Pregnant women with skeletal dysplasia are at an increased risk of maternal and perinatal morbidity and mortality [1, 2, 20]. Recently, a multidisciplinary, international, consensus-based best practice guideline was provided as a minimum standard of care to minimize associated health risks, and to improve outcomes for pregnant women with skeletal dysplasia [21]. The guidelines concluded, that the increased risks of pregnancy in these situations are related to multiple factors such as cardiopulmonary and musculoskeletal factors in pregnant women. However, all skeletal dysplasias have their own specific features which may affect fertility and obstetric prognosis. Consequently, detailed data on pregnancies in different skeletal dysplasias is warranted.
Our study evaluated pregnancy outcomes in women with CHH from a unique Finnish cohort including 56 women with genetically confirmed CHH. We were able to review a total of 42 pregnancies in 14 women, 26 of which led to delivery. Typical manifestations of CHH, including severe short stature and immunodeficiency, may have negative impact on fertility and reproduction. However, gynecologic and obstetric problems in patients with CHH have received only scant attention. We have previously published reports on diversity of pubertal development and gynecologic health in CHH [11-13]. To the best of our knowledge, no comprehensive obstetric reports have ever been published, and the very limited data on pregnancies in CHH are based on single case reports [14-15]. This is thus the first study to evaluate reproductive and obstetric outcomes in a larger cohort of women with CHH.
The miscarriage rate in our cohort was 21%, which is not increased compared with rates in the general population (15-25%) [22]. All but one miscarriage occurred during the first trimester. Moreover, 86% (6/7) of women with one or two miscarriages, also had a successful pregnancy and delivery reflecting positive obstetric prognosis. Thus, CHH does not seem to predispose affected women to recurrent miscarriage.
The total number of induced abortions, (12%, 5/42) did not differ from the data for the general population, as reported in the Finnish national pregnancy termination registry [23]. According to the national data, 93% of pregnancy terminations in Finland are performed because of social indications (unplanned pregnancies), compared to only 3.4% for fetal abnormality [23]. In our CHH population, a social indication was reported in 60% (3/5) of the terminations while 40% (2/5) were due to fetal indications. The number of unplanned, terminated pregnancies was thus not increased among the women with CHH. However, the small number of induced abortions does no allow any solid conclusions.
Most of the pregnancies leading to a delivery were full-term. Preterm birth is defined as delivery under 37 completed weeks of gestation. In 2013, in the United States, 11.4% of all babies were born preterm [24]. In Finland in 2018, 5.8% of babies were born under 37 gestational weeks [25]. In our cohort, 96% of babies were born fullterm, and there was only one early preterm birth (pw 25; 1/27 baby born, 3.7%). We did not observe any increase in the rate of complications, such as pregnancy-related hypertensive disorders or gestational diabetes, as compared with the general Finnish and Nordic population [26, 27]. Maternal BMI was increased before pregnancy and an average weight gain during pregnancy was 8.4 kg (18.5 lb). However, according to best-practice guidelines, BMI does not take into consideration body proportions in skeletal dysplasia, and there are no evidence-based recommendations concerning gestational weight gain. A reasonable approximation in short stature women with bone dysplasia is to recommend weight gain in the lowest range, a total of 5-9 kg (11-19.8 lb) over the course of pregnancy [21].
Since the growth of offspring is not generally affected in a recessively inherited disease, normal size of the fetus’ head in a smaller maternal pelvis can cause CPD and result in dystocia. Moreover, breech presentation and malpresentations might be more common in women with short stature. In our study all subjects had a CS, and seven women had recurrent CSs. Recurrent CSs increase the risk for placental abruption, placentation disturbances and post-partum hemorrhage [27]. In our series such complications in women with recurrent CS were not reported. However, a vacuum extraction was required due to CPD and malpresentation twice even in planned CS, highlighting the importance of preparation for intrapartum complications.
The main limitation of this study is the retrospective study design. Number and type of pregnancies and diagnoses during pregnancies were confirmed from national registry. However, information about various subjective symptoms during pregnancy were mainly based on patient interviews and questionnaires. The reliance of self-reported data is subjected to recall bias. This study is by far the largest series reporting outcome of pregnancies in women with CHH. However, as only 14 women altogether were included, the small sample size needs to be acknowledged as a limitation, unavoidable in rare diseases. Phenotypic differences in CHH are wide. Severely affected patients may not try to conceive, they may not conceive spontaneously, or they may not want to participate in the study, and among them obstetric prognosis might be poorer than in this study population. Although we did not systematically collect data on the use of assisted reproductive treatments from the patients, we are aware that these treatments have been used in some instances.
Fertility and reproduction are very important factors in young women’s life. Decision about subjective willingness and capability of carrying a pregnancy should be based on patient´s right to get all potential information preconceptionally. According to best-practice guidelines, preconceptional medical evaluation is recommended to all women with skeletal dysplasia, to consider factors that may impact safety of pregnancy, mode of delivery, and anesthetic management [21]. Due to rarity of skeletal dysplasias, pregnancies need to be assessed and managed in facilities that are aware of the potential complications, and have the skills and resources to anticipate and manage them effectively [21]. Anesthetic assessment should be carried out early in the third trimester because of challenges in anesthetic management and the risk of an emergency CS.