In utero exposure to perfluoroalkyl and polyfluoroalkyl substances and attention and executive function in the offspring: A study in the Danish National Birth Cohort.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and accumulate in humans. PFAS are suspected to affect the neuropsychological function of children, but only few studies have evaluated the association with childhood attention and executive function. OBJECTIVES: To investigate the association between intrauterine exposure to PFAS and offspring attention and executive function. METHODS: A total of 1593 children from the Danish National Birth Cohort, born 1996-2003, were included. The levels of 16 PFAS were measured in maternal plasma during pregnancy. At 5 years of age, the Test of Everyday Attention for Children at Five (TEACh-5) and the Behavior Rating Inventory of Executive Function (BRIEF) were performed. TEACh-5 scores were standardized to a mean of 0 and standard deviation (SD) of 1. BRIEF scores were standardized to a mean of 50 and a SD of 10. The associations between levels of seven PFAS and TEACh-5 and BRIEF were examined by multivariable linear regression adjusted for potential confounders. RESULTS: Perfluorooctane sulfonamide (PFOSA) was associated with poorer selective attention [standardized mean difference (95% confidence interval) -0.5 (-0.7, -0.3), highest versus lowest quartile]. Other PFAS were not clearly associated with selective attention, and we found no clear associations between PFAS exposure and sustained attention. For parent rated executive function, perfluorooctanoate (PFOA) was associated with poorer scores, standardized mean difference 3.8 (95% confidence interval 1.6, 6.0), highest versus lowest quartile. Regarding other PFAS, the associations were less clear. We found no clear associations between any PFAS and executive function rated by preschool teachers. CONCLUSION: Intrauterine exposure to PFOSA was associated with poorer selective attention, while PFOA was associated with poorer executive function. Given the widespread nature of PFAS exposure, these findings may have public health implications, warranting further investigation.

Congenital Heart Defects and the Risk of Spontaneous Preterm Birth.

OBJECTIVES: To estimate the association between major types of congenital heart defects (CHD) and spontaneous preterm birth, and to assess the potential underlying mechanisms. STUDY DESIGN: This nationwide, registry-based study included a cohort of all singleton pregnancies in Denmark from 1997 to 2013. The association between CHD and spontaneous preterm birth was estimated by multivariable Cox regression, adjusted for potential confounders. The following potential mechanisms were examined: maternal genetics (sibling analyses), polyhydramnios, preterm prelabor rupture of membranes, preeclampsia, and indicators of fetal and placental growth. RESULTS: The study included 1 040 474 births. Compared with the general population, CHD was associated with an increased risk of spontaneous preterm birth, adjusted hazard ratio 2.1 (95% CI, 1.9-2.4). Several subtypes were associated with increased risks, including pulmonary stenosis combined with a septal defect, 5.2 (95% CI, 3.7-7.5); pulmonary stenosis or atresia, 3.1 (95% CI, 2.4-4.1); tetralogy of Fallot 2.5 (95% CI, 1.6-3.8); coarctation or interrupted aortic arch 2.2 (95% CI, 1.5-3.2); and hypoplastic left heart syndrome, 2.0 (95% CI, 1.0-4.1). Overall, preterm prelabor rupture of membranes mediated more than one-half of the association. Maternal genetics, polyhydramnios, or indicators of fetal or placental growth did not explain the reported associations. CONCLUSIONS: CHD, especially right ventricular outflow tract obstructions, were associated with an increased risk of spontaneous preterm birth. The risk was carried by the CHD and not by maternal genetics. Moreover, preterm prelabor rupture of membranes was identified as a potential underlying mechanism.

Head circumference at birth and intellectual disability: a nationwide cohort study.

BACKGROUND: Intellectual disability (ID) is a prevalent chronic disability affecting up to 1-3% of the general population. Small head circumference at birth, a surrogate measure of foetal cerebral growth, may be a risk factor for ID. We aimed to investigate the association between the full distribution of head circumference at birth and ID. METHODS: This cohort study was based on Danish nationwide registries and included all Danish singletons born alive from 1997 to 2013. Follow-up ended at October 2015. The data was analysed using a Cox proportional hazards regression model adjusted for a large number of potential confounders. RESULTS: The cohort comprised 986,909 infants. Neither microcephaly nor macrocephaly at birth was consistently associated with the risk of ID. Within the normal range of head circumference, larger head circumference was associated with a decreased risk of ID (HR per standard deviation increase in head circumference z score 0.85, 95% CI 0.81-0.88). The association detected within the normal range was consistent in all sensitivity analyses. CONCLUSIONS: Intrauterine brain growth restriction may be a risk factor for ID.

Head circumference at birth and school performance: a nationwide cohort study of 536,921 children.

BACKGROUND: Early measures of cognitive function are of great public health interest. We aimed to estimate the association between head circumference at birth, a measure of cerebral size, and school performance. METHODS: We conducted a nationwide cohort study of all liveborn singletons in Denmark, 1997-2005. The association between birth head circumference z score and test scores in reading and mathematics from a nationwide mandatory computer-based school test program (7-16 years) was estimated by multivariable linear regression adjusted for potential confounders. RESULTS: The cohort included 536,921 children. Compared to normocephalic children, children with microcephaly [<-2 standard deviations (SD)] had lower mean reading scores: second grade: -0.08 SD (95% CI -0.10 to -0.06), eighth grade: -0.07 SD (95% CI -0.10 to -0.04). Macrocephaly (>+2 SD) was associated with higher scores. In normocephalic children, each SD increase in head circumference was associated with a 0.03 SD (95% CI 0.03 to 0.04) increase in mean reading scores. The results were similar across grades within both reading and mathematics. CONCLUSION: Prenatal brain growth may be causally related to childhood school performance. The demonstrated differences are unlikely to be clinically relevant at the individual level but may be important at a public health level.

Fetal Heart Defects and Measures of Cerebral Size.

OBJECTIVES: To estimate the association between fetal congenital heart defects (CHDs) and measures of brain size throughout pregnancy, from the end of the first trimester to birth. STUDY DESIGN: The cohort consisted of all fetuses scanned in Western Denmark in 2012 and 2013. Anthropometric measures in fetuses with isolated CHDs diagnosed within 12 months after birth were compared with those in the fetuses without CHDs. Z-scores standardized to gestational age were calculated for first trimester biparietal diameter, second trimester head circumference, fetal weight, birthweight, head circumference, and placental weight. RESULTS: We obtained data from 63 349 pregnancies and identified 295 fetuses with isolated CHDs (major n = 145; minor n = 150). The first trimester mean biparietal diameter Z-scores were not different between those with and those without CHDs. The head circumference mean Z-score difference was -0.13 (95% CI, -0.24 to -0.01; P = .03) in the second trimester and -0.22 (95% CI, -0.35 to -0.09; P < .001) at birth. Fetuses with univentricular physiology or tetralogy of Fallot showed the most pronounced compromise in cerebral size. CONCLUSIONS: Our results suggest that the brain alterations inducing an increased risk of impaired neurodevelopment in children with CHDs begin during pregnancy. Although fetuses with univentricular physiology or tetralogy of Fallot exhibited the most pronounced compromise in cerebral size, we recommend neurodevelopmental follow-up for all children with CHDs.

Conditioning on Parity in Studies of Perfluoroalkyl Acids and Time to Pregnancy: An Example from the Danish National Birth Cohort.

BACKGROUND: Previous studies have investigated the associations between perfluoroalkyl acids (PFAAs) in women and time to pregnancy (TTP). Inconsistent results may be explained by differences in conditioning on parity. OBJECTIVES: We used causal directed acyclic graphs to illustrate potential confounding related to previous pregnancies and exposure measurement error due to differences in the interpregnancy interval in pregnancy-based studies that include parous women. We exemplified the potential importance of these issues using data from the Danish National Birth Cohort. METHODS: We used discrete time survival models to estimate associations between maternal plasma PFAAs in early pregnancy and TTP in 638 nulliparous and 613 parous women. RESULTS: PFAA quartiles were not associated with the TTP in nulliparous women. In parous women, higher PFAA quartiles were associated with longer TTP. The strongest associations were estimated for perfluorohexane sulfonate and perfluorooctane sulfonate. PFAA concentrations were higher in women with longer interpregnancy intervals. Accounting for the interpregnancy interval attenuated the estimated associations. CONCLUSIONS: Associations between PFAAs and TTP in parous women may be biased by confounders related to previous pregnancies and exposure measurement error. To avoid these biases, studies that include parous women may need to condition on a) common causes of PFAAs and the TTP in the index pregnancy, b) previous births (a descendant of a collider), c) PFAA levels or common causes of PFAA levels and the TTP in the previous pregnancy (to alleviate collider stratification bias caused by conditioning on previous births), and d) the interpregnancy interval (in pregnancy-based studies). Alternatives would be to restrict studies to nulliparous women or to use toxicokinetic modeling to correct exposure estimates in parous women. These recommendations may be extended to studies of other chemicals with similar toxicokinetic properties. https://doi.org/10.1289/EHP1493.

Directed acyclic graphs: a tool for causal studies in paediatrics.

Many paediatric clinical research studies, whether observational or interventional, have as an eventual aim the identification or quantification of causal relationships. One might ask: does screen time influence childhood obesity? Could overuse of paracetamol in infancy cause wheeze? How does breastfeeding affect later cognitive outcomes? In this review, we present causal directed acyclic graphs (DAGs) to a paediatric audience. DAGs are a graphical tool which provide a way to visually represent and better understand the key concepts of exposure, outcome, causation, confounding, and bias. We use clinical examples, including those outlined above, framed in the language of DAGs, to demonstrate their potential applications. We show how DAGs can be most useful in identifying confounding and sources of bias, demonstrating inappropriate statistical adjustments for presumed biases, and understanding threats to validity in randomised controlled trials. We believe that a familiarity with DAGs, and the concepts underlying them, will be of benefit both to the researchers planning studies, and practising clinicians interpreting them.

Head circumference at birth and childhood developmental disorders in a nationwide cohort in Denmark.

BACKGROUND: Early markers of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may improve the understanding and early recognition of these disorders. We aimed to estimate the association between head circumference at birth, a measure of cerebral size at birth, and the risk of ADHD and ASD. METHODS: We present a register-based cohort study of all Danish singletons born alive between 1997 and 2013. Cox proportional hazards regression was used for the statistical analyses. Sibling-matched analyses were performed to account for unmeasured confounding shared by siblings. RESULTS: The analyses included 986 909 new-borns. Compared to normocephalic children, microcephaly was associated with an increased risk of ADHD (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12, 1.32). Macrocephaly was associated with a decreased risk of ADHD (HR 0.90, 95% CI 0.82, 0.99). Neither microcephaly nor macrocephaly were associated with ASD (HR 1.06, 95% CI 0.94, 1.19 and 1.03, 95% CI 0.90, 1.19). The largest difference was found within the normocephalic children. A head circumference at the lower limit of normocephaly compared to a head circumference at the upper limit was associated with an increased risk of ADHD (HR 1.52, 95% CI 1.43, 1.63). The sibling analyses confirmed the increased risk of ADHD with decreasing head circumference in the normocephalic children. No other clear associations were present in the sibling analyses. CONCLUSIONS: Within normocephalic children, smaller head circumference at birth was associated with a higher risk of ADHD. Restricted foetal brain growth may be a risk factor for the development of ADHD but not ASD.

Cerebral Oxygenation Measurements by Magnetic Resonance Imaging in Fetuses With and Without Heart Defects.

BACKGROUND: Children with major congenital heart defects are risking impaired cerebral growth, delayed cerebral maturation, and neurodevelopmental disorders. We aimed to compare the cerebral tissue oxygenation of fetuses with major heart defects to that of fetuses without heart defects as estimated by the magnetic resonance imaging modality T2*. T2* is low in areas with high concentrations of deoxyhemoglobin. METHODS AND RESULTS: At gestational age mean 32 weeks (early) and mean 37 weeks (late), we compared the fetal cerebral T2* in 28 fetuses without heart defects to that of 15 fetuses with major heart defects: transposition of the great arteries (n=7), coarctation of the aorta/hypoplastic aortic arch (n=5), tetralogy of Fallot (n=1), hypoplastic right heart (n=1), and common arterial trunk (n=1). The women were scanned with a 1.5 T Philips scanner using a breath-hold multiecho gradient echo sequence. Among fetuses without heart defects, the mean T2* value was 157 ms (95% confidence interval [CI], 152-163) early and 125 ms (95% CI, 120-130) late. These figures were significantly lower (mean 14 ms; 95% CI, 6-22; P<0.001) among fetuses with heart defects 143 ms (95% CI, 136-150) early and 111 ms (95% CI, 104-118) late. CONCLUSIONS: Our findings indicate that fetal cerebral T2* is measurable and that fetal cerebral tissue oxygenation measured by T2* is lower in fetuses with heart defects compared with fetuses without heart defects. This corroborates the hypothesis that tissue hypoxia may be a potential pathogenic factor that possibly affects brain development in fetuses with heart defects.

Congenital Heart Defects and Measures of Prenatal Brain Growth: A Systematic Review.

BACKGROUND: We summarize the evidence for an association between congenital heart defects and prenatal brain growth through a systematic literature review. Congenital heart defects are among the most common malformations, affecting approximately six per 1000 live births. The association between congenital heart defects and long-term neurodevelopmental disorders is well established. Increasing evidence suggests an association between impaired prenatal brain growth and neurodevelopmental disorders in children with congenital heart defects. METHODS: Systematic literature searches were performed in PubMed and EMBASE. We included original studies comparing fetuses or newborns with congenital heart defects to reference fetuses or newborns with respect to brain biometrics, including biparietal diameter, brain volume, and head circumference at birth. The study characteristics and the results were extracted and presented in tables. No meta-analysis was undertaken. RESULTS: Twenty-eight studies were included. All except two studies found an association between congenital heart defects and measures of reduced prenatal brain growth. The strongest evidence concerned hypoplastic left heart syndrome, tetralogy of Fallot, and transposition of the great arteries. CONCLUSIONS: The literature suggests an association between congenital heart defects and measures of impaired prenatal brain growth. However, most studies were small and failed to include important potential confounding factors and to address other sources of potential bias as well. Future large-scale studies that address potential confounders are warranted.

Fertility Treatment and Childhood Epilepsy: A Nationwide Cohort Study.

BACKGROUND: Fertility treatment includes hormonal stimulation of the woman and in vitro manipulation of gametes and embryos that may influence prenatal brain development. We aimed to investigate the association between fertility treatment and childhood epilepsy, including specific types of treatment and indications, as well as subtypes of epilepsy. METHODS: In this nationwide birth cohort study, we included all pregnancies in Denmark resulting in live-born singletons, 1995-2003. Children conceived by fertility treatment and children developing epilepsy (until 2013) were identified from Danish national registers. RESULTS: A total of 565,116 pregnancies were included; 8,071 children (1.4%) developed epilepsy. Children conceived after ovulation induction or intrauterine insemination had a slightly higher risk of childhood epilepsy (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.00, 1.31). The association was more pronounced for the subtypes idiopathic generalized and focal epilepsy. Regarding the specific hormonal treatments, only clomiphene citrate was associated with an increased risk of childhood epilepsy, also in a sibling analysis (HR: 2.07; 95% CI: 1.05, 4.08). In vitro fertilization or intracytoplasmic sperm injection was not associated with an overall increased risk of childhood epilepsy but with idiopathic generalized epilepsy (HR: 1.43; 95% CI: 0.99, 2.05). No clear associations were seen regarding other treatment types or indications. CONCLUSIONS: Children conceived by ovulation induction or intrauterine insemination with clomiphene citrate may be at slightly increased risk of childhood epilepsy. Furthermore, children conceived by in vitro fertilization or intracytoplasmic sperm injection may be at slightly increased risk of idiopathic generalized epilepsy.

Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants.

BACKGROUND: Congenital heart defects (CHDs) have been associated with placental anomalies. The nature and the consequences of this association remain poorly understood. We aimed to estimate the associations between all major subtypes of CHD and placental weight at birth, and the association between placental weight and measures of both overall and cerebral growth in fetuses with CHD, as well. METHODS: We included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 7569. We compared mean differences in placental weight z score between newborns with CHD and newborns without CHD by multivariable linear regression adjusted for potential confounders. RESULTS: CHD was associated with a mean z score difference of -0.04 (95% confidence interval, -0.07 to -0.02). Some subtypes were associated with smaller placental size at birth: tetralogy of Fallot, -0.45 (95% confidence interval, -0.58 to -0.31); double-outlet right ventricle, -0.48 (95% confidence interval, -0.87 to -0.10); major ventricular septal defects, -0.41 (95% confidence interval, -0.52 to -0.29). Placental weight z score was associated with birth weight and head circumference z scores in all subtypes. In the 3 mentioned subtypes, the mean deviations from the population mean head circumference and birth weight z scores were reduced by up to 66% with adjustment for placental weight z score. CONCLUSIONS: Three subtypes of CHD were associated with lower placental weight, and placental weight was associated with measures of both overall growth and cerebral growth in fetuses with all subtypes of CHD. In certain subtypes, the described deviations in fetal growth were reduced by up to two-thirds after adjustment for placental weight z score.

Fertility treatment and childhood type 1 diabetes mellitus: a nationwide cohort study of 565,116 live births.

OBJECTIVE: To investigate the association between specific types of fertility treatment and childhood type 1 diabetes mellitus. DESIGN: Nationwide birth cohort study. SETTING: Not applicable. PATIENT(S): All pregnancies resulting in a live-born singleton child in Denmark from 1995 to 2003. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Childhood type 1 diabetes mellitus identified from redeemed prescriptions for insulin until 2013. RESULT(S): The study included 565,116 singleton pregnancies. A total of 14,985 children were conceived by ovulation induction or intrauterine insemination, and 8,490 children were conceived by in vitro fertilization or intracytoplasmic sperm injection. During the follow-up period, 2,011 (0.4%) children developed type 1 diabetes mellitus. The primary analyses showed no association between fertility treatment and childhood type 1 diabetes mellitus. In secondary analyses, ovulation induction or intrauterine insemination with follicle-stimulating hormone was associated with an increased risk of type 1 diabetes mellitus (hazard ratio 3.22; 95% confidence interval 1.20 to 8.64). No clear associations were seen with other types of fertility treatment or with specific treatment indications. CONCLUSION(S): No association between fertility treatment and childhood type 1 diabetes mellitus was found. Ovulation induction or intrauterine insemination with follicle-stimulating hormone may be associated with an increased risk of childhood type 1 diabetes mellitus. However, this finding may be due to chance or to confounding by indication and thus requires further investigation.

Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

OBJECTIVES: To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes. STUDY DESIGN: We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.2 deletion syndrome (n = 155), born 1997-2011. In both cohorts, we analyzed the association between CHD, CHD severity, and indices of fetal growth by multivariable linear regression adjusted for potential confounders. We report mean differences in gestational age specific z-scores compared with newborns without CHD. RESULTS: Down syndrome and 22q11.2 deletion syndrome were both associated with lower mean birth weight and head circumference z-scores. We found no association between CHD or CHD severity and indices of fetal growth. In Down syndrome, the association between any CHD and the mean difference in head circumference z-score was 0.03 (95% CI -0.12, 0.18), and the estimate regarding birth weight z-score was 0.09 (95% CI -0.08, 0.25). The corresponding estimates in 22q11.2 deletion syndrome were 0.00 (95% CI -0.33, 0.32) and -0.09 (95% CI -0.45, 0.26). CONCLUSIONS: We found no association between CHD and fetal growth measures in newborns with Down syndrome or 22q11.2 deletion syndrome. Thus, in certain subtypes of CHD, the contribution of genetic factors to prenatal growth impairment may be more important than circulatory disturbances.

Parental Infertility, Fertility Treatment, and Childhood Epilepsy: A Population-Based Cohort Study.

BACKGROUND: A few studies have indicated an increased risk of epilepsy in children conceived by fertility treatment possibly due to characteristics of the infertile couple rather than the treatment. We therefore aimed to investigate the association between parental infertility, fertility treatment, and epilepsy in the offspring, including the subtypes of epilepsy; idiopathic generalised epilepsy and focal epilepsy. METHODS: This cohort included all pregnancies resulting in liveborn singletons from the Aarhus Birth Cohort, Denmark (1995-2013). Information on time to pregnancy and fertility treatment was obtained from pregnancy questionnaires in early pregnancy. Children developing epilepsy were identified from the Danish National Patient Register and the Danish National Prescription Registry until 2013. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. RESULTS: A total of 60 440 pregnancies were included, and 0.8% of the children developed epilepsy.The primary analyses showed no association between parental infertility or fertility treatment, and the overall risk of childhood epilepsy (hazard rate ratios (HRs); 95% confidence intervals (CIs): 1.08 (0.73, 1.60) and 1.04 (0.71, 1.52)). In secondary analyses, both parental infertility and fertility treatment were associated with an increased risk of idiopathic generalised epilepsy (HRs and 95% CIs: 2.25 (1.10, 4.58) and 2.45 (1.26, 4.75)). No association was seen for focal epilepsy. CONCLUSION: Parental infertility or fertility treatment was not associated with an overall risk of childhood epilepsy. Parental infertility may be associated with an increased risk of idiopathic generalised epilepsy; a subtype of epilepsy believed to be of genetic origin.

Congenital Heart Defects and Indices of Fetal Cerebral Growth in a Nationwide Cohort of 924 422 Liveborn Infants.

BACKGROUND: Neurodevelopmental disorders are the most common and distressful comorbidities associated with congenital heart defects (CHD). Head circumference at birth (HC), a proxy for prenatal cerebral growth, is an established risk factor for neurodevelopmental disorders. METHODS AND RESULTS: In a nationwide cohort, we included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 5519. The association between CHD and growth indices was analyzed by multivariable linear regression, adjusted for potential confounders. We report mean differences in gestational age-specific z scores in comparison with the general population. CHD was associated with lower HC z scores, -0.10 (95% confidence interval [CI], -0.13 to -0.08). Several CHD subtypes were associated with smaller HC, eg, hypoplastic left heart syndrome, -0.39 (95% CI, -0.58 to -0.21); common arterial trunk, -0.41 (95% CI, -0.74 to -0.09); and major ventricular septal defects, -0.25 (95% CI, -0.35 to -0.15). Other single-ventricle defects, transposition of the great arteries, tetralogy of Fallot, and anomalous pulmonary venous return, were also associated with smaller HC. Transposition of the great arteries was associated with smaller HC relative to birth weight, -0.26 (95% CI, -0.39 to -0.13). Major ventricular septal defects were associated with larger HC relative to birth weight. The results were consistent under various conditions, eg, when siblings of infants with CHD (n=5311) or infants with other major malformations (n=24 974) were used as the reference. CONCLUSIONS: Several subtypes of CHD were associated with smaller HC. The associations with major ventricular septal defects, common arterial trunk, and anomalous pulmonary venous return have not previously been described. Only infants with transposition of the great arteries had smaller HC relative to birth weight.

Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort.

BACKGROUND: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known. OBJECTIVES: We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. METHODS: We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008-2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression. RESULTS: Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose-response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were -50 g (95% CI: -123, 23 g) in all births and -62 g (95% CI: -126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. CONCLUSIONS: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds. CITATION: Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB. 2016. Perfluoroalkyl acids in maternal serum and indices of fetal growth: the Aarhus Birth Cohort. Environ Health Perspect 124:848-854; http://dx.doi.org/10.1289/ehp.1510046.