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Objectives Single umbilical artery (SUA) is associated with congenital malformations in most organ systems, but reported findings have not been consistent. While it has been suggested that genetic and persisting environmental factors influence the development of SUA, it is not known whether there is an increased risk of recurrence in a subsequent pregnancy of the same woman. The aims of this study were to investigate the occurrence of, and risk factors for, SUA in Norway, to assess its association with congenital malformations and trisomies 13, 18 and 21 and to study the risk of recurrence of SUA in subsequent pregnancies. Methods This was a population-based study of all (n = 918 933) singleton pregnancies of > 16 weeks' gestation recorded in the Medical Birth Registry of Norway from 1999 to 2014. To identify risk factors and congenital malformations associated with SUA, generalized estimating equations and logistic regression were used to calculate odds ratios (OR) with 95% CIs. ORs were also calculated for the recurrence of SUA in subsequent pregnancy. Results The occurrence of SUA in our population was 0.46% (4241/918 933). Parity ≥ 4, smoking, maternal pregestational diabetes, epilepsy, chronic hypertension, previous Cesarean delivery and conception by assisted reproductive technology increased the odds of having SUA. There was a particularly strong association between SUA and gastrointestinal atresia or stenosis in the neonate, with ORs of 25.8 (95% CI, 17.0-39.1) and 20.3 (95% CI, 13.4-30.9) for esophageal and anorectal atresia or stenosis, respectively, followed by an OR of 5.9 (95% CI, 1.9-18.5) for renal agenesis. SUA was associated with an up to 7-8 times increased risk of congenital heart defects. There was an association with microcephaly, congenital hydrocephalus and other congenital malformations of the brain and spinal cord. Diaphragmatic hernia, limb reductions and cleft lip or palate had a weaker association with SUA, with ORs ranging from 4.8 to 2.8. The associations with trisomy 18 and 13 were equally strong (OR 14.4 (95% CI, 9.3-22.4) and OR 13.6 (95% CI, 6.7-27.8), respectively), and the risk of trisomy 21 was doubled (OR 2.1 (95% CI, 1.2-3.6)). Pregnancies with SUA, with or without an associated malformation, had a 2-fold increased risk for SUA in a subsequent pregnancy. Conclusions SUA is associated strongly with gastrointestinal atresia or stenosis, suggesting common developmental mechanisms. The increased risk of recurrence of SUA suggests that genetic and/or persisting environmental factors influence the risk. We found that SUA had equally strong associations with trisomies 13 and 18. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background: In 2011 Norway granted undocumented women the right to antenatal care and to give birth at a hospital but did not include them in the general practitioner and reimbursement schemes. As a response to limited access to health care, Non-Governmental Organizations (NGO) have been running health clinics for undocumented migrants in Norway’s two largest cities. To further facilitate universal health coverage, there is a need to investigate how pregnant undocumented women use NGO clinics and how this afects their maternal health. We therefore investigated the care received, occurrence of pregnancy-related complications and pregnancy outcomes in women receiving antenatal care at these clinics. Methods: In this historic cohort study we included pregnant women aged 18–49 attending urban NGO clinics from 2009 to 2020 and retrieved their medical records from referral hospitals. We compared women based on region of origin using log-binominal regression to estimate relative risk of adverse pregnancy outcomes. Results: We identifed 582 pregnancies in 500 women during the study period. About half (46.5%) the women sought antenatal care after gestational week 12, and 25.7% after week 22. The women had median 1 (IQR 1–3) antenatal visit at the NGO clinics, which referred 77.7% of the women to public health care. A total of 28.4% of women were referred for induced abortion. In 205 retrieved deliveries in medical records, there was a 45.9% risk for any adverse pregnancy outcome. The risk of stillbirth was 1.0%, preterm birth 10.3%, and emergency caesarean section 19.3%. Conclusion: Pregnant undocumented women who use NGO clinics receive substandard antenatal care and have a high risk of adverse pregnancy outcomes despite low occurrence of comorbidities. To achieve universal health coverage, increased attention should be given to the structural vulnerabilities of undocumented women and to ensure that adequate antenatal care is accessible for them.

Background Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life. Material and methods This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics. Results There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44–0.83] p Conclusion Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.

Objective To explore risk profiles of the different types of postpartum hemorrhage (PPH >500ml or severe PPH >1500ml) and their recurrence risks in a subsequent delivery. Methods With data from The Medical Birth Registry of Norway and Statistics Norway we performed a population-based cohort study including all singleton deliveries in Norway from 1967–2017. Multilevel logistic regression was used to calculate odds ratio (OR), with 95% confidence interval (CI), with different PPH types (PPH >500ml or PPH >1500ml (severe PPH) combined with retained placenta, uterine atony, obstetric trauma, dystocia, or undefined cause) as outcomes. Result We identified 277 746 PPH cases of a total of 3 003 025 births (9.3%) from 1967 to 2017. Retained placenta (and/or membranes) was most often registered as severe PPH (29.3%). Maternal, fetal, and obstetric characteristics showed different associations with the PPH types. Male sex of the neonate was associated with reduced risk of PPH. This effect was strongest on PPH due to retained placenta (adjusted OR, (aOR): 0.80, 95% CI 0.78–0.82), atony (aOR 0.92, 95% CI: 0.90–0.93) and PPH with undefined cause (aOR 0.96, 95% CI: 0.95–0.97). Previous cesarean section showed a strong association with PPH due to dystocia (aOR of 13.2, 95% CI: 12.5–13.9). Recurrence risks were highest for the same type: PPH associated with dystocia (aOR: 6.8, 95% CI: 6.3–7.4), retained placenta and/or membranes (aOR: 5.9, 95% CI: 5.5–6.4), atony (aOR: 4.0, 95% CI: 3.8–4.2), obstetric trauma (aOR: 3.9, 95% CI: 3.5–4.3) and PPH of undefined cause (aOR: 2.2, 95% CI: 2.1–2.3). Conclusion Maternal, fetal and obstetric characteristics had differential effects on types of PPH. Recurrence differed considerably between PPH types. Retained placenta was most frequently registered with severe PPH, and showed strongest effect of sex; delivery of a boy was associated with lower risk of PPH. Previous cesarean increased the risk of PPH due to dystocia.

Purpose This study examines individual aggregation of postpartum hemorrhage (PPH), paternal contribution and how offspring birthweight and sex influence recurrence of PPH. Further, we wanted to estimate the proportion of PPH cases attributable to a history of PPH or current birthweight. Methods We studied all singleton births in Norway from 1967 to 2017 using data from Norwegian medical and administrational registries. Subsequent births in the parents were linked. Multilevel logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PPH defined as blood loss > 500 ml, blood loss > 1500 ml, or the need for blood transfusion in parous women. Main exposures were previous PPH, high birthweight, and fetal sex. We calculated adjusted population attributable fractions for previous PPH and current high birthweight. Results Mothers with a history of PPH had three- and sixfold higher risks of PPH in their second and third deliveries, respectively (adjusted OR 2.9; 95% CI 2.9–3.0 and 6.0; 5.5–6.6). Severe PPH (> 1500 ml) had the highest risk of recurrence. The paternal contribution to recurrence of PPH in deliveries with two different mothers was weak, but significant. If the neonate was male, the risk of PPH was reduced. A history of PPH or birthweight ≥ 4000 g each accounted for 15% of the total number of PPH cases. Conclusion A history of PPH and current birthweight exerted strong effects at both the individual and population levels. Recurrence risk was highest for severe PPH. Occurrence and recurrence were lower in male fetuses, and the paternal influence was weak.

Aim We evaluated the role of placental pathology in predicting adverse outcomes for neonates born extremely preterm (EPT) before 28 weeks of gestation. Methods This was a prospective observational study of 123 extremely preterm singletons born in a hospital in western Norway, and the placentas were classified according to the Amsterdam criteria. The associations between histologic chorioamnionitis (HCA), by the presence or the absence of a foetal inflammatory response (FIR+ or FIR−), maternal vascular malperfusion (MVM) as a whole and adverse neonatal outcomes were evaluated by logistic regression analyses. Adverse outcomes were defined as perinatal death, necrotising enterocolitis (NEC), bronchopulmonary dysplasia (BPD), brain pathology by magnetic resonance imaging at term-equivalent age, retinopathy of prematurity and early-onset neonatal sepsis. The results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results HCA was associated with NEC (OR 12.2, 95% CI 1.1 to 137.1). HCA/FIR+ was associated with BPD (OR 14.9, 95% CI 1.8–122.3) and brain pathology (OR 9.8, 95% CI 1.4–71.6), but HCA/FIR− was not. The only neonatal outcome that MVM was associated with was low birthweight. Conclusion Placental histology provided important information when assessing the risk of adverse neonatal outcomes following EPT birth. publishedVersion

Introduction Isolated single umbilical artery (iSUA) refers to single umbilical artery cords with no other fetal malformations. The association of iSUA to adverse outcome of pregnancy has not been consistently reported, and whether iSUA carries increased risk of third stage of labor complications has not been studied. We aimed to investigate the risk of adverse perinatal outcome, third stage of labor complications, and associated placental and cord characteristics in pregnancies with iSUA. A further aim was to assess the risk of recurrence of iSUA and anomalous cord or placenta characteristics in Norway. Material and methods This was a population-based study of all singleton pregnancies with gestational age >16 weeks at birth using data from the Medical Birth Registry of Norway from 1999 to 2014 (n = 918 933). Odds ratios (OR) with 95% confidence intervals were calculated for adverse perinatal outcome (preterm birth, perinatal and intrauterine death, low Apgar score, transferral to neonatal intensive care ward, placental and cord characteristics [placental weight, cord length and knots, anomalous cord insertion, placental abruption and previa]), and third stage of labor complications (postpartum hemorrhage and the need for manual placental removal or curettage) in pregnancies with iSUA, and recurrence of iSUA using generalized estimating equations and logistic regression. Results Pregnancies with iSUA carried increased risk of adverse perinatal outcome (OR 5.06, 95% confidence interval [CI] 4.26-6.02) and perinatal and intrauterine death (OR 5.62, 95% CI 4.69-6.73), and a 73% and 55% increased risk of preterm birth and small-for-gestational-age neonate, respectively. The presence of iSUA also carried increased risk of a small placenta, placenta previa and abruption, anomalous cord insertion, long cord, cord knot and third stage of labor complications. Women with iSUA, long cord or anomalous cord insertion in one pregnancy carried increased risk of iSUA in the subsequent pregnancy. Conclusions The presence of ISUA was associated with a more than five times increased risk of intrauterine and perinatal death and with placental and cord complications. The high associated risk of adverse outcome justifies follow up with assessment of fetal wellbeing in the third trimester, intrapartum surveillance and preparedness for third stage of labor complications.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Introduction Studies on the family aggregation of postpartum hemorrhage (PPH) are scarce and with inconsistent results, and to what extent current birthweight influences recurrence between relatives remains to be studied. Further, family aggregation of PPH has been studied from an individual, but not from a public heath perspective. We aimed to investigate family aggregation of PPH in Norway, how birthweight influences these effects, and to estimate the proportion of PPH cases attributable to a family history of PPH and current birthweight. Material and methods Using data from the Medical Birth Registry of Norway, Statistics Norway, and Central Population Registry of Norway we identified individuals as newborns, parents, grandparents, and full and half-siblings, and studied 1 002 687 mother–offspring, 841 164 father–offspring, and 761 011 both-parents–offspring pairs. We used multilevel logistic regression to calculate odds ratios (OR) with 95% CI. Results If the birth of the mother but not of the father involved PPH, then the OR of PPH (>500 mL) in the next generation was 1.44 (95% CI 1.39–1.49). If the birth of the father but not of the mother involved PPH, then OR was 1.12 (95% CI 1.08–1.16). These effects were stronger in severe PPH. Recurrence between siblings was highest between full sisters (OR 1.47, 95% CI 1.41–1.52), followed by maternal half-sisters, paternal half-sisters, and partners of full brothers. A family history of PPH or birthweight of 4000 g or more accounted for ≤5% and 15% of the total number of PPH cases, respectively. Conclusions A history of PPH in relatives influenced the recurrence risk of PPH in a dose–response pattern consistent with the anticipated proportion of shared genes. The recurrence was highest through the maternal line. publishedVersion

Women of reproductive age who present with abdominal pain and purulent vaginal discharge are commonly seen in primary health care and gynaecological outpatient clinics. Their symptoms are often caused by sexually transmitted infections and efficiently treated with empiric antibiotics. However, in some cases diagnostics are more challenging.We present the case history of a woman in her twenties with multiple sclerosis under rituximab treatment. She presented with a wide range of symptoms over twelve months, including upper and lower respiratory tract infections, urinary bladder urgency, chronic abdominal pain, diarrhoea, bloody stools, weight loss and fatigue. She underwent urological and gastroenterological examinations which yielded normal findings. After the onset of genital discomfort and copious amounts of vaginal discharge, gynaecological examination and routine microbiological testing of discharge were negative. Finally, she presented with septicaemia and progressive abdominal pain. Laparoscopy was performed due to absence of recovery after initial transvaginal ultrasound-guided aspiration of ovarian cysts. The microbe Ureaplasma urealyticum was detected in ovarian pus. Treatment with doxycycline resulted in full recovery.It is important to consider opportunistic microbes in immunocompromised patients, as they might pose a major diagnostic challenge and require the involvement of several specialties.

Objective To assess whether parents who were born small for gestational age (below the 10th birthweight centile, SGA) have increased risk of severe or mild placental abruption. To assess whether a history of SGA in other family members modifies this intergenerational effect. Design Prospective population-based observational study. Setting The Medical Birth Registry of Norway. Population From 1967 to 2013, 785 333 mother–offspring pairs, 643 066 father–offspring pairs, 272 941 maternal tetrads (i.e. her offspring, sibling, and niece/nephew), and 265 505 paternal tetrads were identified. Methods Cohort study based on linked data from the Medical Birth Registry of Norway. Main outcome measures Relative risk (RR) of severe placental abruption (preterm birth, birthweight below the 10th centile, or perinatal death) and mild placental abruption (other cases) in families with SGA. Results Mothers who were born SGA had increased risk of severe placental abruption (RR 1.5; 95% confidence interval, 95% CI 1.3–1.8), but not mild abruption. The paternal effects were weaker. The combined effect of SGA in the mother and her sibling on severe abruption was twofold (RR 2.4; 95% CI 1.7–3.3) compared with birthweight centiles ≥10 for both. Similarly, the effect of adding an SGA niece/nephew was twofold (RR 2.3; 95% CI 1.3–3.9), whereas the combined effect of SGA in the mother, her sibling and her niece/nephew was fourfold (RR 3.6; 95% CI 1.9–6.8). Conclusions Women who were born SGA have an increased risk of severe placental abruption. The corresponding paternal effect was modest. A history of SGA in other family members increases the generational effect. Tweetable abstract Women born small for gestational age have excess risk of placental abruption.

Hypertensive disorders of pregnancy (HDP) tend to recur from one pregnancy to the next. The aims of the study were to assess the recurrence risk according to type of HDP defined by gestational age at birth and to examine whether recurrence is associated with the following additional risk factors for HDP: maternal age, smoking, inter delivery interval, diabetes, body mass index, as well as fetal growth restriction, and to assess temporal trends in these associations. All women with two singleton births in the Medical Birth Registry of Norway 1967-2012 (n= 742 980) were included in this population based cohort study. Logistic regression was used to calculate odds ratios for the risk of recurrent HDP according to type of HDP. The highest odds ratio of recurrence was observed for the same type of HDP based on gestational age at delivery. After gestational hypertension and term preeclampsia the risk increased tenfold for the same type to recur, whereas after late and early preterm preeclampsia, the risk increased 27 and 97 fold, respectively. The recurrence of early preterm preeclampsia was less influenced by additional risk factors than term HDP. Recurrence of early preterm HDP was significantly lower from 1993 onwards. Recurrent HDP tended to be of the same type as the previous HDP. Risk of recurrence associated with additional risk factors were observed particularly after term. The odds ratio of recurrence of early preterm HDP was significantly lower from 1993 onwards. This article is protected by copyright. All rights reserved.

Anomalous cord insertion is associated with increased risk of adverse maternal and perinatal outcome. Our aim was to study whether anomalous cord insertion is associated with prelabor rupture of membranes (PROM), preterm PROM (pPROM), long or short umbilical cord, and time trend of spontaneous preterm birth (SPTB) and anomalous cord insertion.A population-based register study using data from the Medical Birth Register of Norway including all singleton births (gestational age16 weeks and45 weeks) during 1999-2013 (n = 860 465) to calculate odds ratios (ORs) for PROM, pPROM, SPTB, and cord length (95th or5th centile) according to the cord insertion site by logistic regression with adjustment for possible confounders. We also assessed time trends of SPTB and anomalous cord insertion.Velamentous insertion of the cord was associated with an increased risk of PROM (OR 1.6, 95% CI 1.5-1.7), pPROM (OR 2.7, 95% CI 2.4-3.0), SPTB (OR 2.0, 95% CI 1.9-2.2), and a short cord (OR 1.7, 95% CI 1.5-1.8). Marginal insertion was to a lesser extent associated with these complications. Occurrences of SPTB and anomalous insertion declined. The decline in SPTB persisted after including an interaction term between anomalous insertion and time.Velamentous and, to a lesser extent, marginal cord insertions were associated with increased risk of PROM, pPROM, SPTB, and short cord. This suggests a common pathogenesis behind altered function of the membranes, cord, and placenta. The decline in SPTB could not be explained by the reduction in the occurrence of anomalous cord insertion.

Circadian rhythmicity is fundamental to human physiology, and is present even during fetal life in normal pregnancies. The impact of maternal endocrine disease on the fetal circadian rhythm is not well understood. The present study aimed to determine the fetal circadian rhythm in pregnancies complicated by pregestational diabetes mellitus (PGDM), compare it with a low-risk reference population, and identify the effects of maternal glycemic control and morning cortisol concentrations. Long-term fetal electrocardiogram recordings were made in 40 women with PGDM at 28 and 36 weeks of gestation. Two recordings were made in 18 of the women (45.0%) and one recording was made in 22 (55.0%). The mean fetal heart rate (fHR) and the fHR variation (root mean square of squared differences) were extracted in 1-min epochs, and circadian rhythmicity was detected by cosinor analysis. The study cohort was divided based on HbA1c levels and morning cortisol concentrations. Statistically, significant circadian rhythms in the fHR and the fHR variation were found in 45 (100%) and 44 (95.7%) of the 45 acceptable PGDM recordings, respectively. The rhythms were similar to those of the reference population. However, there was no statistically significant population-mean rhythm in the fHR among PGDM pregnancies at 36 weeks, indicating an increased interindividual variation. The group with higher HbA1c levels (6.0%) had no significant population-mean fHR rhythm at 28 or 36 weeks, and no significant fHR-variation rhythm at 36 weeks. Similarly, the group with a lower morning cortisol concentration (≤8.8 µg/dl) had no significant population-mean fHR-variation rhythm at 28 and 36 weeks. These findings indicate that individual fetal rhythmicity is present in pregnancies complicated by PGDM. However, suboptimal maternal glycemic control and a lower maternal morning cortisol concentration are associated with a less-well-synchronized circadian system of the fetus.

Background Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control. Methods In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA 1c assessed. Results The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p1C . Conclusions In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

INTRODUCTION Fetal biometry is used for determining gestational age and estimated date of delivery (EDD). However, the accuracy of the EDD depends on the assumed length of pregnancy included in the calculation. This study aimed at assessing the actual pregnancy length and accuracy of EDD prediction based on fetal head circumference measured at the second trimester. MATERIAL AND METHODS This was a population-based observational study with the following inclusion criteria: singleton pregnancy, head circumference dating in the second trimester, spontaneous onset or induction of delivery ≥ 294 days of gestation, live birth. The EDD was set anticipating a pregnancy length of 282 days. Bias in the prediction of EDD was defined as the difference between the actual date of birth and the EDD. RESULTS Head circumference measurements were available for 21 451 pregnancies. Ultrasound-dated pregnancies had a median pregnancy length of 283.03 days, corresponding to a method bias of 1.03 days (95% CI; 0.89-1.16). This bias was dependent on the head circumference at dating, ranging from -1.58 days (95% CI; -3.54 to 1.12) to 3.42 days (95% CI; 1.98-4.31). The median pregnancy length, based on the last menstrual period of women with a regular menstrual cycle (n = 12 985), was 283.15 days (95% CI; 282.91-283.31). A total of 5685 (22.9%, 95% CI; 22.4% to 23.4%) and 886 women (3.6%, 95% CI; 3.3%-3.8%) were still pregnant 7 and 14 days after the EDD, respectively. CONCLUSIONS Second trimester head circumference measurements can be safely used to predict EDD. A revision of the pregnancy length to 283 days will reduce the bias of EDD prediction to a level comparable with other methods.

To assess whether anomalous cord insertion is associated with risk of complications in the third stage of labor.A population-based study.Norwegian Medical Birth Register.All singleton births (gestational age16 weeks and45 weeks) during the period 1999-2011 (n = 738,443 singletons). Deliveries by cesarean were excluded, leaving 628,680 vaginal singleton deliveries for the analyses.Calculation of odds ratios for complications in the third stage of labor (postpartum hemorrhage, manual delivery of the placenta, curettage) in velamentous and marginal cord insertion by logistic regression with adjustment for confounders.Complications in the third stage of labor, postpartum hemorrhage, manual placental removal and curettage.Anomalous cord insertion was associated with an increased risk of complications in the third stage of labor, the risk being higher for velamentous than for marginal insertion. The risks persisted after adjusting for possible confounding factors. Velamentous cord insertion carried a 5.6% risk of a need for manual removal of the placenta, compared with the risk of 1.1% for nonvelamentous insertion (odds ratio = 5.21, 95% confidence interval 4.71-5.76) in vaginal delivery, and we found increased risks of curettage (odds ratio = 3.29, 95% confidence interval 2.87-3.77) and postpartum hemorrhage (odds ratio = 2.06, 95% confidence interval 1.77-2.39).Marginal and especially velamentous cord insertion is associated with an increased risk of hemorrhage in the third stage of labor, need for manual removal of the placenta and curettage. Anomalous cord insertion can be identified prenatally and so possibly influence obstetric management.

Objectives To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length. Design Population based registry study. Setting Medical Birth Registry of Norway 1999–2013. Population All singleton births (gestational age>22weeks

Congenital heart block (CHB) may develop in the fetus of Ro/SSA autoantibody-positive women. A population-based recurrence rate of only 12% however suggests that factors other than maternal autoantibodies influence the risk of developing CHB.1 In the present study, we aimed to identify genetic contribution to the disease by analysing HLA associations in European families with a Ro/SSA antibody-positive mother and at least one child affected by CHB. HLA allele genotypes were imputed for 173 families comprising 635 individuals (291 parents, 173 cases and 167 unaffected siblings) from Sweden, Norway, Finland and Italy (online supplementary table 1) based on 5636 tag SNPs. Parental HLA allele transmission frequencies to patients with CHB were assessed and OR and significance of the association with CHB calculated. We considered nominal P values

Introduction A validation of data regarding the placenta, cord and membranes in Medical Birth Registry of Norway (MBRN) is lacking. Here we investigate the inter- and intra-observer agreement of observations regarding the placenta, cord and membranes to the MBRN in two institutions. Material and methods We conducted a dual center validation study of data regarding placenta, cord and membranes. In the inter-observer study, 196 placentas in two institutions were examined by the attending midwife and a blinded colleague, whereas in the intra-observer study registrations by the attending midwife on 195 placentas were compared with her own registrations to the MBRN. In a separate sample consisting of 51 placental pathology reports, midwives’ registrations to the MBRN were compared with the pathology report. For categorical and continuous variables, agreement was assessed by kappa value and paired sample t-test, respectively. Results Inter-observer agreement between two midwives for cord insertion site and bi-placenta, cord knots and vessel anomalies were good (kappa values >0.79 and >0.96, respectively). The inter- and intra-observer study showed no significant differences regarding placental weight and cord length (p = 0.31 and 0.28, p = 0.71 and 0.39, respectively). The inter-observer agreement between the pathology reports and midwives’ registrations was good for gross placental and cord variants (kappa 0.73–1.0), but there were significant differences in placental weight and cord length (p < 0.0001). Conclusions The results suggest that the validity of data regarding placenta and cord in the MBRN is sufficiently high to justify future large-scale epidemiologic research based on this database.

After birth, the hepatic artery buffer response helps to maintain liver perfusion. Here, the authors establish a Doppler technique to measure fetal hepatic artery flow velocity and test the hypothesis that the buffer response also operates prenatally. Women with low-risk pregnancies were recruited to a longitudinal study (N = 161). Measurement techniques and reference ranges for hepatic artery velocities and pulsatility index (PI) were established. Ductus venosus peak velocity (V(DVps)) represented the portocaval pressure gradient, and umbilical venous flow (Q(UV)) represented portal flow. Reference ranges were established for the more accessible left hepatic artery branch. Hepatic artery PI was lower in fetuses with V(DVps)10th centile (P.05) and in those with Q(UV)10th centile ( P.0001). Conversely, hepatic artery PI was higher in those with Q(UV)90th centile (P.0001). The authors establish a method for measuring fetal hepatic arterial blood velocity, provide reference ranges, and show that the hepatic artery buffer response operates prenatally.

Introduction. Centiles of middle cerebral artery pulsatility index and cerebroplacental ratio are useful for predicting adverse perinatal outcomes. A ‘conditional centile’ is conditioned by a previous measurement reflecting degree of individual change over time. Here we test whether such centiles are independent predictors and whether their combination improves prediction. Material and methods. This prospective longitudinal study included 220 pregnant women diagnosed with or at risk of having a small-for-gestational-age fetus. Serial Doppler measurements of the umbilical artery and middle cerebral artery pulsatility indexs were used to calculate cerebroplacental ratio. Preterm birth, operative delivery due to fetal distress, admission to neonatal intensive care unit, 5-min Apgar score

Objective 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. Methods This was a cross-sectional observational study. Sixty-four fetuses with IUGR (estimated weight ≤ 2.5th percentile) underwent ultrasound examination. The diameter, velocity, and blood flow were determined in the DV and intra-abdominal umbilical vein (UV), and the fraction of shunting and DV : UV diameter ratios were calculated. Placental compromise was classified according to either normal umbilical artery (UA) pulsatility index (PI), UA-PI > 97.5th percentile, or absent or reversed end-diastolic flow velocity (A/REDV). Regression analysis was used to construct mean values, and SD scores were used to determine differences compared with a reference population (n = 212) after ln- or power-transformation. Results In the 64 growth-restricted fetuses, the average DV shunting was 39% compared with 25% in the reference group (overall P 97.5th percentile, and A/REDV were 31%, 35%, and 57%, respectively. Fetuses with IUGR and normal UA-PI (SD score: mean, 0.48; 95% CI, 0.04–0.92) did not shunt significantly more than did the reference fetuses (SD score: mean, 0.0; 95% CI, − 0.15 to 0.15), but those with UA-PI > 97.5th percentile (SD score: mean, 0.85; 95% CI, 0.41–1.29), and particularly those with A/REDV (SD score: mean, 1.56; 95% CI, 1.0–2.12) did shunt significantly more. With more DV shunting, these fetuses distributed correspondingly less umbilical blood to the liver, one of the mechanisms being a lower perfusion pressure as reflected in the lower DV blood velocity (P < 0.0001). Conclusions DV shunting is higher and the umbilical blood flow to the liver is less in fetuses with IUGR, particularly in those with the most severe umbilical hemodynamic compromise. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy. Methods We conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy. Results After preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4–7 fold higher than after term birth (odds ratios 3.5; 95% confidence interval (CI) 3.0–4.0 to 6.5; 95% CI 5.1–8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2–3 times higher than after term birth (odds ratios 1.6; 95% CI 1.5–1.8 to 2.6; 95% CI 2.0–3.4). After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3–3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6–1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy. Conclusions The results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia.

ObjectivesTo determine the prevalence of, and risk factors for anomalous insertions of the umbilical cord, and the risk for adverse outcomes of these pregnancies.DesignPopulation-based registry study.SettingMedical Birth Registry of Norway 1999-2009.PopulationAll births (gestational age >16 weeks to MethodsDescriptive statistics and odds ratios (ORs) for risk factors and adverse outcomes based on logistic regressions adjusted for confounders.Main outcome measuresVelamentous or marginal cord insertion. Abruption of the placenta, placenta praevia, pre-eclampsia, preterm birth, operative delivery, low Apgar score, transferral to neonatal intensive care unit (NICU), malformations, birthweight, and perinatal death.ResultsThe prevalence of abnormal cord insertion was 7.8% (1.5% velamentous, 6.3% marginal) in singleton pregnancies and 16.9% (6% velamentous, 10.9% marginal) in twins. The two conditions shared risk factors; twin gestation and pregnancies conceived with the aid of assisted reproductive technology were the most important, while bleeding in pregnancy, advanced maternal age, maternal chronic disease, female foetus and previous pregnancy with anomalous cord insertion were other risk factors. Velamentous and marginal insertion was associated with an increased risk of adverse outcomes such as placenta praevia (OR = 3.7, (95% CI = 3.1-4.6)), and placental abruption (OR = 2.6, (95% CI = 2.1-3.2)). The risk of pre-eclampsia, preterm birth and delivery by acute caesarean was doubled, as was the risk of low Apgar score, transferral to NICU, low birthweight and malformations. For velamentous insertion the risk of perinatal death at term was tripled, OR = 3.3 (95% CI = 2.5-4.3).ConclusionThe prevalence of velamentous and marginal insertions of the umbilical cord was 7.8% in singletons and 16.9% in twin gestations, with marginal insertion being more common than velamentous. The conditions were associated with common risk factors and an increased risk of adverse perinatal outcomes; these risks were greater for velamentous than for marginal insertion.

Objective To determine the venous and arterial hemodynamics underlying macrosomic fetal growth. Methods Fifty-eight healthy women who previously had given birth to a large neonate were included in a prospective longitudinal study. Of these, 29 gave birth to neonates with birth weight ≥ 90th percentile and were included in the statistical analysis. Umbilical vein blood flow and Doppler measurements of the ductus venosus, left portal vein and the hepatic, splenic, superior mesenteric, cerebral and umbilical arteries were repeated at 3–5 examinations during the second half of pregnancy and compared with the corresponding reference values. Ultrasound biometry was used to estimate fetal weight. Results Umbilical blood flow increased faster in macrosomic fetuses, showed less blunting near term and was also significantly higher when normalized for estimated fetal weight (P < 0.0001). The portocaval perfusion pressure of the liver (expressed by the ductus venosus systolic blood velocity) and the left portal vein blood velocity (expressing umbilical venous distribution to the right liver lobe) were significantly higher. Systolic velocity was higher in the splenic, superior mesenteric, cerebral and umbilical arteries, while the pulsatility index was unaltered in the cerebral, hepatic, splenic and mesenteric arteries, but lower in the umbilical artery. Conclusions There is an augmented umbilical flow in macrosomic fetuses particularly near term, also when normalized for estimated fetal weight, providing increased liver perfusion, including the right liver lobe. Signs of increased vascular cross section and flow are also seen on the arterial side but not expressed in the pulsatility index of organs with prominent auto-regulation (i.e. brain, liver, spleen and gut). Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE. Fetal liver blood supply is an important determinant of fetal growth and adaptation. Most fetal liver blood supply is from the umbilical vein, but the portal vein contributes 14-20% and studies of low-risk pregnancies suggest the splanchnic arteries are also involved in the homeostasis of fetal liver perfusion. Here we determine the circulatory pattern of the fetal liver in intrauterine growth restriction (IUGR). DESIGN. Cross-sectional study. POPULATION. Thirty-one IUGR fetuses (estimated fetal weight5th centile). METHODS. Pulsatility index (PI) measurements of the umbilical, middle cerebral, splenic, hepatic, and superior mesenteric arteries were compared with a reference population and related to umbilical venous flow, umbilico-caval pressure gradient (assessed by ductus venosus peak velocity) and venous distribution within the liver (assessed by flow velocity in the left portal vein). RESULTS. Thirteen of 31 IUGR fetuses had umbilical artery PI97.5 centile and 13 showed a middle cerebral artery brain-sparing pattern (PI Z-score- 2). In IUGR, umbilical venous flow was lower and less umbilical blood was distributed to the right liver lobe, while the umbilico-caval pressure gradient was kept normal. The hepatic and splenic arteries, but not the superior mesenteric artery, had low PI compared with the reference population. CONCLUSIONS. IUGR fetuses with increased or normal umbilical artery PI maintained venous perfusion pressure to the liver while distributing less umbilical blood to the right liver lobe. They showed regional splanchnic arterial redistribution with low splenic and hepatic artery PI, implying increased portal venous flow and direct arterial contribution to hepatic perfusion, respectively.

Objectives 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. Methods A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18–41 weeks constituted the reference population. A second group of 64 pregnancies with an estimated fetal weight ⩽ 2.5th percentile constituted the study group. Ultrasound measurements of inner diameters and velocities at the fetal left and right ventricular outlets and intra-abdominal umbilical vein were used to determine combined left and right cardiac output (CCO) and the fraction distributed to the placenta. Placental compromise was graded according to umbilical artery waveform: pulsatility index normal, > 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used to establish normal ranges and to compare groups. Results During gestational weeks 18–41 the normal CCO/kg was on average 400 mL/min/kg and the fraction directed to the placenta was on average 32%, while after 32 weeks it was 21%. In intrauterine growth restriction the CCO/kg was not significantly different, but the fraction to the placenta was lower (P < 0.001). This effect was more pronounced in severe placental compromise (P < 0.001). Conclusions Normally, one third of the fetal CCO is distributed to the placenta in most of the second half of pregnancy, and one fifth near term. In placental compromise this fraction is reduced while CCO/kg is maintained at normal levels, signifying an increased recirculation of umbilical blood in the fetal body. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Human parvovirus B19 infection is a common and usually benign disease in children, but may cause severe complications in pregnancy. We determined the proportion of the pregnant population at risk of infection and present a recent cluster of cases with fetal complications, hoping to raise the general awareness.Five cases of fetal parvovirus B19 infection during 2001--2 illustrate the delay in diagnosis, treatment and outcome. During the same period, the number of positive and negative serological tests was noted for the catchment area and the entire country. Additionally, 206 consecutive pregnant women were tested to determine susceptibility.Out of the five cases of fetal complications, all had cardiac involvement, three had anaemia, and two fetuses died. Lag-time to fetal diagnosis was six, eight, and 13 weeks for those with known maternal disease. In Norway, seroconversion is similar to that found in other Nordic countries; 36 % (74/206) of the pregnant population is seronegative. In Norway, parvovirus B19 infection is more frequently reported in the January-June period. A third of the pregnant population is susceptible to infection. Early testing in cases of exposure or suspected infection in pregnancy is recommended in order to ensure appropriate follow-up and treatment.