Foetal sex determination at the second trimester anomaly scan in Denmark

Foetal sex determination by ultrasound has been studied for years and results on how and when to assess the foetal gender are well-described [1-5]. Direct visualisation with sagittal, transverse and tangential projections in the second and third trimester and the sagittal sign in late first and early second trimester can determine both male and female genitals [1-6].

Determining the foetal gender is medically indicated in cases of sex-linked diseases, syndromes, malformations or multiple pregnancy [7, 8]. In the second-trimester anomaly scan, however, foetal sex determination is not mandatory, and guidelines are sparse and inadequate with no technical requirements for standard views or documentation of gender findings [9-13]. It seems that there is more focus on why not to disclose the foetal sex in an ethical perspective than on how to determine the foetal sex professionally. Thus, detection of ambiguous or malformed external genitals may be incomplete. Pajkrt et al reported a diagnostic approach to foetal genital anomalies, but the assessment did not address the prevalence of genital malformations and the accuracy of sex determination [14]. A Swedish study of 16,775 foetuses examined in weeks 18 and 32 showed a prevalence of minor structural genital malformations at 3.8/1,000 and major malformations at 0.7/1,000 [15].

Foetal sex is often predominantly reported on parental request. Several studies show that approximately 57-75% of expecting parents request foetal sex determination at the second-trimester scan [2, 6, 16]. But on basis of the large Swedish SWEPP study, Larsson et al showed that as much as 95.8% of pregnant women have discussed foetal sex determination with their partner prior to the ultrasound examination [16]. Other studies have shown that incorrectly determined or undesired foetal sex may influence the mother in terms of obstetrical complications, psychological and marital problems [17]. The schism between the professional diagnosis of genital malformations and the parental expectations of foetal sex disclosure raises a need to differentiate the abilities and registration of the ultrasound examinations.

At 92% uptake, Danish healthcare offers a first-trimester screening for chromosomal abnormalities and major defects and a second-trimester anomaly scan in all pregnancies. All ultrasound examinations are registered in the Astraia database (Astraia software gmbh, Munich, Germany), and foetal sex at birth is reported to the Danish National Birth register. However, national data on foetal sex determination are not included, and accuracy is not assessed. Thus, the aim of this study was not to describe detection of genital malformations, but to provide an initial overview on the practice of foetal sex determination by the second-trimester anomaly scan in Denmark and the accuracy of the foetal sex determinations undertaken at two Danish foetal medicine departments.

METHODS

Practice of foetal sex determination

Data on the practice of foetal sex determination were collected through structured phone interviews of one random sonographer from each of the 23 Danish foetal medicine departments in the course of March 2012. The questions concerned the experiences of foetal sex determination offered in each unit: time of examination in pregnancy, staff performing the examination, the information given on the subject (oral, written, website), registration, image documentation, quality criteria and accuracy assessment. Responses with a quantitative content were registered in Excel and calculated as absolute numbers.

Accuracy of foetal sex determination

Quality assessment of foetal sex determination was studied through retrospective quantitative comparison of foetal sex determined and registered in the Astraia database at the second-trimester anomaly scan with reported foetal sex from the birth register at two foetal medicine departments in Denmark: one regional hospital (n = 1,164) and one university hospital (n = 4,622). The sample included foetal sex from all singleton pregnancies (n = 5,786) with live births in 2011 and data on foetal sex determination from the anomaly scan undertaken at gestational week 18 + 0 – 21 + 6. Live births with a possible chorionic villus sampling (CVS) or amniocentesis (AC) undertaken during pregnancy were included in the study, as information on genetic testing was not available in the dataset. Non-invasive prenatal testing (NIPT) was not introduced on a larger scale in Denmark until 2015; and it was most often performed without foetal sex determination due to inaccuracy of the test in this regard. In addition, data on foetal malformations were not available in the dataset. Sonographers and foetal medicine doctors at both hospitals conducted the ultrasound examinations. Both departments used Voluson E8 Expert and Voluson 730 Expert ultrasound devices (GE Healthcare, Chicago, USA) with predominantly 2D and 3D/4D abdominal transducers. Data were registered in Excel and transferred and analysed in SPSS statistics version 21.0 (IBM Copenhagen, Denmark). Fisher’s exact test was used and p < 0.05 were considered statistically significant.

Trial registration: This study was approved by the Danish Data Protection Agency (record number: 2012-41-0050).

RESULTS

Practice of foetal sex determination

The phone interviews (Table 1) showed that all 23 departments conducted foetal sex determination at the second trimester anomaly scan. The scans were considered not mandatory, as there was no national guideline on foetal sex determination. All sonographers indicated that they only disclosed the foetal sex on parental request. Danish departments provided information about foetal sex determination to the pregnant couples predominantly orally (Table 1). Oral information was not standardised as to include the possibilities and limitations of the gender examination. The majority of the pregnant couples requested disclosure of the foetal sex. All sonographers expressed that their greatest focus was on conducting the anomaly scan according to second trimester national guidelines.

Overall, 70% of the departments registered the foetal sex from ultrasound in the second trimester in the Astraia database (Table 1). Ultrasound images as documentation of the foetal gender finding were obtained in 39% of departments. Quality requirements concerning standard views to determine foetal sex were present in 9% of the departments. For the remaining departments, technical details on ultrasound projections for correct foetal sex assessment were not
written but trained by new staff during their apprenticeship. No departments conducted any postnatal quality assessment of the foetal sex determination.

Accuracy of foetal sex determination

Table 2 shows how foetal sex at each scan was categorised in the Astraia database. Foetuses with sex determination were categorised as either; “normal female”, “normal male” or “genital normal – sex not requested”. Foetuses with no sex determinations were categorised as either; “not examined”, “sex not possible to determine” or “empty box/not filled”. In total, foetal sex was determined in 86.7% of all second-trimester anomaly scans. The difference in obtained foetal sex determination between hospitals was highly significant, p = 0.0002 (Table 2). The reasons why foetuses did not have their sex determined in terms of inconclusive/ambiguous or malformed genitals were not possible to extract from the present data.

As shown in Table 3, the overall accuracy of foetal sex determination was 99.2%, and there was no significant difference between the rate recorded at the two hospitals. Furthermore, as demonstrated in Table 4, the accuracy of sex determination did not differ between females and males.

A total of six sonographers and four foetal medicine doctors at the regional hospital and 20 sonographers and 14 foetal medicine doctors at the university hospital conducted the second-trimester anomaly scans described in this study. The level of experience of the members of staff was not registered.

DISCUSSION

This study has the strength of providing a national overview of the manner in which foetal sex determination was practiced in all Danish foetal medicine departments at the second-trimester anomaly scan. International knowledge on the practice of foetal sex determination is limited because previous studies have focused mainly on foetal sex determination on medical indication or on selected populations.

Foetal sex determination was performed in all Danish foetal medicine departments at the second-trimester anomaly scan. This finding is in line with a previous publication by Jylhä et al [18] showing that, in Finland, the majority of antenatal screening units (84%) undertook foetal sex determination at the second-trimester scan. However, as in Denmark, foetal sex determination was not mandatory, and guidelines were absent.

Evaluation in Denmark and Finland of the foetal genitalia was not systematic and this might imply a lack of professional security in determining the foetal sex and excluding genital malformations. The level of quality assessment in the present study and existing studies underpins the need for international guidelines on
foetal sex determination. The sonographers and doctors can improve their professional abilities only through an initial focus on the basic requirements of sagittal, transverse and tangential views.

In Denmark and in Finland, foetal sex was disclosed only on parental request, and sonographers underlined that foetal sex determination seemed important to the majority of the pregnant couples [2, 6, 16, 18]. The parental curiosity about the sex of their future child is universal, but it seems that most existing guidelines focus on ethical restrictions in the disclosure of the foetal sex, some even with disclaimers, instead of including recommendations on how to perform the ultrasound examination. Ethical issues and gender-specific preferences may play a role in parental choices according to ethnicity, parity and age. However, correct sex determination should be the first step towards a more detailed and strengthened examination of foetal genitals.

To our knowledge, the most recent study of second-trimester sex determination from 2009 included 2,780 unselected patients [6]. The strength of this study is the large number of included patients from an unselected population; and the results of 5,786 anomaly scans with 86.7% of cases accessed is comparable to previous studies including rates of foetal sex determination at an equivalent gestational week of 89.4-98.2% [2, 6]. Previous studies have shown that improper foetal position or high maternal BMI influence the possibility of obtaining sufficient images and thereby the accuracy of foetal sex determination [15, 16, 19]. However, such data were not available in this study. The significant difference between the regional and the university hospital in obtaining foetal sex determination may reflect differences in coding practice, as registration of sex determination was retrospective and covered a period without national recommendations or guidelines.

The 99.2% accuracy of foetal sex determination is comparable with previously published second-trimester scans, being in the range of 96.7-99.4% [2, 6]. The accuracy, however, still leaves 8/1,000 foetuses with an incorrectly assigned gender. Carefully extrapolating this finding to a Danish birth cohort from 2017 (n = 61,397), approximately 425 foetuses would have an incorrect sex assigned. These couples are accordingly at risk of unnecessary psychological stress and confusion [17]. If foetal sex determination is performed, it should be standardised and at a high level to avoid false diagnoses.

A limitation is that foetuses with genetic examination and thereby foetal sex determined were not excluded from this study. Accordingly, we may have overestimated the accuracy of sex determination in the study population. However, in the Danish population, the number of foetuses with genetic testing is below 5%, and it therefore seems likely that our conclusions are reliable.

Ambiguous or malformed genitals are of great importance in prenatal examination as shown by Pajkrt et al [14] and taking into consideration also the Swedish study presenting a prevalence of minor structural genital malformations at 3.8/1,000 and major malformations at 0.7/1,000 [15]. Unfortunately, data on genital malformations were not available in this dataset, and an evaluation of the detection of genital malformations therefore cannot be performed, which is a limitation of this study. In future research, it is highly recommended to focus on the detection of genital malformations as well as on the group of foetuses who did not have their sex determined. As shown by Stocker and Evens [1], determining the female sex was significantly more difficult than determining the male sex (p < 0.001). Subsequent studies have shown either no significant difference in female versus male sex determination or even superior results in females, but study populations vary according to gestational age at the scan and sample sizes ranging from 353 to 2,780 scans [2, 6]. Thus, the present Danish study contributes with new data on the practice of foetal sex determination by the second-trimester anomaly scan in Denmark and according to our data, the accuracy did not differ between males and females.

CONCLUSIONS

This study demonstrated that the practice of foetal sex determination in Denmark was characterised by varying approaches and no quality assessment at the second-trimester anomaly scan. Incorrect sex was determined in eight out of 1,000 foetuses. Consequently, better detection rates are needed. Examination of the foetal genitals should be considered mandatory at the second-trimester anomaly scan in line with the examination of other foetal organs. Although detection of malformed or ambiguous genitals was not an aim of this study, the topic is highly relevant, and guidelines are requested. Following this work, a national guideline on foetal sex determination was developed by the Danish Foetal Medicine Society [20] and accordingly listed by the Nordic Federation of Obstetrics and Gynaecology. Foetal sex determination including sagittal, transverse and tangential projections, is now recommended as an integral part of the Danish second-trimester anomaly scan.

*CORRECTION PER 1 APRIL 2020
The original article found a statistical difference in foetal sex determination between female and male foetuses. Unfortunately, after the paper was published a miscalculation was identified – and the correct calculation shows no difference in foetal sex determination between female and male foetuses. Accordingly, corrections have been made in Table 4 and in the manuscript.

CORRESPONDENCE: Gitte Størup. E-mail: birgitte.stoerup@rn.dk

ACCEPTED: 14 October 2019

CONFLICTS OF INTEREST: none. Disclosure forms provided by the authors are available with the full text of this article at Ugeskriftet.dk/dmj