0-2.0; para >2 versus para-0: OR 3.2; 95% CI: 1.8-5.8), haematological disease (OR 2.1; 95% CI: 1.0-4.2), history of major surgery (OR 1.4; 95% CI: 1.1-1.8). For the clinically most important antibodies, anti-K, anti-c and other Rh-nonD-antibodies RBC transfusion was the most important risk factor, especially for anti-K (OR 96.4; 95%-CI: 56.6-164.1); 83% of the K-sensitised women had a history of RBC transfusion. Pregnancy-related risk factors were a prior male child (OR 1.7; 95% CI: 1.2-2.3) and caesarean section (OR 1.7; 95% CI: 1.1-2.7). CONCLUSIONS: RBC transfusion is by far the most important independent risk factor for non-RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy-related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD-positive para-0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.

Women's attitude towards prenatal screening for red blood cell antibodies, other than RhD.

BACKGROUND: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies. METHODS: Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires. MAIN OUTCOME MEASURES: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures. PARTICIPANTS: 233 pregnant women, distributed over five groups, according to the screening result. RESULTS: Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics. CONCLUSION: Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. STUDY DESIGN AND METHODS: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. RESULTS: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. CONCLUSION: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

Ethnic differences in TSH but not in free T4 concentrations or TPO antibodies during pregnancy.

OBJECTIVE: To describe the TSH, free T4 and thyroid peroxidase antibody (TPO-Ab) concentrations during pregnancy among four ethnic groups and to determine reference values for these parameters during normal pregnancy. METHODS: Cross-sectional study of a cohort of 3270 pregnant women living in the city of Amsterdam. Blood samples were drawn at first booking in the first or second trimester. TSH, free T4 and TPO-Ab concentrations were determined. Four ethnic groups were studied: Dutch, Surinam, Turkish and Moroccan. RESULTS: Plasma TSH increased and free T4 decreased from the first to the second trimester of pregnancy for all the ethnic groups. Ethnic differences were observed in TSH concentrations, with Dutch females having the highest TSH levels compared to the other three ethnic groups. The median TSH difference was 0.16 mU/l between the Dutch and Moroccan women, 0.15 mU/l between the Dutch and Surinam women and 0.10 mU/l between the Dutch and Turkish women. These could not be explained by differences in age, parity and current smoking status. No differences were seen in free T4 concentrations between the four ethnic groups. The prevalence of TPO-Ab was comparable across the ethnic groups (about 6% in each); the concentration of TPO-Ab was also comparable among the ethnic groups. The Dutch women had a higher lower-limit (2.5 percentile) of the TSH reference range than the Surinam, Turkish and Moroccan women, ranging from 0.14 mU/l for the Surinam and Moroccan to 0.27 mU/l for the Dutch women. CONCLUSION: The increase in TSH and decrease in free T4 values during pregnancy correspond to previous reported studies. Pregnant Dutch women had consistently higher TSH values than the ethnic group, but corresponding free T4 levels and TPO-Ab did not differ between these ethnic groups.