Maria Lundgren

Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study

Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)—those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy—or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.

Antipsychotics During Pregnancy Relation to Fetal and Maternal Metabolic Effects

CONTEXT Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. OBJECTIVE To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. DESIGN Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. SETTING Swedish national health registers. PARTICIPANTS All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n = 169), (2) other antipsychotics (n = 338), or (3) no antipsychotics (n = 357,696). MAIN OUTCOME MEASURES Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. RESULTS Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). CONCLUSIONS Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.

School Performance After Preterm Birth

Background: An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. Methods: We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. Results: Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31–33 weeks was on average 3.85 (95% confidence interval = −4.36 to −3.35) centiles lower than for children born at 40 weeks. For births at 22–24 weeks, the corresponding figure was −23.15 (−30.32 to −15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. Conclusions: Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women

Background There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women. Methods This study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between womens heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories. Results Every cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants. Conclusions Among Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.

Obesity rates in two generations of Swedish women entering pregnancy, and associated obesity risk among adult daughters.

We examined changes in obesity rates in two generations of Swedish women entering pregnancy, and assessed the effects of maternal body mass index (BMI) on the risk of overweight or obesity among adult daughters. This study covered an intergenerational retrospective cohort of 26,561 Swedish mothers and their 26,561 first-born daughters. There was a 4-fold increase in obesity rates, which rose from 3.1% among women entering pregnancy in 1982–1988 to 12.3% among their daughters in 2000–2008 (p < 0.0001) when entering pregnancy. The greater the maternal BMI, the greater the odds of overweight and/or obesity among daughters. Underweight mothers had half the odds of having an overweight or obese daughter in comparison to mothers of normal BMI (p < 0.0001). In contrast, the odds ratio of obese mothers having obese daughters was 3.94 (p < 0.0001). This study showed a strong association between maternal obesity and the risk of obesity among their first-born daughters. In addition, we observed a considerable increase in obesity rates across generations in mother-daughter pairs of Swedish women entering pregnancy. Thus, it is important to have preventative strategies in place to halt the worsening intergenerational cycle of obesity.

Association Between Preterm Birth and Lower Adult Height in Women

We examined whether being born preterm was associated with changes in adult anthropometry in women. We assessed data on 201,382 women (born in 1973–1988) from the Swedish Birth Register. The mean age was 26.0 years. Of the women in our cohort, 663 were born very preterm (<32 weeks of gestation), 8,247 were born moderately preterm (at least 32 weeks but <37 weeks), and 192,472 were born at term (37–41 weeks). Subgroup analyses were carried out among siblings and also after adjustment for maternal anthropometric data. Statistical tests were 2-sided. Decreasing gestational age was associated with lower height (−1.1 mm per week of gestation; P < 0.0001), so that women who were born very preterm were on average 12 mm shorter than women who were born moderately preterm (P < 0.0001) and 17 mm shorter than women born at term (P < 0.0001). Compared with women who were born at term, those who were born very preterm had 2.9 times higher odds of short stature (<155.4 cm), and those born moderately preterm had 1.43 times higher odds. Subgroup analyses showed no differences between women born moderately preterm and those born at term but accentuated differences from women born very preterm. Among siblings (n = 2,388), very preterm women were 23 mm shorter than those born at term (P = 0.003), with a 20-mm difference observed in subgroup analyses (n = 27,395) that were adjusted for maternal stature (P < 0.001). A shorter final height was associated with decreasing gestational age, and this association was particularly marked in women born very preterm.

First-borns have greater BMI and are more likely to be overweight or obese: a study of sibling pairs among 26 812 Swedish women

Background A number of large studies have shown phenotypic differences between first-borns and later-borns among adult men. In this study, we aimed to assess whether birth order was associated with height and BMI in a large cohort of Swedish women. Methods Information was obtained from antenatal clinic records from the Swedish National Birth Register over 20 years (1991–2009). Maternal anthropometric data early in pregnancy (at approximately 10–12 weeks of gestation) were analysed on 13 406 pairs of sisters who were either first-born or second-born (n=26 812). Results Early in pregnancy, first-born women were of BMI that was 0.57 kg/m2 (2.4%) greater than their second-born sisters (p<0.0001). In addition, first-borns had greater odds of being overweight (OR 1.29; p<0.0001) or obese (OR 1.40; p<0.0001) than second-borns. First-borns were also negligibly taller (+1.2 mm) than their second-born sisters. Of note, there was a considerable increase in BMI over the 18-year period covered by this study, with an increment of 0.11 kg/m2 per year (p<0.0001). Conclusions Our study corroborates other large studies on men, and the steady reduction in family size may contribute to the observed increase in adult BMI worldwide.

Born Small for Gestational Age and Poor School Performance – How Small Is Too Small?

Aim: To assess the relationship between severity of small for gestational age (SGA) and the risk of poor school performance, and to investigate whether adult stature modifies this risk. Methods: 1,088,980 Swedish children born at term between 1973 and 1988 were categorized into severe SGA (less than –3 standard deviations (SD) of expected birth weight), moderate SGA (–2.01 to –3 SD), mild SGA (–1.01 to –2 SD), and appropriate for gestational age (–1 to 0.99 SD). The risk of poor school performance at the time of graduation from compulsory school (grades <10th percentile) was calculated using unconditional logistic regression models and adjusted for socio-economic factors. In a sub-analysis, we stratified boys by adult stature, and adjusted for maternal but not paternal height. Results: All SGA groups were significantly associated with an increased risk of poor school performance, with adjusted odds ratios and 95% confidence intervals ranging from 1.85 (1.65–2.07) for severe SGA to 1.25 (1.22–1.28) for mild SGA. In the sub-analysis, all birth weight groups were associated with an increased risk of poor school performance among boys with short stature compared to those with non-short stature. Conclusion: Mild SGA is associated with a significantly increased risk of poor school performance, and the risk increases with severity of SGA. Further, this risk diminishes after adequate catch-up growth.

Body Mass Index, Overweight, and Obesity in Swedish Women Born Post-term

BACKGROUND There is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. METHODS Data were collected at first antenatal visit (~10-12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (≥43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110). RESULTS Increasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2) . The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term. CONCLUSIONS Post-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation.