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Background: 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., Objective: 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., Study Design: 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)., Results: 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])., Conclusion: Our finding did not support the hypothesis that 1 universal standard birthweight curve can be applied to all populations., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.)

Introduction: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated., Material and Methods: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas., Results: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30)., Conclusions: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed., (2021 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Background: High levels of nitrate ( NO 3 - ) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent., Objectives: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term ( ≥ 37  wk gestation) live-born singletons., Methods: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable., Results: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of - 9.71   g (95% confidence interval: - 14.60 , - 4.81 ) was predicted at 25  mg / L (half the value of the European Union drinking water standard) compared with 0  mg / L   NO 3 - . Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO 3 - and head circumference or LBW., Discussion: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings. https://doi.org/10.1289/EHP7331.

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.)

Objective: To explore the relationship between small fetal second-trimester head circumference (HC) and pregnancy outcome and identify a cutoff point for offering genetic testing., Method: Data from second-trimester scans in Denmark were linked to national registers. Fetuses with anomalies diagnosed before this scan were excluded. Fetuses were grouped according to HC z-score., Results: We included 352 515 singleton fetuses. The mean HC was significantly larger among males than among females with z-scores averaging 0.52 more in males. Small HC was associated with chromosomal anomaly, malformations of the CNS and heart, miscarriage/perinatal death, termination, preterm delivery, and intrauterine growth restriction (test for trend: P < .001 for all outcomes). Fetuses in the group with z-score less than -3 had the highest incidence of adverse outcome, irrespective of fetal sex. In the groups with z-scores between -3 and -2.5, and between -2.5 and -2, risk of adverse outcome was lower for females than males for all outcome categories., Conclusion: Small HC in second trimester is a prognostic marker for adverse outcome. The smaller the HC, the higher the risk of adverse outcome. We suggest an HC cutoff point of -2 SD for males and -2.5 SD for females for offering genetic testing., (© 2019 John Wiley & Sons, Ltd.)

Objective: To evaluate the risk of adverse pregnancy outcome when trisomy 16 confined to the placenta is diagnosed and to identify possible prognostic markers for adverse outcomes in these pregnancies., Method: Registered cases (n = 49) of trisomy 16 diagnosed prenatally in Denmark from 1990 to 2013 were included., Results: Twenty-five of the pregnancies intended to be continued had confined placental trisomy 16 mosaicism (CPM16). Adverse pregnancy outcome was seen in 17 CPM16 pregnancies (68%), ranging from mild small for gestational age (SGA) to fetal malformations and intrauterine demise. For cases ascertained by combined first trimester screening, the median concentration of pregnancy associated plasma protein A (PAPP-A) was 0.17 MoM (IQR: 0.11 MoM). Adverse pregnancy outcome showed a trend toward an association with a high frequency of trisomic cells. Eight children (32%) were born at term with a normal birth weight and no malformations., Conclusion: The risk of adverse pregnancy outcome in case of CPM16 is correlated to ascertainment by combined first trimester screening and tends to be associated with a high frequency of trisomic cells in the placenta. We recommend that variables including ascertainment, the frequency of trisomic cells, and the maternal serum concentration of PAPP-A are taken into consideration when evaluating the prognosis in CPM16 while acknowledging that these factors are strongly correlated., (© 2018 John Wiley & Sons, Ltd.)

Background: Placenta-mediated complications are leading causes of maternal and fetal morbidity and mortality. We hypothesized that a preconception history of venous thromboembolism (VTE) is associated with increased risk of placenta-mediated pregnancy complications., Methods: A nationwide population-based cohort study of all singleton pregnancies leading to delivery from 1997 to 2012 (n = 964 967). We obtained data on placenta-mediated pregnancy complications from the Danish Medical Birth Registry and data on VTE before pregnancy from the Danish National Patient Registry. We computed absolute risks, crude and adjusted risk differences (RDs) using a binomial regression model, and crude and adjusted risk ratios (RRs) from a modified Poisson regression model., Results: Overall, 1419 women had a preconception history of VTE, while 578 112 did not. Preeclampsia occurred in 4.2% of pregnancies in the VTE group and in 2.7% of pregnancies in a comparison cohort (adjusted RD = 1.3%, 95% confidence interval (CI) 0.6-2.0%; adjusted RR = 1.5, 95% CI 1.3-1.8). Stillbirth occurred in 0.7% of pregnancies in the VTE group and in 0.4% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI 0.02-0.6%; adjusted RR = 1.8, 95% CI 1.1-3.0). Placental abruption occurred in 0.8% of pregnancies in the VTE group and in 0.5% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI - 0.05-0.6%; adjusted RR = 1.6, 95% CI 1.1-2.4). Small-for-gestational-age infants accounted for 10.9% of live births in the VTE group and 9.8% of live births in the comparison cohort (adjusted RD = 0.6%, 95% CI - 0.5-1.7%; adjusted RR = 1.1, 95% CI 0.9-1.3)., Conclusion: Women with a history of VTE were at increased risk of placenta-mediated complications., (© 2015 International Society on Thrombosis and Haemostasis.)

Objectives: To assess the impact of systemic lupus erythematosus (SLE) on pregnancy outcome in a cohort of incident pregnant lupus patients referred to a Danish university hospital during 1990-2010., Method: All pregnant lupus patients were referred to the university hospital from a stable referral area with approximately 1.4 million inhabitants. Eighty-four pregnancies in 39 women were registered using the Danish National Registry and retrospective reviewing of medical records, laboratory results, and midwifery records from the Department of Rheumatology, the Department of Obstetrics and Gynaecology, and possible other departments. Data were compared to 29 059 births during 2005-2010, covering all births from the referral area., Results: The 84 SLE pregnancies resulted in 62 live births. SLE flares developed in 46.4%, pre-eclampsia in 8.3%, and HELLP syndrome in 4.8% of cases. Significantly higher rates of premature delivery (p=0.0032), caesarean section (p=0.015), hypertension (p=0.025), and intrauterine growth retardation (IUGR) (p=0.003) were found. Disease activity significantly (p=0.021) increased the risk of prematurity threefold. Antiphospholipid antibody (aPL) presence significantly (p=0.002) increased the risk of spontaneous abortion threefold. Two babies died after extreme preterm birth. Two had neonatal lupus syndrome (NLS) and one had congenital heart block (CHB). Birth weight and length were significantly lower in the SLE cohort. An unexpectedly high number of cardiac septum defects (9.7%) were observed., Conclusions: From a stable referral area, an incident cohort of SLE pregnancies were mostly successful, but maternal and foetal complications were observed in one-half and one-third of cases, respectively. Outcome risk factors were identified. A possible new observation is a high frequency of cardiac septum defects.

The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11-1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97-1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.

Context: Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited., Objective: To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes., Design, Setting, and Participants: Registry-based cohort study based on all liveborn singleton infants in Denmark, delivered between November 2, 2009, and September 30, 2010. In propensity score-matched analyses, we estimated prevalence odds ratios (PORs) of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy., Main Outcome Measures: Major birth defects, preterm birth, and small size for gestational age., Results: From a cohort of 53,432 infants (6989 [13.1%] exposed to the influenza A[H1N1]pdm09 vaccine during pregnancy [345 in the first trimester and 6644 in the second or third trimester]), 660 (330 exposed) were included in propensity score-matched analyses of adverse fetal outcomes associated with first-trimester exposure. For analysis of small size for gestational age after second- or third-trimester exposure, 13,284 (6642 exposed) were included; for analyses of preterm birth, 12,909 (6543 exposed) were included. A major birth defect was diagnosed in 18 of 330 infants (5.5%) exposed to the vaccine in the first trimester, compared with 15 of 330 unexposed infants (4.5%) (POR, 1.21; 95% CI, 0.60-2.45). Preterm birth occurred in 31 of 330 infants (9.4%) exposed in the first trimester, compared with 24 of 330 unexposed infants (7.3%) (POR, 1.32; 95% CI, 0.76-2.31), and in 302 of 6543 infants (4.6%) with second- or third-trimester exposure, compared with 295 of 6366 unexposed infants (4.6%) (POR, 1.00; 95% CI, 0.84-1.17). Small size for gestational age was observed in 25 of 330 infants (7.6%) with first-trimester exposure compared with 31 of 330 unexposed infants (9.4%) (POR, 0.79; 95% CI, 0.46-1.37), and in 641 of 6642 infants (9.7%) with second- or third-trimester exposure, compared with 657 of 6642 unexposed infants (9.9%) (POR, 0.97; 95% CI, 0.87-1.09)., Conclusions: In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction.

Objectives: Exposure to prenatal stress may affect neurodevelopment of the fetus, but whether this exposure increases the risk of cerebral palsy (CP) later in life is unknown. We aimed to examine the association between maternal bereavement during the prenatal time period and CP in childhood., Methods: We conducted a nationwide cohort study by linking information from nationwide registers. All 1,501,894 singletons born in Denmark from 1979 to 2004 were followed up from birth to the end of 2006. We identified 39,601 children whose mothers lost a close relative (child, spouse, parent, sibling) during pregnancy or up to 1 year before pregnancy and they were classified as the exposed group. The outcome of interest was the diagnosis of CP as registered in the National Hospital Register. We used Cox Regression to estimate the hazard ratios (HRs)., Results: Exposure to maternal bereavement after the loss of a child during the prenatal period was associated with an increased risk of CP among children born preterm without intrauterine growth retardation (HR 2.26, 95% CI, 1.09-3.79) and among children born at term with intrauterine growth retardation (HR 2.01, 95% CI, 1.04-3.89). Prenatal stress after maternal bereavement by loss of other relatives was not associated with an increased risk of CP., Conclusions: Our data suggest that extremely severe stress in prenatal life could increase the susceptibility for CP among children born preterm or with impaired fetal growth.

Background: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. The time trends in maternal social disadvantage in relation to fetal growth were examined in the context of a universal welfare state under changing macroeconomic conditions over a 24-year period., Methods: All births in Denmark from 1981 to 2004 were included, and the association between maternal social disadvantage and birthweight was examined for gestational age z-scores over time using linear regression., Results: All measures of social disadvantage were associated with decreased fetal growth (p<0.001), but with considerable differences in the magnitude of the associations. The association was strongest for non-Western ethnicity (-0.28 z-score), low education (-0.19), teenage motherhood (-0.14), single motherhood (-0.13) and poverty (-0.12) and weakest for unemployment (-0.04). The deficit in fetal growth increased over time for all associations except for unemployment. Also, the measures of social adversity increasingly clustered within individuals over time., Conclusion: Maternal social disadvantage is associated with decreased fetal growth in a welfare state. Social disadvantage is increasingly clustered so that fewer pregnancies are exposed, but those exposed suffer a greater disadvantage in fetal growth. The economic upturn in the last decade did not appear to weaken the association between maternal social disadvantage and decreased fetal growth.

Babies born of infertile couples, regardless of treatment, have a higher risk of preterm birth and low birthweight, conditions associated with delayed development. We examined developmental milestones in singletons as a function of parental infertility [time to pregnancy (TTP) > 12 months] and infertility treatment. From the Danish National Birth Cohort (1997-2003), we identified 37 897 singletons born of fertile couples (TTP < or = 12 months), 4351 born of infertile couples conceiving naturally (TTP > 12 months), and 3309 born after infertility treatment. When the children were about 18 months old, mothers reported 12 developmental milestones by responding to structured questions. We defined a failure to achieve the assessed milestone or the minimal numbers of milestones in a summary (motor, or cognitive/language skills) as delay. Naturally conceived children born of infertile couples had a pattern of psychomotor development similar to that of children born of fertile couples, but increasing TTP correlated with a modest delay. When the analysis was restricted to infertile couples (treated and untreated), children born after treatment showed a slight delay in cognitive/language development (odds ratio 1.24, [95% confidence interval 1.01, 1.53]) for not meeting at least three out of six cognitive/language milestones); children born after intracytoplasmic sperm injection (ICSI) had the highest estimated relative risk of delay for most milestones, especially motor milestones. These results suggest that a long TTP may be associated with a modest developmental delay. Infertility treatment, especially ICSI, may be associated with a slight delay for some of these early milestones.

Objective: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality., Methods: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less), 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age., Results: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among untreated and 1.26, 95% CI 0.86-1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution., Conclusion: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases., Level of Evidence: II.

The authors examined the relation between fish consumption during pregnancy and fetal growth among 44,824 women from the Danish National Birth Cohort (1996-2002). They evaluated the associations between consumption of total fish, fatty fish, and lean fish in midpregnancy and birth weight, birth length, and head circumference among singleton full-term infants. Fish consumption was ascertained by food frequency questionnaire. The birth of infants classified below the 10th percentile for gestational age and gender was significantly increased among women who consumed more than 60 g of fish per day, as compared with women who consumed 5 g or less per day. Adjusted odds ratios were 1.24 (95% confidence interval (CI): 1.03, 1.49) for birth weight and 1.21 (95% CI: 1.01, 1.43) for head circumference. The adjusted odds ratio was borderline significant for birth length (odds ratio = 1.20, 95% CI: 1.00, 1.45). These increases in risk were followed by small decreases in average values for these growth measures. Furthermore, the inverse association for total fish consumption could be explained by consumption of fatty fish, while no association was found for lean fish. These results indicate that consumption of fatty fish, a known route of exposure to persistent organic pollutants, could be associated with reduced fetal growth.

Background: To estimate the association between severe maternal life events and infants small for gestational age at different gestational ages at birth., Methods: From 1980 to 1992 all women exposed to severe life events such as death or first hospitalization for cancer or acute myocardial infarction in partners or children during pregnancy or up to 485 days before were identified through national registers. We included all 3,402 exposed pregnancies and 19,551 unexposed pregnancies randomly selected to the control cohort and performed adjusted stratified Cox proportional hazards regression analyses with time-dependent covariates., Results: These life events were not associated with SGA in general, but exposed infants born before 32 weeks of gestation had twice the risk for being born with a birth weight

To examine whether fetal growth indicators and other prenatal factors were associated with the use of anti-asthma medications during the first year of life, we conducted a follow-up study based on birth registry and prescription registry data of the county of North Jutland, Denmark. We identified 9705 singletons born between 1 April 1996 and 31 December 1997. They were followed to the end of the first year of life by linkage with a prescription registry. Prescription for asthma was defined as both a beta-agonist and an inhaled glucocorticoid prescription. A prescription for asthma was presented to 3.8% of the infants during the first year of life. Maternal asthma, male gender, maternal smoking, multiparous births, young maternal age, and maternal non-cohabitation were associated with the risk of receiving a prescription for asthma. There were slightly increased trends in the risk with birth weight and placental weight. The increased risk was more pronounced in the groups of birth weight > or = 3800 g (adjusted OR: 1.23, 95% CI: 0.88-1.73) and placental weight > or = 750 g (adjusted OR: 1.44, 95% CI: 1.10-1.88). The increased risk was also associated with a high ponderal index of > or = 2.7 g/cm3 (adjusted OR: 1.37, 95% CI: 1.06-1.76).

Objective: Our study aimed to compare the birth outcomes in offspring of women with ulcerative colitis with controls without the disease., Methods: A cohort study of 1531 newborns to mothers with ulcerative colitis, and 9092 controls, based on linkage between the Danish National Registry of Patients and the Danish Birth Registry from 1982 to 1992., Results: Among the births to women with ulcerative colitis, 569 took place before and 962 after the first hospitalization for ulcerative colitis. We found no increased risk of either low birth weight or intrauterine growth retardation for newborns born before or after the mothers' first hospitalization. The risk of preterm birth was increased when birth occurred after the mothers' first hospitalization (odds ratio = 1.4, 95% confidence interval = 1.1-1.9), and particularly when the first hospitalization for ulcerative colitis took place during pregnancy (odds ratio = 3.4, 95% confidence interval = 1.8-6.4)., Conclusions: In the offspring of women with ulcerative colitis, we found no increased risk of low birth weight or signs of intrauterine growth retardation. The risk of preterm birth was increased in the offspring of women with ulcerative colitis, particularly when the first hospitalization for ulcerative colitis occurred during pregnancy.

Background: There is conflicting evidence about the frequency of adverse pregnancy outcomes among women with schizophrenia., Aims: To investigate the risk of preterm birth, low birth weight and intra-uterine growth retardation among women with schizophrenia., Method: A total of 2212 births to 1537 women with schizophrenia in Denmark were compared with a random sample of all deliveries in Denmark in 1973-1993 (122,931 births to 72,742 women)., Results: The children of women with schizophrenia were at increased risk of preterm delivery (relative risk = 1.46, 95% CI = 1.19-1.79), low birth weight (relative risk = 1.57, 95% CI = 1.36-1.82) and small for gestational age (relative risk = 1.34, 95% CI = 1.17-1.53)., Conclusions: Women with schizophrenia are at increased risk of adverse pregnancy outcome. This may be associated with an increased mortality and general morbidity and risk of schizophrenia in their children.

Background: Some studies have found an association between spontaneous abortion and adverse birth outcome in the subsequent pregnancy, but results are conflicting, maybe due to lack of confounder control., Methods: Using population-based registries we identified a cohort of 45 449 women having a livebirth preceded by a spontaneous abortion ('abortion cohort'), and a random sample of 9752 women with two consecutive livebirths ('reference cohort'). We examined the risk of preterm (<37 weeks gestation) and very preterm delivery (<34 weeks), low birthweight and growth retardation in both births in the reference cohort compared with births following an abortion, controlling for social factors and interpregnancy interval., Results: Compared to second births in the reference cohort, the abortion cohort had higher risks for preterm (odds ratio [OR] = 1.74, 95% CI: 1.5-2.0) and very preterm delivery (OR = 2.17, 95% CI : 1.7-2.7), low birthweight (OR = 1.76, 95% CI: 1.5-2.1), and growth retardation (OR = 1.50, 95% CI: 1.4-1.6). In the reference cohort 3.9% of the pregnancies ended as preterm deliveries, 1 % as very preterm, 3.3% as low birthweight, and 8.1% as growth retarded. Women with two or more previous abortions had a higher risk for preterm and very preterm delivery. When first liveborns of women in the reference cohort were compared with first liveborns in the abortion cohort, only deliveries before 34 and 37 weeks' gestation were associated with previous abortion., Conclusions: Spontaneous abortion is associated with preterm delivery (both <34 and <37 weeks) in the subsequent pregnancy. Women who become pregnant following an abortion should receive special attention in the antenatal clinics.

Objective: To estimate the risk of having a low birthweight infant associated with changes in social, environmental, and genetic factors., Design: Population based, historical cohort study using the Danish medical birth registry and Statistic Denmark's fertility database., Subjects: All women who had a low birthweight infant (< 2500 g) (index birth) and a subsequent liveborn infant (outcome birth) in Denmark between 1980 and 1992 (exposed cohort, n = 11,069) and a random sample of the population who gave birth to an infant weighing > or = 2500 g and to a subsequent liveborn infant (unexposed cohort, n = 10,211)., Main Outcome Measures: Risk of having a low birthweight infant in the outcome birth as a function of changes in male partner, area of residence, type of job, and social status between the two births., Results: Women in the exposed cohort showed a high risk (18.5%) of having a subsequent low birthweight infant while women in the unexposed cohort had a risk of 2.8%. After adjustment for initial social status, a decline in social status increased the absolute risk of having a low birthweight infant by about 5% in both cohorts, though this was significant only in the unexposed cohort. Change of male partner did not modify the risk of low birth weight in either cohort., Conclusion: Having had a low birthweight infant and a decline in social status are strong risk factors for having a low birthweight infant subsequently.

A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns.