Grand multiparity, which is defined by women who has had five or more of births at more than 20 weeks of gestation, is associated with increased risk for both the pregnant mother and her newborn [1]. The perinatal complications associated with grand multiparity include stillbirth [1], preterm labor [2], gestational diabetes mellitus (GDM) [2, 3], gestational hypertension, fetal malpresentation, postpartum hemorrhage [4], as well as lower Apgar scores in neonates, a higher risk for low-birth weight, fetal macrosomia, and neonatal intensive care unit (NICU) admission [4]. However, our previous study showed that such complications, such as bleeding, GDM, or hypertension, in grand multiparous Jordanian women were primarily associated with advanced maternal age rather than grand multiparity itself [5].

To reduce the incidence and severity of adverse pregnancy outcomes in grand multiparity, developed countries have started improving the standards of perinatal care [6]. Mainly, universal screening of pregnant women for thyroid dysfunction should be implemented to avoid missing detection of clinical or subclinical hypothyroidism in pregnant women [7], which can be associated with adverse pregnancy outcomes such as preterm delivery, low birth weight, placental abruption [8], and hypertensive disorders during pregnancy [9]. Additionally, adding thyroid testing to prenatal screening should be cost-effective compared to selective screening [10].

Additionally, universal screening for GDM should be recommended at the initial antenatal care visit for early diagnosis of glucose intolerance in pregnancy, especially in grand multiparous women, as there is increased association of GDM with parity [11], and advanced maternal age women, as GDM is strongly associated with age $\ge$35 years [12]. GDM diagnosed at 24–28 weeks of gestation may already have affected fetal abdominal obesity [13]. However, most modern recommendations declared the best time for performing screening by oral glucose tolerance test (OGTT) using a 1-step strategy as 24–28 weeks of gestation [14].

Since 2015, the Jordan University hospital (JUH) has implemented a new standard of perinatal care, including universal screening for thyroid stimulating hormone (TSH), OGTT, and morphology and growth scans in accordance with recent international guidelines [15, 16]. While there is a wealth of research on improving perinatal outcomes using a variety of protocols, we did not find studies that focused on grand multiparous pregnant women with advanced maternal age. Furthermore, since complications such as thyroid diseases, hypertension, and GDM were primarily associated with advanced maternal age, the present study was conducted to compare the impact of implementing a universal screening perinatal protocol versus the selective screening for grand multiparous pregnant women aged $\ge$35 years on the incidence of pregnancy complications and the associated risk factors. Such a study should enhance the knowledge regarding the importance of universal screening especially in grand multiparty communities.

Recent research identified grand multiparity as a risk factor for adverse perinatal outcomes [2, 3, 4]. This, however, is a debatable issue, as a decline in the prevalence and severity of adverse outcomes in grand multiparity has been reported due to improvement in perinatal care protocols [17]. Moreover, complications were found to be independently associated with increased maternal age which frequently goes hand in hand with increasing parity [4, 5]. This study was directed towards comparison between perinatal outcomes before and after implementing new perinatal care standards, including universal screening for thyroid disease and gestational diabetes, as well as performing morphology and growth scans in a modern academic tertiary referral center. The study revealed that pregnancy complications such as gestational diabetes, gestational hypertension, and polyhydramnios were detected in pregnant women more often after the introduction of universal screening. A recent opinion papper advocates patient-specific approach and risk assessment may possibly minimize cesarean delivery rates in lower-risk cases or avoid labor when hazards exceed predefined thresholds, thus stabilizing or improving maternal-fetal outcomes [18].

In the present study, however, it is apparent that women who followed new perinatal care standards had significantly lower rates of cesarean section. Due to the retrospective nature of this research, it was not possible to exclude other factors unrelated to the screening protocol that may have influenced the mode of delivery. However, as the women in both groups were considered “low risk” from an obstetric history point of view, and there were no significant differences between both groups in relation to age, parity, BMI, booking status, gestational age at delivery, and birthweight, the reduction in cesarean section rate is likely to be at least partially attributed to the implementation of a universal screening program.

This study revealed that universal screening for glucose tolerance and gestational hypertension, showed that abnormal results occurred in small numbers of cases. GDM and gestational hypertension were detected in pregnant women 7 and 4 times more often after the introduction of total screening according to new protocols. However, these statistically insignificant results are probably due to the limited number of participants. The universal screening for GDM using OGTT was associated with increasing in identification of women with GDM and severe hyperglycemia and lead to improving of neonatal outcomes for those with GDM. However, there was no evidence of benefit or reduction of adverse effects on neonatal outcomes in the general obstetric population [19]. The latter findings were supported by a study conducted in Finland, where comprehensive screening did not improve pregnancy and neonatal outcomes compared to risk-based practice [20]. One research revealed that universal GDM screening might lead to decreasing the mean birthweight and macrosomia rates [21]. However, universal screening for GDM at 24–28 weeks of gestation can result in the over-diagnosis of GDM, leading to increasing pressure on health care services and on patients without clear benefits [22]. While selective screening leads to missing one sixth of GDM cases, these cases seemed milder, and less likely to lead to perinatal complications. For this reason, screening can be avoided in low-risk women [23].

The present study showed that universal screening detected more cases of polyhydramnios. In general, and in all pregnancies, the percentage of polyhydramnios ranges from 0.2 to 1.6% [24]. However, it is reported that polyhydramnios is associated with multiple pregnancies, GDM, fetal anemia, and other reasons [25]. Poorly managed GDM may result in fetal hyperglycemia, leading to increased osmotic diuresis and polyurea. In the present study, however, none of the women with polyhydramnios from the universal screening group had GDM. Since both groups were grand multiparity and had similar maternal age and frequency of anemia, other reasons may have contributed to polyhydramnios.

The data available regarding abnormal TSH levels in the first trimester and their association with adverse pregnancy outcomes are contradictory. While some studies did not find an effect on adverse pregnancy outcomes [26], others found that it is associated with perinatal loss and miscarriages, as well as with pre-eclampsia, dystocia in labor, prematurity [9, 23] and respiratory distress syndrome in offspring [27]. Universal screening of TSH levels versus selective testing for thyroid dysfunction did not show apparent differences in pregnancy outcomes [28, 29], while it increases diagnosis and treatment of thyroid dysfunction [30]. This can be explained by the fact that in the general population mild thyroid dysfunctions are mainly detected [28]. On the other hand, just testing high-risk pregnant women leads to missing approximately 40% of all hypothyroid patients [31], especially those with subclinical hypothyroidism [32, 33]. Again, selective screening of TSH in pregnant women of low risk, as recommended by the American Thyroid Association, does not result in a significant drop in the detection rate of pregnant women who qualify for L-T4 treatment [34]. In the face of these controversies, the number of healthcare providers who are performing universal screening for thyroid disease in pregnancy, contrary to society guidelines, are increasing all over the world [10]. Regardless of the screening strategy adopted by the provider, all pregnant women should be verbally screened at the initial prenatal visit for any history of thyroid dysfunction [6], as timely screening and detection of gestational thyroid disorders, as well as active intervention, can significantly improve pregnancy outcomes [35].

This study has limitations that should be noted. Firstly, the study was a retrospective study conducted in a single facility covering the Northern region of Jordan. Thus, the results might only be representative of some of the population. Secondly, the small sample size meant that abnormal results of screening tests occurred in small number of cases, hindering analysis of perinatal outcomes in women with thyroid dysfunction and GDM. Thirdly, the study enrolled a low-risk group of pregnant women, therefore, the results cannot be generalized to the whole population.

The issue of screening aimed at detecting thyroid dysfunction and/or gestational diabetes is still controversial. Despite the recommendations of world associations to conduct this screening only in high-risk groups, the healthcare systems of many countries practice universal screening, citing that selective screening leads to a high number of missed cases. On the other hand, universal screening can lead to over diagnosis and unnecessary intervention. At the same time, it is uncertain whether this leads to a significant improvement in perinatal outcomes, and raises issues of cost-effectiveness.

The present study revealed that implementing new perinatal care protocols, including universal screening TSH, OGTT, and morphological and growth scans, significantly decreased the rate of cesarean section in grand multiparous women with advanced maternal age. Further studies on a large sample size are needed to obtain more representative results among women in high-risk group for GDM and thyroid dysfunction.

BMI, body mass index; GDM, gestational diabetes mellitus; IUGR, intrauterine growth restriction; JUH, Jordan University Hospital; LGA, large for gestational age; L-T4, levothyroxine; NICU, neonatal intensive care unit; OGTT, oral glucose tolerance test; SGA, small for gestational age; TSH, thyroid stimulating hormone.

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

FT was responsible for the conceptualization of this research. FT, NM, AQ, KF, NAH and FA contributed to the literature review, data collection, data analysis, and manuscript preparation. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethical approval of this research was obtained from Deanship of academic research at The University of Jordan and Institutional Review Board (IRB) of Jordan University Hospital (JUH) (2017/115) in accordance with the Helsinki Declaration and JUH guidelines. Furthermore, the IRB waived obtaining an informed consent with strict JUH guidelines not to breach patients’ confidentiality.

We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.

This research received no external funding.

The authors declare no conflict of interest.