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BACKGROUND: Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent.OBJECTIVE: This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies.STUDY DESIGN: All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first-trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses.RESULTS: The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton pregnancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm deliveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%).CONCLUSION: Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

Additional file 3. Malformations associated with genetic disorders.

Additional file 1: Box 1. The Danish abortion legislation.

Additional file 2: Box 2. The Danish prenatal screening program.

Introduction: The aim was to investigate the parental decisions about prenatal screening and diagnosis among infants with trisomy 21 (T21) in a national cohort with high uptake of combined first-trimester screening (cFTS). Material and Methods: This was a nationwide population-based study including infants born in 2009-2012. Information from the cFTS, fetal karyotype results and pregnancy outcome was obtained from the Danish Fetal Medicine Database on all women with a cFTS risk assessment. Cut-off for referral for invasive testing was ≥1:300. Karyotype results from pregnancies with no cFTS were obtained from the Danish Cytogenetic Central Registry. Results: The uptake rate of cFTS was 91.6%, and 82.8% (8,032/9,704) of the screen-positive women opted for invasive testing. Overall, 82.2% (454/552) chose to terminate an affected pregnancy. In the 4-year period, 102 of 232,962 singletons were born alive with T21. The cFTS risk was true-positive, false-negative or not obtained in 21.6, 48.0 and 30.4%, respectively, of these pregnancies. Discussion: In this large national cohort, 4.4 per 10,000 live-born infants had T21. Of 102 infants with T21 from 2009 to 2012, 52.0% were born after the women had not opted for cFTS or were true-positive but declined invasive testing or termination, and 48.0% were born after a false-negative risk assessment.

OBJECTIVES: To estimate the prevalence of kidney anomalies at second trimester ultrasound screening, and furthermore, to investigate pregnancy outcomes and the pattern of additional malformations.METHODS: We previously identified all women attending second-trimester ultrasound scans in Denmark between 1 January 2007 and 31 December 2012. Using the Astraia databases and the Danish National Patient Registry, we identified all fetuses with kidney anomalies diagnosed prenatally in these women. In addition to the prevalence of fetuses with kidney anomalies, we estimated the live birth prevalence ratio of non-urinary malformations, comparing the prevalences in infants with and without prenatally diagnosed kidney anomalies.RESULTS: The prevalence of fetuses with kidney anomalies at second trimester scans was 11.4 per 10 000 fetuses. Among the 412 fetuses identified, 127 pregnancies were terminated. For live born children the prevalence of additional non-urinary malformations was four times higher (95% CI: 3-5) compared with the prevalence among children without prenatal kidney anomalies. Digestive system anomalies were particularly prevalent.CONCLUSION: These population-based data provide additional insight into the course of pregnancy and birth outcomes following prenatal diagnoses of kidney anomalies. © 2016 John Wiley & Sons, Ltd.

OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months in children exposed prenatally to progesterone compared to placebo and evaluate their medical histories up to 8 years of age.METHODS: This follow-up of the Danish participants in the PREDICT study included 989 surviving children from 498 pregnancies. PREDICT is a placebo-controlled randomized trial examining progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed, and neurophysiological development was evaluated by the parent-completed Ages and Stages Questionnaire (ASQ) at either 48 or 60 months after the estimated date of delivery. We used the method of generalized estimating equation to account for the correlation within twins.RESULTS: A total of 492 children had been exposed to progesterone prenatally and 497 to placebo. There were no differences between the groups in number or length of admissions, and we found no overall differences in rates of diagnoses. However, the odds ratio for a diagnosis related to the heart was 1.66 (95%CI 0.80;3.37) in favor of placebo among all children, 2.29 (1.02;5.12) in dichorionic twins, and 8.19 (1.02;65.6) in all children when outpatient diagnoses were excluded. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared to placebo (P=0.03). In dichorionic twins, the risk of having a low ASQ score (CONCLUSIONS: Second and third trimester exposure to progesterone does not seem to have long-term harmful effects on children, but future studies should focus on cardiac disease in the offspring.CLINICAL TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials. gov, www.clinicaltrials.gov, NCT00329914.

OBJECTIVE: To describe early and late fetal growth in pregnancies conceived after gastric bypass surgery in relation to time from surgery to conception of pregnancy.METHODS: National cohort study on 387 Danish women, who had laparoscopic or open gastric bypass surgery prior to a singleton pregnancy in which first trimester screening was performed between January 2008 and June 2011. Data were derived from national registers (Danish National Registry of Patients and Danish National Birth Registry, Pregnancy Complications and Abortion - clinical quality database (PreCAb) and the Danish Fetal Medicine Database). Main outcome measures were early and late fetal growth in relation to time from bariatric surgery to conception of the pregnancy. Early fetal growth was expressed as "Fetal Growth Index": the ratio between the estimated number of days from first trimester ultrasound to second trimester ultrasound biometries and the actual calender time elapsed in days. Late fetal growth was expressed as the observed versus expected birthweight according to gestational age (GA).RESULTS: The surgery-to-conception interval ranged from 3 to 1851 days with a mean value of 502 (SD, 351) days. The mean "fetal growth index" was 0.99 (SD, 0.02) days/day and thus significantly lower than in the background population (mean, 1.04 (SD, 0.09) days/day, pCONCLUSION: Fetal growth index was lower than reported in the background population. No correlation was found between the surgery-to-conception interval and early or late fetal growth in pregnancies conceived after gastric bypass surgery.

Objective To assess the relationship between the finding of fetal femur diaphysis length (FL) below the 5th percentile at the second-trimester scan and pregnancy outcome, in a population in which more than 90% of women attend first-trimester screening. Methods This was a retrospective study of all Danish singleton pregnancies with a 17–22-week anomaly scan between 1 January 2008 and 30 June 2011. Information on FL and gestational age (GA) at anomaly scan, on birth weight and GA at delivery and on chromosomal abnormalities was obtained from the Danish Fetal Medicine Database. Results Short FL was identified in 2718 (1.8%) of 147 766 fetuses and was present in 11 (16.2%) of the 68 fetuses affected by trisomy 21 (positive likelihood ratio (LR+) 8.8 (95% CI, 5.1–15.2)). Trisomy 13/18 and unbalanced autosomal structural abnormalities were also associated with a short FL in three (12.0%, LR+ 6.5 (95% CI, 2.3–18.9)) and eight (32.0%, LR+ 17.4 (95% CI, 9.8–30.9)) of the cases, respectively. The risk of a fetus having trisomy 21, trisomy 18, trisomy 13 or an unbalanced autosomal structural abnormality was 1 : 123 (95% CI, 79–192), given a short FL. Pregnancies with a fetus with short FL were more often affected by early preterm delivery (before 34 weeks) (5.6%; odds ratio (OR) = 4.2 (95% CI, 3.5–4.9)) and small-for-gestational-age (SGA) infants (13.9%; OR = 4.3 (95% CI, 3.8–4.8)). Conclusion Short FL at the second-trimester anomaly scan is associated with a significantly higher relative risk of chromosomal abnormalities, and a substantially higher absolute risk for SGA and early preterm delivery. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd

To assess the detection rate of triploidy at first-trimester screening for trisomy 21 and evaluate outcome in triploid pregnancies.