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Purpose: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. Methods: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. Results: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02–1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09–1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02–1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. Conclusion: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure to pregabalin are uncertain. Objective: To investigate the association between prenatal exposure to pregabalin and the risks of adverse birth and postnatal neurodevelopmental outcomes. Methods: This study was conducted using population-based registries in Denmark, Finland, Norway, and Sweden (2005–2016). We compared pregabalin exposure against no exposure to antiepileptics and against active comparators lamotrigine and duloxetine. We obtained pooled propensity score-adjusted estimates of association using fixed-effect and Mantel–Haenszel (MH) meta-analyses. Results: The total number of pregabalin-exposed births was 325/666,139 (0.05%) in Denmark, 965/643,088 (0.15%) in Finland, 307/657,451 (0.05%) in Norway, and 1275/1,152,002 (0.11%) in Sweden. The adjusted prevalence ratios (aPRs) with 95% confidence interval (CI) following pregabalin exposure versus no exposure were 1.14 (0.98–1.34) for major congenital malformations and 1.72 (1.02–2.91) for stillbirth, which attenuated to 1.25 (0.74–2.11) in MH meta-analysis. For the remaining birth outcomes, the aPRs were close to or attenuated toward unity in analyses using active comparators. Adjusted hazard ratios (95% CI) contrasting prenatal pregabalin exposure versus no exposure were 1.29 (1.03–1.63) for ADHD and attenuated when using active comparators, 0.98 (0.67–1.42) for autism spectrum disorders, and 1.00 (0.78–1.29) for intellectual disability. Conclusions: Prenatal exposure to pregabalin was not associated with low birth weight, preterm birth, small for gestational age, low Apgar score, microcephaly, autism spectrum disorders, or intellectual disability. On the basis of the upper value of the 95% confidence interval, increased risks greater than 1.8 were unlikely for any major congenital malformation and ADHD. For stillbirth and most groups of specific major congenital malformations, the estimates attenuated in MH meta-analysis. [ABSTRACT FROM AUTHOR]

Introduction: Umbilical cord blood gas analysis provides information about intrapartum hypoxia and is considered an important measure of quality in maternity care. Universal measurement of umbilical cord pH (UC‐pH), as part of umbilical cord blood gas analysis, has been recommended in Denmark since 2009. The recommendation is that UC‐pH is measured from the umbilical cord artery (pHUA) and vein (pHUV). The aim of this study was to evaluate the national implementation of universal measurement of UC‐pH. Material and methods: The study consisted of two parts. First, an evaluation of the implementation, that is, the proportion of births with measured UC‐pH since the recommendation was introduced. Second, an evaluation of the cases in which UC‐pH was missing. This analysis only involved births with gestational age ≥35 + 0 weeks. Results: In the period 2009 to 2018 there were 560 889 singleton, live births with registered gestational age in Denmark. The proportion of births with measured pHUA and pHUV increased from 12.4% in 2009 to 82.8% in 2015 and then declined to 76.9% in 2018 (p < 0.001). When comparing the group with missing pH from one or both vessels to the group with both pHUA and pHUV we found lower occurrence of pregnancy and births complications in the first group, body mass index ≥35 (unadjusted RR: 0.89, 95% CI: 0.85–0.93), pregnancy induced medical conditions (RR: 0.86, 95% CI: 0.84–0.89), fetal distress during birth (RR: 0.77, 95% CI: 0.76–0.79), emergency cesarean section (RR: 0.80, 95% CI: 0.78–0.83) and serious births events (RR: 0.80, 95% CI: 0.74–0.86). In contrast, the occurrence of placental insufficiency (RR: 1.07, 95% CI: 1.03–1.11), small for gestational age (RR: 1.36, 95% CI: 1.30–1.43, for <2.3th percentile), hypothermia treatment (RR: 1.60, 95% CI: 1.21–2.14) and neonatal death (RR: 1.96, 95% CI: 1.40–2.74) were higher in the group without measured pHUA and pHUV. Conclusions: The use of UC‐pH measurement has increased markedly in Denmark since universal measurement was recommended in 2009. Missing UC‐pH from one or both vessels was associated with less complicated pregnancies and with small for gestational age, hypothermia treatment and neonatal death. [ABSTRACT FROM AUTHOR]

Objectives: Prematurity, being small for gestational age and early neonatal ward admission are the major neonatal conditions that may interfere with breastfeeding supportive practices in infants born at gestational age ≥35+0 weeks. We aimed to investigate the associations between gestational age, small for gestational age, early neonatal ward admission and exclusive breastfeeding at one and four months. Methods: A register-based cohort-study of all Danish singletons with gestational age ≥35+0 weeks born in 2014–2015. In Denmark, health visitors routinely conduct free home visits throughout infants' first year and thereby report breastfeeding data to The Danish National Child Health Register. These data were linked with data from other national registers. Logistic regression models estimated the odds ratio for exclusive breastfeeding at one and four months, adjusted for confounding variables. Results: The study population comprised 106,670 infants. Compared to gestational age 40 weeks, the adjusted odds ratio for exclusive breastfeeding at one month showed a decreasing tendency from gestational age ≥42 (n = 2,282) (1.07; 95% confidence interval (CI) 0.97–1.17) to 36 weeks (n = 2,062) (0.80; 95% CI 0.73–0.88). Small for gestational age (n = 2,342) was associated with decreased adjusted odds ratio for exclusive breastfeeding at one month (0.84; 95% CI 0.77–0.92). Neonatal ward admission was associated with increased adjusted odds ratio for exclusive breastfeeding at one month among late preterm infants (gestational age 35–36 weeks; n = 3,139) (1.31; 95% CI 1.12–1.54), as opposed to among early term (gestational age 37–38 weeks; n = 19,171) (0.84; 95% CI 0.77–0.92) and term infants (gestational age >38 weeks; n = 84,360) (0.89; 95% CI 0.83–0.94). The associations seemed to persist at four months. Conclusions: Decreasing gestational age and small for gestational age were associated with decreased exclusive breastfeeding rates. Neonatal ward admission was associated with increased exclusive breastfeeding rates among late preterm infants, whereas the opposite was observed among early term and term infants. [ABSTRACT FROM AUTHOR]

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37–41), between March 12 and April 14, 2015–2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1–31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05–1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor a (anti-TNFa) agents and adverse birth outcomes. METHODS: This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n51,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis. RESULTS: Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFa agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFa and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection. DISCUSSION: Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFa had a minor role. The association between anti-TNFa agents and pediatric infection could be partially explained by maternal CD. [ABSTRACT FROM AUTHOR]

Introduction: We identified risk factors and outcomes associated with SARS‐CoV‐2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS‐CoV‐2 during pregnancy in national health registers in Denmark. Material and methods: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS‐CoV‐2 test during pregnancy with non‐infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID‐19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS‐CoV‐2 diagnosis in pregnancy in the registers. Results: SARS‐CoV‐2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28–2.07). Risk factors for severe COVID‐19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04–1.09), asthma (RR 7.47, 95% CI 3.51–15.90) and gestational age at the time of infection (gestational age 28–36 vs < 22: RR 3.53, 95% CI 1.75–7.10). SARS‐CoV‐2‐infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04–1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00–1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01–5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01–2.19) and small‐for‐gestational age children (aHR 1.28, 95% CI 1.05–1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS‐CoV‐2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9–100.0) and a positive predictive value of 82.1 (95% CI 80.4–83.7). Conclusions: Women infected with SARS‐CoV‐2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS‐CoV‐2 infection during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Depression or depressive symptoms are common among pregnant women. The use of antidepressants during pregnancy has grown steadily. The risk of offspring being born small for gestational age or prematurely when exposed to duloxetine during pregnancy is not established. Objective: We aimed to investigate the association between duloxetine exposure during pregnancy and offspring being born small for gestational age or prematurely. Methods: We conducted an observational study including live births in Sweden and Denmark (2004–2016). Duloxetine exposure during early (0–140 days) or late (141 to delivery) pregnancy compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, venlafaxine-exposed, and duloxetine discontinuers. Results: In total, 2,083,467 pregnancies were identified, where 1589 and 450 were duloxetine exposed in early and late pregnancy, respectively. For small for gestational age, no increased risk was seen for duloxetine across comparators. In the early and late exposure windows, propensity score-matched odds ratios for small for gestational age ranged between 0.64 (95% confidence interval 0.44–0.95) and 1.48 (95% confidence interval 0.85–2.57). For preterm birth, the findings differed across comparators and exposure-time windows, but trended towards an increased risk for duloxetine-exposed when compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, and duloxetine discontinuers in both early exposure and late exposure. The odds ratios ranged between 1.17 and 2.04, of which some did not reach statistical significance. No clear association was observed when compared with venlafaxine exposed, 0.91 (95% confidence interval 0.73–1.14) for early exposure and 1.26 (95% confidence interval 0.86–1.86) for late exposure. Most preterm births (79.2%) occurred in weeks 33–36 of gestation. Conclusions: Duloxetine exposure during pregnancy is unlikely to increase the risk of small for gestational age. Although not consequently statistically significant across comparisons, a trend towards an increased risk of preterm birth was observed for duloxetine exposed. Therefore, an increased risk of preterm birth cannot be excluded, especially for women exposed to duloxetine throughout pregnancy. [ABSTRACT FROM AUTHOR]

Background: The safety of fathers' use of antidiabetic drugs in terms of child outcomes is an important clinical question. We aimed to assess the risk of adverse birth and early childhood outcomes after fathers' use of antidiabetics prior to conception. Methods: A nationwide cohort study based on Danish health registries. The study comprised all live born singleton children in Denmark (1997 through 2018). Children were categorized according to fathers' filled prescriptions for antidiabetic drugs three months prior to conception. Exposed cohorts: children born after paternal use of insulin or non-insulin anti-hyperglycemic agents. The unexposed constituted children born by fathers not treated with antidiabetics prior to conception. We examined adverse birth outcomes (preterm birth, small for gestational age (SGA)), and adverse childhood outcomes in the first year of life (major congenital malformations (MCMs), and infections diagnosed at a hospital). Results: A total of 1,318,684 children were included. In all, 5527 children were born after paternal use of insulin, 2121 after use of non-insulin anti-hyperglycemic agents, and 1,311,036 were unexposed. After fathers' use of insulin we did not find increased risk of adverse outcomes. After fathers' use of metformin, the adjusted OR of MCMs was 1.40 (95% CI 1.11–1.76). After fathers' use of sulfonylureas, the adjusted OR of SGA was 1.80 (95% CI 1.11–2.93), and for child gastrointestinal infections the adjusted HR was 1.76 (95% CI 1.04–2.99). Conclusions: Fathers' use of insulin was reassuring. Metformin and sulfonylureas were associated with selected adverse outcomes. Our findings suggest an additional 14 MCMs per 1000 fathers exposed to metformin prior to conception. As there is no meaningful supporting biological rationale, these findings should be confirmed in a different population prior to clinical consequences being drawn. [ABSTRACT FROM AUTHOR]

Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006–18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56–2.35)] and SGA [1.93 (1.45–2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52–7.55) for PTB and 3.90 (1.46–10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94–4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66–2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment. [ABSTRACT FROM AUTHOR]

Background: Mothers with multiple sclerosis are at increased risk of preterm birth and small for gestational age infants. Both conditions pose a risk of morbidity, including early-life infections., Objective: This study aimed to assess the risk of infections in the first 3 years of life among children born preterm or small for gestational age to mothers with multiple sclerosis., Methods: We used Danish national health registers to establish the study cohort of all births by women with MS born from 1995 to 2023. In Cox regression models, we estimated hazard ratios (HRs) of infections in preterm or small for gestational age children., Results: Preterm children had an adjusted HR of 1.49 (95% confidence interval (95% CI) 1.15-1.93) for hospital-diagnosed infection and 0.88 (95% CI 0.72-1.06) for antibiotic prescriptions. Small for gestational age children had an adjusted HR of 0.81 (95% CI 0.54-1.22) for hospital-diagnosed infection and 1.07 (95% CI 0.82-1.38) for antibiotic prescriptions., Conclusion: Children born preterm to mothers with multiple sclerosis had an increased risk of hospital-diagnosed infections in the first 3 years of life, but not of mild-to-moderate infections evaluated on prescriptions. Children born small for gestational age did not have an increased risk of infections., Competing Interests: Approvals and EthicsThe study was approved by the Danish Data Protection Agency under the current joint notification of the Region of Southern Denmark (j.no. 20-12114). According to Danish law and legislation, ethical review board approval or patient consent is not required for register-based studies. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: It remains unclear if migrants have different odds for adverse outcomes associated with gestational diabetes mellitus (GDM).Objective: We investigated if the associations between GDM and adverse pregnancy outcomes are modified by country of origin and examined the odds of these outcomes according to GDM status and country of origin.Methods: Data were extracted from a nationwide register-based study of singleton deliveries in Denmark, 2004-2015. We used logistic regression models and tested for interaction.Results: Among the 710 413 singleton deliveries, 2.6% had GDM and 14.4% were immigrants. Country of origin modified the association between GDM and pre-eclampsia, large for gestational age (LGA), and small for gestational age (SGA) but not between GDM and planned or emergency cesarean section and preterm delivery. GDM increased the risk of pre-eclampsia among women from Denmark (OR 1.28; 95% CI, 1.18-1.39), Lebanon (OR 3.34; 95% CI, 1.35-8.26), and Morocco (OR 2.28; 95% CI, 1.16-6.88). GDM was associated with increased odds of LGA among women from most countries, particularly women from Sri Lanka (OR 4.20; 95% CI, 2.67-6.61), and was associated with reduced odds of SGA in some countries. Compared with Danish-born women with GDM, the odds of LGA were significantly lower and the odds of SGA higher among women with GDM from India, Lebanon, Pakistan, Iraq, and Somalia.Conclusions: Our study documents that different immigrant groups have higher odds of different GDM-associated adverse pregnancy outcomes and also among countries of origin often grouped together. This highlights the importance of increased awareness to both immigrant background and GDM status in the clinical assessment. [ABSTRACT FROM AUTHOR]

Background: The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.Methods and Findings: A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.Conclusions: Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Compared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors.Methods and Findings: This registry-based cohort study with nationwide data from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (<37 weeks, versus ≥37), and very preterm birth (<32 weeks, versus ≥32). Singletons born after fresh-ET had lower mean birthweight (-51 g, 95% CI -58 to -45, p < 0.001) and increased odds of small for gestational age (odds ratio [OR] 1.20, 95% CI 1.08 to 1.34, p < 0.001), while those born after frozen-ET had higher mean birthweight (82 g, 95% CI 70 to 94, p < 0.001) and increased odds of large for gestational age (OR 1.84, 95% CI 1.56 to 2.17, p < 0.001), compared to naturally conceived siblings. Conventional population analyses gave similar results. Compared to naturally conceived siblings, mean gestational age was lower after fresh-ET (-1.0 days, 95% CI -1.2 to -0.8, p < 0.001), but not after frozen-ET (0.3 days, 95% CI 0.0 to 0.6, p = 0.028). There were increased odds of preterm birth after fresh-ET (OR 1.27, 95% CI 1.17 to 1.37, p < 0.001), and in most models after frozen-ET, versus naturally conceived siblings, with somewhat stronger associations in population analyses. For very preterm birth, population analyses showed increased odds for both fresh-ET (OR 2.03, 95% CI 1.90 to 2.12, p < 0.001) and frozen-ET (OR 1.66, 95% CI 1.42 to 1.94, p < 0.001) compared with natural conception, but results were notably attenuated within siblings (OR 1.18, 95% CI 1.0 to 1.41, p = 0.059, and OR 0.92, 95% CI 0.67 to 1.27, p = 0.6, for fresh-ET and frozen-ET, respectively). Sensitivity analyses in full siblings, in siblings born within 3-year interval, by birth order, and restricting to single embryo transfers and blastocyst transfers were consistent with the main analyses. Main limitations were high proportions of missing data on maternal body mass index and smoking.Conclusions: We found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias.Trial Registration: ClinicalTrials.gov ISRCTN11780826. [ABSTRACT FROM AUTHOR]

Study Question: Is birth weight for gestational age associated with infertility in adulthood among men and women?Summary Answer: Being born small for gestational age (SGA) was associated with infertility in adulthood among men.What Is Known Already: Fetal growth restriction may affect fertility, but results from previous studies have been inconsistent.Study Design, Size, Duration: In this population-based cohort study, we used data from a Danish birth cohort, including 5594 men and 5342 women born between 1984 and 1987. Information on infertility was obtained from Danish health registers during the period from the participants' 18th birthday and up until 31 December 2017.Participants/materials, Setting, Methods: Participants were men and women born in two Danish municipalities, Aalborg and Odense. Information on birth weight and gestational age was obtained from birth records, and information on infertility diagnoses and fertility treatment was retrieved from the Danish National Patient Registry (NPR) and the Danish In Vitro Fertilisation (IVF) registry. Information on potential maternal confounders was obtained from questionnaires during pregnancy and was included in adjusted analyses. Logistic regression analysis was used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for infertility according to birth weight for gestational age.Main Results and the Role Of Chance: Men born SGA had a 55% higher risk of being diagnosed with or treated for infertility compared to men born appropriate for gestational age (AGA) (adjusted OR = 1.55, 95% CI: 1.09-2.21). The association attenuated after exclusion of men born with hypospadias or cryptorchidism (OR = 1.37, 95% CI: 0.93-2.01). No association was found between women's birth weight for gestational age and risk of infertility (adjusted OR = 1.00, 95% CI: 0.73-1.37).Limitations, Reasons For Caution: Estimation of gestational age is associated with some uncertainty and might have caused non-differential misclassification. The study design implicitly assumed similar distribution of reproductive and health-seeking behaviour across the groups that were compared.Wider Implications Of the Findings: Men born SGA had a higher risk of infertility. Genital malformations may account for part of the observed association, but this must be explored further.Study Funding/competing Interest(s): This study was supported by Health, Aarhus University. No competing interests are declared.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of isolated single umbilical artery (iSUA) confirmed at the mid-trimester anomaly scan and adverse pregnancy outcome and congenital malformations with up to 10 years postnatal follow up., Methods: This retrospective cohort study included 116,501 singleton pregnancies consecutively enrolled in first trimester screening for aneuploidies and mid-trimester anomaly scan at three University Hospitals in the Capital Region of Copenhagen, Denmark.Data from the Danish Fetal Medicine Database (2008-2017) were verified by manually scrutinizing pre- and postnatal records. The main outcomes of interest were intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, cesarean section and unrecognized pre- and postnatal congenital malformations., Results: In total, 775 pregnancies with iSUA were identified. Isolated SUA were associated with a significantly increased risk of IUFD (OR 4.16, 95% CI 2.06-8.44), SGA < 3 rd centile (aOR 2.41, 95% 1.85-3.14) and SGA < 10 th centile (aOR 1.84, 95% CI 1.53-2.21), but not with preterm delivery or cesarean section. The laterality of the missing artery was not associated with SGA. In total, 4.3% of pregnancies with iSUA had unrecognized congenital malformations. 1.5% with iSUA had congenital cardiovascular malformations, which were considered minor., Conclusion: Isolated SUA is associated with IUFD and SGA, supporting surveillance during third trimester. If, during the mid-trimester scan, the sonographer achieves thorough, extended cardiac views and finds no additional malformation other than SUA, fetal echocardiography seems not to be needed.

It is a matter of debate whether 1 universal standard, such as the International Fetal and Newborn Growth Consortium for the 21st Century standard, can be applied to all populations. The primary objective was to establish a Danish newborn standard based on the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard to compare the percentiles of these 2 standards. A secondary objective was to compare the prevalence and risk of fetal and neonatal deaths related to small for gestational age defined by the 2 standards when used in the Danish reference population. This was a register-based nationwide cohort study. The Danish reference population included 375,318 singletons born at 33 to 42 weeks of gestation in Denmark between January 1, 2008, and December 31, 2015. The Danish standard cohort included 37,811 newborns who fulfilled the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard. Birthweight percentiles were estimated using smoothed quantiles for each gestational week. The outcomes included birthweight percentiles, small for gestational age (defined as a birthweight of 3rd percentile), and adverse outcomes (defined as either fetal or neonatal death). At all gestational ages, the Danish standard median birthweights at term were higher than the International Fetal and Newborn Growth Consortium for the 21st Century standard median birthweights: 295g for females and 320 g for males. Therefore, the estimates of the prevalence rate of small for gestational age within the entire population were different: 3.9% (n=14,698) using the Danish standard vs 0.7% (n=2640) using the International Fetal and Newborn Growth Consortium for the 21st Century standard. Accordingly, the relative risk of fetal and neonatal deaths among small-for-gestational-age fetuses differed by SGA status defined by the different standards (4.4 [Danish standard] vs 9.6 [International Fetal and Newborn Growth Consortium for the 21st Century standard]). Our finding did not support the hypothesis that 1 universal standard birthweight curve can be applied to all populations. [ABSTRACT FROM AUTHOR]

Objectives To investigate the associations of interpregnancy interval (IPI) with miscarriage, stillbirth, preterm delivery and small for gestational age delivery. Methods The study population comprised all women who had a live birth and at least one subsequent pregnancy in Denmark during the period from 1994 to 2010 (N = 328,577). Linear regression was used to estimate risk differences for miscarriage, stillbirth, preterm delivery and small for gestational age delivery according to IPI. Results The results were heterogeneous: the risk of miscarriage increased monotonically with the length of the IPI. Compared to women with IPIs of 18-23 months, women with IPIs of 0-5 months experienced 18.7 (13.1-24.2) fewer miscarriages per 1000 pregnancies, while women with IPIs of ≥ 60 months experienced 28.7 (23.4-34.0) more miscarriages per 1000 pregnancies. We found that women with IPIs of ≥ 60 months had 1.7 (0.4-3.0) more stillbirths per 1000 births compared to women with IPIs of 18-23 months. U-shaped associations were seen for preterm delivery and small for gestational age delivery with women with IPIs of 18-23 months experiencing the lowest risks of these outcomes. Conclusions for Practice The heterogeneity in associations between IPI and adverse pregnancy outcomes suggests that different mechanisms of action may be at play at various times in the antepartum period. While the finding for miscarriage suggests that fecundity is an important determinant for IPI, the findings for preterm delivery and small for gestational age delivery suggest the coexistence of the maternal depletion syndrome mechanism and the physiological regression mechanism and the finding for stillbirth speaks against a strict maternal depletion syndrome explanation. [ABSTRACT FROM AUTHOR]

Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991–2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2–5 mg/L) (OR = 1.04, 95% CI: 1.03–1.06) and third category (>5–25 mg/L) (OR = 1.02, 95% CI: 1.00–1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01–1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA. [ABSTRACT FROM AUTHOR]

Background: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring., Methods: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment., Results: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39)., Conclusions: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased., (© 2023. The Author(s).)

Background The mechanisms underlying the association between maternal age (both young and older maternal age) and adverse perinatal outcomes are unclear.Methods We examined the association of maternal age at first birth with preterm birth (<37 weeks gestation) and small for gestational age (SGA) in a cohort of 264 695 Danish women, each of which had at least one sister in the cohort (n = 121 859 sibling groups). We compared cohort analyses with sister-controlled analyses. The sister-controlled analyses control for all observed and unobserved characteristics that are identical or very similar between sisters, such as childhood socio-economic characteristics—a confounder we hypothesized would exaggerate the young maternal age–adverse outcomes association but mask the older maternal age–adverse outcome association.Results There was a U-shaped association of maternal age with risk of preterm birth (lowest risk age 24–30 years) and SGA (lowest risk age 26–30 years) in cohort analyses. In analyses with sister control, there was a J-shaped association of maternal age with preterm birth, with a monotonic increase in risk across the maternal age range from 24 years of maternal age. For SGA, risk increased across the age range in sister-controlled analyses, being lowest at age 15 years and highest at age 45 years (thought with wide confidence intervals at the extremes of the age distribution).Conclusions Our findings suggest that different mechanisms underlie the association of younger and older maternal age with adverse perinatal outcomes. Socio-economic position and other characteristics shared by sisters appear to explain most of the association of young maternal age with adverse perinatal outcomes, but the association of older maternal age with preterm birth, and SGA is not explained by this confounding and may even be masked by it. [ABSTRACT FROM AUTHOR]

Objective To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk. Design Population-based case–control study. Setting Danish Cerebral Palsy Register in eastern Denmark and Danish Medical Birth Register. Population or Sample 271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982–1990 in eastern Denmark. Methods Data were abstracted from medical records, and a priori asphyxia-related conditions and other risk factors were selected for analysis. Each factor was classified according to the time at which it was likely to first be present. Main outcome measures Spastic CP. Results Placental and cord complications accounted for the majority of asphyxia conditions. In multivariate analysis, placental infarction was significantly associated with a four-fold increased risk for spastic quadriplegia and cord around the neck was significantly associated with a three-fold increased risk for spastic CP overall. The combination of placental infarction and being small for gestational age (SGA) afforded an especially high risk for spastic quadriplegia. Placental and cord complications were present in 21% of cases and 12% of controls. Conclusions The risk for spastic quadriplegia from placental infarction may be linked in some cases with abnormal fetal growth (17% of all children with spastic quadriplegia and 3% of control children both had an infarction and were SGA)—suggesting an aetiologic pathway that encompasses both factors. The risk for spastic CP from cord around the neck is not accounted for by other prepartum or intrapartum factors we examined. Considering the relative timing of risk factors provides a useful framework for studies of CP aetiology. [ABSTRACT FROM AUTHOR]

OBJECTIVE. The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005. METHODS. Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001-2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants. RESULTS. The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of <32 weeks, who survived for ≥5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures. CONCLUSIONS. The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, persistent organic pollutants widely spread throughout the environment and human populations. They have been found to interfere with fetal growth in some animal models, but whether a similar effect is seen in humans is uncertain. OBJECTIVES: We investigated the association between plasma levels of PFOS and PFOA in pregnant women and their infants' birth weight and length of gestation. METHODS: We randomly selected 1,400 women and their infants from the Danish National Birth Cohort among those who completed all four computer-assisted telephone interviews, provided the first blood samples between gestational weeks 4 and 14, and who gave birth to a single live-born child without congenital malformation. PFOS and PFOA were measured by high performance liquid chromatography-tandem mass spectrometer. RESULTS: PFOS and PFOA levels in maternal plasma were on average 35.3 and 5.6 ng/mL, respectively. Only PFOA levels were inversely associated with birth weight (adjusted β = -10.63 g; 95% confidence interval, -20.79 to -0.47 g). Neither maternal PFOS nor PFOA levels were consistently associated with the risk for preterm birth or low birth weight. We observed no adverse effects for maternal PFOS or PFOA levels on small for gestational age. CONCLUSION: Our nationwide cohort data suggest an inverse association between maternal plasma PFOA levels and birth weight. Because of widespread exposure to these chemicals, our findings may be of potential public health concern. [ABSTRACT FROM AUTHOR]

Context: It remains unclear if migrants have different odds for adverse outcomes associated with gestational diabetes mellitus (GDM)., Objective: We investigated if the associations between GDM and adverse pregnancy outcomes are modified by country of origin and examined the odds of these outcomes according to GDM status and country of origin., Methods: Data were extracted from a nationwide register-based study of singleton deliveries in Denmark, 2004-2015. We used logistic regression models and tested for interaction., Results: Among the 710 413 singleton deliveries, 2.6% had GDM and 14.4% were immigrants. Country of origin modified the association between GDM and pre-eclampsia, large for gestational age (LGA), and small for gestational age (SGA) but not between GDM and planned or emergency cesarean section and preterm delivery. GDM increased the risk of pre-eclampsia among women from Denmark (OR 1.28; 95% CI, 1.18-1.39), Lebanon (OR 3.34; 95% CI, 1.35-8.26), and Morocco (OR 2.28; 95% CI, 1.16-6.88). GDM was associated with increased odds of LGA among women from most countries, particularly women from Sri Lanka (OR 4.20; 95% CI, 2.67-6.61), and was associated with reduced odds of SGA in some countries. Compared with Danish-born women with GDM, the odds of LGA were significantly lower and the odds of SGA higher among women with GDM from India, Lebanon, Pakistan, Iraq, and Somalia., Conclusions: Our study documents that different immigrant groups have higher odds of different GDM-associated adverse pregnancy outcomes and also among countries of origin often grouped together. This highlights the importance of increased awareness to both immigrant background and GDM status in the clinical assessment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Sudden cardiac death (SCD) constitutes a major health problem worldwide. We investigated whether birth weight (BW), small for gestational age (SGA), and large for gestational age are associated with altered risk of SCD among the young (aged 1-36 years). Methods and Results We included all people born in Denmark from 1973 to 2008 utilizing the Danish Medical Birth Register. All SCDs in Denmark in 2000 to 2009 have previously been identified. We defined 5 BW groups, SGA, and large for gestational age as exposure and SCD as the outcome. We estimated the age-specific relative risk of SCD with 95% CI. Additionally, we investigated if SGA and large for gestational age are associated with pathological findings at autopsy. The study population for the BW analyses comprised 2 234 501 people with 389 SCD cases, and the SGA and large for gestational age analyses comprised 1 786 281 people with 193 SCD cases. The relative risk for SCD was 6.69 for people with BW between 1500 and 2499 g (95% CI, 2.38-18.80, P <0.001) and 5.89 for people with BW ≥4500 g (95% CI, 1.81-19.12, P =0.003) at age 5 years. BW 2500 to 3400 g was the reference group. Compared with an appropriate gestational age, the relative risk for SGA was 2.85 (95% CI, 1.35-6.00, P =0.006) at age 10 years. For the autopsied cases, the relative risk of sudden arrhythmic death syndrome at age 5 years was 4.19 for SGA (95% CI, 1.08-16.22, P =0.038). Conclusions We found an association between BW and SCD in the young, with an increased risk among SGA infants. In addition, we found an association between SGA and sudden arrhythmic death syndrome.

The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions. NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.

Objective: Exploring associations between antenatal detection of fetal growth restriction (FGR) and adverse outcome., Design: Retrospective, observational, register-based study., Setting: Zealand, Denmark., Population or Sample: Children born from 1 September 2012 to 31 August 2015., Methods: Diagnoses from birth until 1 January 2018 were retrieved from The National Patient Registry. Detection was defined as estimated fetal weight less than the 2.3rd centile. Cox regression was used to associate detection status with the hazard rate of adverse outcome, adjusted for fetal weight deviation, maternal age, ethnicity, body mass index and smoking., Main Outcome Measures: Adverse neonatal outcome, adverse neuropsychiatric outcome, respiratory disorders, endocrine disorders, gastrointestinal/urogenital disorders., Results: A total of 2425 FGR children were included. An association was found for gastrointestinal/urogenital disorders (hazard ratio [HR] 1.68, 95% CI 1.26-2.23, P < 0.001) and respiratory disorders (HR 1.22, 95% CI 1.02-1.46, P = 0.03) in detected versus undetected infants. For adverse neuropsychiatric outcome, HR was 1.32 (95% CI 1.00-1.75, P = 0.05). There was no evidence of an association between detection and adverse neonatal outcome (HR 1.00, 95% CI 0.62-1.61, P = 0.99) and endocrine disorders (HR 1.39, 95% CI 0.88-2.19, P = 0.16). Detected infants were smaller (median -28% versus -25%, P < 0.0001), more often born preterm (odds ratio [OR] 4.15, 3.12-5.52, P < 0.0001) and more often born after induction or caesarean section (OR 5.19, 95% CI 4.13-6.51, P < 0.0001). Stillbirth risk was increased in undetected FGR fetuses (OR 2.63, 95% CI 1.37-5.04, P = 0.004)., Conclusions: We found an association between detection of FGR and risk of adverse childhood conditions, possibly caused by prematurity. Iatrogenic prematurity may be inevitable in stillbirth prevention, but is accompanied by a risk of long-term childhood conditions., Tweetable Abstract: Antenatal detection of growth-restricted fetuses is associated with adverse childhood outcomes but fewer intrauterine deaths., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Background We hypothesized that women with congenital heart disease (CHD) are at increased risk of giving birth preterm, including very and moderately preterm and giving birth to infants small for gestational age (SGA). We aimed to investigate this in a nation-wide study with focus on the potential modifying effect of socioeconomic status. Methods and Results We performed a cohort study using Danish nation-wide registers between 1997 and 2014. The exposure, maternal CHD, was subdivided into simple, moderate and complex based on severity of defects. Outcomes were preterm birth and SGA. Cox regression was used to estimate hazard ratios (HR). A total of 933 149 births including 3745 births among women with CHD were studied. The risk of giving birth preterm and SGA were higher among women with CHD as compared with women without CHD; for example, adjusted hazard ratios of preterm birth according to severity: simple 1.33 (95% CI, 1.11-1.59), moderate 1.45 (95% CI, 1.14-1.83) and complex 3.26 (95% CI, 2.41-4.40). Same pattern was seen for very and moderately preterm births and SGA. Education was a strong predictor of both preterm birth and SGA but did not modify the association between maternal congenital heart disease and preterm birth ( P =0.38) or SGA ( P =0.99). Conclusions Women with CHD were at increased risk of preterm birth both, moderately and very preterm, as well as giving birth to infants SGA. Education was a strong predictor of both preterm birth and SGA but the association between CHD and risk of preterm birth and SGA was independent of educational level.

Objective: To study perinatal outcomes in singletons born after intrauterine insemination (IUI) compared with children born after in vitro fertilization (IVF), intracytoplasmic sperm injection, and spontaneous conception (SC), and to assess predictors of poor outcome in singletons born after IUI, exploring the effect of ovarian stimulation., Design: National cohort study, 2007-2012., Setting: Danish national registries., Patient(s): Four thousand two hundred twenty-eight singletons born after insemination with partner semen (IUI-H) and 1,881 singletons born after insemination with donor semen., Intervention(s): None., Main Outcome Measure(s): Preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA)., Result(s): Children born after IUI-H had higher risks of PTB, LBW, and SGA vs. SC singletons (adjusted odds ratios [aOR] 1.3; 95% confidence interval (CI), 1.1-1.5; 1.4; 95% CI, 1.2-1.7; and 1.4; 95% CI, 1.2-1.6), respectively. Compared with IVF, risk of SGA was similar, but risks of PTB and LBW were lower (aOR 0.6; 95% CI, 0.5-0.8; and 0.8; 95% CI, 0.6-0.9). Compared with intracytoplasmic sperm injection, no differences were found. For children born after IUI with donor semen, results were similar to those for IUI-H. Risks of LBW and SGA were higher in IUI singletons born after ovarian stimulation with clomiphene citrate, compared with natural-cycle IUI (aOR 1.5; 95% CI, 1.1-2.1 and 1.6; 95% CI, 1.1-2.4). Treatment with follicle-stimulating hormone vs. natural-cycle IUI did not seem to affect perinatal outcomes., Conclusion(s): Singletons born after IUI had higher risk of adverse perinatal outcomes compared with SC children, similar to ICSI, but favorable outcomes compared with IVF. Stimulation with clomiphene citrate was associated with higher risk of SGA compared with natural-cycle IUI, but follicle-stimulating hormone treatment did not seem to be associated with adverse outcomes., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Preterm and growth restricted infants may have developmental delays and deviations from normal organ function related to the gastrointestinal tract and the central nervous system. Since both organ systems are hypothesised to be involved in the pathogenesis of infantile colic, a condition characterised by excessive crying during the first months of life, impaired fetal growth and preterm birth may be risk factors for infantile colic., Methods: A total of 62,761 liveborn singletons from the Danish National Birth Cohort (1996 to 2002) were studied. Infantile colic was defined according to Wessel's modified criteria based on maternal interview conducted at 6 months post-partum., Results: A total of 2605 (4.2%) infants were born preterm, 54,441 (86.7%) at term, and 5715 (9.1%) post-term. A total of 4964 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. The risk for infantile colic increased with decreasing gestational age after adjustment for covariates. The highest odds [odds ratio (95% confidence interval)] was observed for infants born before 32 completed gestational weeks (1.5 [95% CI 1.0, 2.2], reference: 40 gestational weeks). Small for gestational age infants (birthweight below 10th percentile) had an increased odds of infantile colic (1.2 [95% CI 1.1, 1.3]) in all gestational age groups., Conclusions: We observed an increased risk of infantile colic in preterm and small for gestational age infants in a large cohort. Our results suggest that the aetiology of infantile colic may be found in the prenatal, perinatal, and neonatal period., (© 2013 John Wiley & Sons Ltd.)