Search

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, characterized by subfertility, increased risk of metabolic diseases, and pregnancy complications. Previous studies diverge regarding the association between maternal PCOS and newborn anthropometrics., Objective: To explore the association between maternal PCOS and newborn anthropometrics and the modifying effects of maternal body mass index, PCOS phenotype, and gestational diabetes., Design, Setting, and Participants: This cohort study followed up women from the first half of pregnancy to birth and combined data from 3 clinical trials of pregnant women with PCOS and a reference population consisting of participants in the Norwegian Mother, Father, and Child Cohort (MoBa) Study, with data from the Medical Birth Registry of Norway. The recruitment period for the clinical trials was between October 1, 2000, and August 31, 2017, and for MoBa, between July 1, 1999, and December 31, 2008. Participants included women with singleton pregnancies and live-born children. Data were analyzed from January 1 to June 15, 2023., Exposure: Maternal PCOS status., Main Outcomes and Measures: Newborn birth weight, birth length, and head circumference as continuous variables and z scores, and ponderal index (calculated as the birth weight in grams × 100 divided by the birth length in centimeters cubed), placenta weight, and ratio of birth weight to placenta weight (BWPW)., Results: The cohort included 390 pregnant women with PCOS (mean [SD] age, 29.6 [4.2] years) and 68 708 women in the reference group (mean [SD] age, 30.4 [4.5] years). Offspring in the PCOS group had lower birth weight, birth length, and head circumference than in the reference group offspring. The estimated mean differences in z scores were -0.26 (95% CI, -0.38 to -0.14) for birth weight, -0.19 (95% CI, -0.33 to -0.05) for birth length, and -0.13 (95% CI, -0.26 to -0.01) for head circumference. The PCOS group also had a lower ponderal index (-0.04 [95% CI, -0.07 to -0.004] g × 100/cm3) and placenta weight (-24 [95% CI, -43 to -5)] g), and higher BWPW ratio (0.4 [95% CI, 0.3 to 0.5]). The association between growth restriction and PCOS was more apparent when additionally adjusting for body mass index. Neither PCOS phenotype nor gestational diabetes diagnosis was associated with neonatal anthropometry in women with PCOS., Conclusions and Relevance: In this cohort of mother-infant pairs, maternal PCOS status was associated with lower birth weight, shorter birth length, and smaller head circumference in the offspring. This growth restriction was more pronounced when adjusting for BMI, providing insight into the association between PCOS and body mass index. The study contributed to the understanding of how PCOS affects the offspring.

Background and Objectives: Previous studies have shown that individuals with low birth weight (LBW) or small for gestational age (SGA) have higher risk of kidney failure. This study investigates birth-related exposures and risk of CKD and other kidney diagnoses., Design, Setting, Participant, & Measurements: The Medical Birth Registry of Norway has registered extensive medical data on all births in Norway since 1967. The Norwegian Patient Registry has registered diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008. Data from these registries were linked, and risk of CKD and other groups of kidney disease were analyzed using logistic regression statistics. LBW (below the tenth percentile), SGA (birth weight below the tenth percentile for gestational age), and preterm birth (<37 weeks) were analyzed as exposures., Results: A total of 2,663,010 individuals were included. After a mean follow-up of 26 years (maximum 50 years), 4495 had been diagnosed with CKD and 12,818 had been diagnosed with other groups of kidney disease. LBW was associated with an odds ratio (OR) for CKD of 1.72 (95% confidence interval [95% CI], 1.60 to 1.90), SGA with an OR of 1.79 (95% CI, 1.65 to 1.94), and preterm birth with an OR of 1.48 (95% CI, 1.33 to 1.66). Analyses using diagnosis of CKD at stages 3-5 as end point showed similar results. Results were similar for men and women. We analyzed adjusted ORs for other groups of kidney disease and found that LBW was associated with an adjusted OR of 1.44 (95% CI, 1.33 to 1.56) for acute kidney disease, 1.24 (95% CI, 1.14 to 1.36) for GN, 1.35 (95% CI, 1.17 to 1.56) for cystic kidney disease, and 1.15 (95% CI, 1.06 to 1.25) for kidney disease resulting from kidney or urinary tract malformations., Conclusions: LBW, SGA, and preterm birth are associated with higher risk of CKD in the first 50 years of life. Risk of other groups of kidney disease was less pronounced., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020&#95;08&#95;17&#95;CJN04080320.mp3., (Copyright © 2020 by the American Society of Nephrology.)

Background: The association between pregnancy complications and women's later cardiovascular disease has, primarily, been evaluated in studies lacking information on important covariates. This report evaluates the prospective associations between pregnancy-related risk factors (preeclampsia/eclampsia, gestational hypertension, pregestational and gestational diabetes mellitus, preterm delivery, and fetal growth restriction) and pharmacologically treated hypertension within 10 years after pregnancy, while adjusting for a wide range of covariates., Methods and Results: Prepregnancy normotensive women participating in the MoBa (Norwegian Mother and Child Cohort Study) from January 2004 through July 2009 were linked to the Norwegian Prescription Database to identify women with pharmacologically treated hypertension beyond the postpartum period of 3 months. The burden of hypertension associated with pregnancy-related risk factors was evaluated using an attributable fraction method. A total of 1480 women developed pharmacologically treated hypertension within the follow-up among 60 027 women (rate of hypertension, 3.6/1000 person-years). The proportion of hypertension associated with a history of preeclampsia/eclampsia, gestational hypertension, preterm delivery, and pregestational or gestational diabetes mellitus was 28.6% (95% confidence interval, 25.5%-31.6%) on the basis of multivariable analyses adjusting for numerous covariates. The proportion was similar for women with a healthy prepregnancy body mass index (18.5-24.9 kg/m 2 ; attributable fraction (AF)% 25.9%; 95% confidence interval, 21.3%-30.3%), but considerably higher for nulliparous women at baseline within the first 5 years of follow-up. Small-for-gestational age, however, did not increase subsequent hypertension risk in multivariable analyses., Conclusions: A structured postpartum follow-up of high-risk women identified through pregnancy-related risk factors would facilitate personalized preventive strategies to postpone or avoid onset of premature cardiovascular events., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Purpose: Various factors may affect intrauterine foetal growth, amongst which conditions such as epilepsy and the use of anti-epileptic drugs (AED) may play a role. This study investigated intrauterine growth of foetuses in women with epilepsy, as compared with controls, and explored whether intrauterine growth was affected by prenatal exposure to AED., Method: Data were obtained from prospectively registered data regarding pregnancy and prenatal and perinatal factors in women in Oppland County in Norway. The final analysis included information from 166 mothers with epilepsy and 287 children. The control group consisted of 40,553 pregnancies in women without epilepsy registered in the same database., Results: There was a significantly higher risk of the ponderal index being below the 10th percentile and infants being small for gestational age (SGA) in the epilepsy group; exposure to AED increased the risk. The frequency of SGA and low ponderal index was highest in Lamotrigine exposed infants. In the AED group, head circumference was significantly smaller among Carbamazepine exposed., Conclusion: Impaired intrauterine growth of foetuses in women with epilepsy was identified. The frequency of SGA and low ponderal index was highest in Lamotrigine exposed infants. The epilepsy group had a higher risk profile for having smaller babies, in being younger at age, lower in body weight and more frequent smokers. However despite these differences, the effects of epilepsy and AED exposure were significant. The ponderal index may be a useful supplement to more established measures assessing intrauterine growth in epilepsy., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression., Methods: A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g., Results: In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g., Conclusion: Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.

Objective: To construct a diet score for assessing degree of adherence to a healthy and environmentally friendly New Nordic Diet (NND) and to investigate its association with adequacy of gestational weight gain and fetal growth in a large prospective birth cohort., Design: Main exposure was NND adherence, categorized as low, medium or high adherence. Main outcomes were adequacy of gestational weight gain, described as inadequate, optimal or excessive according to the 2009 Institute of Medicine guidelines, and fetal growth, categorized as being small, appropriate or large for gestational age. Associations of NND adherence with gestational weight gain and fetal growth were estimated with multinomial logistic regression in crude and adjusted models., Setting: Norway., Subjects: Women (n 66 597) from the Norwegian Mother and Child Cohort Study (MoBa)., Results: Higher NND adherence implied higher energy and nutrient intakes, higher nutrient density and a healthier macronutrient distribution. Normal-weight women with high as compared with low NND adherence had lower adjusted odds of excessive gestational weight gain (OR=0·93; 95 % CI 0·87, 0·99; P=0·024). High as compared with low NND adherence was associated with reduced odds of the infant being born small for gestational age (OR=0·92; 95 % CI 0·86, 0·99; P=0·025) and with higher odds of the baby being born large for gestational age (OR=1·07; 95 % CI 1·00, 1·15; P=0·048)., Conclusions: The NND score captures diet quality. Adherence to a regional diet including a large representation of fruits and vegetables, whole grains, potatoes, fish, game, milk and drinking water during pregnancy may facilitate optimal gestational weight gain in normal-weight women and improve fetal growth in general.

Background: Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia., Method: A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n=873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ‘ birth weight for gestational age’ and ‘ birth length for gestational age’. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria., Results: The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend=0.005). Compared with the reference group (z scores 0.01–1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (

Aims: We aimed to explore associations between drugs dispensed to the father prior to conception and pregnancy outcomes, such as pre-term birth, perinatal mortality, foetal growth retardation and birth defects., Methods: In this cohort study, two population-based registries, the Medical Birth Registry of Norway and the Norwegian Prescription Database, were linked. The study cohort consisted of 340 000 pregnancies in 2004-10. The association between specific drugs dispensed to the fathers during the last 3 months prior to conception and pregnancy outcomes was explored by estimating odds ratios (ORs) using multivariate logistic regression., Results: About one quarter (26%) of the fathers were dispensed at least one drug during the last 3 months prior to conception and 1.3% were dispensed at least one drug requiring special attention. Overall, the odds of different adverse pregnancy outcomes were not increased when the father had been dispensed drugs, i.e. the OR and 95% confidence intervals (CIs) for any birth defect when the fathers had been dispensed any drug were 0.99 (0.94, 1.0). When the fathers had been dispensed diazepam we found increased risk of perinatal mortality and growth retardation, with OR and 95% CIs of 2.2 (1.2, 3.9) and 1.4 (1.2, 1.6), respectively., Conclusions: Large studies are necessary to reveal increased risk of rare outcomes as specific birth defects. Our study did not indicate that paternal drug exposure is an important risk factor for adverse pregnancy outcomes., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

We assessed whether fetal growth restriction without pregnancy-induced hypertension (PIH) is associated with the different clinical subgroups of PIH in the subsequent pregnancy. We also assessed the maternal and paternal contributions to this effect. Pairs of first and second, second and third, third and fourth, and fourth and fifth births were identified among all of the births in Norway: 137 375 pairs with same mother and father, 18 376 pairs with same mother and different fathers, and 18 916 pairs with same father and different mothers. Second births in each pair were restricted to those that occurred in 1998-2005. Odds ratios to predict early onset, severe, and mild preeclampsia and transient hypertension in the second birth from birth weight <1500 g in the first compared with 3500 to 3999 g were 13.8, 7.1, 3.5, and 2.2, respectively. Odds ratios to predict early onset, severe, and mild preeclampsia and transient hypertension from birth weight below the 2.5th percentile compared with percentiles 10.0 to 89.9 were 4.2, 2.5, 2.1, and 1.7, respectively. Men who fathered a child with low birth weight in 1 woman were not more likely to later father a PIH pregnancy in another woman. The results indicate that placental dysfunction and PIH share a genetic factor that can be expressed as fetal growth restriction in 1 pregnancy and PIH in a subsequent pregnancy. Future genetic study is needed to confirm whether the association is caused by delayed genetic expression of endothelial dysfunction and whether the clinical subgroups of PIH have different genetic backgrounds.

Background: The hypothesis of intrauterine origin of adult disease is debated. We tested whether intrauterine growth restriction is associated with later kidney function., Study Design: Prospective cohort study., Setting & Participants: 7,457 Norwegian adults aged 20 to 30 years participating in the population-based Nord Trøndelag Health Study (1995-1997) with data for birth weight, gestational age, and maternal and perinatal risk factors registered at the Medical Birth Registry of Norway., Predictor: Birth weight expressed as an SD score (SDS) to adjust for gestational age and sex. Subjects with a birth weight SDS less than -2.0, -2.0 to -1.3, and -1.3 to 1.3 were defined as very small, small, and appropriate for gestational age, corresponding to less than the 3rd, 3rd to 10th, and 10th to 90th percentiles, respectively., Outcome & Measurements: Kidney function estimated using the Cockcroft-Gault and isotope dilution mass spectrometry-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Values less than the sex-specific 10th percentile were defined as low-normal kidney function., Results: Compared with men with birth weight appropriate for gestational age (n = 2,755), odds ratios for low-normal creatinine clearance (<100 mL/min) were 1.66 (95% confidence interval [CI], 1.16 to 2.37) if small for gestational age (n = 261) and 2.40 (95% CI, 1.46 to 3.94) if very small for gestational age (n = 101). Kidney function estimated using the MDRD Study equation gave similar results. Women (n = 3,126, 283, and 112, respectively) had odds ratios of 1.65 (95% CI, 1.17 to 2.35) and 2.00 (95% CI, 1.21 to 3.29) for low-normal creatinine clearance (<80 mL/min), whereas the association was not significant using the MDRD Study equation. Using linear regression, creatinine clearance decreased by 4.0 mL/min (95% CI, 3.3 to 4.6) in men and 2.9 mL/min (95% CI, 2.2 to 3.5) in women per 1-SDS decrease. Adjusting for possible confounders did not influence results., Limitations: Selection bias could be a problem because the participation rate was 49%, but there were no statistically significant differences between participants and nonparticipants regarding maternal and perinatal characteristics. Adjusting kidney function for body size can be a special problem in people with intrauterine growth restriction., Conclusions: Although effects were still small in young adulthood, intrauterine growth restriction was significantly associated with low-normal kidney function. The effect was weaker and less consistent in women compared with men.

Objective: The aims were to examine the long-term functional outcome and risk of mood disorders in adulthood in individuals with foetal growth retardation., Method: In a prospective cohort study of 7806 individuals aged 20-30 years, using linked data from the Health Survey of Nord-Trøndelag (HUNT-2) and the Medical Birth Registry of Norway, we studied the long-term effects of being born with a birth weight below the 10th percentile for gestational age (SGA)., Results: SGA individuals had lower educational level (OR: 1.33), lower socioeconomic functioning level (OR: 1.77) and more frequent reported mood disorder in adulthood (OR: 1.26). Analyses of a substratum of infants born at term showed almost identical results., Conclusion: Foetal growth retardation measured as SGA shows a moderate risk for lower education and socioeconomic level and for anxiety and/or depression in young adulthood. Issues concerning interventions for children at risk should be considered.

Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the effect of maternal multiple sclerosis (MS) on pregnancy, delivery, and birth outcome in 649 births by MS mothers and 2.1 million control births. The mothers with MS had a higher proportion of neonates small for gestational age and also more frequent induction and operative interventions during delivery.

Objective: To evaluate the effects of early- and late-onset preeclampsia on fetal growth and body proportion., Methods: This was a population-based study based on records of 672,130 pregnancies from the Medical Birth Registry of Norway during 1967-1998. Women with a prior birth, multiple births, those without valid data on the last menstrual period or newborn's crown-heel length, and chronic maternal disease were excluded., Results: In newborns of women with preeclampsia, mean birth weight, crown-heel length, and ponderal index were 4.4%, 0.8%, and 2.6% lower than in births without preeclampsia, respectively. In preterm births, mean differences in birth weight ranged from -11% to -23% against near-equal birth weights in term births. Mean differences in crown-heel length and ponderal index ranged from -1% to -5% and from -5% to -10% before term, respectively. In late preeclampsia, rates of birth weight and crown-heel length above the 90th and 97.5th percentiles and ponderal index above the 97.5th percentile were slightly but significantly higher than in term births without preeclampsia (odds ratios = 1.1-1.5). However, infants born to mothers with preterm preeclampsia were less likely to be heavy, long, or with high ponderal index for gestational age (odds ratios = 0.4-0.6)., Conclusion: Our results support the hypothesis that preeclampsia is an etiologically heterogeneous disorder that occurs in at least two subsets, one with normal or enhanced placental function, and another involving placental dysfunction and fetal growth restriction, often with asymmetric fetal body proportion, reduced fetal length, and preterm delivery. In future studies, distinguishing between the two subtypes may be important.

Background: Unexplained antepartum stillbirth and sudden infant death syndrome (SIDS) are major contributors to perinatal and infant mortality in the western world. A relation between them has been suggested. As an equivalent of SIDS, only cases validated by post mortem examination are diagnosed as sudden intrauterine unexplained death (SIUD)., Objective: To test the hypothesis that SIDS and SIUD have common risk factors., Methods: Registration comprised all stillbirths in Oslo and all infant deaths in Oslo and the neighbouring county, Akershus, Norway during 1986-1995. Seventy six cases of SIUD and 78 of SIDS were found, along with 582 random controls surviving infancy, all singletons. Odds ratios were obtained by multiple logistic regression analysis., Results: Whereas SIUD was associated with high maternal age, overweight/obesity, smoking, and low education, SIDS was associated with low maternal age, smoking, male sex, multiparity, proteinuria during pregnancy, and fundal height exceeding +2 SD. Thus the effects of maternal age were opposite in SIUD and SIDS (adjusted odds ratio 1.39 (95% confidence interval 1.17 to 1.66) per year, p < 0.0005). Heavy smoking, male sex, and a multiparous mother was less likely in SIUD than in SIDS (0.22 (0.06 to 0.83), 0.22 (0.07 to 0.78), and 0.03 (<0.01 to 0.17) respectively). Overweight/obesity and low fundal height were more common in SIUD than in SIDS (7.45 (1.49 to 37.3) and 13.8 (1.56 to 122) respectively)., Conclusions: The differences in risk factors do not support the hypothesis that SIDS and SIUD have similar determinants in maternal or fetal characteristics detectable by basic antenatal care.

Aims: To evaluate whether being born small for gestational age (SGA) was associated with an increased frequency of preschool behavioral problems., Study Design: Follow-up study at 5 years of age., Subjects: A population based cohort of 318 term infants who were SGA, defined as having a birthweight less than the 15th percentile for gestational age, and without major handicap such as cerebral palsy or mental retardation, and a random control sample of 307 appropriate for gestational age (AGA) infants., Outcome Measures: The Personality Inventory for Children and the Yale Children's Inventory (completed by the mothers), and child behavior during psychometric testing., Results: Behavior problems was not more common among the SGA children. The results were not confounded by a wide range of parental demographic and child rearing factors, including maternal non-verbal problem solving abilities, child rearing style, and maternal psychological distress. However, the parental factors explained 13% of the variance in a summary score of child behavior compared to 1% explained by SGA vs. AGA status. The SGA children were not more sensitive to the negative impacts of parental risk factors than AGA controls. The study does not address the outcome of severely growth-retarded SGA infants., Conclusion: Being born moderately SGA is not a significant risk factor for preschool behavior problems.

Objective: To evaluate the effect of low birth weight adjusted for gestational age in first pregnancies on preeclampsia in second pregnancies and to estimate the proportion of preeclampsia in second pregnancies attributable to histories of LBW for gestational age., Methods: We conducted a cohort study based on linked data from the Medical Birth Registry of Norway, which covered all births in 1967-1992., Results: Women who delivered infants under the third percentile birth weight were three times more likely to have initial or recurrent preeclampsia in second pregnancies than those who delivered infants at or above the tenth percentile. After adjusting for maternal age, year of birth, interpregnancy interval, education, chronic hypertension, diabetes mellitus, and change of partner, the increased risk persisted. Birth weight below the tenth percentile in the first delivery accounted for 10% of the total cases of preeclampsia in the second pregnancy and 30% of recurrent cases., Conclusion: A history of low birth weight adjusted for gestational age is associated significantly with subsequent occurrence as well as recurrence of preeclampsia. These findings are consistent with the hypothesis of a shared etiologic factor or recurrent pathophysiologic mechanism for preeclampsia and fetal growth restriction. A history of fetal smallness for gestational age is found in a substantial proportion of all cases of preeclampsia and thus seems to be important in the etiology of preeclampsia.

Background: Quality assessment of perinatal care can be carried out by classifying perinatal deaths. In the following we have analyzed the geographical contrasts in perinatal deaths according to the Nordic-Baltic perinatal death classification in a sparsely populated Norwegian county., Material and Methods: All stillbirths (> or =28 weeks of gestation) and neonatal deaths (gestational age > or =22 weeks; death < or =28 days) in 1986-96 from Nordland county (240,000 inhabitants) were classified. For comparison the county was geographically divided into six general local hospital areas and one central hospital area., Results: The classification showed a well acceptable inter and intra observer variation. One hundred and seventy-one stillbirths and 155 neonatal deaths were analyzed. The death rate (pr 1,000 births) for single, non-malformed, antenatal stillbirths was higher in the central hospital area than in the local hospital areas (3.22 vs. 2.02). The death rate for extreme preterm infants (22-27 weeks of gestation) was on the other hand higher in the local hospital areas (2.45 vs. 1.05). One of the general local hospital areas was singled out with an especially high neonatal death rate among extreme preterm infants. This was to some extent explained by the death of extreme preterm twins and triplets., Conclusion: The Nordic-Baltic perinatal death classification system is a consistent and reproducible tool also for studying perinatal death in restricted geographical areas. The observed contrasts in perinatal deaths were used as basis for programs aimed at improving perinatal care. The observation of an unexplained increased number of antenatal stillbirths in the central hospital area resulted in a program for prospective recording and better characterization of the placenta and umbilical cord. Proposals for a better antenatal program preventing extreme preterm birth of twins for the whole county has been launched. In utero transfer to a hospital with a neonatal intensive care unit seems crucial in improving the prognosis for these infants.

Retarded intrauterine growth has been linked to increased risk of perinatal mortality and morbidity, sudden infant death and poorer health later in life. The independent variables used in these studies are mainly neonatal size parameters, such as weight, ponderal index and ratios of head and abdominal measures. These are, in terms of foetal development and growth, crude parameters. This paper discusses the concepts of growth retardation used in most clinical and epidemiological studies. It is again emphasized that small for gestational age (SGA) and intrauterine growth retardation (IUGR) are different concepts. SGA is a size parameter that may or may not reflect restricted foetal growth and is therefore of limited value. Even IUGR, defined as retarded foetal growth rate, may be a too crude a criterion to select foetuses with short- and long-term health risks. Other biophysical measurements, such as foetal blood flow patterns and biochemical parameters, may be helpful in a better selection of these foetuses and infants. Furthermore, different causes of IUGR, e.g. poor maternal nutrition versus insufficient placental function, may not have the same effects on the foetus. The discrepancies in the results of studies on the relationship between IUGR or foetal malnutrition and short- and long-term health risks may be explained by the crudeness of the independent variables used. In the future, research on the biology of the developing human foetus should be more focused in the studies of the relationship between the intrauterine environment and nutrition and risk of poor health later in life.

Background and Method: Small-for-gestational-age (SGA) infants represent a heterogeneous group of normal and growth-retarded children. To assess the familial aggregation of reduced fetal growth, birth weights in both maternal and paternal relatives of 1246 index children in the Scandinavian SGA Study were compared across groups defined by the SGA outcome of the index child as well as that of earlier siblings., Results: Mean maternal birth weight +/- SEM was 3127 +/- 54 g for mothers who had experienced two SGA births as opposed to 3424 +/- 22 for mothers with no SGA births. Mean paternal birth weight was 3497 +/- 88 g and 3665 +/- 24 in the same two groups. The odds ratio (with 95% confidence interval) for having a mother with birth weight below the 10th percentile was 1.74 (0.85-3.58) for the group where two SGA births had occurred compared to no SGA births and it was 2.49 (1.22-5.07) for having a father with birth weight below the 10th percentile. There was no correlation between maternal and paternal birth weights., Conclusions: The association also to paternal birth weight suggests the presence of genetic or common environmental factors in explaining the tendency to have SGA children. Although taking parental birth weights into consideration will aid in diagnosing growth-retardation in a SGA child, SGA remains a heterogeneous group where familial and non-familial cases will be difficult to separate.

Background: The purpose was to determine the usefulness of maternal serum concentrations of human chorionic gonadotropin (hCG), human placental lactogen (hPL) and estriol as predictors of fetal growth., Method: From a large cohort serum obtained serially at 17, 25, 33 and 37 weeks of gestation were analyzed for randomly selected pregnancies resulting in small for gestational age (SGA, n = 102) and non-SGA (n = 112) infants., Results: There were no significant correlations between birthweight ratio (ratio of birthweight to mean weight for gestational age) and hCG, but between birthweight ratio on one hand and estriol for all stages of pregnancy (r = 0.19-0.38, p < 0.01 - p < 0.001) and hCL except at 33 weeks (r = 0.11-0.40, p ns-p < 0.001) on the other. There were statistically significant, but small median differences and substantial overlaps between the SGA and non-SGA infants for hCG at 17 and 37 weeks, for hPL at 17, 33 and 37 weeks, and for estriol at all the stages of pregnancy. The sensitivity and positive predictive value of low hormone concentrations (below the 10th percentile) in predicting the birth of an SGA infant were in the range of 6-26% and 17-39%, respectively. The corresponding specificity and prediction of a non-SGA infant from normal levels were 91-93% and 85-88%., Conclusions: HPL and estriol, but not hCG concentrations, are positively related to the size of the fetus, but the relationships are too weak to be of predictive value in an unselected population.

Background: We wanted to examine if infants who were small for gestational age (SGA) at term had increased perinatal mortality or morbidity compared to non-SGA infants, and if this could be related to the infant's body proportions, or to whether the mother previously had delivered a low-birthweight infant ("repeater") or not ("non-repeater")., Methods: From a cohort of 5722 para 1 and para 2 women, we compared perinatal mortality in 541 SGA (birthweight < 10th percentile) and 4737 non-SGA infants. From the same cohort, early neonatal morbidity was studied in 368 SGA and 462 control infants without congenital malformations., Results: SGA infants had a 6.4 (95% CI: 2.6-15.7) higher risk of perinatal death than controls, but when infants who died with congenital malformations were excluded, this risk was not significantly increased. SGA infants were more often transferred to an intensive care unit than controls (1.7, 95% CI: 1.0-2.9). Among SGA births, infants with asymmetric body proportions (i.e. low ponderal index) more often had symptoms in the neonatal period (RR: 2.5; 95% CI: 1.4-4.3) and were more often transferred to an intensive care unit (3.4; 95% CI: 1.6-7.4) than symmetric SGA infants, whereas there were no differences between SGA infants of repeaters and non-repeaters., Conclusions: We found that SGA infants had higher perinatal mortality than controls, but this was due to a higher prevalence of congenital malformations. Among SGA infants without malformations, our results indicated increased neonatal morbidity in infants with asymmetric body proportions.

In order to elucidate whether maternal plurality affects offspring intrauterine growth, the relationship between birthweight and gestational age of twins and singletons and those of their first singleton liveborn children in Norway was studied using data from the Medical Birth Registry. The population-based sample consisted of 49,698 mother-offspring pairs (48,842 with singleton and 856 with twin-mothers). In bivariate analyses, no significant differences in mean birthweight and gestational age of offspring of twin and singleton mothers were found, although the mean birthweight and gestational age of the twin-mothers themselves were significantly lower than those of singletons (819 g and 14 days respectively). In multiple regression analysis, the expected birthweight of offspring was 230.3 g (95% CI: 193.2-267.4 g) higher when the mother was a twin than when the mother was a singleton, when controlling for non-standardised maternal birthweight. When adjusting for relative maternal birthweight (z-score), the association between maternal plurality and offspring birthweight was not statistically significant. The results suggest that being born as a twin has no substantial consequences on offspring growth in utero and show that mean differences in birthweight between twins and singletons should be standardised when both groups are included in multivariate studies.

Background: The purpose was to compare growth patterns and psychomotor development of healthy small-for-gestational-age (SGA) and non-SGA infants, and identify factors predictive of outcome at 13 months of age., Method: A total of 265 SGA infants and 329 non-SGA controls were identified from a multicenter cohort of 5722 para 1 and 2 women who had been followed during pregnancy. The infants were examined at 2 days and at 13 months of age. Psychomotor development at 13 months was assessed with The Bayley Scale of Infant Development., Results: The SGA infants showed partial catch-up growth, but had still lower (mean +/- SEM, p < 0.0001) weight (9750 +/- 65 vs 10505 +/- 67 g), crown-heel length (75.9 +/- 0.2 vs 77.5 +/- 0.2 cm) and head circumference (46.9 +/- 0.1 vs 47.7 +/- 0.1 cm) than the non-SGA infants at 13 months. The SGA children scored equally well on the motor (PDI 106.8 +/- 1.0 vs 107.2 +/- 0.8) but lower on the mental scale (MDI 112.1 +/- 0.8 vs 116.5 +/- 0.7, p < 0.0001) of the Bayley Scale, and the asymmetric SGA scored lower than the symmetric SGA infants (MDI 110.2 +/- 1.3 vs 113.3 +/- 0.9, p = 0.05). In a multivariate regression analysis the parents' growth parameters had the greatest effect on growth measures at 13 months while education and maternal smoking had no significant effect. SGA vs non-SGA status had the greatest effect on growth velocities during infancy. For mental development only SGA vs non-SGA status and the mothers' education made significant contributions, but only accounted for 6% of the variance., Conclusion: The negative impact of intrauterine factors on growth are partly abolished by catch-up growth during infancy, and growth parameters at one year of age are mostly determined by genetic factors even in SGA infants. Decreased intrauterine growth may possibly have a negative effect on brain growth and mental developmental potential.

Background: It has been suggested that the effect of maternal smoking on fetal growth is partly mediated through nutritional factors., Objective: To assess the effects of maternal smoking on birthweight in term pregnancies among mothers with different anthropometric stature., Design: A prospective study from early pregnancy of healthy parous women and their infants., Setting: Three Scandinavian university hospitals covering all deliveries from well defined geographic areas., Subjects: Smoking (774) and non-smoking (325) mothers, para 1 and 2 and with > 36 weeks gestational length., Main Outcome Measure: Birthweight., Results: Maternal age, smoking, pre-pregnancy weight, height, body mass index and pregnancy weight gain all independently influenced birthweight. Smoking mothers had significantly lower pre-pregnancy weight and lower body mass index compared to nonsmoking mothers. The negative influence of smoking on birthweight appeared to be uniformly distributed throughout all the different maternal height and weight groups., Conclusions: Birthweight was negatively related to amount cigarettes smoked per day, and no protective effect could be demonstrated from higher maternal weight, pregnancy weight gain or body mass index.

Background: Fetuses of women who repeat small-for-gestational-age births in successive pregnancies may have a different intrauterine growth pattern than SGA birth of non-repeater mothers. Also repeated SGA births may grow differently depending on whether the tendency to repeat is due to some external factors such as cigarette smoking ("false repeaters") or due to genetic or intrinsic factors ("true repeaters")., Material and Methods: Fetal growth were compared in a "nested case-control" study within a longitudinal (cohort) study, comparing three types of SGA births, 23 of "true repeater" mothers, 46 of "false repeater" mothers and 65 of non-repeater mothers, and these were compared with 1017 non-SGA births. Fetal growth was compared using a regression analysis based on repeated measurements (four for each woman)., Results: For mean abdominal diameter the "true repeater" SGA births grew more slowly towards the end of pregnancy. However, the growth curves show only minor differences between the three types of SGA births, but the patterns are grossly different from the growth of non-SGA births (controls)., Conclusion: The intrauterine growth retardation starts early in pregnancy, and is not strikingly different between births of repeater and non-repeater mothers.

Background: The purpose of this study was to examine if placentas of small- for-gestational-age (SGA) and non-SGA infants differ with respect to proliferative cell activity., Method: Cell cycle distribution was studied in placentas from 181 SGA (birthweight < 10th percentile) and 528 non-SGA births by flow cytometry measurements of relative DNA content., Results: The fraction of cells in various cell cycle phases (G1-, S- and G2-phases) did not differ with gestational age from 30 to 43 weeks in either of the groups. The placentas of the SGA infants had a significantly lower mean (+/-1 SEM) growth fraction than placentas of non-SGA infants (S-phase 5.2 +/- 0.2 vs 5.5 +/- 0.1, p = 0.05, and G2-fraction 5.4 +/- 0.2 vs 6.3 +/- 0.1, p < 0.001), but the overlaps of the distributions were large. Thus sensitivity, specificity and predictive values of low fractions did not differ substantially-from a purely random prediction of SGA., Conclusions: Cell division in the placenta is maintained until and beyond term. Placentas of SGA infants have on average, lower proliferative activity than placentas of non-SGA infants, but the difference is too small to be of predictive value in identifying intrauterine growth retardation.

Background: We wanted to analyze the association between small-for-gestational-age (SGA) births, defined as a newborn with a birthweight below the 15th percentile-for-gestational age, and socioeconomic and psychosocial risk factors., Methods: Information on social background, psychological status, and life events was collected prospectively by use of questionnaires in the second and third trimester of pregnancy. The respondents were 1552 women who expected their second or third child and took part in a Scandinavian multicenter study of fetal growth and perinatal outcome., Results: No significant differences were found in relational stress, state and trait anxiety, depression, and physical strain between SGA and non-SGA births, whereas smoking around time of conception and low prepregnant body mass were significant SGA birth predictors. Maternal and paternal education of nine years or less increased the SGA birth risk (RR 1.46 (95% CL 1.12; 1.92) and RR 1.34 (95% CL 1.01; 1.79), respectively. The increased risk from a low maternal education was still significant when body mass and low paternal education were controlled, but not after adjustment for maternal smoking. A protective effect of paternal, but not maternal, education of 12 years or more was also observed and retained its effect when maternal smoking and body mass were controlled., Conclusion: In this seemingly homogeneous Scandinavian population, parental education and maternal body proportion and life style influenced the prevalence of small-for-gestational-age births. Relational stress, anxiety, depression, and physical strain did not influence birth outcome.

The Scandinavian part of the NICHD study of successive small-for-gestational-age (SGA) births included 5722 parous women from Trondheim and Bergen (in Norway) and Uppsala (in Sweden). Study enrollment took place from January 1986 through March 1988. The aim of the main study was to investigate factors associated with inhibited intrauterine growth. This paper reports on the fetal, perinatal, and neonatal deaths among the births in the study in relation to different risk factors. The cause of deaths were analyzed to see if there were any associations with the risk factors. There was a total of 84 deaths, 65 of these were fetal, perinatal or neonatal deaths and included in this analysis. The remaining 19 are for different reasons excluded. Thirty-two (60%) of the autopsies regarded the high risk group who comprised only 42.4% of the total study population. The high risk group was selected using the following risk criteria: a previous low weight birth or perinatal death, maternal low weight (pre-pregnancy weight < 50 kg), the presence of a chronic maternal disease, and smoking at the time of conception. A significant association was found between perinatal mortality and the presence of one or more of the defined risk criteria (relative risk 2.0; 95% CI 1.2, 3.4). Asphyxia and related disorders was the most important single cause of death and was found to be associated with the maternal risk factors (RR 3.9; 95% CI 1.5, 9.8). A significant association was found between maternal risk factors and SGA autopsies (RR 3.9; 95% CI 1.7, 8.9). No association was found between asphyxia and SGA. It is concluded that women with risk factors based on complications in a previous pregnancy are more prone to stillbirths, perinatal, and neonatal deaths, and with asphyxia as the most prominent cause of death.