Maternal physical activity affects yolk sac size and growth in early pregnancy, but girls and boys use different strategies.

This longitudinal study investigated the impact of actigraphy-measured maternal physical activity on yolk sac size during early development. The yolk sac, a transient extraembryonic organ, plays a crucial role in embryonic development and is involved in metabolism, nutrition, growth, and hematopoiesis. Prospectively collected data from 190 healthy women indicated that their total daily physical activity, including both light and moderate-vigorous activity, was associated with yolk sac growth dynamics depending on embryonic sex and gestational age. Higher preconception maternal physical activity was linked to a larger yolk sac at 7 weeks (95% CI [0.02-0.13 mm]) and a smaller yolk sac at 10 weeks' gestation (95% CI [- 0.18 to - 0.00]) in male embryos; in female embryos, the yolk sac size was increased at 10 weeks' gestation (95% CI [0.06-0.26]) and was, on average, 24% larger than that in male embryos (95% CI [0.12-0.38]). Considering the pattern of other maternal effects on yolk sac size-e.g., body composition and sleep duration-we suggest that physiological yolk sac adaptations occur in short, sex-specific time windows and can be influenced by various maternal factors.

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction.

BACKGROUND: Fetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. AIM: Echocardiographic assessment of heart function in FGR neonates first three days after birth. STUDY DESIGN: Prospective observational study. SUBJECTS: FGR- and non-FGR neonates. OUTCOME MEASURES: M-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e' of the atrioventricular plane day one, two and three after birth. RESULTS: Compared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e' (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e' (15 (7) %, p = 0.049), right a' (18 (6) %, p = 0.001), left E/e' (25 (10) %, p = 0.015) and right E/e' (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. CONCLUSIONS: FGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.

Cardiac morphology in neonates with fetal growth restriction.

OBJECTIVE: Assess effects of fetal growth restriction (FGR) on cardiac modelling in premature and term neonates. STUDY DESIGN: Prospective echocardiographic study of a cohort of FGR neonates (n = 21) and controls (n = 41) with normal prenatal growth and circulation. RESULTS: Unadjusted for gestational age, birth weight, sex, and twin/singleton, Late-FGR neonates had smaller hearts than controls, with globular left ventricles and symmetrical right ventricles. Adjusted estimates showed smaller left ventricles and similarly sized right ventricles, with symmetrical left and right ventricles. Early-FGR (compared with Late-FGR) had smaller hearts and globular left ventricles in unadjusted estimates, but after adjustment, sizes and shapes were similar. CONCLUSION: FGR had significant impact on cardiac modelling, seen in both statistical models unadjusted and adjusted for gestational age, birth weight, sex, and twin/singleton. The adjustments, however, refined the results and revealed more specific effects of FGR, thus underscoring the importance of statistical adjustments in such studies.

Effect of maternal sleep on embryonic development.

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h-1d-1, 95%CI [0.35-0.09], P < 0.01), and CRL increased (0.92 mm·h-1d-1, 95%CI [1.77-0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight.

OBJECTIVES: To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. METHODS: In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). RESULTS: The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). CONCLUSIONS: The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.

Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy.

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies. Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h *TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling. Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19-52 mm), mean TAMxV (8.83-16.14 cm/s), and QSVC (15.4-192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156-1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.

Sleep and physical activity from before conception to the end of pregnancy in healthy women: a longitudinal actigraphy study.

BACKGROUND: Sleep and physical activity changes are common in pregnancy, but longitudinal data starting before conception are scarce. Our aim was to determine the changes of the daily total sleep time (TST) and physical activity duration (PAD) from before conception to end of pregnancies in respect of pregestational maternal factors. METHODS: This longitudinal observational study formed part of the CONIMPREG research project and recruited healthy women planning to become pregnant. Sleep and physical activity were recorded around-the-clock for ≥4 days via actigraphy before conception and during each trimester of pregnancy. Data were adjusted according to pregestational maternal body composition, parity and age. RESULTS: Among 123 women with eligible data, the unadjusted mean (95% confidence interval) TST increased from 415.3 min (405.5-425.2 min) before conception to 458.0 min (445.4-470.6 min) in the 1st trimester, remaining high through the 2nd and 3rd trimesters. Variation was substantial before conception (±2SD range: 307-523 min). The unadjusted mean PAD before conception was 363.7 min (±2SD range: 120-608 min), decreasing sharply to 262.1 min in the first trimester and more gradually thereafter. Vigorous and moderate activity decreased more than light activity. TST and PAD were significantly associated with age, parity, and pregestational body fat percentage; lean body mass was negatively correlated with TST. Results were generally unaffected by seasonal variations. CONCLUSION: Marked variations were found in pregestational TST and PAD. Healthy women slept ≥30 min longer during pregnancy, while PAD decreased by ≥ 90 min in early pregnancy and continued to decrease thereafter.

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study.

BACKGROUND: Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. METHODS: This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20-41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. RESULTS: SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. CONCLUSIONS: Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term.

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Gynaecological fistulae after surgery or radiotherapy. / Gynekologiske fistler etter kirurgi eller strålebehandling.

BACKGROUND: Gynaecological fistulae cause urinary and/or faecal incontinence. Haukeland University Hospital has systematically recorded treatments for gynaecological fistulae, since 2012 in its capacity as the Norwegian National Unit for Gynaecological Fistulae. This study describes characteristics of and therapeutic outcomes for gynaecological fistulae caused by surgery and/or radiotherapy. MATERIAL AND METHOD: We have conducted a retrospective cohort study of women who were treated at the Department of Gynaecology and Obstetrics, Haukeland University Hospital, in the period 1995-2019 for gynaecological fistulae due to surgery or radiotherapy. RESULTS: Surgery or radiotherapy was the cause of gynaecological fistulae in 182 of a total of 411 women. 163 of them consented to the study, 124/163 (76 %) with fistulae following surgery and 39/163 (24 %) with fistulae following radiotherapy. The post-surgical fistulae were mainly urogenital (91/124: 73 %) and most often caused by a hysterectomy (n = 71) or urinary incontinence procedure (n = 11). Post-radiotherapy fistulae were mainly enterogenital (34/39: 87 %), with rectal cancer (n = 22) and cervical cancer (n = 11) as the most frequent types of cancer. The main procedure was vaginal fistuloplasty, which was carried out on 100/124 (81 %) of women with post-surgical fistula and 7/39 (18 %) of those with post-radiotherapy fistula. Catheter drainage or stomy alone resulted in healing in 14/163 (9 %) of all patients. A total of 117/124 (94 %) of women with post-surgical fistula achieved healing, compared with 10/39 (26 %) with post-radiotherapy fistula. 28/39 (72 %) of the latter had a permanent urostomy or enterostomy. INTERPETATION: Gynaecological fistulae caused by surgery have a good healing rate, while post-radiotherapy fistulae are more often permanent.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

INTRODUCTION: Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. MATERIAL AND METHODS: In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41 weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. RESULTS: Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R = 0.10; P = .051), or UCR and Q-UCR (R = 0.09; P = .11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. CONCLUSIONS: Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Altered development of fetal liver perfusion in pregnancies with pregestational diabetes.

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 HbA1c assessed. RESULTS: The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C. 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.

Incidence of gynecological fistula and its surgical treatment: A national registry-based study.

INTRODUCTION: Gynecological fistula (affecting female genital organs) leads to involuntary loss of urine or feces. In industrialized societies, fistulas occur mostly as complications of surgery, radiation therapy or inflammatory bowel disease. We sought to determine the incidence of gynecological fistula and type of surgical treatment provided in Norway. MATERIAL AND METHODS: This was a retrospective national cohort study of women treated for gynecological fistula (International Classification of Disease-10 code N82) during 2008-2014, identified from the mandatory Norwegian Patient Registry. To compare groups, we utilized Chi-square or non-parametric tests. RESULTS: In all, 1627 women (.06% of the female Norwegian population) had 4475 hospital admissions with a diagnosis of gynecological fistula. In total, 1214/1627 (75%) had fistula as the main diagnosis: 346 (29%) a urogenital fistula, 672 (55%) an enterogenital, 38 (3%) a genitocutaneous and 22 (2%) both urinary and enteral fistula. Surgery for gynecological fistula was performed in 723 women, an incidence rate of 4.2 per 100 000 person-years (95% confidence interval [CI] 4.2-4.3); gynecological procedures (mostly vaginal/perineal) were performed in 163 women (23%), urological in 43 (6%), enteral in 267 (37%) and surgery involving multiple pelvic compartments in 250 (35%). Women undergoing fistula surgery had a median of three hospital contacts (95% CI 3-3), for 370 women (52%), the procedure was performed by a gynecologist, and 212 of these (29%) were also operated by urologists or gastroenterologists. CONCLUSIONS: Gynecological fistula is rare in Norway, with an overall incidence of 6/10 000 in the female population, whereas the incidence of surgically treated fistula is 4.2/100 000. However, the condition represents considerable morbidity for the individual patient.

The fetal circadian rhythm in pregnancies complicated by pregestational diabetes is altered by maternal glycemic control and the morning cortisol concentration.

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.

Estimated date of delivery based on second trimester fetal head circumference: A population-based validation of 21 451 deliveries.

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.