Svein Rasmussen

Fetal and maternal contributions to risk of pre-eclampsia: population based study

Abstract Objective: To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressed in the fetus contribute to the mothers risk of pre-eclampsia and whether mothers susceptibility to pre-eclampsia is related to maternal inheritance by mitochondrial DNA. Design: Linked data on pregnancies of different women who had children with the same father, and subsequently linked data on pregnancies of half sisters who either had same mother and different fathers or had same father and different mothers. Setting: Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7 million) and the Norwegian Central Population Register. Main outcome measures: Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relative risks approximated by odds ratios. Results: If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different woman her risk of developing pre-eclampsia is 1.8 (95% confidence interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and with whom she shares the same mother but different fathers the risk of pre-eclampsia is 1.6 (0.9 to2.6). If the two sisters have the same father but different mothers the risk is 1.8 (1.01 to 2.9). Conclusions: Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus being affected by paternal genes. Mitochondrial genes, which are transmitted by mothers, do not seem to contribute to the risk. Key messages Paternal genes in the fetus may contribute substantially to a pregnant womans risk of pre-eclampsia The role of the fetus may be as important as that of the mother Purely maternal inheritance (specifically by mitochondrial DNA) is probably not involved in pre-eclampsia Search for specific genes that predispose for pre-eclampsia should include the fetus as well as the mother

Blood flow and the degree of shunting through the ductus venosus in the human fetus.

OBJECTIVES Our goal was to determine the degree of shunting through the ductus venosus in the human fetus and its possible association with fetal growth. STUDY DESIGN Blood flow in the umbilical vein and the fetal ductus venosus was measured in 197 low-risk pregnancies in a cross-sectional ultrasonographic study at a gestational age of 18 to 41 weeks. The degree of shunting was compared to birth weight and ponderal index. RESULTS The average fraction shunted through the ductus venosus was 28% to 32% at 18 to 20 weeks, decreased to 22% at 25 weeks, and reached 18% at 31 weeks (with wide ranges expressed in the 10th and 90th percentiles). Fetuses <10th percentile for birth weight had significantly more shunting (1.4%) than those >90th percentile (95% confidence interval, 0.1%-2.7%; P =.04). CONCLUSIONS In the human fetus a higher proportion of umbilical blood is directed to the liver and less is shunted through the ductus venosus, in comparison with what has previously been shown in animal experiments.

Fetal cardiac output, distribution to the placenta and impact of placental compromise.

Intrauterine growth restriction is a common clinical problem, but the underlying hemodynamic changes are not well known. Our aim was to determine the normal distribution of fetal cardiac output to the placenta during the second half of pregnancy, and to assess the changes imposed by growth restriction with various degrees of placental compromise.

Pregnancy outcome in women before and after cervical conisation : population based cohort study

Objectives To examine the consequences of cervical conisation in terms of adverse outcome in subsequent pregnancies. Design Population based cohort study. Data sources Data on cervical conisation derived from the Cancer Registry of Norway and on pregnancy outcome from the Medical Birth Registry of Norway, 1967-2003. 15 108 births occurred in women who had previously undergone cervical conisation and 57 136 who subsequently underwent cervical conisation. In the same period there were 2 164 006 births to women who had not undergone relevant treatment (control). Results The proportion of preterm delivery was 17.2% in women who gave birth after cervical conisation versus 6.7% in women who gave birth before cervical conisation and 6.2% in women who had not undergone cervical conisation. The relative risk of a late abortion (<24 weeks’ gestation) was 4.0 (95% confidence interval 3.3 to 4.8) in women who gave birth after cervical conisation compared with no cervical conisation. The relative risk of delivery was 4.4 (3.8 to 5.0) at 24-27 weeks, 3.4 (3.1 to 3.7) at 28-32 weeks, and 2.5 (2.4 to 2.6) at 33-36 weeks. The relative risk of preterm delivery declined during the study period and especially of delivery before 28 weeks’ gestation. Conclusion Cervical conisation influences outcome in subsequent pregnancies in terms of an increased risk of preterm delivery, especially in the early gestational age groups in which the clinical significance is highest. A careful clinical approach should be taken in the selection of women for cervical conisation and in the clinical care of pregnancies after a cervical conisation.

Neonatal outcomes in offspring of women with anxiety and depression during pregnancy

SummaryBackground: The presence of mental disorder during pregnancy could affect the offspring.Aims: To examine the effects of anxiety disorder and depression in pregnant women on neonatal outcomes, and to compare neonatal outcomes between offspring of attendees and non-attendees in a general population-based health survey.Method: Pregnant women (n = 680) were identified from the population-based health study of Nord-TrØndelag County (HUNT-2) by linkage with the Medical Birth Registry of Norway. The women rated themselves on the Hospital Anxiety and Depression Rating Scale (HADS). Outcome variables were gestational length, birth weight, and Apgar scores.Results: HADS-defined anxiety disorder during pregnancy was associated with lower Apgar score at one minute (score < 8; odds ratio = 2.27; p = .03) and five minutes (score < 8; odds ratio = 4.49; p = .016). No confounders were identified. Anxiety disorder and depression during pregnancy was not associated with low birth weight or preterm delivery. Offspring of non-attendees had a lower birth weight (77 g; t = 3.27; p = 0.001) and a shorter gestational length (1.8 days; t = 2.76; p = 0.006) than that of offspring of attendees, a difference that may be explained by a higher load of psychosocial risk factors among the non-attendees.Conclusion: In our study that may be biased towards the healthier among pregnant women, anxiety disorder or depression during pregnancy were not strong risk factors for adverse neonatal outcomes although low Apgar score in offspring of women with anxiety disorder may indicate poor neonatal adaptation.

Longitudinal reference ranges for estimated fetal weight

Objective. The aims of the present study were to establish reference ranges for the growth of estimated fetal weight (EFW) between gestational weeks 20 and 42 and to determine the effect of fetal and maternal factors. Methods. This prospective longitudinal study was based on 634 low‐risk pregnancies and a total of 1799 examinations. Gestational age was computed from last menstrual period. Head circumference, abdominal circumference, and femur length were measured using ultrasound, and EFW was calculated using the formula of Combs et al. The statistical analysis was based on regression analysis and multilevel modeling. Results. Intrauterine growth expressed by EFW showed a continuous pattern until term. Males were calculated to be 5% heavier than female fetuses at 20 gestational weeks and 3% at 40 weeks. Otherwise, the fetal and maternal effects on intrauterine growth correspond to a weight shift of 1.3% for breech/nonbreech, 2.5% for each increase in maternal height tertile, and −4% for smoking/nonsmoking. Maternal age higher than 34 years had a significant increased EFW of 4.5% compared with maternal age less than 24 years. Cephalic index in the third tertile had a 1.1% lower EFW compared with the first tertile. Maternal weight, body mass index, and parity did not influence the EFW. Terms for customization to individualize the growth patterns are presented. Conclusions. The present growth chart is recommended as robust reference ranges for assessing EFW and growth. Fetal and maternal variables can be added into the models to individualize the prediction of EFW.

Fetal growth and body proportion in preeclampsia

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 newborns 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.

Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements

To establish reference ranges suitable for serial assessments of the fetal middle cerebral (MCA) and umbilical (UA) artery blood flow velocities, pulsatility index (PI) and cerebroplacental pulsatility ratio and to provide terms for calculating conditional reference intervals suitable for individual serial measurements.

Ductus venosus shunting in growth-restricted fetuses and the effect of umbilical circulatory compromise

To determine the degree of ductus venosus (DV) shunting in fetuses with intrauterine growth restriction (IUGR) and the effect of various degrees of umbilical circulatory compromise.

Trends in Risk Factors for Obstetric Anal Sphincter Injuries in Norway

OBJECTIVE: To investigate risk factors for obstetric anal sphincter injuries in a large population-based data set, and to assess to what extent changes in these risk factors could account for trends in obstetric anal sphincter injuries. METHODS: This is a population-based cohort study on data from the Medical Birth Registry of Norway between 1967 and 2004, including all vaginal singleton deliveries of vertex-presenting fetuses weighing 500 g or more. Women with their first birth before 1967 and births with previous obstetric anal sphincter injuries were excluded, leaving 1,673,442 births for study. The outcome variable was third- and fourth-degree obstetric anal sphincter injuries. The associations of obstetric anal sphincter injuries with possible risk factors were estimated by odds ratios (ORs) obtained by logistic regression. RESULTS: The occurrence of obstetric anal sphincter injuries increased from 0.5% in 1967 to 4.1% in 2004. After adjusting for demographic and other risk factors, as well as possible confounders, the increase of obstetric anal sphincter injuries persisted, although reduced (unadjusted OR 7.1; 95% confidence interval [CI] 6.8–7.4; adjusted OR 5.6; 95% CI 5.3–5.9). Obstetric anal sphincter injuries were significantly associated with maternal age 30 years or older, vaginal birth order of one, previous cesarean delivery, instrumental delivery, episiotomy, type 1 diabetes, gestational diabetes, induction of labor by prostaglandin, size of maternity unit, birth weight 3,500 g or more, head circumference 35 cm or more, and African or Asian country of birth. CONCLUSION: Risk of obstetric anal sphincter injuries considerably increased in Norway in 1967 to 2004. Changes in the risk factors studied could only partially explain this increase. LEVEL OF EVIDENCE: II